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Showing 100 Latest Publications
TitleDate Created
A Binary Host Plant Volatile Lure Combined With Acetic Acid to Monitor Codling Moth (Lepidoptera: Tortricidae).Thursday, August 27, 2015
Knight AL, Basoalto E, Katalin J, El-Sayed AM,
Environmental entomology. 15-Jul-2015
Field studies were conducted in the United States, Hungary, and New Zealand to evaluate the effectiveness of septa lures loaded with ethyl (E,Z)-2,4-decadienoate (pear ester) and (E)-4,8- dimethyl-1,3,7-nonatriene (nonatriene) alone and in combination with an acetic acid co-lure for both sexes of codling moth, Cydia pomonella (L.). Additional studies were conducted to evaluate these host plant volatiles and acetic acid in combination with the sex pheromone, (E,E)-8,10-dodecadien-1-ol (codlemone). Traps baited with pear ester/nonatriene + acetic acid placed within orchards treated either with codlemone dispensers or left untreated caught significantly more males, females, and total moths than similar traps baited with pear ester + acetic acid in some assays. Similarly, traps baited with codlemone/pear ester/nonatriene + acetic acid caught significantly greater numbers of moths than traps with codlemone/pear ester + acetic acid lures in some assays in orchards treated with combinational dispensers (dispensers loaded with codlemone/pear ester). These data suggest that monitoring of codling moth can be marginally improved in orchards under variable management plans using a binary host plant volatile lure in combination with codlemone and acetic acid. These results are likely to be most significant in orchards treated with combinational dispensers. Significant increases in the catch of female codling moths in traps with the binary host plant volatile blend plus acetic acid should be useful in developing more effective mass trapping strategies.
Electrophysiological and Behavioral Responses of Chrysopa phyllochroma (Neuroptera: Chrysopidae) to Plant Volatiles.Thursday, August 27, 2015
Xu X, Cai X, Bian L, Luo Z, Xin Z, Chen Z,
Environmental entomology. 12-Jul-2015
The lacewing Chrysopa phyllochroma Waesmael is a polyphagous predator of many pests. Releasing lacewings is an important component of biological control programs, but it is difficult to establish populations on field crops. Electrophysiological and behavioral responses to 10 common plant volatiles were recorded to screen for lacewing-attracting compounds. Electroantennographic assays indicated that all of the tested compounds elicited responses from C. phyllochroma. Three green-leaf volatiles-(E)-2-hexenal, (Z)-3-hexenyl acetate, and (Z)-3-hexenol-produced the strongest responses. Weaker responses were observed to six terpenes-ocimene, linalool, (3E)-4,8-dimethyl-1,3,7-nonatriene, (E,E)-α-farnesene, limonene, and nerolidol-and to methyl salicylate. Using a Y-tube olfactometer, the behavioral assays of the eight most active compounds demonstrated that four-(Z)-3-hexenyl acetate, (Z)-3-hexenol, (3E)-4,8-dimethyl-1,3,7-nonatriene, and linalool-were significant attractants for C. phyllochroma at specific concentrations. Three common plant volatile compounds-(Z)-3-hexenyl acetate, (3E)-4,8-dimethyl-1,3,7-nonatriene, and linalool-were also found to significantly enhance female ovipositing, resulting in a concentration of eggs. These observations are important for lacewing release as a pest control measure because they suggest means for retaining individuals and establishing populations using common plant volatiles.
Mechanism of Resistance Acquisition and Potential Associated Fitness Costs in Amyelois transitella (Lepidoptera: Pyralidae) Exposed to Pyrethroid Insecticides.Friday, August 28, 2015
Demkovich M, Siegel JP, Higbee BS, Berenbaum MR,
Environmental entomology. Jun-2015
The polyphagous navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), is the most destructive pest of nut crops, including almonds and pistachios, in California orchards. Management of this insect has typically been a combination of cultural controls and insecticide use, with the latter increasing substantially along with the value of these commodities. Possibly associated with increased insecticide use, resistance has been observed recently in navel orangeworm populations in Kern County, California. In studies characterizing a putatively pyrethroid-resistant strain (R347) of navel orangeworm, susceptibility to bifenthrin and β-cyfluthrin was compared with that of an established colony of susceptible navel orangeworm. Administration of piperonyl butoxide and S,S,S-tributyl phosphorotrithioate in first-instar feeding bioassays with the pyrethroids bifenthrin and β-cyfluthrin produced synergistic effects and demonstrated that cytochrome P450 monooxygenases and carboxylesterases contribute to resistance in this population. Resistance is therefore primarily metabolic and likely the result of overexpression of specific cytochrome P450 monooxygenases and carboxylesterase genes. Resistance was assessed by median lethal concentration (LC50) assays and maintained across nine generations in the laboratory. Life history trait comparisons between the resistant strain and susceptible strain revealed significantly lower pupal weights in resistant individuals reared on the same wheat bran-based artificial diet across six generations. Time to second instar was greater in the resistant strain than the susceptible strain, although overall development time was not significantly different between strains. Resistance was heritable and may have an associated fitness cost, which could influence the dispersal and expansion of resistant populations in nut-growing areas in California.
An Induced Susceptibility Response in Soybean Promotes Avirulent Aphis glycines (Hemiptera: Aphididae) Populations on Resistant Soybean.Friday, August 28, 2015
Varenhorst AJ, McCarville MT, O'Neal ME,
Environmental entomology. Jun-2015
Observations of virulent Aphis glycines Matsumura populations on resistant soybean in North America occurred prior to the commercial release of Rag genes. Laboratory assays confirmed the presence of four A. glycines biotypes in North America defined by their virulence to the Rag1 and Rag2 genes. Avirulent and virulent biotypes can co-occur and potentially interact on soybean, which may result in induced susceptibility. We conducted a series of experiments to determine if the survival of avirulent biotypes on susceptible and resistant soybean containing the Rag1 or Rag1 + Rag2 genes was affected by the presence of either avirulent or virulent conspecifics. Regardless of virulence to Rag genes, initial feeding by conspecifics increased the survival of subsequent A. glycines populations on both susceptible and resistant soybean. Avirulent populations increased at the same rate as virulent populations if the resistant plants were initially colonized with virulent aphids. These results are the first to demonstrate that virulent A. glycines increase the suitability of resistant soybean for avirulent conspecifics, thus explaining the lack of genetic differentiation observed in North America between A. glycines populations on resistant and susceptible soybean. These results suggest the occurrence of virulence toward Rag genes in North America may be overestimated. In addition this may alter the selection pressure for virulence genes to increase in a population. Therefore, insect resistance management models for A. glycines may need to incorporate induced susceptibility factors to determine the relative durability of resistance genes.
Domestication in Murtilla (Ugni molinae) Reduced Defensive Flavonol Levels but Increased Resistance Against a Native Herbivorous Insect.Friday, August 28, 2015
Chacón-Fuentes M, Parra L, Rodriguez-Saona C, Seguel I, Ceballos R, Quiroz A,
Environmental entomology. Jun-2015
Plant domestication can have negative consequences for defensive traits against herbivores, potentially reducing the levels of chemical defenses in plants and consequently their resistance against herbivores. We characterized and quantified the defensive flavonols from multiple cultivated ecotypes with wild ancestors of murtilla, Ugni molinae Turcz, an endemic plant from Chile, at different times of the year, and examined their effects on a native insect herbivore, Chilesia rudis Butler (Lepidoptera: Arctiidae). We hypothesized that domestication results in a decrease in flavonol levels in U. molinae plants, and that this negatively affected C. rudis performance and preference. Ethanolic extracts were made from leaves, stems, and fruit of murtilla plants for flavonol analysis. Flavonols identified were kaempferol, quercetin, rutin, and quercetin 3-D-β-glucoside, the last two being the most abundant. More interestingly, we showed differences in flavonol composition between wild and cultivated U. molinae that persisted for most of the year. Relative amounts of all four flavonols were higher in wild U. molinae leaves; however, no differences were found in the stem and fruit between wild and cultivated plants. In choice and no-choice assays, C. rudis larvae gained more mass on, and consumed more leaf material of, wild as compared with cultivated U. molinae plants. Moreover, when applied to leaves, larvae ate more leaf material with increasing concentrations of each flavonol compound. Our study demonstrates that domestication in U. molinae reduced the amount of flavonols in leaves as well as the performance and preference of C. rudis, indicating that these compounds stimulate feeding of C. rudis.
The Endosymbiont Arsenophonus Provides a General Benefit to Soybean Aphid (Hemiptera: Aphididae) Regardless of Host Plant Resistance (Rag).Friday, August 28, 2015
Wulff JA, White JA,
Environmental entomology. Jun-2015
Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), invokes substantial chemical treatment and economic cost in North America. Resistant soybean genotypes hold promise as a low-impact control methodology, but soybean aphid "biotypes" capable of development on resistant soy cast doubt on the durability of soy resistance. We hypothesized that variation in soybean aphid ability to colonize resistant soy is partially attributable to a bacterial symbiont of soybean aphid, Arsenophonus. We used microinjection to manipulate Arsenophonus infection in both virulent and avirulent aphid biotypes, resulting in five pairs of infected versus uninfected isolines. These isolines were subjected to various population growth rate assays on resistant Rag versus susceptible soybean. We found that aphid virulence on Rag soybean was not dependent on Arsenophonus: virulent aphid biotypes performed well on Rag soybean, and avirulent aphid biotypes performed poorly on Rag soybean, regardless of whether Arsenophonus was present or not. However, we did find that Arsenophonus-infected clones on average performed significantly better than their paired uninfected isolines. This pattern was not consistently evident on every date for every clone, either in the population assays nor when we compared lifetime fecundity of individual aphids in a separate experiment. Nevertheless, this overall benefit for infected aphids may be sufficient to explain the high frequency of Arsenophonus infection in soybean aphids.
Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons.Thursday, August 27, 2015
Balagopal A, Barin B, Quinn J, Rogers R, Sulkowski MS, Stock PG,
PloS one. 31-03-2015
Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210-429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7-4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02-0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01-4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.
Nut consumption is inversely associated with both cancer and total mortality in a Mediterranean population: prospective results from the Moli-sani study.Friday, August 28, 2015
Bonaccio M, Di Castelnuovo A, De Curtis A, Costanzo S, Bracone F, Persichillo M, Donati MB, de Gaetano G, Iacoviello L,
The British journal of nutrition. Sep-2015
Nut intake has been associated with reduced inflammatory status and lower risk of CVD and mortality. The aim of this study was to examine the relationship between nut consumption and mortality and the role of inflammation. We conducted a population-based prospective investigation on 19 386 subjects enrolled in the Moli-sani study. Food intake was recorded by the Italian version of the European Project Investigation into Cancer and Nutrition FFQ. C-reactive protein, leucocyte and platelet counts and the neutrophil:lymphocyte ratio were used as biomarkers of low-grade inflammation. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard models. During a median follow-up of 4·3 years, 334 all-cause deaths occurred. As compared with subjects who never ate nuts, rare intake (≤2 times/month) was inversely associated with mortality (multivariable HR=0·68; 95 % CI 0·54, 0·87). At intake ≥8 times/month, a greater protection was observed (HR=0·53; 0·32, 0·90). Nut intake (v. no intake) conveyed a higher protection to individuals poorly adhering to the Mediterranean diet (MD). A significant reduction in cancer deaths (HR=0·64; 95 % CI 0·44, 0·94) was also observed, whereas the impact on CVD deaths was limited to an inverse, but not significant, trend. Biomarkers of low-grade inflammation were reduced in nut consumers but did not account for the association with mortality. In conclusion, nut intake was associated with reduced cancer and total mortality. The protection was stronger in individuals with lower adherence to MD, whereas it was similar in high-risk groups (diabetics, obese, smokers or those with the metabolic syndrome), as compared with low-risk subjects. Inflammation did not explain the observed relationship.
Direct-to-Consumer Genetic Testing: A Systematic Review of European Guidelines, Recommendations, and Position Statements.Thursday, August 27, 2015
Rafiq M, Ianuale C, Ricciardi W, Boccia S,
Genetic testing and molecular biomarkers. 27-Aug-2015
Professional societies and associations are currently more suggestive of potential disadvantages of DTC GT, recommending improved genetic literacy of both populations and health professionals, and implementation research on the genetic tests to integrate public health genomics into healthcare systems.
α-Solanine induces ROS-mediated autophagy through activation of endoplasmic reticulum stress and inhibition of Akt/mTOR pathway.Thursday, August 27, 2015
Hasanain M, Bhattacharjee A, Pandey P, Ashraf R, Singh N, Sharma S, Vishwakarma AL, Datta D, Mitra K, Sarkar J,
Cell death & disease. 27-8-2015
α-Solanine is a glycoalkaloid found in species of the nightshade family including potato. It was primarily reported to have toxic effects in humans. However, there is a growing body of literature demonstrating in vitro and in vivo anticancer activity of α-solanine. Most of these studies have shown activation of apoptosis as the underlying mechanism in antitumor activity of α-solanine. In this study, we report α-solanine as a potential inducer of autophagy, which may act synergistically or in parallel with apoptosis to exert its cytotoxic effect. Induction of autophagy was demonstrated by several assays including electron microscopy, immunoblotting of autophagy markers and immunofluorescence for LC3 (microtubule-associated protein 1 (MAP1) light chain-3) puncta. α-Solanine-induced autophagic flux was demonstrated by additionally enhanced - turnover of LC3-II and - accumulation of LC3-specific puncta after co-incubation of cells with either of the autophagolysosome inhibitors - chloroquine and - bafilomycin A1. We also demonstrated α-solanine-induced oxidative damage in regulating autophagy where pre-incubation of cells with reactive oxygen species (ROS) scavenger resulted in suppression of CM-H2DCFDA (5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester) fluorescence as well as decrease in LC3-II turnover. α-Solanine treatment caused an increase in the expression of endoplasmic reticulum (ER) stress proteins (BiP, activating transcription factor 6 (ATF6), X-box-binding protein 1, PERK, inositol-requiring transmembrane kinase/endonuclease 1, ATF4 and CCAAT-enhancer-binding protein (C/EBP)-homologous protein) suggesting activation of unfolded protein response pathway. Moreover, we found downregulation of phosphorylated Akt (Thr(308) and Ser(473)), mammalian target of rapamycin (mTOR; Ser(2448) and Ser(2481)) and 4E-BP1 (Thr(37/46)) by α-solanine implying suppression of the Akt/mTOR pathway. Collectively, our results signify that α-solanine induces autophagy to exert anti-proliferative activity by triggering ER stress and inhibiting Akt/mTOR signaling pathway.
The Efficacy of Combining EGFR Monoclonal Antibody With Chemotherapy for Patients With Advanced Nonsmall Cell Lung Cancer: A Meta-Analysis From 9 Randomized Controlled Trials.Friday, August 28, 2015
Sheng J, Yang YP, Zhao YY, Qin T, Hu ZH, Zhou T, Zhang YX, Hong SD, Ma YX, Zhao HY, Huang Y, Zhang L,
Medicine. Aug-2015
Although epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) have been proved synergistic effect when combined with cytotoxic agents for advanced nonsmall cell lung cancer (NSCLC), the results of relevant clinical trials remain controversial. The purpose of this meta-analysis was to assess the advantage and toxicity profile of chemotherapy plus EGFR-mAbs versus chemotherapy alone for patients with NSCLC.We rigorously searched electronic databases for eligible studies reporting EGFR-mAbs combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC. The primary outcome was overall survival (OS). Pooled results were calculated using proper statistical methods.Nine phase II/III randomized controlled trials involved a total of 4949 participants were included. In general, compared with chemotherapy alone, the addition of EGFR-mAbs significantly improved OS (hazard ratio [HR] = 0.91, 95% confidence interval [CI]: 0.86-0.97, P = 0.006), progression-free survival (HR = 0.83, 95% CI: 0.87-0.98, P = 0.01), response rate (odd ratio [OR] = 1.28, 95% CI: 1.12-1.47, P = 0.0003), and disease control rate (OR = 1.17, 95% CI: 1.01-1.36, P = 0.04). Subgroup analysis showed that apparent OS benefit present in patients with squamous NSCLC (HR = 0.83, 95% CI: 0.74-0.93, P = 0.001), and those treatment-naive population (HR = 0.88, 95% CI: 0.82-0.95, P = 0.0006). Several manageable adverse events were markedly increased by EGFR-mAbs, such as acne-like rash, infusion reactions, and diarrhea. The risk for some ≥Grade 3 toxicities, such as leukopenia, febrile neutropenia, and thromboembolic events were slightly increased by the addition of EGFR-mAbs. In general, the toxicities of the combination strategy were tolerable and manageable.The addition of EGFR-mAbs to chemotherapy provided superior clinical benefit along with acceptable toxicities to patients with advanced NSCLC, especially those harboring squamous cancer and treatment-naive. Further validation in front-line investigation, proper selection of the potential benefit population by tumor histology, and development of prognostic biomarkers are warranted for future research and clinical application of EGFR-mAbs.
High Temperature, High Ambient CO2 Affect the Interactions between Three Positive-Sense RNA Viruses and a Compatible Host Differentially, but not Their Silencing Suppression Efficiencies.Thursday, August 27, 2015
Del Toro FJ, Aguilar E, Hernández-Walias FJ, Tenllado F, Chung BN, Canto T,
PloS one. 28-8-2015
We compared infection of Nicotiana benthamiana plants by the positive-sense RNA viruses Cucumber mosaic virus (CMV), Potato virus Y (PVY), and by a Potato virus X (PVX) vector, the latter either unaltered or expressing the CMV 2b protein or the PVY HCPro suppressors of silencing, at 25°C vs. 30°C, or at standard (~401 parts per million, ppm) vs. elevated (970 ppm) CO2 levels. We also assessed the activities of their suppressors of silencing under those conditions. We found that at 30°C, accumulation of the CMV isolate and infection symptoms remained comparable to those at 25°C, whereas accumulation of the PVY isolate and those of the three PVX constructs decreased markedly, even when expressing the heterologous suppressors 2b or HCPro, and plants had either very attenuated or no symptoms. Under elevated CO2 plants grew larger, but contained less total protein/unit of leaf area. In contrast to temperature, infection symptoms remained unaltered for the five viruses at elevated CO2 levels, but viral titers in leaf disks as a proportion of the total protein content increased in all cases, markedly for CMV, and less so for PVY and the PVX constructs. Despite these differences, we found that neither high temperature nor elevated CO2 prevented efficient suppression of silencing by their viral suppressors in agropatch assays. Our results suggest that the strength of antiviral silencing at high temperature or CO2 levels, or those of the viral suppressors that counteract it, may not be the main determinants of the observed infection outcomes.
Hydrocortisone supresses inflammatory activity of metalloproteinase - 8 in carotid plaque.Friday, August 28, 2015
Gabriel SA, Antonangelo L, Capelozzi VL, Beteli CB, Camargo Júnior Od, Aquino JL, Caffaro RA,
Revista brasileira de cirurgia cardiovascular : órgão oficial da Sociedade Brasileira de Cirurgia Cardiovascular. Sep-2015
Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.
Exposure assessment issues in epidemiology studies of phthalates.Thursday, August 27, 2015
Johns LE, Cooper GS, Galizia A, Meeker JD,
Environment international. 24-Aug-2015
In conclusion, the measurement of urinary metabolite concentrations in urine could serve as a valuable approach to estimating exposure to phthalates in environmental epidemiology studies. Careful consideration of the strengths and limitations of this approach when interpreting study results is required.
Assessment of Circulating MicroRNAs for the Diagnosis and Disease Activity Evaluation in Patients with Ulcerative Colitis by Using the Nanostring Technology.Thursday, August 27, 2015
Polytarchou C, Oikonomopoulos A, Mahurkar S, Touroutoglou A, Koukos G, Hommes DW, Iliopoulos D,
Inflammatory bowel diseases. 6-Aug-2015
Circulating microRNAs provide a novel diagnostic and prognostic marker for patients with UC. The use of an FDA-approved platform could accelerate the application of microRNA screening in a gastrointenstinal clinical setting. When used in combination with current diagnostic and disease activity assessment modalities, microRNAs could improve both IBD screening and care management.
Metagenomic Analysis of Crohn's Disease Patients Identifies Changes in the Virome and Microbiome Related to Disease Status and Therapy, and Detects Potential Interactions and Biomarkers.Thursday, August 27, 2015
Pérez-Brocal V, García-López R, Nos P, Beltrán B, Moret I, Moya A,
Inflammatory bowel diseases. 6-Aug-2015
The bacterial community reflects the disease status of individuals more accurately than their viral counterparts. However, numerous viral biomarkers specifically associated with CD disease were identified. Because viruses can modulate bacterial communities, the correlation networks between both communities constitute a step forward in unraveling their interactions under normal and CD disease conditions.
miR-378b Promotes Differentiation of Keratinocytes through NKX3.1.Thursday, August 27, 2015
Wang XL, Zhang T, Wang J, Zhang DB, Zhao F, Lin XW, Wang Z, Shi P, Pang XN,
PloS one. 06-8-2015
MicroRNA (miRNA) is a kind of short non-coding RNA, involved in various cellular processes. During keratinocyte differentiation, miRNAs act as important regulators. In this study, we demonstrated by microarray assay that the expression of miR-378b significantly increased during keratinocytes differentiation. Our findings showed that miR-378b could inhibit proliferation, migration and differentiation in keratinocytes. Luciferase reporter assays showed that miR-378b directly target NKX3.1. Silencing of NKX3.1 could coincide with the effects of miR-24 overexpression. In conclusion, our results demonstrate miR-378b promote keratinocytes differentiation by targeting NKX3.1. Manipulation of miR-378b may afford a new strategy to clinic treatment of skin injury and repair.
In vitro M-like cells genesis through a tissue-engineered triple-culture intestinal model.Thursday, August 27, 2015
Araújo F, Pereira C, Costa J, Barrias C, Granja PL, Sarmento B,
Journal of biomedical materials research. Part B, Applied biomaterials. 27-Aug-2015
Although fewer in number, M-cells are considered antigen sampling cells, acting as a gateway for antigens from the gut lumen and presenting an impressive aptitude for particle transcytosis. These features make M-cells attractive targets for oral drug delivery studies, but this has been poorly explored. New and reproducible tissue-like in vitro models for studying intestinal sampling and permeability mechanisms are needed. The combination of different cell players in such models offers improved microenvironments with higher physiologic relevance. Here, a tissue-engineered model was established, by co-culturing Caco-2 absorptive cells, HT29-MTX mucus-producing cells and Raji B lymphocytes. After 3 weeks of cell co-culture, the presence of M-like cells was evidenced by the loss of brush-border organization, detected by the lack of microvilli. The triple-culture model showed to be efficient for insulin transport, a process that was influenced by the tightness of junctions between epithelial cells and the presence of mucus and M-like cells. Ultimately, the proposed tissue-engineered model provides a more complete and reliable tool to perform drug permeability tests, as compared to traditional models, and may also find applicability as an in vitro system to study transdifferentiation mechanisms of M cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
Using solution state NMR spectroscopy to probe NMR invisible gelators.Thursday, August 27, 2015
Wallace M, Iggo JA, Adams DJ,
Soft matter. 27-Aug-2015
Supramolecular hydrogels are formed via the self-assembly of gelator molecules upon application of a suitable trigger. The exact nature of this self-assembly process has been widely investigated as a practical understanding is vital for the informed design of these materials. Solution-state NMR spectroscopy is an excellent non-invasive tool to follow the self-assembly of supramolecular hydrogels. However, in most cases the self-assembled aggregates are silent by conventional (1)H NMR spectroscopy due to the low mobility of the constituent molecules, limiting NMR spectroscopy to following only the initial assembly step(s). Here, we present a new solution-state NMR spectroscopic method which allows the entire self-assembly process of a dipeptide gelator to be followed. This gelator forms transparent hydrogels by a multi-stage assembly process when the pH of an initially alkaline solution is lowered via the hydrolysis of glucono-δ-lactone (GdL). Changes in the charge, hydrophobicity and relative arrangement of the supramolecular aggregates can be followed throughout the assembly process by measuring the residual quadrupolar couplings (RQCs) of various molecular probes (here, (14)NH4(+) and isopropanol-d8), along with the NMR relaxation rates of (23)Na(+). The initially-formed aggregates comprise negatively charged fibrils which gradually lose their charge and become increasingly hydrophobic as the pH falls, eventually resulting in a macroscopic contraction of the hydrogel. We also demonstrate that the in situ measurement of pH by NMR spectroscopy is both convenient and accurate, representing a useful tool for the characterisation of self-assembly processes by NMR.
Facile synthesis of core/shell ZnO/ZnS nanofibers by electrospinning and gas-phase sulfidation for biosensor applications.Thursday, August 27, 2015
Baranowska-Korczyc A, Sobczak K, Dłużewski P, Reszka A, Kowalski BJ, Kłopotowski Ł, Elbaum D, Fronc K,
Physical chemistry chemical physics : PCCP. 27-Aug-2015
This study describes a new method of passivating ZnO nanofiber-based devices with a ZnS layer. This one-step process was carried out in H2S gas at room temperature, and resulted in the formation of core/shell ZnO/ZnS nanofibers. This study presents the structural, optical and electrical properties of ZnO/ZnS nanofibers formed by a 2 nm ZnS sphalerite crystal shell covering a 5 nm ZnO wurtzite crystal core. The passivation process prevented free carriers from capture by oxygen molecules and significantly reduced the impact of O2 on nanostructure conductivity. The conductivity of the nanofibers was increased by three orders of magnitude after the sulfidation, the photoresponse time was reduced from 1500 s to 30 s, and the cathodoluminescence intensity increased with the sulfidation time thanks to the removal of ZnO surface defects by passivation. The ZnO/ZnS nanofibers were stable in water for over 30 days, and in phosphate buffers of acidic, neutral and alkaline pH for over 3 days. The by-products of the passivation process did not affect the conductivity of the devices. The potential of ZnO/ZnS nanofibers for protein biosensing is demonstrated using biotin and streptavidin as a model system. The presented ZnS shell preparation method can facilitate the construction of future sensors and protects the ZnO surface from dissolving in a biological environment.
Hot off the press.Thursday, August 27, 2015
Hill RA, Sutherland A,
Natural product reports. 27-Aug-2015
A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as sigillin A from Ceratophysella sigillata.
Profilin-1 mediated cell-cycle arrest: Searching for drug targets.Thursday, August 27, 2015
Moens PD, Coumans JV,
Cell cycle (Georgetown, Tex.). 27-Aug-2015
A Simple Label Switching Algorithm for Semisupervised Structural SVMs.Thursday, August 27, 2015
Balamurugan P, Shevade S, Sundararajan S,
Neural computation. 27-Aug-2015
In structured output learning, obtaining labeled data for real-world applications is usually costly, while unlabeled examples are available in abundance. Semisupervised structured classification deals with a small number of labeled examples and a large number of unlabeled structured data. In this work, we consider semisupervised structural support vector machines with domain constraints. The optimization problem, which in general is not convex, contains the loss terms associated with the labeled and unlabeled examples, along with the domain constraints. We propose a simple optimization approach that alternates between solving a supervised learning problem and a constraint matching problem. Solving the constraint matching problem is difficult for structured prediction, and we propose an efficient and effective label switching method to solve it. The alternating optimization is carried out within a deterministic annealing framework, which helps in effective constraint matching and avoiding poor local minima, which are not very useful. The algorithm is simple and easy to implement. Further, it is suitable for any structured output learning problem where exact inference is available. Experiments on benchmark sequence labeling data sets and a natural language parsing data set show that the proposed approach, though simple, achieves comparable generalization performance.
Expression of Flotilin-2 and Acrosome Biogenesis Are Regulated by MiR-124 during Spermatogenesis.Thursday, August 27, 2015
Wu Y, Zhong A, Zheng H, Jiang M, Xia Z, Yu J, Chen L, Huang X,
PloS one. 27-8-2015
MicroRNAs (miRNAs) are a class of short non-coding RNA molecules, which diversely regulate gene expression in organisms. Although the regulatory role of these small RNA molecules has been recently explored in animal spermatogenesis, the role of miR-124 in male germ cells is poorly defined. In our previous study, flotillin-2 was investigated as a novel Golgi-related protein involved in sperm acrosome biogenesis. The current study was designed to analyze the contribution of miR-124 in the regulation of flotillin-2 expression during mouse acrosome biogenesis. Luciferase assays revealed the target effects of miR-124 on flotillin-2 expression. Following intratesticular injection of miR-124 in 3-week-old male mice, quantitative real-time RT-PCR and western blot analysis were employed to confirm the function of miR-124 in regulating flotillin-2 after 48 hours. Sperm abnormalities were assessed 3 weeks later by ordinary optical microscopy, the acrosome abnormalities were also assessed by PNA staining and transmission electron microscopy. The results showed the proportion of sperm acrosome abnormalities was significantly higher than that of the control group. The expression of flotillin-2 and caveolin-1 was significantly downregulated during acrosome biogenesis. These results indicated that miR-124 could potentially play a role in caveolin-independent vesicle trafficking and modulation of flotillin-2 expression in mouse acrosome biogenesis.
Investigation of the effectiveness of disinfectants against planktonic and biofilm forms of P. aeruginosa and E. faecalis cells using a compilation of cultivation, microscopic and flow cytometric techniques.Thursday, August 27, 2015
Juzwa W, Myszka K, Białas W, Dobrucka R, Konieczny P, Czaczyk K,
Biofouling. Aug-2015
This study evaluated the effectiveness of selected disinfectants against bacterial cells within a biofilm using flow cytometry, the conventional total viable count test and scanning electron microscopy (SEM). A flow cytometric procedure based on measurement of the cellular redox potential (CRP) was demonstrated to have potential for the rapid evaluation of activity against biofilm and planktonic forms of microbes. Quaternary ammonium compound-based disinfectant (QACB) demonstrated a higher level of anti-microbial activity than a performic acid preparation (PAP), with mean CRP values against P. aeruginosa cells of 2 and 1.33 relative fluorescence units (RFU) vs 63.33 and 61.33 RFU for 8 and 24 h cultures respectively. Flow cytometric evaluation of the anti-biofilm activity demonstrated a higher efficacy of QACB compared to PAP for P. aeruginosa cells of 1 and 0.66 RFU vs 18.33 and 22.66 RFU for 8 and 24 h cultures respectively. SEM images of treated P. aeruginosa cells demonstrated disinfectant-specific effects on cell morphology.
Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.Thursday, August 27, 2015
Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J,
PLoS pathogens. Aug-2015
There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.
Monitoring the Photocleaving Dynamics of Colloidal MicroRNA-Functionalized Gold Nanoparticles Using Second Harmonic Generation.Thursday, August 27, 2015
Kumal RR, Landry CR, Abu-Laban M, Hayes DJ, Haber LH,
Langmuir : the ACS journal of surfaces and colloids. 27-Aug-2015
Photoactivated drug delivery systems using gold nanoparticles provide the promise of spatiotemporal control of delivery that is crucial for applications ranging from regenerative medicine to cancer therapy. In this study, we use second harmonic generation (SHG) spectroscopy to monitor the light-activated controlled release of oligonucleotides from the surface of colloidal gold nanoparticles. MicroRNA is functionalized to spherical gold nanoparticles using a nitrobenzyl linker that undergoes photocleaving upon ultraviolet irradiation. The SHG signal generated from the colloidal nanoparticle sample is shown to be a sensitive probe for monitoring the photocleaving dynamics in real time. The photocleaving irradiation wavelength is scanned to show maximum efficiency on resonance at 365 nm and the kinetics are investigated at varying irradiation powers to demonstrate that the nitrobenzyl photocleaving is a one-photon process. Additional characterization methods including electrophoretic mobility measurements, extinction spectroscopy, and fluorimetry are used to verify the SHG results, leading to a better understanding of the photocleaving dynamics for this model oligonucleotide therapeutic delivery system.
Anti-infective control in human bronchiolar epithelial cells by mucin phenotypic changes following uptake of N-acetyl-L-cysteine.Thursday, August 27, 2015
Koizumi C, Yamada M, Ishizaki K, Ueda T, Sakurai K,
Free radical research. 27-Aug-2015
Uptake of NAC by human bronchiolar epithelial cells prevented bacterial infection and upregulated membranous, but not gel-forming, MUC expression along with the increase of intracellular antioxidant level under co-culture conditions with S. pneumonia.
MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection.Thursday, August 27, 2015
Muhammad SA, Fatima N, Syed NI, Wu X, Yang XF, Chen JY,
PloS one. 27-8-2015
Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections.
One-step (18)F labeling of biomolecules using organotrifluoroborates.Thursday, August 27, 2015
Liu Z, Lin KS, Bénard F, Pourghiasian M, Kiesewetter DO, Perrin DM, Chen X,
Nature protocols. Sep-2015
Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step (18)F-labeling method that obviates the need for HPLC purification. Within 30 min, (18)F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/μmol (1.1-3.0 Ci/μmol). The entire procedure, including the precursor preparation and (18)F radiolabeling, takes 7-10 d.
Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among Different Tsetse Species.Thursday, August 27, 2015
Zhao X, Silva TL, Cronin L, Savage AF, O'Neill M, Nerima B, Okedi LM, Aksoy S,
PLoS neglected tropical diseases. Aug-2015
Tsetse are vectors of pathogenic trypanosomes, agents of human and animal trypanosomiasis in Africa. Components of tsetse saliva (sialome) are introduced into the mammalian host bite site during the blood feeding process and are important for tsetse's ability to feed efficiently, but can also influence disease transmission and serve as biomarkers for host exposure. We compared the sialome components from four tsetse species in two subgenera: subgenus Morsitans: Glossina morsitans morsitans (Gmm) and Glossina pallidipes (Gpd), and subgenus Palpalis: Glossina palpalis gambiensis (Gpg) and Glossina fuscipes fuscipes (Gff), and evaluated their immunogenicity and serological cross reactivity by an immunoblot approach utilizing antibodies from experimental mice challenged with uninfected flies. The protein and immune profiles of sialome components varied with fly species in the same subgenus displaying greater similarity and cross reactivity. Sera obtained from cattle from disease endemic areas of Africa displayed an immunogenicity profile reflective of tsetse species distribution. We analyzed the sialome fractions of Gmm by LC-MS/MS, and identified TAg5, Tsal1/Tsal2, and Sgp3 as major immunogenic proteins, and the 5'-nucleotidase family as well as four members of the Adenosine Deaminase Growth Factor (ADGF) family as the major non-immunogenic proteins. Within the ADGF family, we identified four closely related proteins (TSGF-1, TSGF-2, ADGF-3 and ADGF-4), all of which are expressed in tsetse salivary glands. We describe the tsetse species-specific expression profiles and genomic localization of these proteins. Using a passive-immunity approach, we evaluated the effects of rec-TSGF (TSGF-1 and TSGF-2) polyclonal antibodies on tsetse fitness parameters. Limited exposure of tsetse to mice with circulating anti-TSGF antibodies resulted in a slight detriment to their blood feeding ability as reflected by compromised digestion, lower weight gain and less total lipid reserves although these results were not statistically significant. Long-term exposure studies of tsetse flies to antibodies corresponding to the ADGF family of proteins are warranted to evaluate the role of this conserved family in fly biology.
Downregulation of Long Noncoding RNA Meg3 Affects Insulin Synthesis and Secretion in Mouse Pancreatic Beta Cells.Thursday, August 27, 2015
You L, Wang N, Yin D, Wang L, Jin F, Zhu Y, Yuan Q, De W,
Journal of cellular physiology. 27-Aug-2015
Increasing evidence indicates that long noncoding RNAs (lncRNAs) are involved in diverse biological process. Mouse maternal expressed gene 3 (Meg3), is an imprinted gene and essential for development. Here, we explored the relationship between Meg3 and the function of mouse beta cells in vitro and vivo. Real-time PCR analyses revealed Meg3 was more abundantly expressed in Balb/c mouse islets than exocrine glands. Moreover, the expression of Meg3 in islets was decreased in T1DM (NOD female mice) and T2DM (db/db mice) models. Meg3 expression was modulated dynamically by glucose in Min6 cells and isolated mouse islets. The function role of Meg3 was investigated in Min6 cells and normal mouse by knockdown of Meg3 using small interfering RNA. After suppression of Meg3 expression in vitro, insulin synthesis and secretion were impaired and the rate of beta cells apoptosis was increased. Moreover, knockdown of Meg3 in vivo led to the impaired glucose tolerance and decreased insulin secretion, consisted with the reduction of insulin positive cells areas by immunochemistry assays. Notably, islets from Meg3 interference groups showed significant decrease of Pdx-1 and MafA expression in mRNA and protein levels. These results indicate that Meg3 may function as a new regulator of maintaining beta cells identity via affecting insulin production and cell apoptosis. This article is protected by copyright. All rights reserved.
Efficient cell pairing in droplets using dual-color sorting.Thursday, August 27, 2015
Hu H, Eustace D, Merten CA,
Lab on a chip. 27-Aug-2015
The use of microfluidic droplets has become a powerful tool for the screening and manipulation of cells. However, currently this is restricted to assays involving a single cell type. Studies on the interaction of different cells (e.g. in immunology) as well as the screening of antibody-secreting cells in assays requiring an additional reporter cell, have not yet been successfully demonstrated. Based on Poisson statistics, the probability for the generation of droplets hosting exactly one cell of two different types is just 13.5%. To overcome this limitation, we have developed an approach in which different cell types are stained with different fluorescent dyes. Subsequent to encapsulation into droplets, the resulting emulsion is injected into a very compact sorting device allowing for analysis at high magnification and fixation of the cells close to the focal plane. By applying dual-color sorting, this furthermore enables the specific collection and analysis of droplets with exactly two different cells. Our approach shows an efficiency of up to 86.7% (more than 97% when also considering droplets hosting one or more cells of each type), and, hence, should pave the way for a variety of cell-based assays in droplets.
Integrating high-dimensional transcriptomics and image analysis tools into early safety screening: a proof-of-concept for a new early drug development strategy.Thursday, August 27, 2015
Verbist BM, Verheyen GR, Vervoort L, Crabbe M, Beerens D, Bosmans C, Jaensch S, Osselaer S, Talloen W, Van Den Wyngaert I, Van Hecke G, Wuyts D, Van Goethem F, Göhlmann HW,
Chemical research in toxicology. 27-Aug-2015
During drug discovery and development, the early identification of adverse effects is expected to reduce costly late stage failures of candidate drugs. As risk/safety assessment takes place rather late during the development process and due to the limited predictivity of animal models to the human situation, modern unbiased high-dimensional biology read-outs are sought, such as molecular signatures of in vivo response using high-throughput cell-based assays. In this theoretical proof-of-concept we provide findings of an in-depth exploration of a single chemical core structure. Via transcriptional profiling we identified a subset of close analogs which commonly down-regulate tubulin genes across cellular contexts, suggesting possible spindle poison effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test) and the identification of a characteristic aggregate-formation phenotype via exploratory high content imaging validated the initial findings. SAR analysis triggered the synthesis of a new set of compounds and allowed us to extend the series showing the genotoxic effect. We demonstrate the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery. We share our thoughts on how this approach may be incorporated into drug development strategies.
Biomarkers and novel agents in esophago-gastric cancer: are we making progress?Friday, August 28, 2015
Dahle-Smith A, Petty RD,
Expert review of anticancer therapy. Sep-2015
Esophago-gastric cancer (EGC) provides a formidable healthcare challenge. Conventional chemotherapy provides modest survival benefit in patients with advanced disease especially in the second-line setting. The recent paradigm shift in the oncology community towards targeting growth factor pathways and the immune system using novel targeted agents has now demonstrated clinical utility in EGC, but recent trial results have highlighted the complexity of disease pathogenesis and significant challenges remain. Here, we describe the current role of targeted therapies in EGC, and their corresponding biomarkers. We aim to provide a comprehensive review of the current climate of novel agents and their biomarkers in advanced EGC.
Drug transporters in breast cancer: response to anthracyclines and taxanes.Friday, August 28, 2015
Kümler I, Stenvang J, Moreira J, Brünner N, Nielsen DL,
Expert review of anticancer therapy. Sep-2015
Despite the advances that have taken place in the past decade, including the development of novel molecular targeted agents, cytotoxic chemotherapy remains the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes are the two main chemotherapeutic options used on a routine basis. Although effective, their usefulness is limited by the inevitable development of resistance, a lack of response to drug-induced cancer cell death. A large body of research has resulted in the characterization of a plethora of mechanisms involved in resistance; ATP-binding cassette transporter proteins, through their function in xenobiotic clearance, play an important role in resistance. We review here the current evidence for drug transporters as biomarkers and the benefit of adding drug transporter modulators to conventional chemotherapy.
Cerebellar ataxia induced by 3-AP affects immunological function.Thursday, August 27, 2015
Jiang YY, Cao BB, Wang XQ, Peng YP, Qiu YH,
Neuro endocrinology letters. 27-Aug-2015
Cerebellar ataxia alters cellular and humoral immunity.
New perspectives in human tear analysis?Thursday, August 27, 2015
Kukumberg P, Karlík M, Beňová-Liszeková D, Beno M, Pechan T, Farkas R,
Neuro endocrinology letters. 27-Aug-2015
The human tear has the primary function to lubricate the cornea and to be the first-line protective surface against pathogens. Due to difficulties with their collection, tears are rarely utilized in clinical medicine. Nevertheless, these exocrine secretions could be very valuable as a source of potential biomarkers. Direct and prompt regulations of the tears production via parasympathetic tract of nucleus lacrimalis (n. VII) in pons Varoli throughout n. maxillaris of n. V enables to reveal changes in tear composition as an indicative response to various neuropsychiatric entities. Plasma, urine, and cerebrospinal fluid have been studied extensively in clinical medicine, but tears attracted only marginal interest so far. However, due to major advances in proteomics technique we can readily identify and quantify hundreds to thousands of proteins in single experiment. This can contribute to our understanding of complex biological phenomena and diseases. In our previous studies, we found deviations of human saliva and sweat structures in patients suffering from panic disorder (Kukumberg et al. 2009). Currently, we aim to compare proteins of human tears of healthy subjects with tear proteome of patients affected by different neuropsychiatric disorders.
Quantitative detection of rare interphase chromosome breaks and translocations by high-throughput imaging.Thursday, August 27, 2015
Burman B, Misteli T, Pegoraro G,
Genome biology. 27-8-2015
We report a method for the sensitive detection of rare chromosome breaks and translocations in interphase cells. HiBA-FISH (High-throughput break-apart FISH) combines high-throughput imaging with the measurement of the spatial separation of FISH probes flanking target genome regions of interest. As proof-of-principle, we apply hiBA-FISH to detect with high sensitivity and specificity rare chromosome breaks and translocations in the anaplastic large cell lymphoma breakpoint regions of NPM1 and ALK. This method complements existing approaches to detect translocations by overcoming the need for precise knowledge of translocation breakpoints and it extends traditional FISH by its quantitative nature.
Activation of Six1 Expression in Vertebrate Sensory Neurons.Thursday, August 27, 2015
Sato S, Yajima H, Furuta Y, Ikeda K, Kawakami K,
PloS one. 3-8-2015
SIX1 homeodomain protein is one of the essential key regulators of sensory organ development. Six1-deficient mice lack the olfactory epithelium, vomeronasal organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor neural differentiation in the distal part of the cranial ganglia. Simultaneous loss of both Six1 and Six4 leads to additional abnormalities such as small trigeminal ganglion and abnormal dorsal root ganglia (DRG). The aim of this study was to understand the molecular mechanism that controls Six1 expression in sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we focused on the sensory ganglia-specific Six1 enhancer (Six1-8) conserved between chick and mouse. In vivo reporter assays using both animals identified an important core region comprising binding consensus sequences for several transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU homeodomain and basic-helix-loop-helix proteins. The results provided information on upstream factors and signals potentially relevant to Six1 regulation in sensory neurons. We also report the establishment of a new transgenic mouse line (mSix1-8-NLSCre) that expresses Cre recombinase under the control of mouse Six1-8. Cre-mediated recombination was detected specifically in ISL1/2-positive sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination in SOX10-positive glial cells and central nervous system and ability to induce recombination in a subset of neurons derived from the olfactory placode/epithelium. This mouse model can be potentially used to advance research on sensory development.
Chitosan nanoparticle-mediated delivery of MiRNA-34a decreases prostate tumor growth in the bone and its expression induces non-canonical autophagy.Thursday, August 27, 2015
Gaur S, Wen Y, Song JH, Parikh NU, Mangala LS, Blessing AM, Ivan C, Wu SY, Varkaris A, Shi Y, Lopez-Berestein G, Frigo DE, Sood AK, Gallick GE,
Oncotarget. 22-Jul-2015
While several new therapies are FDA-approved for bone-metastatic prostate cancer (PCa), patient survival has only improved marginally. Here, we report that chitosan nanoparticle-mediated delivery of miR-34a, a tumor suppressive microRNA that downregulates multiple gene products involved in PCa progression and metastasis, inhibited prostate tumor growth and preserved bone integrity in a xenograft model representative of established PCa bone metastasis. Expression of miR-34a induced apoptosis in PCa cells, and, in accord with downregulation of targets associated with PCa growth, including MET and Axl and c-Myc, also induced a form of non-canonical autophagy that is independent of Beclin-1, ATG4, ATG5 and ATG7. MiR-34a-induced autophagy is anti-proliferative in prostate cancer cells, as blocking apoptosis still resulted in growth inhibition of tumor cells. Thus, combined effects of autophagy and apoptosis are responsible for miR-34a-mediated prostate tumor growth inhibition, and have translational impact, as this non-canonical form of autophagy is tumor inhibitory. Together, these results provide a new understanding of the biological effects of miR-34a and highlight the clinical potential for miR-34a delivery as a treatment for bone metastatic prostate cancer.
A challenge for theranostics: is the optimal particle for therapy also optimal for diagnostics?Thursday, August 27, 2015
Dreifuss T, Betzer O, Shilo M, Popovtzer A, Motiei M, Popovtzer R,
Nanoscale. 27-Aug-2015
Theranostics is defined as the combination of therapeutic and diagnostic capabilities in the same agent. Nanotechnology is emerging as an efficient platform for theranostics, since nanoparticle-based contrast agents are powerful tools for enhancing in vivo imaging, while therapeutic nanoparticles may overcome several limitations of conventional drug delivery systems. Theranostic nanoparticles have drawn particular interest in cancer treatment, as they offer significant advantages over both common imaging contrast agents and chemotherapeutic drugs. However, the development of platforms for theranostic applications raises critical questions; is the optimal particle for therapy also the optimal particle for diagnostics? Are the specific characteristics needed to optimize diagnostic imaging parallel to those required for treatment applications? This issue is examined in the present study, by investigating the effect of the gold nanoparticle (GNP) size on tumor uptake and tumor imaging. A series of anti-epidermal growth factor receptor conjugated GNPs of different sizes (diameter range: 20-120 nm) was synthesized, and then their uptake by human squamous cell carcinoma head and neck cancer cells, in vitro and in vivo, as well as their tumor visualization capabilities were evaluated using CT. The results showed that the size of the nanoparticle plays an instrumental role in determining its potential activity in vivo. Interestingly, we found that although the highest tumor uptake was obtained with 20 nm C225-GNPs, the highest contrast enhancement in the tumor was obtained with 50 nm C225-GNPs, thus leading to the conclusion that the optimal particle size for drug delivery is not necessarily optimal for imaging. These findings stress the importance of the investigation and design of optimal nanoparticles for theranostic applications.
Comparing the Hem- and Lymphangiogenic Profile of Conjunctival and Uveal Melanoma Cell Lines.Thursday, August 27, 2015
Refaian N, Schlereth SL, Koch KR, Notara M, Hos D, Mescher M, Iden S, Bosch JJ, Jager MJ, Cursiefen C, Heindl LM,
Investigative ophthalmology & visual science. 1-Aug-2015
Conjunctival melanoma cell lines did not show a higher prolymphangiogenic potential, and UM cell lines did not show a higher prohemangiogenic potential. Accordingly, other mechanisms within the tumor microenvironment might account for the diverging metastatic patterns of conjunctival versus uveal melanomas.
[Investigation of the changes in Candida epidemiology].Thursday, August 27, 2015
Çiçek B, Yılmaz H, Mutlu Yılmaz E, Esen Ş, Birinci A,
Mikrobiyoloji bulteni. Jul-2015
The incidence of fungal infections has increased in recent years. Antifungal resistance is a major problem with increasing frequency due to the widespread use of antifungal agents in infections. Identification of the Candida species and susceptibility patterns with the appropriate tests for resistance and selection of the empirical agents used for treatment are important. The aim of the study was to evaluate the changes of the epidemiology of Candida species and minimum inhibitory concentrations (MIC) of the antifungal agents, isolated in Mycology Laboratory of Ondokuz Mayıs University Faculty of Medicine, between 1 January 2009 to 1 July 2012. The study was performed retrospectively based on records in the mycology unit and checked comparatively with the automation system in the hospital. The recurrent reproductions of the same patient were excluded. For the identification of Candida species API®ID 32C (bioMerieux, France) system was used. Information on the isolated material, patient's age, gender and the inpatients' clinics were recorded. The susceptibility of Candida species isolated from blood cultures were studied with Etest (bioMerieux, France) method. A total of 1238 isolates were included in the study. The most common species isolated from clinical samples was C.albicans with a rate of 51.1% (n= 632), followed by C.tropicalis with a rate of 15.8% (n= 195). Among the pediatric intensive care unit (ICU) patients C.parapsilosis 42% (n= 17) was the most common isolate and the second most common isolate was C.albicans 32% (n= 13). However, in the adult ICU the most common isolate was C.albicans 34% (n= 13) and the second was C.parapsilosis 31% (n= 12). When the distribution of Candida species were analyzed from the records of last four years, the frequency rate of C.albicans and non-albicans species was found as 51.1% (n= 632) and %48.9 (n= 606), respectively. Based on these data, a comparison was made between the years and no difference between the two groups in terms of the distribution of fungi within the specified time (x²: 3.2, df: 1, p: 0.073) was determined. Of the Candida species isolated from blood cultures, seven isolates (2.2%) were resistant to fluconazole in the study period. The differences of MIC levels in fluconazole were detected between the years 2010-2012 and 2011-2012. The geometric mean of the MICs in 2012 increased significantly compared to 2010 and 2011 (p< 0.01). There was no resistance to amphotericin B except for intrinsically resistant Candida lusitaniae. There were no significant differences among amphotericin MIC values between years (p> 0.05). According to the sensitivity results, fluconazole is still seen as an option that can be used for the first choice. Although it remains as the first antifungal choice, antifungal susceptibility testing of the identified fungi will help the clinician for the plan and continuation of the treatment.
Nutritional Supplementation Is a Necessary Complement to Dietary Counseling among Tuberculosis and Tuberculosis-HIV Patients.Thursday, August 27, 2015
Bacelo AC, Ramalho A, Brasil PE, Cople-Rodrigues CD, Georg I, Paiva E, Argolo SV, Rolla VC,
PloS one. 28-8-2015
Although with a limited number of patients, the evidence does not support that dietary counseling is effective to recover from malnutrition in our population.
SERS Nanoparticles in Medicine: From Label-Free Detection to Spectroscopic Tagging.Thursday, August 27, 2015
Lane LA, Qian X, Nie S,
Chemical reviews. 27-Aug-2015
Molecular modeling, in-silico screening and molecular dynamics of PfPRL-PTP of P. falciparum for identification of potential anti-malarials.Thursday, August 27, 2015
Patel S, Joshi D, Soni R, Sharma D, Bhatt TK,
Journal of biomolecular structure & dynamics. 27-Aug-2015
Millions of death occurs every year due to malaria. Growing resistance against existing drugs for treatment of malaria has exaggerated the problem further. There is an intense demand of identifying drug targets in malaria parasite. PfPRL-PTP protein is PRL group of phosphatase and one of the interesting drug targets being involved in three important pathways of malaria parasite (Secretion, phosphorylation and prenylation). Therefore, in this study, we have modeled three-dimensional structure of PfPRL-PTP followed by validation of 3D structure using RAMPAGE, Verify 3D and other structure validation tools. We could identify 12 potential inhibitory compounds using in-silico screening of NCI library against PfPRL-PTP with Glide. The Molecular dynamics simulation was also performed using GROMACS on PfPRL-PTP model alone and PfPRL-PTP -inhibitor complex. This study of identifying potential drug-like molecules would add up to the process of drug discovery against malaria parasite.
Albumin Kinetics in Patients Undergoing Major Abdominal Surgery.Thursday, August 27, 2015
Norberg Å, Rooyackers O, Segersvärd R, Wernerman J,
PloS one. 27-8-2015
clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492.
2-Phenyl-APB-144-Induced Retinal Pigment Epithelium Degeneration and Its Underlying Mechanisms.Thursday, August 27, 2015
Hirai SI, Kurashima H, Nakamura D, Komatsu T, Yasuda Y, Habashita-Obata S, Ichikawa S, Katsuta O, Iwawaki T, Kohno K,
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 27-Aug-2015
Organelle pH alterations and autophagy impairments are involved in APB-induced RPE cell death. Inhibition of eIF2α dephosphorylation protected the RPE in vivo and in vitro. These findings suggested that APB-induced retinopathy is a valuable animal model for exploring the mechanism of RPE-driven retinopathy.
Three-Dimensional Environment Sustains Hematopoietic Stem Cell Differentiation into Platelet-Producing Megakaryocytes.Thursday, August 27, 2015
Pietrzyk-Nivau A, Poirault-Chassac S, Gandrille S, Derkaoui SM, Kauskot A, Letourneur D, Le Visage C, Baruch D,
PloS one. 27-8-2015
Hematopoietic stem cells (HSC) differentiate into megakaryocytes (MK), whose function is to release platelets. Attempts to improve in vitro platelet production have been hampered by the low amplification of MK. Providing HSC with an optimal three-dimensional (3D) architecture may favor MK differentiation by mimicking some crucial functions of the bone marrow structure. To this aim, porous hydrogel scaffolds were used to study MK differentiation from HSC as well as platelet production. Flow cytometry, qPCR and perfusion studies showed that 3D was suitable for longer kinetics of CD34+ cell proliferation and for delayed megakaryocytic differentiation far beyond the limited shelf-life observed in liquid culture but also increased production of functional platelets. We provide evidence that these 3D effects were related to 1) persistence of MK progenitors and precursors and 2) prolongation of expression of EKLF and c-myb transcription factors involved in early MK differentiation. In addition, presence of abundant mature MK with increased ploidy and impressive cytoskeleton elongations was in line with expression of NF-E2 transcription factor involved in late MK differentiation. Platelets produced in flow conditions were functional as shown by integrin αIIbβ3 activation following addition of exogenous agonists. This study demonstrates that spatial organization and biological cues synergize to improve MK differentiation and platelet production. Thus, 3D environment constitutes a powerful tool for unraveling the physiological mechanisms of megakaryopoiesis and thrombopoiesis in the bone marrow environment, potentially leading to an improved amplification of MK and platelet production.
Protein Composition of Infectious Spores Reveals Novel Sexual Development and Germination Factors in Cryptococcus.Thursday, August 27, 2015
Huang M, Hebert AS, Coon JJ, Hull CM,
PLoS genetics. Aug-2015
Spores are an essential cell type required for long-term survival across diverse organisms in the tree of life and are a hallmark of fungal reproduction, persistence, and dispersal. Among human fungal pathogens, spores are presumed infectious particles, but relatively little is known about this robust cell type. Here we used the meningitis-causing fungus Cryptococcus neoformans to determine the roles of spore-resident proteins in spore biology. Using highly sensitive nanoscale liquid chromatography/mass spectrometry, we compared the proteomes of spores and vegetative cells (yeast) and identified eighteen proteins specifically enriched in spores. The genes encoding these proteins were deleted, and the resulting strains were evaluated for discernable phenotypes. We hypothesized that spore-enriched proteins would be preferentially involved in spore-specific processes such as dormancy, stress resistance, and germination. Surprisingly, however, the majority of the mutants harbored defects in sexual development, the process by which spores are formed. One mutant in the cohort was defective in the spore-specific process of germination, showing a delay specifically in the initiation of vegetative growth. Thus, by using this in-depth proteomics approach as a screening tool for cell type-specific proteins and combining it with molecular genetics, we successfully identified the first germination factor in C. neoformans. We also identified numerous proteins with previously unknown functions in both sexual development and spore composition. Our findings provide the first insights into the basic protein components of infectious spores and reveal unexpected molecular connections between infectious particle production and spore composition in a pathogenic eukaryote.
Nanoparticle Probes for the Detection of Cancer Biomarkers, Cells, and Tissues by Fluorescence.Thursday, August 27, 2015
Chinen AB, Guan CM, Ferrer JR, Barnaby SN, Merkel TJ, Mirkin CA,
Chemical reviews. 27-Aug-2015
Salivary Lipid Peroxidation in Patients With Generalized Chronic Periodontitis and Acute Coronary Syndrome.Thursday, August 27, 2015
Nguyen TT, Ngo LQ, Promsudthi A, Surarit R,
Journal of periodontology. 27-Aug-2015
This study was the first to investigate salivary MDA levels in ACS patients and their correlations to serum hsCRP and plasma fibrinogen levels. Our results indicated that salivary MDA level could be a biomarker for cardiovascular and/or periodontal diseases.
Multifactor Regulation of the MdtJI Polyamine Transporter in Shigella.Thursday, August 27, 2015
Leuzzi A, Di Martino ML, Campilongo R, Falconi M, Barbagallo M, Marcocci L, Pietrangeli P, Casalino M, Grossi M, Micheli G, Colonna B, Prosseda G,
PloS one. 27-8-2015
The polyamine profile of Shigella, the etiological agent of bacillary dysentery in humans, differs markedly from that of E. coli, its innocuous commensal ancestor. Pathoadaptive mutations such as the loss of cadaverine and the increase of spermidine favour the full expression of the virulent phenotype of Shigella. Spermidine levels affect the expression of the MdtJI complex, a recently identified efflux pump belonging to the small multi-drug resistance family of transporters. In the present study, we have addressed the regulation of the mdtJI operon in Shigella by asking which factors influence its expression as compared to E. coli. In particular, after identifying the mdtJI promoter by primer extension analysis, in vivo transcription assays and gel-retardation experiments were carried out to get insight on the silencing of mdtJI in E. coli. The results indicate that H-NS, a major nucleoid protein, plays a key role in repressing the mdtJI operon by direct binding to the regulatory region. In the Shigella background mdtJI expression is increased by the high levels of spermidine typically found in this microorganism and by VirF, the plasmid-encoded regulator of the Shigella virulence regulatory cascade. We also show that the expression of mdtJI is stimulated by bile components. Functional analyses reveal that MdtJI is able to promote the excretion of putrescine, the spermidine precursor. This leads us to consider the MdtJI complex as a possible safety valve allowing Shigella to maintain spermidine to a level optimally suited to survival within infected macrophages and, at the same time, prevent toxicity due to spermidine over-accumulation.
Anti-signal recognition particle antibody in patients without inflammatory myopathy: a survey of 6180 patients with connective tissue diseases.Thursday, August 27, 2015
Hanaoka H, Kaneko Y, Suzuki S, Takada T, Hirakata M, Takeuchi T, Kuwana M,
Scandinavian journal of rheumatology. 27-Aug-2015
The prevalence of anti-SRP antibody was 0.5% in a cohort of Japanese patients with CTD, and one-third of them did not have inflammatory myopathy. Sera from patients with inflammatory myopathy recognized SRP54 more strongly than in those without myopathy.
Detection of immunogenic proteins from Anopheles sundaicussalivary glands in the human serum.Friday, August 28, 2015
Armiyanti Y, Nuryady MM, Arifianto RP, Nurmariana E, Senjarini K, Fitri LE, Sardjono TW,
Revista da Sociedade Brasileira de Medicina Tropical. Aug-2015
These results support the potential use of immunogenic proteins from the salivary glands of Anopheles as candidate markers of bite exposure or in malaria vaccines.
Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy.Friday, August 28, 2015
Coelho EA, Chávez-Fumagalli MA, Costa LE, Tavares CA, Soto M, Goulart LR,
Revista da Sociedade Brasileira de Medicina Tropical. Aug-2015
Phage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.
Unsupervised overnight closed loop insulin delivery during free living: analysis of randomised cross-over home studies in adults and adolescents with type 1 diabetes.Thursday, August 27, 2015
Thabit H, Elleri D, Leelarathna L, Allen J, Lubina-Solomon A, Stadler M, Walkinshaw E, Iqbal A, Choudhary P, Wilinska M, Barnard K, Heller S, Amiel S, Evans M, Dunger D, Hovorka R,
Lancet (London, England). 26-Feb-2015
Diabetes UK, Juvenile Diabetes Research Foundation, NIHR Cambridge Biomedical Research Centre.
Proteomic analysis to identify biomarkers in the primary tumour that predict response to neoadjuvant chemotherapy in liver metastases.Thursday, August 27, 2015
Sutton P, Evans J, Jones R, Malik H, Vimalachandran D, Palmer D, Goldring C, Kitteringham N,
Lancet (London, England). 26-Feb-2015
Cancer Research UK.
Evaluation of carotid plaque inflammation in patients with active rheumatoid arthritis using (18)F-fluorodeoxyglucose PET-CT and MRI: a pilot study.Thursday, August 27, 2015
Skeoch S, Williams H, Cristinacce P, Hockings P, James J, Alexander Y, Waterton J, Bruce I,
Lancet (London, England). 26-Feb-2015
North West England MRC Clinical Pharmacology and Therapeutics Clinical Research Fellowship, National Institute for Health Research, AstraZeneca-University of Manchester Strategic Alliance Fund.
Effect of UBE2L3 genotype on regulation of the linear ubiquitin chain assembly complex in systemic lupus erythematosus.Thursday, August 27, 2015
Lewis M, Vyse S, Shields A, Boeltz S, Gordon P, Spector T, Lehner P, Walczak H, Vyse T,
Lancet (London, England). 26-Feb-2015
Arthritis Research UK, Wellcome Trust, George Koukis Foundation, European Community's Seventh Framework Programme.
The roles of DEAD box helicases in the life cycle of HIV-1.Thursday, August 27, 2015
Sithole N, Williams C, Vaughan A, Lever A,
Lancet (London, England). 26-Feb-2015
Wellcome Trust.
Role of vitamin D in endothelial function and endothelial repair in clinically stable systemic lupus erythematosus.Thursday, August 27, 2015
Reynolds J, Ray D, Alexander MY, Bruce I,
Lancet (London, England). 26-Feb-2015
North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics (funding from UK Medical Research Council (grant number G1000417/94909), ICON, Astra Zeneca, GlaxoSmithKline, Medicines Evaluation Unit).
Arsenic, antimony, and Leishmania: has arsenic contamination of drinking water in India led to treatment- resistant kala-azar?Thursday, August 27, 2015
Perry M, Wyllie S, Prajapati V, Menten J, Raab A, Feldmann J, Chakraborti D, Sundar S, Boelaert M, Picado A, Fairlamb A,
Lancet (London, England). 26-Feb-2015
Wellcome Trust.
Novel plasma microRNA biomarkers for the identification of colitis-associated carcinoma.Thursday, August 27, 2015
Patel M, Verma A, Aslam I, Pringle H, Singh B,
Lancet (London, England). 26-Feb-2015
Royal College of Surgeons of England.
The role of BUB and CDC proteins in low-grade breast cancers.Thursday, August 27, 2015
Mukherjee A, Joseph C, Craze M, Chrysanthou E, Ellis IO,
Lancet (London, England). 26-Feb-2015
Pathological Society of Great Britain and Northern Ireland, National Institute for Health Research.
Assessment of glycogen phosphorylase isoenzyme BB as a biomarker for pre-eclampsia and small for gestational age.Thursday, August 27, 2015
McCarthy F, Doyle A, Khashan A, Kenny L,
Lancet (London, England). 26-Feb-2015
National Institute for Health Research, SCOPE Study was funded by the Health Research Board. This work was performed in the Irish Centre for Fetal and Neonatal Translational Research and partly supported by Science Foundation Ireland.
Characteristics of immunosuppressive regulatory T cells in cutaneous squamous cell carcinomas and role in metastasis.Thursday, August 27, 2015
Lai C, August S, Behar R, Polak M, Ardern-Jones M, Theaker J, Al-Shamkhani A, Healy E,
Lancet (London, England). 26-Feb-2015
Wellcome Trust, National Institute for Health Research.
Inhibition of complement C3 and fibrinogen interaction: a potential novel therapeutic target to reduce cardiovascular disease in diabetes.Thursday, August 27, 2015
King R, Tiede C, Simmons K, Fishwick C, Tomlinson D, Ajjan R,
Lancet (London, England). 26-Feb-2015
Sir Jules Thorn Charitable Trust.
Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines.Thursday, August 27, 2015
Khaled YS, Wright K, Melcher A, Jayne D,
Lancet (London, England). 26-Feb-2015
National Institute for Health Research.
Genome-wide transcription profiling in neutrophils in acute respiratory distress syndrome.Thursday, August 27, 2015
Juss J, Herre J, Begg M, Bradley G, Lennon M, Amour A, House D, Hessel EM, Summers C, Condliffe AM, Chilvers ER,
Lancet (London, England). 26-Feb-2015
National Institute for Health Research, GlaxoSmithKline.
Regulation of neutrophilic inflammation in lung injury induced by community-acquired pneumonia.Thursday, August 27, 2015
José R, Williams A, Sulikowski M, Brealey D, Brown J, Chambers R,
Lancet (London, England). 26-Feb-2015
Wellcome Trust.
A role for helminth parasites in achieving immunological tolerance in transplantation.Thursday, August 27, 2015
Johnston C, McSorley H, Smyth D, Anderton S, Wigmore S, Maizels R,
Lancet (London, England). 26-Feb-2015
Wellcome Trust.
Multidimensional endotypes of asthma: topological data analysis of cross-sectional clinical, pathological, and immunological data.Thursday, August 27, 2015
Hinks T, Zhou X, Staples K, Dimitrov B, Manta A, Petrossian T, Lum P, Smith C, Ward J, Howarth P, Walls A, Gadola SD, Djukanović R,
Lancet (London, England). 26-Feb-2015
Wellcome Trust.
Effect of tissue inhibitor of metalloproteinases 3 on DLK1 shedding in cultured human pre-adipocytes and implications for adipose tissue remodelling.Thursday, August 27, 2015
Fenech M, Gavrilovic J, Turner J,
Lancet (London, England). 26-Feb-2015
British Heart Foundation, Diabetes Research and Wellness Foundation Open Funding 2011.
CD4+CD28- T-cell expansions in ANCA-associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial.Thursday, August 27, 2015
Chanouzas D, Dyall L, Dale J, Moss P, Morgan M, Harper L,
Lancet (London, England). 26-Feb-2015
Wellcome Trust, Vasculitis UK.
Identification of novel biomarkers in plasma for prediction of treatment response in patients with heart failure.Thursday, August 27, 2015
Cao TH, Quinn PA, Sandhu JK, Voors AA, Lang CC, Parry HM, Mohan M, Jones DJ, Ng LL,
Lancet (London, England). 26-Feb-2015
European Union's Seventh Framework Programme (BIOSTAT-CHF), John and Lucille van Geest Foundation.
CD57 expression in CD8 T cells and development of cutaneous squamous cell carcinoma in renal transplant recipients: a prospective cohort study.Thursday, August 27, 2015
Bottomley M, Harden P, Wood K,
Lancet (London, England). 26-Feb-2015
Wellcome Trust, Oxford University Hospitals Research Services Committee.
Pleiotropic effects of statins in hypercholesterolaemia: a prospective observational study using a lipoproteomic based approach.Thursday, August 27, 2015
Bhandari S, Gupta P, Quinn P, Sandhu J, Hakimi A, Jones D, Ng L,
Lancet (London, England). 26-Feb-2015
British Heart Foundation.
Tumour metabolism in squamous cell carcinoma of the head and neck: an in-vitro study of the consequences of TP53 mutation and therapeutic implications.Thursday, August 27, 2015
Wilkie M, Lau A, Vlatkovic N, Jones T, Boyd M,
Lancet (London, England). 26-Feb-2015
Cancer Research UK, Royal College of Surgeons of England.
Immunoprofile from tissue microarrays to stratify familial breast cancer patients.Thursday, August 27, 2015
Schirosi L, De Summa S, Tommasi S, Paradiso A, Sambiasi D, Popescu O, Simone G, Mangia A,
Oncotarget. 3-Aug-2015
Familial breast cancer (BC) is a heterogeneous disease with variable prognosis. The identification of an immunoprofile is important to predict tumor behavior for the routine clinical management of familial BC patients. Using immunohistochemistry on tissue microarrays, we studied 95 familial BCs in order to analyze the expression of some biomarkers involved in different pathways. We used unsupervised hierarchical clustering analyses (HCA), performed using the immunohistochemical score data, to define an immunoprofile able to characterize these tumors. The analyses on 95 and then on a subset of 45 tumors with all biomarkers contemporarily evaluable, revealed the same biomarker and patient clusters. Focusing on the 45 tumors we identified a group of patients characterized by the low expression of estrogen receptor (P = 0.009), progesterone receptor (P < 0.001), BRCA1 (P = 0.005), nuclear Na+/H+ exchanger regulatory factor 1 (NHERF1) (P = 0.026) and hypoxia inducible factor-1 alpha (P < 0.001), and also by the higher expression of MIB1 (P = 0.043), cytoplasmic NHERF1 (P = 0.004), cytoplasmic BRCT-repeat inhibitor of hTERT expression (P = 0.001), vascular endothelial growth factor (VEGF) (P = 0.024) and VEGF receptor-1 (P = 0.029). This immunoprofile identified a more aggressive tumor phenotype associated also with a larger tumor size (P = 0.012) and G3 grade (P = 0.006), confirmed by univariate and multivariate analyses. In conclusion, the clinical application of HCA of immunohistochemical data could allow the assessment of prognostic biomarkers to be used simultaneously. The 10 protein expression panel might be used to identify the more aggressive tumor phenotype in familial BC and to direct patients towards a different clinical therapy.
Different Mechanisms of Regulation of the Warburg Effect in Lymphoblastoid and Burkitt Lymphoma Cells.Thursday, August 27, 2015
Mushtaq M, Darekar S, Klein G, Kashuba E,
PloS one. 3-8-2015
Our data suggest that aerobic glycolysis, or the Warburg effect, in BL cells is regulated by MYC expressed at high levels, whereas in LCLs, HIF1A is responsible for this phenomenon.
High-Throughput All-Optical Analysis of Synaptic Transmission and Synaptic Vesicle Recycling in Caenorhabditis elegans.Thursday, August 27, 2015
Wabnig S, Liewald JF, Yu SC, Gottschalk A,
PloS one. 27-8-2015
Synaptic vesicles (SVs) undergo a cycle of biogenesis and membrane fusion to release transmitter, followed by recycling. How exocytosis and endocytosis are coupled is intensively investigated. We describe an all-optical method for identification of neurotransmission genes that can directly distinguish SV recycling factors in C. elegans, by motoneuron photostimulation and muscular RCaMP Ca2+ imaging. We verified our approach on mutants affecting synaptic transmission. Mutation of genes affecting SV recycling (unc-26 synaptojanin, unc-41 stonin, unc-57 endophilin, itsn-1 intersectin, snt-1 synaptotagmin) showed a distinct 'signature' of muscle Ca2+ dynamics, induced by cholinergic motoneuron photostimulation, i.e. faster rise, and earlier decrease of the signal, reflecting increased synaptic fatigue during ongoing photostimulation. To facilitate high throughput, we measured (3-5 times) ~1000 nematodes for each gene. We explored if this method enables RNAi screening for SV recycling genes. Previous screens for synaptic function genes, based on behavioral or pharmacological assays, allowed no distinction of the stage of the SV cycle in which a protein might act. We generated a strain enabling RNAi specifically only in cholinergic neurons, thus resulting in healthier animals and avoiding lethal phenotypes resulting from knockdown elsewhere. RNAi of control genes resulted in Ca2+ measurements that were consistent with results obtained in the respective genomic mutants, albeit to a weaker extent in most cases, and could further be confirmed by opto-electrophysiological measurements for mutants of some of the genes, including synaptojanin. We screened 95 genes that were previously implicated in cholinergic transmission, and several controls. We identified genes that clustered together with known SV recycling genes, exhibiting a similar signature of their Ca2+ dynamics. Five of these genes (C27B7.7, erp-1, inx-8, inx-10, spp-10) were further assessed in respective genomic mutants; however, while all showed electrophysiological phenotypes indicative of reduced cholinergic transmission, no obvious SV recycling phenotypes could be uncovered for these genes.
Exercise on Progenitor Cells in Healthy Subjects and Patients with Type 1 Diabetes.Thursday, August 27, 2015
Waclawovsky G, Umpierre D, Figueira FR, de Lima ES, Alegretti AP, Schneider L, Matte US, Rodrigues TC, Schaan BD,
Medicine and science in sports and exercise. 27-Aug-2015
Despite the increased vascular reactivity in both groups after both exercise sessions, EPCs were only influenced by exercise in controls. The unchanged number of EPCs in T1DM after exercise sessions might indicate a blunted endothelium regenerating capacity, revealing an early deterioration of the functional arterial characteristics not disclosed by only evaluating vascular functional variables.
Free 25(OH)D and Calcium Absorption, PTH and Markers of Bone Turnover.Thursday, August 27, 2015
Aloia J, Dhaliwal R, Mikhail M, Shieh A, Stolberg A, Ragolia L, Fazzari M, Abrams SA,
The Journal of clinical endocrinology and metabolism. 27-Aug-2015
There was no advantage of measuring free over total 25(OH)D in assessing the response of calcium absorption, PTH and markers of bone turnover to vitamin D. Free 25(OH)D responded to increasing doses of vitamin D in a similar fashion to total 25(OH)D.
Dual enzyme-responsive "turn-on" fluorescence sensing systems based on in situ formation of 7-hydroxy-2-iminocoumarin scaffolds.Thursday, August 27, 2015
Debieu S, Romieu A,
Organic & biomolecular chemistry. 27-Aug-2015
A new strategy for the simultaneous fluorogenic detection of two distinct enzyme activities namely hydrolase (amidase or esterase) and reductase is described. This innovative biosensing method is based on the powerful "covalent-assembly" principle that involves in situ synthesis of a fluorophore from a non-fluorescent caged precursor and through domino reactions triggered by the two analytes of interest. To establish this approach, penicillin G acylase (PGA) (or pig liver esterase (PLE)) and nitroreductase (NTR) were chosen as model enzymes, and original bis-O-protected 2,4-dihydroxycinnamonitrile derivatives acting as dual-reactive probes readily convertible to highly fluorescent 7-hydroxy-2-iminocoumarin scaffolds upon reacting with the two selected enzymes were synthesised. The two phenolic groups available within the core structure of these probes play a pivotal role in generating iminocoumarin scaffold through an intramolecular cyclisation reaction (hydroxyl group in C-2 position) and in enhancing its push-pull character (hydroxyl group in C-4 position). Their orthogonal and temporary protection with two different enzyme-labile masking groups is the cornerstone in the design of this novel class of fluorogenic "turn-on" probes. Their evaluation using fluorescence-based in vitro assays and HPLC-fluorescence/-MS analyses have enabled us both to demonstrate the claimed activation mechanism (in particular the specific order in which the two enzymes react with the probe) and to highlight the potential utility of these advanced chemical tools in multi-analyte sensing applications.
Enzyme-Free Detection of Mutations in Cancer DNA Using Synthetic Oligonucleotide Probes and Fluorescence Microscopy.Thursday, August 27, 2015
Miotke L, Maity A, Ji H, Brewer J, Astakhova K,
PloS one. 27-8-2015
Overall, the novel assay we describe could become a new approach to rapid, reliable and enzyme-free diagnostics of cancer or other associated DNA targets. Importantly, stoichiometry of wild type and mutant targets is conserved in our assay, which allows for an accurate estimation of mutant abundance when the detection limit requirement is met. Using fluorescence microscopy, this approach presents the opportunity to detect DNA at single-molecule resolution and directly in the biological sample of choice.
Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study.Thursday, August 27, 2015
Rahgozar S, Amirian T, Qi M, Shahshahan Z, Entezar-E-Ghaem M, Ghasemi Tehrani H, Miroliaei M, Krilis SA, Giannakopoulos B,
PloS one. 27-8-2015
Patients with pre-eclampsia had substantially lower levels of free thiol angiotensinogen compared to healthy pregnant controls, whilst maintaining similar total angiotensinogen levels in the plasma. Hence, elevated levels of plasma oxidized angiotensinogen may be a contributing factor to hypertension in the setting of pre-eclampsia.
Ultrasensitive and specific measurement of protease activity using functionalized photonic crystals.Thursday, August 27, 2015
Gupta B, Mai K, Lowe SB, Wakefield D, Di Girolamo N, Gaus K, Reece PJ, Gooding JJ,
Analytical chemistry. 27-Aug-2015
Herein is presented a microsensor technology as a diagnostic tool for detecting specific matrix metalloproteinases (MMPs) at very low concentrations. MMP-2 and MMP-9 are detected using label free porous silicon (PSi) photonic crystals that have been made selective for a given MMP by filling the nanopores with synthetic polymeric substrates containing a peptide sequence for that MMP. Proteolytic cleavage of the peptide sequence results in a shift in wavelength of the main peak in the reflectivity spectrum of the PSi device, which is dependent on the amount of MMP present. The ability to detect picogram amounts of MMP-2 and MMP-9 released primary retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells stimulated with lipopolysaccharide (LPS) is demonstrated. It was found that both cell types secrete higher amounts of MMP-2 than MMP-9 in their stimulated state, with RPE cells producing higher amounts of MMPs than IPE cells. The microsensor performance was compared to conventional protease detection systems, including zymography and enzyme linked immunosorbent assay (ELISA). It was found that the PSi microsensors were more sensitive than gelatin zymography; PSi microsensors detected the presence of both MMP-2 and MMP-9 while zymography could only detect MMP-2 levels. The MMP-2 and MMP-9 quantification correlated well with the ELISA. This new method of detecting protease activity shows superior performance to conventional protease assays and has the potential for translation to high-throughput multiplexed analysis.
The effects of carbamazepine on macroinvertebrate species: Comparing bivalves and polychaetes biochemical responses.Thursday, August 27, 2015
Freitas R, Almeida Â, Pires A, Velez C, Calisto V, Schneider RJ, Esteves VI, Wrona FJ, Figueira E, Soares AM,
Water research. 5-Aug-2015
In the present study, the bivalve Scrobicularia plana and the polychaete Diopatra neapolitana were exposed to an increasing carbamazepine (CBZ) concentration gradient. Both species are among the most widely used bioindicators, and CBZ is one of the most commonly found drugs in the aquatic environment. After a chronic exposure (28 days), the results obtained revealed that CBZ induced biochemical alterations in both species. Our findings demonstrated that S. plana and D. neapolitana reduced the CBZ accumulation rate at higher CBZ concentrations, probably due to their capacity to decrease their feeding rates at stressful conditions. Nevertheless, this defence mechanism was not enough to prevent both species from oxidative stress. In fact, S. plana and D. neapolitana were not able to efficiently activate their antioxidant defence mechanisms which resulted in the increase of lipid peroxidation, especially at the highest CBZ concentrations. Comparing both species, it seems that S. plana was the most sensitive species since stronger biochemical alterations were observed in this species.
Triggerable Degradation of Polyurethanes for Tissue Engineering Applications.Thursday, August 27, 2015
Xu C, Huang Y, Wu J, Tang L, Hong Y,
ACS applied materials & interfaces. 27-Aug-2015
Tissue engineered and bioactive scaffolds with different degradation rates are required for the regeneration of diverse tissues/organs. To optimize tissue regeneration in different tissues, it is desirable that the degradation rate of scaffolds can be manipulated to comply with various stages of tissue regeneration. Unfortunately, the degradation of most degradable polymers rely solely on passive controlled degradation mechanisms. To overcome this challenge, we report a new family of reduction-sensitive biodegradable elastomeric polyurethanes containing various amounts of disulfide bonds (PU-SS), in which degradation can be initiated and accelerated with the supplement of a biological product - antioxidant-glutathione (GSH). The polyurethanes can be processed into films and electrospun fibrous scaffolds. Synthesized materials exhibited robust mechanical properties and high elasticity. Accelerated degradation of the materials was observed in the presence of GSH, and the rate of such degradation depends on the amount of disulfide present in the polymer backbone. The polymers and their degradation products exhibited no apparent cell toxicity while the electrospun scaffolds supported fibroblast growth in vitro. The in vivo subcutaneous implantation model showed that the polymers prompt minimal inflammatory responses, and, as anticipated, the polymer with the higher disulfide bond amount had a faster degradation in vivo. This new family of polyurethanes offers tremendous potential of directed scaffold degradation to promote maximal tissue regeneration.
Correlation between radiation dose and p53 protein expression levels in human lymphocytes.Thursday, August 27, 2015
Cavalcanti MB, Fernandes TS, Silva EB, Amaral A,
Anais da Academia Brasileira de Ciencias. 25-Aug-2015
The aim of this research was to evaluate the relationship between p53 protein levels and absorbed doses from in vitro irradiated human lymphocytes. For this, samples of blood from 23 donors were irradiated with 0.5; 1; 2; and 4 Gy from a Cobalt-60 source, and the percentages of lymphocytes expressing p53 were scored using Flow Cytometry. The subjects were divided into 3 groups, in accordance with the p53 levels expressed per radiation dose: low (Group I), high (Group II), and excessive levels (Group III). For all groups, the analyses showed that the p53 expression levels increase with the absorbed dose. Particularly for groups I and II, the correlation between this protein expression and the dose follows the linear-quadratic model, such as for radioinduced chromosomal aberrations. In conclusion, our findings indicate possible applications of this approach in evaluating individual radiosensitivity prior to radiotherapeutical procedures as well as in medical surveillance of occupationally exposed workers. Furthermore, due to the rapidity of flow-cytometric analyses, the methodology here employed would play an important role in emergency responses to a large-scale radiation incident where many people may have been exposed.
Natural Products From Marine Algae. Preface.Wednesday, August 26, 2015
Stengel DB, Connan S,
Methods in molecular biology (Clifton, N.J.). 2015
Wading through the noise of "multi-omics" to identify prognostic biomarkers in hepatocellular carcinoma.Friday, August 28, 2015
Pineda-Solis K, McAlister V,
Hepatobiliary surgery and nutrition. Aug-2015
Multi-omics, the molecular analysis of genes, transcriptional RNA and proteins, allows researchers document the mechanism of action of a target gene. However multi-omics may result in an avalanche of information when used to screen a population. It is very difficult to discern a pattern or signal related to a disease or its progression. Differential multi-omics exploits our ability to see differences between subjects who are similar in all respects except for the outcome being tested. Twin studies are an example of this. Miao and colleagues compared two patients who had diverse outcomes following treatment of multi-focal hepatocellular carcinoma (HCC) to identify seven candidates as the responsible genes. In a larger cohort of patients with HCC they narrowed the field down to a single target down. By looking at progression of HCC, they isolated TTK, a protein kinase which disrupts the interaction of the tumour suppressor p53 with the oncogene MDM2. TTK-high tumours recurred 3 times faster than TTK-low tumours.
Luteolin inhibits progestin-dependent angiogenesis, stem cell-like characteristics, and growth of human breast cancer xenografts.Friday, August 28, 2015
Cook MT, Liang Y, Besch-Williford C, Goyette S, Mafuvadze B, Hyder SM,
SpringerPlus. 2015
Luteolin effectively blocks progestin-dependent human breast cancer tumor growth and the stem cell-like phenotype in human breast cancer cells.
Characterization of 13 microsatellite markers for Calochortus gunnisonii (Liliaceae) from Illumina MiSeq sequencing.Thursday, August 27, 2015
Fuller RS, Frietze S, McGlaughlin ME,
Applications in plant sciences. Aug-2015
These primers will be useful for genetic and evolutionary studies across C. gunnisonii's range within the southern and central Rocky Mountains. Furthermore, these markers have proven valuable for cross-species amplifications within Calochortus.
Microsatellite markers for studies with the carnivorous plant Philcoxia minensis (Plantaginaceae).Thursday, August 27, 2015
Scatigna AV, Oliveira FA, Mantello CC, Francisco PM, Souza AP, Simões AO,
Applications in plant sciences. Aug-2015
The 12 polymorphic microsatellite markers are suitable for studies in genetic diversity and structure, mating system, and gene flow in P. minensis and also may be useful for similar issues regarding the related species P. bahiensis.
An empirical review: Characteristics of plant microsatellite markers that confer higher levels of genetic variation.Thursday, August 27, 2015
Merritt BJ, Culley TM, Avanesyan A, Stokes R, Brzyski J,
Applications in plant sciences. Aug-2015
During microsatellite marker development, researchers must choose from a pool of possible primer pairs to further test in their species of interest. In many cases, the goal is maximizing detectable levels of genetic variation. To guide researchers and determine which markers are associated with higher levels of genetic variation, we conducted a literature review based on 6782 genomic microsatellite markers published from 1997-2012. We examined relationships between heterozygosity (H e or H o) or allele number (A) with the following marker characteristics: repeat type, motif length, motif region, repeat frequency, and microsatellite size. Variation across taxonomic groups was also analyzed. There were significant differences between imperfect and perfect repeat types in A and H e. Dinucleotide motifs exhibited significantly higher A, H e, and H o than most other motifs. Repeat frequency and motif region were positively correlated with A, H e, and H o, but correlations with microsatellite size were minimal. Higher taxonomic groups were disproportionately represented in the literature and showed little consistency. In conclusion, researchers should carefully consider marker characteristics so they can be tailored to the desired application. If researchers aim to target high genetic variation, dinucleotide motif lengths with large repeat frequencies may be best.
Relationships Between Pharmacovigilance, Molecular, Structural, and Pathway Data: Revealing Mechanisms for Immune-Mediated Drug-Induced Liver Injury.Friday, August 28, 2015
Ho SS, McLachlan AJ, Chen TF, Hibbs DE, Fois RA,
CPT: pharmacometrics & systems pharmacology. Jul-2015
Immune-mediated drug-induced liver injury (IMDILI) can be devastating, irreversible, and fatal in the absence of successful transplantation surgery. We present a novel approach that combines the methods of pharmacoepidemiology with in silico molecular modeling to identify specific features in toxic ligands that are associated with clinical features of IMDILI. Specifically, from pharmacovigilance data multivariate logistic regression identified 18 drugs associated with IMDILI (P < 0.00015). Eleven of these drugs, along with their known and proposed metabolites, constituted a training set used to develop a four-point pharmacophore model (sensitivity 75%; specificity 85%). Subsequently, this information was combined with information from immune-pathway reviews and genetic-association studies and complemented with ligand-protein docking simulations to support a hypothesis implicating two putative targets within separate, possibly interacting, immune-system pathways: the major histocompatibility complex within the adaptive immune system and Toll-like receptors (TLRs), in particular TLR-7, which represent pattern recognition receptors of the innate immune system.
Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers.Friday, August 28, 2015
Nayak S, Lee D, Patel-Hett S, Pittman DD, Martin SW, Heatherington AC, Vicini P, Hua F,
CPT: pharmacometrics & systems pharmacology. Jul-2015
A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors' concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment.
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