bluuebunny/crossref_metadata_2025_split huggingface dataset:
NS5A inhibitors for the treatment of hepatitis C infection
Authors: Gitto Stefano , Gamal Nesrine , Andreone Pietro 
Published: December 2016

AbstractToday, we are witnessing a new era for the treatment of hepatitis C with excellent rates of virologic response and very good safety profiles. Among the many classes of direct‐acting antivirals, the inhibitors of nonstructural protein 5A are particularly interesting. NS5A is a phosphorylated protein with a relevant role in viral replication. HCV‐NS5A inhibitors show high potency, very good safety profile and high barrier to resistance. The amazing in vitro effectiveness of this class is associated with great efficacy in clinical trials in combination protocols with antivirals of other classes, with sustained virological response (SVR) obtained in more than 90% of patients. Herein, we sought to review the current knowledge regarding the NS5A protease complex inhibitors with special emphasis on clinical efficacy and development of viral resistance.
Hepatitis C viraemia reversibly maintains subset of antigen‐specific T‐bet+ tissue‐like memory B cells
Authors: Chang L.‐Y. , Li Y. , Kaplan D. E. 
Published: December 2016

SummaryBackground: Chronic antigen exposure and/or ageing increases the frequency of T‐box expressed in T cells (T‐bet)‐expressing B‐lymphocytes in mice. The frequency and significance of B‐cell T‐bet expression during chronic hepatitis C (HCV) infection in human subjects has never been described. Methods: Healthy controls, cirrhotic and noncirrhotic HCV‐infected patients, and non‐HCV patients with cirrhosis were recruited. Peripheral blood mononuclear cells were phenotyped for expression of T‐bet and related markers by flow cytometry. In a subset of patients who underwent antiviral therapy and were cured of HCV infection (sustained virological response), the dynamics of T‐bet expression in B cells was monitored. After cure, convalescent B cells were tested for T‐bet expression after re‐exposure to infected plasma or recombinant HCV proteins. Results: Forty‐nine patients including 11 healthy donors, 30 hepatitis C‐infected individuals (nine with liver cancer, 13 with cirrhosis, eight without cirrhosis) and eight patients with cirrhosis due to non‐HCV‐related cause were recruited. We found that B cells in patients with chronic HCV exhibited increased frequency of T‐bet+ B cells relative to noninfected individuals (median 11.5% v. 2.2%, P<.0001) but that there were no significant differences between noncirrhotic, cirrhotic and cancer‐bearing infected individuals. T‐Bet+ B cells expressed higher levels of CD95, CXCR3, CD11c, CD267 and FcRL5 compared to T‐bet− B cells and predominantly exhibit a tissue‐like memory CD27−CD21− phenotype independent of HCV infection. T‐bet+ B cells in HCV‐infected patients were more frequently class‐switched IgD−IgG+ (40.4% vs. 26.4%, P=.012). Resolution of HCV infection with direct‐acting antiviral (DAA) therapy leads to a marked reduction in the frequency of T‐bet+ B cells (median 14.1% pretreatment v. 6.7% end of treatment v. 6.1% SVR12, P≤.01). Re‐exposure of convalescent (cured) B cells to viremic plasma and recombinant HCV E2 protein led to re‐expression of T‐bet. Conclusion: Chronic antigenemia in chronic HCV infection induces and maintains an antigen‐specific T‐bet+ B cell. These B cells share markers with tissue‐like memory B cells. Antigen‐driven T‐bet expression may be a critical suppressor of B‐cell activation in chronic HCV infection.
Transient severe tricuspid regurgitation after transplantation of an extremely oversized donor heart in a child—Does size matter? A case report
Authors: Birnbaum J. , Ulrich S. M. , Schramm R. , Hagl C. , Lehner A. , Fischer M. , Haas N. A. , Heineking B. 
Published: December 2016

AbstractIn pediatric heart transplantation, the size of the donor organ is an important criterion for organ allocation. Oversized donor hearts are often accepted with good results, but some complications in relation to a high donor‐recipient ratio have been described. Our patient was transplanted for progressive heart failure in dilated cardiomyopathy. The donor‐to‐recipient weight ratio was 3 (donor weight 65 kg, recipient weight 22 kg). The intra‐operative echocardiography before chest closure showed excellent cardiac function, no tricuspid valve regurgitation, and a normal central venous pressure. After chest closure, central venous pressure increased substantially and echocardiography revealed a severe tricuspid insufficiency. As other reasons for right ventricular dysfunction, that is, myocardial ischemia, pulmonary hypertension, and rejection, were excluded, we assumed that the insufficiency was caused by an alteration of the right ventricular geometry. After 1 week, the valve insufficiency regressed to a minimal degree. In pediatric heart transplant patients with a high donor‐to‐recipient weight ratio, the outlined complication may occur. If other reasons for right ventricular heart failure can be ruled out, this entity is most likely caused by an acute and transient alteration of the right ventricular geometry that may disappear over time.
Light Regulation of Alternative Pre‐mRNA Splicing in Plants
Authors: Zhang Hangxiao , Lin Chentao , Gu Lianfeng 
Published: December 2016

AbstractAlternative splicing (AS) is a major post‐transcriptional mechanism to enhance the diversity of proteome in response to environmental signals. Among the numerous external signals perceived by plants, light is the most crucial one. Plants utilize complex photoreceptor signaling networks to sense different light conditions and adjust their growth and development accordingly. Although light‐mediated gene expression has been widely investigated, little is known regarding the mechanism of light affecting AS to modulate mRNA at the post‐transcriptional level. In this minireview, we summarize current progresses on how light affects AS, and how sensory photoreceptors and retrograde signaling pathways may coordinately regulate AS of pre‐mRNAs. In addition, we also discuss the possibility that AS of the mRNAs encoding photoreceptors may be involved in feedback control of AS. We hypothesize that light regulation of the expression and activity of splicing factors would be a major mechanism of light‐mediated AS. The combination of genetic study and high‐throughput analyses of AS and splicing complexes in response to light is likely to further advance our understanding of the molecular mechanisms underlying light control of AS and plant development.
A pupil size response model to assess fear learning
Authors: Korn Christoph W. , Staib Matthias , Tzovara Athina , Castegnetti Giuseppe , Bach Dominik R. 
Published: December 2016

AbstractDuring fear conditioning, pupil size responses dissociate between conditioned stimuli that are contingently paired (CS+) with an aversive unconditioned stimulus, and those that are unpaired (CS‐). Current approaches to assess fear learning from pupil responses rely on ad hoc specifications. Here, we sought to develop a psychophysiological model (PsPM) in which pupil responses are characterized by response functions within the framework of a linear time‐invariant system. This PsPM can be written as a general linear model, which is inverted to yield amplitude estimates of the eliciting process in the central nervous system. We first characterized fear‐conditioned pupil size responses based on an experiment with auditory CS. PsPM‐based parameter estimates distinguished CS+/CS‐ better than, or on par with, two commonly used methods (peak scoring, area under the curve). We validated this PsPM in four independent experiments with auditory, visual, and somatosensory CS, as well as short (3.5 s) and medium (6 s) CS/US intervals. Overall, the new PsPM provided equal or decisively better differentiation of CS+/CS‐ than the two alternative methods and was never decisively worse. We further compared pupil responses with concurrently measured skin conductance and heart period responses. Finally, we used our previously developed luminance‐related pupil responses to infer the timing of the likely neural input into the pupillary system. Overall, we establish a new PsPM to assess fear conditioning based on pupil responses. The model has a potential to provide higher statistical sensitivity, can be applied to other conditioning paradigms in humans, and may be easily extended to nonhuman mammals.
Asymmetric Effects of Exchange Rate Changes and the J‐curve: New Evidence from 61 Malaysia–Thailand Industries
Authors: Bahmani‐Oskooee Mohsen , Aftab Muhammad 
Published: December 2016

AbstractResearch on the impact of currency depreciation on the trade balance is now moving in a new direction by incorporating nonlinear dynamic adjustment of the exchange rate and by using a nonlinear approach to error‐correction modeling and cointegration. Using these advances, researchers find not only more evidence of the J‐curve effect, but also new evidence of asymmetric effects of exchange rate changes on the trade balance. We contribute to this line of research by using monthly trade flow data from 61 two‐digit industries that trade between Malaysia and Thailand, and show that not only does currency depreciation have favorable effects on the trade balance of more industries, but the long‐run effects are asymmetric in 26 out of 61 cases. In line with current literature, our nonlinear model performs much better than the linear model when industry level data are used.
Identification of Bicarbonate as a Trigger and Genes Involved with Extracellular DNA Export in Mycobacterial Biofilms
Authors: Rose Sasha J. , Bermudez Luiz E. 
Published: December 2016

ABSTRACT

Extracellular DNA (eDNA) is an integral biofilm matrix component of numerous pathogens, including nontuberculous mycobacteria (NTM). Cell lysis is the source of eDNA in certain bacteria, but the source of eDNA remains unidentified for NTM, as well as for other eDNA-containing bacterial species. In this study, conditions affecting eDNA export were examined, and genes involved with the eDNA export mechanism were identified. After a method for monitoring eDNA in real time in undisturbed biofilms was established, different conditions affecting eDNA were investigated. Bicarbonate positively influenced eDNA export in a pH-independent manner in
Mycobacterium avium
,
M. abscessus
, and
M. chelonae
. The surface-exposed proteome of
M. avium
in eDNA-containing biofilms revealed abundant carbonic anhydrases. Chemical inhibition of carbonic anhydrases with ethoxzolamide significantly reduced eDNA export. An unbiased transposon mutant library screen for eDNA export in
M. avium
identified many severely eDNA-attenuated mutants, including one not expressing a unique FtsK/SpoIIIE-like DNA-transporting pore, two with inactivation of carbonic anhydrases, and nine with inactivation of genes belonging to a unique genomic region, as well as numerous mutants involved in metabolism and energy production. Complementation of nine mutants that included the FtsK/SpoIIIE and carbonic anhydrase significantly restored eDNA export. Interestingly, several attenuated eDNA mutants have mutations in genes encoding proteins that were found with the surface proteomics, and many more mutations are localized in operons potentially encoding surface proteins. Collectively, our data strengthen the evidence of eDNA export being an active mechanism that is activated by the bacterium responding to bicarbonate.

IMPORTANCE
Many bacteria contain extracellular DNA (eDNA) in their biofilm matrix, as it has various biological and physical functions. We recently reported that nontuberculous mycobacteria (NTM) can contain significant quantities of eDNA in their biofilms. In some bacteria, eDNA is derived from dead cells, but that does not appear to be the case for all eDNA-containing organisms, including NTM. In this study, we found that eDNA export in NTM is conditionally dependent on the molecules to which the bacteria are exposed and that bicarbonate positively influences eDNA export. We also identified genes and proteins important for eDNA export, which begins to piece together a description of a mechanism for eDNA. Better understanding of eDNA export can give new targets for the development of antivirulence drugs, which are attractive because resistance to classical antibiotics is currently a significant problem.
Colorectal cancer mortality 10 years after a single round of guaiac faecal occult blood test (gFOBT) screening: experiences from a Danish screening cohort
Authors: Bjerrum Andreas , Andersen Ole , Fischer Anders , Lindebjerg Jan , Lynge Elsebeth 
Published: December 2016

BackgroundIn Denmark, colorectal cancer (CRC) is the third most frequent cancer. Randomised trials have shown that guaiac faecal occult blood test (gFOBT) screening can reduce CRC mortality, but a recent large randomised study from Finland did not find any effect. A feasibility study was carried out in Denmark in 2005–2006 where residents aged 50–74 years in 2 Danish counties were invited once to participate in gFOBT screening. We used the unique Danish registers to assess the impact of gFOBT screening in this group on CRC incidence and mortality.MethodsIn this cohort study, we followed a group comprising 166 277 individuals invited to screening and a reference group comprising the remaining 1 240 348 Danes of the same age. We linked the Danish population and health service registers to obtain information about colonoscopies, polypectomies, incident CRC and cause of death.ResultsAfter a median follow-up time of 8.9 years, the CRC mortality was significantly lower in the screening group than in the reference group with an adjusted HR (aHR) of 0.92 (95% CI 0.86 to 0.99), while the aHR for all-cause mortality was 0.95 (95% CI 0.94 to 0.96). For screening participants, the aHR for CRC mortality and all-cause mortality was 0.72 (0.64 to 0.80) and 0.59 (0.57 to 0.60), respectively.ConclusionsAbout 10 years after a single round of gFOBT screening, we found a significant 8% deficit in CRC mortality in the screening group compared with other Danes. We found almost the same deficit in all-cause mortality, and on this basis, it is not possible to conclude that one screening round had an effect on CRC mortality. Our study indicated that close monitoring of the outcome of CRC screening is warranted.
Breast feeding initiation rate across Western countries: does religion matter? An ecological study
Authors: Bernard Jonathan Y , Cohen Emmanuel , Kramer Michael S 
Published: December 2016

BackgroundBreast feeding initiation rates remain below 80% in some Western countries. Many individual-level determinants are known; however, less is known regarding cultural and societal determinants, such as religion, that could explain population-level variations. We examined the correlations of the proportions of Catholics and Protestants with the breast feeding initiation rates across and within Western countries.MethodsUsing publicly available data, we carried out an ecological study comparing the proportions of Catholics and Protestants with the rates of breast feeding initiation. We correlated data at the country level, and additionally explored within-country data in five Western countries: France (Departments), Ireland (counties), the UK (countries), Canada (provinces) and the USA (states). Our analyses accounted for human development index, gross domestic product and population density.ResultsWe observed a negative correlation (r=−0.30) between the proportion of Catholics and the rate of breast feeding initiation in Western countries. This correlation was consistent when using within-country data in France (r=−0.27), Ireland (r=−0.23), the UK (r=−0.79) and Canada (r=−0.62). In the USA, the positive correlation (r=0.26) between a state's proportion of Catholics and its breast feeding initiation rate was confounded by race, education and socioeconomic status (SES). After controlling for education and SES, the state proportion of non-Hispanic white Catholics was negatively correlated (r=−0.29) with the rate of breast feeding initiation.ConclusionsIn this ecological study, we found consistent negative correlations between Catholicism and breast feeding initiation rates. Qualitative and quantitative studies at the individual level are needed to confirm and explain our findings. Our results suggest that women living in a country or region where Catholicism has historically dominated are less likely to initiate breast feeding, and that breast feeding promotion policies should be adapted to better fit populations' cultural and religious norms.
Hydrogen absorption in palladized MCM-41
Authors: Guthrie Colin P. , Reardon Eric J. 
Published: December 2016

Hydrogen absorption by palladium (Pd) in Pd/MCM-41 was studied at 298.2 ± 0.1 K and between 0.5 and 1.0 atm [Formula: see text]. Mass percent Pd loadings of 0.81%, 1.10%, 1.16%, and 2.30% of total Pd/MCM-41 were used. Absorption was measured in gas-tight stainless steel cells equipped with computer-logged pressure transducers. The average maximum hydrogen absorption for all samples was 0.85 ± 0.18 H/Pd. An apparent trend of increasing hydrogen absorption as the mass percent loading of Pd increased was determined to be non-significant. Similar experiments using Pd black showed a lower absorption of 0.79 ± 0.09 H/Pd.
The NCI-60 Methylome and Its Integration into CellMiner
Authors: Reinhold William C. , Varma Sudhir , Sunshine Margot , Rajapakse Vinodh , Luna Augustin , Kohn Kurt W. , Stevenson Holly , Wang Yonghong , Heyn Holger , Nogales Vanesa , Moran Sebastian , Goldstein David J. , Doroshow James H. , Meltzer Paul S. , Esteller Manel , Pommier Yves 
Published: December 2016

Abstract
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (∼21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and miRNA transcripts, DNA copy number, and protein levels. Here, we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2.0 (https://discover.nci.nih.gov/cellminer). Among new insights, transcript versus DNA methylation correlations revealed the epithelial/mesenchymal gene functional category as being influenced most heavily by methylation. DNA methylation and copy number integration with transcript levels yielded an assessment of their relative influence for 15,798 genes, including tumor suppressor, mitochondrial, and mismatch repair genes. Four forms of molecular data were combined, providing rationale for microsatellite instability for 8 of the 9 cell lines in which it occurred. Individual cell line analyses showed global methylome patterns with overall methylation levels ranging from 17% to 84%. A six-gene model, including PARP1, EP300, KDM5C, SMARCB1, and UHRF1 matched this pattern. In addition, promoter methylation of two translationally relevant genes, Schlafen 11 (SLFN11) and methylguanine methyltransferase (MGMT), served as indicators of therapeutic resistance or susceptibility, respectively. Overall, our database provides a resource of pharmacologic data that can reinforce known therapeutic strategies and identify novel drugs and drug targets across multiple cancer types. Cancer Res; 77(3); 601–12. ©2016 AACR.
The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in Drosophila Imaginal Tissues
Authors: Xie Gengqiang , Chen Hanqing , Jia Dongyu , Shu Zhiqiang , Palmer William Hunt , Huang Yi-Chun , Zeng Xiankun , Hou Steven X. , Jiao Renjie , Deng Wu-Min 
Published: December 2016

Abstract
Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression upon snr1-depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role in Drosophila imaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood. Cancer Res; 77(4); 862–73. ©2017 AACR.
RB Loss Promotes Prostate Cancer Metastasis
Authors: Thangavel Chellappagounder , Boopathi Ettickan , Liu Yi , Haber Alex , Ertel Adam , Bhardwaj Anshul , Addya Sankar , Williams Noelle , Ciment Stephen J. , Cotzia Paolo , Dean Jeffry L. , Snook Adam , McNair Chris , Price Matt , Hernandez James R. , Zhao Shuang G. , Birbe Ruth , McCarthy James B. , Turley Eva A. , Pienta Kenneth J. , Feng Felix Y. , Dicker Adam P. , Knudsen Karen E. , Den Robert B. 
Published: December 2016

Abstract
RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. Cancer Res; 77(4); 982–95. ©2016 AACR.
Glioblastoma Therapy Can Be Augmented by Targeting IDH1-Mediated NADPH Biosynthesis
Authors: Wahl Daniel R. , Dresser Joseph , Wilder-Romans Kari , Parsels Joshua D. , Zhao Shuang G. , Davis Mary , Zhao Lili , Kachman Maureen , Wernisch Stefanie , Burant Charles F. , Morgan Meredith A. , Feng Felix Y. , Speers Corey , Lyssiotis Costas A. , Lawrence Theodore S. 
Published: December 2016

Abstract
NADPH is a critical reductant needed in cancer cells to fuel the biosynthesis of deoxynucleotides and antioxidants and to sustain stress-survival responses after radiation-induced DNA damage. Thus, one rational strategy to attack cancer cells is to target their heavy reliance on NADPH. Here, we report that the isocitrate dehydrogenase IDH1 is the most strongly upregulated NADPH-producing enzyme in glioblastoma (GBM). IDH1 silencing in GBM cells reduced levels of NADPH, deoxynucleotides, and glutathione and increased their sensitivity to radiation-induced senescence. Rescuing these metabolic restrictions was sufficient to reverse IDH1-mediated radiosensitization. In a murine xenograft model of human GBM, we found that IDH1 silencing significantly improved therapeutic responses to fractionated radiotherapy, when compared with either treatment alone. In summary, our work offers a mechanistic rationale for IDH1 inhibition as a metabolic strategy to improve the response of GBM to radiotherapy. Cancer Res; 77(4); 960–70. ©2016 AACR.