bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competence for Genetic Transformation in Streptococcus pneumoniae: Mutations in σ
A
Bypass the ComW Requirement for Late Gene Expression
Authors: Tovpeko Yanina , Bai Junqin , Morrison Donald A. 
Published: June 2016

ABSTRACT

Streptococcus pneumoniae
is able to integrate exogenous DNA into its genome by natural genetic transformation. Transient accumulation of high levels of the only
S. pneumoniae
alternative σ factor is insufficient for development of full competence without expression of a second competence-specific protein, ComW. The Δ
comW
mutant is 10
4
-fold deficient in the yield of recombinants, 10-fold deficient in the amount of σ
X
activity, and 10-fold deficient in the amount of σ
X
protein. The critical role of ComW during transformation can be partially obviated by σ
A
mutations clustered on surfaces controlling affinity for core RNA polymerase (RNAP). While strains harboring σ
A
mutations in the
comW
mutant background were transforming at higher rates, the mechanism of transformation restoration was not clear. To investigate the mechanism of transformation restoration, we measured late gene expression in σ
A
* suppressor strains. Restoration of late gene expression was observed in Δ
comW
σ
A
* mutants, indicating that a consequence of the σ
A
* mutations is, at least, to restore σ
X
activity. Competence kinetics were normal in Δ
comW
σ
A
* strains, indicating that strains with restored competence exhibit the same pattern of transience as wild-type (WT) strains. We also identified a direct interaction between ComW and σ
X
using the yeast two-hybrid (Y2H) assay. Taken together, these data are consistent with the idea that ComW increases σ
X
access to core RNAP, pointing to a direct role of ComW in σ factor exchange during genetic transformation. However, the lack of late gene shutoff in Δ
comW
mutants also points to a potential new role for ComW in competence shutoff.

IMPORTANCE
The sole alternative sigma factor of the streptococci, SigX, regulates development of competence for genetic transformation, a widespread mechanism of adaptation by horizontal gene transfer in this genus. The transient appearance of this sigma factor is strictly controlled at the levels of transcription and stability. This report shows that it is also controlled at the point of its substitution for SigA by a second transient competence-specific protein, ComW.
cis
-Encoded Small RNAs, a Conserved Mechanism for Repression of Polysaccharide Utilization in Bacteroides
Authors: Cao Yanlu , Förstner Konrad U. , Vogel Jörg , Smith C. Jeffrey 
Published: June 2016

ABSTRACT

Bacteroides
is a major component of the human gut microbiota which has a broad impact on the development and physiology of its host and a potential role in a wide range of disease syndromes. The predominance of this genus is due in large part to expansion of paralogous gene clusters, termed
p
olysaccharide
u
tilization
l
oci (PULs), dedicated to the uptake and catabolism of host-derived and dietary polysaccharides. The nutritive value and availability of polysaccharides in the gut vary greatly; thus, their utilization is hierarchical and strictly controlled. A typical PUL includes regulatory genes that induce PUL expression in response to the presence of specific glycan substrates. However, the existence of additional regulatory mechanisms has been predicted to explain phenomena such as hierarchical control and catabolite repression. In this report, a previously unknown layer of regulatory control was discovered in
Bacteroides fragilis
. Exploratory transcriptome sequencing (RNA-seq) analysis revealed the presence of
cis
-encoded antisense small RNAs (sRNAs) associated with 15 (30%) of the
B. fragilis
PULs. A model system using the Don (degradation of N-glycans) PUL showed that the
donS
sRNA negatively regulated Don expression at the transcriptional level, resulting in a decrease in N-glycan utilization. Additional studies performed with other
Bacteroides
species indicated that this regulatory mechanism is highly conserved and, interestingly, that the regulated PULs appear to be closely linked to the utilization of host-derived glycans rather than dietary plant polysaccharides. The findings described here demonstrate a global control mechanism underlying known PUL regulatory circuits and provide insight into regulation of
Bacteroides
physiology.

IMPORTANCE
The human gut is colonized by a dense microbiota which is essential to the health and normal development of the host. A key to gut homeostasis is the preservation of a stable, diverse microbiota.
Bacteroides
is a dominant genus in the gut, and the ability of
Bacteroides
species to efficiently compete for a wide range of glycan energy sources is a crucial advantage for colonization. Glycan utilization is mediated by a large number of
p
olysaccharide
u
tilization
l
oci (PULs) which are regulated by substrate induction. In this report, a novel family of antisense sRNAs is described whose members repress gene expression in a distinct subset of PULs. This repression downregulates PUL expression in the presence of energy sources that are more readily utilized such as glucose, thereby allowing efficient glycan utilization.
HIV Genome-Wide Protein Associations: a Review of 30 Years of Research
Authors: Li Guangdi , De Clercq Erik 
Published: June 2016

SUMMARYThe HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle.
Sources of social support associated with health and quality of life: a cross-sectional study among Canadian and Latin American older adults
Authors: Bélanger Emmanuelle , Ahmed Tamer , Vafaei Afshin , Curcio Carmen Lucia , Phillips Susan P , Zunzunegui Maria Victoria 
Published: June 2016

ObjectivesTo examine whether the association between emotional support and indicators of health and quality of life differs between Canadian and Latin American older adults.DesignCross-sectional analysis of the International Mobility in Aging Study (IMIAS). Social support from friends, family members, children and partner was measured with a previously validated social network and support scale (IMIAS-SNSS). Low social support was defined as ranking in the lowest site-specific quartile. Prevalence ratios (PR) of good health, depression and good quality of life were estimated with Poisson regression models, adjusting for age, gender, education, income and disability in activities of daily living.SettingKingston and Saint-Hyacinthe in Canada, Manizales in Colombia and Natal in Brazil.Participants1600 community-dwelling adults aged 65–74 years, n=400 at each site.Outcome measuresLikert scale question on self-rated health, Center for Epidemiological Studies Depression Scale and 10-point analogical quality-of-life (QoL) scale.ResultsRelationships between social support and study outcomes differed between Canadian and Latin American older adults. Among Canadians, those without a partner had a lower prevalence of good health (PR=0.90; 95% CI 0.82 to 0.98), and those with high support from friends had a higher prevalence of good health (PR=1.09; 95% CI 1.01 to 1.18). Among Latin Americans, depression was lower among those with high levels of support from family (PR=0.63; 95% CI 0.48 to 0.83), children (PR=0.60; 95% CI 0.45 to 0.80) and partner (PR=0.57; 95% CI 0.31 to 0.77); good QoL was associated with high levels of support from children (PR=1.54; 95% CI 1.20 to 1.99) and partner (PR=1.31; 95% CI 1.03 to 1.67).ConclusionsAmong older adults, different sources of support were relevant to health across societies. Support from friends and having a partner were related to good health in Canada, whereas in Latin America, support from family, children and partner were associated with less depression and better QoL.
Protocol for a cluster randomised trial of a communication skills intervention for physicians to facilitate survivorship transition in patients with lymphoma
Authors: Parker Patricia A , Banerjee Smita C , Matasar Matthew J , Bylund Carma L , Franco Kara , Li Yuelin , Levin Tomer T , Jacobsen Paul B , Astrow Alan B , Leventhal Howard , Horwitz Steven , Kissane David W 
Published: June 2016

IntroductionSurvivors of cancer often describe a sense of abandonment post-treatment, with heightened worry, uncertainty, fear of recurrence and limited understanding of what lies ahead. This study examines the efficacy of a communication skills training (CST) intervention to help physicians address survivorship issues and introduce a new consultation focused on the use of a survivorship care plan for patients with Hodgkin's lymphoma and diffuse large B-cell lymphoma.Methods and analysisSpecifically, this randomised, 4-site trial will test the efficacy of a survivorship planning consultation (physicians receive CST and apply these skills in a new survivorship-focused office visit using a survivorship plan) with patients who have achieved complete remission after completion of first-line therapy versus a control arm in which physicians are trained to subsequently provide a time-controlled, manualised wellness rehabilitation consultation focused only on discussion of healthy nutrition and exercise as rehabilitation postchemotherapy. The primary outcome for physicians will be uptake and usage of communication skills and maintenance of these skills over time. The primary outcome for patients is changes in knowledge about lymphoma and adherence to physicians’ recommendations (eg, pneumococcus and influenza vaccinations); secondary outcomes will include perceptions of the doctor–patient relationship, decreased levels of cancer worry and depression, quality of life changes, satisfaction with care and usage of healthcare. This study will also examine the moderators and mediators of change within our theoretical model derived from Leventhal's Common-Sense Model of health beliefs.Ethics and disseminationThis study was approved by the Institutional Review Boards at Memorial Sloan Kettering Cancer Centers and all other participating sites. This work is funded by the National Cancer Institute (R01 CA 151899 awarded to DWK and SH as coprincipal investigators). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute (NCI) or the National Institutes of Health (NIH). The study findings will be disseminated to the research and medical communities through publication in peer-reviewed journals and through presentations at local, national and international conferences.Trial registration numberNCT01483664.
Antidepressant use and violent crimes among young people: a longitudinal examination of the Finnish 1987 birth cohort
Authors: Hemminki Elina , Merikukka Marko , Gissler Mika , Wahlbeck Kristian , Savolainen Jukka , Ristikari Tiina , Aaltonen Mikko 
Published: June 2016

BackgroundThe use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), has been questioned due to poor efficacy and safety. We examined whether young violent offenders were more likely antidepressant users prior to their first violent offence than other young persons.MethodsThe study is a follow-up of children born in Finland in 1987 (n=59 120), linking national registers to each other using personal identity codes. Data on psychotropic drug use came from a register of reimbursed drugs and data on crimes from a register on court convictions (after the age of 14 years). Participants were followed until the age of 18 years, and for some analyses until the end of the follow-up (mean 21 years). To adjust for differences in background characteristics, regression analyses for antidepressant use were made, using the no-conviction group as the reference.ResultsProportions of young people convicted by the age of 18 years were: 5% of boys (1.7% for violent crimes) and 1% (0.5%) of girls. Antidepressant use (both overall and for SSRIs) prior to violent crime was more common among those convicted than among those without convictions. Among boys with repeated violent crimes, it was also more common than among boys with non-violent crimes. Adjustment for differences in background characteristics decreased the associations between antidepressant use and violent crime, but did not eliminate them.ConclusionsThe results add further evidence for caution in prescribing antidepressants among young persons. It also calls for a reanalysis of violence measures in the original trial data.
Hsp90 Inhibitor Ganetespib Sensitizes Non–Small Cell Lung Cancer to Radiation but Has Variable Effects with Chemoradiation
Authors: Wang Yifan , Liu Hui , Diao Lixia , Potter Adam , Zhang Jianhu , Qiao Yawei , Wang Jing , Proia David A. , Tailor Ramesh , Komaki Ritsuko , Lin Steven H. 
Published: June 2016

Abstract
Purpose: HSP90 inhibition is well known to sensitize cancer cells to radiation. However, it is currently unknown whether additional radiosensitization could occur in the more clinically relevant setting of chemoradiation (CRT). We used the potent HSP90 inhibitor ganetespib to determine whether it can enhance CRT effects in NSCLC.
Experimental Design: We first performed in vitro experiments in various NSCLC cell lines combining radiation with or without ganetespib. Some of these experiments included clonogenic survival assay, DNA damage repair, and cell-cycle analysis, and reverse-phase protein array. We then determined whether chemotherapy affected ganetespib radiosensitization by adding carboplatin–paclitaxel to some of the in vitro and in vivo xenograft experiments.
Results: Ganetespib significantly reduced radiation clonogenic survival in a number of lung cancer cell lines, and attenuated DNA damage repair with irradiation. Radiation caused G2–M arrest that was greatly accentuated by ganetespib. Ganetespib with radiation also dose-dependently upregulated p21 and downregulated pRb levels that were not apparent with either drug or radiation alone. However, when carboplatin–paclitaxel was added, ganetespib was only able to radiosensitize some cell lines but not others. This variable in vitro CRT effect was confirmed in vivo using xenograft models.
Conclusions: Ganetespib was able to potently sensitize a number of NSCLC cell lines to radiation but has variable effects when added to platinum-based doublet CRT. For optimal clinical translation, our data emphasize the importance of preclinical testing of drugs in the context of clinically relevant therapy combinations. Clin Cancer Res; 22(23); 5876–86. ©2016 AACR.
MiR-548an, Transcriptionally Downregulated by HIF1α/HDAC1, Suppresses Tumorigenesis of Pancreatic Cancer by Targeting Vimentin Expression
Authors: Zhu Shuai , He Chi , Deng Shijiang , li Xiang , Cui Shipeng , Zeng Zhu , Liu Mingliang , Zhao Shufeng , Chen Jingyuan , Jin Yan , Chen Hengyu , Deng Shichang , Liu Yang , Wang Chunyou , Zhao Gang 
Published: June 2016

Abstract
Hypoxic microenvironments contribute to the tumorigenesis of numerous cancers by regulating the expression of a subset of miRNAs called “hypoxiamiRs.” However, the function and mechanism of these deregulated miRNAs in hypoxic microenvironments within pancreatic cancers remain undefined. This study demonstrates that miR-548an is significantly downregulated in pancreatic cancer tissues and correlates with increased tumor size, advanced TNM stage, distant metastasis, and poor prognosis. Moreover, the overexpression of miR-548an significantly inhibited the proliferation and invasion of pancreatic cancer cells in vitro and in vivo. We further revealed that hypoxia-induced factor-1α (HIF-1α) induces the downregulation of miR-548an in pancreatic cancer cells during hypoxia. Our co-IP and ChIP assays revealed that HIF-1α and histone deacetylase 1 (HDAC1) form a complex and bind to the hypoxia response elements (HRE) on the miR-548an promoter. In addition, inhibition of HDAC1 with trichostatin A antagonizes the suppression of miR-548 by hypoxia. Our dual luciferase assay validated that miR-548an directly binds to the 3′ untranslated region of vimentin mRNA. The downregulation of vimentin suppresses the proliferation and invasion of pancreatic cancer cells in vitro and in vivo. In addition, vimentin was inversely correlated with miR-548an expression in pancreatic cancer samples. In conclusion, our findings suggest that the HIF-1α–HDAC1 complex transcriptionally inhibits miR-548an expression during hypoxia, resulting in the upregulation of vimentin that facilitates the pancreatic tumorigenesis. Mol Cancer Ther; 15(9); 2209–19. ©2016 AACR.
Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity
Authors: Weaver Alice N. , Burch M. Benjamin , Cooper Tiffiny S. , Della Manna Deborah L. , Wei Shi , Ojesina Akinyemi I. , Rosenthal Eben L. , Yang Eddy S. 
Published: June 2016

Abstract
Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1. In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch–FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC.
Implications: Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883–91. ©2016 AACR.
Review of Software Fault-Tolerance Methods for Reliability Enhancement of Real-Time Software Systems
Authors: Verma Anjushi , Ghartaan Ankur , Gayen Tirthankar 
Published: June 2016

Real time systems are those systems which must guarantee to response correctly within strict time constraint or within deadline. Failures can arise from both functional errors as well as timing bugs. Hence, it is necessary to provide temporal correctness of programs used in real time applications in addition to providing functional correctness. Although, there are several researches concerned with achieving fault tolerance in the presence of various functional and operational errors but many of them did not address the problem concerned with the timing bugs which is an important issue in real time systems. As for real time systems, many times it becomes a necessity for a given service to be delivered within the specified time deadline. Therefore, this paper reviews the existing approaches from the perspective of real time systems to analyse the shortcomings of these approaches to present a versatile and cost effective approach in the presence of timing bugs for providing fault tolerance to enhance the reliability of the real time software applications.
Machine Learning Techniques on Multidimensional Curve Fitting Data Based on R- Square and Chi-Square Methods
Authors: P Vidyullatha , Rao D. Rajeswara 
Published: June 2016

<p>Curve fitting is one of the procedures in data analysis and is helpful for prediction analysis showing graphically how the data points are related to one another whether it is in linear or non-linear model. Usually, the curve fit will find the concentrates along the curve or it will just use to smooth the data and upgrade the presence of the plot. Curve fitting checks the relationship between independent variables and dependent variables with the objective of characterizing a good fit model. Curve fitting finds mathematical equation that best fits given information. In this paper, 150 unorganized data points of environmental variables are used to develop Linear and non-linear data modelling which are evaluated by utilizing 3 dimensional ‘Sftool’ and ‘Labfit’ machine learning techniques. In Linear model, the best estimations of the coefficients are realized by the estimation of R- square turns in to one and in Non-Linear models with least Chi-square are the criteria. </p>