bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of the Rac1-IRSp53-Wave2-Arp2/3 Signaling Pathway in HIV-1 Gag Particle Release in CD4 T Cells
Authors: Thomas Audrey , Mariani-Floderer Charlotte , López-Huertas Maria Rosa , Gros Nathalie , Hamard-Péron Elise , Favard Cyril , Ohlmann Theophile , Alcamí José , Muriaux Delphine 
Published: May 2015

ABSTRACT
During HIV-1 assembly, the Gag viral proteins are targeted and assemble at the inner leaflet of the cell plasma membrane. This process could modulate the cortical actin cytoskeleton, located underneath the plasma membrane, since actin dynamics are able to promote localized membrane reorganization. In addition, activated small Rho GTPases are known for regulating actin dynamics and membrane remodeling. Therefore, the modulation of such Rho GTPase activity and of F-actin by the Gag protein during virus particle formation was considered. Here, we studied the implication of the main Rac1, Cdc42, and RhoA small GTPases, and some of their effectors, in this process. The effect of small interfering RNA (siRNA)-mediated Rho GTPases and silencing of their effectors on Gag localization, Gag membrane attachment, and virus-like particle production was analyzed by immunofluorescence coupled to confocal microscopy, membrane flotation assays, and immunoblot assays, respectively. In parallel, the effect of Gag expression on the Rac1 activation level was monitored by G-LISA, and the intracellular F-actin content in T cells was monitored by flow cytometry and fluorescence microscopy. Our results revealed the involvement of activated Rac1 and of the IRSp53-Wave2-Arp2/3 signaling pathway in HIV-1 Gag membrane localization and particle release in T cells as well as a role for actin branching and polymerization, and this was solely dependent on the Gag viral protein. In conclusion, our results highlight a new role for the Rac1-IRSp53-Wave2-Arp2/3 signaling pathway in the late steps of HIV-1 replication in CD4 T lymphocytes.

IMPORTANCE
During HIV-1 assembly, the Gag proteins are targeted and assembled at the inner leaflet of the host cell plasma membrane. Gag interacts with specific membrane phospholipids that can also modulate the regulation of cortical actin cytoskeleton dynamics. Actin dynamics can promote localized membrane reorganization and thus can be involved in facilitating Gag assembly and particle formation. Activated small Rho GTPases and effectors are regulators of actin dynamics and membrane remodeling. We thus studied the effects of the Rac1, Cdc42, and RhoA GTPases and their specific effectors on HIV-1 Gag membrane localization and viral particle release in T cells. Our results show that activated Rac1 and the IRSp53-Wave2-Arp2/3 signaling pathway are involved in Gag plasma membrane localization and viral particle production. This work uncovers a role for cortical actin through the activation of Rac1 and the IRSp53/Wave2 signaling pathway in HIV-1 particle formation in CD4 T lymphocytes.
Functional Analysis of the 60-Nucleotide Duplication in the Respiratory Syncytial Virus Buenos Aires Strain Attachment Glycoprotein
Authors: Hotard Anne L. , Laikhter Elizabeth , Brooks Kelsie , Hartert Tina V. , Moore Martin L. 
Published: May 2015

ABSTRACT

There are two subgroups of respiratory syncytial virus (RSV), A and B, and within each subgroup, isolates are further divided into clades. Several years ago, multiple subgroup B isolates which contained a duplication of 60 nucleotides in the glycoprotein (G) gene were described. These isolates were given a new clade designation of BA based on the site of isolation, Buenos Aires, Argentina. BA RSV strains have since become the predominant circulating clade of RSV B viruses. We hypothesized that the duplicated region in G serves to enhance the function of G in the virus life cycle. We generated recombinant viruses that express a consensus BA G gene or a consensus BA G gene lacking the duplication (G
Δdup
). We determined that the duplicated region functions during virus attachment to cells. Additionally, we showed that
in vitro
, the virus containing the duplication has a fitness advantage compared to the virus without the duplication. Our data demonstrate that the duplicated region in the BA strain G protein augments virus attachment and fitness.

IMPORTANCE
Respiratory syncytial virus (RSV) is an important pathogen for infants for which there is no vaccine. Different strains of RSV circulate from year to year, and the predominating strains change over time. Subgroup B RSV strains with a duplication in the attachment glycoprotein (G) emerged and then became the dominant B genotype. We found that a recombinant virus harboring the duplication bound more efficiently to cells and was more fit than a recombinant strain lacking the duplication. Our work advances a mechanism for an important natural RSV mutation.
Vaccine-Induced Linear Epitope-Specific Antibodies to Simian Immunodeficiency Virus SIVmac239 Envelope Are Distinct from Those Induced to the Human Immunodeficiency Virus Type 1 Envelope in Nonhuman Primates
Authors: Shen Xiaoying , Duffy Ryan , Howington Robert , Cope Alethea , Sadagopal Shanmugalakshmi , Park Haesun , Pal Ranajit , Kwa Suefen , Ding Song , Yang Otto O. , Fouda Genevieve G. , Le Grand Roger , Bolton Diane , Esteban Mariano , Phogat Sanjay , Roederer Mario , Amara Rama R. , Picker Louis J. , Seder Robert A. , McElrath M. Juliana , Barnett Susan , Permar Sallie R. , Shattock Robin , DeVico Anthony L. , Felber Barbara K. , Pavlakis George N. , Pantaleo Giuseppe , Korber Bette T. , Montefiori David C. , Tomaras Georgia D. 
Published: May 2015

ABSTRACT
To evaluate antibody specificities induced by simian immunodeficiency virus (SIV) versus human immunodeficiency virus type 1 (HIV-1) envelope antigens in nonhuman primate (NHP), we profiled binding antibody responses to linear epitopes in NHP studies with HIV-1 or SIV immunogens. We found that, overall, HIV-1 Env IgG responses were dominated by V3, with the notable exception of the responses to the vaccine strain A244 Env that were dominated by V2, whereas the anti-SIVmac239 Env responses were dominated by V2 regardless of the vaccine regimen.
Outcomes of antiretroviral treatment in HIV-infected adults: a dynamic and observational cohort study in Shenzhen, China, 2003–2014
Authors: Huang Peng , Tan Jingguang , Ma Wenzhe , Zheng Hui , Lu Yan , Wang Ning , Peng Zhihang , Yu Rongbin 
Published: May 2015

ObjectivesTo report 10-year outcomes of virological and immunological treatment failure rates and risk factors.DesignProspective cohort study.SettingShenzhen, China.Participants2172 HIV-positive adults in the national treatment database of Shenzhen from December 2003 to January 2014.InterventionAntiretroviral therapy according to the Chinese national treatment guidelines.Outcome measuresVirological and immunological treatment failure rates.ResultsOf the 3099 patients surveyed, 2172 (70.1%) were included in the study. The median age was 33 years; 78.2% were male and 51.8% were infected through heterosexual contact. The median follow-up time was 31 months (IQR, 26–38). A total of 81 (3.7%) patients died, whereas 292 (13.4%) and 400 (18.4%) patients experienced virological and immunological failures, respectively. Adjusted Cox regression analysis indicated that baseline viral load (HR=2.19, 95% CI 1.52 to 4.48 for patients with a baseline viral load greater than or equal to 1 000 000 copies/mL compared to those with less than 10 000 copies/mL) and WHO stage (HR=4.16, 95% CI 2.01 to 10.57 for patients in WHO stage IV compared with those in stage I) were significantly associated with virological failure. The strongest risk factors for immunological treatment failure were a low CD4 cell count (HR=0.46, 95% CI 0.32 to 0.66 for patients with CD4 cell counts of 50–99 cells/mm3compared to those with less than 50 cells/mm3) and higher baseline WHO stage at treatment initiation (HR=2.15, 95% CI 1.38 to 3.34 for patients in WHO stage IV compared to those in stage I).ConclusionsSustained virological and immunological outcomes show that patients have responded positively to long-term antiretroviral treatment with low mortality. This 10-year data study provides important information for clinicians and policymakers in the region as they begin to evaluate and plan for the future needs of their own rapidly expanding programmes.
SurgiCal Obesity Treatment Study (SCOTS): protocol for a national prospective cohort study of patients undergoing bariatric surgery in Scotland
Authors: Logue Jennifer , Stewart Sally , Munro Jane , Bruce Julie , Grieve Eleanor , Lean Mike , Lindsay Robert S , Bruce Duff , Ali Abdulmajid , Briggs Andrew , Sattar Naveed , Ford Ian 
Published: May 2015

IntroductionThe efficacy of bariatric surgery for large-scale, long-term weight loss is well established. However, many questions remain over the continual benefits and cost-effectiveness of that weight loss for overall health, particularly when accounting for potential complications and adverse events of surgery. Health research institutes in the UK and the USA have called for high-quality longitudinal cohort studies of patients undergoing bariatric surgery, assessing outcomes such as surgical complications, mortality, diabetes remission, microvascular complications, cardiovascular events, mental health, cost and healthcare use.Methods and analysisSurgiCal Obesity Treatment Study (SCOTS) is a national, prospective, observational, cohort study of patients undergoing primary bariatric surgical procedures in Scotland. This study aims to recruit 2000 patients and conduct a follow-up for 10 years postbariatric surgery using multiple data collection methods: surgeon-recorded data, electronic health record linkage, and patient-reported outcome measures. Outcomes measured will include: mortality, weight change, diabetes, surgical, cardiovascular, cancer, behavioural, reproductive/urological and nutritional variables. Healthcare utilisation and economic productivity will be collected to inform cost-effectiveness analysis.Ethics and disseminationThe study has received a favourable ethical opinion from the West of Scotland Research Ethics committee. All publications arising from this cohort study will be published in open-access peer-reviewed journals. All SCOTS investigators (all members of the research team at every recruiting site) will have the ability to propose research suggestions and potential publications using SCOTS data; a publications committee will approve all requests for use of SCOTS data and propose writing committees and timelines. Lay-person summaries of all research findings will be published simultaneously on the SCOTS website (http://www.scotsurgeystudy.org.uk).
Thromboembolic resolution assessed by CT pulmonary angiography after treatment for acute pulmonary embolism
Authors: Kroft Lucia J. M. , Erkens Petra M. G. , Douma Renée A. , Mos Inge C. M. , Jonkers Gé , Hovens Marcel M. C. , Durian Marc F. , Cate Hugo ten , Beenen Ludo F. M. , Kamphuisen Pieter Willem , Huisman Menno V. , den Exter Paul L. , van Es Josien ,   for the Prometheus Follow-Up Investigators
Published: May 2015

SummaryThe systematic assessment of residual thromboembolic obstruction after treatment for acute pulmonary embolism (PE) has been under-studied. This assessment is of potential clinical importance, should clinically suspected recurrent PE occur, or as tool for risk stratification of cardiopulmonary complications or recurrent venous thromboembolism (VTE). This study aimed to assess the rate of PE resolution and its implications for clinical outcome. In this prospective, multi-center cohort study, 157 patients with acute PE diagnosed by CT pulmonary angiography (CTPA) underwent follow-up CTPA-imaging after six months of anticoagulant treatment. Two expert thoracic radiologists independently assessed the presence of residual thromboembolic obstruction. The degree of obstruction at baseline and follow-up was calculated using the Qanadli obstruction index. All patients were followed-up for 2.5 years. At baseline, the median obstruction index was 27.5 %. After six months of treatment, complete PE resolution had occurred in 84.1 % of the patients (95 % confidence interval (CI): 77.4–89.4 %). The median obstruction index of the 25 patients with residual thrombotic obstruction was 5.0 %. During follow-up, 16 (10.2 %) patients experienced recurrent VTE. The presence of residual thromboembolic obstruction was not associated with recurrent VTE (adjusted hazard ratio: 0.92; 95 % CI: 0.2–4.1). This study indicates that the incidence of residual thrombotic obstruction following treatment for PE is considerably lower than currently anticipated. These findings, combined with the absence of a correlation between residual thrombotic obstruction and recurrent VTE, do not support the routine use of follow-up CTPA-imaging in patients treated for acute PE.
Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran
Authors: Reilly Paul A. , Bernstein Richard , Dubiel Robert , Eikelboom John , Glund Stephan , Huisman Menno V. , Hylek Elaine , Kam Chak-Wah , Kamphuisen Pieter W. , Kreuzer Joerg , Levy Jerrold H. , Sellke Frank , Stangier Joachim , Steiner Thorsten , Wang Bushi , Weitz Jeffrey I. , Pollack Charles V. 
Published: May 2015

SummaryIdarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect of dabigatran in animals and in healthy volunteers. The Study of the REVERS al E ffects of Idarucizumab in Patients on A ctive D abigatran (RE-VERSE AD™) is a global phase 3 prospective cohort study aimed at investigating idarucizumab in dabigatran-treated patients who present with uncontrollable or life-threatening bleeding, and in those requiring urgent surgery or intervention. We describe the rationale for, and design of the trial (clinicaltrials.gov NCT02104947).
Third Trimester Fetal Heart Rate Predicts Phenotype and Mutation Burden in the Type 1 Long QT Syndrome
Authors: Winbo Annika , Fosdal Inger , Lindh Maria , Diamant Ulla-Britt , Persson Johan , Wettrell Göran , Rydberg Annika 
Published: May 2015

Background—
Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype.

Methods and Results—

This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110
KCNQ1
mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29–41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute;
P
<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute;
P
<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (
r
=0.700;
P
<0.001), and postnatal QTc (
r
=−0.762;
P
<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation;
P
<1.0×10
–23
). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute,
P
<0.0001.

Conclusions—
In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias.
The Impact of Lifecourse Socioeconomic Position on Cardiovascular Disease Events in African Americans: The Jackson Heart Study
Authors: Gebreab Samson Y. , Diez Roux Ana V. , Brenner Allison B. , Hickson DeMarc A. , Sims Mario , Subramanyam Malavika , Griswold Michael E. , Wyatt Sharon B. , James Sherman A. 
Published: May 2015

Background

Few studies have examined the impact of lifecourse socioeconomic position (
SEP
) on cardiovascular disease (
CVD
) risk among African Americans.

Methods and Results

We used data from the Jackson Heart Study (
JHS
) to examine the associations of multiple measures of lifecourse
SEP
with
CVD
events in a large cohort of African Americans. During a median of 7.2‐year follow‐up, 362 new or recurrent
CVD
events occurred in a sample of 5301 participants aged 21 to 94. Childhood
SEP
was assessed by using mother's education, parental home ownership, and childhood amenities. Adult
SEP
was assessed by using education, income, wealth, and public assistance. Adult
SEP
was more consistently associated with
CVD
risk in women than in men: age‐adjusted hazard ratios for low versus high income (95% CIs), 2.46 (1.19 to 5.09) in women and 1.50 (0.87 to 2.58) in men,
P
for interaction=0.1244, and hazard ratio for low versus high wealth, 2.14 (1.39 to 3.29) in women and 1.06 (0.62 to 1.81) in men,
P
for interaction=0.0224. After simultaneous adjustment for all adult
SEP
measures, wealth remained a significant predictor of
CVD
events in women (
HR
=1.73 [1.04, 2.85] for low versus high). Education and public assistance were less consistently associated with
CVD
. Adult
SEP
was a stronger predictor of
CVD
events in younger than in older participants (
HR
for high versus low summary adult
SEP
score 3.28 [1.43, 7.53] for participants ≤50 years, and 1.90 (1.36 to 2.66) for participants >50 years,
P
for interaction 0.0846). Childhood
SEP
was not associated with
CVD
risk in women or men.

Conclusions

Adult
SEP
is an important predictor of
CVD
events in African American women and in younger African Americans. Childhood
SEP
was not associated with
CVD
events in this population.
Exploring information-seeking processes by businesses: analyzing source and channel choices in business-to-government service interactions
Authors: van den Boer Yvon , Pieterson Willem , van Dijk Jan , Arendsen Rex 
Published: May 2015

With the rise of electronic channels it has become easier for businesses to consult various types of information sources in information-seeking processes. Governments are urged to rethink their role as reliable information source and the roles of their (electronic) service channels to provide efficient service support. This article addresses how governments cope with the availability of numerous sources and channels and focuses on similarities, differences and interdependencies between source and channel selection processes. Individual and group interviews were held with businesses throughout the Netherlands. The results indicate that some factors influence source and channel choices (e.g. task characteristics), others influence only channel choice (e.g. situational factors, channel characteristics). Source and relationship characteristics uncover interdependencies between both, since these source-related concepts influence channel choices. Further insight is needed to increase our understanding and come to an integrated theory of source and channel choices in information-seeking processes. Points for practitioners The channels used by the government are in their own control (i.e. information quality); however, other sources and their channels are outside their control. Management of these sources can be realized through strategic partnerships with crucial sources. The first implication is that governments provide content to other sources, which these sources can use for advice to its customers. The second implication concerns the use of cross-referrals between sources and their channels. For instance, the government website contains a recommendation to call an advisor for specific information since this source-channel combination provides only general information.
Environmental Violence and Its Consequences
Authors: de la Cueva Salcedo Horacio 
Published: May 2015

Environmental changes happen all the time. Changing environments bring about selection of organisms, and there is no organism that does not modify its environment to make a living, survive, and reproduce. These changes are the main motors of evolution and, consequently, the main cause of biodiversity. Environmental violence—unsustainable use and extraction of natural resources—is the way capitalist economies exploit nature. The extinction rates associated with the current unsustainable use of resources are sufficient to assume that we are experiencing a sixth mass extinction event. The rate at which humans are transforming the environment leaves no time for evolutionary adaptation. We need to reduce environmental violence for life to maintain its normal processes. Without knowledge of nature and the consequences of violence against nature, we will become another of the planet’s extinct species. Los cambios ambientales ocurren todo el tiempo. Los ambientes cambiantes propician la selección de organismos y no hay organismo que no modifique su ambiente para subsistir y reproducirse. Estos cambios son los principales motores de la evolución y por lo tanto la causa principal de la biodiversidad. La violencia ambiental—el uso y la extracción insostenibles de los recursos naturales—es la manera en que las economías capitalistas explotan la naturaleza. Las tasas de extinción asociadas con el uso insostenible de los recursos son suficientes para considerar que estamos experimentando la sexta extinción masiva de especies. El ritmo al cual los seres humanos están transformando el ambiente no deja tiempo para la adaptación evolutiva. Necesitamos reducir la violencia ambiental para que la vida pueda mantener sus procesos normales. Sin el conocimiento de la naturaleza y de las consecuencias de la violencia contra ella, nos convertiremos en otra de las especies extintas de nuestro planeta.
Hypochondriasis: treatment options for a diagnostic quagmire
Authors: Starcevic Vladan 
Published: May 2015

Objective: This article presents the conceptual and diagnostic conundrums surrounding hypochondriasis and reviews current treatment options for this disorder. Conclusions: The removal of hypochondriasis from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and its replacement with two new diagnostic entities have been controversial. It appears that the Eleventh Revision of the International Classification of Diseases will take a more cautious approach and emphasise the links between hypochondriasis, obsessive-compulsive disorder and other anxiety disorders. The cornerstone of any treatment approach to hypochondriasis is establishing a good therapeutic relationship with the patient. Psychological treatments, especially cognitive-behavioural therapy, have been more useful than pharmacotherapy, but there is much room for improving treatment outcomes.