bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques
Authors: Smith S. Abigail , Kilgore Katie M. , Kasturi Sudhir Pai , Pulendran Bali , Hunter Eric , Amara Rama R. , Derdeyn Cynthia A. 
Published: December 2015

ABSTRACT
Mucosal surfaces are vulnerable to human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection and thus are key sites for eliciting vaccine-mediated protection. Vaccine protocols carried out at the Yerkes Primate Research Center utilized SIVmac239-based immunization strategies with intrarectal and intravaginal SIVsmE660 challenge of rhesus macaques. We investigated whether there were genetic signatures associated with SIVsmE660 intrarectal and intravaginal transmissions in vaccinated and unvaccinated monkeys. When transmitted/founder (T/F) envelope (Env) sequences from 49 vaccinated and 15 unvaccinated macaques were compared to each other, we were unable to identify any vaccine breakthrough signatures. In contrast, when the vaccinated and control T/F Envs were combined and compared to the challenge stock, residues at gp120 positions 23, 45, 47, and 70 (Ile-Ala-Lys-Asn [I-A-K-N]) emerged as signatures of mucosal transmission. However, T/F Envs derived from intrarectal and intravaginal infections were not different. Our data suggest that the vaginal and rectal mucosal environments both imposed a strong selection bias for SIVsmE660 variants carrying I-A-K-N that was not further enhanced by immunization. These findings, combined with the strong conservation of A-K-N in most HIV-2/SIVsmm isolates and the analogous residues in HIV-1/SIVcpz isolates, suggest that these residues confer increased transmission fitness to SIVsmE660.

IMPORTANCE
Most HIV-1 infections occur across a mucosal barrier, and it is therefore important to understand why these sites are vulnerable and how to protect them with a vaccine. To gain insight into these questions, we studied rhesus macaques that were vaccinated with SIVmac239 and unvaccinated controls to determine whether the SIVsmE660 viral variants that infected these two groups were different. We did not find differences between viral variants in the absence versus presence of vaccination-induced immunity, but we did find that the SIVsmE660 viral variants that infected the monkeys, regardless of vaccination, were different from the dominant population found in the viral challenge inoculum. Our data suggest that the mucosal environments of the vagina and rectum both impose a strong selection for the SIVsmE660 variants in the challenge inoculum that are most like SIV and HIVs that circulate in nature.
Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles
Authors: Poirier Enzo Z. , Mounce Bryan C. , Rozen-Gagnon Kathryn , Hooikaas Peter Jan , Stapleford Kenneth A. , Moratorio Gonzalo , Vignuzzi Marco 
Published: December 2015

ABSTRACT
Low-fidelity RNA-dependent RNA polymerases for many RNA virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. Additionally, for many RNA viruses, replication to high titers results in the production of defective interfering particles (DIs) that also attenuate infection. We hypothesized that fidelity, recombination, and DI production are tightly linked. We show that a Sindbis virus mutator replicating at a high multiplicity of infection manifests an earlier and greater accumulation of DIs than its wild-type counterpart. The isolated DIs interfere with the replication of full-length virus in a dose-dependent manner. Importantly, the ability of the mutator virus to overproduce DIs could be linked to an increased recombination frequency. These data confirm that RNA-dependent RNA polymerase fidelity and recombination are inversely correlated for this mutator. Our findings suggest that defective interference resulting from higher recombination rates may be more detrimental to RNA virus mutators than the increase in mutational burden.

IMPORTANCE
Replication, adaptation, and evolution of RNA viruses rely in large part on their low-fidelity RNA-dependent RNA polymerase. Viruses artificially modified in their polymerases to decrease fidelity (mutator viruses) are attenuated
in vivo
, demonstrating the important role of fidelity in viral fitness. However, attenuation was attributed solely to the modification of the viral mutation rate and the accumulation of detrimental point mutations. In this work, we described an additional phenotype of mutator viruses: an increased recombination rate leading to defective interfering particle (DI) overproduction. Because DIs are known for their inhibitory effect on viral replication, our work suggests that fidelity variants may be attenuated
in vivo
via several mechanisms. This has important implications in the development of fidelity variants as live attenuated vaccine strains.
Qualitative review of hazing in collegiate and school sports: consequences from a lack of culture, knowledge and responsiveness
Authors: Diamond Alex B , Callahan S Todd , Chain Kelly F , Solomon Gary S 
Published: December 2015

BackgroundAs with most mental health disorders, the topic of hazing is not exclusive to the student athlete. However, it is also clear that the unique set of situations faced by athletes create a set of additional and difficult challenges to their mental and physical well-being. A deep-rooted culture, a lack of knowledge about hazing and its causal relationships, and a failure to act by teammates and adults all play a role in the propagation of this danger. Also, in an era where the popular press similarly celebrates and chastises episodes of hazing, it is increasingly crucial to turn to the scientific literature for guidance.PurposeTo provide a comprehensive review of the scientific research on hazing in sports and to make recommendations for enhancing the approach and assistance to those in need on an individual and societal level.Study designQualitative literature review of hazing in collegiate and school sports.MethodsDatabases including PubMed, Google Scholar, SPORTDiscus, EMBASE and MEDLINE were searched using standardised terms, alone and in combination, including ‘hazing’, ‘bullying’, ‘sport’, ‘athlete’, ‘college’, ‘school’ and ‘youth’.FindingsDespite increased attention to its dangers, hazing remains pervasive throughout the sports world. However, many do not recognise those actions as consistent with hazing. A change in culture, increased education and awareness, along with methodologically sound strategies for action must occur in order to reduce the ill effects and cycle of hazing. To date, current information and efforts are lacking.
Exercise Programme in Endometrial Cancer; Protocol of the Feasibility and Acceptability Survivorship Trial (EPEC-FAST)
Authors: Smits Anke , Lopes Alberto , Das Nagindra , Bekkers Ruud , Massuger Leon , Galaal Khadra 
Published: December 2015

IntroductionObesity has been associated with impaired quality of life and poorer outcomes in endometrial cancer survivors. Lifestyle interventions promoting exercise and weight reduction have been proposed for survivorship care. However, studies evaluating exercise programmes for endometrial cancer survivors are lacking.PurposeThe objective of this study is to evaluate the feasibility of an individualised exercise intervention for endometrial cancer survivors to improve quality of life.Methods and analysisThis is a feasibility study in which women will undergo a 10-week exercise programme with a personal trainer. The study population comprises women with confirmed diagnosis of endometrial cancer, who have completed surgical treatment with curative intent, and are aged 18 years or older. The study will take place at the Royal Cornwall Hospital Trust, UK. Feasibility will be evaluated in terms of recruitment, adherence and compliance to the programme. Secondary outcomes are quality of life, psychological distress, fatigue, pain and complication rates. In addition, the acceptability of the programme will be assessed.Ethics and disseminationEthical approval was obtained through the Exeter NRES Committee. The study results will be used to optimise the intervention content, and may serve as the foundation for a larger definitive trial. Results will be disseminated through peer-review journals, congresses, relevant clinical groups and presented on the Trust's website.Trial registration number:NCT02367950; pre-results.
Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system)
Authors: Ostovar Afshin , Nabipour Iraj , Larijani Bagher , Heshmat Ramin , Darabi Hossein , Vahdat Katayoun , Ravanipour Maryam , Mehrdad Neda , Raeisi Alireza , Heidari Gholamreza , Shafiee Gita , Haeri Mohammadjavad , Pourbehi Mohammadreza , Sharifi Farshad , Noroozi Azita , Tahmasebi Rahim , Aghaei Meybodi Hamidreza , Assadi Majid , Farrokhi Shokrollah , Nemati Reza , Amini Mohammad Reza , Barekat Maryam , Amini Abdullatif , Salimipour Houman , Dobaradaran Sina , Moshtaghi Darab 
Published: December 2015

PurposeThe main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events.ParticipantsBetween March 2013 and October 2014, a total of 3000 men and women aged ≥60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%).Findings to dateBaseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at –80°C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men.Future plansRisk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration.
First-principles study of structural, elastic and thermodynamic properties of AuIn2
Authors: Wu Hai Ying , Chen Ya Hong , Deng Chen Rong , Yin Peng Fei , Cao Hong 
Published: December 2015

The structural, elastic and thermodynamic properties of [Formula: see text] in the [Formula: see text] structure under pressure have been investigated using ab initio plane wave pseudopotential method within the generalized gradient approximation. The calculated structural parameters and equation of state are in excellent agreement with the available experimental and theoretical results. The elastic constants of [Formula: see text] at ambient condition are calculated, and the bulk modulus obtained from these calculated elastic constants agrees well with the experimental data. The pressure dependence of the elastic constants, bulk modulus, shear modulus and Young’s modulus has also been investigated. The Debye temperature presents a slight increase with pressure. [Formula: see text] exhibits ductibility and low hardness characteristics, the ductibility increases while the hardness decreases with the increasing of pressure. The pressure effect on the heat capacity and thermal expansion coefficient for [Formula: see text] is much larger.
Do technical studies reduce subsurface risk in hydrocarbon exploration: and if not, how do they add value?
Authors: Peel Frank J. , White Jonathan 
Published: December 2015

Abstract
The title ‘The Value of Outcrop Studies in Reducing Subsurface Uncertainty and Risk’ might suggest that we expect new information to improve prospect risk, but this is not correct. Gaining new information generally does change our estimate of prospect risk: the change may be up or down, and the average of all possibilities is zero change. You cannot acquire data for the purpose of increasing the probability of success. We should expect that: (a) the expected value of the risk of a single prospect, post-data, is equal to the prior (pre-data) value; and (b) risk should become worse for the majority of prospects. New information adds value, not from changing pre-drill risk, but from decisions made as a consequence. The main value added is from identifying prospects not to drill, thereby saving the cost of likely dry holes, and by choosing the ones to test first, accelerating revenue from a successful outcome. Further value is added if the new information leads to the identification of new prospects or new plays, or suggests follow-on potential elsewhere in the region. Value may also be added if the new information is negative for a whole region, enabling us to focus our attention elsewhere.
Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity
Authors: Kim Dong Joon , Roh Eunmiri , Lee Mee-Hyun , Oi Naomi , Lim Do Young , Kim Myoung Ok , Cho Yong-Yeon , Pugliese Angelo , Shim Jung-Hyun , Chen Hanyong , Cho Eun Jin , Kim Jong-Eun , Kang Sun Chul , Paul Souren , Kang Hee Eun , Jung Ji Won , Lee Sung-Young , Kim Sung-Hyun , Reddy Kanamata , Yeom Young Il , Bode Ann M. , Dong Zigang 
Published: December 2015

Abstract
Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials. Cancer Res; 76(5); 1146–57. ©2015 AACR.
Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling
Authors: Catalano Veronica , Dentice Monica , Ambrosio Raffaele , Luongo Cristina , Carollo Rosachiara , Benfante Antonina , Todaro Matilde , Stassi Giorgio , Salvatore Domenico 
Published: December 2015

Abstract
Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2–D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that drug-induced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. Cancer Res; 76(5); 1237–44. ©2015 AACR.
Targeting the WASF3–CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion
Authors: Teng Yong , Bahassan Abdulaziz , Dong Dayong , Hanold Laura E. , Ren Xiaoou , Kennedy Eileen J. , Cowell John K. 
Published: December 2015

Abstract
Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function. Here, we show that genetic knockdown of CYFIP1 in cancer cells led to the destabilization of the WASF3 complex, loss of WASF3 function, and suppressed invasion. Based on existing crystallographic data, we developed stapled peptides, referred to as WASF Helix Mimics (WAHM), that target an α-helical interface between WASF3 and CYFIP1. Treatment of highly invasive breast and prostate cancer cells with WAHM inhibitor peptides significantly reduced motility and invasion in vitro. Mechanistic investigations revealed that these inhibitors suppressed the interaction between Rac and the WASF3 complex, which has been shown to promote cell migration. Furthermore, peptide-mediated inhibition of WASF3 also resulted in the dysregulation of known downstream targets such as MMP-9 and KISS1. Finally, we demonstrate that this invasive phenotype is specific to WASF3 as depletion of WASF1 and WASF2, which can also bind to CYFIP1, did not affect invasion. Collectively, our findings suggest that targeting WASF3 function with WAHM peptides could represent a promising therapeutic strategy for preventing tumor invasion and metastasis. Cancer Res; 76(4); 965–73. ©2015 AACR.
Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition in Hematologic Malignancies
Authors: Adams Clare M. , Hiebert Scott W. , Eischen Christine M. 
Published: December 2015

Abstract
Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc-driven B-cell lymphoma and five other hematopoietic malignancies. We determined that Myc-mediated transcriptional repression of the miR-15 and let-7 families in malignant cells was relieved upon HDACi, and Myc was required for their upregulation. The miR-15 and let-7 families then targeted and downregulated the antiapoptotic genes Bcl-2 and Bcl-xL, respectively, to induce HDACi-mediated apoptosis. Notably, Myc also transcriptionally upregulated these miRNA in untransformed cells, indicating that this Myc-induced miRNA-mediated apoptotic pathway is suppressed in malignant cells, but becomes reactivated upon HDACi. Taken together, our results reveal a previously unknown mechanism by which Myc induces apoptosis independent of the p53 pathway and as a response to HDACi in malignant hematopoietic cells. Cancer Res; 76(3); 736–48. ©2015 AACR.
Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study
Authors: Markt Sarah C. , Flynn-Evans Erin E. , Valdimarsdottir Unnur A. , Sigurdardottir Lara G. , Tamimi Rulla M. , Batista Julie L. , Haneuse Sebastien , Lockley Steven W. , Stampfer Meir , Wilson Kathryn M. , Czeisler Charles A. , Rider Jennifer R. , Mucci Lorelei A. 
Published: December 2015

Abstract
Background: Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer.
Methods: We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer.
Results: In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15–8.10).
Conclusions: We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes.
Impact: We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men. Cancer Epidemiol Biomarkers Prev; 25(2); 302–8. ©2015 AACR.