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Showing papers by "University of Texas Medical Branch published in 2018"


Journal ArticleDOI
TL;DR: Induction of labor at 39 weeks in low‐risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but it did result in less frequency of cesarean delivery.
Abstract: Background The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain. Methods In this multicenter trial, we randomly assigned...

623 citations


Journal ArticleDOI
09 Oct 2018-Mbio
TL;DR: The role of complement is tested using a mouse model and it is shown that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged, suggesting that inhibition of complement signaling might be an effective treatment option following coronavirus infection.
Abstract: Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3–/–), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3–/– mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3–/– mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3–/– mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic. IMPORTANCE The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

559 citations


Journal ArticleDOI
TL;DR: These guidelines are meant to be a practical diagnostic reference for the pathologist, however, some new pathologic predictors of prognosis and response to therapy are also included.
Abstract: Context.— Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective.— To provide updated, practical guidelines for the pathologic diagnosis of MM. Data Sources.— Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. Conclusions.— There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of s...

421 citations


Journal ArticleDOI
TL;DR: This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.
Abstract: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words ‘sport nutrition’. Consequently, staying current with the relevant literature is often difficult. This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches. This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.

404 citations


Journal ArticleDOI
TL;DR: G gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43), to provide insight into how microbiota metabolites regulate Th1cell functions to maintain intestinal homeostasis.
Abstract: T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43−/− CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag−/− recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1−/− Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis. T cells play a critical role in intestinal homeostasis, with increasing evidence suggesting a role for the microbiome metabolome in modulating this response. Here the authors show short-chain fatty acids promote IL-10 production in Th1 cells.

319 citations


Journal ArticleDOI
TL;DR: The prevalence of sexting has increased in recent years and increases as youth age, and further research focusing on nonconsensual sexts is necessary to appropriately target and inform intervention, education, and policy efforts.
Abstract: Importance The existing literature on sexting among youth shows that sexting is a predictor of sexual behavior and may be associated with other health outcomes and risky behaviors. However, there remains a lack of consensus on the prevalence of sexting, which is needed to inform future research, intervention, and policy development. Objective To provide a meta-analytic synthesis of studies examining the prevalence of multiple forms of sexting behavior, analyzed by age, sex, geography, and method of sexting. Data Sources In an academic setting, electronic searches in MEDLINE, PsycINFO, EMBASE, and Web of Science were conducted for the period January 1990 to June 2016, yielding 1147 nonduplicate records. Study Selection Studies were included if participants were younger than 18 years and the prevalence of sexting explicit images, videos, or messages was reported. Data Extraction and Synthesis Literature review and data extraction followed established PRISMA guidelines. Two independent reviewers extracted all relevant data. Random-effects meta-analyses were used to derive the mean prevalence rates. Thirty-nine studies met final inclusion criteria. Main Outcomes and Measures Meta-analyses of the prevalence of sending, receiving, and forwarding without consent, as well as having one’s sext forwarded without consent. Results Among 39 included studies, there were 110 380 participants; the mean age was 15.16 years (age range, 11.9-17.0 years), and on average 47.2% were male. Studies were available for sending (n = 34), receiving (n = 20), forwarding without consent (n = 5), and having a sext forwarded without consent (n = 4). The mean prevalences for sending and receiving sexts were 14.8% (95% CI, 12.8%-16.8%) and 27.4% (95% CI, 23.1%-31.7%), respectively. Moderator analyses revealed that effect sizes varied as a function of child age (prevalence increased with age), year of data collection (prevalence increased over time), and sexting method (higher prevalence on mobile devices compared with computers). The prevalence of forwarding a sext without consent was 12.0% (95% CI, 8.4%-15.6%), and the prevalence of having a sext forwarded without consent was 8.4% (95% CI, 4.7%-12.0%). Conclusions and Relevance The prevalence of sexting has increased in recent years and increases as youth age. Further research focusing on nonconsensual sexting is necessary to appropriately target and inform intervention, education, and policy efforts.

306 citations


Journal ArticleDOI
TL;DR: This work discusses Dengue, yellow fever, chikungunya, and Zika viruses, recent arrivals in the Western Hemisphere, and a few other viruses with the potential to emerge through all of these mechanisms.
Abstract: Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.

295 citations


Journal ArticleDOI
TL;DR: The studies demonstrated that microbiota metabolites SCFA promoted IEC RegIIIγ and β-defensins in a GPR43-dependent manner, providing a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis.

273 citations


Journal ArticleDOI
TL;DR: In this article, a review of phytoremediation techniques for heavy metal contamination in agricultural land and freshwater sources is presented, where the authors describe the fundamental principles of the process, mechanism, and influencing factors.

251 citations


Journal ArticleDOI
TL;DR: relevant in-place operational countermeasures onboard ISS are reviewed and a myriad of potential immune countermeasures for exploration missions are discussed, including nutritional supplementation and functional foods, exercise and immunity, pharmacological options, and vaccination to mitigate herpes (and possibly other) virus risks are discussed.
Abstract: Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.

223 citations


Journal ArticleDOI
TL;DR: Accumulating evidence suggests that targeting STAT3 may enhance anti-cancer immune responses and rescue the suppressed immunologic microenvironment in tumors.

Journal ArticleDOI
20 Jun 2018-PLOS ONE
TL;DR: The concept of saturation in salience is advanced and probing to increase the amount of information collected per respondent to increase sample efficiency is focused on.
Abstract: Sample size determination for open-ended questions or qualitative interviews relies primarily on custom and finding the point where little new information is obtained (thematic saturation). Here, we propose and test a refined definition of saturation as obtaining the most salient items in a set of qualitative interviews (where items can be material things or concepts, depending on the topic of study) rather than attempting to obtain all the items. Salient items have higher prevalence and are more culturally important. To do this, we explore saturation, salience, sample size, and domain size in 28 sets of interviews in which respondents were asked to list all the things they could think of in one of 18 topical domains. The domains-like kinds of fruits (highly bounded) and things that mothers do (unbounded)-varied greatly in size. The datasets comprise 20-99 interviews each (1,147 total interviews). When saturation was defined as the point where less than one new item per person would be expected, the median sample size for reaching saturation was 75 (range = 15-194). Thematic saturation was, as expected, related to domain size. It was also related to the amount of information contributed by each respondent but, unexpectedly, was reached more quickly when respondents contributed less information. In contrast, a greater amount of information per person increased the retrieval of salient items. Even small samples (n = 10) produced 95% of the most salient ideas with exhaustive listing, but only 53% of those items were captured with limited responses per person (three). For most domains, item salience appeared to be a more useful concept for thinking about sample size adequacy than finding the point of thematic saturation. Thus, we advance the concept of saturation in salience and emphasize probing to increase the amount of information collected per respondent to increase sample efficiency.

Journal ArticleDOI
TL;DR: The results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics and interferes with interferon production through interaction with TBK1.
Abstract: Virus-host interactions determine an infection outcome. The Asian lineage of Zika virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the NS1 gene after 2012 that enhances mosquito infection. Here we report that the same mutation confers NS1 to inhibit interferon-β induction. This mutation enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon-β induction; reversing the mutation in an epidemic ZIKV strain invigorates the virus for interferon-β induction; these mutational effects are lost in IRF3-knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also suppress interferon-β production through targeting distinct components of the RIG-I pathway; however, for these proteins, no antagonistic difference is observed among various ZIKV strains. Our results support the mechanism that ZIKV has accumulated mutation(s) that increases the ability to evade immune response and potentiates infection and epidemics.

Journal ArticleDOI
TL;DR: This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby hist one H1 is evicted while ubiquitin and 53BP1 accumulate over the entire γH2AX domains.

Journal ArticleDOI
TL;DR: This work presents ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata that can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods.
Abstract: Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.

Journal ArticleDOI
TL;DR: This review examines the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors, and highlights the role of a noncoding RNA produced by flavIViruses to impair antiviral host immune responses.
Abstract: Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune ...

Journal ArticleDOI
TL;DR: Assessing nearly 14,000 women from a contemporary United States database, this is the largest known study examining the relationship between response to NC and molecular subtype and predictors thereof and degree of response is associated with OS.
Abstract: This is the largest study to date evaluating response rates and pathologic complete response (pCR) and predictors thereof, based on molecular subtype, in women with breast cancer having undergone neoadjuvant chemotherapy (NC). The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer having received NC. Patients were divided into four subtypes: luminal A, luminal B, Her2, or triple negative (TN). Multivariable logistic regression ascertained factors associated with developing pCR. Kaplan–Meier analysis evaluated overall survival (OS) between patients by degree of response to NC when stratifying patients by subtype. Of a total of 13,939 women, 322 (2%) were luminal A, 5941 (43%) luminal B, 2274 (16%) Her2, and 5402 (39%) TN. Overall, 19% of all patients achieved pCR, the lowest in luminal A (0.3%) and the highest in Her2 (38.7%). Molecular subtype was an independent predictor of both pCR and OS in this population. Clinical downstaging was associated with improved survival, mostly in women with luminal B, Her2, and TN subtypes. Subgroup analysis of the pCR population demonstrated 5-year OS in the luminal B, Her2, and TN cohorts of 93.0, 94.2, and 90.6%, respectively (Her2 vs. TN, p = 0.016). Assessing nearly 14,000 women from a contemporary United States database, this is the largest known study examining the relationship between response to NC and molecular subtype. Women with luminal A disease are the least likely to undergo pCR, with the highest rates in Her2 disease. Degree of response is associated with OS, especially in luminal B, Her2, and TN patients. Despite the comparatively higher likelihood of achieving pCR in TN cases, this subgroup may still experience a survival detriment, which has implications for an ongoing national randomized trial.

Journal ArticleDOI
TL;DR: The study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.
Abstract: Clinical trials had provided evidence for the benefit effect of antihypertensive treatments in preventing future cardiovascular disease (CVD) events; however, the association between hypertension, whether treated/untreated or controlled/uncontrolled and risk of mortality in US population has been poorly understood. A total of 13,947 US adults aged ≥18 years enrolled in the Third National Health and Nutrition Examination Survey (1988–1994) were used to conduct this study. Mortality outcome events included all-cause, CVD-specific, heart disease-specific and cerebrovascular disease-specific deaths, which were obtained from linked 2011 National Death Index (NDI) files. During a median follow-up of 19.1 years, there were 3,550 all-cause deaths, including 1,027 CVD deaths. Compared with normotensives, treated but uncontrolled hypertensive patients were at higher risk of all-cause (HR = 1.62, 95%CI = 1.35–1.95), CVD-specific (HR = 2.23, 95%CI = 1.66–2.99), heart disease-specific (HR = 2.19, 95%CI = 1.57–3.05) and cerebrovascular disease-specific (HR = 3.01, 95%CI = 1.91–4.73) mortality. Additionally, untreated hypertensive patients had increased risk of all-cause (HR = 1.40, 95%CI = 1.21–1.62), CVD-specific (HR = 1.77, 95%CI = 1.34–2.35), heart disease-specific (HR = 1.69, 95%CI = 1.23–2.32) and cerebrovascular disease-specific death (HR = 2.53, 95%CI = 1.52–4.23). No significant differences were identified between normotensives, and treated and controlled hypertensives (all p > 0.05). Our study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.

Journal ArticleDOI
TL;DR: Deviations/variations from this artful coordination of the initial steps of DNA repair and the assembly of the transcriptional machinery to launch the prompt and preferential expression of redox-regulated genes may be the etiological links between guanine oxidation and various cellular pathologies and diseases during ageing processes.
Abstract: Oxidative stress and the resulting damage to genomic DNA are inevitable consequences of endogenous physiological processes, and they are amplified by cellular responses to environmental exposures. One of the most frequent reactions of reactive oxygen species with DNA is the oxidation of guanine to pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG). Despite the vulnerability of guanine to oxidation, vertebrate genes are primarily embedded in GC-rich genomic regions, and over 72% of the promoters of human genes belong to a class with a high GC content. In the promoter, 8-oxoG may serve as an epigenetic mark, and when complexed with the oxidatively inactivated repair enzyme 8-oxoguanine DNA glycosylase 1, provide a platform for the coordination of the initial steps of DNA repair and the assembly of the transcriptional machinery to launch the prompt and preferential expression of redox-regulated genes. Deviations/variations from this artful coordination may be the etiological links between guanine oxidation and various cellular pathologies and diseases during ageing processes.

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TL;DR: The family Rhabdoviridae comprises viruses with negative-sense (-) single-stranded RNA genomes of 10.8-16.1 kb that infect plants and animals including mammals, birds, reptiles and fish, as well as arthropods which serve as single hosts or act as biological vectors for transmission to animals or plants.
Abstract: The family Rhabdoviridae comprises viruses with negative-sense (–) single-stranded RNA genomes of 10.8–16.1 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants and animals including mammals, birds, reptiles and fish, as well as arthropods which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish and agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Rhabdoviridae, which is available at www.ictv.global/report/rhabdoviridae.

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TL;DR: Among a large and geographically diverse cohort of nulliparous women with singleton gestations, non-Hispanic black women are most likely to experience preterm birth, hypertensive disease of pregnancy, and small-for-gestational-age (SGA) birth.

Journal ArticleDOI
Gaya K. Amarasinghe1, Nidia G. Aréchiga Ceballos, Ashley C. Banyard, Christopher F. Basler2, Sina Bavari3, Andrew J. Bennett4, Kim R. Blasdell5, Thomas Briese6, Alexander Bukreyev7, Yíngyún Caì8, Charles H. Calisher9, Cristine Campos Lawson8, Kartik Chandran10, Colin A. Chapman11, Colin A. Chapman12, Colin A. Chapman13, Charles Y. Chiu14, Kang Seuk Choi, Peter L. Collins8, Ralf G. Dietzgen15, Valerian V. Dolja16, Olga Dolnik17, Leslie L. Domier18, Ralf Dürrwald19, John M. Dye3, Andrew J. Easton20, Hideki Ebihara21, Juan Emilio Echevarría22, Anthony R. Fooks, Pierre Formenty23, Ron A. M. Fouchier24, Conrad M. Freuling25, Elodie Ghedin26, Tony L. Goldberg4, Roger Hewson27, Masayuki Horie11, Timothy H. Hyndman28, Dàohóng Jiāng29, Robert Kityo30, Gary P. Kobinger31, Hideki Kondō32, Eugene V. Koonin8, Mart Krupovic33, Gael Kurath34, Robert A. Lamb35, Benhur Lee36, Eric M. Leroy, Piet Maes37, Andrea Maisner17, Denise A. Marston, Sunil K. Mor38, Thomas Müller25, Elke Mühlberger39, Víctor Manuel Neira Ramírez40, Sergey V. Netesov41, Terry Fei Fan Ng14, Norbert Nowotny42, Norbert Nowotny43, Gustavo Palacios3, Jean L. Patterson44, Janusz T. Paweska, Susan Payne45, Karla Prieto3, Bertus K. Rima46, Paul A. Rota47, Dennis Rubbenstroth48, Martin Schwemmle48, Stuart G. Siddell49, Sophie J. Smither50, Qisheng Song51, Timothy Song26, Mark D. Stenglein9, David M. Stone, Ayato Takada52, Robert B. Tesh7, Luciano M. Thomazelli53, Keizō Tomonaga11, Noël Tordo33, Jonathan S. Towner47, Nikos Vasilakis7, Sonia Vázquez-Morón22, Claudio Verdugo54, Viktor E. Volchkov55, Victoria Wahl, Peter J. Walker15, David Wang1, Lin-Fa Wang56, James F. X. Wellehan57, Michael R. Wiley58, Michael R. Wiley7, Anna E. Whitfield59, Yuri I. Wolf8, Gōngyín Yè60, Yǒng Zhèn Zhāng61, Jens H. Kuhn8 
Washington University in St. Louis1, Georgia State University2, United States Army Medical Research Institute of Infectious Diseases3, University of Wisconsin-Madison4, Commonwealth Scientific and Industrial Research Organisation5, Columbia University6, University of Texas Medical Branch7, National Institutes of Health8, Colorado State University9, Yeshiva University10, Kyoto University11, Wildlife Conservation Society12, McGill University13, University of California, San Francisco14, University of Queensland15, Oregon State University16, University of Marburg17, University of Illinois at Chicago18, Robert Koch Institute19, University of Warwick20, Mayo Clinic21, Carlos III Health Institute22, World Health Organization23, Erasmus University Rotterdam24, Friedrich Loeffler Institute25, New York University26, Public Health England27, Murdoch University28, Huazhong Agricultural University29, Makerere University30, Laval University31, Okayama University32, Pasteur Institute33, United States Geological Survey34, Northwestern University35, Icahn School of Medicine at Mount Sinai36, Katholieke Universiteit Leuven37, University of Minnesota38, Boston University39, University of Chile40, Novosibirsk State University41, University of Veterinary Medicine Vienna42, University of Medicine and Health Sciences43, Texas Biomedical Research Institute44, Texas A&M University45, Queen's University Belfast46, Centers for Disease Control and Prevention47, University of Freiburg48, University of Bristol49, Defence Science and Technology Laboratory50, University of Missouri51, Hokkaido University52, University of São Paulo53, Austral University of Chile54, École normale supérieure de Lyon55, National University of Singapore56, University of Florida57, University of Nebraska Medical Center58, North Carolina State University59, Zhejiang University60, Chinese Center for Disease Control and Prevention61
TL;DR: The updated taxonomy of the order Mononegavirales is presented as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and additional taxonomic proposals that may affect the order in the near future are summarized.
Abstract: In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

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09 Aug 2018-Cell
TL;DR: This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.

Journal ArticleDOI
TL;DR: In this article, the authors present a preclinical and clinical action plan for the repurposing of PARP inhibitors for non-oncological indications, such as acute ischaemic stroke, traumatic brain injury, septic shock, acute pancreatitis, severe asthma and severe acute lung injury.
Abstract: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors. This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

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Piet Maes1, S. V. Alkhovsky, Yīmíng Bào2, Martin Beer3, Monica Birkhead, Thomas Briese4, Michael J. Buchmeier5, Charles H. Calisher6, Rémi N. Charrel7, Il-Ryong Choi8, Christopher S. Clegg, Juan Carlos de la Torre9, Eric Delwart10, Joseph L. DeRisi10, Patrick L. Di Bello11, Francesco Di Serio, Michele Digiaro, Valerian V. Dolja12, Christian Drosten13, Tobiasz Druciarek11, Jiang Du14, Hideki Ebihara15, Toufic Elbeaino, Rose C. Gergerich11, Amethyst Gillis, Jean-Paul J. Gonzalez16, Anne-Lise Haenni17, Jussi Hepojoki18, Jussi Hepojoki19, Udo Hetzel18, Udo Hetzel19, Thiện Hồ11, Ni Hong20, Rakesh K. Jain21, Petrus Jansen van Vuren, Qi Jin14, Miranda Gilda Jonson22, Sandra Junglen, Karen E. Keller23, Alan Kemp, Anja Kipar19, Anja Kipar18, Nikola O. Kondov24, Eugene V. Koonin25, Richard Kormelink26, Yegor Korzyukov19, Mart Krupovic27, Amy J. Lambert28, Alma G. Laney29, Matthew LeBreton, Igor S. Lukashevich30, Marco Marklewitz, Wanda Markotter, Giovanni P. Martelli31, Robert R. Martin23, Nicole Mielke-Ehret32, H.-P. Mühlbach32, Beatriz Navarro, Terry Fei Fan Ng10, Márcio Roberto Teixeira Nunes33, Gustavo Palacios34, Janusz T. Paweska, Clarence J. Peters33, Alexander Plyusnin19, Sheli R. Radoshitzky34, Víctor Romanowski35, Pertteli Salmenperä19, Maria S. Salvato36, Hélène Sanfaçon, Takahide Sasaya37, Connie S. Schmaljohn34, Bradley S. Schneider, Yukio Shirako38, Stuart G. Siddell39, Tarja Sironen19, Mark D. Stenglein6, Nadia Storm, Hari Kishan Sudini40, Robert B. Tesh33, Ioannis E. Tzanetakis11, Mangala Uppala40, Olli Vapalahti19, Nikos Vasilakis33, Peter J. Walker41, Guoping Wang20, Liping Wang20, Yanxiang Wang20, Taiyun Wei42, Michael R. Wiley34, Michael R. Wiley43, Yuri I. Wolf25, Nathan D. Wolfe44, Zhìqiáng Wú14, Wenxing Xu45, Wenxing Xu20, Li Yang46, Zuòkūn Yāng20, Shyi-Dong Yeh47, Yǒng-Zhèn Zhāng46, Yàzhōu Zhèng20, Xueping Zhou, Chénxī Zhū20, Florian Zirkel13, Jens H. Kuhn25 
Katholieke Universiteit Leuven1, Chinese Academy of Sciences2, Friedrich Loeffler Institute3, Columbia University4, University of California, Irvine5, Colorado State University6, Aix-Marseille University7, International Rice Research Institute8, Scripps Research Institute9, University of California, San Francisco10, University of Arkansas System11, Oregon State University12, University of Bonn13, Peking Union Medical College14, Mayo Clinic15, Kansas State University16, University of Paris17, University of Zurich18, University of Helsinki19, Huazhong Agricultural University20, Indian Agricultural Research Institute21, Seoul National University22, United States Department of Agriculture23, Systems Research Institute24, National Institutes of Health25, Wageningen University and Research Centre26, Pasteur Institute27, Centers for Disease Control and Prevention28, North Carolina State University29, University of Louisville30, University of Bari31, University of Hamburg32, University of Texas Medical Branch33, United States Army Medical Research Institute of Infectious Diseases34, National University of La Plata35, University of Maryland, Baltimore36, National Agriculture and Food Research Organization37, University of Tokyo38, University of Bristol39, International Crops Research Institute for the Semi-Arid Tropics40, University of Queensland41, Fujian Agriculture and Forestry University42, University of Nebraska Medical Center43, Global Viral44, Chinese Ministry of Agriculture45, Chinese Center for Disease Control and Prevention46, National Chung Hsing University47
TL;DR: The updated taxonomy of the family Arenaviridae and the order Bunyavirales is presented as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and additional taxonomic proposals that may affect the order in the near future are summarized.
Abstract: In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

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TL;DR: The overarching message is that effective treatment and control of hypertension improves cardiovascular outcomes, but many knowledge gaps persist, including the contribution of hypertensive disorders of pregnancy to cardiovascular disease risk, the role of hormone replacement, blood pressure targets for elderly women, and so on.

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TL;DR: A peptide (P2C) is identified that mediates transduction of Cas9 RNP from the female hemolymph to the developing mosquito oocytes, resulting in heritable gene editing of the offspring with efficiency as high as 0.3 mutants per injected mosquito.
Abstract: Cas9-mediated gene editing is a powerful tool for addressing research questions in arthropods. Current approaches rely upon delivering Cas9 ribonucleoprotein (RNP) complex by embryonic microinjection, which is challenging, is limited to a small number of species, and is inefficient even in optimized taxa. Here we develop a technology termed Receptor-Mediated Ovary Transduction of Cargo (ReMOT Control) to deliver Cas9 RNP to the arthropod germline by injection into adult female mosquitoes. We identify a peptide (P2C) that mediates transduction of Cas9 RNP from the female hemolymph to the developing mosquito oocytes, resulting in heritable gene editing of the offspring with efficiency as high as 0.3 mutants per injected mosquito. We demonstrate that P2C functions in six mosquito species. Identification of taxa-specific ovary-specific ligand–receptor pairs may further extend the use of ReMOT Control for gene editing in novel species.

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TL;DR: MyoVision is new software that overcomes limitations by performing high-content analysis of muscle cross sections with minimal manual input and improves upon previously reported automatic techniques and analyzes images without requiring significant human input and correction.
Abstract: Scientists currently analyze images of immunofluorescently labeled skeletal muscle using time-consuming techniques that require sustained human supervision. As well as being inefficient, these tech...

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16 Nov 2018-Science
TL;DR: A small-molecule drug that acts as a potent and selective active-site inhibitor that stops OGG1 from recognizing its DNA substrate and hampers Ogg1 binding to and repair of 8-oxoG is developed, which is well tolerated by mice and presents a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.
Abstract: The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1 -deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.

Journal ArticleDOI
01 Jun 2018-Gut
TL;DR: CD177+ neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production and Targeting CD177+Neutrophils may be beneficial for treatment of IBD.
Abstract: Background Neutrophils are accumulated in inflamed mucosa of IBD and play an important role in the pathogenesis. CD177 is expressed in neutrophils specifically and upregulated during inflammation. However, the role of CD177 + neutrophils in pathogenesis of IBD remains elusive. Materials and methods Expression of CD177 was analysed in peripheral blood and intestinal mucosa from patients with IBD using quantitative RT-PCR, flow cytometry and immunohistochemistry. CD177 + and CD177 − neutrophils were isolated to determine gene differences by RNA sequencing. Colitis was established in CD177 −/− and wild-type mice in response to dextran sulfate sodium (DSS) insults to determine the role of CD177 + neutrophils in IBD. Results CD177 + neutrophils were markedly increased in peripheral blood and inflamed mucosa from patients with active IBD compared with healthy controls. RNA sequencing revealed that differential gene expression between CD177 + and CD177 − neutrophils from patients with IBD was associated with response to bacterial defence, hydrogen peroxide and reactive oxygen species (ROS). CD177 + neutrophils produced lower levels of proinflammatory cytokines (ie, interferon-γ, interleukin (IL)-6, IL-17A), but higher levels of IL-22 and transforming growth factor-β, and exhibited increased bactericidal activities (ie, ROS, antimicrobial peptides, neutrophil extracellular trap) compared with CD177 − subset. CD177 −/− mice developed more severe colitis on DSS insults compared with wild-type mice. Moreover, CD177 deficiency led to compromised intestinal barrier and impaired antibacterial immunity through decreased production of IL-22 by CD177 − neutrophils. Conclusions CD177 + neutrophils represent functionally activated population and play a protective role in IBD through increased bactericidal activity and IL-22 production. Targeting CD177 + neutrophils may be beneficial for treatment of IBD.