bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 gp120 Activates the STAT3/Interleukin-6 Axis in Primary Human Monocyte-Derived Dendritic Cells
Authors: Del Cornò Manuela , Donninelli Gloria , Varano Barbara , Da Sacco Letizia , Masotti Andrea , Gessani Sandra 
Published: July 2014

ABSTRACTDendritic cells (DCs) are fundamental for the initiation of immune responses and are important players in AIDS immunopathogenesis. The modulation of DC functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. Impairment of DC function may result from bystander effects of HIV-1 envelope proteins independently of direct HIV-1 infection. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to HIV-1 R5 gp120 resulted in the CCR5-dependent production of interleukin-6 (IL-6) via mitogen-activated protein kinase (MAPK)/NF-κB pathways. IL-6 in turn activated STAT3 by an autocrine loop. Concomitantly, gp120 promoted an early activation of STAT3 that further contributed to IL-6 induction. This activation paralleled a concomitant upregulation of the STAT3 inhibitor PIAS3. Notably, STAT3/IL-6 pathway activation was not affected by the CCR5-specific ligand CCL4. These results identify STAT3 as a key signaling intermediate activated by gp120 in MDDCs and highlight the existence of a virus-induced dysregulation of the IL-6/STAT3 axis. HIV-1 gp120 signaling through STAT3 may provide an explanation for the impairment of DC function observed upon HIV exposure.IMPORTANCEThis study provides new evidence for the molecular mechanisms and signaling pathways triggered by HIV-1 gp120 in human DCs in the absence of productive infection, emphasizing a role of aberrant signaling in early virus-host interaction, contributing to viral pathogenesis. We identified STAT3 as a key component in the gp120-mediated signaling cascade involving MAPK and NF-κB components and ultimately leading to IL-6 secretion. STAT3 now is recognized as a key regulator of DC functions. Thus, the identification of this transcription factor as a signaling molecule mediating some of gp120's biological effects unveils a new mechanism by which HIV-1 may deregulate DC functions and contribute to AIDS pathogenesis.
Genogroup IV and VI Canine Noroviruses Interact with Histo-Blood Group Antigens
Authors: Caddy Sarah , Breiman Adrien , le Pendu Jacques , Goodfellow Ian 
Published: July 2014

ABSTRACT
Human noroviruses (HuNV) are a significant cause of viral gastroenteritis in humans worldwide. HuNV attaches to cell surface carbohydrate structures known as histo-blood group antigens (HBGAs) prior to internalization, and HBGA polymorphism among human populations is closely linked to susceptibility to HuNV. Noroviruses are divided into 6 genogroups, with human strains grouped into genogroups I (GI), II, and IV. Canine norovirus (CNV) is a recently discovered pathogen in dogs, with strains classified into genogroups IV and VI. Whereas it is known that GI to GIII noroviruses bind to HBGAs and GV noroviruses recognize terminal sialic acid residues, the attachment factors for GIV and GVI noroviruses have not been reported. This study sought to determine the carbohydrate binding specificity of CNV and to compare it to the binding specificities of noroviruses from other genogroups. A panel of synthetic oligosaccharides were used to assess the binding specificity of CNV virus-like particles (VLPs) and identified α1,2-fucose as a key attachment factor. CNV VLP binding to canine saliva and tissue samples using enzyme-linked immunosorbent assays (ELISAs) and immunohistochemistry confirmed that α1,2-fucose-containing H and A antigens of the HBGA family were recognized by CNV. Phenotyping studies demonstrated expression of these antigens in a population of dogs. The virus-ligand interaction was further characterized using blockade studies, cell lines expressing HBGAs, and enzymatic removal of candidate carbohydrates from tissue sections. Recognition of HBGAs by CNV provides new insights into the evolution of noroviruses and raises concerns regarding the potential for zoonotic transmission of CNV to humans.

IMPORTANCE
Infections with human norovirus cause acute gastroenteritis in millions of people each year worldwide. Noroviruses can also affect nonhuman species and are divided into 6 different groups based on their capsid sequences. Human noroviruses in genogroups I and II interact with histo-blood group antigen carbohydrates, bovine noroviruses (genogroup III) interact with alpha-galactosidase (α-Gal) carbohydrates, and murine norovirus (genogroup V) recognizes sialic acids. The canine-specific strains of norovirus are grouped into genogroups IV and VI, and this study is the first to characterize which carbohydrate structures they can recognize. Using canine norovirus virus-like particles, this work shows that representative genogroup IV and VI viruses can interact with histo-blood group antigens. The binding specificity of canine noroviruses is therefore very similar to that of the human norovirus strains classified into genogroups I and II. This raises interesting questions about the evolution of noroviruses and suggests it may be possible for canine norovirus to infect humans.
Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 Antagonizes Beta Interferon Expression by Targeting the NF-κB Essential Modulator
Authors: Huang Chen , Zhang Qiong , Guo Xue-kun , Yu Zhi-bin , Xu Ao-Tian , Tang Jun , Feng Wen-hai 
Published: July 2014

ABSTRACT
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious pathogen that causes severe diseases in pigs and great economic losses to the swine industry worldwide. Type I interferons (IFNs) play a crucial role in antiviral immunity. In the present study, we demonstrated that infection with the highly pathogenic PRRSV strain JXwn06 antagonized type I IFN expression induced by poly(I·C) in both porcine alveolar macrophages (PAMs) and blood monocyte-derived macrophages (BMo). Subsequently, we showed that the inhibition of poly(I·C)-induced IFN-β production by PRRSV was dependent on the blocking of NF-κB signaling pathways. By screening PRRSV nonstructural and structural proteins, we demonstrated that nonstructural protein 4 (nsp4), a viral 3C-like serine protease, significantly suppressed IFN-β expression. Moreover, we verified that nsp4 inhibited NF-κB activation induced by signaling molecules, including RIG-I, VISA, TRIF, and IKKβ. nsp4 was shown to target the NF-κB essential modulator (NEMO) at the E349-S350 site to mediate its cleavage. Importantly, nsp4 mutants with defective protease activity abolished its ability to cleave NEMO and inhibit IFN-β production. These findings might have implications for our understanding of PRRSV pathogenesis and its mechanisms for evading the host immune response.

IMPORTANCE
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major agent of respiratory diseases in pigs. Like many other viruses, PRRSV has evolved a variety of strategies to evade host antiviral innate immunity for survival and propagation. In this study, we show that PRRSV nsp4 is a novel antagonist of the NF-κB signaling pathway, which is responsible for regulating the expression of type I interferons and other crucial cytokines. We then investigated the underlying mechanism used by nsp4 to suppress NF-κB-mediated IFN-β production. We found that nsp4 interfered with the NF-κB signaling pathway through the cleavage of NEMO (a key regulator of NF-κB signaling) at the E349-S350 site, leading to the downregulation of IFN-β production induced by poly(I·C). The data presented here may help us to better understand PRRSV pathogenesis.
Differential Responses of Plasmacytoid Dendritic Cells to Influenza Virus and Distinct Viral Pathogens
Authors: Thomas Jaime M. , Pos Zoltan , Reinboth Jennifer , Wang Richard Y. , Wang Ena , Frank Gregory M. , Lusso Paolo , Trinchieri Giorgio , Alter Harvey J. , Marincola Francesco M. , Thomas Emmanuel 
Published: July 2014

ABSTRACT
Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis.

IMPORTANCE
Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole.
Prospective cohort study of fever incidence and risk in elderly persons living at home
Authors: Yokobayashi Kenichi , Matsushima Masato , Watanabe Takamasa , Fujinuma Yasuki , Tazuma Susumu 
Published: July 2014

ObjectiveTo determine the incidence of fever among elderly persons under home medical management, diagnosis at fever onset and outcomes from a practical standpoint.DesignProspective cohort study.Setting5 clinics in residential areas of Tokyo that process an average of 50–200 outpatients/day.ParticipantsPatients (n=419) aged ≥65 years who received home medical management from the five clinics between 1 October 2009 and 30 September 2010.Main outcome measuresFever (≥37.5°C or ≥1.5°C above usual body temperature), diagnosis at onset and outcomes (cure at home, hospitalisation and death).ResultsThe incidence of fever was 2.5/1000 patient-days (95% CI 2.2 to 2.8). Fever occurred at least once (229 fever events) among one-third of the participants during the study period. Fever was more likely to arise in the wheelchair users or bedridden than in ambulatory individuals (HR 1.9 (95% CI 1.3 to 2.8; p<0.01); in patients with moderate-to-severe rather than those with none-to-mild cognitive impairment (HR, 1.7 (95% CI 1.1 to 2.6, p=0.01); and in those whose care-need levels were ≥3 rather than ≤2 (HR, 4.5 (95% CI 2.9 to 7.0; p<0.01). The causes of fever were pneumonia/bronchitis (n=103), skin and soft tissue infection (n=26), urinary tract infection (n=22) and the common cold (n=13). Fever was cured in 67% and 23% of patients at home and in hospital, respectively, and 5% of patients each died at home and in hospital. Antimicrobial agents treated 153 (67%) events in the home medical care setting.ConclusionsFever was more likely to occur in those requiring higher care levels and the main cause of fever was pneumonia/bronchitis. Healthcare providers should consider the conditions of elderly residents with lower objective functional status.
‘It would not be tolerated in any other profession except medicine’: survey reporting on undergraduates’ exposure to bullying and harassment in their first placement year
Authors: Timm Anja 
Published: July 2014

ObjectivesTo determine the extent to which undergraduate medical students experience (and/or witness) bullying and harassment during their first year on full-time placements and to compare with new General Medical Council (GMC) evidence on bullying and harassment of doctors in training.SettingA UK university offering medical and nursing undergraduate programmes.Participants309 medical and nursing undergraduate students with 30–33 weeks’ placement experience (123 medical students and 186 nursing students); overall response rate: 47%.Primary and secondary outcome measures(A) students’ experience of bullying and harassment; (B) witnessing bullying and harassment; (C) actions taken by students; (D) comparison of medical and nursing students’ data.ResultsWithin 8 months of starting clinical placements, a fifth of medical and a quarter of nursing students reported experiencing bullying and harassment. Cohorts differ in the type of exposure reported and in their responses. Whereas some nursing students follow incidences with query and challenge, most medical students acquiesce.ConclusionsBullying and harassment of medical (and nursing) students—as well as witnessing of such incidents—occurs as soon as students enter the clinical environment. This augments evidence published by the GMC in its first report on undermining of doctors in training (December 2013). The data suggest differences between nursing and medical students in how they respond to such incidents.
Do short birth intervals have long-term implications for parental health? Results from analyses of complete cohort Norwegian register data
Authors: Grundy Emily , Kravdal Øystein 
Published: July 2014

BackgroundShort and very long interbirth intervals are associated with worse perinatal, infant and immediate maternal outcomes. Accumulated physiological, mental, social and economic stresses arising from raising children close in age may also mean that interbirth intervals have longer term implications for the health of mothers and fathers, but few previous studies have investigated this.MethodsDiscrete-time hazards models were estimated to analyse associations between interbirth intervals and mortality risks for the period 1980–2008 in complete cohorts of Norwegian men and women born during 1935–1968 who had had two to four children. Associations between interbirth intervals and use of medication during 2004–2008 were also analysed using ordinary least-squares regression. Covariates included age, year, education, age at first birth, parity and change in coparent since the previous birth.ResultsMothers and fathers of two to three children with intervals between singleton births of less than 18 months, and mothers of twins, had raised mortality risks in midlife and early old age relative to parents with interbirth intervals of 30–41 months. For parents with three or four children, longer average interbirth intervals were associated with lower mortality. Short intervals between first and second births were also positively associated with medication use. Very long intervals were not associated with raised mortality or medication use when change of coparent since the previous birth was controlled.ConclusionsClosely spaced and multiple births may have adverse long-term implications for parental health. Delayed entry to parenthood and increased use of fertility treatments mean that both are increasing, making this a public health issue which needs further investigation.
Suicide in adults released from prison in Queensland, Australia: a cohort study
Authors: Spittal Matthew J , Forsyth Simon , Pirkis Jane , Alati Rosa , Kinner Stuart A 
Published: July 2014

BackgroundPrevious research has demonstrated elevated mortality following release from prison. We contrasted the risk of opioid overdose death with the risk of suicide in a cohort of adults released from prison in Queensland, Australia over a 14-year-period. We examine risk factors for suicide in the cohort, and make comparisons with the general population.MethodWe constructed a retrospective cohort of all adults released from prison between 1994 and 2007 and linked this to the National Death Index for deaths up to 31 December 2007.ResultsWe identified 41 970 individuals released from prison. Of the 2158 deaths in the community, 371 were suicides (crude mortality rate (CMR) 13.7/10 000 person-years) and 396 were due to drug-related causes (CMR 14.6/10 000 person-years). We observed a spike in drug-related deaths in the first 2 weeks after release from prison but no such pattern was observed for suicide. Being married (HR 0.40) and number of prior imprisonments (HR 3.1 for ≥5 prior incarcerations compared with none) independently predicted suicide. Age, sex, Indigenous status, length of incarceration and offence history were not associated with suicide. The standardised mortality ratios indicated that released women were 14.2 times and released men 4.8 times more likely to die from suicide than would be expected in the population.ConclusionsThis study demonstrates that the rate of suicide in adults released from prison is similar to the rate of drug-related deaths. Strategies that provide support to vulnerable people after release may reduce suicide in this population.
Advances in the study of naturally fractured hydrocarbon reservoirs: a broad integrated interdisciplinary applied topic
Authors: Spence Guy H. , Couples Gary D. , Bevan Tim G. , Aguilera Roberto , Cosgrove John W. , Daniel Jean-Marc , Redfern Jonathan 
Published: July 2014

Abstract
Naturally fractured reservoirs, within which porosity, permeability pathways and/or impermeable barriers formed by the fracture network interact with those of the host rock matrix to influence fluid flow and storage, can occur in sedimentary, igneous and metamorphic rocks. These reservoirs constitute a substantial percentage of remaining hydrocarbon resources; they create exploration targets in otherwise impermeable rocks, including under-explored crystalline basement, and they can be used as geological stores for anthropogenic carbon dioxide. Their complex fluid flow behaviour during production has traditionally proved difficult to predict, causing a large degree of uncertainty in reservoir development. The applied study of naturally fractured reservoirs seeks to constrain this uncertainty and maximize production by developing new understanding, and is necessarily a broad, integrated, interdisciplinary topic. Some of the methods, challenges and advances in characterizing the interplay of rock matrix and fracture networks relevant to fluid flow and hydrocarbon recovery are reviewed and discussed via the contributions in this volume.
Mudarrisūn e muḥaddiṯūn a Damasco negli awāmir sulṭāniyyah (1876-1908)
Authors: Sicari Daniele 
Published: July 2014

The Center for Historical Documentation of Damascus, which was founded in 1960, houses a relevant variety of first-hand sources dating back to the Ottoman period, which prove to be fundamental in order to better define some peculiar aspects of history of Bilād al-Šām, such as the role of ʿulamāʾ and transmission of knowledge.
As far as this is concerned, the awāmir sulṭāniyyah represent an essential part of the documentation, not only for the number of biographical data about mudarrisūn and muḥadditūn who were living and teaching in Damascus, but also for the particular relationship that they established with the main cultural institutions of the city, such as the traditional madāris.
Through the analysis of the awāmir, which still require a specific attention by the Oriental studies, our research focuses on some representative cases, in order to give evidence of the cultural richness and the extraordinary ferment in a period most marked by administrative, social and institutional reforms.
Somewhere Over the Rainbow: How to Make Effective Use of Colors in Meteorological Visualizations
Authors: Stauffer Reto , Mayr Georg J. , Dabernig Markus , Zeileis Achim 
Published: July 2014

AbstractResults of many atmospheric science applications are processed graphically. Visualizations are a powerful tool to display and communicate data. However, to create effective figures, a wide scope of challenges has to be considered. Therefore, this paper offers several guidelines with a focus on colors. Colors are often used to add additional information or to code information. Colors should (i) allow humans to process the information rapidly, (ii) guide the reader to the most important information, and (iii) represent the data appropriately without misleading distortion. The second and third requirements necessitate tailoring the visualization and the use of colors to the specific purpose of the graphic. A standard way of deriving color palettes is via transitions through a particular color space. Most of the common software packages still provide default palettes derived in the red–green–blue (RGB) color model or “simple” transformations thereof. Confounding perceptual properties such as hue and brightness make RGB-based palettes more prone to misinterpretation. Switching to a color model corresponding to the perceptual dimensions of human color vision avoids these problems. The authors show several practically relevant examples using one such model, the hue–chroma–luminance (HCL) color model, to explain how it works and what its advantages are. Moreover, the paper contains several tips on how to easily integrate this knowledge into software commonly used by the community. The guidelines and examples should help readers to switch over to the alternative HCL color model, which will result in a greatly improved quality and readability of visualized atmospheric science data for research, teaching, and communication of results to society.