bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influenza A Virus Genotype Determines the Antiviral Function of NF-κB
Authors: Dam Sharmistha , Kracht Michael , Pleschka Stephan , Schmitz M. Lienhard 
Published: June 2016

ABSTRACTThe role of NF-κB in influenza A virus (IAV) infection does not reveal a coherent picture, as pro- and also antiviral functions of this transcription factor have been described. To address this issue, we used clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9)-mediated genome engineering to generate murine MLE-15 cells lacking two essential components of the NF-κB pathway. Cells devoid of either the central NF-κB essential modulator (NEMO) scaffold protein and thus defective in IκB kinase (IKK) activation or cells not expressing the NF-κB DNA-binding and transactivation subunit p65 were tested for propagation of the SC35 virus, which has an avian host range, and its mouse-adapted variant, SC35M. While NF-κB was not relevant for replication of SC35M, the absence of NF-κB activity increased replication of the nonadapted SC35 virus. This antiviral effect of NF-κB was most prominent upon infection of cells with low virus titers as they usually occur during the initiation phase of IAV infection. The defect in NF-κB signaling resulted in diminished IAV-triggered phosphorylation of interferon regulatory factor 3 (IRF3) and expression of the antiviral beta interferon (IFN-β) gene. To identify the viral proteins responsible for NF-κB dependency, reassortant viruses were generated by reverse genetics. SC35 viruses containing the SC35M segment encoding neuraminidase (NA) were completely inert to the inhibitory effect of NF-κB, emphasizing the importance of the viral genotype for susceptibility to the antiviral functions of NF-κB.IMPORTANCEThis study addresses two different issues. First, we investigated the role of the host cell transcription factor NF-κB in IAV replication by genetic manipulation of IAVs by reverse genetics combined with targeted genome engineering of host cells using CRISPR-Cas9. The analysis of these two highly defined genetic systems indicated that the IAV genotype can influence whether NF-κB displays an antiviral function and thus might in part explain incoherent results from the literature. Second, we found that perturbation of NF-κB function greatly improved the growth of a nonadapted IAV, suggesting that NF-κB may contribute to the maintenance of the host species barrier.
Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection
Authors: Dagenais-Lussier Xavier , Aounallah Mouna , Mehraj Vikram , El-Far Mohamed , Tremblay Cecile , Sekaly Rafick-Pierre , Routy Jean-Pierre , van Grevenynghe Julien 
Published: June 2016

ABSTRACT

Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant
N
-acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection.

IMPORTANCE
The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection.
Crystallographic control on lithium isotope fractionation in Archean to Cenozoic lithium-cesium-tantalum pegmatites
Authors: Magna Tomáš , Novák Milan , Cempírek Jan , Janoušek Vojtěch , Ullmann Clemens V. , Wiechert Uwe 
Published: June 2016

Abstract
The age distribution of lithium-cesium-tantalum (LCT) pegmatites largely overlaps with major phases of collisional orogenic events and assembly of supercontinents. Some of the largest known LCT pegmatite deposits formed in very short intervals, 2.7–2.5 Ga and 1.9–1.8 Ga, corresponding to two major pulses of continental crust growth. However, the exact process of generation and segregation of large volumes of Li-bearing pegmatite liquids, perhaps involving disequilibrium fractional crystallization and leaving residual melts enriched in fluxing elements such as B, F, H2O, Li, and P, remains obscure. The new data on Li contents and isotope compositions in major mineral phases from temporally and geographically separated pegmatite bodies document extreme variations in δ7Li values among individual large LCT pegmatite bodies, in particular Archean occurrences. The observed &gt;10‰ variations in δ7Li values for the same mineral phases from different localities (i.e., beryl, petalite, spodumene, lepidolite, amblygonite, muscovite) contrast with globally homogeneous Li isotope systematics of major mineral phases from unmodified mantle rocks. Consistent Li isotope offsets between coexisting mineral phases are best explained by Li isotope fractionation as a function of the bond length between Li and neighboring ions (O, OH, F). We suggest that spatially distinct Li isotope patterns act as fingerprints for different pegmatites and can be explained by the preexisting Li isotope differences of their crustal sources at the time of pegmatite formation owing to differences in crustal age and evolution. This would imply secular evolution of the continental crust over Earth history toward present-day globally broadly uniform crustal 7Li/6Li ratios (δ7Li ∼0‰). The differences among Archean occurrences could reflect possible Archean paleogeography and could be linked with different thermal regimes of individual cratons as a consequence of variations in crustal thickness. One possible application of the new data set may be in source verification of gem-quality stones by using Li isotopes.
Obliquity-forced climate during the Early Triassic hothouse in China
Authors: Li Mingsong , Huang Chunju , Hinnov Linda , Ogg James , Chen Zhong-Qiang , Zhang Yang 
Published: June 2016

Abstract
The start of the Mesozoic Era is marked by roughly 5 m.y. of Earth system upheavals, including unstable biotic recovery, repeated global warming, ocean anoxia, and perturbations in the global carbon cycle. Intervals between crises were comparably hospitable to life. The causes of these upheavals are unknown, but are thought to be linked to recurrent Siberian volcanism. Here, two marine sedimentary successions at Chaohu and Daxiakou (South China) are evaluated for paleoclimate change from astronomical forcing. In these sections, gamma-ray variations indicative of terrestrial weathering reveal enhanced obliquity cycling over prolonged intervals, characterized by a 32.8 k.y. periodicity with strong 1.2 m.y. modulations. These suggest a 22 h length of day and 1.2 m.y. interaction between the orbital inclinations of Earth and Mars. Comparing the 1.2 m.y. obliquity modulation cycles in these sections with Early Triassic records of global sea level, temperature, redox, and biotic evolution suggests that long-term astronomical forcing was involved in the repeated climatic and biotic upheavals that took place throughout the Early Triassic.
Water loss and the origin of thick ultramylonites
Authors: Finch Melanie A. , Weinberg Roberto F. , Hunter Nicholas J.R. 
Published: June 2016

Abstract
Hydrolytic weakening has been suggested as a major process facilitating strain localization, in line with many studies that found a positive correlation between water content and intensity of deformation. We examine the role of water in the unusually thick ultramylonite of the El Pichao shear zone, northwestern Argentina. We used Fourier transform infrared spectroscopy to measure water content in quartz and feldspar, comparing ultramylonitic rocks to mylonites and weakly deformed rocks. Quartz and feldspar in ultramylonites contained half the water of weakly deformed rocks, contrary to findings in previous studies. We propose that the kilometer-thick ultramylonite formed in three stages: (1) localized deformation and recrystallization caused release of intracrystalline water to grain boundaries, which promoted grain-boundary sliding, forming the ultramylonite; (2) high pressure in the shear zone continuously expelled intercrystalline water to the surroundings, drying the boundaries and leading to strain hardening; and (3) water migrated to less deformed rocks causing hydrolytic weakening, repeating the cycle and widening the ultramylonite.
Formation of continental fragments: The Tamayo Bank, Gulf of California, Mexico
Authors: Abera R. , van Wijk J. , Axen G. 
Published: June 2016

Abstract
We present a model for microcontinent formation that is based on the structure of the Tamayo trough in the Gulf of California, Mexico. Potential field modeling of a transect through the Tamayo trough and Tamayo Bank suggests that the crust of the Tamayo trough is oceanic, and that the Tamayo Bank is a detached continental fragment. The oceanic crust that separates the Tamayo Bank from the mainland of Mexico is thin (5 km), so oceanic spreading was probably magma starved before it ceased. Such a thin crust has also been described on the Aegir Ridge in the North Atlantic, which became extinct after the Jan Mayen microcontinent separated from Greenland. In our model for the origin of microcontinents, the locus of plate spreading jumps to the weakened continental margin when the spreading ridge becomes amagmatic and the force required for continued extension at the ridge increases. A microcontinent is formed when the ridge jumps into a continental margin, and an asymmetric ocean basin or microplate is formed when the ridge jumps within oceanic crust.
Ethnic differences in prediabetes and diabetes in the Suriname Health Study
Authors: Krishnadath Ingrid S K , Nahar-van Venrooij Lenny M , Jaddoe Vincent W V , Toelsie Jerry R 
Published: June 2016

BackgroundDiabetes is increasing worldwide, and information on risk factors to develop targeted interventions is limited. Therefore, we analyzed data of the Suriname Health Study to estimate the prevalence of prediabetes and diabetes. We also explored whether ethnic differences in prediabetes or diabetes risk could be explained by biological, demographic, lifestyle, anthropometric, and metabolic risk factors.MethodThe study was designed according to the WHO Steps guidelines. Fasting blood glucose levels were measured in 3393 respondents, aged 15–65 years, from an Amerindian, Creole, Hindustani, Javanese, Maroon or Mixed ethnic background. Prediabetes was defined by fasting blood glucose levels between 6.1 and 7.0 mmol/L and diabetes by fasting blood glucose levels ≥7.0 mmol/L or ‘self-reported diabetes medication use.’ For all ethnicities, we analyzed sex, age, marital status, educational level, income status, employment, smoking status, residence, physical activity, body mass index, waist circumference, hypertension, and the levels of triglyceride, total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol.ResultsThe prevalence of prediabetes was 7.4%, while that of diabetes was 13 0%. From these diabetes cases, 39.6% were not diagnosed previously. No ethnic differences were observed in the prevalence of prediabetes. For diabetes, Hindustanis (23.3%) had twice the prevalence compared to other ethnic groups (4.7–14.2%). The associations of the risk factors with prediabetes or diabetes varied among the ethnic groups. The differences in the associations of ethnic groups with prediabetes or diabetes were partly explained by these risk factors.ConclusionsThe prevalence of diabetes in Suriname is high and most elevated in Hindustanis. The observed variations in risk factors among ethnic groups might explain the ethnic differences between these groups, but follow-up studies are needed to explore this in more depth.
Perceptions of risk and predictive testing held by the first-degree relatives of patients with rheumatoid arthritis in England, Austria and Germany: a qualitative study
Authors: Stack Rebecca J , Stoffer Michaela , Englbrecht Mathias , Mosor Erika , Falahee Marie , Simons Gwenda , Smolen Josef , Schett Georg , Buckley Chris D , Kumar Kanta , Hansson Mats , Hueber Axel , Stamm Tanja , Raza Karim 
Published: June 2016

ObjectivesThe family members of patients with rheumatoid arthritis (RA) are at increased risk of developing RA and are potential candidates for predictive testing. This study explored the perceptions of first-degree relatives of people with RA about being at risk of RA and engaging in predictive testing.Methods34 first-degree relatives (siblings and offspring) of patients with RA from the UK, Germany and Austria participated in semistructured interviews about their perceptions of RA risk and the prospect of predictive testing. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.ResultsFirst-degree relatives were aware of their susceptibility to RA, but were unsure of the extent of their risk. When considering their future risk, some relatives were concerned about the potential impact that RA would have on their lives. Relatives were concerned that knowing their actual risk would increase their anxiety and would affect decisions about their future. Also, relatives were concerned about the levels of uncertainty associated with predictive testing. Those in favour of knowing their future risk felt that they would need additional support to understand the risk information and cope with the emotional impact of this information.ConclusionsIdentifying individuals at risk of RA may allow targeted interventions to reduce the risk and consequence of future disease; however, relatives have concerns about predictive testing and risk information. The development of strategies to quantify and communicate risk needs to take these views into account and incorporate approaches to mitigate concerns and minimise the psychological impact of risk information.
Regional variation of patient behaviour and reasons for consultation in the general practice of Northern Germany: protocol for an observational study
Authors: Schäfer Ingmar , Hansen Heike , Pohontsch Nadine , Bole Laura , Wagner Hans-Otto , Führ Miriam , Lühmann Dagmar , Scherer Martin 
Published: June 2016

IntroductionInappropriate supply and an increasing demand on the healthcare system have been of concern for health policy in Germany for at least 15 years. In the primary care setting, this especially relates to an undersupply of general practitioners (GPs) in the countryside. In addition, there seem to be other regional differences, for example, a difference in accessing primary and secondary care between rural and urban areas. Despite these findings, regional differences in health services have not been studied extensively in Germany. Therefore, this study aims to explore regional variations of patient populations and reasons for accessing primary medical care.Methods and analysisWe will conduct a cross-sectional observational study based on standardised interviews with 240 GPs and ∼1200 patients. Data collection started on 10 June 2015 and will probably be completed by 31 October 2016. We will include all districts and cities within 100 km from Hamburg and assign them according to the type of regions: rural, urban and environs. All eligible GPs will be invited to participate. Each practice will recruit up to 15 patients, aged 18 years or older. Questionnaires are based on a preliminary qualitative study and were pretested. Data will be analysed with descriptive statistics and regression modelling strategies adjusted for confounders and the GP-induced cluster structure.Ethics and disseminationOur study was approved by the Ethics Committee of the Medical Association of Hamburg and is conducted in accordance with the Declaration of Helsinki. Study participants give written informed consent before data collection and data is pseudonymised. Survey data and person identifiers are stored separately in locked cabinets and have restricted availability. The results of our study will be presented at conferences and published in peer-reviewed journals.Trial registration numberNCT02558322; Pre-results.
Estimated association between dwelling soil contamination and internal radiation contamination levels after the 2011 Fukushima Daiichi nuclear accident in Japan
Authors: Tsubokura Masaharu , Nomura Shuhei , Sakaihara Kikugoro , Kato Shigeaki , Leppold Claire , Furutani Tomoyuki , Morita Tomohiro , Oikawa Tomoyoshi , Kanazawa Yukio 
Published: June 2016

ObjectivesMeasurement of soil contamination levels has been considered a feasible method for dose estimation of internal radiation exposure following the Chernobyl disaster by means of aggregate transfer factors; however, it is still unclear whether the estimation of internal contamination based on soil contamination levels is universally valid or incident specific.MethodsTo address this issue, we evaluated relationships between in vivo and soil cesium-137 (Cs-137) contamination using data on internal contamination levels among Minamisoma (10–40 km north from the Fukushima Daiichi nuclear power plant), Fukushima residents 2–3 years following the disaster, and constructed three models for statistical analysis based on continuous and categorical (equal intervals and quantiles) soil contamination levels.ResultsA total of 7987 people with a mean age of 55.4 years underwent screening of in vivo Cs-137 whole-body counting. A statistically significant association was noted between internal and continuous Cs-137 soil contamination levels (model 1, p value <0.001), although the association was slight (relative risk (RR): 1.03 per 10 kBq/m2increase in soil contamination). Analysis of categorical soil contamination levels showed statistical (but not clinical) significance only in relatively higher soil contamination levels (model 2: Cs-137 levels above 100 kBq/m2compared to those <25 kBq/m2, RR=1.75, p value <0.01; model 3: levels above 63 kBq/m2compared to those <11 kBq/m2, RR=1.45, p value <0.05).ConclusionsLow levels of internal and soil contamination were not associated, and only loose/small associations were observed in areas with slightly higher levels of soil contamination in Fukushima, representing a clear difference from the strong associations found in post-disaster Chernobyl. These results indicate that soil contamination levels generally do not contribute to the internal contamination of residents in Fukushima; thus, individual measurements are essential for the precise evaluation of chronic internal radiation contamination.
Group-based exercise in daily clinical practice to improve physical fitness in men with prostate cancer undergoing androgen deprivation therapy: study protocol
Authors: Østergren Peter , Ragle Anne-Mette , Jakobsen Henrik , Klausen Tobias Wirenfeldt , Vinther Anders , Sønksen Jens 
Published: June 2016

IntroductionLevel 1 evidence supports the use of supervised exercise to mitigate the adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. The data, however, have been generated in controlled research settings and might not be transferable to daily clinical practice. This article describes the design of an ongoing prospective observational study to evaluate the potential benefits of exercise in daily clinical practice.Methods and analysisMen diagnosed with prostate cancer starting or already receiving ADT at our facility are invited to participate in a 12-week exercise programme implemented as the standard of care. Exclusion criteria are opioid-demanding treatment for skeletal pain, an Eastern Cooperative Oncology Group (ECOG) performance status above 2 or the inability to perform floor and machine exercises independently. The intervention consists of an initial educational session of 1½ hours followed by 12 weeks of group-based supervised training two times a week. The focus of the exercise is progressive resistance training in combination with aerobic training. Participants are measured at baseline, after 12 weeks and after 24 weeks as part of the programme. Primary endpoints of this study are changes in physical fitness evaluated by the 30 s Chair-Stand Test and Graded Cycling Test with Talk Test. Secondary endpoints include changes in quality of life, body composition and safety of exercise. Inclusion started in August 2014, with 169 participants being included by December 2015.Ethics and disseminationThe study has been reviewed by the Scientific Ethical Committee of the Capital Region of Denmark (reference number H-3-2013-FSP39). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums.Trial registration numberNCT02631681; Pre-results.
High birth weight in a suburban hospital in Cameroon: an analysis of the clinical cut-off, prevalence, predictors and adverse outcomes
Authors: Choukem Simeon-Pierre , Njim Tsi , Atashili Julius , Hamilton-Shield Julian P , Mbu Robinson 
Published: June 2016

Background and aimsHigh birth weight (HBW) increases the risk of maternal and fetal morbidity and mortality. Its prevalence and adverse outcomes may be reduced if risk factors are identified and managed during pregnancy. The cut-off value for HBW remains debatable. The objectives of this study were to identify the optimal cut-off value and determine the prevalence, predictors and adverse outcomes of HBW in a suburban area of Cameroon.DesignA 6-year retrospective register analysis and a 3-month prospective phase.SettingA secondary care level (regional) hospital in the city of Buea (southwest region of Cameroon).ParticipantsWomen who delivered in this hospital over a 6-year period (retrospective phase) and consenting pregnant mothers and their infants (singletons, born at >28 weeks gestation) (prospective phase).Outcome measures90th centile of birth weights; prevalence of HBW defined as birth weight above the 90th centile; sociodemographic, maternal and obstetrical factors associated with HBW; maternal and neonatal adverse outcomes of HBW.ResultsOf the 4941 newborns reviewed in registers, the 90th centile of birth weights was 3850 g. Using this new cut-off, we obtained a prevalence of 14.0% for HBW in the 200 newborns included in the prospective phase. This was significantly higher than the prevalence (9.5%) yielded when the traditional cut-off of 4000 g was used (p=0.003). None of the factors assessed was independently associated with HBW. Newborns with HBW were more likely to have shoulder dystocia (p<0.01), and their mothers more likely to suffer from prolonged labour (p=0.01) and postpartum haemorrhage (p<0.01).ConclusionsThe results of this study suggest that the cut-off for HBW in this population should be 3850 g. Thus, 3 of every 10 babies born with HBW in this hospital are likely not receiving optimal postnatal care because 4000 g is currently used to qualify for additional support.