julilili42/papers huggingface dataset:
Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity
2016-01-19

Abstract Background Gastrointestinal hormone release and the regulation of appetite and body weight are thought to be dysbalanced in obesity. However, human data investigating the expression of gastrointestinal hormones in the obese are rare. We studied the expression of ghrelin, leptin, and the serotonergic system in stomach tissue and serum of obese and non‐obese individuals. Methods Gastric tissue and serum were collected from 29 adult obese ( BMI 48.7 ± 10.6 kg/m 2 ; mean ± SD ) who underwent laparoscopic sleeve gastrectomy. Gastric biopsies, surgery specimen or serum was obtained from 35 adult non‐obese humans ( BMI 22.7 ± 1.9 kg/m 2 ). Ghrelin, ghrelin O‐acyl transferase ( GOAT ), leptin, leptin receptor, and tryptophan hydroxylase 1 ( TPH 1) mRNA expression were measured by qRT ‐ PCR . Serotonin (5 HT ) and leptin protein concentration were quantified in tissue extracts and serum; GOAT and ghrelin‐positive cells were immunohistologically quantified in tissue. Additionally, 21 blood immune markers were analyzed. Key Results In gastric tissue, GOAT ‐positive cells were reduced ( p &lt; 0.01), but ghrelin‐positive cells and mRNA were increased (both p &lt; 0.05) in obese compared with non‐obese individuals. Gastric leptin ( p &lt; 0.001) and leptin receptor ( p &lt; 0.001) mRNA expression, as well as leptin concentrations in serum ( p &lt; 0.001), were increased in obese compared with non‐obese individuals. Serum 5 HT was reduced ( p &lt; 0.05), while tissue 5 HT and TPH 1 mRNA were reduced only by trend. Interleukin 1 receptor a (IL1Ra), IL ‐8, IL ‐12, and monocyte chemoattractant protein 1 (IL1Ra) were increased and IL 1Ra correlated negatively with serum leptin. Conclusions &amp; Inferences Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation.
Assessment of a new point-of-care system for detection of prostate specific antigen
2016-01-19

The POC system obtained good concordance to elaborate laboratory measurement. In a screening scenario, the system provides quick and reliable PSA measurement, especially in the PSA range up to 4 ng/ml.
Financial inclusion and poverty alleviation: How to achieve the desired results
2016-01-19

Did you realize that there are more than 2.5 billion individuals with no ledgers on the planet, and the majority of them are in Asia? Also, under one quarter of the world's 2.4 billion poor have a financial balance. Dealing with their cash utilizing formal money related administrations – investment accounts, advances, protection, and settlements — is a magnificent, unpleasant, incomprehensible dream for some, numerous families.
Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab
2016-01-20

Abstract Purpose: To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients. Experimental Design: Frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan–Meier and Cox regression analysis, including calibration and discrimination by C-statistics. Results: Low baseline LDH, absolute monocyte counts (AMC), Lin−CD14+HLA-DR−/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. Patients (43.5%) presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2–0) was also associated with OS (P &amp;lt; 0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort. Conclusions: A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g., PD-1 antibodies, is warranted. Clin Cancer Res; 22(12); 2908–18. ©2016 AACR.
Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2
2016-01-20

In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. LC-MS analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. In addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 putative congeners have been detected. Nine compounds, carbamidocyclophanes M−U, were isolated, and their structural elucidation by 1D and 2D NMR experiments in combination with HRMS and ECD analysis revealed that they are brominated analogues of chlorinated carbamidocyclophanes. Quantification of the carbamidocyclophanes showed that chloride is the preferably utilized halide, but incorporation is reduced in the presence of bromide. Evaluation of the antibacterial activity of 30 [7.7]paracyclophanes and related derivatives against selected pathogenic Gram-positive and Gram-negative bacteria exhibited remarkable effects especially against methicillin- and vancomycin-resistant staphylococci and Mycobacterium tuberculosis. For deeper insights into the mechanisms of biosynthesis, the carbamidocyclophane biosynthetic gene cluster in Nostoc sp. CAVN2 was studied. The gene putatively coding for the carbamoyltransferase has been identified. Based on bioinformatic analyses, a possible biosynthetic assembly is discussed.
On the Evolutionary History of Uleiella chilensis, a Smut Fungus Parasite of Araucaria araucana in South America: Uleiellales ord. nov. in Ustilaginomycetes
2016-01-20

The evolutionary history, divergence times and phylogenetic relationships of Uleiella chilensis (Ustilaginomycotina, smut fungi) associated with Araucaria araucana were analysed. DNA sequences from multiple gene regions and morphology were analysed and compared to other members of the Basidiomycota to determine the phylogenetic placement of smut fungi on gymnosperms. Divergence time estimates indicate that the majority of smut fungal orders diversified during the Triassic-Jurassic period. However, the origin and relationships of several orders remain uncertain. The most recent common ancestor between Uleiella chilensis and Violaceomyces palustris has been dated to the Lower Cretaceous. Comparisons of divergence time estimates between smut fungi and host plants lead to the hypothesis that the early Ustilaginomycotina had a saprobic lifestyle. As there are only two extant species of Araucaria in South America, each hosting a unique Uleiella species, we suggest that either coevolution or a host shift followed by allopatric speciation are the most likely explanations for the current geographic restriction of Uleiella and its low diversity. Phylogenetic and age estimation analyses, ecology, the unusual life-cycle and the peculiar combination of septal and haustorial characteristics support Uleiella chilensis as a distinct lineage among the Ustilaginomycotina. Here, we describe a new ustilaginomycetous order, the Uleiellales to accommodate Uleiella. Within the Ustilaginomycetes, Uleiellales are sister taxon to the Violaceomycetales.
How the innate immune system trains immunity: lessons from studying atopic dermatitis and cutaneous bacteria
2016-01-20

Summary The skin is the largest organ at the interface between environment and host. It plays a major protective role against pathogens as physical barrier, as site of first recognition, and as orchestrator of consecutive immune responses. In this process, immunological crosstalk between skin‐resident and immune cells is required, and fixed innate immune responses were previously believed to orchestrate adaptive immunity of B and T lymphocytes. Today, we understand that diverse qualities of immune responses to different microbes need to be regulated by also varying responses at the level of first microbe recognition through receptors of the innate immune system. Only fine‐tuning of the innate immune system allows for the orchestration of immune responses to the microbiota in the absence of inflammation as well as to pathogens in the context of protective responses including inflammation. Understanding how innate immunity precisely adapts is also important for diseases such as atopic dermatitis (AD) with chronic inflammation. In this review, we present data on how the innate immune system actually fine‐tunes its responses with special focus on the immunological consequences of cutaneous innate immune sensing through TLR2. These new insights are highly relevant for understanding microbiota‐associated state of health, immune defense, and the pathogenesis underlying chronic cutaneous inflammation as seen in AD.
Epoxomicin and Eponemycin Biosynthesis Involves gem‐Dimethylation and an Acyl‐CoA Dehydrogenase‐Like Enzyme
2016-01-20

Abstract The α′,β′‐epoxyketone moiety of proteasome inhibitors confers high binding specificity to the N‐terminal threonine in catalytic proteasome β‐subunits. We recently identified the epoxomicin and eponemycin biosynthetic gene clusters and have now conducted isotope‐enriched precursor feeding studies and comprehensive gene deletion experiments to shed further light on their biosynthetic pathways. Leucine and two methyl groups from S‐adenosylmethionine were readily incorporated into the epoxyketone warhead, suggesting decarboxylation of the thioester intermediate. Formation of the α′,β′‐epoxyketone is likely mediated by conserved acyl‐CoA dehydrogenase‐like enzymes, as indicated by complete loss of epoxomicin and eponemycin production in the respective knockout mutants. Our results clarify crucial questions in the formation of epoxyketone compounds and lay the foundation for in vitro biochemical studies on the biosynthesis of this pharmaceutically important class of proteasome inhibitors.
Sediment Reallocations due to Erosive Rainfall Events in the Three Gorges Reservoir Area, Central China
2016-01-20

Abstract Soil erosion by water outlines a major threat to the Three Gorges Reservoir Area in China. A detailed assessment of soil conservation measures requires a tool that spatially identifies sediment reallocations due to rainfall–runoff events in catchments. We applied EROSION 3D as a physically based soil erosion and deposition model in a small mountainous catchment. Generally, we aim to provide a methodological frame that facilitates the model parametrization in a data scarce environment and to identify sediment sources and deposits. We used digital soil mapping techniques to generate spatially distributed soil property information for parametrization. For model calibration and validation, we continuously monitored the catchment on rainfall, runoff and sediment yield for a period of 12 months. The model performed well for large events (sediment yield &gt; 1 Mg) with an averaged individual model error of 7.5%, while small events showed an average error of 36.2%. We focused on the large events to evaluate reallocation patterns. Erosion occurred in 11.1% of the study area with an average erosion rate of 49.9 Mg ha −1 . Erosion mainly occurred on crop rotation areas with a spatial proportion of 69.2% for ‘corn‐rapeseed’ and 69.1% for ‘potato‐cabbage’. Deposition occurred on 11.0%. Forested areas (9.7%), infrastructure (41.0%), cropland (corn‐rapeseed: 13.6%, potato‐cabbage: 11.3%) and grassland (18.4%) were affected by deposition. Because the vast majority of annual sediment yields (80.3%) were associated to a few large erosive events, the modelling approach provides a useful tool to spatially assess soil erosion control and conservation measures. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus
2016-01-21

The 14th–18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague’s persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.
Peptides in headlock – a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy
2016-01-21

Abstract Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a β-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once bound, the peptide is fastened by two nanobody side chains that clamp it in a headlock fashion. Exploiting this unusual binding mode, we generated a novel nanobody-derived capture and detection system. Matrix-coupled nanobody enables the fast and efficient isolation of epitope-tagged proteins from prokaryotic and eukaryotic expression systems. Additionally, the fluorescently labeled nanobody visualizes subcellular structures in different cellular compartments. The high-affinity-binding and modifiable peptide tag of this system renders it a versatile and robust tool to combine biochemical analysis with microscopic studies.
Design and Development of Microsomal Prostaglandin E2 Synthase-1 Inhibitors: Challenges and Future Directions
2016-01-21

Microsomal prostaglandin E2 synthase (mPGES)-1 is responsible for the massive prostaglandin E2 (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. The first selective mPGES-1 inhibitors recently entered clinical trials. Major challenges for drug development have been the high plasma protein binding of lead structures, interspecies discrepancies, nuisance inhibition, sophisticated enzyme assays, and limited structural information about the mPGES-1 inhibitor binding site. Since most of these drawbacks could be solved during the past few years, we are standing at the threshold of a new era of mPGES-1-targeting anti-inflammatory drugs. This perspective introduces mPGES-1 as a key player within the network of eicosanoid biosynthesis and summarizes our current understanding of its structure and mechanism. Moreover, we present high-throughput and in silico screening techniques and discuss the structure-activity relationship and pharmacological potential of major mPGES-1 inhibitor classes in light of recent insights from pharmacophore models and cocrystallization studies.
Tree species and functional traits but not species richness affect interrill erosion processes in young subtropical forests
2016-01-21

Abstract. Soil erosion is seriously threatening ecosystem functioning in many parts of the world. In this context, it is assumed that tree species richness and functional diversity of tree communities can play a critical role in improving ecosystem services such as erosion control. An experiment with 170 micro-scale run-off plots was conducted to investigate the influence of tree species and tree species richness as well as functional traits on interrill erosion in a young forest ecosystem. An interrill erosion rate of 47.5 Mg ha−1 a−1 was calculated. This study provided evidence that different tree species affect interrill erosion differently, while tree species richness did not affect interrill erosion in young forest stands. Thus, different tree morphologies have to be considered, when assessing soil erosion under forest. High crown cover and leaf area index reduced interrill erosion in initial forest ecosystems, whereas rising tree height increased it. Even if a leaf litter cover was not present, the remaining soil surface cover by stones and biological soil crusts was the most important driver for soil erosion control. Furthermore, soil organic matter had a decreasing influence on interrill erosion. Long-term monitoring of soil erosion under closing tree canopies is necessary, and a wide range of functional tree traits should be considered in future research.
Exploring reference group effects on teachers’ nominations of gifted students.
2016-01-21

Teachers are often asked to nominate students for enrichment programs for gifted children, and studies have repeatedly indicated that students’ intelligence is related to their likelihood of being nominated as gifted. However, it is unknown whether class-average levels of intelligence influence teachers’ nominations as suggested by theory—and corresponding empirical results—concerning reference group effects. Herein, it was hypothesized that when students’ individual fluid and crystallized intelligence scores were similar, students from classes with higher average levels of intelligence would have a lower probability of being nominated for an enrichment program for gifted children than students from classes with lower average levels of intelligence. Furthermore, we investigated whether 3 teacher variables—experience with giftedness, beliefs about the changeability of intelligence, and the belief that giftedness is holistic or domain specific—would influence the expected reference group effect. In a study comprising data from 105 teachers and 1,468 of their (German) third-grade students, we found support not only for a positive association between students’ individual intelligence scores and the probability that students would be nominated as gifted but also, more importantly, for the proposed reference group effect: When controlling for individual levels of intelligence, students’ probability of being nominated was higher in classes with lower average levels of intelligence. In addition, the results showed that this reference group effect was stronger when teachers saw giftedness as holistic rather than domain specific. Also, depending on teachers’ kinds of experience with giftedness, the reference group effect varied in size. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
Long‐term chemical evolution and modification of continental basement brines – a field study from the Schwarzwald, SW Germany
2016-01-21

Abstract Highly saline, deep‐seated basement brines are of major importance for ore‐forming processes, but their genesis is controversial. Based on studies of fluid inclusions from hydrothermal veins of various ages, we reconstruct the temporal evolution of continental basement fluids from the Variscan Schwarzwald (Germany). During the Carboniferous (vein type i), quartz–tourmaline veins precipitated from low‐salinity (&lt;4.5wt% NaCl + CaCl 2 ), high‐temperature (≤390°C) H 2 O‐NaCl‐( CO 2 ‐ CH 4 ) fluids with Cl/Br mass ratios = 50–146. In the Permian (vein type ii), cooling of H 2 O‐NaCl‐( KC l‐CaCl 2 ) metamorphic fluids (T ≤ 310°C, 2–4.5wt% NaCl + CaCl 2 , Cl/Br mass ratios = 90) leads to the precipitation of quartz‐Sb‐Au veins. Around the Triassic–Jurassic boundary (vein type iii), quartz–haematite veins formed from two distinct fluids: a low‐salinity fluid (similar to (ii)) and a high‐salinity fluid (T = 100–320°C, &gt;20wt% NaCl + CaCl 2 , Cl/Br mass ratios = 60–110). Both fluids types were present during vein formation but did not mix with each other (because of hydrogeological reasons). Jurassic–Cretaceous veins (vein type iv) record fluid mixing between an older bittern brine (Cl/Br mass ratios ~80) and a younger halite dissolution brine (Cl/Br mass ratios &gt;1000) of similar salinity, resulting in a mixed H 2 O‐NaCl‐CaCl 2 brine (50–140°C, 23–26wt% NaCl + CaCl 2 , Cl/Br mass ratios = 80–520). During post‐Cretaceous times (vein type v), the opening of the Upper Rhine Graben and the concomitant juxtaposition of various aquifers, which enabled mixing of high‐ and low‐salinity fluids and resulted in vein formation (multicomponent fluid H 2 O‐NaCl‐CaCl 2 ‐( SO 4 ‐ HCO 3 ), 70–190°C, 5–25wt% NaCl‐CaCl 2 and Cl/Br mass ratios = 2–140). The first occurrence of highly saline brines is recorded in veins that formed shortly after deposition of halite in the Muschelkalk Ocean above the basement, suggesting an external source of the brine's salinity. Hence, today's brines in the European basement probably developed from inherited evaporitic bittern brines. These were afterwards extensively modified by fluid–rock interaction on their migration paths through the crystalline basement and later by mixing with younger meteoric fluids and halite dissolution brines.
TGF-β1 and TGF-β2 abundance in liver diseases of mice and men
2016-01-21

TGF-β1 is a major player in chronic liver diseases promoting fibrogenesis and tumorigenesis through various mechanisms. The expression and function of TGF-β2 have not been investigated thoroughly in liver disease to date. In this paper, we provide evidence that TGF-β2 expression correlates with fibrogenesis and liver cancer development.Using quantitative realtime PCR and ELISA, we show that TGF-β2 mRNA expression and secretion increased in murine HSCs and hepatocytes over time in culture and were found in the human-derived HSC cell line LX-2. TGF-β2 stimulation of the LX-2 cells led to upregulation of the TGF-β receptors 1, 2, and 3, whereas TGF-β1 treatment did not alter or decrease their expression. In liver regeneration and fibrosis upon CCl4 challenge, the transient increase of TGF-β2 expression was accompanied by TGF-β1 and collagen expression. In bile duct ligation-induced fibrosis, TGF-β2 upregulation correlated with fibrotic markers and was more prominent than TGF-β1 expression. Accordingly, MDR2-KO mice showed significant TGF-β2 upregulation within 3 to 15 months but minor TGF-β1 expression changes. In 5 of 8 hepatocellular carcinoma (HCC)/hepatoblastoma cell lines, relatively high TGF-β2 expression and secretion were observed, with some cell lines even secreting more TGF-β2 than TGF-β1. TGF-β2 was also upregulated in tumors of TGFα/cMyc and DEN-treated mice. The analysis of publically available microarray data of 13 human HCC collectives revealed considerable upregulation of TGF-β2 as compared to normal liver.Our study demonstrates upregulation of TGF-β2 in liver disease and suggests TGF-β2 as a promising therapeutic target for tackling fibrosis and HCC.