bluuebunny/crossref_metadata_2025_split huggingface dataset:
Including Regional Knowledge Improves Baseflow Signature Predictions in Large Sample Hydrology
Authors: Gnann Sebastian J. , McMillan Hilary K. , Woods Ross A. , Howden Nicholas J. K. 
Published: November 2020

AbstractA catchment's hydrological response is controlled by climatic forcing and by the landscape through which water moves. Yet when we compare large samples of catchments, we often find climate to be the only good predictor of the hydrological response and a lot of variability is left unexplained. This contradicts extensive evidence from field and regional studies which shows the importance of catchment form (e.g., geology) on catchment hydrological processes, particularly on baseflow processes. We hypothesize that this is due to limitations in (a) the catchment attributes we use to inform our analyses and (b) the hydrological signatures we use to describe the hydrological response. To test these hypotheses, we use a large sample of catchment data across the contiguous United States. By reviewing literature from several U.S. regions, we show that region‐specific knowledge is underutilized in large sample studies. To organize the findings from these regions, we propose and apply a framework based on standardized perceptual models. Informed by these perceptual models, we use both available and newly calculated catchment attributes to show that baseflow signature predictions can be improved regionally. Multiple baseflow signatures are needed to better distinguish between different baseflow sources, such as the subsurface, surface water bodies, and snow. We conclude with pointing at potential future directions and argue that we should aim at a more systematic and hydrologically motivated selection of catchment attributes and hydrological signatures.
Crystalline iron oxides stimulate methanogenic benzoate degradation in marine sediment-derived enrichment cultures
Authors: Aromokeye David A , Oni Oluwatobi E , Tebben Jan , Yin Xiuran , Richter-Heitmann Tim , Wendt Jenny , Nimzyk Rolf , Littmann Sten , Tienken Daniela , Kulkarni Ajinkya C , Henkel Susann , Hinrichs Kai-Uwe , Elvert Marcus , Harder Tilmann , Kasten Sabine , Friedrich Michael W 
Published: November 2020

Abstract
Elevated dissolved iron concentrations in the methanic zone are typical geochemical signatures of rapidly accumulating marine sediments. These sediments are often characterized by co-burial of iron oxides with recalcitrant aromatic organic matter of terrigenous origin. Thus far, iron oxides are predicted to either impede organic matter degradation, aiding its preservation, or identified to enhance organic carbon oxidation via direct electron transfer. Here, we investigated the effect of various iron oxide phases with differing crystallinity (magnetite, hematite, and lepidocrocite) during microbial degradation of the aromatic model compound benzoate in methanic sediments. In slurry incubations with magnetite or hematite, concurrent iron reduction, and methanogenesis were stimulated during accelerated benzoate degradation with methanogenesis as the dominant electron sink. In contrast, with lepidocrocite, benzoate degradation, and methanogenesis were inhibited. These observations were reproducible in sediment-free enrichments, even after five successive transfers. Genes involved in the complete degradation of benzoate were identified in multiple metagenome assembled genomes. Four previously unknown benzoate degraders of the genera Thermincola (Peptococcaceae, Firmicutes), Dethiobacter (Syntrophomonadaceae, Firmicutes), Deltaproteobacteria bacteria SG8_13 (Desulfosarcinaceae, Deltaproteobacteria), and Melioribacter (Melioribacteraceae, Chlorobi) were identified from the marine sediment-derived enrichments. Scanning electron microscopy (SEM) and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) images showed the ability of microorganisms to colonize and concurrently reduce magnetite likely stimulated by the observed methanogenic benzoate degradation. These findings explain the possible contribution of organoclastic reduction of iron oxides to the elevated dissolved Fe2+ pool typically observed in methanic zones of rapidly accumulating coastal and continental margin sediments.
Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings
Authors: Ramoz Nicolas , Hoertel Nicolas , Nobile Bénédicte , Voegeli Géraldine , Nasr Ariane , Le Strat Yann , Courtet Philippe , Gorwood Philip 
Published: November 2020

AbstractPolymorphisms of genes involved in the hypothalamic–pituitary–adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6–8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C–rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.
Molecular basis of CTCF binding polarity in genome folding
Authors: Nora Elphège P. , Caccianini Laura , Fudenberg Geoffrey , So Kevin , Kameswaran Vasumathi , Nagle Abigail , Uebersohn Alec , Hajj Bassam , Saux Agnès Le , Coulon Antoine , Mirny Leonid A. , Pollard Katherine S. , Dahan Maxime , Bruneau Benoit G. 
Published: November 2020

AbstractCurrent models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin. Using an inducible complementation system, we find that CTCF mutants lacking the N-terminus cannot insulate TADs properly. Cohesin remains at CTCF sites in this mutant, albeit with reduced enrichment. Given the orientation of CTCF motifs presents the N-terminus towards cohesin as it translocates from the interior of TADs, these observations explain how the orientation of CTCF binding sites translates into genome folding patterns.
Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation
Authors: Jain Akanksha , Ulman Vladimir , Mukherjee Arghyadip , Prakash Mangal , Cuenca Marina B. , Pimpale Lokesh G. , Münster Stefan , Haase Robert , Panfilio Kristen A. , Jug Florian , Grill Stephan W. , Tomancak Pavel , Pavlopoulos Anastasios 
Published: November 2020

AbstractMany animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.
Structural insights into the mechanism of rhodopsin phosphodiesterase
Authors: Ikuta Tatsuya , Shihoya Wataru , Sugiura Masahiro , Yoshida Kazuho , Watari Masahito , Tokano Takaya , Yamashita Keitaro , Katayama Kota , Tsunoda Satoshi P. , Uchihashi Takayuki , Kandori Hideki , Nureki Osamu 
Published: November 2020

AbstractRhodopsin phosphodiesterase (Rh-PDE) is an enzyme rhodopsin belonging to a recently discovered class of microbial rhodopsins with light-dependent enzymatic activity. Rh-PDE consists of the N-terminal rhodopsin domain and C-terminal phosphodiesterase (PDE) domain, connected by 76-residue linker, and hydrolyzes both cAMP and cGMP in a light-dependent manner. Thus, Rh-PDE has potential for the optogenetic manipulation of cyclic nucleotide concentrations, as a complementary tool to rhodopsin guanylyl cyclase and photosensitive adenylyl cyclase. Here we present structural and functional analyses of the Rh-PDE derived from Salpingoeca rosetta. The crystal structure of the rhodopsin domain at 2.6 Å resolution revealed a new topology of rhodopsins, with 8 TMs including the N-terminal extra TM, TM0. Mutational analyses demonstrated that TM0 plays a crucial role in the enzymatic photoactivity. We further solved the crystal structures of the rhodopsin domain (3.5 Å) and PDE domain (2.1 Å) with their connecting linkers, which showed a rough sketch of the full-length Rh-PDE. Integrating these structures, we proposed a model of full-length Rh-PDE, based on the HS-AFM observations and computational modeling of the linker region. These findings provide insight into the photoactivation mechanisms of other 8-TM enzyme rhodopsins and expand the definition of rhodopsins.
Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin
Authors: Dyring-Andersen Beatrice , Løvendorf Marianne Bengtson , Coscia Fabian , Santos Alberto , Møller Line Bruun Pilgaard , Colaço Ana R. , Niu Lili , Bzorek Michael , Doll Sophia , Andersen Jørgen Lock , Clark Rachael A. , Skov Lone , Teunissen Marcel B. M. , Mann Matthias 
Published: November 2020

AbstractHuman skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combine advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantify 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and previously undescribed proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (https://skin.science/).
Bryophytes are predicted to lag behind future climate change despite their high dispersal capacities
Authors: Zanatta F. , Engler R. , Collart F. , Broennimann O. , Mateo R. G. , Papp B. , Muñoz J. , Baurain D. , Guisan A. , Vanderpoorten A. 
Published: November 2020

AbstractThe extent to which species can balance out the loss of suitable habitats due to climate warming by shifting their ranges is an area of controversy. Here, we assess whether highly efficient wind-dispersed organisms like bryophytes can keep-up with projected shifts in their areas of suitable climate. Using a hybrid statistical-mechanistic approach accounting for spatial and temporal variations in both climatic and wind conditions, we simulate future migrations across Europe for 40 bryophyte species until 2050. The median ratios between predicted range loss vs expansion by 2050 across species and climate change scenarios range from 1.6 to 3.3 when only shifts in climatic suitability were considered, but increase to 34.7–96.8 when species dispersal abilities are added to our models. This highlights the importance of accounting for dispersal restrictions when projecting future distribution ranges and suggests that even highly dispersive organisms like bryophytes are not equipped to fully track the rates of ongoing climate change in the course of the next decades.
Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington’s disease
Authors: Stepanova P. , Srinivasan V. , Lindholm D. , Voutilainen M. H. 
Published: November 2020

AbstractHuntington’s disease (HD) is a neurodegenerative disorder with a progressive loss of medium spiny neurons in the striatum and aggregation of mutant huntingtin in the striatal and cortical neurons. Currently, there are no rational therapies for the treatment of the disease. Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) located protein with neurotrophic factor (NTF) properties, protecting and restoring the function of dopaminergic neurons in animal models of PD more effectively than other NTFs. CDNF is currently in phase I–II clinical trials on PD patients. Here we have studied whether CDNF has beneficial effects on striatal neurons in in vitro and in vivo models of HD. CDNF was able to protect striatal neurons from quinolinic acid (QA)-induced cell death in vitro via increasing the IRE1α/XBP1 signalling pathway in the ER. A single intrastriatal CDNF injection protected against the deleterious effects of QA in a rat model of HD. CDNF improved motor coordination and decreased ataxia in QA-toxin treated rats, and stimulated the neurogenesis by increasing doublecortin (DCX)-positive and NeuN-positive cells in the striatum. These results show that CDNF positively affects striatal neuron viability reduced by QA and signifies CDNF as a promising drug candidate for the treatment of HD.
Simple method for large-scale production of macrophage activating factor GcMAF
Authors: Nabeshima Yoko , Abe Chiaki , Kawauchi Takeshi , Hiroi Tomoko , Uto Yoshihiro , Nabeshima Yo-ichi 
Published: November 2020

AbstractHuman group-specific component protein (Gc protein) is a multifunctional serum protein which has three common allelic variants, Gc1F, Gc1S and Gc2 in humans. Gc1 contains an O-linked trisaccharide [sialic acid-galactose-N-acetylgalactosamine (GalNAc)] on the threonine420(Thr420) residue and can be converted to a potent macrophage activating factor (GcMAF) by selective removal of sialic acid and galactose, leaving GalNAc at Thr420. In contrast, Gc2 is not glycosylated. GcMAF is considered a promising candidate for immunotherapy and antiangiogenic therapy of cancers and has attracted great interest, but it remains difficult to compare findings among research groups because different procedures have been used to prepare GcMAF. Here, we present a simple, practical method to prepare high-quality GcMAF by overexpressing Gc-protein in a serum-free suspension culture of ExpiCHO-S cells, without the need for a de-glycosylation step. We believe this protocol is suitable for large-scale production of GcMAF for functional analysis and clinical testing.
Evening home lighting adversely impacts the circadian system and sleep
Authors: Cain Sean W. , McGlashan Elise M. , Vidafar Parisa , Mustafovska Jona , Curran Simon P. N. , Wang Xirun , Mohamed Anas , Kalavally Vineetha , Phillips Andrew J. K. 
Published: November 2020

AbstractThe regular rise and fall of the sun resulted in the development of 24-h rhythms in virtually all organisms. In an evolutionary heartbeat, humans have taken control of their light environment with electric light. Humans are highly sensitive to light, yet most people now use light until bedtime. We evaluated the impact of modern home lighting environments in relation to sleep and individual-level light sensitivity using a new wearable spectrophotometer. We found that nearly half of homes had bright enough light to suppress melatonin by 50%, but with a wide range of individual responses (0–87% suppression for the average home). Greater evening light relative to an individual’s average was associated with increased wakefulness after bedtime. Homes with energy-efficient lights had nearly double the melanopic illuminance of homes with incandescent lighting. These findings demonstrate that home lighting significantly affects sleep and the circadian system, but the impact of lighting for a specific individual in their home is highly unpredictable.
Dual antiplatelet therapy reduced stroke risk in transient ischemic attack with positive diffusion weighted imaging
Authors: Pei Lu-lu , Chen Pei , Fang Hui , Cao Yuan , Guo Yi-nan , Zhang Rui , Zhao Lu , Gao Yuan , Wu Jun , Sun Shi-lei , Wang Xiao-ying , Lo Eng H. , Buonanno Ferdinando S. , Ning Ming-ming , Xu Yu-ming , Song Bo 
Published: November 2020

AbstractDual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan–Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30–0.97; p = 0.037). However, the benefit didn’t exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14–1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.
Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes
Authors: Onengut-Gumuscu Suna , Paila Umadevi , Chen Wei-Min , Ratan Aakrosh , Zhu Zhennan , Steck Andrea K. , Frohnert Brigitte I. , Waugh Kathleen C. , Webb-Robertson Bobbie-Jo M. , Norris Jill M. , Lange Leslie A. , Rewers Marian J. , Rich Stephen S. 
Published: November 2020

AbstractType 1 diabetes arises from the autoimmune destruction of insulin-producing beta-cells of the pancreas, resulting in dependence on exogenously administered insulin to maintain glucose homeostasis. In this study, our aim was to identify genetic risk factors that contribute to progression from islet autoimmunity to clinical type 1 diabetes. We analyzed 6.8 million variants derived from whole genome sequencing of 160 islet autoantibody positive subjects, including 87 who had progressed to type 1 diabetes. The Cox proportional-hazard model for survival analysis was used to identify genetic variants associated with progression. We identified one novel region, 20p12.1 (TASP1; genome-wide P < 5 × 10–8) and three regions, 1q21.3 (MRPS21–PRPF3), 2p25.2 (NRIR), 3q22.1 (COL6A6), with suggestive evidence of association (P < 8.5 × 10–8) with progression from islet autoimmunity to type 1 diabetes. Once islet autoimmunity is initiated, functional mapping identified two critical pathways, response to viral infections and interferon signaling, as contributing to disease progression. These results provide evidence that genetic pathways involved in progression from islet autoimmunity differ from those pathways identified once disease has been established. These results support the need for further investigation of genetic risk factors that modulate initiation and progression of subclinical disease to inform efforts in development of novel strategies for prediction and intervention of type 1 diabetes.
Efficacy based ginger fingerprinting reveals potential antiproliferative analytes for triple negative breast cancer
Authors: Zhao Lihan , Rupji Manali , Choudhary Ishita , Osan Remus , Kapoor Shobhna , Zhang Hong-Jie , Yang Chunhua , Aneja Ritu 
Published: November 2020

AbstractGinger (Zingiber officinale) is one of the most widely consumed dietary supplements worldwide. Its anticancer potential has been demonstrated in various studies. However, ginger roots obtained from different geographical locations showed extensive variability in their activities, mainly due to differences in the levels of bioactive compounds. Here we evaluated the effect of these differences on the anticancer activity of ginger by performing efficacy-based fingerprinting. We characterized the fingerprint profiles of 22 ginger samples using liquid chromatography-mass spectroscopy, followed by a principal component analysis (PCA) and pearson correlation analysis. We also evaluated the anti-proliferative effects (IC50) of these samples on triple-negative breast cancer cells using the MTT assays. The supervised PCA identified a subset of analytes whose abundance strongly associated with the IC50 values of the ginger extracts, providing a link between ginger extract composition and in vitro anticancer efficacy. This study demonstrated that variation in the ginger fingerprint profiles resulting from differences in their chemical composition could have a significant impact on efficacy and bioactivity of ginger extracts. Also, this first-of-a-kind efficacy-based fingerprinting approach proposed here can identify potent anticancer candidates from the ginger fingerprint without the need for isolating individual components from the extracts.