bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZC3H18 specifically binds and activates the BRCA1 promoter to facilitate homologous recombination in ovarian cancer
Authors: Kanakkanthara Arun , Huntoon Catherine J. , Hou Xiaonan , Zhang Minzhi , Heinzen Ethan P. , O’Brien Daniel R. , Oberg Ann L. , John Weroha S. , Kaufmann Scott H. , Karnitz Larry M. 
Published: October 2019

AbstractReduced BRCA1 expression causes homologous recombination (HR) repair defects in high-grade serous ovarian cancers (HGSOCs). Here, we demonstrate thatBRCA1is transcriptionally activated by a previously unknown function of ZC3H18. We show that ZC3H18 is a DNA-binding protein that interacts with an E2F site in theBRCA1promoter where it facilitates recruitment of E2F4 to an adjacent E2F site to promoteBRCA1transcription. Consistent with ZC3H18 role in activating BRCA1 expression, ZC3H18 depletion inducesBRCA1promoter methylation, reduces BRCA1 expression, disrupts HR, and sensitizes cells to DNA crosslinkers and poly(ADP-ribose) polymerase inhibitors. Moreover, in patient-derived xenografts and primary HGSOC tumors,ZC3H18andE2F4mRNA levels are positively correlated withBRCA1mRNA levels, further supporting ZC3H18 role in regulatingBRCA1. Given thatZC3H18lies within 16q24.2, a region with frequent copy number loss in HGSOC, these findings suggest thatZC3H18copy number losses could contribute to HR defects in HGSOC.
Sex-biased gene expression is repeatedly masculinized in asexual females
Authors: Parker Darren J. , Bast Jens , Jalvingh Kirsten , Dumas Zoé , Robinson-Rechavi Marc , Schwander Tanja 
Published: October 2019

AbstractMales and females feature strikingly different phenotypes, despite sharing most of their genome. A resolution of this apparent paradox is through differential gene expression, whereby genes are expressed at different levels in each sex. This resolution, however, is likely to be incomplete, leading to conflict between males and females over the optimal expression of genes. Here we test the hypothesis that gene expression in females is constrained from evolving to its optimum level due to sexually antagonistic selection on males, by examining changes in sex-biased gene expression in five obligate asexual species of stick insect, which do not produce males. We predicted that the transcriptome of asexual females would be feminized as asexual females do not experience any sexual conflict. Contrary to our prediction we find that asexual females feature masculinized gene expression, and hypothesise that this is due to shifts in female optimal gene expression levels following the suppression of sex.
Structural basis for substrate specificity and regulation of nucleotide sugar transporters in the lipid bilayer
Authors: Parker Joanne L. , Corey Robin A. , Stansfeld Phillip J. , Newstead Simon 
Published: October 2019

AbstractNucleotide sugars are the activated form of monosaccharides used by glycosyltransferases during glycosylation. In eukaryotes the SLC35 family of solute carriers are responsible for their selective uptake into the Endoplasmic Reticulum or Golgi apparatus. The structure of the yeast GDP-mannose transporter, Vrg4, revealed a requirement for short chain lipids and a marked difference in transport rate between the nucleotide sugar and nucleoside monophosphate, suggesting a complex network of regulatory elements control transport into these organelles. Here we report the crystal structure of the GMP bound complex of Vrg4, revealing the molecular basis for GMP recognition and transport. Molecular dynamics, combined with biochemical analysis, reveal a lipid mediated dimer interface and mechanism for coordinating structural rearrangements during transport. Together these results provide further insight into how SLC35 family transporters function within the secretory pathway and sheds light onto the role that membrane lipids play in regulating transport across the membrane.
High efficiency and fast van der Waals hetero-photodiodes with a unilateral depletion region
Authors: Wu Feng , Li Qing , Wang Peng , Xia Hui , Wang Zhen , Wang Yang , Luo Man , Chen Long , Chen Fansheng , Miao Jinshui , Chen Xiaoshuang , Lu Wei , Shan Chongxin , Pan Anlian , Wu Xing , Ren Wencai , Jariwala Deep , Hu Weida 
Published: October 2019

AbstractVan der Waals (vdW) heterodiodes based on two-dimensional (2D) materials have shown tremendous potential in photovoltaic detectors and solar cells. However, such 2D photovoltaic devices are limited by low quantum efficiencies due to the severe interface recombination and the inefficient contacts. Here, we report an efficient MoS2/AsP vdW hetero-photodiode utilizing a unilateral depletion region band design and a narrow bandgap AsP as an effective carrier selective contact. The unilateral depletion region is verified via both the Fermi level and the infrared response measurements. The device demonstrates a pronounced photovoltaic behavior with a short-circuit current of 1.3 μA and a large open-circuit voltage of 0.61 V under visible light illumination. Especially, a high external quantum efficiency of 71%, a record high power conversion efficiency of 9% and a fast response time of 9 μs are achieved. Our work suggests an effective scheme to design high-performance photovoltaic devices assembled by 2D materials.
Individualized recovery of gut microbial strains post antibiotics
Authors: Koo Hyunmin , Hakim Joseph A. , Crossman David K. , Kumar Ranjit , Lefkowitz Elliot J. , Morrow Casey D. 
Published: October 2019

AbstractTo further understand the impact of antibiotics on the gastrointestinal tract microbial community, the intra-individual recovery pattern of specific microbial strains was determined using metagenomic sequencing coupled with strain-tracking analyses. In a study where 18 individuals were administered a single antibiotic (cefprozil), new microbial genomic variants (herein strains) were transiently detected in 15 individuals, while in a second study that used a cocktail of three antibiotics (meropenem, gentamicin, and vancomycin), all 12 participants had either permanent or transient strain changes. The presence of distinct microbial genomic variants indicates a pattern of strain recovery that is intra-individual specific following disruption of the human gastrointestinal tract with antibiotics.
Changes in soil bacterial community diversity following the removal of invasive feral pigs from a Hawaiian tropical montane wet forest
Authors: Wehr Nathaniel H. , Kinney Kealohanuiopuna M. , Nguyen Nhu H. , Giardina Christian P. , Litton Creighton M. 
Published: October 2019

AbstractNonnative, invasive feral pigs (Sus scrofa) modify habitats by disturbing soils and vegetation, which can alter biogeochemical processes. Soil microbial communities drive nutrient cycling and therefore also play important roles in shaping ecosystem structure and function, but the responses of soil microbes to nonnative ungulate removal remains poorly studied. We examined changes in the soil bacterial community over a ~25 year chronosequence of feral pig removal in tropical montane wet forests on the Island of Hawai’i. We extracted bacterial eDNA from soil samples collected inside and outside of ungulate exclosures along this chronosequence and sequenced the eDNA using the Illumina platform. We found that ungulate removal increased diversity of soil bacteria, with diversity scores positively correlated with time since removal. While functional and phylogenetic diversity were not significantly different between pig present and pig removed soils, soil bulk density, which decreases following the removal of feral pigs, was a useful predictor of dissimilarity among sites and correlated to changes in functional diversity. Additionally, increases in soil porosity, potassium, and calcium were correlated to increases in functional diversity. Finally, sites with greater mean annual temperatures were shown to have higher scores of both functional and phylogenetic diversity. As such, we conclude that feral pigs influence overall bacterial community diversity directly while influencing functional diversity indirectly through alterations to soil structure and nutrients. Comparatively, phylogenetic differences between communities are better explained by mean annual temperature as a climatic predictor of community dissimilarity.
Assessing effects from four years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle, 2013–2017
Authors: Downs Sara H. , Prosser Alison , Ashton Adam , Ashfield Stuart , Brunton Lucy A. , Brouwer Adam , Upton Paul , Robertson Andrew , Donnelly Christl A. , Parry Jessica E. 
Published: October 2019

AbstractThe objective was to measure the association between badger culling and bovine tuberculosis (TB) incidents in cattle herds in three areas of England between 2013–2017 (Gloucestershire and Somerset) and 2015–2017 (Dorset). Farming industry-selected licensed culling areas were matched to comparison areas. A TB incident was detection of new Mycobacterium bovis infection (post-mortem confirmed) in at least one animal in a herd. Intervention and comparison area incidence rates were compared in central zones where culling was conducted and surrounding buffer zones, through multivariable Poisson regression analyses. Central zone incidence rates in Gloucestershire (Incidence rate ratio (IRR) 0.34 (95% CI 0.29 to 0.39, p < 0.001) and Somerset (IRR 0.63 (95% CI 0.58 to 0.69, p < 0.001) were lower and no different in Dorset (IRR 1.10, 95% CI 0.96 to 1.27, p = 0.168) than comparison central zone rates. The buffer zone incidence rate was lower for Gloucestershire (IRR 0.64, 95% CI 0.58 to 0.70, p < 0.001), no different for Somerset (IRR 0.97, 95% CI 0.80 to 1.16, p = 0.767) and lower for Dorset (IRR 0.45, 95% CI 0.37 to 0.54, p < 0.001) than comparison buffer zone rates. Industry-led culling was associated with reductions in cattle TB incidence rates after four years but there were variations in effects between areas.
Heart Rate and Heart Rate Variability Correlate with Clinical Reasoning Performance and Self-Reported Measures of Cognitive Load
Authors: Solhjoo Soroosh , Haigney Mark C. , McBee Elexis , van Merrienboer Jeroen J. G. , Schuwirth Lambert , Artino Anthony R. , Battista Alexis , Ratcliffe Temple A. , Lee Howard D. , Durning Steven J. 
Published: October 2019

AbstractCognitive load is a key mediator of cognitive processing that may impact clinical reasoning performance. The purpose of this study was to gather biologic validity evidence for correlates of different types of self-reported cognitive load, and to explore the association of self-reported cognitive load and physiologic measures with clinical reasoning performance. We hypothesized that increased cognitive load would manifest evidence of elevated sympathetic tone and would be associated with lower clinical reasoning performance scores. Fifteen medical students wore Holter monitors and watched three videos depicting medical encounters before completing a post-encounter form and standard measures of cognitive load. Correlation analysis was used to investigate the relationship between cardiac measures (mean heart rate, heart rate variability and QT interval variability) and self-reported measures of cognitive load, and their association with clinical reasoning performance scores. Despite the low number of participants, strong positive correlations were found between measures of intrinsic cognitive load and heart rate variability. Performance was negatively correlated with mean heart rate, as well as single-item cognitive load measures. Our data signify a possible role for using physiologic monitoring for identifying individuals experiencing high cognitive load and those at risk for performing poorly during clinical reasoning tasks.
A paradox of local abundance amidst regional rarity: the value of montane refugia for Persian leopard conservation
Authors: Farhadinia Mohammad S. , McClintock Brett T. , Johnson Paul J. , Behnoud Pouyan , Hobeali Kaveh , Moghadas Peyman , Hunter Luke T. B. , Macdonald David W. 
Published: October 2019

AbstractThe population densities of leopards vary widely across their global range, influenced by prey availability, intraguild competition and human persecution. In Asia, particularly the Middle East and the Caucasus, they generally occur at the lower extreme of densities recorded for the species. Reliable estimates of population density are important for understanding their ecology and planning their conservation. We used a photographic spatial capture-recapture (SCR) methodology incorporating animal movement to estimate density for the endangered Persian leopardPanthera pardus saxicolorin three montane national parks, northeastern Iran. We combined encounter history data arising from images of bilaterally asymmetrical left- and right-sided pelage patterns using a Bayesian spatial partial identity model accommodating multiple “non-invasive” marks. We also investigated the effect of camera trap placement on detection probability. Surprisingly, considering the subspecies’ reported low abundance and density based on previous studies, we found relatively high population densities in the three national parks, varying between 3.10 ± SD 1.84 and 8.86 ± SD 3.60 individuals/100 km2. The number of leopards detected in Tandoureh National Park (30 individuals) was larger than estimated during comparable surveys at any other site in Iran, or indeed globally. Capture and recapture probabilities were higher for camera traps placed near water resources compared with those placed on trails. Our results show the benefits of protecting even relatively small mountainous areas, which accommodated a high density of leopards and provided refugia in a landscape with substantial human activity.
Circular RNA differential expression in blood cell populations and exploration of circRNA deregulation in pediatric acute lymphoblastic leukemia
Authors: Gaffo Enrico , Boldrin Elena , Dal Molin Anna , Bresolin Silvia , Bonizzato Annagiulia , Trentin Luca , Frasson Chiara , Debatin Klaus-Michael , Meyer Lueder H. , te Kronnie Geertruij , Bortoluzzi Stefania 
Published: October 2019

AbstractCircular RNAs (circRNAs) are abundantly expressed in the haematopoietic compartment, but knowledge on their diversity among blood cell types is still limited. Nevertheless, emerging data indicate an array of circRNA functions exerted through interactions with other RNAs and proteins, by translation into peptides, and circRNA involvement as regulatory molecules in many biological processes and cancer mechanisms. Interestingly, the role of specific circRNAs in leukemogenesis has been disclosed by a few studies, mostly in acute myeloid leukemia. In this study, circRNA expression in B-cells, T-cells and monocytes of healthy subjects is described, including putative new circRNA genes. Expression comparison considered 6,228 circRNAs and highlighted cell population-specific expression and exon usage patterns. Differential expression has been confirmed by qRT-PCR for circRNAs specific of B-cells (circPAX5, circAFF3, circIL4R, and circSETBP1) or T-cells (circIKZF1, circTNIK, circTXK, and circFBXW7), and for circRNAs from intronic (circBCL2) and intergenic regions that were overexpressed in lymphocytes. Starting from this resource of circRNA expression in mature blood cell populations, targeted examination identified striking and generalized upregulated expression of circPAX5, circPVT1 and circHIPK3 in pediatric B-precursor acute lymphoblastic leukemia, and disclosed circRNAs with variable expression across cytogenetic subtypes.
RNA sequencing for ligature induced periodontitis in mice revealed important role of S100A8 and S100A9 for periodontal destruction
Authors: Maekawa Shogo , Onizuka Satoru , Katagiri Sayaka , Hatasa Masahiro , Ohsugi Yujin , Sasaki Naoki , Watanabe Kazuki , Ohtsu Anri , Komazaki Rina , Ogura Kohei , Miyoshi-Akiyama Tohru , Iwata Takanori , Nitta Hiroshi , Izumi Yuichi 
Published: October 2019

AbstractPeriodontitis is an inflammatory disease caused by pathogenic oral microorganisms that induce the destruction of periodontal tissue. We sought to identify the relevant differentially expressed genes (DEGs) and clarify the mechanism underlying the rapid alveolar bone loss by using ligature-induced periodontitis in mice. A silk ligature was tied around the maxillary left second molar in 9-week-old C57BL/6 J male mice.In-vivomicro-CT analysis revealed that ligation induced severe bone loss. RNA-sequencing analysis, to examine host responses at 3 days post-ligation, detected 12,853 genes with fragments per kilobase of exon per million mapped reads ≥ 1, and 78 DEGs. Gene ontology term enrichment analysis revealed the expression profiles related to neutrophil chemotaxis and inflammatory responses were significantly enriched in the ligated gingiva. The expression levels of innate immune response-related genes, includingS100a8andS100a9, were significantly higher in the ligated side. S100A8 was strongly detected by immunohistochemistry at the attached epithelium in ligated sites. Inhibition ofS100A8andS100A9expression revealed that they regulatedIL1BandCTSKexpression in Ca9-22 cells. Thus, innate immune response-related molecules might be associated with the burst-destruction of periodontal tissue in ligature-induced periodontitis. Especially, S100A8 and S100A9 may play an important role in alveolar bone resorption.
Predicting shockwave lithotripsy outcome for urolithiasis using clinical and stone computed tomography texture analysis variables
Authors: Cui Helen W. , Silva Mafalda D. , Mills Andrew W. , North Bernard V. , Turney Benjamin W. 
Published: October 2019

AbstractWe aimed to develop and evaluate a statistical model, which included known pre-treatment factors and new computed tomography texture analysis (CTTA) variables, for its ability to predict the likelihood of a successful outcome after extracorporeal shockwave lithotripsy (SWL) treatment for renal and ureteric stones. Up to half of patients undergoing SWL may fail treatment. Better prediction of which cases will likely succeed SWL will help patients to make an informed decision on the most effective treatment modality for their stone. 19 pre-treatment factors for SWL success, including 6 CTTA variables, were collected from 459 SWL cases at a single centre. Univariate and multivariable analyses were performed by independent statisticians to predict the probability of a stone free (both with and without residual fragments) outcome after SWL. A multivariable model had an overall accuracy of 66% on Receiver Operator Curve (ROC) analysis to predict for successful SWL outcome. The variables most frequently chosen for the model were those which represented stone size. Although previous studies have suggested SWL can be reliably predicted using pre-treatment factors and that analysis of CT stone images may improve outcome prediction, the results from this study have not produced a useful model for SWL outcome prediction.
Prognostic nutritional index may not be a good prognostic indicator for acute myocardial infarction
Authors: Cheng Yisong , Li Hong , Li Dongze , Liang Lianjing , Jia Yu , Zou Liqun , Li Fanghui , Zhu Xingyu , Qian Hong , He Na , Zeng Zhi , Zeng Rui , Cao Yu , Wan Zhi 
Published: October 2019

AbstractThe prognostic nutritional index (PNI) has been applied in acute myocardial infarction (AMI) recently.However, the application of PNI in AMI needs verification. This was a prospective cohort study. Patients diagnosed with AMI were enrolled. PNI was calculated as (serum albumin (SA in g/L)) + (5 × total lymphocyte count (TLC) × 109/L). Modified PNI (mPNI) was analyzed by logistic regression analysis to reset the proportion of SA and TLC. The primary outcome was all-cause death. A total of 598 patients were enrolled; 73 patients died during follow-up. The coefficient of SA and TLC in the mPNI formula was approximately 2:1. The area under the receiver operating characteristic curve of SA, TLC, PNI, mPNI and GRACE in predicting death for patients with AMI was 0.718, 0.540, 0.636, 0.721 and 0.825, respectively. Net reclassification improvement (NRI) between PNI and mPNI was 0.230 (p < 0.001). Integrated discrimination improvement (IDI) was 0.042 (p = 0.001). Decision curve analysis revealed that mPNI had better prognostic value for patients with AMI than PNI; however, it was not superior to SA. Thus, PNI may not a reliable prognostic predictor of AMI; after resetting the formula, the value of PNI in predicting prognosis of AMI is almost entirely due to SA.
The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases
Authors: Guevara Tibisay , Körschgen Hagen , Cuppari Anna , Schmitz Carlo , Kuske Michael , Yiallouros Irene , Floehr Julia , Jahnen-Dechent Willi , Stöcker Walter , Gomis-Rüth F. Xavier 
Published: October 2019

AbstractHuman fetuin-B plays a key physiological role in human fertility through its inhibitory action on ovastacin, a member of the astacin family of metallopeptidases. The inhibitor consists of tandem cystatin-like domains (CY1 and CY2), which are connected by a linker containing a “CPDCP-trunk” and followed by a C-terminal region (CTR) void of regular secondary structure. Here, we solved the crystal structure of the complex of the inhibitor with archetypal astacin from crayfish, which is a useful model of human ovastacin. Two hairpins from CY2, the linker, and the tip of the “legumain-binding loop” of CY1 inhibit crayfish astacin following the “raised-elephant-trunk mechanism” recently reported for mouse fetuin-B. This inhibition is exerted by blocking active-site cleft sub-sites upstream and downstream of the catalytic zinc ion, but not those flanking the scissile bond. However, contrary to the mouse complex, which was obtained with fetuin-B nicked at a single site but otherwise intact, most of the CTR was proteolytically removed during crystallization of the human complex. Moreover, the two complexes present in the crystallographic asymmetric unit diverged in the relative arrangement of CY1 and CY2, while the two complexes found for the mouse complex crystal structure were equivalent. Biochemical studies in vitro confirmed the differential cleavage susceptibility of human and mouse fetuin-B in front of crayfish astacin and revealed that the cleaved human inhibitor blocks crayfish astacin and human meprin α and β only slightly less potently than the intact variant. Therefore, the CTR of animal fetuin-B orthologs may have a function in maintaining a particular relative orientation of CY1 and CY2 that nonetheless is dispensable for peptidase inhibition.