bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaginal Sacrospinous Ligament Fixation Using Tissue Anchoring System Versus a Traditional Technique for Women With Apical Vaginal Prolapse: A Randomized Controlled Trial
Authors: Castro Rodrigo Aquino , Bortolini Maria Augusta Tezelli , Pascom Ana Lívia Garcia , Ledesma Marta , Sardi Juan José Luis , Monteiro Marilene Vale de Castro , Junqueira Sebastián Perez , Fuentes Edna Cortes 
Published: June 2020

Objective
The aim of the study was to compare the efficacy and safety of the tissue anchoring system (TAS) kit versus the traditional technique for sacrospinous ligament fixation (SSLF) to treat apical vaginal wall prolapse.

Methods
A prospective randomized controlled multicenter study of noninferiority involving women with apical prolapse (C-point≥+1). Primary outcome is surgical success as C-point≤−4 at the 1-year follow-up. Secondary outcomes are success according to the composite criteria as C-point≤−4, Ba-point ≤0, and Bp-point ≤0; POP-Q measures of the vaginal compartments; intraoperative findings, complications; reoperation rate; hospital stay; and quality of life and sexual functioning (PISQ-12). It was estimated that 50 individuals per group would yield an 80% power for a noninferiority margin of 15%.

Results
Ninety-nine women were randomized: TAS (n = 55) and traditional SSLF (n = 44). The groups’ preoperative data were similar. Drop-out rate was 11% for 12-month follow-up. Success rates were 90% for TAS and 80% for traditional SSLF (P = 0.0006; absolute difference, 9.8%; 90% confidence interval, −5.2 to 24.8) with the sensivity analyses per-protocol considering only the subjects that completed the 12-month follow-up and 80% versus 73%, respectively (P = 0.0048; absolute difference, 7.3%; 90% confidence interval, −9.6 to 24.2) by sensivity analyses considering the total number of participants randomized and treated with drop-out cases as failure. We detected shorter intraoperative time to dissect and reach the SSL, shorter length of hospitalization, lower rates of urinary tract infection, and lower pain scores in the first 30 days postoperative in the TAS compared with the traditional SSLF groups (P < 0.05). There was an improvement in women’s quality of life that did not differ between groups.

Conclusions
The modified technique of SSLF using the TAS kit is noninferior to the traditional technique for the treatment of apical compartment in 12-month follow-up.
The disordered regions of SETD2 govern H3K36me3 deposition by regulating its proteasome-mediated decay
Authors: Bhattacharya Saikat , Zhang Ning , Li Hua , Workman Jerry L. 
Published: June 2020

ABSTRACTSETD2 is the sole methyltransferase that tri-methylates histone H3 at lysine 36 in mammals. It has an extended N-terminal region which is absent in its yeast homolog Set2. The function of this poorly characterized region in regulating SETD2 stability has been reported. However, how this region regulates SETD2 half-life and the consequences of the cellular accumulation of SETD2 is unclear. Here we show that the SETD2 N-terminal region contains disordered regions and is targeted for degradation by the proteasome. The marked increase in global H3K36me3 that occurs on the removal of the N-terminal segment results in a non-canonical distribution including reduced enrichment over gene bodies and exons. An increased SETD2 abundance leads to widespread changes in transcription and alternative splicing. Thus, the regulation of SETD2 levels through intrinsically disordered region-facilitated proteolysis is important to maintain the fidelity of transcription and splicing related processes.
Harmonized Z-scores calculated from the large scale normal MRI database to evaluate brain atrophy for neurodegenerative disorder
Authors: Maikusa Norihide 
Published: June 2020

AbstractAlzheimer’s disease (AD), the most common type of dementia in elderly individuals, slowly and progressively diminishes cognitive function. Mild cognitive impairment is also a significant risk factor to the onset of AD. Magnetic resonance imaging (MRI) images have become widely used to detection and understand the natural progression not only AD but also neurodegenerative disorders. For this purpose, construct a reliable cognitive normal database is important. However, difference in magnetic field strength, sex and age between normal database and evaluation data-set can be affect the accuracy of detection and evaluation of AD and other neurodegenerative disorders.To solve this problem, we suggest a harmonized Z-score considering differences filed strength, sex and age derived from large cognitive normal subjects dataset ((1235 subjects)) including 1.5 T and 3T T1 brain MRI. And we evaluate our harmonized Z-score of discriminative power of AD, and classification accuracy between stable MCI and progressive MCI.The harmonized Z-score of hippocampus achieved high accuracy (AUC=0.96) for detection AD and moderate accuracy (AUC=0.70) for classification stable MCI and progressive MCI. Theses results shows that our method not only can detect AD with high accuracy and high generalization capability, but also can be valid to classify stable MCI and progressive MCI.
Gastrointestinal parasite community in the critically endangered West African lion
Authors: Kruszka Sofia , Harris Nyeema C. 
Published: June 2020

AbstractLarge carnivores of Africa, such as lions (Panthera leo), suffer from prey depletion and habitat fragmentation, that possibly impact the composition of the gastrointestinal parasite community. West African lions are particularly important, as this population is critically endangered and yet little is known of their gastrointestinal parasite community, which can reflect the health and resilience of the host population. From fecal samples collected in the W-Arly-Pendjari (WAP) transboundary protected area complex in Burkina Faso and Niger, we identified 309 oocysts of at least five different species using fecal flotation and sedimentation tests. We also compared these gastrointestinal parasites to other results from surveys of lions from Southern and East African regions and found similar taxa to previous surveys, but lower species richness across West African samples.
APhelipanche ramosaKAI2 Protein Perceives enzymatically Strigolactones and Isothiocyanates
Authors: de Saint Germain Alexandre , Jacobs Anse , Brun Guillaume , Pouvreau Jean-Bernard , Braem Lukas , Cornu David , Clavé Guillaume , Baudu Emmanuelle , Steinmetz Vincent , Servajean Vincent , Wicke Susann , Gevaert Kris , Simier Philippe , Goormachtig Sofie , Delavault Philippe , Boyer François-Didier 
Published: June 2020

AbstractPhelipanche ramosais an obligate root-parasitic weed threatening major crops in central Europe. For its germination, it has to perceive various structurally diverging host-exuded signals, including isothiocyanates (ITCs) and strigolactones (SLs). However, the receptors involved are still uncharacterized. Here, we identified five putative SL receptors inP. ramosa, of which PrKAI2d3 is involved in seed germination stimulation. We established the high plasticity of PrKAI2d3, allowing interaction with different chemicals, including ITCs. The SL perception mechanism of PrKAI2d3 is similar to that of endogenous SLs in non-parasitic plants. We provide evidence that the PrKAI2d3 enzymatic activity confers hypersensitivity to SLs. Additionally, we demonstrated that methylbutenolide-OH binds PrKAI2d3 and stimulatesP. ramosagermination with a bioactivity comparable to that of ITCs. This study highlights thatP. ramosahas extended its signal perception system during evolution, a fact to be considered in the development of specific and efficient biocontrol methods.
Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
Authors: van Sorge Nina M. , Bonsor Daniel A. , Deng Liwen , Lindahl Erik , Schmitt Verena , Lyndin Mykola , Schmidt Alexej , Nilsson Olof R. , Brizuela Jaime , Boero Elena , Sundberg Eric J. , van Strijp Jos A.G. , Doran Kelly S. , Singer Bernhard B. , Lindahl Gunnar , McCarthy Alex J. 
Published: June 2020

AbstractStreptococcus agalactiae, also known as group BStreptococcus(GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria at mucosal surfaces. Though several GBS adhesins have been identified, the host receptor targets of these adhesins remain unknown. We report here that surface-expressed β protein from GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that the IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessments revealed that this newly identified IgI3 fold is not exclusively present in GBS. Instead, the IgI3 fold is predicted to be present in adhesins from other clinically important human pathogens. We confirmed the interaction between CEACAM1 and the predicted IgI3-containing adhesin in two different streptococcal pathogens. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
RIL-StEp: epistasis analysis of recombinant inbred lines (RILs) reveals candidate interacting genes that control rice seed hull color
Authors: Sakai Toshiyuki , Abe Akira , Shimizu Motoki , Terauchi Ryohei 
Published: June 2020

SummaryStudying epistatic gene interactions is important in understanding genetic architecture of complex traits in organisms. However, due to an enormous number of gene combinations to be analyzed, detection of epistatic gene-gene interactions has been computationally demanding. Here, we show a simple approach RIL-StEp, specialized to Recombinant Inbred Lines (RILs), to study epistasis using single nucleotide polymorphisms (SNPs) information of the genome. We applied the method to reveal epistasis affecting rice seed hull color phenotype, and successfully identified gene pairs that presumably control seed hull color. This method has a potential to enhancing our understanding of genetic architecture of various traits.
Phenotypic melanoma heterogeneity is regulated through cell-matrix interaction-dependent changes in tumor microarchitecture
Authors: Spoerri Loredana , Tonnessen-Murray Crystal A. , Gunasingh Gency , Hill David S. , Beaumont Kimberley A. , Jurek Russell J. , Chauhan Jagat , Vanwalleghem Gilles C. , Fane Mitchell E. , Daignault-Mill Sheena M. , Matigian Nicholas , Boyle Glen M. , Scott Ethan K. , Smith Aaron G. , Stehbens Samantha J. , Schaider Helmut , Gabrielli Brian , Weninger Wolfgang , Goding Colin R. , Haass Nikolas K. 
Published: June 2020

AbstractPhenotypic heterogeneity of cancer cells plays a critical role in shaping treatment response. This type of heterogeneity is organized spatially with specific phenotypes, such as sharply demarcated clusters of proliferating and cell cycle-arrested cells, predominating within discrete domains within a tumor. What determines the occurrence of specific tumor cell phenotypes in distinct microdomains of solid cancers is poorly understood. Here, we show that in melanoma spatial organization of phenotypic heterogeneity is dictated by the expression and activity of MITF. We reveal that this lineage survival oncogene controls ECM composition and organization, and ROCK-driven mechanotransduction through focal adhesion maturation and actin cytoskeleton functionality. In turn, altered tumor microarchitecture and structural integrity impact tumor solid stress which then mediates phenotypic heterogeneity through p27Kip1. Rho-ROCK-myosin signaling is necessary to transmit the effect of the reciprocal cell-ECM regulation into phenotypic heterogeneity. Our findings place cell-ECM crosstalk as a central driver of phenotypic tumor heterogeneity.SignificancePhenotypic heterogeneity is a major culprit of cancer therapy failure. We demonstrate that phenotypic heterogeneity is controlled through tumor cell-ECM crosstalk resulting in altered tumor microarchitecture, mechanotransduction and Rho-ROCK-myosin signaling. Melanoma shares these physical properties with any solid cancer underscoring the importance of our findings for therapeutically targeting this phenomenon.
Neuronal dysfunctions and cognitive deficits in a multi-hit rat model following cumulative effects of early life stressors
Authors: Sarkar Tiyasha , Patro Nisha , Patro Ishan Kumar 
Published: June 2020

AbstractPerinatal protein malnourishment is a leading cause for mental and physical retardation in children with poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors, that may synergistically act to cause neurological disorders at adulthood. In this study, the above mentioned condition is mimicked via a multi-hit rat model in which pups born to protein malnourished mothers (LP) were co-injected with polyinosinic:polycytidylic acid (Poly I:C; viral mimetic) at Postnatal day (PND) 3 and lipopolysaccharide (LPS; bacterial mimetic) at PND 9. Individual exposure of Poly I:C and LPS was also given to LP pups to correlate chronicity of stress. Similar treatments were also given to control pups. Hippocampal cellular apoptosis, β III tubulin catastrophe, altered neuronal profiling and spatial memory impairments were assessed at PND 180, using specific immunohistochemical markers (active caspase 3, β III tubulin, doublecortin), Golgi studies and cognitive mazes (Morris Water Maze and T maze). Increase in cellular apoptosis, loss of dendritic arborization and spatial memory impairments were higher in multi-hit group, than the single-hit groups. Such impairments observed due to multi-hit stress, mimic conditions similar to many neurological disorders and hence it is hypothesized that later life neurological disorders might be an outcome of multiple early life hits.Summary StatementThis study is first of its kind which practically studies the combined effects of major early life stressors like protein malnourishment, viral and bacterial infections on the nervous system.
One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device
Authors: Huang Liping , Ding Longfei , Zhou Jun , Chen Shuiliang , Chen Fang , Zhao Chen , Zhang Yiyi , Xu Jianqing , Hu Wenjun , Ji Jiansong , Xu Hao , Liu Gang L. 
Published: June 2020

AbstractThe spread of SARS-CoV-2 virus in the ongoing global pandemics has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemics. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. We demonstrate that we can detect as few as 30 virus particles in one step within 15 minutes and can quantify the virus concentration linearly in the range of 103vp/ml to 106vp/ml. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.
Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction
Authors: Mainali Rabina , Zabalawi Manal , Long David , Buechler Nancy , Quillen Ellen , Key Chia-Chi , Zhu Xuewei , Parks John S. , Furdui Cristina , Stacpoole Peter W. , Martinez Jennifer , McCall Charles E. , Quinn Matthew A 
Published: June 2020

AbstractDramatic metabolic reprogramming between an anabolic resistance and catabolic tolerance state occurs within the immune system in response to systemic infection with the sepsis syndrome. While metabolic tissues such as the liver are subject to end-organ damage during sepsis and are the primary cause of sepsis death, how their metabolic and energy reprogramming during sepsis state ensures survival is unclear. Employing comprehensive metabolomic screening, targeted lipidomic screening, and transcriptional profiling in a mouse model of septic shock, we show that hepatocyte lipid metabolism, mitochondrial TCA energetics, and redox balance are significantly reprogramed after cecal ligation and puncture (CLP). We identify increases in TCA cycle metabolites citrate, cis-aconitate, and itaconate with reduced fumarate and triglyceride accumulation in septic hepatocytes. Transcription analysis of liver tissue supports and extends the hepatocyte findings. Strikingly, the administration of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) reverses dysregulated hepatocyte metabolism and mitochondrial dysfunction. Our data indicate sepsis promotes hepatic metabolic dysfunction. Furthermore, our data indicate that targeting the mitochondrial PDC/PDK energy home-ostat rebalances transcriptional and metabolic manifestations of sepsis within the liver.
Instability with a purpose: how the visual brain makes decisions in a volatile world
Authors: Cao Robin , Pastukhov Alexander , Aleshin Stepan , Mattia Maurizio , Braun Jochen 
Published: June 2020

AbstractIn ambiguous or conflicting sensory situations, perception is often ‘multistable’ in that it changes abruptly at irregular intervals, shifting perpetually between distinct alternatives. Intriguingly, the interval statistics of these alternations exhibits quasi-universal characteristics, suggesting a general mechanism. Here we show that the stereotypical features of multistable perception, exemplified by binocular rivalry, are reproduced in detail by a hierarchical dynamics operating out of equilibrium. Its constitutive elements are discretely stochastic and idealize the metastability of cortical networks. Independent elements accumulate visual evidence at one level, while groups of coupled elements compete for dominance at another level. As soon as one group dominates perception, feedback inhibition suppresses supporting evidence. This mechanism is corroborated compellingly by unexpected serial dependencies of perceptual alternations. Moreover, it satisfies normative constraints of continuous decision-making. We conclude that multistable perception reflects decision-making in a volatile world: integrating evidence over space and time, choosing categorically between hypotheses, while concurrently evaluating alternatives.
Differential activity and expression of human 5β-reductase (AKR1D1) splice variants
Authors: Appanna Nathan , Gangitano Elena , Dempster Niall J , Morris Karen , George Sherly , Keevil Brian G , Penning Trevor M , Gathercole Laura L , Tomlinson Jeremy W , Nikolaou Nikolaos 
Published: June 2020

AbstractSteroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5β-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these,AKR1D1-002is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid synthesis. However, specific activity and expression ofAKR1D1-001andAKR1D1-006are unknown.AKR1D1-002, AKR1D1-001andAKR1D1-006were measured in human liver biopsies and human hepatoma cell lines by qPCR. Three-dimensional (3D) structures ofAKR1D1variants were determined usingin silicoapproaches.AKR1D1variants were over-expressed in HEK293 cells, and successful overexpression confirmed by qPCR and western blotting. Steroid hormone clearance was measured by mass spectrometry and ELISA, and steroid receptor activation determined by luciferase reporter assays.AKR1D1-002andAKR1D1-001are expressed in human liver, and onlyAKR1D1-006is expressed in human testes. Following over-expression in HEK293 cells, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone or testosterone.We have demonstrated the differential expression and role ofAKR1D1splice variants to regulate steroid hormone clearance and receptor activation. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited role in the regulation of synthetic glucocorticoid action.
The utility of native MS for understanding the mechanism of action of repurposed therapeutics in COVID-19: heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor
Authors: Yang Yang , Du Yi , Kaltashov Igor A. 
Published: June 2020

ABSTRACTThe emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported world-wide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.Abstract Figure