bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Fibrinogen as a Key Anti-Apoptotic Factor in Human Fresh Frozen Plasma for Protecting Endothelial Cells In Vitro
Authors: Yu Qiang , Yang Baibing , Davis Joy M. , Ghosn Jean , Deng Xiyun , Doursout Marie-Francoise , Dong Jing-fei , Wang Run , Holcomb John B. , Wade Charles E. , Ko Tien C. , Cao Yanna 
Published: June 2019

ABSTRACT
Resuscitation with human fresh frozen plasma (FFP) in hemorrhagic shock (HS) patients is associated with improved clinical outcomes. Our group has demonstrated that the beneficial effect of FFP is due to its blockade on endothelial hyperpermeability, thereby improving vascular barrier function. The current study aimed to investigate HS-induced endothelial cell apoptosis, a potential major contributor to the endothelial hyperpermeability, and to determine the effect and the key components/factors of FFP on protecting endothelial cells from apoptosis. We first measured and demonstrated an increase in apoptotic endothelial microparticles (CD146+AnnexinV+) in patients in shock compared to normal subjects, indicating the induction of endothelial cell activation and apoptosis in shock patients. We then transfused HS rats with FFP and showed that FFP blocked HS-induced endothelial cell apoptosis in gut tissue. To identify the anti-apoptotic factors in FFP, we utilized high-performance liquid chromatography, fractionated FFP, and screened the fractions in vitro for the anti-apoptotic effects. We selected the most effective fractions, performed mass spectrometry, and identified fibrinogen as a potent anti-apoptotic factor. Taken together, our findings suggest that HS-induced endothelial apoptosis may constitute a major mechanism underlying the vascular hyperpermeability. Furthermore, the identified anti-apoptotic factor fibrinogen may contribute to the beneficial effects of FFP resuscitation, and therefore, may have therapeutic potential for HS.
Endoscopic Ultrasound in Pediatric Patients With Pancreatobiliary Disease
Authors: Téllez-Ávila Félix I. , Duarte-Medrano Gilberto , Herrera-Mora David , Lopez-Arce Gustavo , Leal-García Mariana , Ramírez-Martínez Maribel , Ramírez-Luna Miguel 
Published: June 2019

Background:
Endoscopic ultrasound (EUS) is one of the greatest advances of the last few decades for the diagnostic and therapeutic approach of gastrointestinal diseases in adults. However, there are limitations to the application of the procedure in the pediatric population. The aim of this study was to describe the diagnostic yield and therapeutic role of EUS in pediatric patients with pancreatobiliary disease.

Materials and Methods:
A retrospective study was performed on a prospective database of pediatric patients who underwent diagnostic and therapeutic endosonographic procedures. All patients seen in a 12-year period were included.

Results:
A total of 54 patients were included, including 32 (59.3%) female individuals, with an average age of 16 (9 to 17) years. EUS was abnormal in 46 (85%) patients. Of the abnormal procedures, 4 (7.4%) corresponded to therapeutic ones. The main indication of the study was recurrent acute pancreatitis in 29 (54%). The main endosonographic findings were microlithiasis in 14 (25.9%), chronic pancreatitis in 9 (16.7%), and pancreatic tumors in 6 (11.1%) patients. Follow-up was performed in 31 (57.4%) patients, 19/31 patients underwent surgery, and 4/31 patients had endoscopic retrograde cholangiopancreatography. The median follow-up was 910 (2 to 3916) days. In 100% of the patients with follow-up, the initial diagnosis of EUS was confirmed.

Conclusion:
EUS is a useful and safe tool in the pediatric population with pancreatobiliary diseases.
Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: Diagnosis and Therapeutic Management and Considerations for Timing of Surgery and Duration of Follow-up After Initial Endoscopic Retrograde Cholangiopancreatography
Authors: Muhammedoğlu Bahtiyar 
Published: June 2019

Introduction:
Ectopic opening of the common bile duct (EO-CBD) is a rare pathology, and its management is important. To date, only a few studies have been conducted for EO-CBD due to its low incidence.

Materials and Methods:
A retrospective review was conducted on 54 patients with available prospective data. Among them, 30 patients (group 1) underwent choledochoduodenostomy for reasons other than anomalous opening, and 24 patients (group 2) had an EO-CBD.

Results:
Endoscopic retrograde cholangiopancreatography (ERCP) was performed for 24 patients with duodenal deformity and apical stenosis. EO-CBD was detected in 2.72% of all patients who underwent ERCP (24/880 ERCPs). The occurrence of hyperbilirubinemia (total bilirubin >1.2 mg/dL) was not significantly different between groups: 3.83±4.57 mg/dL for group 1 and 2.26±2.17 mg/dL for group 2.

Conclusions:
Failed ERCP, giant stones, and recurrent episodes (>2) of cholangitis requiring ERCP constitute indications for surgical treatment in cases of EO-CBD into the duodenum.
Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels
Authors: Kanavy Dona M. , McNulty Shannon M. , Jairath Meera K. , Brnich Sarah E. , Bizon Chris , Powell Bradford C. , Berg Jonathan S. 
Published: June 2019

ABSTRACTBackgroundThe 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that “well-established” functional studies can be used as evidence in variant classification. These guidelines articulated key attributes of functional data, including that assays should reflect the biological environment and be analytically sound; however, details of how to evaluate these attributes were left to expert judgment. The Clinical Genome Resource (ClinGen) designates Variant Curation Expert Panels (VCEPs) in specific disease areas to make gene-centric specifications to the ACMG/AMP guidelines, including more specific definitions of appropriate functional assays. We set out to evaluate the existing VCEP guidelines for functional assays.MethodsWe evaluated the functional criteria (PS3/BS3) of six VCEPs (CDH1, Hearing Loss, Inherited Cardiomyopathy-MYH7, PAH, PTEN, RASopathy). We then established criteria for evaluating functional studies based on disease mechanism, general class of assay, and the characteristics of specific assay instances described in primary literature. Using these criteria, we extensively curated assay instances cited by each VCEP in their pilot variant classification to analyze VCEP recommendations and their use in the interpretation of functional studies.ResultsUnsurprisingly, our analysis highlighted the breadth of VCEP-approved assays, reflecting the diversity of disease mechanisms among VCEPs. We also noted substantial variability between VCEPs in the method used to select these assays and in the approach used to specify strength modifications, as well as differences in suggested validation parameters. Importantly, we observed discrepancies between the parameters VCEPs specified as required for approved assay instances and the fulfillment of these requirements in the individual assays cited in pilot variant interpretation.ConclusionsInterpretation of the intricacies of functional assays often requires expert-level knowledge of the gene and disease and current VCEP recommendations for functional assay evidence are a useful tool to improve the accessibility of functional data. However, our analysis suggests that further guidance is needed to standardize this process and ensure consistency in the application of functional evidence.
Nutritional Supplementation during Pulmonary Rehabilitation in COPD: A Systematic Review
Authors: Aldhahir Abdulelah M , Al Rajah Ahmed M , Aldabayan Yousef S , Drammeh Salifu , Subbu Vanitha , Alqahtani Jaber S , Hurst John R , Mandal Swapna 
Published: June 2019

ABSTRACTBackgroundUptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use. Our objective were to report and summarise the current evidence supporting use of nutritional supplementation to improve outcomes during pulmonary rehabilitation in stable COPD patients.MethodsA systematic search was conducted up to May 7th, 2019 (registration number CRD42018089142). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online (Medline), Allied and Complementary Medicine Database (AMED), the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE (Embase), Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Web of Science.ResultsThis systematic search generated 580 initial matches, of which 24 studies (1035 COPD participants) met the pre-specified criteria and were included. Our analysis does not confirm an impact of nutritional supplementation during PR, but studies, supplements and PR programmes were heterogeneous in nature.ConclusionThere is currently insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD. Therefore, controversy remains and further research is needed.
Fast Klebsiella pneumoniae typing for outbreak reconstruction: an highly discriminatory HRM protocol on wzi capsular gene developed using EasyPrimer tool
Authors: Perini Matteo , Piazza Aurora , Panelli Simona , Carlo Domenico Di , Corbella Marta , Gona Floriana , Vailati Francesca , Marone Piero , Cirillo Daniela Maria , Farina Claudio , Zuccotti Gian Vincenzo , Comandatore Francesco 
Published: June 2019

ABSTRACTIn this work we present EasyPrimer, a user-friendly online tool developed to assist pan-PCR and High Resolution Melting (HRM) primer design. The tool finds the most suitable regions for primer design in a gene alignment and returns a clear graphical representation of their positions on the gene. EasyPrimer is particularly useful in difficult contexts, e.g. on gene alignments of hundreds of sequences and/or on highly variable genes. HRM analysis is an emerging method for fast and cost saving bacterial typing and an HRM scheme of six primer sets on five Multi-Locus Sequence Type (MLST) genes is already available for Klebsiella pneumoniae. We validated the tool designing a scheme of two HRM primer sets on the hypervariable gene wzi of Klebsiella pneumoniae and compared the two schemes. The wzi scheme resulted to have a discriminatory power comparable to the HRM MLST scheme, using only one third of primer sets. Then we successfully used the wzi HRM primer scheme to reconstruct a Klebsiella pneumoniae nosocomial outbreak in few hours. The use of hypervariable genes reduces the number of HRM primer sets required for bacterial typing allowing to perform cost saving, large-scale surveillance programs.
3D imaging of undissected optically clearedAnopheles stephensimosquitoes infected withPlasmodiumparasites
Authors: De Niz Mariana , Kehrer Jessica , Brancucci Nicolas M.B. , Moalli Federica , Reynaud Emmanuel G. , Stein Jens V. , Frischknecht Friedrich 
Published: June 2019

AbstractMalaria is a life-threatening disease, caused by Apicomplexan parasites of thePlasmodiumgenus. TheAnophelesmosquito is necessary for the sexual replication of these parasites and for their transmission to vertebrate hosts, including humans. Imaging of the parasite within the insect vector has been attempted using multiple microscopy methods, most of which are hampered by the presence of the light scattering opaque cuticle of the mosquito. So far, imaging of thePlasmodiummosquito stages depended on either sectioning or surgical dissection of important anatomical sites, such as the midgut and the salivary glands. Optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) enable imaging fields of view in the centimeter scale whilst providing micrometer resolution. In this paper, we present reconstructions of the whole body ofPlasmodium-infected, optically clearedAnopheles stephensimosquitoes and their midguts. The 3D-reconstructions from OPT imaging show detailed features of the mosquito anatomy and enable overall localization of parasites in midguts. Additionally, LSFM imaging of mosquito midguts shows detailed distribution of oocysts in extracted midguts.
Humans are primarily model-based learners in the two-stage task
Authors: da Silva Carolina Feher , Hare Todd A. 
Published: June 2019

AbstractDistinct model-free and model-based learning processes are thought to drive both typical and dysfunctional behaviours. Data from two-stage decision tasks have seemingly shown that human behaviour is driven by both processes operating in parallel. However, in this study, we show that more detailed task instructions lead participants to make primarily model-based choices that have little, if any, simple model-free influence. We also demonstrate that behaviour in the two-stage task may falsely appear to be driven by a combination of simple model-free and model-based learning if purely model-based agents form inaccurate models of the task because of misconceptions. Furthermore, we report evidence that many participants do misconceive the task in important ways. Overall, we argue that humans formulate a wide variety of learning models. Consequently, the simple dichotomy of model-free versus model-based learning is inadequate to explain behaviour in the two-stage task and connections between reward learning, habit formation, and compulsivity.
Lis1 promotes the formation of maximally activated cytoplasmic dynein-1 complexes
Authors: Htet Zaw Min , Gillies John P. , Baker Richard W. , Leschziner Andres E. , DeSantis Morgan E. , Reck-Peterson Samara L. 
Published: June 2019

AbstractCytoplasmic dynein-1 is a molecular motor that drives nearly all minus-end-directed microtubule-based transport in human cells, performing functions ranging from retrograde axonal transport to mitotic spindle assembly1,2. Activated dynein complexes consist of one or two dynein dimers, the dynactin complex, and an “activating adaptor”, with maximal velocity seen with two dimers present (Fig. 1a)3-6. Little is known about how this massive ∼4MDa complex is assembled. Using purified recombinant human proteins, we uncovered a novel role for the dynein-binding protein, Lis1, in the formation of fully activated dynein complexes containing two dynein dimers. Lis1 is required for maximal velocity of complexes activated by proteins representing three different families of activating adaptors: BicD2, Hook3, and Ninl. Once activated dynein complexes have formed, they do not require the presence of Lis1 for sustained maximal velocity. Using cryo-electron microscopy we show that human Lis1 binds to dynein at two sites on dynein’s motor domain, similar to yeast dynein7. We propose that the ability of Lis1 to bind at these sites may function in multiple stages of assembling the motile human dynein/ dynactin/ activating adaptor complex.
Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation
Authors: Valencia Jonathan E. , Feuda Roberto , Mellott Dan O. , Burke Robert D. , Peter Isabelle S. 
Published: June 2019

ABSTRACTOne of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, includingpax6,six1/2,eya, anddac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.
Evolutionary success of a parasitic B chromosome rests on gene content
Authors: Ruiz-Ruano Francisco J. , Navarro-Domínguez Beatriz , López-León María Dolores , Cabrero Josefa , Camacho Juan Pedro M. 
Published: June 2019

AbstractSupernumerary (B) chromosomes are dispensable genomic elements found in most kinds of eukaryotic genomes. Many show drive mechanisms that give them an advantage in transmission, but how they achieve it remains a mystery. The recent finding of protein-coding genes in B chromosomes has opened the possibility that their evolutionary success is based on their genetic content. Using a protocol based on mapping genomic DNA Illumina reads from B-carrying and B-lacking individuals on the coding sequences ofde novotranscriptomes from the same individuals, we identified 25 protein-coding genes in the B chromosome of the migratory locust, 15 of which showed a full coding region. Remarkably, one of these genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C), an E3 ubiquitin ligase involved in the metaphase-anaphase transition. Sequence comparison of A and B chromosome gene paralogs showed that the latter show B-specific nucleotide changes, neither of which putatively impairs protein function. These nucleotide signatures allowed identifying B-derived transcripts in B-carrying transcriptomes, and demonstrated that they show about similar frequency as A-derived ones. Since B-carrying individuals show higher amounts ofapc1transcripts than B-lacking ones, the putatively higher amount of APC1 protein might induce a faster metaphase-anaphase transition in spite of orientation of the two B chromosome chromatids towards the same pole during metaphase, thus facilitating B chromosome non-disjunction. Therefore,apc1is the first protein-coding gene uncovered in a B chromosome that might be responsible for B chromosome drive.Significance StatementThe genome of the migratory locust harbors a parasitic chromosome that arose about 2 million years ago. It is widespread in natural populations from Asia, Africa, Australia and Europe, i.e. all continents where this species lives. The secret for such an extraordinary evolutionary success is unveiled in this report, as B chromosomes in this species contain active protein-coding genes whose transcripts might interfere with gene expression in the host genome (the A chromosomes), thus facilitating B chromosome mitotic and meiotic drive to provide the transmission advantage which grants its success. One of the B-chromosomal genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C) whose expression might provide a mechanistic explanation for B chromosome drive.
‘The Bold are the Sociable’: Personality, sociability and lateralized utilization of brain hemisphere in the juveniles of a megafish Deccan Mahseer (Tor khudree)
Authors: Varma Vishwanath , Vasoya Harsh , Jain Anushka , Binoy VV 
Published: June 2019

AbstractThe present study explored relationships between personality traits; boldness, activity and sociability, and lateralized utilization of brain hemispheres in the hatchery reared juveniles of Deccan Mahseer (Tor khudree), a game fish inhabiting the rivers of central and southern India. Our results revealed a significant positive correlation between boldness and activity in this species when tested in isolation. However, boldness was positively correlated with the time spent near the individual conspecific but not with the individual alien invasive heterospecific tilapia (Oreochromis mossambicus). Although juvenile Deccan mahseer exhibited significant variation in the preference towards conspecific over heterospecific, no divergence in the utilization of right or left eye was seen while observing these individuals suggesting the lack of lateralized utilization of the brain hemispheres. Furthermore, laterality in visual preference failed to show any significant correlation with any of the personality traits tested in this species. Results are discussed in the light of the existing literature on the impact of life in homogenous hatchery conditions on the behaviour, personality traits and cognitive abilities of fishes.Significance statementThe present study is one of the first that focuses on personality and lateralization in Deccan Mahseers, an endangered freshwater megafish. We report a positive linkage between boldness and sociability but do not find any correlation of personality with lateralized utilization of brain hemispheres in diverse social contexts. These findings have implications in the conservation and cultivation of this ecologically, culturally and economically important indigenous fish.
Human condensin I and II drive extensive ATP–dependent compaction of nucleosome–bound DNA
Authors: Kong Muwen , Cutts Erin , Pan Dongqing , Beuron Fabienne , Kaliyappan Thangavelu , Xue Chaoyou , Morris Ed , Musacchio Andrea , Vannini Alessandro , Greene Eric C. 
Published: June 2019

AbstractStructural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin I and II and unveil the architecture of the human condensin II complex, revealing two putative DNA–binding sites. Using single–molecule imaging, we demonstrate that both condensin I and II exhibit ATP-dependent motor activity and promote extensive and reversible compaction of double–stranded DNA. Nucleosomes are incorporated into DNA loops during compaction without being displaced from the DNA, indicating that condensin complexes can readily act upon nucleosome fibers. These observations shed light on critical processes involved in genome organization in human cells.One Sentence SummaryATP–dependent DNA compaction by human condensin complexes.
Large-scale dissection suggests that ultraconserved elements are dispensable for mouse embryonic stem cell survival and fitness
Authors: Schneider Aksana , Hiller Michael , Buchholz Frank 
Published: June 2019

Withdrawal statementThe authors have withdrawn their manuscript from bioRxiv regretfully. During additional experiments for the revision we noticed inconsistencies in some results, which may affect the main conclusion of the manuscript. In particular, we noticed that using different primer pairs, some clones that were classified as homozygous knockouts, are actually not knockouts. These were unexpected findings, but might reflect the recently described larger rearrangements observed using CRISPR technology1,2,3,4. Follow up experiments are ongoing, but we would like to withdraw the manuscript at this point in time to avoid misunderstandings. Therefore, the manuscript should currently not be cited. Any questions regarding the manuscript should be addressed to the corresponding author.