bluuebunny/crossref_metadata_2025_split huggingface dataset:
A machine learning approach predicts essential genes and pharmacological targets in cancer
Authors: Gilvary Coryandar , Madhukar Neel S. , Gayvert Kaitlyn , Foronda Miguel , Perez Alexendar , Leslie Christina S. , Dow Lukas , Pandey Gaurav , Elemento Olivier 
Published: July 2019

ABSTRACTLoss-of-function (LoF) screenings have the potential to reveal novel cancer-specific vulnerabilities, prioritize drug treatments, and inform precision medicine therapeutics. These screenings were traditionally done using shRNAs, but with the recent emergence of CRISPR technology there has been a shift in methodology. However, recent analyses have found large inconsistencies between CRISPR and shRNA essentiality results. Here, we examined the DepMap project, the largest cancer LoF effort undertaken to date, and find a lack of correlation between CRISPR and shRNA LoF results; we further characterized differences between genes found to be essential by either platform. We then introduce ECLIPSE, a machine learning approach, which combines genomic, cell line, and experimental design features to predict essential genes and platform specific essential genes in specific cancer cell lines. We applied ECLIPSE to known drug targets and found that our approach strongly differentiated drugs approved for cancer versus those that have not, and can thus be leveraged to identify potential cancer repurposing opportunities. Overall, ECLIPSE allows for a more comprehensive analysis of gene essentiality and drug development; which neither platform can achieve alone.
Deep Learning For Denoising Hi-C Chromosomal Contact Data
Authors: Highsmith Max , Oluwadare Oluwatosin , Cheng Jianlin 
Published: July 2019

AbstractMotivationThe three-dimensional (3D) organization of an organism’s genome and chromosomes plays a significant role in many biological processes. Currently, methods exist for modeling chromosomal 3D structure using contact matrices generated via chromosome conformation capture (3C) techniques such as Hi-C. However, the effectiveness of these methods is inherently bottlenecked by the quality of the Hi-C data, which may be corrupted by experimental noise. Consequently, it is valuable to develop methods for eliminating the impact of noise on the quality of reconstructed structures.ResultsWe develop unsupervised and semi-supervised deep learning algorithms (i.e. deep convolutional autoencoders) to denoise Hi-C contact matrix data and improve the quality of chromosome structure predictions. When applied to noisy synthetic contact matrices of the yeast genome, our network demonstrates consistent improvement across metrics for contact matrix similarity including: Pearson Correlation, Spearman Correlation and Signal-to-Noise Ratio. Positive improvement across these metrics is seen consistently across a wide space of parameters to both gaussian and poisson noise functions.Contactmrh8x5@mail.missouri.edu and chengji@missouri.edu
Bordetella Colonization Factor A (BcfA) elicits protective immunity againstBordetella bronchisepticain the absence of an additional adjuvant
Authors: Yount Kacy S. , Jennings-Gee Jamie , Caution Kyle , Fullen Audra R. , Corps Kara N. , Quataert Sally , Deora Rajendar , Dubey Purnima 
Published: July 2019

ABSTRACTBordetella bronchiseptica (B. bronchiseptica)is an etiologic agent of respiratory diseases in animals and humans. Despite widespread use of veterinaryB. bronchisepticavaccines, there is limited information on their composition, relative efficacy, and the immune responses they elicit. Furthermore, humanB. bronchisepticavaccines are not available. We leveraged the dual antigenic and adjuvant functions of BcfA to develop acellularB. bronchisepticavaccines in the absence of an additional adjuvant. Balb/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and theBordetellaantigens FHA and Prn were equally protected against challenge with a prototypeB. bronchisepticastrain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine®and provided protection against aB. bronchisepticastrain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection againstBordetellaeand other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA/Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed Balb/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines againstBordetellaeand other pathogens.
Slow cortico-cortical connectivity (2-5Hz) is a new robust signature of conscious states
Authors: Bourdillon Pierre , Hermann Bertrand , Guénot Marc , Bastuji Hélène , Isnard Jean , King Jean-Rémi , Sitt Jacobo , Naccache Lionel 
Published: July 2019

AbstractWhile long-range cortico-cortical functional connectivity has been reported by several studies as a necessary condition of conscious state, precise empirical evidence is still scarce. In the present work we provide such a direct and conclusive evidence in a set of three experiments. In the two first experiments intracranial-EEG was recorded during four distinct states in the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We discovered that long-range FC, computed by the weighted Symbolic-Mutual-Information (wSMI) in the 2-5Hz frequency band was a specific marker of conscious states that could discriminate CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients by revealing that wSMI in the 2-5 Hz range was also able to accurately discriminate patients in the vegetative state (or unresponsive wakefulness syndrome) from patients in the minimally conscious state. Taken together the present results suggest that 2-5Hz FC is a new and robust signature of conscious states.
Does human P-glycoprotein efflux involve transmembrane alpha helix breakage?
Authors: Bonito Cátia A. , Ferreira Maria-José U. , Ferreira Ricardo J. , dos Santos Daniel J. V. A. 
Published: July 2019

AbstractThe occluded conformation suggested in a recent article that revealed a new inward-facing conformation for the human P-glycoprotein may not represent the closing of a gate region but instead an artifact derived from lateral compression in a too small sized nanodisc, used to stabilize the transmembrane domains of the transporter.
Analysis of housekeeping genes in the peripheral blood of retinoblastoma patients
Authors: Martínez-Sánchez Mayra , Hernandez-Monge Jesús , Moctezuma-Dávila Mariana , Rangel-Charqueño Martha , Olivares-Illana Vanesa 
Published: July 2019

AbstractRetinoblastoma is a pediatric neoplasia with a high incidence in non-developed countries. Nowadays the diagnosis is clinical and unfortunately in advanced stages of the diseases, which puts the child’s life risk. The search for molecular diagnosis on retinoblastoma is necessary. Due to their location and tendency to migrate, biopsies of retinoblastoma are not recommended then, peripheral blood samples can be a good source for the search of biomarker. RT qPCR is a sensitive method for gene expression quantification; in order to achieve optimal results, a crucial step is the reference gene choice that cannot be neglected under any circumstance. Six of the most commonly used housekeeping genes; GAPDH, HPRT1, B2M, TBP, RPL13a and 18S, were tested in the blood samples of patients diagnosed with retinoblastoma and healthy controls. The HPRT and TBP were found the most reliable genes whereas GAPDH, that is one of the most commonly used genes for normalisation, together with B2M, RPL13a and 18S have to be avoided. Using the selected reference genes, the Rb mRNA showed significant differences between patients and healthy children whereas no differences were found using to control groups. In the present study, we validate blood samples of patients with retinoblastoma.
Comparative genome analysis of a multidrug-resistant Pseudomonas aeruginosa sequence type 277 clone that harbours two copies of the blaSPM-1 gene and multiple single nucleotide polymorphisms in other resistance-associated genes
Authors: do Nascimento Ana Paula Barbosa , Filho Fernando Medeiros , Sousa Hério , Senger Hermes , Albano Rodolpho Mattos , dos Santos Marcelo Trindade , Carvalho-Assef Ana Paula D’Alincourt , da Silva Fabrício Alves Barbosa 
Published: July 2019

AbstractPseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of blaSPM-1 gene, encoding a metallo-beta-lactamase, in addition to other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify physiological key aspects that may lead to the exposure of new targets for therapy. This study was designed to characterize the genome of Pseudomonas aeruginosa CCBH4851 through the detection of genomic features and genome comparison with other Pseudomonas aeruginosa strains. The CCBH4851 closed genome showed features that were consistent with data reported for the specie. However, comparative genomics revealed the absence of genes important for pathogenesis. On the other hand, CCBH4851 genome contained acquired genomic islands that carry additional virulence and antimicrobial resistance-related genes. The presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations could influence the multidrug-resistant behavior of CCBH4851. Overall, the characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed several features that could directly impact the profile of virulence and antibiotic resistance of this pathogen in infectious outbreaks.
HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
Authors: Rodrigues Lucas S , Nali Luiz H da Silva , Leal Cibele O D , Sabino Ester C , Lacerda Eliana M , Kingdon Caroline C , Nacul Luis , Romano Camila M 
Published: July 2019

AbstractChronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERV–K and HERV–W) was determined in blood from moderately and severely affected ME/CFS patients. HERV-K was overexpressed only in moderately affected individuals and HERV-W showed no difference. This is the first report about HERV-K differential expression in moderate ME/CFS.
Correcting for sparsity and non-independence in glycomic data through a systems biology framework
Authors: Bao Bokan , Kellman Benjamin P. , Chiang Austin W.T. , York Austin K. , Mohammad Mahmoud A. , Haymond Morey W. , Bode Lars , Lewis Nathan E. 
Published: July 2019

AbstractGlycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the roles of glycans, but it remains challenging to properly analyze large glycomics datasets, since the data are sparse (each sample often has only a few measured glycans) and detected glycans are non-independent (sharing many intermediate biosynthetic steps). We address these challenges with GlyCompare, a glycomic data analysis approach that leverages shared biosynthetic pathway intermediates to correct for sparsity and non-independence in glycomics. Specifically, quantities of measured glycans are propagated to intermediate glycan substructures, which enables direct comparison of different glycoprofiles and increases statistical power. Using GlyCompare, we studied diverse N-glycan profiles from glycoengineered erythropoietin. We obtained biologically meaningful clustering of mutant cell glycoprofiles and identified knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures. We further analyzed human milk oligosaccharide profiles and identified novel impacts that the mother’s secretor-status on fucosylation and sialylation. Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
A Combinatorial Approach for Single-cell Variant Detection via Phylogenetic Inference
Authors: Edrisi Mohammadamin , Zafar Hamim , Nakhleh Luay 
Published: July 2019

AbstractSingle-cell sequencing provides a powerful approach for elucidating intratumor heterogeneity by resolving cell-to-cell variability. However, it also poses additional challenges including elevated error rates, allelic dropout and non-uniform coverage. A recently introduced single-cell-specific mutation detection algorithm leverages the evolutionary relationship between cells for denoising the data. However, due to its probabilistic nature, this method does not scale well with the number of cells. Here, we develop a novel combinatorial approach for utilizing the genealogical relationship of cells in detecting mutations from noisy single-cell sequencing data. Our method, called scVILP, jointly detects mutations in individual cells and reconstructs a perfect phylogeny among these cells. We employ a novel Integer Linear Program algorithm for deterministically and efficiently solving the joint inference problem. We show that scVILP achieves similar or better accuracy but significantly better runtime over existing methods on simulated data. We also applied scVILP to an empirical human cancer dataset from a high grade serous ovarian cancer patient.
Association of the gut microbiota with colorectal cancer in a South Asian cohort of patients
Authors: Sahankumari AGP , Gamage Bawantha D. , Malavige Gathsaurie Neelika 
Published: July 2019

AbstractBackgroundAs the gut microbiome is thought to play a role in the pathogenesis of colorectal carcinoma (CRC) and affected by the diet and the genetic composition, we sought to investigate the patterns of gut microbiota that associate with CRC in a South Asian cohort of patients with CRC.MethodologyThe relative abundance of 45 types of gut microbial species were determined in faecal samples of CRC patients (n=24), DM (n=20) and healthy age matched controls (n=44), using a PCR array. Data was analyzed using the specific software for analysis of bacterial DNA quantification.ResultsThe species Bacteroides fragilis (23.9-fold), Bacteroides thetaiotaomicron (8-fold) and Akkermansia muciniphila (5.9 fold) were several-fold over expressed in patients with CRC compared to healthy individuals, whereas bacterial species of the Phylum Proteobactria were under expressed. There was no difference in the abundance of these 3 species of bacteria with tumour stage or gender and age of patients. Aeromonas species, Enterococcus faecium and Shigella dysenteriae (Proteobacteria) were over 100-fold over abundant in those with DM compared to healthy individuals. Although 70.83% of those with CRC also had diabetes, the relative abundance of microbiota in CRC patients were different to those who had diabetes and no CRC.ConclusionsPatients with CRC and DM harbor a markedly different gut microbiota patterns compared to their healthy counterparts. Similar patterns of gut microbial dysbiosis that associate with CRC and DM appear be seen in South Asian populations, compared to Western countries, despite differences in the diet and ethnicity.
Differentiating electrophysiological indices of internal and external performance monitoring: Relationship with perfectionism and locus of control
Authors: Muir Alexandra M. , Carbine Kaylie A. , Goodwin Jayden , Hedges-Muncy Ariana , Endrass Tanja , Larson Michael J. 
Published: July 2019

AbstractThe impact of individual differences on performance monitoring and psychopathology is a question of active debate. Personality traits associated with psychopathology may be related to poor internal performance monitoring (as measured by the error-related negativity [ERN]) but intact external performance monitoring (as measured by the reward positivity [RewP]), suggesting that there are underlying neural differences between internal and external performance monitoring processes. We tested the relationships between individual difference measures of perfectionism, locus of control, and ERN, Pe, and RewP component difference amplitude in a healthy undergraduate sample. A total of 128 participants (69 female, M(SD)age= 20.6(2.0) years) completed two tasks: a modified version of the Eriksen Flanker and a doors gambling task along with the Frost Multidimensional Perfectionism scale, the Rotter Locus of Control scale, and the Levenson Multidimensional Locus of Control scale to quantify perfectionism and locus of control traits, respectively. Linear regressions adjusting for age and gender showed that neither ΔERN nor ΔRewP amplitude were significantly moderated by perfectionism or locus of control scores. Findings suggest that, in psychiatrically-healthy individuals, there is not a strong link between perfectionism, locus of control, and ERN or RewP amplitude. Future research on individual difference measures in people with psychopathology may provide further insight into how these personality traits affect performance monitoring.
Predictive factors in identifying operative risks in cholecystectomies
Authors: Kanlioz Murat , Ekici Ugur 
Published: July 2019

AbstractPurposeThis study aims to forecast findings showing the difficulty of operation in cholecystectomy through pre-operative examinations and reduce morbidity and mortality with the predictive data obtained.Materials and MethodsIn the preoperative period, the followings were measured in patients who will undergo cholecystectomy: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), WBC, Neutrophil ratio (NR), erythrocyte distribution range (RDW), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin (TB), direct bilirubin (DB). Following the preoperative ultrasound (USG), the patients were recorded in two groups as patients with “normal” and “increased” gallbladder wall thickness. Also, the patients were asked if they underwent ERCP and whether they received antibiotic treatment in the last 10 days due to their disease in the preoperative period. The appearance of the peroperative gallbladder was recorded in two groups as “has a normal appearance” or “edematous and/or adherent to peripheral tissues”. Whether or not there is a correlation between the preoperative findings and peroperative appearance was evaluated. The recordings and analyzes were made using SPSS statistics program. Correlation between the data were analyzed by Chi-square test. p<0.05 was considered significant.ResultsThe study achieved statistically significant results for the correlation between the “gallbladder edema and/or adhesion to peripheral tissues” in the peroperative period and the following five parameters: increased WBC, increased NR, increased gallbladder wall thickness at USG, compulsory ERCP and receipt of antibiotic treatment for the disease in the last 10 days.(p<0,05).ConclusionTaking into consideration the presence, in the preoperative period, of some or all of the five criteria-namely, increased WBC, increased NR, increased gallbladder wall thickness at USG, receiving antibiotic treatment for the disease in the last 10 days and undergoing ERCP-in patients with cholelithiasis for whom cholecystectomy is envisaged would make it easier to estimate the degree of difficulty of the surgery and the possibility of encountering difficult and complicated cases.
Comparing the Performance of mScarlet-I, mRuby3, and mCherry as FRET Acceptors for mNeonGreen
Authors: McCullock Tyler W. , MacLean David M. , Kammermeier Paul J. 
Published: July 2019

AbstractFörster Resonance Energy Transfer (FRET) has become an immensely powerful tool to profile intra- and inter-molecular interactions. Through fusion of genetically encoded fluorescent proteins (FPs) researchers have been able to detect protein oligomerization, receptor activation, and protein translocation among other biophysical phenomena. Recently, two bright monomeric red fluorescent proteins, mRuby3 and mScarlet-I, have been developed. These proteins offer much improved physical properties compared to previous generations of monomeric red FPs that should help facilitate more general adoption of Green/Red FRET. Here we assess the ability of these two proteins, along with mCherry, to act as a FRET acceptor for the bright, monomeric, green-yellow FP mNeonGreen using intensiometric FRET and 2-photon Fluorescent Lifetime Imaging Microscopy (FLIM) FRET techniques. We first determined that mNeonGreen was a stable donor for 2-photon FLIM experiments under a variety of imaging conditions. We then tested the red FP’s ability to act as FRET acceptors using mNeonGreen-Red FP tandem construct. With these constructs we found that mScarlet-I and mCherry are able to efficiently FRET with mNeonGreen in spectroscopic and FLIM FRET. In contrast, mNeonGreen and mRuby3 FRET with a much lower efficiency than predicted in these same assays. We explore possible explanations for this poor performance but are unable to definitively determine the cause, all though protein maturation seems to play a role. Overall, we find that mNeonGreen is an excellent FRET donor, and both mCherry and mScarlet-I, but not mRuby3, act as practical FRET acceptors, with mScarlet-I out performing mCherry due it’s higher brightness.
Crystal structures of the closed form ofMycobacterium tuberculosisdihydrofolate reductase in complex with dihydrofolate and antifolates
Authors: Ribeiro João Augusto , Chavez-Pacheco Sair Maximo , de Oliveira Gabriel Stephani , Silva Catharina dos Santos , Giudice João Henrique Pimenta , Libreros-Zúñiga Gerardo Andres , Dias Marcio Vinicius Bertacine 
Published: July 2019

Tuberculosis is a disease caused byMycobacterium tuberculosisand is the leading cause of death from a single infectious pathogen, with a high prevalence in developing countries in Africa and Asia. There still is a need for the development or repurposing of novel therapies to combat this disease owing to the long-term nature of current therapies and because of the number of reported resistant strains. Here, structures of dihydrofolate reductase fromM. tuberculosis(MtDHFR), which is a key target of the folate pathway, are reported in complex with four antifolates, pyrimethamine, cycloguanil, diaverdine and pemetrexed, and its substrate dihydrofolate in order to understand their binding modes. The structures of all of these complexes were obtained in the closed-conformation state of the enzyme and a fine structural analysis indicated motion in key regions of the substrate-binding site and different binding modes of the ligands. In addition, the affinities, throughKdmeasurement, of diaverdine and methotrexate have been determined; MtDHFR has a lower affinity (highestKd) for diaverdine than pyrimethamine and trimethoprim, and a very high affinity for methotrexate, as expected. The structural comparisons and analysis described in this work provide new information about the plasticity of MtDHFR and the binding effects of different antifolates.