bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel real-time PCR assay panel for detection of common respiratory pathogens in a convenient, strip-tube array format
Authors: Hasan Mohammad Rubayet , Mana Hassan Al , Young Virginia , Tang Patrick , Thomas Eva , Tan Rusung , Tilley Peter 
Published: October 2018

AbstractCommercial multiplex assays, built on different chemistries and platforms are widely available for simultaneous detection of pathogens that cause respiratory infections. However, these tests are often difficult to implement in a resource limited setting because of high cost. In this study, we developed and validated a method for simultaneous testing of common respiratory pathogens (Respanel) by real-time PCR in a convenient, strip-tube array format. Primers and probes for sixteen PCR assays were selected from the literature or newly designed. Following optimization of individual PCR assays, strip-tube arrays were prepared by dispensing primer-probe mixes (PPM) into two sets of 8-tube strips. Nucleic acid extracts from specimens were mixed with PCR master mix, and dispensed column-wise into 2X8-wells of a 96-well plate. PPMs from strip-tubes were then added to the wells using a multichannel pipette for real-time PCR. Individual PCR assays were optimized using previously known specimens (n=397) with 91%-100% concordance with culture, DFA or PCR results. Respanel was then tested in a routine manner at two different sites using specimens (n=147) previously tested by Qiagen Resplex I&II or Fast-Track Diagnostics Respiratory Pathogens 21 assays. The sensitivity, specificity and accuracy of Respanel were 94%, 95% and 95%, respectively, against Resplex and 88%, 100% and 99%, respectively, against FTDRP21. Respanel detected 48% more pathogens (p<0.05) than Resplex but the rate of pathogen detection was not significantly different from FTDRP21. Respanel is a convenient and inexpensive assay that is more sensitive than Resplex and comparable to FTDRP21 for the detection of common respiratory pathogens.
Intra-Nuclear Tensile Strain Mediates Reorganization of Epigenetically Marked Chromatin During Cardiac Development and Disease
Authors: Seelbinder Benjamin , Ghosh Soham , Berman Alycia G. , Schneider Stephanie E. , Goergen Craig J. , Calve Sarah , Neu Corey P. 
Published: October 2018

ABSTRACTEnvironmental mechanical cues are critical to guide cell fate. Forces transmit to the nucleus through the Linker of Nucleo- and Cytoskeleton (LINC) complex and are thought to influence the organization of chromatin that is related to cell differentiation; however, the underlying mechanisms are unclear. Here, we investigated chromatin reorganization during murine cardiac development and found that cardiomyocytes establish a distinct architecture characterized by relocation of H3K9me3-modified chromatin from the nuclear interior to the periphery and co-localization to myofibrils. This effect was abrogated in stiff environments that inhibited cardiomyocyte contractility, or after LINC complex disruption, and resulted in the relocation of H3K27me3-modified chromatin instead. By generating high-resolution intra-nuclear strain maps during cardiomyocyte contraction, we discovered that the reorganization of H3K9me3-marked chromatin is influenced by tensile, but not compressive, nuclear strains. Our findings highlight a new role for nuclear mechanosensation in guiding cell fate through chromatin reorganization in response to environmental cues.
Drug-Target Interaction prediction using Multi Graph Regularized Nuclear Norm Minimization
Authors: Mongia Aanchal , Majumdar Angshul 
Published: October 2018

AbstractThe identification of interactions between drugs and target proteins is crucial in pharmaceutical sciences. The experimental validation of interactions in genomic drug discovery is laborious and expensive; hence, there is a need for efficient and accurate in-silico techniques which can predict potential drug-target interactions to narrow down the search space for experimental verification.In this work, we propose a new framework, namely, Multi Graph Regularized Nuclear Norm Minimization, which predicts the interactions between drugs and proteins from three inputs: known drug-target interaction network, similarities over drugs and those over targets. The proposed method focuses on finding a low-rank interaction matrix that is structured by the proximities of drugs and targets encoded by graphs. Previous works on Drug Target Interaction (DTI) prediction have shown that incorporating drug and target similarities helps in learning the data manifold better by preserving the local geometries of the original data. But, there is no clear consensus on which kind and what combination of similarities would best assist the prediction task. Hence, we propose to use various multiple drug-drug similarities and target-target similarities as multiple graph Laplacian (over drugs/targets) regularization terms to capture the proximities exhaustively.Extensive cross-validation experiments on four benchmark datasets using standard evaluation metrics (AUPR and AUC) show that the proposed algorithm improves the predictive performance and outperforms recent state-of-the-art computational methods by a large margin.Author summaryThis work introduces a computational approach, namely Multi-Graph Regularized Nuclear Norm Minimization (MGRNNM), to predict potential interactions between drugs and targets. The novelty of MGRNNM lies in structuring drug-target interactions by multiple proximities of drugs and targets. There have been previous works which have graph regularized Matrix factorization and Matrix completion algorithms to incorporate the standard chemical structure drug similarity and genomic sequence target protein similarity, respectively. We introduce multiple drug-graph laplacian and target-graph laplacian regularization terms to the standard matrix completion framework to predict the missing values in the interaction matrix. The graph Laplacian terms are constructed from various kinds and combinations of similarities over drugs and targets (computed from the interaction matrix itself). In addition to this, we further improve the prediction accuracy by sparsifying the drug and target similarity matrices, respectively. For performance evaluation, we conducted extensive experiments on four benchmark datasets. The experimental results demonstrated that MGRNNM clearly outperforms recent state-of-the-art methods under three different cross-validation settings, in terms of the area under the ROC curve (AUC) and the area under the precision-recall curve (AUPR).
An integrative machine learning approach for prediction of toxicity-related drug safety
Authors: Lysenko Artem , Sharma Alok , Boroevich Keith A , Tsunoda Tatsuhiko 
Published: October 2018

AbstractRecent trends in drug development have been marked by diminishing returns of escalating costs and falling rate of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials as well as the leading cause of drug withdraws after release to market. Computational methods capable of predicting these failures can reduce waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity. We demonstrate that our method (TargeTox) can distinguish potentially idiosyncratically toxic drugs from safe drugs and is also suitable for speculative evaluation of different target sets to support the design of optimal low-toxicity combinations.Summary blurb:Prediction of toxicity-related drug clinical trial failures, withdrawals from market and idiosyncratic toxicity risk by combining biological network analysis with machine learning.
Altered BOLD signal variation in Alzheimer’s disease and frontotemporal dementia
Authors: Tuovinen Timo , Kananen Janne , Rytty Riikka , Moilanen Virpi , Elseoud Ahmed Abou , Remes Anne M , Kiviniemi Vesa ,   ADNI
Published: October 2018

AbstractRecently discovered glymphatic brain clearance mechanisms utilizing physiological pulsations have been shown to fail at removing waste materials such as amyloid and tau plaques in neurodegenerative diseases. Since cardiovascular pulsations are a main driving force of the clearance, this research investigates if commonly available blood oxygen level-dependent (BOLD) signals at 1.5 and 3 T could detect abnormal physiological pulsations in neurodegenerative diseases. Coefficient of variation in BOLD signal (CVBOLD) was used to estimate contribution of physiological signals in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). 17 AD patients and 18 bvFTD patients were compared to 24 control subjects imaged with a 1.5 T setup from a local institute. AD results were further verified with 3 T data from the Alzheimer’s disease neuroimaging initiative (ADNI) repository with 30 AD patients and 40 matched controls. Effect of motion and gray matter atrophy was evaluated and receiver operating characteristic (ROC) analyses was performed.The CVBOLD was higher in both AD and bvFTD groups compared to controls (p < 0.0005). The difference was not explained by head motion or gray matter atrophy. In AD patients, the CVBOLD alterations were localized in overlapping structures in both 1.5 T and 3 T data. Localization of the CVBOLD alterations was different in AD than in bvFTD. Areas where CVBOLD is higher in patient groups than in control group involved periventricular white matter, basal ganglia and multiple cortical structures. Notably, a robust difference between AD and bvFTD groups was found in the CVBOLD of frontal poles. In the analysis of diagnostic accuracy, the CVBOLD metrics area under the ROC for detecting disease ranged 0.85 – 0.96.ConclusionsThe analysis of brain physiological pulsations measured using CVBOLD reveals disease-specific alterations in both AD and bvFTD.
Functionally Coherent Transcription Factor Target Networks Illuminate Control of Epithelial Remodelling
Authors: Overton Ian M. , Sims Andrew H. , Owen Jeremy A. , Heale Bret S. E. , Ford Matthew J. , Lubbock Alexander L. R. , Pairo-Castineira Erola , Essafi Abdelkader 
Published: October 2018

SummaryCell identity is governed by gene expression, regulated by Transcription Factor (TF) binding at cis-regulatory modules. We developed the NetNC software to decode the relationship between TF binding and the regulation of cognate target genes in cell decision-making; demonstrated on nine datasets for the Snail and Twist TFs, and also modENCODE ‘HOT’ regions. Results illuminated conserved molecular networks controlling development and disease, with implications for precision medicine. Predicted ‘neutral’ TF binding accounted for the majority (50% to ≥80%) of candidate target genes from statistically significant peaks and HOT regions had high functional coherence. Expression of orthologous functional TF targets discriminated breast cancer molecular subtypes and predicted novel tumour biology. We identified new gene functions and network modules including crosstalk with notch signalling and regulation of chromatin organisation, evidencing networks that reshape Waddington’s landscape during epithelial remodelling. Predicted invasion roleswere validated using a tractable cell model, supporting our computational approach.
TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation
Authors: Ferrari Roberto , de Llobet Cucalon Lara Isabel , Di Vona Chiara , Le Dilly François , Vidal Enrique , Lioutas Antonios , Oliete Javier Quilez , Jochem Laura , Cutts Erin , Dieci Giorgio , Vannini Alessandro , Teichmann Martin , de la Luna Susana , Beato Miguel 
Published: October 2018

Summary paragraphThe mammalian genome is shaped by the expansion of repetitive elements that provide new regulatory networks for coordinated control of gene expression1 and genome folding2–4. Alu elements (AEs) are selectively retained close to the transcription start site of genes5, show protoenhancer functions6, correlate with the level of chromatin interactions7 and are recognized by transcription factor III (TFIIIC)8, but the relevance of all this is not clear. Here we report regulatory mechanisms that unveil a central role of AEs and TFIIIC in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of pre-marked AEs near cell cycle genes recruit TFIIIC to alter their chromatin accessibility via TFIIIC-mediated acetylation of histone H3 Lysine-18 (H3K18). This facilitates AEs contact with distant CTCF sites near other cell cycle genes promoters, which also become hyperacetylated at H3K18. These changes ensure basal transcription of crucial cell cycle genes, and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor adjusts 3D genome folding and gene expression. We anticipate that expansion of several families of repetitive elements during evolution might have served to generate new genomic cis-regulatory circuits enabling the coordinated regulation of a large set of genes relevant for cellular stress survival. As growth factor withdrawal is a situation relevant in cancer biology, our study identifies TFIIIC as a new potential target for clinical intervention.
Multipoint and large volume fiber photometry with a single tapered optical fiber implant
Authors: Pisano Filippo , Pisanello Marco , Maglie Emanuela , Balena Antonio , Sileo Leonardo , Spagnolo Barbara , Hyun Minsuk , De Vittorio Massimo , Sabatini Bernardo L. , Pisanello Ferruccio 
Published: October 2018

AbstractTechniques to monitor functional fluorescence signal from the brain are increasingly popular in the neuroscience community. However, most implementations are based on flat cleaved optical fibers (FFs) that can only interface with shallow tissue volumes adjacent to the fiber opening. To circumvent this limitation, we exploit modal properties of tapered optical fibers (TFs) to structure light collection over the wide optically active area of the fiber taper, providing an approach to efficiently and selectively collect light from the region(s) of interest. While being less invasive than FFs, TF probes can uniformly collect light over up to 2 mm of tissue and allow for multisite photometry along the taper. Furthermore, by micro-structuring the non-planar surface of the fiber taper, collection volumes from TFs can also be engineered arbitrarily in both shape and size. Owing to the abilities offered by these probes, we envision that TFs can set a novel, powerful paradigm in optically targeting not only the deep brain, but, more in general, any biological system or organ where light collection from the deep tissues is beneficial but challenging because of tissue scattering and absorption.
Comparative analysis of cellular immune responses in conventional and SPF Baboons (Papio spp.)
Authors: Magden Elizabeth R , Nehete Bharti P. , Chitta Sriram , Williams Lawrence E. , Simmons Joe H , Abee Christian R. , Nehete Pramod N. 
Published: October 2018

AbstractBaboons (papio spp.) have served as a successful model of human disease such as cardiac and respiratory, infectious, diabetes, genetics, immunology, aging, and xenotransplantation. The development of an immunologically defined specific-pathogen free (SPF) baboon model has further advanced research, especially with studies involving the immune system and immunosuppression. In this study, we compare normal immunological changes of peripheral blood mononuclear cell (PBMC) subsets, and their function in age-matched conventional and SPF baboons. Our results demonstrate that both groups have comparable numbers of different lymphocyte subsets, but there are phenotypic differences in central and effector memory T cells subsets that are more pronounced in the CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboon groups, PBMC show higher proliferative responses to mitogens PHA and PWM and higher IFN-γ producing cells to Con A and PWM in the conventional group. Plasma levels of the inflammatory cytokine TNF-α were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll like ligands (TLR ligands) TLR-3, TLR-4 and TLR-8 show higher IFN-γ producing cells while PBMC from SPF baboons stimulated with TLR-5 and TLR-6 ligand show higher IFN-γ producing cells. These findings suggest that while the lymphocyte subsets in conventional and SPF baboons share many phenotypic and functional similarities, specific differences exist in immune function of lymphocytes which could impact the quality and quantity of innate and adaptive immune responses. These differences should be considered for better experimental outcomes, specifically in studies measuring immunological endpoints.
Salivary and plasma levels of matrix metalloproteinase-9 and myeloperoxidase at rest and after acute physical exercise in patients with coronary artery disease
Authors: Mahmood Zeid , Enocsson Helena , Bäck Maria , Lundberg Anna K , Jonasson Lena 
Published: October 2018

AbstractBackgroundLow-grade systemic inflammation is a predictor of recurrent cardiac events in patients with coronary artery disease (CAD). Plasma proteins such as matrix metalloproteinase (MMP)-9 and myeloperoxidase (MPO) have been shown to reflect basal as well as stress-induced inflammation in CAD. Measurements of MMP-9 and MPO in saliva might pose several advantages. Therefore, we investigated whether salivary levels of MMP-9 and MPO corresponded to plasma levels in patients with CAD, both at rest and after acute physical exercise.MethodsAn acute bout of physical exercise on a bicycle ergometer was used as a model for stress-induced inflammation. Twenty-three CAD patients performed the test on two occasions 3-6 months apart. Whole unstimulated saliva was collected before, directly after and 30 min after exercise while plasma was collected before and after 30 min. MMP-9 and MPO in saliva and plasma were determined by Luminex.ResultsMMP-9 and MPO levels were 2- to 4-fold higher in saliva than in plasma. Within the saliva compartment, and also to a great extent within the plasma compartments, MMP-9 and MPO showed strong intercorrelations at all time points. However, there were no (or weak) correlations between salivary and plasma MMP-9 and none between salivary and plasma MPO.ConclusionWe conclude that salivary diagnostics cannot be used to assess systemic levels of MMP-9 and MPO in CAD patients, neither at rest nor after acute physical exercise.
Patterns of fish utilisation in a tropical Indo-Pacific mangrove-coral seascape, New Caledonia
Authors: Dubuc A , Waltham N. , Baker R. , Marchand C. , Sheaves M. 
Published: October 2018

AbstractMangrove forests are important habitats for fish. However, their utilisation by fish, and the specific values they confer, are still not fully understood. This study describes how fish use mangrove forests in an Indo-Pacific mangrove-coral reef seascape. Sampling was conducted using underwater video cameras (UVCs) to describe spatial and temporal variations in fish assemblages across a small-scale (~ 2.5 km2) system, and over the tidal and lunar cycle. UVCs were deployed in the two main component habitats of mangrove forests: at the mangrove forest edge, and inside the forest (5 m from the forest edge), to establish patterns of utilisation of fish across the tidal and lunar cycle. Proximity to coral reefs had a strong influence on the mangrove fish community, as most fish recorded were reef-associated. Juveniles of 12 reef species were observed, including two species classified as vulnerable on the IUCN list, and one endemic species. Fish assemblages on the mangrove edge differed significantly from those inside the forest. Most fish utilised the forest edge, with few species making regular use of in-forest habitats, supporting the contention that most fish species remain on the edge and potentially retreat into the forest for opportunistic feeding, or when threatened by larger predators. Species-specific patterns of utilisation varied across the tidal and lunar cycle. Small differences in depth profiles and substrate across the small-scale system had a significant effect on fish assemblages, highlighting the importance of accounting for spatial heterogeneity in these factors. These data provide important information for managers to implement adequate conservation strategies that include broader interconnected habitat mosaics.
Preclinical Modeling of Exposure to a Global Marine Bio-Contaminant: Effects of In Utero Domoic Acid Exposure on Neonatal Behavior and Infant Memory
Authors: Grant Kimberly S. , Crouthamel Brenda , Kenney Caroline , McKain Noelle , Petroff Rebekah , Shum Sara , Jing Jing , Isoherranen Nina , Burbacher Thomas M. 
Published: October 2018

AbstractDomoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the recognition memory assessment, given between 1-2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential visual attention to novel test stimuli. This finding suggests subtle but significant impairment in recognition memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.