bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Assessment of NSAID Prescriptions and Potential Nephrotoxicity Risk in Adult Kidney Transplant Recipients
Authors: Chiasson Jordan M. , Fominaya Cory E. , Gebregziabher Mulugeta , Taber David J. 
Published: March 2019

Background.
Nonsteroidal anti-inflammatory drug (NSAID) use is recommended to be avoided in kidney transplantation, with a paucity of studies assessing their safety within this population. This study aims to use a large cohort of Veterans Affairs (VA) kidney transplantation recipients to assess the risk of acute kidney injury (AKI) with NSAID use.

Methods.
This is a 10-year longitudinal cohort study of adult kidney transplant recipients retrospectively followed in the VA system from 2001 to 2010 that assessed for risk of AKI with NSAID prescriptions. NSAID prescriptions, patient characteristics, and estimated glomerular filtration rates were abstracted from the VA comprehensive electronic health record. NSAID exposure was assessed by duration, dosage, and type. AKI events were defined by ≥50% decrease in estimated glomerular filtration rate. Risk was estimated using longitudinal multivariable generalized logistic regression model.

Results.
About 5100 patients were included with a total of 29 980 years of follow-up; 671 NSAID prescriptions in 273 (5.4%) patients (2.24 per 100 patient-y) with 472 (70%) high dose were identified. High-dose NSAID prescriptions were associated with 2.83 (95% confidence interval [CI], 1.55-5.19; P < 0.001) higher odds of AKI events within a given year; low dose was not associated with AKI (odds ratio, 1.93; 95 % CI, 0.95-6.02; P = 0.256). One 7-day NSAID course was associated with 5% higher odds of increasing AKI events, whereas chronic use (≥180 d) was associated with 3.25 (95% CI, 1.78-5.97; P < 0.001) higher odds of AKI.

Conclusions.
Prescriptions for NSAIDs were uncommon in this cohort but were associated with a significant increase in the risk of AKI, which was impacted by higher NSAID dose and longer NSAID durations.
A comparison of two mathematical models of the cerebrospinal fluid dynamics
Authors: Donatelli Donatella , Marcati Pierangelo , Romagnoli Licia 
Published: March 2019

AbstractIn this paper we provide the numerical simulations of two cerebrospinal fluid dynamics models by comparing our results with the real data available in literature (see Section 4). The models describe different processes in the cerebrospinal fluid dynamics: the cerebrospinal flow in the ventricles of the brain and the reabsorption of the fluid. In the appendix we show in detail the mathematical analysis of both models and we identify the set of initial conditions for which the solutions of the systems of equations do not exhibit blow up. We investigate step by step the accuracy of these theoretical outcomes with respect to the real cerebrospinal physiology and dynamics.The plan of the paper is provided in Section 1.5.
Phylogenetic reclassification of vertebrate melatonin receptors to include Mel1d
Authors: Denker Elsa , Ebbesson Lars O. E. , Hazlerigg David G. , Macqueen Daniel J. 
Published: March 2019

ABSTRACTThe circadian and seasonal actions of melatonin are mediated by high affinity G-protein coupled receptors (melatonin receptors, MTRs), classified into phylogenetically distinct subtypes based on sequence divergence and pharmacological characteristics. Three vertebrate MTR subtypes are currently described: MT1 (MTNR1A), MT2 (MTNR1B), and Mel1c (MTNR1C / GPR50), which exhibit distinct affinities, tissue distributions and signaling properties. We present phylogenetic and comparative genomic analyses supporting a revised classification of the vertebrate MTR family. We demonstrate four ancestral vertebrate MTRs, including a novel molecule hereafter named Mel1d. We reconstructed the evolution of each vertebrate MTR, detailing genetic losses in addition to gains resulting from whole genome duplication events in teleost fishes. We show that Mel1d was lost separately in mammals and birds and has been previously mistaken for an MT1 paralogue. The genetic and functional diversity of vertebrate MTRs is more complex than appreciated, with implications for our understanding of melatonin actions in different taxa. The significance of our findings, including the existence of Mel1d, are discussed in an evolutionary and functional context accommodating a robust phylogenetic assignment of MTR gene family structure.
A genetically adaptable strategy for ribose scavenging in a human gut symbiont plays a diet-dependent role in colon colonization
Authors: Glowacki Robert W. P. , Pudlo Nicholas A. , Tuncil Yunus , Luis Ana S. , Terekhov Anton I. , Hamaker Bruce R. , Martens Eric C. 
Published: March 2019

SummaryEfficient nutrient acquisition in the competitive human gut is essential for microbial persistence. While polysaccharides have been well-studied nutrients for the gut microbiome, other resources such as co-factors and nucleic acids have been less examined. We describe a series of ribose utilization systems (RUSs) that are broadly represented in Bacteroidetes and appear to have diversified to allow access to ribose from a variety of substrates. OneBacteroides thetaiotaomicronRUS variant is critical for competitive gut colonization in a diet-specific fashion. Using molecular genetics, we probed the nature of the ribose source underlying this diet-specific phenotype, revealing that hydrolytic functions in RUS (e.g., to cleave ribonucleosides) are present but dispensable. Instead, ribokinases that are activatedin vivoand participate in cellular ribose-phosphate metabolism are essential. Our results underscore the extensive mechanisms that gut symbionts have evolved to access nutrients and how metabolic context determines the impact of these functionsin vivo.
Non-lethal exposure to H2O2 boosts bacterial survival and evolvability against oxidative stress
Authors: Rodríguez-Rojas Alexandro , Kim Joshua Jay , Johnston Paul , Makarova Olga , Eravci Murat , Weise Christoph , Hengge Regine , Rolff Jens 
Published: March 2019

AbstractUnicellular organisms have the prevalent challenge to survive under oxidative stress of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). ROS are present as by-products of photosynthesis and aerobic respiration. These reactive species are even employed by multicellular organisms as potent weapons against microbes. Although bacterial defences against lethal and sub-lethal oxidative stress have been studied in model bacteria, the role of fluctuating H2O2 concentrations remains unexplored. It is known that sub-lethal exposure of Escherichia coli to H2O2 results in enhanced survival upon subsequent exposure. Here we investigate the priming response to H2O2 at physiological concentrations. The basis and the duration of the response (memory) were also determined by time-lapse quantitative proteomics. We found that a low level of H2O2 induced several scavenging enzymes showing a long half-life, subsequently protecting cells from future exposure. We then asked if the phenotypic resistance against H2O2 alters the evolution of resistance against oxygen stress. Experimental evolution of H2O2 resistance revealed faster evolution and higher levels of resistance in primed cells. Several mutations were found to be associated with resistance in evolved populations affecting different loci but, counterintuitively, none of them was directly associated with scavenging systems. Our results have important implications for host colonisation and infections where microbes often encounter reactive oxygen species in gradients.
TrackUSF, a novel methodology for automated analysis of ultrasonic vocalizations, reveals modified social communication in a rat model of autism
Authors: Netser Shai , Nahardiya Guy , Weiss-Dicker Gili , Dadush Roei , Goussha Yizhaq , Harony-Nicolas Hala , Cohen Lior , Crammer Kobi , Wagner Shlomo 
Published: March 2019

AbstractRodents emit various social ultrasonic vocalizations (USVs), which reflect their emotional state and mediate social interaction. USVs are usually analyzed by manual or semi-automated methodologies categorizing discrete USVs according to their structure in the frequency-time domains. This laborious analysis hinders effective use of USVs for screening animal models of human pathologies associated with modified social behavior, such as autism spectrum disorder (ASD). Here we present a novel, automated methodology for analyzing USVs, termed TrackUSF. To validate TrackUSF, we analyzed a dataset of mouse mating calls and compared the results with a manual analysis by a trained observer. We found that TrackUSF was capable of detecting most USVs, with less than 1% of false-positive detections. We then employed TrackUSF to social vocalizations in Shank3-deficient rats, a rat model of ASD and found, for the first time, that these vocalizations exhibit a spectrum of deviations from pro-social calls towards aggressive calls.
The roles of microtubules and membrane tension in axonal beading, retraction, and atrophy
Authors: Datar Anagha , Ameeramja Jaishabanu , Bhat Alka , Srivastava Roli , Bernal Roberto , Prost Jacques , Callan-Jones Andrew , Pullarkat Pramod A 
Published: March 2019

AbstractAxonal beading—formation of a series of swellings along the axon—and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer’s, Parkinson, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here we report controlled experiments which can induce either beading or retraction and follow the time evolution of these responses. By making quantitative analysis of the shape modes under different conditions, measurement of membrane tension, and using theoretical considerations, we argue that membrane tension is the main driving force that pushes cytosol out of the axon when microtubules are degraded, causing axonal thinning. Under pharmacological perturbation, atrophy is always retrograde and this is set by a gradient in the microtubule stability. The nature of microtubule depolymerization dictates the type of shape transformation vis à vis beading or retraction. Elucidating the mechanisms of these shape transformations will facilitate development of strategies to prevent or arrest axonal atrophy due to neurodegenerative conditions.
NGF-mediated photoablation of nociceptors reduces pain behavior in mice
Authors: Nocchi L , Portulano C , Franciosa F , Doleshall B , Panea M , Roy N , Maffei M , Gargano A , Perlas E , Heppenstall PA 
Published: March 2019

AbstractNerve growth factor (NGF) and its receptors TrkA and p75 play a key role in the development and function of peripheral nociceptive neurons. Here we describe novel technology to selectively photoablate TrkA positive nociceptors through delivery of a phototoxic agent coupled to an engineered NGF ligand and subsequent near infrared (NIR) illumination. We demonstrate that this approach allows for on demand and localized reversal of pain behaviors in mouse models of acute, inflammatory, neuropathic and joint pain. To target peripheral nociceptors we generated a SNAP-tagged NGF derivative, NGFR121Wthat binds to TrkA/p75 receptors but does not provoke signaling in TrkA positive cells or elicit pain behaviors in mice. NGFR121W-SNAPwas coupled to the photosensitizer IRDye®700DX phthalocyanine (IR700) and injected subcutaneously. Following NIR illumination of the injected area, behavioral responses to nociceptive mechanical and sustained thermal stimuli, but not innocuous stimuli, were substantially reduced. Similarly, in models of inflammatory, osteoarthritic and neuropathic pain, mechanical hypersensitivity was abolished for three weeks following a single treatment regime. We demonstrate that this loss of pain behavior coincides with the retraction of neurons from the skin which then re-innervate the epidermis after 3 weeks corresponding with the return of mechanical hypersensitivity. Thus NGFR121W-SNAP-mediated photoablation is a minimally invasive approach to reversibly silence nociceptor input from the periphery, and control pain and hypersensitivity to mechanical stimuli.
Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation
Authors: Ryan Allyson Quinn , Chan Chii Jou , Graner François , Hiiragi Takashi 
Published: March 2019

SummaryMouse blastocyst formation involves lumen formation and cell fate specification. While many studies have investigated how the blastocyst cell lineages are specified through genetics and signaling, studies into the potential role of the fluid lumen have yet to be conducted. We discover that blastocyst fluid emerges by secretion of cytoplasmic vesicles to intercellular space in addition to trans-epithelial flow. We observe that the beginning of epiblast and primitive endoderm spatial segregation directly follows lumen coalescence. Notably, we show that perturbing lumen expansion by pharmacological and biophysical means impair the specification and spatial segregation of primitive endoderm cells within the blastocyst. Combined, our results suggest that blastocyst lumen expansion plays a critical role in guiding cell fate specification and positioning. As epithelial tissues typically form lumina, lumen expansion may provide a general mechanism of cell fate control in many tissues.
Deep Learning on Chaos Game Representation for Proteins
Authors: Löchel Hannah F. , Eger Dominic , Sperlea Theodor , Heider Dominik 
Published: March 2019

AbstractClassification of protein sequences is one big task in bioinformatics and has many applications. Different machine learning methods exist and are applied on these problems, such as support vector machines (SVM), random forests (RF), and neural networks (NN). All of these methods have in common that protein sequences have to be made machine-readable and comparable in the first step, for which different encodings exist. These encodings are typically based on physical or chemical properties of the sequence. However, due to the outstanding performance of deep neural networks (DNN) on image recognition, we used frequency matrix chaos game representation (FCGR) for encoding of protein sequences into images. In this study, we compare the performance of SVMs, RFs, and DNNs, trained on FCGR encoded protein sequences. While the original chaos game representation (CGR) has been used mainly for genome sequence encoding and classification, we modified it to work also for protein sequences, resulting in n-flakes representation, an image with several icosagons.We could show that all applied machine learning techniques (RF, SVM, and DNN) show promising results compared to the state-of-the-art methods on our benchmark datasets, with DNNs outperforming the other methods and that FCGR is a promising new encoding method for protein sequences.
Single and population coding of taste in the gustatory-cortex of awake mice
Authors: Levitan David , Lin Jian-You , Wachutka Joseph , Mukherjee Narendra , Nelson Sacha B. , Katz Donald B. 
Published: March 2019

AbstractElectrophysiological analysis has reveals much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats, and about how these dynamics relate to behavior. With regard to mice, meanwhile, data concerning cortical taste coding have largely been restricted to imaging—a technique that reveals average levels of neural responsiveness, but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3-4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability—the latter responses emerging ~0.5s after the former—with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses—neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomical regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not “gustatopic,” but also go beyond these imaging results to show that mice process tastes through time.
Context-specific effects of facial dominance and trustworthiness on hypothetical leadership decisions
Authors: Ferguson Hannah S. , Owen Anya , Hahn Amanda C. , Torrance Jaimie , DeBruine Lisa M. , Jones Benedict C. 
Published: March 2019

AbstractSocial judgments of faces predict important social outcomes, including leadership decisions. Previous work suggests that facial cues associated with perceptions of dominance and trustworthiness have context-specific effects on leadership decisions. Facial cues linked to perceived dominance have been found to be preferred in leaders for hypothetical wartime contexts and facial cues linked to perceived trustworthiness have been found to be preferred in leaders for hypothetical peacetime contexts. Here we sought to replicate these effects using images of women’s faces. Consistent with previous work, a linear mixed effects model demonstrated that more trustworthy-looking faces were preferred in leaders during times of peace and more dominant-looking faces were preferred in leaders during times of war. These results provide converging evidence for context-specific effects of facial cues on hypothetical leadership judgments.
Supra-threshold perception and neural representation of tones presented in noise in conditions of masking release
Authors: Egger Katharina , Dau Torsten , Epp Bastian 
Published: March 2019

AbstractThe neural representation and perceptual salience of tonal signals presented in different noise maskers were investigated. The properties of the maskers and signals were varied such that they produced different amounts of either monaural masking release, binaural masking release, or a combination of both. The signals were then presented at different levels above their corresponding masked thresholds and auditory evoked potentials (AEPs) were measured. It was found that, independent of the masking condition, the amplitude of the P2 component of the AEP was similar for the same stimulus levels above masked threshold, suggesting that both monaural and binaural effects of masking release were represented at the level of P2 generation. The perceptual salience of the signal was evaluated at equal levels above masked threshold using a rating task. In contrast to the electrophysiological findings, the subjective ratings of the perceptual signal salience were less consistent with the signal level above masked threshold and varied strongly across listeners and masking conditions. Overall, the results from the present study suggest that the P2 amplitude of the AEP represents an objective indicator of the audibility of a target signal in the presence of complex acoustic maskers.
The microbiota regulates inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination
Authors: McMurran Christopher E , de la Fuente Alerie Guzman , Penalva Rosana , Menachem-Zidon Ofra Ben , Dombrowski Yvonne , Gonzalez Ginez A , Zhao Chao , Krause Fynn N , Young Adam MH , Griffin Julian L , Jones Clare A , Hollins Claire , Heimesaat Markus M , Fitzgerald Denise C , Franklin Robin JM 
Published: March 2019

AbstractThe microbiota is now recognised as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress towards therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination – the regeneration of myelin sheaths – also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics negatively influence remyelination and further our understanding of how mammalian regeneration relates to the microbiota.
Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches
Authors: Treveil A , Sudhakar P , Matthews Z J , Wrzesinski T , Jones E J , Brooks J , Olbei M , Hautefort I , Hall L J , Carding S R , Mayer U , Powell P P , Wileman T , Di Palma F , Haerty W , Korcsmáros T 
Published: March 2019

AbstractThe epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. 3Din vitrocultures of human primary epithelial cells, called organoids, have become a key model to study the functions of Paneth cells and goblet cells in normal and diseased conditions. Advances in these models include the ability to skew differentiation to particular lineages, providing a useful tool to study cell type specific function/dysfunction in the context of the epithelium. Here, we use comprehensive profiling of mRNA, microRNA and long non-coding RNA expression to confirm that Paneth cell and goblet cell enrichment of murine small intestinal organoids (enteroids) establishes a physiologically accurate model. We employ network analysis to infer the regulatory landscape altered by skewing differentiation, and using knowledge of cell type specific markers, we predict key regulators of cell type specific functions: Cebpa, Jun, Nr1d1 and Rxra specific to Paneth cells, Gfi1b and Myc specific for goblet cells and Ets1, Nr3c1 and Vdr shared between them. Links identified between these regulators and cellular phenotypes of inflammatory bowel disease (IBD) suggest that global regulatory rewiring during or after differentiation of Paneth cells and goblet cells could contribute to IBD aetiology. Future application of cell type enriched enteroids combined with the presented computational workflow can be used to disentangle multifactorial mechanisms of these cell types and propose regulators whose pharmacological targeting could be advantageous in treating IBD patients with Crohn’s disease or ulcerative colitis.Table of contentsWe demonstrate the application of network biology techniques to increase understanding of intestinal dysbiosis through studying transcriptomics data from Paneth and goblet cell enriched enteroids.