bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin and adiponectin correlations with body composition and lipid profile in children with Autism Spectrum Disorder
Authors: Castro Kamila , Faccioli Larissa Slongo , Perry Ingrid Schweigert , Santos Riesgo Rudimar dos 
Published: April 2019

AbstractLeptin and adiponectin have effects on the regulation of appetite and body composition, but evidence of these relationships in children is still limited. Even though investigations of their role in children with ASD are incipient, the nutritional aspects and eating difficulties that these patients may present are increasingly highlighted, often leading to inadequate nutritional status. This cross-sectional controlled study investigated the levels of adipokines in ASD children in comparison with healthy controls, and their correlations with nutritional aspects and lipid profile. A total of 80 participants (40 ASD and 40 controls) were included and evaluated through anthropometric variables, body composition, and blood samples. ASD participants showed higher levels of leptin, no changes of adiponectin levels in comparison with typically developing children, and a positive correlation between leptin and fat mass. This novel finding supports the role of leptin as a marker of adiposity in ASD children, which is reiterated by the higher leptin/adiponectin ratio and its correlation with fat mass in patients. Inverse correlation of leptin with HDL-cholesterol could only in certain cases be related to the higher adiposity in patients when compared to controls. These results highlight also the importance of assessing the nutritional status of this population.
TeraVR Empowers Precise Reconstruction of Complete 3-D Neuronal Morphology in the Whole Brain
Authors: Wang Yimin , Li Qi , Liu Lijuan , Zhou Zhi , Wang Yun , Kong Lingsheng , Zhong Ning , Chai Renjie , Luo Xiangfeng , Guo Yike , Hawrylycz Michael , Luo Qingming , Gu Zhongze , Xie Wei , Zeng Hongkui , Peng Hanchuan 
Published: April 2019

AbstractNeuron morphology is recognized as a key determinant of cell type, yet the quantitative profiling of a mammalian neuron’s complete three-dimensional (3-D) morphology remains arduous when the neuron has complex arborization and long projection. Whole-brain reconstruction of neuron morphology is even more challenging as it involves processing tens of teravoxels of imaging data. Validating such reconstructions is extremely laborious. We developed TeraVR, an open-source virtual reality annotation system, to address these challenges. TeraVR integrates immersive and collaborative 3-D visualization, interaction, and hierarchical streaming of teravoxel-scale images. Using TeraVR, we produced precise 3-D full morphology of long-projecting neurons in whole mouse brains and developed a collaborative workflow for highly accurate neuronal reconstruction.
Time elapsed between Zika and dengue virus infections affects antibody and T cell responses
Authors: Pérez-Guzmán Erick X. , Pantoja Petraleigh , Serrano-Collazo Crisanta , Hassert Mariah A. , Ortiz-Rosa Alexandra , Rodríguez Idia V. , Giavedoni Luis , Hodara Vida , Parodi Laura , Cruz Lorna , Arana Teresa , White Laura J. , Martínez Melween I. , Weiskopf Daniela , Brien James D. , de Silva Aravinda , Pinto Amelia K. , Sariol Carlos A. 
Published: April 2019

AbstractThe role of Zika virus (ZIKV) immunity on subsequent dengue virus (DENV) infections is relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV exposure. We study the effect of ZIKV infection with various strains on subsequent DENV immune response after 10 and 2 months of ZIKV infection in rhesus macaques. Our results show that a subsequent DENV infection in animals with early- and middle-convalescent periods to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. Previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV, and different time intervals between infections alter the magnitude and durability of such responses—more after longer ZIKV pre-exposure. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.
Oral prescription opioid-seeking behavior in male and female mice
Authors: Phillips Alysabeth G. , McGovern Dillon J. , Lee Soo , Ro Kyu , Huynh David T. , Elvig Sophie K. , Fegan Katelynn N. , Root David H. 
Published: April 2019

AbstractA significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user’s sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.
Estimating Attentional Set-Shifting Dynamics in Varying Contextual Bandits
Authors: Kour George , Morris Genela 
Published: April 2019

ABSTRACTIn this paper, we aim at estimating, on a trial-by-trial basis, the underlying decision-making process of an animal in a complex and changing environment. We propose a method for identifying the set of stochastic policies employed by the agent and estimating the transition dynamics between policies based on its behavior in a multidimensional discrimination task for measuring the properties of attentional set-shifting of the subject (both intra- and extra-dimensional). We propose using theNon-Homogeneous Hidden Markov Models(NHMMs) framework, to consider environmental state and rewards for modeling decision-making processes in a varying version of “Contextual Bandits”. We employ the Expectation-Maximization (EM) procedure for estimating the model’s parameters similar to the Baum-Welch algorithm used to train standard HMMs. To measure the model capacity to estimate underlying dynamics, Monte Carlo analysis is employed on synthetically generated data and compared to the performance of classical HMM.
ThePseudomonas aeruginosaaccessory genome elements influence virulence towardsCaenorhabditis elegans
Authors: Vasquez-Rifo Alejandro , Veksler-Lublinsky Isana , Cheng Zhenyu , Ausubel Frederick M. , Ambros Victor 
Published: April 2019

ABSTRACTMulticellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship betweenPseudomonas aeruginosaand the nematodeCaenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability inP. aeruginosavirulence towardsC. elegans. Natural isolates ofP. aeruginosathat exhibit diverse genomes display a broad range of virulence towardsC. elegans. Using gene association and genetic analysis, we identified accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we found a viral-like mobile element, thetegblock, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in the restriction of accessory genome elements that may be detrimental to virulence.
Predation strategies of the bacterium Bdellovibrio bacteriovorus result in overexploitation and bottlenecks
Authors: Summers J. Kimberley , Kreft Jan-Ulrich 
Published: April 2019

AbstractWith increasing antimicrobial resistance, alternatives for treating infections or removing resistant bacteria are urgently needed, such as the bacterial predator Bdellovibrio bacteriovorus or bacteriophage. Therefore, we need to better understand microbial predator-prey dynamics. We developed mass-action mathematical models of predation for chemostats, which capture the low substrate concentration and slow growth typical for intended application areas of the predators such as wastewater treatment, aquaculture or the gut. Our model predicted that predator survival required a minimal prey size, explaining why Bdellovibrio is much smaller than its prey. A too good predator (attack rate too high, mortality too low) overexploited its prey leading to extinction (tragedy of the commons). Surprisingly, a predator taking longer to produce more offspring outcompeted a predator producing fewer offspring more rapidly (rate versus yield trade-off). Predation was only efficient in a narrow region around optimal parameters. Moreover, extreme oscillations under a wide range of conditions led to severe bottlenecks. A bacteriophage outcompeted Bdellovibrio due to its higher burst size and faster life cycle. Together, results suggest that Bdellovibrio would struggle to survive on a single prey, explaining why it must be a generalist predator and suggesting it is better suited than phage to environments with multiple prey.ImportanceThe discovery of antibiotics led to a dramatic drop in deaths due to infectious disease. Increasing levels of antimicrobial resistance, however, threaten to reverse this progress. There is thus a need for alternatives, such as therapies based on phage and predatory bacteria that kill bacteria regardless of whether they are pathogens or resistant to antibiotics. To best exploit them, we need to better understand what determines their effectiveness. By using a mathematical model to study bacterial predation in realistic slow growth conditions, we found that the generalist predator Bdellovibrio is most effective within a narrow range of conditions for each prey. For example, a minimum prey size is required, and the predator should not be too good as this would result in over-exploitation risking extinction. Together these findings give insights into the ecology of microbial predation and help explain why Bdellovibrio needs to be a generalist predator.
De novoemergence of adaptive membrane proteins from thymine-rich intergenic sequences
Authors: Vakirlis Nikolaos , Acar Omer , Hsu Brian , Coelho Nelson Castilho , Van Oss S. Branden , Wacholder Aaron , Medetgul-Ernar Kate , Iannotta John , McLysaght Aoife , Camacho Carlos J. , O’Donnell Allyson F. , Ideker Trey , Carvunis Anne-Ruxandra 
Published: April 2019

SummaryRecent evidence demonstrates that novel protein-coding genes can arisede novofrom intergenic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of intergenic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Do intergenic translation events yield polypeptides with useful biochemical capacities? The answer to this question remains controversial. Here, we systematically characterized howde novoemerging coding sequences impact fitness. In budding yeast, overexpression of these sequences was enriched in beneficial effects, while their disruption was generally inconsequential. We found that beneficial emerging sequences have a strong tendency to encode putative transmembrane proteins, which appears to stem from a cryptic propensity for transmembrane signals throughout thymine-rich intergenic regions of the genome. These findings suggest that novel genes with useful biochemical capacities, such as transmembrane domains, tend to evolvede novowithin intergenic loci that already harbored a blueprint for these capacities.
Hierarchical recurrent state space models reveal discrete and continuous dynamics of neural activity inC. elegans
Authors: Linderman Scott , Nichols Annika , Blei David , Zimmer Manuel , Paninski Liam 
Published: April 2019

AbstractModern recording techniques enable large-scale measurements of neural activity in a variety of model organisms. The dynamics of neural activity shed light on how organisms process sensory information and generate motor behavior. Here, we study these dynamics using optical recordings of neural activity in the nematodeC. elegans. To understand these data, we develop state space models that decompose neural time-series into segments with simple, linear dynamics. We incorporate these models into a hierarchical framework that combines partial recordings from many worms to learn shared structure, while still allowing for individual variability. This framework reveals latent states of population neural activity, along with the discrete behavioral states that govern dynamics in this state space. We find stochastic transition patterns between discrete states and see that transition probabilities are determined by both current brain activity and sensory cues. Our methods automatically recover transition times that closely match manual labels of different behaviors, such as forward crawling, reversals, and turns. Finally, the resulting model can simulate neural data, faithfully capturing salient patterns of whole brain dynamics seen in real data.
Liquid-Liquid Phase Separation is Driven by Large-Scale Conformational Unwinding and Fluctuations of Intrinsically Disordered Protein Molecules
Authors: Majumdar Anupa , Dogra Priyanka , Maity Shiny , Mukhopadhyay Samrat 
Published: April 2019

ABSTRACTLiquid-liquid phase separation occurs via a multitude of transient, non-covalent, intermolecular interactions resulting in phase transition of intrinsically disordered proteins/regions (IDPs/IDRs) and other biopolymers into mesoscopic, dynamic, non-stoichiometric, supramolecular condensates. IDPs resemble associative polymers possessing stereospecific “stickers” and flexible “spacers” that govern the transient chain-chain interactions and fluidity in phase-separated liquid droplets. However, the fundamental molecular origin of phase separation remains elusive. Here we present a unique case to demonstrate that unusual conformational expansion events coupled with solvation and fluctuations drive phase separation of tau, an IDP associated with Alzheimer’s disease. Using intramolecular excimer emission as a powerful proximity readout, we show the unraveling of polypeptide chains within the protein-rich interior environment that can promote critical interchain contacts. Using highly-sensitive picosecond time-resolved fluorescence depolarization measurements, we directly capture rapid large-amplitude torsional fluctuations in the extended chains that can control the relay of making-and-breaking of noncovalent intermolecular contacts maintaining the internal fluidity. Our observations, together with the existing polymer theories, suggest that such an orchestra of concerted molecular shapeshifting events involving chain expansion, solvation, and fluctuations can provide additional favorable free energies to overcome the entropy of mixing term during phase separation. The interplay of these key molecular parameters can also be of prime importance in modulating the mesoscale material property of liquid-like condensates and their maturation of into pathological gel-like and solid-like aggregates.
A new method of brain stimulation at ultra-high frequency
Authors: Jamali Yousef , Jamali Mohammad , Golshani Mehdi 
Published: April 2019

SummaryNerve stimulation via micro-electrode implants is one of the neurostimulation approaches which is used frequently in the medical treatment of some brain disorders, neural prosthetics, brain-machine interfaces and also in the cyborg. In this method, the electrical stimulation signal can be categorized by the frequency band: low frequency, high frequency, and ultra-high frequency. The stimulation should be less destructive, more smooth, and controllable. In this article, we present a brief description of the mechanism underlying the ultra-high frequency stimulation. In the flowing, from an informatics perspective, we propose a state-of-the-art, low destructive, and highly efficient stimulation method at the low amplitude ultra-high frequency signal. In this method, we have tried to reduce the adaptation of the nerve system by modulating the stimulation signal via a low frequency rectangular random wave. By this method, we could reach the “almost zero discharge” with minimum destructive effect in the experimental test on the fish nervous system.
Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions
Authors: Sahoo Subhransu Sekhar , Majhi Rakesh Kumar , Tiwari Ankit , Acharya Tusar , Kumar P Sanjai , Saha Somdatta , Goswami Chandan , Chattopadhyay Subhasis 
Published: April 2019

AbstractTransient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface. TRPA1-specific activator namely AITC increases intracellular Ca2+-levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+-levels in T cells. Such Ca2+-influx can also be influenced by chelation of intracellular Ca2+ as well as extracellular Ca2+. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN-γ and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.
Reproductive capacity of Varroa destructor in four different honey bee subspecies
Authors: Odemer Richard 
Published: April 2019

ABSTRACTVarroa tolerance as a consequence of host immunity may contribute substantially to reduce worldwide colony declines. Therefore, special breeding programs were established and varroa surviving populations investigated to understand mechanisms behind this adaptation. Here we studied the reproductive capacity in the three most common subspecies of the European honey bee (Carnica, Mellifera, Ligustica) and the F2 generation of a varroa surviving population, to identify if managed host populations possibly have adapted over time already. Both, singly infested drone and worker brood were assessed to determine fertility and fecundity of varroa foundresses in their respective group. We found neither parameter to be significantly different within the four subspecies, demonstrating that no adaptations have occurred in terms of the reproductive success of Varroa destructor. In all groups mother mites reproduce equally successful and are potentially able to cause detrimental damage to their host when not being treated sufficiently. The data further suggests that a population once varroa tolerant does not necessarily inherit this trait to following generations after the F1, which could be of particular interest when selecting populations for resistance breeding. Reasons and consequences are discussed.HIGHLIGHTSVarroa reproduction has been investigated in four different honey bee subspeciesNo differences could be observed, neither in drone nor in worker broodIn managed bee populations, host immunity against V. destructor has not been establishedGRAPHICAL ABSTRACTIllustrations after Gullan & Cranston 2014
Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer’s Disease
Authors: Patel Hamel , Iniesta Raquel , Stahl Daniel , Dobson Richard J.B , Newhouse Stephen J 
Published: April 2019

AbstractBackgroundA significant number of studies have investigated the use of blood-derived gene expression profiling as a biomarker for Alzheimer’s Disease (AD). However, the typical approach of developing classification models trained on subjects with AD and complimentary cognitive healthy controls may result in markers of general illness rather than being AD-specific. Incorporating additional related neurological and age-related disorders during the classification model development process may lead to the discovery of an AD-specific expression signature.MethodsTwo XGBoost classification models were developed and optimised. The first used the typical approach, training on 160 AD and 160 cognitively normal controls, while the second was trained in 6318 AD and 6318 mixed controls. Up-sampling was performed in each training set to the minority classes to avoid sampling bias, and both classification models were evaluated in an independent dataset consisting of 127 AD and 687 mixed controls. The mixed control group represents a heterogeneous ageing population consisting of Parkinson’s Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Bipolar Disorder, Schizophrenia, Coronary Artery Disease, Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease, and cognitively healthy subjects.ResultsThe typical approach resulted in a 74 gene classification model with a validation performance of 58.3% sensitivity, 30.3% specificity, 13.4% PPV and 79.7% NPV. In contrast, the second approach resulted in a 28 gene classification model with an overall improved validation performance of 46.5% sensitivity, 95.6% specificity, 66.3% PPV and 90.6% NPV.ConclusionsThe addition of related neurological and age-related disorders into the AD classification model developmental process identified a more AD-specific expression signature, with improved ability to distinguish AD from other related diseases and cognitively healthy controls. However, this was at the cost of sensitivity. Further improvement is still required to identify a robust blood transcriptomic signature specific to AD.