bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties
Authors: Bouasse Malik , Impheng Hathaichanok , Servant Zoe , Lory Philippe , Monteil Arnaud 
Published: August 2019

AbstractThe excitability of neurons is tightly dependent on their ion channel repertoire. Among these channels, the leak sodium channel NALCN plays a crucial role in the maintenance of the resting membrane potential. Importantly, NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. Unfortunately, the biophysical properties of NALCN are still largely unknown to date, as well as the functional consequences of both IHPRF and CLIFAHDD mutations on NALCN current. Here we have set-up the heterologous expression of NALCN in the neuronal cell line NG108-15 to investigate the electrophysiological properties of NALCN carrying representative IHPRF and CLIFAHDD mutations. Several original properties of the wild-type (wt) NALCN current were retrieved: mainly carried by external Na+, blocked by Gd3+, insensitive to TTX and potentiated by low external Ca2+ concentration. However, we found that this current displays a time-dependent inactivation in the −80/−40 mV range of membrane potential, and a non linear current-voltage relationship indicative of voltage sensitivity. Importantly, no detectable current was recorded with the IHPRF missense mutation p.Trp1287Leu (W1287L), while the CLIFAHDD mutants, p.Leu509Ser (L509S) and p.Tyr578Ser (Y578S), showed higher current densities and slower inactivation, compared to wt NALCN current. This study reveals that heterologous expression of NALCN channel can be achieved in the neuronal cell line NG108-15 to study the electrophysiological properties of wt and mutants. From our results, we conclude that IHPRF and CLIFAHDD missense mutations are loss- and gain-of-function variants, respectively.
A novel nano-particle strengthened titanium alloy with exceptional specific strength
Authors: Dutt Aniket K. , Gwalani Bharat , Tungala Vedavyas , Carl Matthew , Mishra Rajiv S. , Tamirisakandala Sesh A. , Young Marcus L. , Cho Kyu C. , Brennan Raymond E. 
Published: August 2019

AbstractVarious ecological and economical concerns have spurred mankind’s quest for materials that can provide enhanced weight savings and improved fuel efficiency. As part of this pursuit, we have microstructurally tailored an exceptionally high-strength titanium alloy, Ti-6Al-2Sn-4Zr-6Mo (Ti6246) through friction stir processing (FSP). FSP has altered the as-received bimodal microstructure into a unique modulated microstructure comprised of fine acicular α″-laths with nano precipitates within the laths. The sequence of phase transformations responsible for the modulated microstructure and consequently for the strength is discussed with the help of scanning electron microscopy, transmission electron microscopy, and synchrotron X-ray diffraction studies. The specific strength attained in one of the conditions is close to 450 MPa m3/mg, which is about 22% to 85% greater than any commercially available metallic material. Therefore, our novel nano particle strengthened Ti alloy is a potential replacement for many structural alloys, enabling significant weight reduction opportunities.
A VNTR Regulates miR-137 Expression Through Novel Alternative Splicing and Contributes to Risk for Schizophrenia
Authors: Pacheco Ashley , Berger Ralph , Freedman Robert , Law Amanda J. 
Published: August 2019

AbstractThe MIR137HG gene encoding microRNA-137 (miR-137) is genome-wide associated with schizophrenia (SZ), however, the underlying molecular mechanisms remain unknown. Through cloning and sequencing of individual transcripts from fetal and adult human brain tissues we describe novel pri-miR-137 splice variants which exclude the mature miR-137 sequence termed ‘del-miR-137’ that would function to down-regulate miR-137 expression. Sequencing results demonstrate a significant positive association between del-miR-137 transcripts and the length of a proximal variable number tandem repeat (VNTR) element. Additionally, a significantly higher proportion of sequenced transcripts from fetal brain were del-miR-137 transcripts indicating neurodevelopmental splicing regulation. In-silico results predict an independent regulatory function for del-miR-137 transcripts through competitive endogenous RNA function. A case-control haplotype analysis (n = 998) in SZ implicates short VNTR length in risk, with longer lengths imparting a protective effect. Rare high risk haplotypes were also observed indicating multiple risk variants within the region. A second haplotype analysis was performed to evaluate recombination effects excluding the VNTR and results indicate that recombination of the region was found to independently contribute to risk. Evaluation of the evolutionary conservation of the VNTR reveals a human lineage specific expansion. These findings shed further light on the risk architecture of the miR-137 region and provide a novel regulatory mechanism through VNTR length and alternative MIR137HG transcripts which contribute to risk for SZ.
Survival-time dependent increase in neuronal IL-6 and astroglial GFAP expression in fatally injured human brain tissue
Authors: Trautz Florian , Franke Heike , Bohnert Simone , Hammer Niels , Müller Wolf , Stassart Ruth , Tse Rexson , Zwirner Johann , Dreßler Jan , Ondruschka Benjamin 
Published: August 2019

AbstractKnowledge on trauma survival time prior to death following a lethal traumatic brain injury (TBI) may be essential for legal purposes. Immunohistochemistry studies might allow to narrow down this survival interval. The biomarkers interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) are well known in the clinical setting for their usability in TBI prediction. Here, both proteins were chosen in forensics to determine whether neuronal or glial expression in various brain regions may be associated with the cause of death and the survival time prior to death following TBI. IL-6 positive neurons, glial cells and GFAP positive astrocytes all concordantly increase with longer trauma survival time, with statistically significant changes being evident from three days post-TBI (p < 0.05) in the pericontusional zone, irrespective of its definite cortical localization. IL-6 staining in neurons increases significantly in the cerebellum after trauma, whereas increasing GFAP positivity is also detected in the cortex contralateral to the focal lesion. These systematic chronological changes in biomarkers of pericontusional neurons and glial cells allow for an estimation of trauma survival time. Higher numbers of IL-6 and GFAP-stained cells above threshold values in the pericontusional zone substantiate the existence of fatal traumatic changes in the brain with reasonable certainty.
Assessing phenotype order in molecular data
Authors: Lausser Ludwig , Schäfer Lisa M. , Schirra Lyn-Rouven , Szekely Robin , Schmid Florian , Kestler Hans A. 
Published: August 2019

AbstractBiological entities are key elements of biomedical research. Their definition and their relationships are important in areas such as phylogenetic reconstruction, developmental processes or tumor evolution. Hypotheses about relationships like phenotype order are often postulated based on prior knowledge or belief. Evidence on a molecular level is typically unknown and whether total orders are reflected in the molecular measurements is unclear or not assessed. In this work we propose a method that allows a fast and exhaustive screening for total orders in large datasets. We utilise ordinal classifier cascades to identify discriminable molecular representations of the phenotypes. These classifiers are constrained by an order hypothesis and are highly sensitive to incorrect assumptions. Two new error bounds, which are introduced and theoretically proven, lead to a substantial speed-up and allow the application to large collections of many phenotypes. In our experiments we show that by exhaustively evaluating all possible candidate orders, we are able to identify phenotype orders that best coincide with the high-dimensional molecular profiles.
The Thermomechanical Properties of Thermally Evaporated Bismuth Triiodide Thin Films
Authors: Coutinho Natália F. , Cucatti Silvia , Merlo Rafael B. , Silva Filho José Maria C. , Villegas Nelson F. Borrero , Alvarez Fernando , Nogueira Ana F. , Marques Francisco C. 
Published: August 2019

AbstractBismuth triiodide (BiI3) has been studied in recent years with the aim of developing lead-free semiconductors for photovoltaics. It has also appeared in X-ray detectors due to the high density of the Bismuth element. This material is attractive as an active layer in solar cells, or may be feasible for conversion into perovskite-like material (MA3Bi2I9), being also suitable for photovoltaic applications. In this study, we report on the thermomechanical properties (stress, hardness, coefficient of thermal expansion, and biaxial and reduced Young’s moduli) of BiI3 thin films deposited by thermal evaporation. The stress was determined as a function of temperature, adopting the thermally induced bending technique, which allowed us to extract the coefficient of thermal expansion (31 × 10−6 °C−1) and Young’s biaxial modulus (19.6 GPa) for the films. Nanohardness (~0.76 GPa) and a reduced Young’s modulus of 27.1 GPa were determined through nanoindentation measurements.
Multigene phylogeny of root-knot nematodes and molecular characterization of Meloidogyne nataliei Golden, Rose & Bird, 1981 (Nematoda: Tylenchida)
Authors: Álvarez-Ortega Sergio , Brito Janete A. , Subbotin Sergei. A. 
Published: August 2019

AbstractThe root-knot nematodes of the genus Meloidogyne are highly adapted, obligate plant parasites, consisting of nearly one hundred valid species, and are considered the most economically important group of plant-parasitic nematodes. Six Meloidogyne species: M. arenaria, M. hapla, M. incognita, M. microtyla, M. naasi and M. nataliei were previously reported in Michigan, USA. For this study, Meloidogyne nataliei was isolated from the grapevine Vitis labrusca from the type locality in Michigan, USA, and was characterized using isozyme analysis and ribosomal and mitochondrial gene sequences. No malate dehydrogenase activity was detected using macerate of one, five, six, seven or ten females of M. nataliei per well. However, one strong band (EST = S1; Rm: 27.4) of esterase activity was detected when using homogenates of ten egg-laying females per well. Phylogenetic analyses of sequences of the partial 18S ribosomal RNA, D2-D3 of 28S rRNA, internal transcribed spacer of rRNA, mitochondrial cytochrome oxidase subunit I genes and the cytochrome oxidase subunit II-16S rRNA intergeneric fragment from fifty-five valid Meloidogyne species and M. nataliei were conducted using Bayesian inference and maximum likelihood methods. From these results, we infer 11 distinct clades among studied species, with M. nataliei and M. indica composing a basal lineage. Seventy five percent of these species belong to seven clades within the Meloidogyne superclade. Characterization of these clades is provided and evolutionary trends within the root-knot nematodes are discussed.
Metabolomic characterization of myocardial ischemia-reperfusion injury in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention
Authors: Surendran Arun , Aliani Michel , Ravandi Amir 
Published: August 2019

AbstractAim: The aim of the study was to discover the metabolomic changes in plasma that occur during human Ischemia-Reperfusion (I/R) injury and to evaluate the diagnostic utility of plasma metabolomic biomarkers for determination of myocardial injury. Deciphering the details of plasma metabolome in ST-segment elevation myocardial infarction (STEMI) patients before and after primary percutaneous coronary interventions (PPCI) would allow for better understanding of the mechanisms involved during acute myocardial ischemia and reperfusion in humans. We performed a detailed non-targeted metabolomic analysis of plasma from 27 STEMI patients who had undergone PPCI in the first 48 hrs employing a LC-MS approach. Plasma metabolome at ischemic condition was compared to multiple time points after PPCI which allowed us to focus on changes in the reperfusion phase. Classification of the differential metabolites based on chemical taxonomy identified a major role for lipids and lipid-derived molecules. Biochemical pathway analysis identified valine, leucine and isoleucine biosynthesis, vitamin B6 metabolism and glutathione metabolism as the most significant metabolic pathways representing early response to I/R injury. We also identified phenyl alanine, tyrosine, linoleic acid and glycerophospholipid metabolism as the most significant pathways representing late response to I/R injury. A panel of three metabolites pentadecanoic acid, linoleoyl carnitine and 1-linoleoylglycerophosphocholine was discovered to have diagnostic value in determining the extent of I/R injury based on cardiac biomarkers. Using a non-targeted LC-MS approach, we have successfully generated the most comprehensive data to date on significant changes in the plasma metabolome in STEMI patients who had undergone PPCI in the first 48 hrs showing that lipid metabolites represent the largest cohort of molecules undergoing significant change.
DF2726A, a new IL-8 signalling inhibitor, is able to counteract chemotherapy-induced neuropathic pain
Authors: Brandolini Laura , Castelli Vanessa , Aramini Andrea , Giorgio Cristina , Bianchini Gianluca , Russo Roberto , De Caro Carmen , d’Angelo Michele , Catanesi Mariano , Benedetti Elisabetta , Giordano Antonio , Cimini Annamaria , Allegretti Marcello 
Published: August 2019

AbstractChemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of several anti-neoplastics and a main cause of sensory disturbances in cancer survivors, negatively impacting patients’ quality of life. Peripheral nerve degeneration or small fibre neuropathy is generally accepted as the underlying mechanism in the development of CIPN. Recent evidence has contributed to clarify the determinant role of cytokines and chemokines in the process leading to neuronal hyperexcitability. Exposure to oxaliplatin triggers alterations in peripheral neuropathic pathways previously linked to IL-8 pathway. We investigated a novel selective inhibitor of IL-8 receptors, DF2726A, and showed its effects in counteracting CINP pathways, extending the relevance of the activation of IL-8 pathway to the class of platinum chemotherapeutics. Based on our results, we suggest that DF2726A might be a promising candidate for clinical treatment of CIPN conditions due to its efficacy and optimized pharmacokinetic/pharmacodynamic profile.
Feasibility of a T-Shirt-Type Wearable Electrocardiography Monitor for Detection of Covert Atrial Fibrillation in Young Healthy Adults
Authors: Fukuma Nobuaki , Hasumi Eriko , Fujiu Katsuhito , Waki Kayo , Toyooka Tsuguyoshi , Komuro Issei , Ohe Kazuhiko 
Published: August 2019

AbstractCovert atrial fibrillation (AF) accounts for cryptogenic stroke aetiology in elderly patients and in younger populations. However, asymptomatic AF is difficult to diagnose based on a short electrocardiography (ECG) recording. We evaluated the feasibility of a self-applied continuous ECG monitoring device that can record automatically, easily, and noninvasively in a younger population. We investigated community screening for asymptomatic AF using a wireless single-lead ECG with an electrode embedded in a T-shirt. One hundred men with a CHADS2 score ≥1 who were free from AF and <65 years of age were enrolled. We instructed the participants to wear ECG monitoring devices for at least 4 days/week over 2 months. The proportion of participants with newly detected AF (NDAF) and the monitoring time were evaluated. The mean CHADS2 score was 1.43 ± 0.62. The mean patient age was 52.5 ± 5.4 years. The mean monitoring time was 222 ± 199 hours. NDAF continuing for >30 seconds was detected in 10 participants (10.0%). AF continuing for >6 minutes was detected in 2 participants (2.0%). The T-shirt-type wearable ECG monitoring system was suitable for continuous, daily long-term use among young people with high physical activity, and it had the distinct capability of identifying covert AF.
Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
Authors: Logantha Sunil Jit R. J. , Kharche Sanjay R. , Zhang Yu , Atkinson Andrew J. , Hao Guoliang , Boyett Mark R. , Dobrzynski Halina 
Published: August 2019

AbstractIn adult mammalian hearts, atrioventricular rings (AVRs) surround the atrial orifices of atrioventricular valves and are hotbed of ectopic activity in patients with focal atrial tachycardia. Experimental data offering mechanistic insights into initiation and maintenance of ectopic foci is lacking. We aimed to characterise AVRs in structurally normal rat hearts, identify arrhythmia predisposition and investigate mechanisms underlying arrhythmogenicity. Extracellular potential mapping and intracellular action potential recording techniques were used for electrophysiology, qPCR for gene and, Western blot and immunohistochemistry for protein expression. Conditions favouring ectopic foci were assessed by simulations. In right atrial preparations, sinus node (SN) was dominant and AVRs displayed 1:1 impulse conduction. Detaching SN unmasked ectopic pacemaking in AVRs and pacemaker action potentials were SN-like. Blocking pacemaker current If, and disrupting intracellular Ca2+ release, prolonged spontaneous cycle length in AVRs, indicating a role for SN-like pacemaker mechanisms. AVRs labelled positive for HCN4, and SERCA2a was comparable to SN. Pacemaking was potentiated by isoproterenol and abolished with carbachol and AVRs had abundant sympathetic nerve endings. β2-adrenergic and M2-muscarinic receptor mRNA and β2-receptor protein were comparable to SN. In computer simulations of a sick SN, ectopic foci in AVR were unmasked, causing transient suppression of SN pacemaking.
A next generation setup for pre-fractionation of non-denatured proteins reveals diverse albumin proteoforms each carrying several post-translational modifications
Authors: Rhode Heidrun , Muckova Petra , Büchler Rita , Wendler Sindy , Tautkus Bärbel , Vogel Michaela , Moore Thomas , Grosskreutz Julian , Klemm Andree , Nabity Mary 
Published: August 2019

AbstractProteomic biomarker search requires the greatest analytical reproducibility and detailed information on altered proteoforms. Our protein pre-fractionation applies orthogonal native chromatography and conserves important features of protein variants such as native molecular weight, charge and major glycans. Moreover, we maximized reproducibility of sample pre-fractionation and preparation before mass spectrometry by parallelization and automation. In blood plasma and cerebrospinal fluid (CSF), most proteins, including candidate biomarkers, distribute into a multitude of chromatographic clusters. Plasma albumin, for example, divides into 15-17 clusters. As an example of our technique, we analyzed these albumin clusters from healthy volunteers and from dogs and identified cluster-typical modification patterns. Renal disease further modifies these patterns. In human CSF, we found only a subset of proteoforms with fewer modifications than in plasma. We infer from this example that our method can be used to identify and characterize distinct proteoforms and, optionally, enrich them, thereby yielding the characteristics of proteoform-selective biomarkers.
Reconstructing commuters network using machine learning and urban indicators
Authors: Spadon Gabriel , Carvalho Andre C. P. L. F. de , Rodrigues-Jr Jose F. , Alves Luiz G. A. 
Published: August 2019

AbstractHuman mobility has a significant impact on several layers of society, from infrastructural planning and economics to the spread of diseases and crime. Representing the system as a complex network, in which nodes are assigned to regions (e.g., a city) and links indicate the flow of people between two of them, physics-inspired models have been proposed to quantify the number of people migrating from one city to the other. Despite the advances made by these models, our ability to predict the number of commuters and reconstruct mobility networks remains limited. Here, we propose an alternative approach using machine learning and 22 urban indicators to predict the flow of people and reconstruct the intercity commuters network. Our results reveal that predictions based on machine learning algorithms and urban indicators can reconstruct the commuters network with 90.4% of accuracy and describe 77.6% of the variance observed in the flow of people between cities. We also identify essential features to recover the network structure and the urban indicators mostly related to commuting patterns. As previously reported, distance plays a significant role in commuting, but other indicators, such as Gross Domestic Product (GDP) and unemployment rate, are also driven-forces for people to commute. We believe that our results shed new lights on the modeling of migration and reinforce the role of urban indicators on commuting patterns. Also, because link-prediction and network reconstruction are still open challenges in network science, our results have implications in other areas, like economics, social sciences, and biology, where node attributes can give us information about the existence of links connecting entities in the network.
Neural circuitry of social learning in Drosophila requires multiple inputs to facilitate inter-species communication
Authors: Kacsoh Balint Z. , Bozler Julianna , Hodge Sassan , Bosco Giovanni 
Published: August 2019

AbstractDrosophila species communicate the threat of parasitoid wasps to naïve individuals. Communication of the threat between closely related species is efficient, while more distantly related species exhibit a dampened, partial communication. Partial communication between D. melanogaster and D. ananassae about wasp presence is enhanced following a period of cohabitation, suggesting that species-specific natural variations in communication ‘dialects’ can be learned through socialization. In this study, we identify six regions of the Drosophila brain essential for dialect training. We pinpoint subgroups of neurons in these regions, including motion detecting neurons in the optic lobe, layer 5 of the fan-shaped body, the D glomerulus in the antennal lobe, and the odorant receptor Or69a, where activation of each component is necessary for dialect learning. These results reveal functional neural circuits that underlie complex Drosophila social behaviors, and these circuits are required for integration several cue inputs involving multiple regions of the Drosophila brain.