bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway
Authors: Sonthonnax Florian , Besson Benoit , Bonnaud Emilie , Jouvion Grégory , Merino David , Larrous Florence , Bourhy Hervé 
Published: August 2019

AbstractPhosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 (pSTAT1), M interacts with the RelAp43-p105-ABIN2-TPL2 complex, to efficiently inhibit the nuclear factor-κB (NF-κB) pathway. Using transfections, protein-complementation assays, reverse genetics and DNA ChIP, we identified a role of M protein in the control of Jak-Stat signaling pathway, in synergy with the P protein. In unstimulated cells, both M and P proteins were found to interact with JAK1. Upon type-I IFN stimulation, the M switches toward pSTAT1 interaction, which results in an enhanced capacity of P protein to interact with pSTAT1 and restrain it in the cytoplasm. Furthermore, the role for M-protein positions 77, 100, 104 and 110 was also demonstrated in interaction with both JAK1 and pY-STAT1, and confirmed in vivo. Together, these data indicate that M protein cooperates with P protein to restrain in parallel, and sequentially, NF-κB and Jak-Stat pathways.
Robust Microfabrication of Highly Parallelized Three-Dimensional Microfluidics on Silicon
Authors: Yadavali Sagar , Lee Daeyeon , Issadore David 
Published: August 2019

AbstractWe present a new, robust three dimensional microfabrication method for highly parallel microfluidics, to improve the throughput of on-chip material synthesis by allowing parallel and simultaneous operation of many replicate devices on a single chip. Recently, parallelized microfluidic chips fabricated in Silicon and glass have been developed to increase the throughput of microfluidic materials synthesis to an industrially relevant scale. These parallelized microfluidic chips require large arrays (>10,000) of Through Silicon Vias (TSVs) to deliver fluid from delivery channels to the parallelized devices. Ideally, these TSVs should have a small footprint to allow a high density of features to be packed into a single chip, have channels on both sides of the wafer, and at the same time minimize debris generation and wafer warping to enable permanent bonding of the device to glass. Because of these requirements and challenges, previous approaches cannot be easily applied to produce three dimensional microfluidic chips with a large array of TSVs. To address these issues, in this paper we report a fabrication strategy for the robust fabrication of three-dimensional Silicon microfluidic chips consisting of a dense array of TSVs, designed specifically for highly parallelized microfluidics. In particular, we have developed a two-layer TSV design that allows small diameter vias (d < 20 µm) without sacrificing the mechanical stability of the chip and a patterned SiO2 etch-stop layer to replace the use of carrier wafers in Deep Reactive Ion Etching (DRIE). Our microfabrication strategy allows >50,000 (d = 15 µm) TSVs to be fabricated on a single 4” wafer, using only conventional semiconductor fabrication equipment, with 100% yield (M = 16 chips) compared to 30% using previous approaches. We demonstrated the utility of these fabrication strategies by developing a chip that incorporates 20,160 flow focusing droplet generators onto a single 4” Silicon wafer, representing a 100% increase in the total number of droplet generators than previously reported. To demonstrate the utility of this chip for generating pharmaceutical microparticle formulations, we generated 5–9 µm polycaprolactone particles with a CV < 5% at a rate as high as 60 g/hr (>1 trillion particles/hour).
Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy
Authors: Hathout Yetrib , Liang Chen , Ogundele Michael , Xu Ganggang , Tawalbeh Shefa M. , Dang Utkarsh J , Hoffman Eric P. , Gordish-Dressman Heather , Conklin Laurie S. , van den Anker John N. , Clemens Paula R. , Mah Jean K. , Henricson Erik , McDonald Craig 
Published: August 2019

AbstractExtensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed in independent cohorts and across different laboratories. In these previous studies, glucocorticoids and age were two major confounding variables. In this new study, using SomaScan technology and focusing on a subset of young DMD patients who were not yet treated with glucocorticoids, we identified 108 elevated and 70 decreased proteins in DMD relative to age matched healthy controls (p value < 0.05 after adjusting for multiple testing). The majority of the elevated proteins were muscle centric followed by cell adhesion, extracellular matrix proteins and a few pro-inflammatory proteins. The majority of decreased proteins were of cell adhesion, however, some had to do with cell differentiation and growth factors. Subsequent treatment of this group of DMD patients with glucocorticoids affected two major groups of pharmacodynamic biomarkers. The first group consisted of 80 serum proteins that were not associated with DMD and either decreased or increased following treatment with glucocorticoids, and therefore were reflective of a broader effect of glucocorticoids. The second group consisted of 17 serum proteins that were associated with DMD and these tended to normalize under treatment, thus reflecting physiologic effects of glucocorticoid treatment in DMD. In summary, we have identified a variety of circulating protein biomarkers that reflect the complex nature of DMD pathogenesis and response to glucocorticoids.
Inhibition of GATA2 restrains cell proliferation and enhances apoptosis and chemotherapy mediated apoptosis in human GATA2 overexpressing AML cells
Authors: Menendez-Gonzalez Juan Bautista , Sinnadurai Samantha , Gibbs Alex , Thomas Leigh-anne , Konstantinou Maria , Garcia-Valverde Alfonso , Boyer Magali , Wang Zhengke , Boyd Ashleigh S. , Blair Allison , Morgan Rhys G. , Rodrigues Neil P. 
Published: August 2019

AbstractGATA2, a zinc finger transcription factor predominantly expressed in hematopoietic cells, acts as an essential regulator of hematopoietic stem cell generation, survival and functionality. Loss and gain of GATA2 expression has been implicated in myelodysplastic syndrome and acute myeloid leukemia (AML) yet the precise biological impact of GATA2 expression on human AML cell fate decisions remains ambiguous. Herein, we performed large-scale bioinformatics that demonstrated relatively frequent GATA2 overexpression in AML patients as well as select human AML (or AML-like) cell lines. By using shRNAi to target GATA2 in these AML cell lines, and an AML cell line expressing normal levels of GATA2, we found that inhibition of GATA2 caused attenuated cell proliferation and enhanced apoptosis exclusively in AML cell lines that overexpress GATA2. We proceeded to pharmacologically inhibit GATA2 in concert with AML chemotherapeutics and found this augmented cell killing in AML cell lines that overexpress GATA2, but not in an AML cell line expressing normal levels of GATA2. These data indicate that inhibition of GATA2 enhances chemotherapy-mediated apoptosis in human AML cells overexpressing GATA2. Thus, we define novel insights into the oncogenic role of GATA2 in human AML cells and suggest the potential utilization of transient GATA2 therapeutic targeting in AML.
Advancement through epidermis using tape stripping technique and Reflectance Confocal Microscopy
Authors: Olesen Caroline Meyer , Fuchs Christine Sofie Krohn , Philipsen Peter Alshede , Hædersdal Merete , Agner Tove , Clausen Maja-Lisa 
Published: August 2019

AbstractThe tape stripping technique is increasingly used in research regarding skin barrier function. However, number of tape strips varies between studies, and literature considering advancement into stratum corneum/epidermis in relation to number of tape strips is scarce. The aim of this pilot study was to assess the advancement through epidermis using tape stripping technique in healthy volunteers. A total of ten healthy volunteers were included. From all volunteers 0, 5, 15 and 35 consecutive tape strips (D-squame) were taken from four adjacent skin areas on the middle volar forearm, followed by Reflectance Confocal Microscopy (RCM) of the four areas to assess epidermal thickness. Squame Scan was used to determine amount of protein removed. Stratum corneum was completely removed in all volunteers after 35 tape strips. Advancement into epidermis was predominantly achieved by the first 15 tape strips, removing 25% of the total epidermis, whereas 35 tape strips removed 33% of epidermis. Protein removal per tape decreased with increasing depth. Information on advancement into the epidermis according to number of tape strips taken, is a significant step forward. The possibility to obtain samples from different layers of epidermis may lead to an improved understanding of skin barrier properties.
Pessimistic outcome expectancy does not explain ambiguity aversion in decision-making under uncertainty
Authors: Ahrends C. , Bravo F. , Kringelbach M. L. , Vuust P. , Rohrmeier M. A. 
Published: August 2019

AbstractWhen faced with a decision, most people like to know the odds and prefer to avoid ambiguity. It has been suggested that this aversion to ambiguity is linked to people’s assumption of worst possible outcomes. We used two closely linked behavioural tasks in 78 healthy participants to investigate whether such pessimistic prior beliefs can explain ambiguity aversion. In the risk-taking task, participants had to decide whether or not they place a bet, while in the beliefs task, participants were asked what they believed would be the outcome. Unexpectedly, we found that in the beliefs task, participants were not overly pessimistic about the outcome in the ambiguity condition and in fact closer to optimal levels of decision-making than in the risk conditions. While individual differences in pessimism could explain outcome expectancy, they had no effect on ambiguity aversion. Consequently, ambiguity aversion is more likely caused by general caution than by expectation of negative outcomes despite pessimism-dependent subjective weighting of probabilities.
Neuromuscular and biomechanical functions subserving finger dexterity in musicians
Authors: Kimoto Yudai , Oku Takanori , Furuya Shinichi 
Published: August 2019

AbstractExceptional finger dexterity enables skillful motor actions such as those required for musical performance. However, it has been not known whether and in what manner neuromuscular or biomechanical features of the fingers subserve the dexterity. We aimed to identify the features firstly differentiating the finger dexterity between trained and untrained individuals and secondly accounting for the individual differences in the dexterity across trained individuals. To this aim, two studies were conducted. The first study compared the finger dexterity and several neuromuscular and biomechanical characteristics of the fingers between pianists and non-musicians. As a measure of the dexterity, we used the maximum rate of repetitive finger movements. The results showed no differences in any biomechanical constraints of the fingers between the two groups (i.e. anatomical connectivity between the fingers and range of motion). However, the pianists exhibited faster finger movements and more independent control of movements between the fingers. These observations indicate expertise-dependent enhancement of the finger dexterity and reduction of neuromuscular constraints on movement independence between the fingers. The second study assessed individual differences in the finger dexterity between trained pianists. A penalized regression determined an association of the maximum movement speed of the fingers with both muscular strength and biomechanical characteristics of the fingers, but not with neuromuscular constraints of the fingers. None of these features covaried with measures of early and deliberate piano practice. These findings indicate that distinct biological factors of finger motor dexterity differentiate between the effects of piano practicing and individual differences across skilled pianists.
Human metallo-β-lactamase enzymes degrade penicillin
Authors: Diene Seydina M. , Pinault Lucile , Keshri Vivek , Armstrong Nicholas , Khelaifia Saber , Chabrière Eric , Caetano-Anolles Gustavo , Colson Philippe , La Scola Bernard , Rolain Jean-Marc , Pontarotti Pierre , Raoult Didier 
Published: August 2019

AbstractNonribosomal peptides are assemblages, including antibiotics, of canonical amino acids and other molecules. β-lactam antibiotics act on bacterial cell walls and can be cleaved by β-lactamases. β-lactamase activity in humans has been neglected, even though eighteen enzymes have already been annotated such in human genome. Their hydrolysis activities on antibiotics have not been previously investigated. Here, we report that human cells were able to digest penicillin and this activity was inhibited by β-lactamase inhibitor, i.e. sulbactam. Penicillin degradation in human cells was microbiologically demonstrated on Pneumococcus. We expressed a MBLAC2 human β-lactamase, known as an exosome biogenesis enzyme. It cleaved penicillin and was inhibited by sulbactam. Finally, β-lactamases are widely distributed, archaic, and have wide spectrum, including digesting anticancer and β-lactams, that can be then used as nutriments. The evidence of the other MBLAC2 role as a bona fide β-lactamase allows for reassessment of β-lactams and β-lactamases role in humans.
RTMS parameters in tinnitus trials: a systematic review
Authors: Schoisswohl Stefan , Agrawal Kushal , Simoes Jorge , Neff Patrick , Schlee Winfried , Langguth Berthold , Schecklmann Martin 
Published: August 2019

AbstractOver the past few years extensive body of research was produced investigating the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus with heterogeneous results. This heterogeneity is exemplified by two recently published large-scale clinical trials reporting different outcomes. Technical aspects of rTMS were suspected as a potential source for this incongruency. The aim of this systematic review is to examine the overall efficacy as well as to identify possible technical factors relevant for the effectiveness of rTMS tinnitus trials. Via a literature search appropriate original research papers were identified and rTMS parameters were extracted from each study arm for subsequent statistical analysis with respect to observed effects (significant vs. not significant pre-post rTMS effects). Our findings indicate that verum rTMS is superior to sham rTMS as demonstrated by the proportion of significant pre-post contrasts. Some relevant rTMS parameters (e.g., pulse waveform) are not reported. Lower rTMS stimulation intensity was associated with significant effects in verum rTMS arms. An additional stimulation of the DLPFC to the temporal cortex was not found to promote efficacy. Future research should consider differential effects of rTMS induced by technical parameters and strive for an exhaustive reporting of relevant rTMS parameters.
Graphene–ferroelectric transistors as complementary synapses for supervised learning in spiking neural network
Authors: Chen Yangyang , Zhou Yue , Zhuge Fuwei , Tian Bobo , Yan Mengge , Li Yi , He Yuhui , Miao Xiang Shui 
Published: August 2019

AbstractThe hardware design of supervised learning (SL) in spiking neural network (SNN) prefers 3-terminal memristive synapses, where the third terminal is used to impose supervise signals. In this work we address this demand by fabricating graphene transistor gated through organic ferroelectrics of polyvinylidene fluoride. Through gate tuning not only is the nonvolatile and continuous change of graphene channel conductance demonstrated, but also the transition between electron-dominated and hole-dominated transport. By exploiting the adjustable bipolar characteristic, the graphene–ferroelectric transistor can be electrically reconfigured as potentiative or depressive synapse and in this way complementary synapses are realized. The complementary synapse and neuron circuit is then constructed to execute remote supervise method (ReSuMe) of SNN, and quick convergence to successful learning is found through network-level simulation when applying to a SL task of classifying 3 × 3-pixel images. The presented design of graphene–ferroelectric transistor-based complementary synapses and quantitative simulation may indicate a potential approach to hardware implementation of SL in SNN.
High-speed low-crosstalk detection of a 171Yb+ qubit using superconducting nanowire single photon detectors
Authors: Crain Stephen , Cahall Clinton , Vrijsen Geert , Wollman Emma E. , Shaw Matthew D. , Verma Varun B. , Nam Sae Woo , Kim Jungsang 
Published: August 2019

AbstractQubits used in quantum computing suffer from errors, either from the qubit interacting with the environment, or from imperfect quantum logic gates. Effective quantum error correcting codes require a high fidelity readout of ancilla qubits from which the error syndrome can be determined without affecting data qubits. Here, we present a detection scheme for 171Yb+ qubits, where we use superconducting nanowire single photon detectors and utilize photon time-of-arrival statistics to improve the fidelity and speed. Qubit shuttling allows for creating a separate detection region where an ancilla qubit can be measured without disrupting a data qubit. We achieve an average qubit state detection time of 11 μs with a fidelity of 99.931(6). The detection crosstalk error, defined as the probability that the data qubit coherence is lost due to the process of detecting an ancilla qubit, is reduced to ~2 × 10−5 by creating a separation of 370 μm between them.
The deficiency of miR-214-3p exacerbates cardiac fibrosis via miR-214-3p/NLRC5 axis
Authors: Yang Kun , Shi Jiaran , Hu Zhujun , Hu Xiaosheng 
Published: August 2019

Abstract
Cardiac fibrosis is a common pathological feature of many cardiovascular diseases. The regulatory mechanisms of miRNAs in cardiac fibrosis are still unknown. Previous studies on miR-214-3p in cardiac fibroblasts reached contradictory conclusions. Thus the role of miR-214-3p in cardiac fibrosis deserves further exploration. Using a combination of in vitro and in vivo studies, we identified miR-214-3p as an important regulator of cardiac fibrosis, and the proliferation and activation of cardiac fibroblasts. We demonstrated that the expression of miR-214-3p is down-regulated in TGF-β1-treated myofibroblasts and transverse aortic constriction (TAC)-induced murine model. Additionally, miR-214-3pflox/flox/FSP1-cre mice and miR-214-3pwt/wt/FSP1-cre mice were subjected to TAC operation or sham operation, and the conditional knockout of miR-214-3p in cardiac fibroblasts aggravates TAC-induced cardiac fibrosis. In vitro, our results indicate that miR-214-3p is an important repressor for fibroblasts proliferation and fibroblast-to-myofibroblast transition by functionally targeting NOD-like receptor family CARD domain containing 5 (NLRC5). In conclusion, our findings show that the deficiency of miR-214-3p exacerbates cardiac fibrosis and reveal a novel miR-214-3p/NLRC5 axis in the regulation of cardiac fibrosis.
Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2
Authors: Wang Yongshun , Jin Pianpian , Liu Jingjin , Xie Xiang 
Published: August 2019

Abstract
Emerging studies have demonstrated that microRNAs (miRs) participate in the development of multiple metabolic complications including cardiovascular diseases. Among them, circulating level of liver-secreted miR-122 was closely correlated with several consequence of heart diseases in clinical studies, and overexpression of miR-122 impaired cardiomyocyte function. However, it was unknown whether miR-122 could regulate cardiac biology in obesity. Therefore, present study was to disclose the role of miR-122 in cardiac metabolic disorders and potential molecular mechanisms. Through utilizing clinical samples and high fat diet-fed mice, we investigated the physiological roles of miR-122 in obesity-related cardiomyopathy. Besides, present study explored the mitochondrial function under exosomal miR-122 stimulation in mouse primary cardiomyocytes. In clinical samples and obese mice, the circulating level of exosomal miR-122 was positively correlated with cardiac dysfunctional parameters, including reduction in ejection fraction (EF) and increased levels of NT-proBNP. Human plasma exosomes transported miR-122 into mouse primary cardiomyocytes, and impaired mitochondrial ATP production and oxygen consumption, whereas miR-122 sponge improved these inhibitory effects. In dietary-induced mice, increased hepatic and circulating exosomal miR-122 deteriorated cardiac structure and functional index, and inhibited mitochondrial function. Liver-specific blockage of miR-122 attenuated abnormal cardiac remodeling. Mechanistically, miR-122 directly bound and suppressed mitochondrial protein ADP-ribosylation factor-like 2 (Arl-2) in vitro and in vivo. Knockdown of Arl-2 abolished the mitochondrial benefits of miR-122 sponge in exosome-treated mouse primary cardiomyocytes.
In conclusions, our present study firstly showed that liver-secreted exosomal miR-122 played a critical role in the development of metabolic cardiomyopathy, and miR-122/mitochondrial Arl-2 signaling affected cardiac energy homeostasis.
Speech Errors and Phonological Awareness in Children Ages 4 and 5 Years With and Without Speech Sound Disorder
Authors: Brosseau-Lapré Françoise , Roepke Elizabeth 
Published: August 2019

Purpose
The aim of this study was to examine the relationship between types of speech errors produced by children with speech sound disorders (SSD) and children with typical speech and language development (TD) and phonological awareness (PA) skills.

Method
Participants were 40 children, half with SSD and half with TD, ages 4 and 5 years. They completed standard speech, language, and PA tests as well as produced single words varying in length from 1 to 5 syllables. Production of each consonant was classified as either correct production, omission, substitution, and distortion; errors were also classified as typical or atypical.

Results
The children with SSD produced similar proportions of each type of speech errors in mono-, di-, and multisyllabic words. In contrast, the children with TD produced much lower, but not significantly different, proportions of omissions, substitutions, distortions, and typical speech errors at each word length. They produced no atypical errors in monosyllabic words and were significantly more likely to produce them in multisyllabic words. Proportions of omissions and atypical speech errors were significantly correlated with PA performance. Variance in PA skills was predicted partly by vocabulary, language skills, and age; omissions accounted for an additional 5% of variance in PA. Other types of speech errors did not account for additional significant variance in PA performance.

Conclusions
Poorer PA skills were found to be associated with omissions and atypical speech errors. Research is required to investigate the potential of omission and atypical error use in predicting which children are likely to receive diagnoses of SSD and later literacy difficulties.