bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-31 uncouples skin inflammation from itch sensation in allergic dermatitis
Authors: Fassett Marlys S. , Braz Joao M. , Castellanos Carlos A. , Schroeder Andrew W. , Sadeghi Mahsa , Mar Darryl J. , Zhou Connie J. , Shin Jeoung-Sook , Basbaum Allan I. , Ansel K. Mark 
Published: May 2021

ABSTRACTDespite a robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the effects of IL-31 and its receptor IL31RA on both inflammation and pruritus in mouse models of dermatitis, including chronic topical house dust mite (HDM) exposure. Unexpectedly, Il31 deficiency increased cutaneous adaptive type 2 cytokine-producing cells and serum IgE. In addition, M2-like macrophages capable of fueling feedforward pro-inflammatory loops were selectively enriched in Il31ra-deficient skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of allergic skin inflammation. In contrast, Il31-deficient mice displayed a deficit in HDM-induced scratching. Itch reduction occurred despite intact – and in some cases increased – responsiveness of sensory neurons to other pruritogens released during HDM challenge, highlighting the non-redundant contribution of IL-31-receptive sensory afferents to pruritus in environmental allergen-induced dermatitis. When present, therefore, IL-31 uncouples circuits driven by sensory neurons and immune cells that converge in inflamed skin.
Structural basis for template switching by a group II intron-encoded non-LTR-retroelement reverse transcriptase
Authors: Lentzsch Alfred M. , Stamos Jennifer L. , Yao Jun , Russell Rick , Lambowitz Alan M. 
Published: May 2021

AbstractReverse transcriptases (RTs) can template switch during cDNA synthesis, enabling them to join discontinuous nucleic acid sequences. Template switching plays crucial roles in retroviral replication and recombination, is used for adapter addition in RNA-seq, and may contribute to retroelement fitness by enabling continuous cDNA synthesis on damaged templates. Here, we determined an X-ray crystal structure of a template-switching complex of a group II intron RT bound simultaneously to an acceptor RNA and donor RNA template/DNA heteroduplex with a 1-nt 3’-DNA overhang. The latter mimics a completed cDNA after non-templated addition (NTA) of a nucleotide complementary to the 3’ nucleotide of the acceptor as required for efficient template switching. The structure showed that the 3’ end of the acceptor RNA binds in a pocket formed by an N-terminal extension (NTE) present in non-long-terminal-repeat (LTR)-retroelement RTs and the RT fingertips loop, with the 3’ nucleotide of the acceptor base paired to the 1-nt 3’-DNA overhang and its penultimate nucleotide base paired to the incoming dNTP at the RT active site. Analysis of structure-guided mutations identified amino acids that contribute to acceptor RNA binding and a phenylalanine near the RT active site that mediates NTA. Mutation of the latter residue decreased multiple sequential template switches in RNA-seq. Our results provide new insights into the mechanisms of template switching and NTA by RTs, suggest how these reactions could be improved for RNA-seq, and reveal common structural features for template switching by non-LTR-retroelement RTs and viral RNA-dependent RNA polymerases.
Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression
Authors: Bruinstroop Eveline , Zhou Jin , Tripathi Madhulika , Yau Winifred W. , Boelen Anita , Singh Brijesh Kumar , Yen Paul M. 
Published: May 2021

AbstractObjectiveNon-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from hepatosteatosis to progressive non-alcoholic steatohepatitis that can lead to cirrhosis. Humans with low levels of the prohormone thyroxine (T4) have a higher incidence of NAFLD and thyroid hormone treatment is very promising in all patients with NAFLD. Deiodinase 1 (Dio1) is a hepatic enzyme that converts T4 to the bioactive T3, and therefore regulates intracellular thyroid hormone availability in the liver. The role of this intracellular regulation was investigated during the progression of NAFLD.MethodsWe investigated intracellular thyroid hormone metabolism in two NAFLD models: wildtype mice fed Western diet with fructose and Leprdp mice fed a methionine- and choline-deficient diet. AAV8-mediated liver-specific Dio1 knockdown was employed to investigate the role of Dio1 during the progression of NAFLD. Intrahepatic thyroid hormone levels, deiodinase activity and metabolic parameters were measured.ResultsDio1 expression and activity were increased in the early stages of NAFLD and were associated with an increased T3/T4 ratio. Prevention of this increase by AAV8-mediated liverspecific Dio1 knockdown increased hepatic triglycerides and cholesterol as well as decreased pACC/ACC ratio and acylcarnitine levels suggesting there was lower β-oxidation. Dio1 siRNA KD in hepatic cells treated with fatty acids showed increased lipid accumulation and decreased oxidative phosphorylation.ConclusionHepatic Dio1 gene expression was modulated by dietary conditions, increased during hepatosteatosis and early NASH, and regulated hepatic triglyceride content. These early adaptations likely represent compensatory mechanisms to reduce hepatosteatosis and prevent NASH progression.
Nerve recovery from treatment with a vascularized nerve graft compared to an autologous non-vascularized nerve graft in animal models: a systematic review and meta-analysis
Authors: Broeren Berend O. , Duraku Liron S. , Hundepool Caroline A. , Walbeehm Erik T. , Zuidam J. Michiel , Hooijmans Carlijn R. , De Jong Tim 
Published: May 2021

AbstractBackgroundTreatment of nerve injuries proves to be a worldwide clinical challenge. Vascularized nerve grafts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous non-vascularized nerve graft. However, there is no adequate clinical evidence for the beneficial effect of vascularized nerve grafts and they are still disputed in clinical practice.ObjectiveTo systematically review whether vascularized nerve grafts give a superior nerve recovery compared to non-vascularized nerve autografts regarding histological and electrophysiological outcomes in animal models.Material and methodsPubMed and Embase were systematically searched. The inclusion criteria were as follows: 1) the study was an original full paper which presented unique data; 2) a clear comparison between a vascularized and a non-vascularized autologous nerve transfer was made; 3) the population study were animals of all genders and ages. A standardized mean difference and 95% confidence intervals for each comparison was calculated to estimate the overall effect. Subgroup analyses were conducted on graft length, species and time frames.ResultsFourteen articles were included in this review and all of them were included in the meta-analyses. A vascularized nerve graft resulted in a significantly larger diameter, higher nerve conduction velocity and axonal count compared to an autologous non-vascularized nervegraft. However, during sensitivity analysis the effect on axonal count disappeared. No significant difference was observed in muscle weight.ConclusionTreating a nerve gap with a vascularized graft results in superior nerve recovery compared to non-vascularized nerve autografts in three out of four outcome measurements. However, this conclusion needs to be taken with some caution due to the inherent limitations of this meta-analysis. We recommend future studies to be performed under conditions more closely resembling human circumstances and to use long nerve defects.
Discovery of potential drug-like compounds against Viral protein (VP40) of Marburg Virus using pharmacophoric based virtual screening from ZINC database
Authors: Quazi Sameer , Malik Javed , Suman Komal Singh , Capuzzo Arnaud Martino , Haider Zeshan 
Published: May 2021

ABSTRACTMarburg virus (MARV) has been confirmed to cause extreme hemorrhagic fever (HFM) in human and animals. The effective and suitable vaccine to treat the MARV virus is not commercialized in public and demands rigorously tested on several scales. This research used a CADD (Computer-Aided Drug Design) computational based technology to find novel drug-like compounds that could inhibit the replicating of the VP40. The pharmacophoric features bases screening was done using an online computational based software, “ZINC Pharmer”. We retrieved about 32456 compounds mainly focused on the properties of pharmacophores from the ZINC database. Lipinski’s rule was also used to predict these drug-like compounds. as well as molecular coupling-dependent screening and selection of VP40 screening ligand complexes based on S-rank (lower than reference) and value of root, mean square (RMSD) (bottom) to examine for reference) using the Molecular Working Environment (MOE) machine. As a result, 100 compounds were found to have a close interaction with MARV VP40, followed by the Binding energy (BE) analysis of these 100 compounds. Only 50 were the strongest binding energy than favipiravir [reference inhibitor] after using the MOE-LigX algorithm to compare their binding energy. After that, ADMET analysis predicted only five compounds (ZINC95457352, ZINC38752258, ZINC38752253, ZINC39272175, and ZINC38752377) passed the ADMET parameters and have the strongest inhibitory effect against the MARV’s VP40. It has been suggested that these “drug-like” candidates have an increased ability to inhibit MARV replication, leading to treatment of MARVD.
Sex differences in microRNA expression in first and third trimester human placenta
Authors: Flowers Amy E. , Gonzalez Tania L. , Joshi Nikhil V. , Eisman Laura E. , Clark Ekaterina L. , Buttle Rae A. , Sauro Erica , DiPentino Rosemarie , Lin Yayu , Wu Di , Wang Yizhou , Santiskulvong Chintda , Tang Jie , Lee Bora , Sun Tianyanxin , Chan Jessica L. , Wang Erica T. , Jefferies Caroline , Lawrenson Kate , Zhu Yazhen , Afshar Yalda , Tseng Hsian-Rong , Williams John , Pisarska Margareta D. 
Published: May 2021

AbstractMaternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be the result of sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing was used to identify miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n=113) and parturition (n=47). Sequencing and differential expression (DE) analysis identified 432 mature miRNAs expressed in the first trimester female, 425 in the first trimester male, 400 in the third trimester female, and 508 in the third trimester male placenta (baseMean >10). Of these, 11 sexually dimorphic (FDR<0.05, baseMean >10) miRNAs were identified in the first and 4 miRNAs were identified in the third trimester, including miR-361-5p, significant in both trimesters, all upregulated in females. Across gestation, 207 miRNAs were DE across gestation, common to both females and males, miR-4483, the most DE across gestation. There were twice as many female-specific differences across gestation as male-specific (44 miRNAs vs 21 miRNAs), indicating that miRNA abundance across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex independent and sex specific placenta miRNA atlas across gestation which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.Summary SentenceSex dimorphism in miRNA expression is more pronounced in first compared to third trimester placenta, and there are twice as many female-specific gestational differences, indicating miRNA abundance across human gestation is also sexually dimorphic.
Chaperones directly and efficiently disperse stress-triggered biomolecular condensates
Authors: Yoo Haneul , Bard Jared A.M. , Pilipenko Evgeny , Drummond D. Allan 
Published: May 2021

AbstractHeat shock triggers formation of intracellular protein aggregates and induction of a molecular disaggregation system. Although this system (Hsp100/Hsp70/Hsp40 in most cellular life) can disperse aggregates of model misfolded proteins, its activity on these model substrates is puzzlingly weak, and its endogenous heat-induced substrates have largely eluded biochemical study. Recent work has revealed that several cases of apparent heat-induced aggregation instead reflect evolved, adaptive biomolecular condensation. In budding yeast Saccharomyces cerevisiae, the resulting condensates depend on molecular chaperones for timely dispersal in vivo, hinting that condensates may be major endogenous substrates of the disaggregation system. Here, we show that the yeast disaggregation system disperses heat-induced biomolecular condensates of poly(A)-binding protein (Pab1) orders of magnitude more rapidly than aggregates of the most commonly used model substrate, firefly luciferase. Pab1 condensate dispersal also differs from aggregate dispersal in its molecular requirements, showing no dependence on small heat-shock proteins and a strict requirement for type II Hsp40. Unlike luciferase, Pab1 is not fully threaded (and thus not fully unfolded) by the disaggregase Hsp104 during dispersal, which we show can contribute to the extreme differences in dispersal efficiency. The Hsp70-related disaggregase Hsp110 shows some Pab1 dispersal activity, a potentially important link to animal systems, which lack cytosolic Hsp104. Finally, we show that the long-observed dependence of the disaggregation system on excess Hsp70 stems from the precise mechanism of the disaggregation system, which depends on the presence of multiple, closely spaced Hsp70s for Hsp104 recruitment and activation. Our results establish heat-induced biomolecular condensates of Pab1 as a direct endogenous substrate of the disaggregation machinery which differs markedly from previously studied foreign substrates, opening a crucial new window into the native mechanistic behavior and biological roles of this ancient system.
Piezo1 activation using Yoda1 inhibits macropinocytosis and proliferation of cancer cells
Authors: Kuriyama Masashi , Hirose Hisaaki , Masuda Toshihiro , Shudou Masachika , Arafiles Jan Vincent V. , Imanishi Miki , Maekawa Masashi , Hara Yuji , Futaki Shiroh 
Published: May 2021

AbstractMacropinocytosis is a type of endocytosis accompanied by actin rearrangement-driven membrane deformation, such as lamellipodia formation and membrane ruffling, followed by macropinosome formation. A certain number of mammalian mechanosensors are sensitive to membrane deformation and tension. However, it remains unclear whether macropinocytosis is regulated by mechanosensors. Focusing on the mechanosensitive ion channel Piezo1, we found that Yoda1, a Piezo1 agonist, potently inhibits macropinocytosis induced by epidermal growth factor (EGF). Although studies with Piezo1 knockout cells suggest that Piezo1 itself is not physiologically indispensable for macropinocytosis regulation, Yoda1 inhibited ruffle formation depending on the extracellular Ca2+ influx through Piezo1 and on the activation of the calcium-activated potassium channel KCa3.1. This suggests that Ca2+ ions can regulate EGF-stimulated macropinocytosis. Moreover, Yoda1 impaired cancer cell proliferation, suggesting the impact of macropinocytosis inhibition. We propose the potential for cancer therapy by macropinocytosis inhibition through the regulation of a mechanosensitive channel activity.
Nitric oxide synthase neurons in the preoptic hypothalamus are sleep-active and contribute to regulating NREM and REM sleep and lowering body temperature
Authors: Harding Edward C. , Ba Wei , Zahir Reesha , Yu Xiao , Yustos Raquel , Hsieh Bryan , Lignos Leda , Vyssotski Alexei L. , Constandinou Timothy , Franks Nicholas P. , Wisden William 
Published: May 2021

ABSTRACTWhen mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM active. This is the first instance of a predominantly NREM-active population in the PO area, or to our knowledge, elsewhere in the brain. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 hours, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer. In particular, mice were warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.
The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae
Authors: Terhorst Allegra , Sandikci Arzu , Neurohr Gabriel E. , Whittaker Charles A. , Szórádi Tamás , Holt Liam J. , Amon Angelika 
Published: May 2021

AbstractTemperature sensitive cell division cycle (cdc-ts) cells are unable to progress through the cell cycle at the restrictive temperature due to mutations in genes essential to cell cycle progress. Cells harboring cdc-ts mutations increase in cell volume upon arrest but eventually stop growing. We found that this attenuation in growth was due to selective downregulation of ribosome concentration. We saw similar ribosome downregulation in cells arrested in the cell cycle through alpha factor addition, rapamycin addition, and entrance into stationary phase. In all cell cycle arrests studied, cells activated the Environmental Stress Response (ESR), a key transcriptional response to many stressors in S. cerevisiae. When we combined cell cycle arrest with hyperactivation of the Ras/PKA pathway, ESR activation was prevented, cells were unable to downregulate their ribosomes, and cell viability was decreased. Our work uncovers a key role for the environmental stress response in coupling cell cycle progression to biomass accumulation.
The effects of internal and external innovation strategies on process innovation in Vietnamese firms
Authors: Phung Thuy Minh Thu , Tran Dat Tho , Vermeulen Patrick Alexander Maria , Knoben Joris 
Published: May 2021

Purpose
This paper aims to investigate the antecedents of process innovation to provide more alternates for Vietnamese firms as they are still struggling to find an appropriate innovation strategy.

Design/methodology/approach
The research analyzes the separate impacts of each innovation strategy on process innovation using logistic regression models. Data were collected using a stratified random sampling method.

Findings
The results show that having an innovation strategy is good for innovation, regardless of whether the strategy is internal or external. Internal and external strategies are proved not complements but substitutes. However, the internal strategy seems to be most beneficial. Weak institutional settings further strengthen the importance of internal strategies, whereas strong institutional settings favor external strategies.

Originality/value
This paper analyzes the impact of different innovation strategies on process innovation in Vietnamese firms using firm-level data. The findings strongly recommend that in weak institutional settings such as Vietnam, firms should focus on an internal strategy because the emphasis on external innovation strategies might be a western bias stemming from research in mostly strong institutional contexts.
Mode identification method of low-frequency oscillation for power system based on ambient data
Authors: Yan Hong-Yan , Hwang Jin Kwon 
Published: May 2021

Purpose
The purpose of this paper is to improve the online monitoring level of low-frequency oscillation in the power system. A modal identification method of discrete Fourier transform (DFT) curve fitting based on ambient data is proposed in this study.

Design/methodology/approach
An autoregressive moving average mathematical model of ambient data was established, parameters of low-frequency oscillation were designed and parameters of low-frequency oscillation were estimated via DFT curve fitting. The variational modal decomposition method is used to filter direct current components in ambient data signals to improve the accuracy of identification. Simulation phasor measurement unit data and measured data of the power grid proved the correctness of this method.

Findings
Compared with the modified extended Yule-Walker method, the proposed approach demonstrates the advantages of fast calculation speed and high accuracy.

Originality/value
Modal identification method of low-frequency oscillation based on ambient data demonstrated high precision and short running time for small interference patterns. This study provides a new research idea for low-frequency oscillation analysis and early warning of power systems.
Soccer game optimization-based power flow for distribution networks
Authors: Venkatesan Yogambari , Palanivelu Aravindhababu 
Published: May 2021

Purpose
The purpose of the paper is to develop a simple, efficient and robust power flow (PF) method for ill-conditioned distribution networks (DNs).

Design/methodology/approach
It first formulates the PF problem as an optimization problem of minimizing the node power mismatches, while treating the corrections of node voltages as problem variables and then uses soccer game optimization (SGO), an artificial intelligent algorithm simulating the behavior of soccer game players in scoring goals, in solving the formulated PF problem.

Findings
It studies the performances of the developed method on four standard test DNs and exhibits that the method is superior in respect of accuracy, robustness and computational speed than those of existing methods.

Originality/value
It suggests a novel and new PF method using SGO and portrays that the proposed method is as accurate as any other PF method, robust like non-Newton type of PF methods and faster than Newton type of PF methods.