bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition
Authors: Xu Wanfeng , Che Yuan , Zhang Quan , Huang Hai , Ding Chujie , Wang Yun , Wang Guangji , Cao Lijuan , Hao Haiping 
Published: January 2020

SUMMARYCaspase-4 directly senses and is activated by cytosolic LPS in conditions of pathogen infection. It is unclear whether and how caspase-4 detects host derived factors for triggering pyroptosis. Here we show that mitochondrial permeability transition (MPT) promotes the assembly of a protein complex comprised of Apaf-1 and caspase-4 (caspase-11 in mice), defined herein as pyroptosome, for the execution of facilitated pyroptosis. MPT induced by bile acids and calcium overload, and specifically by an adenine nucleotide translocator 1 (ANT1) activator, triggered pyroptosome assembly. Different from the direct cleavage of GSDMD by LPS-activated caspase-4, caspase-4 activated in the Apaf-1 pyroptosome proceeds to cleave caspase-3 and thereby gasdermin E (GSDME) to induce pyroptosis. Caspase-11 initiated and GSDME executed pyroptosis underlies cholesteric liver failure. These findings identify Apaf-1 pyroptosome as a pivotal machinery for cells sensing MPT signals and may shed lights on understanding how cells execute pyroptosis under sterile conditions.HighlightsBile acids trigger caspase-4/11 and GSDME dependent pyroptosisCaspase-4/11 is a general sensor of mitochondrial permeability transition (MPT)MPT drives Apaf-1/capase-4 pryoptosome assemblyCaspase-11 and GSDME mediated pyroptosis underlies cholesteric liver damageeTOC BlurbPersistent mitochondrial permeability transition elicited by bile acids, calcium overload and specifically ANT1 activators drives assembly of Apaf-1-capase-4/11 pyroptosome triggering GSDME dependent pryroptosis.
ASC oligomer favor caspase-1CARDdomain recruitment after intracellular potassium efflux
Authors: Martín-Sánchez Fátima , Compan Vincent , Tapia-Abellán Ana , Gómez-Sánchez Ana I. , Baños María C. , Schmidt Florian I. , Pelegrín Pablo 
Published: January 2020

AbstractSignaling through the inflammasome is important for the inflammatory response. Low concentrations of intracellular K+are associated with the specific oligomerization and activation of the NLRP3 inflammasome, a type of inflammasome involved in sterile inflammation. Subsequent to NLRP3 oligomerization, ASC protein binds and form oligomeric filaments culminating in large protein complexes named ASC specks. ASC specks are also initiated from different inflammasome scaffolds, as AIM2, NLRC4 or Pyrin. ASC oligomers induce the recruitment of caspase-1 through interactions between their respective caspase activation and recruitment domains (CARD), and favoring its activation. So far ASC oligomerization and caspase-1 activation are considered as a K+-independent process. Here we found that ASC oligomers change their structure upon low intracellular K+independently of NLRP3 and allow the ASCCARDdomain to be more accessible for the recruitment of pro-caspase-1CARDdomain. Therefore, conditions that decrease intracellular K+not only drive NLRP3 responses, but also enhance the recruitment of pro-caspase-1 by ASC specks formed by different inflammasomes, indicating that intracellular K+homeostasis is a key regulatory step for inflammasome regulation.
A unified computational model for cortical post-synaptic plasticity
Authors: Mäki-Marttunen Tuomo , Iannella Nicolangelo , Edwards Andrew G. , Einevoll Gaute T. , Blackwell Kim T. 
Published: January 2020

AbstractCortical synapses possess a machinery of signalling pathways that leads to various modes of post-synaptic plasticity. Such pathways have been examined to a great detail separately in many types of experimental studies. However, a unified picture on how multiple biochemical pathways collectively shape the observed synaptic plasticity in the neocortex is missing. Here, we built a biochemically detailed model of post-synaptic plasticity that includes the major signalling cascades, namely, CaMKII, PKA, and PKC pathways which, upon activation by Ca2+, lead to synaptic potentiation or depression. We adjusted model components from existing models of intracellular signalling into a single-compartment simulation framework. Furthermore, we propose a statistical model for the prevalence of different types of membrane-bound AMPA-receptor tetramers consisting of GluR1 and GluR2 subunits in proportions suggested by the biochemical signalling model, which permits the estimation of the AMPA-receptor-mediated maximal synaptic conductance. We show that our model can reproduce neuromodulator-gated spike-timing-dependent plasticity as observed in the visual cortex. Moreover, we demonstrate that our model can be fit to data from many cortical areas and that the resulting model parameters reflect the involvement of the pathways pinpointed by the underlying experimental studies. Our model explains the dependence of different forms of plasticity on the availability of different proteins and can be used for the study of mental disorder-associated impairments of cortical plasticity.Significance statementNeocortical synaptic plasticity has been studied experimentally in a number of cortical areas, showing how interactions between neuromodulators and post-synaptic proteins shape the outcome of the plasticity. On the other hand, non-detailed computational models of long-term plasticity, such as Hebbian rules of synaptic potentiation and depression, have been widely used in modelling of neocortical circuits. In this work, we bridge the gap between these two branches of neuroscience by building a detailed model of post-synaptic plasticity that can reproduce observations on cortical plasticity and provide biochemical meaning to the simple rules of plasticity. Our model can be used for predicting the effects of chemical or genetic manipulations of various intracellular signalling proteins on induction of plasticity in health and disease.
Prior selection prevents the loss of an ecosystem cycle during acidification
Authors: van Moorsel Sofia J. , Marleau Justin N. , Negrín Dastis Jorge O. , Bazerghi Charles , Fugère Vincent , Petchey Owen L. , Gonzalez Andrew 
Published: January 2020

AbstractEcosystem processes vary temporally due to variation in environmental variables, such as when diurnal variation in sunlight causes diurnal cycles in net primary production. This variability can be characterized by its frequency and amplitude, used to define “normal” functioning of an ecosystem. Relatively little research has addressed how normal modes of variability, such as diurnal cycles, are lost or recovered, following anthropogenic stress. We conducted an aquatic mesocosm experiment to test whether prior application of environmental stress, in the form of moderate acidification, affected the diurnal cycle of dissolved oxygen when exposed to severe acidification. High-frequency data from sensor loggers deployed in 12 mesocosms showed that severe acidification caused a temporary loss of diurnal variation in dissolved oxygen concentration. However, pre-exposure to an acidic environment resulted in the persistence of the diurnal cycle. We hypothesize that pre-exposure shifted the community to acid tolerant genotypes and/or species of algae and other photosynthetic organisms. Our findings suggest that the stability of ecosystem cycles is intrinsically liked to the stress tolerance of the species assemblage.
Curcumin Analogues as the Inhibitors of TLR4 Pathway in Inflammation and Their Drug Like Potentialities: A Computer-based Study
Authors: Ullah Md. Asad , Johora Fatema Tuz , Sarkar Bishajit , Araf Yusha , Rahman MD. Hasanur 
Published: January 2020

AbstractIn this study Curcumin and their different analogues have been analyzed as the inhibitors of signaling proteins i.e., Cycloxygenase-2 (COX-2), Inhibitor of Kappaβ Kinase (IKK) and TANK binding kinase-1 (TBK-1) of Toll Like Receptor 4 (TLR4) pathway involved in inflammation using computational tools. Multiple analogues showed better binding affinity than the approved drugs for the respective targets. Upon continuous computational exploration 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK and TBK-1 respectively. Then their drug like potentialities were analyzed in different experiments where they also performed sound and similar. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.
Protective Population Behavior Change in Outbreaks of Emerging Infectious Disease
Authors: Lodge Evans K. , Schatz Annakate M. , Drake John M. 
Published: January 2020

ABSTRACTDuring outbreaks of emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission. This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks. We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak.
Thermodynamics of Homopeptide Aggregation
Authors: Phan Tam T. M. , Schmit Jeremy D. 
Published: January 2020

ABSTRACTAmyloid aggregates are found in many neurodegenerative diseases including Huntington’s, Alzheimer’s, and prion diseases. The precise role of the aggregates in disease progression has been difficult to elucidate due to the diversity of aggregated states they can adopt. Here we study the formation of fibrils and oligomers by exon 1 of huntingtin protein. We show that the oligomer states are consistent with polymer micelles that are limited in size by the stretching entropy of the polyglutamine region. The model shows how the sequences flanking the amyloid core modulate aggregation behavior. The N17 region promotes aggregation through weakly attractive interactions, while the C38 tail opposes aggregation via steric repulsion. We also show that the energetics of cross-βstacking by polyglutamine would produce fibrils with many alignment defects, but minor perturbations from the flanking sequences are sufficient to reduce the defects to the level observed in experiment. We conclude with a discussion of the implications of this model for other amyloid forming molecules.
Warming-enhanced priority effects at population and community levels in aquatic bacteria
Authors: Vass Máté , Székely Anna J. , Lindström Eva S. , Osman Omneya A. , Langenheder Silke 
Published: January 2020

AbstractThe immigration history of communities can profoundly affect community composition. For instance, early-arriving species can have a lasting effect on community structure by reducing the immigration success of late-arriving ones through priority effects. Warming could possibly enhance priority effects by increasing growth rates of early-arriving bacteria. Here we implemented a full-factorial experiment with aquatic bacteria where both temperature and dispersal rate of a better-adapted community were manipulated to test their effects on the importance of priority effects, both on a community and a population level. Our results suggest that priority effects in aquatic bacteria might be primarily driven by niche preemption and strengthened by increasing temperature as warming increased the resistance of recipient communities against dispersal, and decreased the relative abundance of successfully established late-arriving bacteria. However, warming-enhanced priority effects were not always found and their strengths differed between recipient communities and dispersal rates. Nevertheless, our findings highlight the importance of context dependence of priority effects and the potential role of warming in mitigating the effects of invasion.
Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice
Authors: Binning William , Hogan-Cann Aja E. , Sakae Diana Yae , Maksoud Matthew , Ostapchenko Valeriy , Al-Onaizi Mohammed , Matovic Sara , Lu Wei-Yang , Prado Marco A. M. , Inoue Wataru , Prado Vania F. 
Published: January 2020

AbstractMicroglia express muscarinic G protein-coupled receptors (GPCRs) that sense cholinergic activity and are activated by acetylcholine to potentially regulate microglial functions. Knowledge about how distinct types of muscarinic GPCR signaling regulate microglia functionin vitroandin vivois still poor, partly due to the fact that some of these receptors are also present in astrocytes and neurons. We generated mice expressing the hM3Dq Designer Receptor Exclusively Activated by Designer Drugs (DREADD) selectively in microglia to investigate the role of muscarinic M3Gq-linked signaling. We show that activation of hM3Dq using clozapine N-oxide (CNO) elevated intracellular calcium levels and increased phagocytosis of FluoSpheresin vitro. Acute treatment with CNOin vivodid not affect male mouse behavior, however chronic CNO treatment decreased sickness behavior triggered by lipopolysaccharide (LPS) treatment. Interestingly, whereas acute treatment with CNO increased synthesis of cytokine mRNA, chronic treatment attenuated LPS-induced cytokine mRNA changes in the brain, likely explaining the improvement in sickness behavior by chronic hM3Dq activation. No effect of CNO was observed in DREADD-negative mice. These results suggest that chronic activation of M3 muscarinic receptors (the hM3Dq progenitor) in microglia, and potentially other Gq-coupled GPCRs, preconditions microglia to decrease their response to further immunological challenges. Our results indicate that hM3Dq can be a useful tool to modulate neuroinflammation and study microglial immunological memoryin vivo, which may be applicable for manipulations of neuroinflammation in neurodegenerative and psychiatric diseases.HighlightsMicroglial function was manipulated by specific activation of hM3Dq signaling.Chronic hM3Dq activation prevented LPS-induced sickness behavior in mice.Microglial hM3Dq signaling modulated expression of pro-inflammatory cytokines.
A variant inSMOC2,inhibiting BMP signaling by competitively binding to BMPR1B, causes multiple epiphyseal dysplasia
Authors: Long Feng , Li Lin , Shi Hongbiao , Li Pengyu , Guo Shaoqiang , Ma Yuer , Li Yan , Wei Shijun , Gao Fei , Gao Shang , Wang Meitian , Duan Ruonan , Wang Xiaojing , Yang Kun , Liu Ai , Wang Anran , Chen Xiao , Sun Wenjie , Li Xi , Li Jiangxia , Liu Qiji 
Published: January 2020

AbstractPreviously study showed that SMOC, a matricellular protein, inhibits BMP signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In our study, exome sequencing revealed a missense mutation (c.1076T>G, p.Leu359Arg) in EC domain of SMOC2 in a Chinese family with multiple epiphyseal disease (MED). The pathogenicity of this SMOC2 variant was verified bySmoc2L359R/L359Rknock-in mice. Of note, decreasing phosphorylation of SMAD1/5/9 was detected in growth plates and primary chondrocytes fromSmoc2L359R/L359Rmice. Furthermore, binding affinity of mutant SMOC2 with collagen IX and HSPG in the extracellular matrix of cartilage were reduced while binding affinity with BMPRIB was intact. In addition, in contrast to previously results, that SMOC2 cannot antagonize BMP activity in the presence of a constitutively activated BMP receptor. These results support thatSMOC2with p.Leu359Arg variant act as an antagonist of canonical BMP pathway by competitively binding with BMP receptors.
DeepTE: a computational method for de novo classification of transposons with convolutional neural network
Authors: Yan Haidong , Bombarely Aureliano , Li Song 
Published: January 2020

AbstractMotivationTransposable elements (TEs) classification is an essential step to decode their roles in genome evolution. With a large number of genomes from non-model species becoming available, accurate and efficient TE classification has emerged as a new challenge in genomic sequence analysis.ResultsWe developed a novel tool, DeepTE, which classifies unknown TEs using convolutional neural networks. DeepTE transferred sequences into input vectors based on k-mer counts. A tree structured classification process was used where eight models were trained to classify TEs into super families and orders. DeepTE also detected domains inside TEs to correct false classification. An additional model was trained to distinguish between non-TEs and TEs in plants. Given unclassified TEs of different species, DeepTE can classify TEs into seven orders, which include 15, 24, and 16 super families in plants, metazoans, and fungi, respectively. In several benchmarking tests, DeepTE outperformed other existing tools for TE classification. In conclusion, DeepTE successfully leverages convolutional neural network for TE classification, and can be used to precisely identify and annotate TEs in newly sequenced eukaryotic genomes.AvailabilityDeepTE is accessible athttps://github.com/LiLabAtVT/DeepTEContactsongli@vt.edu
Implantation technique, safety and complications of robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy
Authors: Chaitanya Ganne , Romeo Andrew K. , Ilyas Adeel , Irannejad Auriana , Toth Emilia , Elsayed Galal , Bentley J. Nicole , Riley Kristen O. , Pati Sandipan 
Published: January 2020

AbstractIntroductionDespite numerous imaging studies highlighting the importance of thalamus in surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei in patients with suspected temporal lobe epilepsy (TLE).MethodsAfter obtaining informed consent, 24 adults with drug-resistant suspected TLE undergoing Stereo-EEG evaluation were enrolled in this prospective study. The trajectory of one electrode planned for clinical sampling the operculo-insular cortex was modified to extend to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior thalamus (ANT) (N=13) and the medial group of thalamic nuclei (MED) (N=11), including mediodorsal (MD) and centromedian (CeM) were targeted. The post-implantation CT was co-registered to the pre-operative MRI, and Morel’s thalamic atlas was used to confirm the accuracy of implantation.ResultsTen out of 13 (77%) in the ANT group and 10 out of 11 patients (90%) in the medial group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical level entry site were noted in 20.8% of patients and they did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from the medial group at the entry point i.e., precentral gyrus in the former and postcentral gyrus in the latter.ConclusionsUsing judiciously planned robot-assisted SEEG, we demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes, or comprising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.
Investigation into the development and historical roots of collection development by referenced publication year spectroscopy
Authors: Malik Basharat Ahmad , Ahmadi Ashiya 
Published: January 2020

Purpose
The purpose of this study is the application of a recently developed quantitative method named Referenced Publication Year Spectroscopy (RPYS) in the spectrum of Collection Development. RPYS portrays peak years to be recognized in citations in a research field that guarantees to assist in the identification of significant contributions and groundbreaking revelations in a research field.

Design/methodology/approach
Preliminary data of the study has been extracted from Web of Science (WoS) by using two phrases “collection development” and “collection building” to search in terms of the topic (comprising four parts: title, abstract, author keywords and KeyWords Plus). The search was restricted to the time period 1974-2017, which formulated a data set of 1,682 documents covering 29,017 cited references. The program CRExplorer (www.crexplorer.net) was used for the extraction of cited references from the data sets downloaded from WoS. Further analysis was performed manually using MS-Excel 2016.

Findings
The present study identified seminal works, which contributed to a high extent to the evolution and development of collection development. The analysis of all cited references using the RPYS method showed nine peaks, which present historical roots of collection development and revealed that the basic idea of this very subfield of library science dates centuries back. Moreover, the results of the investigation on most effective documents (in the form of peaks) revealed that the field of collection development significantly influenced by the works of authors such as Gabriel Naudé, Gabriel Peignot, Giulio Petzholdt, P L Gross, E M Gross, Richard Trueswell, Allen Kent, Ross Atkinson, etc.

Practical implications
The analysis of works cited in publications helps to ascertain important intellectual contributions related to a particular domain of knowledge. It not only helps in extracting the most important works but also it helps to reconstruct the history of a specific research field by examining the specific role of the cited references. Therefore, the results of the study could be useful for researchers, practitioners, scholars and more specifically bibliophiles, bibliographers and librarians to gain a better understanding of seminal works in the spectrum of collection development.

Originality/value
To the best of authors’ knowledge, the present research work is unique and novel in the spectrum of collection development, which explored and examined the pivotal works in the field by using the RPYS method.