bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPIKE-TRIGGERED INTRASPINAL MICROSTIMULATION IMPROVES MOTOR PERFORMANCE IN AN AMBULATORY RAT MODEL OF SPINAL CORD INJURY
Authors: Borrell Jordan A. , Gattozzi Domenico , Krizsan-Agbas Dora , Jaeschke Matthew W. , Nudo Randolph J. , Frost Shawn B. 
Published: June 2021

AbstractThe purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS) results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). Experiments were carried out in adult male Sprague Dawley rats with 175 kdyn moderate T8 contusion injury. Rats were randomly assigned to one of two groups: Control or Activity Dependent Stimulation (ADS) therapy. Four weeks post-SCI, all rats were implanted with a recording electrode in the left hindlimb motor cortex and a fine-wire, custom-made stimulating electrode in the contralateral lumbar spinal cord. Intracortical and intraspinal microstimulation were used to find sites of similar hip representation areas, which were paired together for ADS therapy. In the ADS therapy group, spike-stimulus conditioning was administered for 4 hours/day, 4 days/week, for 4 weeks via a tethered cable in a testing chamber. During therapy sessions, single-unit spikes were discriminated in real time in the hindlimb motor cortex and used to trigger stimulation in the spinal cord ventral horn. The optimal stimulus intensity (50% ISMS movement threshold) and spike-stimulus delay (10ms) determined in preliminary anesthetized preparations were used during ADS. Control rats were similarly implanted with electrodes but did not receive stimulation therapy. Motor performances of each rat were evaluated before SCI contusion, once a week post-SCI for four weeks (prior to electrode implantation), and once a week post-conditioning for four weeks. Behavioral testing included BBB scoring, Ledged Beam walking, Horizontal Ladder walking, treadmill kinematics via the DigiGait and TreadScan system, and open field walking using OptiTrack kinematic analysis. BBB scores were significantly improved in ADS rats compared to Control rats after 1 week of therapy. In the ADS therapy rats, BBB scores were significantly improved after two weeks of ADS therapy when compared to pre-therapy. Foot fault scores on the Horizontal Ladder were significantly lower in ADS rats compared to pre-therapy ADS and Control rats after 1 week of therapy and returned to pre-injury measures after three weeks of ADS therapy. The Ledged Beam test and kinematic analysis using the DigiGait and TreadScan system showed deficits after SCI in both ADS and Control rats but there were no significant differences between groups after 4 weeks of ADS therapy. These results show that activity dependent stimulation after spinal cord injury using spike-triggered ISMS enhances behavioral recovery of locomotor function as measured by the BBB score and the Horizontal Ladder task.
Time-scales modulate optimal lysis-lysogeny decision switches and near-term phage fitness
Authors: Shivam Shashwat , Li Guanlin , Lucia-Sanz Adriana , Weitz Joshua S. 
Published: June 2021

AbstractTemperate phage can initiate lysis or lysogeny after infecting a bacterial host. The genetic switch between lysis and lysogeny is mediated by phage regulatory genes as well as host and environmental factors. Recently, a new class of decision switches was identified in phage of the SPbeta group, mediated by the extracellular release of small, phage-encoded peptides termed arbitrium. Arbitrium peptides can be taken up by bacteria prior to infection, modulating the decision switch in the event of a subsequent phage infection. Increasing concentration of arbitrium increases the chance that a phage infection will lead to lysogeny, rather than lysis. Although prior work has centered on the molecular mechanisms of arbitrium-induced switching, here we focus on how selective pressures impact the benefits of plasticity in switching responses. In this work, we examine the possible advantages of near-term adaptation of communication-based decision switches used by the SPbeta-like group. We combine a nonlinear population model with a control theoretic approach to evaluate the relationship between a putative phage reaction norm (i.e., the probability of lysogeny as a function of arbitrium) and the near-term time horizon. We show the adaptive potential of communication-based lysis-lysogeny responses and find that optimal switching between lysis to lysogeny increases near-term fitness compared to fixed responses. We further find that plastic responses are robust to the inclusion of cellular-level stochasticity. These findings provide a principled basis to explore the long-term evolution of phage-encoded decision systems mediated by extracellular decision-signaling molecules, and the feedback between phage reaction norms and ecological context.
Fatty acid dysregulation in the anterior cingulate cortex of depressed suicides with a history of child abuse
Authors: Perlman Kelly , Chouinard-Watkins Raphaël , Tanti Arnaud , Cisbani Giulia , Orri Massimiliano , Turecki Gustavo , Bazinet Richard P , Mechawar Naguib 
Published: June 2021

AbstractChild abuse (CA) strongly increases the lifetime risk of suffering from major depression and predicts an unfavorable course for the illness. Severe CA has been associated with a specific dysregulation of oligodendrocyte function and thinner myelin sheaths in the human anterior cingulate cortex (ACC) white matter. Given that myelin is extremely lipid-rich, it is plausible that these findings may be accompanied by a disruption of the lipid profile that composes the myelin sheath. This is important to explore since the composition of fatty acids (FA) in myelin phospholipids can influence its stability, permeability, and compactness. Therefore, the objective of this study was to quantify and compare FA concentrations in postmortem ACC white matter in the choline glycerophospholipid pool (ChoGpl), a key myelin phospholipid pool, between adult depressed suicides with a history of CA (DS-CA) matched depressed suicides without CA (DS) and healthy non-psychiatric controls (CTRL). Total lipids were extracted according to the Folch method and separated into respective classes using thin-layer chromatography. FA methyl esters from the ChoGpl fraction were quantified using gas chromatography. Our analysis revealed a strong age-related decrease in most FAs, and specific effects of CA in FAs from the arachidonic acid synthesis pathway, which was further validated with RNA-sequencing data. Furthermore, the concentration of most FAs was found to decrease with age. By extending the previous molecular level findings linking CA with altered myelination in the ACC, these results provide further insights regarding white matter alterations associated with early-life adversity.
Epigenetic therapy targets the 3D epigenome in endocrine-resistant breast cancer
Authors: Achinger-Kawecka Joanna , Stirzaker Clare , Portman Neil , Campbell Elyssa , Chia Kee-Ming , Du Qian , Laven-Law Geraldine , Nair Shalima S. , Yong Aliza , Wilkinson Ashleigh , Clifton Samuel , Milioli Heloise H. , Alexandrou Sarah , Caldon C. Elizabeth , Song Jenny , Khoury Amanda , Meyer Braydon , Gee Julia M.W. , Schmitt Anthony , Wong Emily S. , Hickey Theresa E. , Lim Elgene , Clark Susan J. 
Published: June 2021

AbstractThree-dimensional (3D) epigenome remodelling is an important mechanism of gene deregulation in cancer. However, its potential as a target to overcome therapy resistance remains largely unaddressed.Here we show that FDA-approved epigenetic therapy Decitabine (5-Aza-mC) suppresses tumour growth in preclinical metastatic ER+ breast tumour xenograft models. Decitabine-induced genome-wide DNA hypomethylation results in large-scale 3D epigenome deregulation, including de-compaction of higher order chromatin structure and loss of topologically associated domain boundary insulation. Significant DNA hypomethylation at ER-enhancer elements was associated with gain in ER binding, creation of ectopic 3D enhancer-promoter interactions and concordant activation of ER-mediated transcription pathways. Importantly long-term withdrawal of epigenetic therapy partially restores methylation at ER-enhancer elements, resulting in loss of ectopic 3D enhancer-promoter interactions and associated gene repression.Our study illustrates how epigenetic therapy has potential to target ER+ endocrine-resistant breast cancer by DNA methylation-dependent rewiring of 3D chromatin interactions associated with suppression of tumour growth.
Classical swine fever virus NS5A inhibits NF-κB signaling by targeting NEMO
Authors: Li Jiaying , Yu Haixiao , Jiang Wenjin , Ma Ping , Feng Zezhong , Lu Yang , Tu Changchun , Sun Jinfu 
Published: June 2021

AbstractThe NS5A non-structural protein of classical swine fever virus (CSFV) is a multifunctional protein involved in viral genomic replication, protein translation and regulation of cellular signaling pathways, and assembly of infectious virus particles. Previous report showed that NS5A inhibited nuclear factor kappa B (NF-κB) signaling induced by poly(I:C); however, the mechanism was not elucidated. Here, we report that NS5A interacts with NF-κB essential modulator (NEMO),a regulatory subunit of the IκB kinase (IKK) complex, and that the zinc finger domain of NEMO essential for NEMO ubiquitination and IKK activation is required for the interaction of NEMO with NS5A. Viral infection or NS5A expression by itself reduced the protein level of NEMO. Mechanistic analysis revealed that NS5A mediated proteasomal degradation of NEMO. Ubiquitination assay showed that NS5A induced K27-but not K48-linked polyubiquitination of NEMO. In addition, NS5A blocked k63-linked polyubiquitination of NEMO, thereby inhibiting activation of IKK and NF-κB. These findings indicate that NS5A inhibits NF-κB signaling by mediating proteasomal degradation of NEMO and blocking k63-linked polyubiquitination of NEMO, thereby revealing a novel mechanism by which CSFV inhibits host innate immunity.ImportanceClassical swine fever (CSF) is a economically important swine viral disease leading to hemorrhagic fever and immuno-suppression. In order to successfully infect and replicate in a host cell, viruses have evolved various strategies to antagonize host innate immunity. It is known that CSFV non-structural protein Npro interacts with interferon regulatory factor 3 (IRF3) and mediates its proteasomal degradation, thereby inhibiting the production of type I interferon. However, no other mechanism by which CSFV antagonizes host innate immunity has so far been reported. Here, we show that NS5A inhibits NF-κB signaling by mediating proteasomal degradation of NEMO and by blocking k63-linked polyubiquitination of NEMO, thereby revealing a novel mechanism by which CSFV antagonizes host innate immunity.
Inhibition of N-myristoyltransferase Promotes Naive Pluripotency in Mouse and Human Pluripotent Stem Cells
Authors: Yoshida Junko , Watanabe Hitomi , Yamauchi Kaori , Nishikubo Takumi , Isotani Ayako , Ohtsuka Satoshi , Niwa Hitoshi , Akutsu Hidenori , Umezawa Akihiro , Suemori Hirofumi , Takashima Yasuhiro , Kondoh Gen , Takeda Junji , Horie Kyoji 
Published: June 2021

SUMMARYNaive and primed states are distinct states of pluripotency during early embryonic development that can be captured and converted to each other in vitro. To elucidate the regulatory mechanism of pluripotency, we performed a recessive genetic screen of homozygous mutant mouse embryonic stem cells (mESCs) and found that suppression of N-myristoyltransferase (Nmt) promotes naive pluripotency. Disruption of Nmt1 in mESCs conferred resistance to differentiation. Suppression of Nmt in mouse epiblast stem cells (mEpiSCs) promoted the conversion from the primed to the naive state. This effect was independent of Src, which is a major substrate of Nmt and is known to promote differentiation of mESCs. Suppression of Nmt in naive-state human induced pluripotent stem cells (hiPSCs) increased the expression of the naive-state marker. These results indicate that Nmt is a novel target for the regulation of naive pluripotency conserved between mice and humans.
Contamination detection and microbiome exploration with GRIMER
Authors: Piro Vitor C. , Renard Bernhard Y. 
Published: June 2021

AbstractBackgroundContamination detection is a important step that should be carefully considered in early stages when designing and performing microbiome studies to avoid biased outcomes. Detecting and removing true contaminants is challenging, especially in low-biomass samples or in studies lacking proper controls. Interactive visualizations and analysis platforms are crucial to better guide this step, to help to identify and detect noisy patterns that could potentially be contamination. Additionally, external evidence, like aggregation of several contamination detection methods and the use of common contaminants reported in the literature could help to discover and mitigate contamination.ResultsWe propose GRIMER, a tool that performs automated analyses and generates a portable and interactive dashboard integrating annotation, taxonomy and metadata. It unifies several sources of evidence to help detect contamination. GRIMER is independent of quantification methods and directly analyses contingency tables to create an interactive and offline report. Reports can be created in seconds and are accessible for non-specialists, providing an intuitive set of charts to explore data distribution among observations and samples and its connections with external sources. Further, we compiled and used an extensive list of possible external contaminant taxa and common contaminants with 210 genera and 627 species reported in 22 published articles.ConclusionGRIMER enables visual data exploration and analysis, supporting contamination detection in microbiome studies. The tool and data presented are open-source and available at:https://gitlab.com/dacs-hpi/grimer.
Reproductive skew, fitness costs, and winner-loser effects in social-dominance evolution
Authors: Leimar Olof , Bshary Redouan 
Published: June 2021

AbstractSocial hierarchies can increase reproductive skew in group-living animals. Using game theory we investigate how the opportunity for differently ranked individuals to acquire resources influences reproductive skew, costs of hierarchy formation, and winner and loser effects. Individuals adjust their aggressive and submissive behaviour through reinforcement learning. The learning is based on perceived rewards and penalties, which depend on relative fighting ability. From individualbased simulations we determine evolutionary equilibria of traits that control an individual’s learning. We examine situations that differ in the extent of monopolisation of contested resources by dominants and in the amounts of uncontested resources that are distributed independently of rank. With costly fighting, we find that stable dominance hierarchies form, such that reproductive skew mirrors the distribution of resources over ranks. Individuals pay substantial costs of interacting, in particular in high-skew situations, with the highest costs paid by intermediately ranked individuals. For cases where dominants monopolise contested resources there are notable winner and loser effects, with winner effects for high ranks and very pronounced loser effects for lower ranks. The effects are instead weak when acquired resources increase linearly with rank. We compare our results on contest costs and winner-loser effects with field and experimental observations.
Comparison of undirected frequency-domain connectivity measures for cerebro-peripheral analysis
Authors: Gross Joachim , Kluger Daniel S. , Abbasi Omid , Chalas Nikolas , Steingräber Nadine , Daube Christoph , Schoffelen Jan-Mathijs 
Published: June 2021

AbstractAnalyses of cerebro-peripheral connectivity aim to quantify ongoing coupling between brain activity (measured by MEG/EEG) and peripheral signals such as muscle activity, continuous speech, or physiological rhythms (such as pupil dilation or respiration). Due to the distinct rhythmicity of these signals, undirected connectivity is typically assessed in the frequency domain. This leaves the investigator with two critical choices, namely a) the appropriate measure for spectral estimation (i.e., the transformation into the frequency domain) and b) the actual connectivity measure. As there is no consensus regarding best practice, a wide variety of methods has been applied. Here we systematically compare combinations of six standard spectral estimation methods (comprising fast Fourier and continuous wavelet transformation, bandpass filtering, and short-time Fourier transformation) and six connectivity measures (phase-locking value, Gaussian-Copula mutual information, Rayleigh test, weighted pairwise phase consistency, magnitude squared coherence, and entropy). We provide performance measures of each combination for simulated data (with precise control over true connectivity), a single-subject set of real MEG data, and a full group analysis of real MEG data. Our results show that, overall, wppc and gcmi tend to outperform other connectivity measures, while entropy was the only measure sensitive to bimodal deviations from a uniform phase distribution. For group analysis, choosing the appropriate spectral estimation method appeared to be more critical than the connectivity measure. We discuss practical implications (sampling rate, SNR, computation time, and data length) and aim to provide recommendations tailored to particular research questions.
Oleate metabolism using kinetic 13C dilution strategy deciphered the potential role of global transcription regulator arcA in Escherichia coli
Authors: Jindal Shikha , Jyoti Poonam , Venkatesh K.V. , Masakapalli Shyam Kumar 
Published: June 2021

AbstractMicrobial metabolism of long-chain fatty acids (LCFA; > C12) is of relevance owing to their presence in various nutrient niches. Microbes have evolved to metabolize LCFA by expressing relevant genes coordinated by various transcriptional regulators. Among the global transcriptional regulators, the metabolic control conferred by arcA (aerobic respiration control) under a LCFA medium is lacking. This work is targeted to unravel the metabolic features of E.coli MG1655 and its knockout strain ΔarcA under oleate (C18:1) as a sole carbon source, providing novel insights into the flexibility of the global regulators in maintaining the cellular physiology. Owing to the availability and cost of stable isotope LCFA tracers, we adopted a novel kinetic 13C dilution strategy. This allowed us to quantify the 13C dilution rates in the amino acids that retro-biosynthetically shed light on the central metabolic pathways in actively growing cells. Our data comprehensively mapped oleate oxidization in E.coli via the pathways of β-oxidation, TCA cycle, anaplerotic and gluconeogenesis. Interestingly, arcA knockout showed expeditious growth (~60%) along with an increased oleate utilization rate (~55%) relative to the wild-type. ΔarcA also exhibited higher 13C dilution rates (> 20%) in proteinogenic amino acids than the wild-type. Overall, the study established the de-repression effect conferred by ΔarcA in E.coli, which resulted in a phenotype with reprogrammed metabolism favouring higher oleate assimilation. The outcomes suggest rational metabolic engineering of regulators as a strategy to develop smart cells for enhanced biotransformation of LCFA. This study also opens an avenue for adopting a kinetic 13C dilution strategy to decipher the cellular metabolism of a plethora of substrates, including other LCFA in microbes.
Carnivores cross irrigation canals more often through overpasses than through culverts
Authors: Azedo Rita , Ilhéu Ana , Santos Sara , Vaz Pedro G. 
Published: June 2021

ABSTRACTAs rainfall becomes scarcer or more erratic, we rely more on irrigation systems for water provision. Impacts of irrigation canals such as the barrier effect on wildlife movements are poorly documented. Although canal culverts and overpasses can be used by wildlife, little is known about their crossing patterns to guide barrier effect mitigation efforts. Over 7 years, we recorded medium-sized carnivore crossings by video-surveillance through 30 culverts and 28 overpasses in a large irrigation project in south-central Portugal. We examined the influence of the structures’ features and landscape context on the likelihood of canal crossing. Culvert crossings were positively influenced by the proportion of nearby montado, a high nature value farming system. Overpass crossings were more likely in areas away from paved roads and with more nearby wetlands. Overpasses increased the crossing rates by about 11 % relative to culverts and both were crossed more often in landscapes with evenly distributed land uses. In the project area, 20% of the montado has recently transitioned to irrigated agriculture, and wetlands have increased by 43%. It is therefore plausible that the increase in the crossing rate of overpasses relative to culverts will be accentuated. Our study produced the first evidence of a contrast in crossing rates among irrigation canal crossing structures. We have shown that the landscape can be a driver of animal crossings but irrigation projects can in turn be transformative of the landscape. Broadly, the fact that the deployment of irrigation canals may favor some land uses over others creates a conundrum that needs careful consideration when planning barrier effect mitigation interventions.
Antecedents of CSR disclosure in an emerging economy: evidence from the banking industry
Authors: de Oliveira Kleber Vasconcellos , Lustosa Paulo Roberto B. , Freire Fatima de Souza , de Carvalho Frederico A. 
Published: June 2021

PurposeThis study examines the factors which affect the adoption of corporate social responsibility (CSR) disclosure practices in line with Global Reporting Initiative (GRI) guidelines in Brazil's banking industry.Design/methodology/approachThe analysis comprised the deposits (demand and savings), fee income, employee expenses, regulatory capital (Basel ratio) and ownership structure of all Brazilian banks from 2006 to 2017. The sample totalled 1,613 firm-year observations. The authors used three binary regression models (logit, probit and complementary log-log) in order to choose the one that best fits the model proposed. The authors controlled for size, profitability, leverage and liquidity.FindingsThe main results show positive relationships between CSR reporting and both savings deposits and fee income. The authors also found that state-owned (foreign private-owned) banks have a positive (negative) relationship with probability of CSR disclosure. A negative relationship was found between CSR disclosure and regulatory capital, indicating that banks are more likely to publish GRI reports as they approach the minimum levels of the Basel ratio.Research limitations/implicationsSome banks may disclose CSR reports which do not adhere to the GRI guidelines; these were not captured in this study.Practical implicationsThe estimated model aids understanding of factors influencing CSR disclosure in the banking industry in an emerging economy, which may help bank regulators to adopt new approaches in their supervisory and regulatory roles.Originality/valueThis work is the first to document that both fee income and banks' regulatory capital are related to CSR disclosure. Furthermore, this study investigates the entire banking industry of a Latin American country over the longest and most up-to-date period the authors are aware of.