bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two types of motor inhibition after action errors in humans
Authors: Guan Yao , Wessel Jan R. 
Published: June 2022

ABSTRACTAdaptive behavior requires the ability to appropriately react to action errors. Post-error slowing of response times (PES) is one of the most reliable phenomena in cognitive neuroscience. It has been proposed that PES is partially achieved through inhibition of the motor system. However, there is no direct evidence for this link – or indeed, that the motor system is physiologically inhibited after errors altogether. Here, we used transcranial magnetic stimulation and electromyography to measure cortico-spinal excitability (CSE) across four experiments using a Simon task, in which human participants sometimes committed errors. Errors were followed by reduced CSE at two different time points, and in two different modes. Shortly after error commission (250ms) CSE was broadly suppressed – i.e., even task-unrelated motor effectors were inhibited. During the preparation of the subsequent response, CSE was specifically reduced at task-related effectors only. This latter effect was directly related to PES, with stronger CSE suppression accompanying greater PES. This suggests that PES is achieved through increased inhibitory control during post-error responses. To provide converging evidence, we then re-analyzed an openly-available EEG dataset that contained both Simon- and Stop-signal tasks using independent component analysis. We found that the same neural source component that indexed action-cancellation in the stop-signal task also showed clear PES-related activity during post-error responses in the Simon task. Together, these findings provide clear evidence that post-error adaptation is partially achieved through motor inhibition. Moreover, inhibition is engaged in two modes (first non-selective, then selective), aligning with recent multi-stage theories of error processing.
Preclinical safety evaluation of continuous UV-A lighting in an operative setting
Authors: Guenter Rachael , Zheng-Pywell Rui , Herring Brendon , Murphy Madisen , Benner Kevin , Rose J. Bart 
Published: June 2022

ABSTRACTBackgroundGermicidal ultraviolet (UV-C) light has been shown as an effective modality for disinfection in laboratory settings and in the operative room. Traditionally, short-wavelength UV-C devices, which have previously been shown to cause DNA damage, are utilized only for disinfection in pre- and post-operative settings and are not continuously active during operations. Continuous use of intraoperative UV light can potentially decrease pathogens and subsequent surgical site infections (SSIs), which arise in approximately 5-15% of operative cases. SSIs are a significant determinant of patient morbidity, readmission rates, and overall cost. Therefore, a method of UV light disinfection with a low risk of DNA damage is needed so that greater antimicrobial protection can be afforded to patients during the entirety of their surgical procedures. A new disinfection device that harnesses longer-wavelength UV-A light to disinfect the surgical field throughout the entirety of the procedure, including pre- and post-operation, has been developed.MethodsThis study aimed to determine if intraoperatively administered UV-A light was safe, as defined by the minimal presence of DNA damage and safe amounts of reflection upon medical personnel. Using in vitro models, we examined the differential impacts of UV-C and UV-A light on DNA damage and repair pathways. In a murine model, we looked at the difference in production of DNA damage photoproducts between UV-A and UV-C exposure.ResultsOur results show UV-A light does not induce a significant amount of DNA damage at the cellular or tissue level. Furthermore, a preclinical porcine study showed that surgical personnel were exposed to safe levels of UV-A irradiance from an overhead UV-A light used during an operation. The amount of UV-A transmitted through surgical personal protective equipment (PPE) also remained within safe levels.ConclusionsIn conclusion, we found that UV-A may be a safe for intraoperative use.
Locus-specific enrichment analysis of 5-hydroxymethylcytosine reveals novel genes associated with breast carcinogenesis
Authors: Ramasamy Deepa , Rao Arunagiri Kuha Deva Magendhra , Balaiah Meenakumari , Rangan Arvinden Vittal , Sundersingh Shirley , Veluswami Sridevi , Thangarajan Rajkumar , Mani Samson 
Published: June 2022

AbstractBackgroundAn imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remains elusive. In this study, we describe the landscape of 5-mC and 5-hmC and their association with breast cancer development.ResultsWe found a distinguishable global loss of 5-hmC in the localized and invasive types of breast cancer, which correlate strongly with TET expression. Genome-wide analysis revealed a unique 5-mC and 5-hmC signature in breast cancer. The differentially methylated regions (DMRs) were primarily concentrated in the proximal regulatory regions such as the promoters and UTRs, while the differentially hydroxymethylated regions (DhMRs) were densely packed in the distal regulatory regions such as the intergenic regions (>-5 kb from TSSs). Our results indicate 4809 DMRs and 4841 DhMRs associated with breast cancer. Validation of nine 5-hmC enriched loci in a distinct set of breast cancer and normal samples, positively correlated with their corresponding gene expression. The novel 5-hmC candidates such as TXNL1, CNIH3, and BNIPL implicate a pro-oncogenic role in breast cancer. Therefore, 5-hmC modified regions could be used as promising diagnostic and therapeutic markers for breast cancer.ConclusionGlobal loss of 5-hmC is associated with down-regulation of the TET 1 and TET3 genes. Genome-wide profiling has revealed a profound imbalance in the region-specific distribution of 5-mC and 5-hmC in breast cancer. Predominant 5-hmC modifications are localized at distal gene regulatory sites. Novel 5-hmC candidates associated with breast cancer have been identified. Hence, these results provide new insights in the loci-specific accumulation of 5-mC and 5-hmC which are aberrantly methylated and demethylated in breast cancer.
Whole genome-based characterization of multi-drug resistant Enterobacter and Klebsiella aerogenes isolates from Lebanon
Authors: Merhi Georgi , Amayri Sara , Bitar Ibrahim , Araj George F. , Tokajian Sima 
Published: June 2022

AbstractBackgroundEnterobacter spp. are rod-shaped Gram-negative opportunistic pathogens belonging to Enterobacterales. This study aimed at the molecular and genomic characterization of multi-drug resistant Enterobacter spp. isolates recovered from hospitalized patients in a tertiary care hospital in Lebanon.MaterialsA total of 59 Enterobacter spp. clinical isolates consisting of 41 carbapenem-resistant and 18 susceptible by E-test were included in this study. Genotypic identification through whole-genome sequencing was performed and confirmed in silico. Resistance and plasmid profiles were studied using ResFinder4.0 and Plasmid-Finder2.1. Multi-locus sequence typing (MLST) was used to determine the isolates’ clonality.ResultsANI identified and confirmed that 47 (80%) isolates were E. hormaechei, 11 (18%) were Klebsiella aerogenes and 1 (2%) was an E. cloacae. Carbapenem-resistance was detected among 41 isolates all showing an MIC90 of ≥ 32 µg/ml for ertapenem, imipenem, and meropenem. blaNDM-1 (58.5%), blaACT-16 (54%), and blaOXA-1 (54%) were the most common detected β-lactamases, while blaCTX-M-15 gene (68%) was the main detected extended-spectrum β-lactamase (ESBL) encoding gene. Chromosomal ampC gene, carbapenemase encoding genes, and porin modifications were among the detected carbapenem resistance determinants. The carbapenemase encoding genes were linked to three well-defined plasmid Inc groups, IncFII/IncFIB, IncX3, and IncL. MLST typing revealed the diversity within the studied isolates, with ST114 being the most common amongst the studied E. hormaechei.ConclusionThe spread of carbapenem-resistant isolates in clinical settings in Lebanon is a serious challenge. Screening and continuous monitoring through WGS analysis could effectively limit the dissemination of drug-resistant isolates in hospitalized patients.ImportanceDrug resistance is an increasing global public health threat that involves most disease-causing organisms and antimicrobial drugs. Drug-resistant organisms spread in healthcare settings, and resistance to multiple drugs is common. Our study demonstrated the mechanisms leading to resistance against the last resort antimicrobial agents among members of the Enterobacteriaceae family. The spread of carbapenem-resistant bacteria in clinical settings is a serious challenge. Screening and continuous monitoring could effectively limit the dissemination of drug-resistant isolates in hospitalized patients.
A patient-centric characterization of systemic recovery from SARS-CoV-2 infection
Authors: Ruffieux Hélène , Hanson Aimee L. , Lodge Samantha , Lawler Nathan G. , Whiley Luke , Gray Nicola , Nolan Tui , Bergamaschi Laura , Mescia Federica ,   CITIID-NIHR BioResource COVID-19 Collaboration, Kingston Nathalie , Bradley John R. , Holmes Elaine , Wist Julien , Nicholson Jeremy K. , Lyons Paul A. , Smith Kenneth G.C. , Richardson Sylvia , Bantug Glenn , Hess Christoph 
Published: June 2022

AbstractThe biology driving individual patient responses to SARS-CoV-2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data, covering a year post disease onset, from 215 SARS-CoV-2 infected subjects with differing disease severities. Our analyses revealed distinct “systemic recovery” profiles with specific progression and resolution of the inflammatory, immune, metabolic and clinical responses, over weeks to several months after infection. In particular, we found a strong intra-patient temporal covariation of innate immune cell numbers, kynurenine- and host lipid-metabolites, which suggested candidate immunometabolic pathways putatively influencing restoration of homeostasis, the risk of death and of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery on the patient level, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online toolhttp://shiny.mrc-bsu.cam.ac.uk/apps/covid-systemic-recovery-prediction-app, designed to test our findings prospectively.Graphical abstract
An open source plant kinase chemogenomics set
Authors: Ercoli Maria Florencia , Ramos Priscila Zonzini , Jain Rashmi , Pilotte Joseph , Dong Oliver Xiaoou , Thompson Ty , Wells Carrow I. , Elkins Jonathan M. , Edwards Aled M , Couñago Rafael M. , Drewry David H. , Ronald Pamela C. 
Published: June 2022

Abstract129 protein kinases, selected to represent the diversity of the rice (Oryza sativa) kinome, were cloned and tested for expression in E. coli. 40 of these rice kinases were purified and screened using differential scanning fluorimetry (DSF) against 627 diverse kinase inhibitors, with a range of structures and activities targeting diverse human kinases. 37 active compounds were then tested for their ability to modify primary root development in Arabidopsis. Of these, 14 compounds caused a significant reduction of primary root length and two slightly increased root elongation compared with control plants. Two inhibitory compounds bind to the predicted orthologue of Arabidopsis PSKR1, one of two receptors for PSK, a small sulfated peptide that positively controls root development. Inhibition could not be rescued by the exogenous addition of the PSK peptide, suggesting that chemical treatment may inhibit both PSKR1 and its closely related receptor PSKR2. Of the compounds acting as root growth inhibitors in Arabidopsis, six conferred the same effect in rice. Compound RAF265 (CHIR-265), previously shown to bind the human kinase BRAF (B-Raf proto-oncogene, serine/threonine kinase), also binds to nine highly conserved rice kinases tested. The binding of human and rice kinases to the same compound suggests that human kinase inhibitor sets will be useful for dissecting the function of plant kinases.
Brain injuries and complex motor learning suppress Olig2 in a subpopulation of oligodendrocyte precursor cells
Authors: Fang Li-Pao , Liu Qing , Meyer Erika , Welle Anna , Huang Wenhui , Scheller Anja , Kirchhoff Frank , Bai Xianshu 
Published: June 2022

AbstractOligodendrocyte precursor cells (OPCs) are uniformly distributed in the mammalian brain, however their function is rather heterogeneous in respect to their origin, location, receptor/channel expression and age. The basic helix-loop-helix transcription factor Olig2 is expressed in all OPCs as a pivotal determinant of their differentiation. Here, we identified a subset (2-26%) of OPCs lacking Olig2 in various brain regions including cortex, corpus callosum, CA1 and dentate gyrus. These Olig2 negative (Olig2neg) OPCs were enriched in the juvenile brain and decreased subsequently with age, being rarely detectable in the adult brain. However, the loss of this population was not due to apoptosis or microglia-dependent phagocytosis. Unlike Olig2pos OPCs, these subset cells could not be labelled for the mitotic marker Ki67. And, accordingly, BrdU was incorporated only by a three-day long-term labeling but not by a two-hour short pulse, suggesting these cells do not proliferate any more but were derived from proliferating OPCs. The Olig2neg OPCs exhibited a less complex morphology than Olig2pos ones. Olig2neg OPCs preferentially remain in a precursor stage rather than differentiating into highly branched oligodendrocytes. Changing the adjacent brain environment, e.g. by acute injuries or by complex motor learning tasks stimulated the transition of Olig2pos OPCs to Olig2neg cells in the adult. Taken together, our results demonstrate that OPCs transiently suppress Olig2 upon changes of the brain activity.Table of Contents ImageMain points: A subset of OPCs do not express Olig2, of which population peaks in the juvenile brain while wanes with age. Plastic changes of the brain by acute injuries or complex motor learning stop the expression of Olig2 in OPCs.
Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity
Authors: Sun Simón(e) D. , Levenstein Daniel , Li Boxing , Mandelberg Nataniel , Chenouard Nicolas , Suutari Benjamin S. , Sanchez Sandrine , Tian Guoling , Rinzel John , Buzsáki György , Tsien Richard W. 
Published: June 2022

SummaryNeurons use various forms of negative feedback to maintain their synaptic strengths within an operationally useful range. While this homeostatic plasticity is thought to distinctly counteract the destabilizing positive feedback of Hebbian plasticity, there is considerable overlap in the molecular components mediating both forms of plasticity. The varying kinetics of these components spurs additional inquiry into the dynamics of synaptic homeostasis. We discovered that upscaling of synaptic weights in response to prolonged inactivity is nonmonotonic. Surprisingly, this seemingly oscillatory adaptation involved transient appropriation of molecular effectors associated with Hebbian plasticity, namely CaMKII, L-type Ca2+ channels, and Ca2+-permeable AMPARs, and homeostatic elements such as calcineurin. We created a dynamic model that shows how traditionally “Hebbian” and “homeostatic” mechanisms can cooperate to autoregulate postsynaptic Ca2+ levels. We propose that this combination of mechanisms allows excitatory synapses to adapt to prolonged activity changes and safeguard the capability to undergo future strengthening on demand.
Adaptive oscillators provide a hard-coded Bayesian mechanism for rhythmic inference
Authors: Doelling Keith B. , Arnal Luc H. , Assaneo M. Florencia 
Published: June 2022

AbstractBayesian theories of perception suggest that the human brain internalizes a model of environmental patterns to reduce sensory noise and improve stimulus processing. The internalization of external regularities is particularly manifest in the time domain: humans excel at predictively synchronizing their behavior with external rhythms, as in dance or music performance. The neural processes underlying rhythmic inferences are debated: whether predictive perception relies on high-level generative models or whether it can readily be implemented locally by hard-coded intrinsic oscillators synchronizing to rhythmic input remains unclear. Here, we propose that these seemingly antagonistic accounts can be conceptually reconciled. In this view, neural oscillators may constitute hard-coded physiological priors – in a Bayesian sense – that reduce temporal uncertainty and facilitate the predictive processing of noisy rhythms. To test this, we asked human participants to track pseudo-rhythmic tone sequences and assess whether the final tone was early or late. Using a Bayesian model, we account for various aspects of participants’ performance and demonstrate that the classical distinction between absolute and relative mechanisms can be unified under this framework. Next, using a dynamical systems perspective, we successfully model this behavior using an adaptive frequency oscillator which adjusts its spontaneous frequency based on the rate of stimuli. This model better reflects human behavior than a canonical nonlinear oscillator and a predictive ramping model, both widely used for temporal estimation and prediction. Our findings suggest that an oscillator may be considered useful as a potential heuristic for a rhythmic prior in the Bayesian sense. Together, the results show that adaptive oscillators provide an elegant and biologically plausible means to subserve (bayesian) rhythmic inference, thereby reconciling numerous empirical observations and a priori incompatible frameworks for temporal inferential processes.
A novel fully-automated system for lifelong continuous phenotyping of mouse cognition and behaviour
Authors: Ho Hinze , Kejzar Nejc , Sasaguri Hiroki , Saito Takashi , Saido Takaomi C. , De Strooper Bart , Bauza Marius , Krupic Julija 
Published: June 2022

AbstractComprehensive ethologically-relevant behavioural phenotyping in rodent experiments is essential for deciphering the neural basis of animal cognition. Automated home-cage monitoring systems present a valuable tool to fulfil this need. However, they often involve complex animal training routines, water or food deprivation, and probe a limited range of behaviours. Here, we present a new fully automated AI-driven home-cage system for cognitive and behavioural phenotyping in mice. The system incorporates spontaneous alternation T-maze, novel-object recognition and object-in-place recognition tests combined with monitoring of an animal’s position, water consumption, quiescence and locomotion patterns, all carried out continuously and simultaneously in an unsupervised fashion over long periods of time. Mice learnt the tasks rapidly without any need for water or food restrictions. We applied ethomics approach to show that combined statistical properties of multiple behaviours can be used to discriminate between mice with hippocampal, medial entorhinal and sham lesions and accurately predict genotype of Alzheimer’s disease mouse models on an individual animal level, surpassing the performance of several gold standard cognitive tests. This technology could enable large-scale behavioural screening for genes and neural circuits underlying spatial memory and other cognitive processes.
Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia
Authors: Liu Sanzhen , Lin Guifang , Ramachandran Sowmya R. , Cruppe Giovana , Cook David , Pedley Kerry F. , Valent Barbara 
Published: June 2022

ABSTRACTGlobal wheat production is seriously threatened by the filamentous fungal pathogen, Magnaporthe oryzae, causing wheat blast disease. The pathogen was first identified in South America and recently spread across continents to Bangladesh (South Asia) and Zambia (South-central Africa). M. oryzae strains closely related with a South American field isolate B71 was found to have caused the wheat blast outbreaks in South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Using an improved reference genome for B71 and whole genome sequences of isolates from Bangladesh, Zambia, and South America, we found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates. Structural variation analysis using whole genome short-read sequencing data indicate all isolates closely related to B71 maintained at least one supernumerary mini-chromosome and, interestingly, some Zambian isolates contain more than one mini-chromosome. Long-read sequencing and de novo genome assemblies of two Zambian isolates show that both contain a mini-chromosome similar to the B71 mini-chromosome, although pervasive structural variation exists among them. Genome assemblies also provide evidence that one Zambian isolate carries an additional mini-chromosome that is highly divergent from the B71 mini-chromosome. Our findings show that while the core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome during the multiple introductions, and the rapid sequence and structural variation suggests the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.
Simplified Drainless Outpatient Female-to-Male Gender-Affirming Bilateral Mastectomy
Authors: Knudson Sean A. , DeLeon Ashley , Crane Curtis N. , Santucci Richard A. 
Published: June 2022

AbstractPurposeFemale-to-male gender-affirming top surgery is growing in demand. We ventured to further improve double-incision free nipple graft bilateral mastectomy by utilizing a streamlined method of eliminating dead space and abandoning the practice of postoperative drain placement.MethodsPatients with gender dysphoria and who underwent streamlined gender-affirming top surgery without drain placement were retrospectively reviewed from August 2017 to June 2020. A literature review was conducted to identify comparative studies with historical complication data. Patient outcomes were analyzed against this aggregated data.ResultsOne-hundred and seven patients underwent 214 simplified double incision free nipple graft bilateral mastectomies in an outpatient surgery center. Mean patient age was 27.2 ± 10.4 years. The overall complication rate was 13.1 percent. Hematoma occurred in 2 patients (1.9%). Seroma occurred in 10 patients (9.3%). Wound dehiscence occurred in 2 patients (1.9%). Elective revision rate was 3/107 (2.8%). One patient had acute reoperation due to major hematoma (0.9%). Compared with eleven studies of pooled historical outcomes of patients with drain placement, analysis revealed the drainless group had significantly higher rates of seroma (p = 0.003353), but significantly lower rates of revision (p = 1.37×10−12). Aggregation of our data with two past drainless studies was compared to the eleven drain inclusive studies, revealing significantly lower rates of hematoma (p = 0.001069), nipple areola complex necrosis (p = 0.01034), and revision (p = 2.20×10−16).ConclusionSimplified, drainless, outpatient double incision free nipple graft bilateral mastectomy can be performed with comparable outcomes to historical data.