bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the functional role of gamma synchronization in the retinogeniculate system of the cat
Authors: Neuenschwander Sergio , Rosso Giovanne , Branco Natalia , Freitag Fabio , Tehovnik Edward J. , Schmidt Kerstin E. , Baron Jerome 
Published: July 2022

AbstractFast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies carried out under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multi-electrode recordings of spiking activity in the retina and the LGN of the cat, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were non-oscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent upon halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.
Muscle synergies are flexibly recruited during gait pattern exploration using motor control-based biofeedback
Authors: Spomer Alyssa M. , Yan Robin Z. , Schwartz Michael H. , Steele Katherine M. 
Published: July 2022

ABSTRACTUnderstanding how the central nervous system coordinates diverse motor outputs has been a topic of extensive investigation. While it is generally accepted that a small set of synergies underlies many common activities, such as walking, whether synergies are equally robust across a broader array of gait patterns or can be flexibly modified remains unclear. Here, we evaluated the extent to which synergies changed as nondisabled adults (n = 14) explored gait patterns using custom biofeedback. Secondarily, we used Bayesian Additive Regression Trees to identify factors which were predictive of synergy modulation. Participants performed 41.1 ± 8.0 gait patterns using biofeedback, during which synergy recruitment changed depending on the type and magnitude of gait pattern modification. Specifically, a consistent set of synergies was recruited to accommodate small deviations from baseline, but additional synergies emerged for larger gait changes. Synergy complexity was similarly modulated; complexity decreased for 82.6% of the attempted gait patterns, however, distal gait mechanics were highly predictive of these changes. In particular, greater ankle dorsiflexion moments and knee flexion through stance, as well as greater knee extension moments at initial contact corresponded to a reduction in synergy complexity. Taken together, these results suggest that the central nervous system preferentially adopts a low-dimensional, largely invariant control strategy, but can modify that strategy to produce diverse gait patterns. Beyond improving understanding of how synergies are recruited during gait, study outcomes may also help identify parameters that can be targeted with interventions to alter synergies and improve motor control following neurological injury.
To praise or to blame? Neural signals predict divergent responses to moral hypocrisy
Authors: Liu Jinting , Yang Jiamiao , Cui Fang 
Published: July 2022

AbstractMoral hypocrisy is common in society and could be discouraged if observers always respond negatively. Understanding the observers’ responses to moral hypocrisy is critical for promoting genuine morality. This study took the perspective from the observers and compared their behavioral and neural responses to moral hypocrisy versus clear moral/immoral acts. Behaviorally, we found that claiming to help but avoiding the cost of help (i.e., moral hypocrisy) was endorsed as more moral than rejecting to help and even received monetary praise from 40% of observers. Neurally, moral hypocrisy versus clear moral acts elicited reduced responses in the reward system (e.g., ventromedial prefrontal cortex) and increased responses in regions responsible for disgust (e.g., anterior insula). The neural signals together with the interplay to the mentalizing network (e.g., temporoparietal junction) predicted divergent responses, even five months later. Our findings provide behavioral and neural accounts of how hypocrisy is perceived and why it prevails.Significance StatementFrom the perspective of a third-party observer, this study showed that moral hypocrisy is indeed deceptive and induces observers’ divergent responses of praise or blame.Claiming to help but avoiding the cost of help (i.e., moral hypocrisy) was considered more moral than rejecting to help and even received monetary praise from 40% of observers.Using fMRI, this study revealed that the divergent behavioral responses to moral hypocrisy could be predicted and classified by the activations of the reward system (e.g., ventromedial prefrontal cortex) and regions responsible for disgust (e.g., anterior insula) as well as the functional connectivity with the mentalizing network (e.g., right temporoparietal junction), even five months later.
A phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis (The LASER-TBM Trial)
Authors: Davis Angharad G , Wasserman Sean , Stek Cari , Maxebengula Mpumi , Liang C. Jason , Stegmann Stephani , Koekemoer Sonya , Jackson Amanda , Kadernani Yakub , Bremer Marise , Daroowala Remy , Aziz Saalikha , Goliath Rene , Sai Louise Lai , Sihoyiya Thandi , Denti Paolo , Lai Rachel PJ , Crede Thomas , Naude Jonathan , Szymanski Patryk , Vallie Yakoob , Banderker Ismail Abbas , Moosa Muhammed S , Raubenheimer Peter , Candy Sally , Offiah Curtis , Wahl Gerda , Vorster Isak , Maartens Gary , Black John , Meintjes Graeme , Wilkinson Robert J 
Published: July 2022

ABSTRACTBackgroundDrug regimens which include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in Tuberculous Meningitis (TBM). Safety data on their use in combination and in the context of HIV is needed to inform clinical trial design.MethodsWe conducted a phase 2 open-label parallel-design RCT to assess safety of high-dose rifampicin, linezolid and aspirin in HIV-associated TBM. Participants were randomised (1.4:1:1) to three treatment arms (arm 1, standard of care (SOC); arm 2 SOC + additional rifampicin (up to 35mg/kg/day)) + linezolid 1200mg/day reducing after 28/7 to 600mg/day; arm 3, as per arm 2 + aspirin 1000mg/day) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed.Results52 participants were randomised. 59% had mild disease (MRC Grade 1) vs 39% (Grade 2) vs 2% (Grade 3). 33% of participants had microbiologically-confirmed TBM; vs 41% ‘possible’ or 25% ‘probable’. AESI or death occurred in 10/16 (arm 3) vs 4/14 (arm 2) vs 6/20 (arm 1) (p=0.083). The cumulative proportion of AESI or death (Kaplan-Meier method) demonstrated worse outcomes in arm 3 vs arm 1 (p=0.04), however only one event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (Modified Rankin Scale) at day 56 between the three arms.ConclusionsHigh-dose rifampicin and adjunctive linezolid can safely be added to SOC in HIV-associated TBM. Larger studies are required to evaluate whether potential toxicity associated with these interventions, particularly aspirin, is outweighed by mortality or morbidity benefit.SUMMARYIn this phase 2a randomised control trial we demonstrate that high-doserifampicin and adjunctive linezolid is safe in adult HIV-associated tuberculous meningitis. Larger studies are required to evaluate potential toxicity with aspirin, in relation to benefit on morbidity and mortality.
Prediction of celiac disease associated epitopes and motifs in a protein
Authors: Tomer Ritu , Patiyal Sumeet , Dhall Anjali , Raghava Gajendra P. S. 
Published: July 2022

AbstractCeliac disease (CD) is an autoimmune gastrointestinal disorder which causes immune-mediated enteropathy against gluten. The gluten immunogenic peptides have the potential to trigger immune responses which leads to damage the small intestine. HLA-DQ2 and HLA-DQ8 are major alleles that bind to epitope/antigenic region of gluten and induce celiac disease. There is a need to identify CD associated epitopes in protein-based foods and therapeutics. In addition, prediction of CD associated epitope/peptide is also required for developing antigen-based immunotherapy against celiac disease. In this study, computational tools have been developed to predict CD associated epitopes and motifs. Dataset used in this study for training, testing and evaluation contain experimentally validated CD associated and non-CD associate peptides. Our analysis support existing hypothesis that proline (P) and glutamine (Q) are highly abundant in CD associated peptides. A model based on density of P&Q in peptides has been developed for predicting CD associated which achieve maximum AUROC 0.98. We discovered CD associated motifs (e.g., QPF, QPQ, PYP) which occurs specifically in CD associated peptides. We also developed machine learning based models using peptide composition and achieved maximum AUROC 0.99. Finally, we developed ensemble method that combines motif-based approach and machine learning based models. The ensemble model-predict CD associated motifs with 100% accuracy on an independent dataset, not used for training. Finally, the best models and motifs has been integrated in a web server and standalone software package “CDpred”. We hope this server anticipate the scientific community for the prediction, designing and scanning of CD associated peptides as well as CD associated motifs in a protein/peptide sequence (https://webs.iiitd.edu.in/raghava/cdpred/).Key PointsCeliac disease is one of the prominent autoimmune diseasesGluten immunogenic peptides are responsible for celiac diseaseMapping of celiac disease associated epitopes and motifs on a proteinsIdentification of proline and glutamine rich regionsA web server and software package for predicting CD associate peptidesAuthor’s BiographyRitu Tomer is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Sumeet Patiyal is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Anjali Dhall is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Soil bacterial and fungal communities show within field heterogeneity that varies by land management and distance metric
Authors: Seaton Fiona M. , Griffiths Rob I. , Goodall Tim , Lebron I , Norton Lisa R. 
Published: July 2022

AbstractIncreasing interest in the use of microbial metrics to evaluate soil health raises the issue of how fine-scale heterogeneity can affect microbial community measurements. Here we analyse bacterial and fungal communities of over 100 soil samples across 17 pasture farms and evaluate beta diversity at different scales. We find large variation in microbial communities between different points in the same field, and if Aitchison distance is used we find that within-field variation is as high as between-farm variation. However, if Bray-Curtis or Jaccard distance are used this variation is partially explained by differences in soil pH and vegetation and is higher under mob grazing for fungi. Hence, field scale variation in microbial communities can impact the evaluation of soil health.
Deciphering structural asymmetry of the habenula in the human brain
Authors: Abuduaini Yilamujiang , Pu Yi , Thompson Paul M. , Kong Xiang-Zhen 
Published: July 2022

AbstractFunctional laterality of the habenula has been suggested in both animal models and the humans. Understanding this evolutionarily conserved brain feature is of fundamental importance and has been attracting attention due to its potential role in human cognition and a variety of neuropsychiatric disorders such as depression and schizophrenia. Deciphering structural asymmetry of the human habenula remains to be challenging. Here, we present a large-scale meta-analysis of the left-right differences in the habenular volume in the human brain with 52 datasets (N = 1,427), and also assessed the potential moderating effects of the sampling variability and other methodological factors. Results showed significant heterogeneity in the left-right differences across the datasets, which seems to be mainly due to different MRI scanners and segmentation approaches used. While little evidence was found for the volume asymmetry across all the datasets, the most pronounced and significant leftward asymmetry was found in the datasets from 3 T scanners and when using manual segmentation approaches. We did not find significant disorder-related differences relative to healthy controls in either the left-right asymmetry or the unilateral volume. This study not only provides useful data for future studies of brain imaging and methodological developments related to precision habenula measurements, but also helps to understand potential roles of habenular laterality in health and disorders.
Anticipation of appetitive operant action induces sustained dopamine release in the nucleus accumbens
Authors: Goedhoop Jessica , Arbab Tara , Willuhn Ingo 
Published: July 2022

ABSTRACTThe mesolimbic dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. These implications are commonly investigated in either Pavlovian or operant reinforcement paradigms, where only the latter requires instrumental action. To parse contributions of reward- and action-related information to dopamine signals, we directly compared the two paradigms: rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. Task conditions were identical with the exception of the operant-lever response requirement. Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire five-second cue presentation (preceding the required action). This dopamine “ramp” was unaffected by probabilistic reward delivery, occurred exclusively prior to operant actions, and was not related to task performance or task acquisition, as it persisted throughout the two-week daily behavioral training. Instead, the ramp flexibly increased in duration with longer cue presentation, seemingly modulating the initial cue-onset triggered dopamine release (i.e., the reward-prediction error (RPE) signal), as both signal amplitude and sustain diminished when reward timing was made more predictable. Thus, our findings suggest that RPE and action components of dopamine release can be differentiated temporally into phasic and ramping/sustained signals, respectively, where the latter depends on the former and presumably reflects the anticipation or incentivization of appetitive action, conceptually akin to motivation.Significance StatementIt is unclear whether the components of dopamine signals that are related to reward-associated information and reward-driven approach behavior can be separated. Most studies investigating the dopamine system utilize either Pavlovian or operant conditioning, which both involve the delivery of reward and necessitate appetitive approach behavior. Thus, used exclusively, neither paradigm can disentangle the contributions of these components to dopamine release. However, by combining both paradigms in the same study, we find that anticipation of a reward-driven operant action induces a modulation of reward-prediction-associated dopamine release, producing so-called “dopamine ramps”. Therefore, our findings provide new insight into dopamine ramps, and suggest that dopamine signals integrate reward and appetitive action in a temporally distinguishable, yet dependent, manner.
Integrated Analysis of T cell Repertoire and Transcriptome Identifies Mechanisms of Regulatory T cell (Treg) Suppression of Acute Graft-versus-Host-Disease
Authors: Lohmeyer Juliane K. , Hirai Toshihito , Turkoz Mustafa , Buhler Stephane , Ramos Teresa Lopes , Köhler Natalie , Baker Jeanette , Ji Xuhuai , Villard Jean , Chalandon Yves , Simonetta Federico , Negrin Robert S. 
Published: July 2022

AbstractCD4+FOXP3+ regulatory T cells have demonstrated efficacy in graft-versus-host disease (GvHD) prevention and treatment. Preclinical and clinical studies indicate that Treg are able to protect from GvHD without interfering with the graft-versus-tumor (GvT) effect of hematopoietic cell transplantation (HCT), although the underlying molecular mechanisms are largely unknown. To elucidate Treg suppressive function during in vivo suppression of acute GvHD, we performed paired T cell receptor (TCRα, TCRβ genes) repertoire sequencing and RNA sequencing analysis on conventional T cells (Tcon) and Treg before and after transplantation in an MHC major-mismatch mouse model of HCT. We show that both Treg and Tcon underwent clonal restriction and that Treg did not interfere with the activation of alloreactive Tcon clones and the breadth of their TCR repertoire, however, markedly suppressed their expansion. Transcriptomic analysis revealed that Treg predominantly affected the transcriptome of CD4 Tcon and to a lesser extent of CD8 Tcon, modulating the transcription of genes encoding pro- and anti-inflammatory molecules as well as enzymes involved in metabolic processes, inducing a switch from glycolysis to oxidative phosphorylation. Finally, Treg did not interfere with the induction of gene sets involved in the GvT effect. Our results shed light into the mechanisms of acute GvHD suppression by Treg and will support the clinical translation of this immunoregulatory approach.Key Points- Regulatory T cells modulate conventional T cells transcriptome during GvHD suppression by affecting several, non-redundant pathways.- Regulatory T cells undergo activation and clonal expansion during GvHD suppression.
Widespread of horizontal gene transfer events in eukaryotes
Authors: Li Kun , Yan Fazhe , Duan Zhongqu , Adelson David L. , Wei Chaochun 
Published: July 2022

SummaryHorizontal gene transfer (HGT) is the transfer of genetic material between distantly related organisms. While most genes in prokaryotes can be horizontally transferred, HGT events in eukaryotes are considered as rare, particularly in mammals. Here we reported the identification of HGT regions (HGTs), which are genomic sequence fragments indicating the occurrence of HGT events, in human, mouse, cow, lizard, frog, zebrafish, fruit fly, nematode, Arabidopsis and yeast. By comparing the genomes of these 10 representative eukaryotes with 1,496 eukaryotic genomes, 16,098 bacteria and 11,695 viruses, we found between 10 and 243 non-redundant HGTs per species, and most of these HGTs were previously unknown. These HGTs have transformed their host genomes with various numbers of copies and have impacted hundreds, even thousands of genes. We listed several examples of HGTs and proposed some possible routes that HGT events occurred. Further analysis showed that the majority of the 1,496 eukaryotes with full length genome sequences also contain HGTs. Our findings reveal that HGT is widespread in eukaryotic genomes, and HGT is a ubiquitous driver of genome evolution for eukaryotes.
Modifying the trajectory of epicardial leads can substantially reduce MRI-induced RF heating in pediatric patients with a cardiac implantable electronic device
Authors: Jiang Fuchang , Bhusal Bhumi , Nguyen Bach , Monge Michael , Webster Gregory , Kim Daniel , Bonmassar Giorgio , Popsecu Andrada R. , Golestanirad Laleh 
Published: July 2022

AbstractPurposeInfants and children with congenital heart defects, inherited arrhythmia syndromes, and congenital cardiac conduction disorders often receive epicardial implantable electronic devices. Unfortunately, once an epicardial device is implanted, the patient is no longer eligible to receive MRI exams due to an elevated risk of RF heating. Here we show that a simple modification in the trajectory of epicardial leads can substantially and reliably reduce RF heating during MRI at 1.5 T, with benefits extending to abandoned leads.MethodsElectromagnetic simulations were performed to assess RF heating of two common epicardial lead trajectories exhibiting different degrees of coupling with MRI incident electric fields. Experiments in anthropomorphic phantoms implanted with commercial cardiac implantable electronic devices (CIEDs) confirmed the findings.ResultsSimulations of an epicardial lead with a trajectory where the excess length of the lead was looped and placed on the anterior surface of the heart showed a 9-fold reduction in 0.1g-averaged SAR compared to the lead with excess length looped on the inferior surface of the heart. Repeated experiments with a commercial epicardial device confirmed the results, showing a 16-fold reduction in the average temperature rise for fully implanted systems with leads following low-SAR trajectories, and a 20-fold reduction in RF heating on an abandoned lead.ConclusionSurgical modification of epicardial lead trajectory can substantially reduce RF heating at 1.5 T, with benefits extending to abandoned leads.
Antithymocyte globulin inhibits CD8+ T cell effector functions via the paracrine induction of PDL-1 on monocytes
Authors: Copic Dragan , Direder Martin , Klas Katharina , Bormann Daniel , Laggner Maria , Ankersmit Hendrik Jan , Mildner Michael 
Published: July 2022

AbstractAntithymocyte globulins (ATG) are T cell depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with high risk of graft rejection. Previously described effects besides depletion of T cells suggest additional modes of action and identified further cellular targets. Here, we examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG on a single cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Analysis of the paracrine factors present in plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines including Interferon-γ (IFN-γ). Furthermore, we identify an increase of surface expression of programmed cell death 1 ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we show that this induction is dependent on activation of JAK/STAT signaling via binding of IFN-γ to Interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrate that the modulation of the immune-regulatory axis of Programmed cell death protein 1 (PD1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including proliferation and granzyme B release of activated T cells. Together our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.One Sentence SummaryATG increases PDL-1 on CD14+-monocytes and inhibits T cell effector functions.