Biology subjects

Nagy, T.

Publications and source records attributed to Nagy, T..

8 recordsLinked to original sources

bioRxiv2024

The effect of unilateral hand muscle contraction on frontal alpha asymmetry and inhibitory control in intrinsic reward contexts, a randomized controlled trial

Challenged inhibitory control has been implicated in various disorders, including addiction. Previous research suggests that asymmetry of frontal brain activity, indexed by frontal alpha asymmetry (FAA), is associated with inhibitory control and could be a target for neuromodulatory intervention. Some evidence suggests that unilateral muscle contraction (UMC) can modulate FAA; however, experimental evidence is scarce. We conducted a randomized controlled trial, with 65 participants (Mage = 26.6; SD = 7.4), 37 of whom were females. We collected EEG data to calculate FAA and assessed inhibitory performance using the Stop Signal Task (SST) in neutral and intrinsic reward (palatable food) conditions, both before and after a unilateral left-hand muscle contraction task aimed at enhancing right relative to left frontal activity. We found a significant main effect of group on FAA. Specifically, UMC group was associated with higher right relative to left frontal activity, associated with resting state inhibitory activity. Event-related potential analyses revealed a significant dissociation between the stop N2 and stop P3 components as a function of time. More specifically, as time progressed, the stop N2 was enhanced, while the stop P3 was reduced. These results did not lead to observable changes in the behavioral index of stopping. In conclusion, UMC did not affect any behavioral and brain activity indices. There is some indication of a potential effect on FAA. However, this effect could reflect coincidental differences in trait FAA. Our findings provide new insights into the temporal dynamics of brain activity indices of inhibitory control.

neuroscience↗

bioRxiv2023

No Evidence of Transcranial Direct Current Stimulation on Frontal Brain Asymmetry and Inhibitory Control: A Randomized Controlled Trial

Prior research links self-regulation failure to psychiatric disorders. While the left and right dorsolateral prefrontal cortices are associated with distinct components of self-regulation--approach and inhibitory systems, respectively--existing measures are considered indirect. Our preregistered study explored frontal alpha asymmetry (FAA) as a potential biomarker for self-regulation. We explored whether the assumed effects of transcranial direct current stimulation (tDCS) on behavioral and brain activity indices of inhibitory control are mediated through changes in FAA. We used a randomized controlled sham-feedback design with 65 healthy humans (46 females). Before and after 2 mA anodal tDCS on the right frontal site, we collected resting-state EEG data to assess FAA scores, and participants also completed a stop signal task with neutral and intrinsic reward (food) conditions. The tDCS had no impact on FAA or any behavioral or neural indices of inhibitory control. However, event-related potential analyses revealed a correlation between inhibitory brain activity in the reward condition and trait FAA. Higher right relative to left frontal brain activity was linked to lower early-onset inhibitory activity, possibly originating from the inferior Frontal Gyrus, but correlated with higher late-onset inhibitory control, presumably originating from the superior Frontal Gyrus. While tDCS yielded unexpected outcomes in FAA and inhibitory control metrics, we found an interesting dissociation regarding the lateralization of frontal brain activity and early and late onset inhibitory brain activity.

neuroscience↗

bioRxiv2023

The effect of transcranial direct current stimulation of the dorsolateral prefrontal cortex on behavioral and brain activity indices of visuospatial attention in intrinsic reward contexts

Research indicates a connection between frontal brain activity asymmetry and self-regulation, particularly, approach and inhibitory tendencies. However, the underlying brain mechanism remains unclear. Our preregistered study used transcranial direct current stimulation (tDCS) to overcome limitations in prior correlational studies, investigating the link between frontal alpha asymmetry (FAA), a potential neuromarker and a treatment target for relevant psychiatric disorders, and the behavioral and brain activity components related to approach and avoidance tendencies, as observed in a visuospatial cueing (VSC) paradigm. We utilized a randomized sham-controlled design with 65 healthy participants. Participants resting-state EEG was recorded to calculate FAA scores before and after 2 mA anodal tDCS to the right frontal site. They also completed a VSC task with neutral and intrinsic reward-associated (food) conditions. Results indicated no impact of tDCS on FAA or behavioral attentional bias/disengagement. Surprisingly, secondary analyses revealed tDCS enhancing attentional bias for rewards, as seen in enhanced Late Directing Attention Positivity and P1 effect. However, these effects did not translate into observable behavioral changes. The observed effects are consistent with a noradrenergic mechanism rather than asymmetry of brain activity.

neuroscience↗

bioRxiv2021

Structure, immunogenicity, and conformation-dependent receptor binding of the post-fusion human metapneumovirus F protein

Human metapneumovirus (hMPV) is an important cause of acute viral respiratory infection. As the only target of neutralizing antibodies, the hMPV fusion (F) protein has been a major focus for vaccine development and targeting by drugs and monoclonal antibodies (mAbs). While X-ray structures of trimeric pre-fusion and post-fusion hMPV F proteins from genotype A, and monomeric pre-fusion hMPV F protein from genotype B have been determined, structural data for the post-fusion conformation for genotype B is lacking. We determined the crystal structure of this protein and compared the structural differences of post-fusion hMPV F between hMPV A and B genotypes. We also assessed the receptor binding properties of the hMPV F protein to heparan sulfate. A library of heparan sulfate (HS) oligomers was used to verify the HS binding activity of hMPV F, and several compounds showed binding to predominantly pre-fusion hMPV F, but had limited binding to post-fusion hMPV F. Furthermore, mAbs to antigenic sites III and the 66-87 intratrimeric epitope block heparan binding. In addition, we evaluated the efficacy of post-fusion hMPV B2 F protein as a vaccine candidate in BALB/c mice. Mice immunized with hMPV B2 post-fusion F protein showed a balanced Th1/Th2 immune response and generated neutralizing antibodies against both subgroup A2 and B2 hMPV strains, which protected the mice from hMPV challenge. Antibody competition analysis revealed the antibodies generated by immunization target two known antigenic sites (III and IV) on hMPV F. Overall, this study provides new characteristics of the hMPV F protein informative for vaccine and therapy development. ImportanceHuman metapneumovirus (hMPV) is an important cause of viral respiratory disease. In this paper, we report the X-ray crystal structure of the hMPV fusion (F) protein in the post-fusion conformation from genotype B. We also assessed binding of the hMPV F protein to heparin and heparan sulfate, a previously reported receptor for the hMPV F protein. Furthermore, we determined the immunogenicity and protective efficacy of post-fusion hMPV B2 F protein, which is the first study using a homogenous conformation of the protein. Antibodies generated in response to vaccination give a balanced TH1/TH2 response and target two previously discovered neutralizing epitopes.

microbiology↗

bioRxiv2020

Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats.

Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (ED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a high ED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. The aim of the current study was to investigate the effect of long-term (6 months) consumption of high ED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the Nucleus of the Solitary Tract, and the development of systemic inflammation. Male Sprague-Dawley rats were fed a low ED diet (5% fat) for two weeks and then switched to a high ED (45% fat) diet for 26 weeks. Twenty-four hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, and 1, 4, 8, and 26 weeks after introduction of the high ED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were used for 16S rRNA genome sequencing. High ED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after four weeks of high ED diet. We further observed changes in the serum cytokine profile after 26 weeks of high ED feeding. These data suggest that microbiota dysbiosis is the first response of the organism to high ED diets and this, in turn, detrimentally affects liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers.

physiology↗

bioRxiv2019

ChIPSummitDB: A ChIP-seq-based database of human transcription factor binding sites and the topological arrangements of the proteins bound to them

ChIP-Seq reveals genomic regions where proteins, e.g. transcription factors (TFs) interact with DNA. A substantial fraction of these regions, however, do not contain the cognate binding site for the TF of interest. This phenomenon might be explained by protein-protein interactions and co-precipitation of interacting gene regulatory elements. We uniformly processed 3,727 human ChIP-Seq data sets and determined the cistrome of 292 TFs, as well as the distances between the TF binding motif centers and the ChIP-Seq peak summits. ChIPSummitDB enables the analysis of ChIP-Seq data using multiple approaches. The 292 cistromes and corresponding ChIP-Seq peak sets can be browsed in GenomeView. Overlapping SNPs can be inspected in dbSNPView. Most importantly, the MotifView and PairShiftView pages show the average distance between motif centers and overlapping ChIP-Seq peak summits and distance distributions thereof, respectively. In addition to providing a comprehensive human TF binding site collection, the ChIPSummitDB database and web interface allows for the examination of the topological arrangement of TF complexes genome-wide. ChIPSummitDB is freely accessible at http://summit.med.unideb.hu/summitdb/. The database will be regularly updated and extended with the newly available human and mouse ChIP-Seq data sets.

bioinformatics↗

bioRxiv2017

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of two distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Our analyses discern two biologically distinct variants of anaplastic meningioma with potential prognostic and therapeutic significance.

genomics↗

bioRxiv2017

CRISPulator: A Discrete Simulation Tool For Pooled Genetic Screens

The rapid adoption of CRISPR technology has enabled biomedical researchers to conduct CRISPR-based genetic screens in a pooled format. The quality of results from such screens is heavily dependent on optimal screen design, which also affects cost and scalability. We present CRISPulator, a computational tool that simulates the impact of screen parameters on the robustness of screen results, thereby enabling users to build intuition and insights that will inform their experimental strategy. We illustrate its power by deriving non-obvious rules for optimal screen design.

bioinformatics↗