Biology subjects

Ebrahimi, M.

Publications and source records attributed to Ebrahimi, M..

17 recordsLinked to original sources

bioRxiv2026

Divergence in neurodivergent brains: mapping the relationship between developmental trajectories in functional connectivity and clinical outcomes

Brain network development differs between neurodivergent (ND) and neurotypical (NT) youth, but its developmental trajectory, and relationship to clinical outcomes, remains unclear. We examined age-related changes in functional network connectivity and clinical symptoms in 861 participants (5-21 years) from the Healthy Brain Network, including NT youth and those with Neurodevelopmental Disorders (NDDs) and generalized anxiety disorder (GAD). Functional connectivity during movie-watching was modeled using generalized additive models across eight large-scale networks to characterize nonlinear developmental trajectories. Divergence in connectivity profiles between ND and NT groups first emerged during late childhood and were largest during adolescence. Importantly, divergence in connectivity patterns followed a similar trajectory path, but preceded, divergence in clinical outcomes. These findings identify adolescence as a sensitive period when differences in patterns of brain activity and clinical differences become increasingly pronounced, highlighting a potential window for targeted intervention.

neuroscience↗

bioRxiv2026

Integrated gene-catalog and genome-resolved metagenomics reveal taxonomic and metabolic differences in the gut microbiome in irritable bowel syndrome

Background: Irritable bowel syndrome is a common gastrointestinal disorder with heterogeneous symptoms and incompletely understood pathophysiology. Gut microbiome dysbiosis has been repeatedly associated with IBS, but the extent to which taxonomic changes are accompanied by gene-level and genome-resolved differences in microbial functional potential and inferred microbial community structure remains unclear. Results: We conducted a case-control shotgun metagenomic study of stool samples from patients with IBS and healthy controls. Taxonomic profiling identified distinct IBS associated compositional patterns, including enrichment of Klebsiella pneumoniae and Streptococcus parasanguinis and depletion of SCFA-associated taxa such as Phascolarctobacterium and Faecalibacterium prausnitzii. Overall microbial community composition differed between IBS and healthy controls. Assembly-based analysis generated a cohort-specific catalog of 934,495 nonredundant microbial genes. Functional profiling identified differences in carbohydrate-active enzyme families involved in dietary and host-derived glycan metabolism. Genome-resolved analysis recovered 154 nonredundant high-quality metagenome-assembled genomes and identified distinct taxonomic patterns, including HC associated Bifidobacterium longum and IBS associated Dialister invisus, CAG-177 sp003538135, and CAG-568 sp000434395. Metabolic analysis of the recovered genomes further revealed IBS associated enrichment of pathways related to fatty acid biosynthesis and elongation, de novo purine biosynthesis, and histidine degradation. Together, these findings demonstrate that IBS-associated microbiome differences extend beyond community composition to gene-level and genome-resolved functional potential. Conclusions: This study provides a multilayered view of the IBS gut microbiome by integrating read-based taxonomic profiling, a cohort-specific microbial gene catalog, functional annotation, genome-resolved reconstruction, and metabolic-module analysis. IBS was characterized by depletion of SCFA-associated taxa, enrichment of facultative anaerobic and opportunistic taxa, altered representation of carbohydrate-active enzyme families, and distinct genome-resolved metabolic patterns. The convergence of taxonomic, gene-catalog, and MAG-level findings highlights coordinated differences in microbial composition and encoded metabolic potential in IBS and identifies candidate microbial populations and functions for validation in larger cohorts and targeted mechanistic studies.

microbiology↗

bioRxiv2025

In-cell structure of a LINC complex reveals the molecular basis for membrane remodelling and head-to-tail coupling in sperm cells

In eukaryotic cells, LINC complexes physically bridge the two nuclear membranes to cytoskeletal filaments, transmitting mechanical forces to the nucleus. Due to their dynamic and membrane-embedded nature, their architecture in native membranes has been hitherto elusive. Here, we combine in-situ electron cryo-tomography, AlphaFold predictions and molecular dynamics simulations to determine the sub-nanometer-resolution architecture of the trimeric [~]130 kDa SUN5-Nesprin3 LINC complex in human spermatozoa. The structure reveals a hexagonal lattice that stitches the nuclear envelope, creating a rigid interface that links the sperm nucleus to the flagellum. Our structure unveils a unique membrane-anchoring mechanism: a SUN5 KASH-lid {beta}-hairpin and a Nesprin3 amphipathic helix insert into the outer nuclear membrane, leading to cooperative remodelling of the nuclear envelope shape by the extended LINC lattice, which results in flattening the caudal sperm nucleus. Our integrative data provides key insights into the architecture and role of a LINC complex in situ, revealing molecular details of a severe male infertility phenotype.

biochemistry↗

bioRxiv2025

The Developmental Trajectory of the Social Brain: A Movie-Based Exploration from childhood to adolescence

In childhood and adolescence, functional brain networks go through different stages of development, and the levels of connectivity within and between these networks change with age. The developmental trajectory of these large-scale networks of the brain have been extensively investigated; however, many aspects of our social brain and its developmental patterns remain unclear. This study employed a cross-sectional design to investigate the brains of 753 children and adolescents (ages 5-15) while they watched a movie. This research investigates the functional distinctness and developmental synchronicity of brain areas implicated in social cognition, such as empathy and affective and cognitive theory of mind, across childhood and adolescence using generalized additive models and inter-region group analysis. Our findings suggest that social cognition components networks such as cognitive and affective theory of mind and empathy exhibit distinct developmental trajectories throughout childhood and adolescence. The findings support the theory that social cognitive networks are developmentally distinct from each other, even in the absence of task-specific paradigms.

neuroscience↗

bioRxiv2025

Effect of membrane composition on interaction and permeation of a mycobacterial siderophore

1Iron acquisition is a crucial determinant of Mycobacterium tuberculosis (Mtb) survival and pathogenesis, as the bacterium must scavenge iron from the host environment during infection. To achieve this, Mtb synthesizes two structurally distinct siderophores, mycobactin (MBT) and carboxymycobactin (cMBT), efficiently chelate iron and facilitate its uptake. While MBT remains embedded in the membrane due to its hydrophobicity, cMBT is secreted to scavenge extracellular iron. Despite their biological importance, the dynamics of siderophore-membrane interactions remain poorly understood. In this study, we employ coarse-grained molecular dynamics simulations to investigate the spontaneous flip-flop of iron-bound MBT (Fe-MBT) across the mycobacterial membrane. Our results reveal that Fe-MBT flip-flop occurs on a significantly slower timescale compared to generic bacterial lipids, with rates nearly an order of magnitude lower. The lipid composition of the membrane plays a critical role in modulating this process, with mycobacterial membranes exhibiting a higher degree of lipid order and reduced Fe-MBT mobility compared to generic bacterial membranes. Furthermore, we show that flip-flop transitions are relatively fast, occurring within 100 ns and, in some cases, on the order of a few nanoseconds. Our findings contribute to a mechanistic understanding of siderophore dynamics in Mtb membranes and provide a foundation for future studies on iron acquisition and potential drug targeting strategies.

biophysics↗

bioRxiv2025

Intermittent Fasting Reprograms Chromatin Accessibility to Modulate Gene Expression in Brain and Muscle

Intermittent fasting (IF), a dietary regimen that mimics the natural feeding patterns observed across diverse organisms--from single-celled life to mammals--is thought to activate systemic survival responses and confer health benefits. However, the molecular mechanisms underlying these effects remain poorly understood. In this study, we utilized ATAC-Seq and RNA-Seq to investigate how IF influences chromatin accessibility and gene expression in brain and muscle tissues of mice, compared to ad libitum feeding. Our results reveal that IF induces significant changes in chromatin accessibility, modulating pathways related to metabolism, ribosome function, HIF-1 signaling, and glycolysis. Motif analysis identified tissue-specific transcription factors enriched in IF-regulated regions, including Sp1, Mef2a, NeuroD2, Banp, and NFIA in the brain, and SMAD4, TCF4, STAT5B, NKX3-1, and ZEB2 in muscle. Integrative analysis of ATAC-Seq and RNA-Seq data demonstrated that IF upregulates 50 genes and downregulates 15 in the cortex, while upregulating 31 genes and downregulating 10 in muscle. These gene expression changes are linked to pathways associated with neuroprotection and enhanced muscle function, offering mechanistic insights into the health benefits of IF. Our findings underscore the role of IF-induced chromatin remodeling in driving adaptive gene regulation.

bioinformatics↗

bioRxiv2024

Engineering CD3 Subunits with Endoplasmic Reticulum Retention Signal Facilitates Allogeneic CAR T Cell Production

The success of autologous CAR T cell therapies has driven interest in developing off-the-shelf allogeneic CAR T cells as a scalable and readily available option for broader patient access. Most of the current approaches involve the knockout of T cell receptor (TCR) subunits via genome editing for preventing graft-versus-host disease (GvHD). However, clinical translation of these methods faces challenges due to manufacturing complexities and emerging safety concerns like unintended long deletions and chromosomal loss. In this study, we explored an alternative approach by engineering synthetic CD3 subunits containing an endoplasmic reticulum retention (ERR) signal to suppress TCR surface expression by disrupting its trafficking to the plasma membrane. We screened multiple CD3-ERR candidate designs to identify the construct with the highest efficacy in TCR downregulation. The selected candidate, CD3{zeta}-ERR, was further characterized, demonstrating its ability to minimize TCR-mediated activation and alloreactivity without affecting T cell phenotype, cell cycle and cytokine-induced expansion. Subsequent assays revealed that CD3{zeta}-ERR CD19 CAR T cells retained their CAR-mediated cytotoxic function against CD19+ malignant cells. This study presents an alternative approach for TCR downregulation that circumvents genome editing. By using a transgene compatible with conventional viral vector delivery, this approach holds promise for scalable clinical-grade manufacturing of allogeneic CAR T cell therapies. Translational Impact StatementOur study introduces a scalable method to engineer allogeneic CAR T cells by reducing TCR expression without genome editing, thereby minimizing the risk of immune rejection (GvHD) while maintaining antitumor efficacy. This approach offers a practical and clinically translatable solution for producing "off-the-shelf" CAR T cell therapies, potentially broadening access to these life-saving treatments and streamlining their integration into existing clinical manufacturing processes.

immunology↗

bioRxiv2024

Extensive Surveillance of Mosquitoes and molecular investigation of Arboviruses in central Iran; First Record of Molecular Identification of Culex tarsalis in Qom Province

BackgroundArboviruses are one of the greatest threats to animal and public health. Culicidae family is one of the most important vectors for the transmission of Arboviruses in the world. According to the geographical, demographic and climatic features of Qom city in Iran, it can be a suitable region for vectors and therefore transmission of Arboviruses. MethodsIn this study, which was conducted between 2019 and 2020 in different parts of Qom city, 83,414 mosquitoes were collected and after evaluating the species of mosquitoes based on morphological and molecular detection, the presence of alphaviruses, flaviviruses and phleboviruses were evaluated using genus specific RT-PCR assays. ResultsIn this study, Culex tarsalis, Culex theilerivoucher, Culex quinquefasciatus and most importantly for the first time in Iran Culex tarsalis were detected. No alphavirus, flavivirus and phlebovirus infection was identified in collected mosquitoes. ConclusionClimatic and weather changes are the basis for the growth and spread of vectors and consequently the spread of arboviral diseases, and this issue seems to be very important on the necessity of increasing and continuing entomological and virological studies. Author SummaryArboviruses pose significant threats to animal and public health globally, with mosquitoes from the Culicidae family serving as key vectors in their transmission. This study focuses on Qom city, Iran, which, due to its unique geographical, demographic, and climatic characteristics, provides a potentially suitable environment for these vectors. Over the course of 2019 to 2020, researchers collected 83,414 mosquitoes across various locations within Qom. Through morphological and molecular analysis, they identified species such as Culex tarsalis, Culex theileri, and Culex quinquefasciatus, notably reporting Culex tarsalis in Iran for the first time. Using genus-specific RT-PCR assays, the study evaluated the presence of alphaviruses, flaviviruses, and phleboviruses in the collected samples but found no evidence of infection. These findings underscore the importance of ongoing entomological and virological research, particularly given the potential for climatic changes to influence vector growth and the spread of arboviral diseases.

molecular biology↗

bioRxiv2022

Computing absolute binding affinities by Streamlined Alchemical Free Energy Perturbation

Free Energy Perturbation (FEP) is a powerful but challenging computational technique for estimating differences in free energy between two or more states. This document is intended both as a tutorial and as an adaptable protocol for computing free energies of binding using free energy perturbations in NAMD. We present the Streamlined Alchemical Free Energy Perturbation (SAFEP) framework. SAFEP shifts the computational frame of reference from the ligand to the binding site itself. This both simplifies the thermodynamic cycle and makes the approach more broadly applicable to superficial sites and other less common geometries. As a practical example, we give instructions for calculating the absolute binding free energy of phenol to lysozyme. We assume familiarity with standard procedures for setting up, running, and analyzing molecular dynamics simulations using NAMD and VMD. While simulation times will vary, the human tasks should take no more than 3 to 4 hours for a reader without previous training in free energy calculations or experience with the VMD Colvars Dashboard. Sample data are provided for all key calculations both for comparison and readers convenience.

biophysics↗

bioRxiv2022

Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis

The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, we characterized the depth-dependent composition and structure of normal and osteoarthritic human femoral condyle cartilage (n = 47) and related them to their viscoelastic and constituent-specific mechanical properties. We observed that, in superficial cartilage, the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus (collagen pretension). Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus (a measure of nonlinear mechanical behavior). The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the disorganization of the collagen network was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan degradation and collagen disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical response of the collagen network. Further, the results also highlight that proteoglycan degradation and collagen disorganization increase the viscosity of cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.

biophysics↗

bioRxiv2021

The Expression Pattern of miR-17, -24, -124 and -145 as Diagnostic Factor for Metastatic Gastric Cancer; a Lesson from Gastric Cancer Stem cells

BackgroundDistant metastasis of Gastric Cancer (GC) causes more than 700 000 deaths worldwide. Cancer Stem Cells (CSCs) are a subpopulation of cancer cells responsible for aggressiveness and chemoresistance in clinical settings. MicroRNAs (miRNAs) emerge as important players in regulating self-renewal and metastasis in CSCs. Understanding the role of miRNAs in CSCs offer a potential diagnostic tool for GC patients. This study is aimed to identify miRNAs that target both stemness and metastasis in gastric cancer stem cells (GCSCs) and differentially expressed in metastatic GC patients as diagnostic biomarkers for GC metastasis. MethodsWe investigate the gene expression profile of patients using the GEO database and Rstudio software. To obtain the regulatory networks and miRNAs, the STRING and miRwalk database used. The gastric cancer tissues were obtained from Iranian National Tumor Bank (INTB) to validate the results. ResultsOur results indicated three important regulatory cores affecting the immune systems regulation, tumor progress, and metastasis. Based on the bioinformatics results, four miRNAs miR-17-5p, miR-24-3p, miR-124-3p, and miR-145-5p, were selected, and their expression pattern was evaluated in 10 patients metastatic tumors compared to 10 nonmetastatic tumors by real-time PCR. The expression level of mir-17, -24, and -124 was upregulated about 8, 10, 60 folds, respectively, and miR-145 was down-regulated 4.5 folds in metastatic tumors compared to nonmetastatic tumors. Conclusionthe high expression level of miR-17, -24, -124, and low level of miR-145 in GC patients samples could be a potential biomarker for the presence of GCSCs and the diagnosis of metastasis.

cancer biology↗

bioRxiv2020

Electrophysiological analysis of healthy and dystrophic 3D bioengineered skeletal muscle tissues

Recently, methods for creating three-dimensional (3D) human skeletal muscle tissues from myogenic cell lines have been reported. Bioengineered muscle tissues are contractile and respond to electrical and chemical stimulation. In this study we provide an electrophysiological analysis of healthy and dystrophic 3D bioengineered skeletal muscle tissues. We focus on Duchenne muscular dystrophy (DMD), a fatal muscle disorder involving the skeletal muscle system. The dystrophin gene, which when mutated causes DMD, encodes for the Dystrophin protein, which anchors the cytoskeletal network inside of a muscle cell to the extracellular matrix outside the cell. Here, we enlist a 3D in vitro model of DMD muscle tissue, to evaluate an understudied aspect of DMD, muscle cell electrical properties uncoupled from presynaptic neural inputs. Our data shows that electrophysiological aspects of DMD are replicated in the 3D bioengineered skeletal muscle tissue model. Furthermore, we test a block co-polymer, poloxamer 188, and demonstrate capacity for improving the membrane potential in DMD muscle.Therefore, this study serves as the baseline for a new in vitro method to examine potential therapies directed at muscular disorders.

cell biology↗

bioRxiv2020

Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis

The mechanical properties and tension of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue development a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and measurements of tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in the muscle tissue. High resolution 3D video microscopy of engineered muscle development, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.Competing Interest StatementTB and AH have filed a patent for the presented chamber system.View Full Text

biophysics↗

bioRxiv2019

Application of Different Types of Lactic Acid Bacteria Inoculant on Ensiled Rice Straw; Effects on Silage Quality, Rumen Fermentation, Methane Production and Microbial Population

Bacterial inoculants are known to improve quality of silage. The objectives of the present study were to evaluate the effects of different types of lactic acid bacteria (LAB; L. plantarum, L. salivarius, L. reuteri, L. brevis and S. bovis) inoculation (106 g-1 DM) on rice straw silage quality and to examine these effects on ruminal fermentation characteristics, digestibility and microbial populations in an in vitro condition. Inoculated rice straw was ensiled for 15 and 30 days. For in vitro study, rumen liquor was obtained from two rumen fistulated mature cows fed on mixed forage and concentrate at 60:40 ratio twice daily. Inoculation of LAB improved (P0.05) the rice straw silage quality such as increased dry matter and crude protein contents, decreased pH and butyric acid, and increased propionic acid and LAB contents especially after 30 days of ensiling. Results from in vitro study revealed that addition of LAB to the rice straw silage improved fermentation characteristics such as increased total volatile fatty acids and dry matter digestibility (P0.05). LAB treatments also decreased methane production and methane/total gas ratio after 15 and 30 days of ensiling. From the rumen microbial population perspective, cellulolytic, and fungal zoospores were enhanced while protozoa and methanogens were decreased by the LAB treatments. Based on these results, it could be concluded that inoculating rice straw silage with LAB (especially for L. plantarum and S. bovis) improved silage quality, rumen fermentation parameters and microbial populations in vitro. However, in vivo studies need to confirm those effects.

physiology↗

bioRxiv2019

TGFβ signaling curbs cell fusion and muscle regeneration

Fusion of muscle progenitor cells is necessary for skeletal muscle development and repair. Cell fusion is a multistep process involving cell migration, adhesion, membrane remodeling and actin-nucleation pathways to generate multinucleated myotubes. While the cellular and molecular mechanisms promoting muscle cell fusion have been intensely investigated in recent years, molecular brakes restraining cell-cell fusion events to control syncytia formation have remained elusive. Here, we show that transforming growth factor beta (TGF{beta}) signaling is active in adult muscle cells throughout the fusion process and reduce muscle cell fusion independently of the differentiation step. In contrast, inhibition of TGF{beta} signaling enhances cell fusion and promotes branching between myotubes. Pharmacological modulation of the pathway in vivo perturbs muscle regeneration after injury. Exogenous addition of TGF{beta} protein results in a loss of muscle function while inhibition of the TGF{beta} pathway induces the formation of giant myofibres. Transcriptome analyses and functional assays revealed that TGF{beta} acts on actin dynamics and reduce cell spreading through modulation of actin-based protrusions. Together our results reveal a signaling pathway that limits mammalian myoblast fusion and add a new level of understanding to the molecular regulation of myogenesis.

cell biology↗

bioRxiv2018

The First Implication of Image Processing Techniques on Influenza A Virus Sub-Typing Based on HA/NA Protein Sequences, using Convolutional Deep Neural Network

Increase in influenza A virus host range throughout its evolution has given rise to major concerns worldwide. Although the increasing host range mechanism of the virus is largely unknown; persistent genetic mutations have been blamed as a key factor in the re-organization of the host response and the host range. To uncover the underlying core bases of the two important antigenic proteins of influenza virus (HA and NA), functional data mining and image processing analysis of over 8000 protein sequences of different HA and NA subtypes were performed. Each amino acid sequence in HA or NA proteins sat as a feature or variable and two polynomial datasets were created and subjected into conventional prediction models. The average accuracies of these predictive models for HA subtype classifications ranged from 38.9% for SVM to 87.2% for Decision Tree models. NA subtype classification with conventional prediction models varied from 81.3% to 99.87% for SVM and KNN models, respectively. Then amino acid sequence datasets were converted to binary images; subtypes feature sat as target variable, and target label determined by image processing convolution neural network. The performances of Image processing models (convolutional neural network) on binary images for both HA and NA datasets reached to 100%; and the application of Gabor2 filter decreased the time for the predicting model to reach the best performance for HA subtype; while it increased the epochs time for NA subtype classification.\n\nFor the first time ever, converting influenza virus HA and NA amino acid sequences into the binary image datasets and their classifications by convolution neural network increased the prediction accuracies and performances to the highest possible point. The finding of this paper paves new avenues for virus classification based on antigenic HA and NA amino acid profiles, and easily classifying and predicting the possible future emerging strains of pandemic influenza.

bioinformatics↗

bioRxiv2018

14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface

Pseudomonas are a common cause of hospital acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, a hydrophobic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3{beta}:ExoS and -ExoT complexes presented here reveal an extensive novel binding interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the hydrophobic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the hydrophobic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the hydrophobic C-terminal segment.\n\nShort summaryCrystal structures of Pseudomonas exotoxins-S and -T identify a novel hydrophobic interface with 14-3-3 proteins, and we show that 14-3-3 activates these toxins independent of their phosphopeptide groove binding C-termini, by preventing their aggregation.

biochemistry↗