Biology subjects

Hosseini, M.

Publications and source records attributed to Hosseini, M..

At least 19 recordsLinked to original sources

bioRxiv2026

The 2-feature Simultaneous Type/ Serial Token Model of temporal feature conjunctions: Successes are merely fortunate conjunctions.

Resolving the binding problem, i.e., how we integrate perceptual features in space and time to perceive objects, people and events as coherent wholes instead of masses of free-floating features, has been a central goal of cognitive scientists for decades. Conjunction errors occur whenever features are mis-bound leading to illusory percepts that were not actually presented. A specific kind of Rapid Serial Visual Presentation experiment induces temporal illusory conjunctions, called distractor intrusion errors. Despite these errors being well-established, current theories and models provide limited explanations. We present the 2-feature Simultaneous Type/Serial Token (2f-ST2) Model, the latest addition to the family of ST2-models, which simulates the most important behavioural and electrophysiological distractor intrusion findings. These include response distributions, reaction time patterns, and evoked electrophysiology responses. Importantly, we simulate these results across diverse empirical paradigms, implementing a range of stimulus sets, temporal dynamics, and involving multiple responses after each trial, without needing to modify our model's architecture or core parameters. Our findings are discussed in relation to theories of selective attention and working-memory binding. We argue that the 2f-ST2 model is more parsimonious than the leading theory of distractor-intrusions (the focussed-attention/sophisticated-guessing model), since it uses only a single binding mechanism, implying that correct bindings are simply fortunate conjunctions. The 2f-ST2 model further makes predictions for stimulus-competition, subjective-visibility and human electrophysiology. In summary, the ST2-model is a general framework for understanding how perception, temporal attention and working-memory interact, and the 2f-ST2 model extends the framework to distractor intrusions, thus explaining temporal feature binding.

neuroscience↗

bioRxiv2026

CD59 organizes the plasma membrane to sustain oncogenic Ras-MAPK signaling and is a targetable vulnerability in acute myeloid leukemia

Acute myeloid leukemia (AML) is a clinically heterogeneous disease. Although the genetic abnormalities associated with poor prognosis are well defined, how they drive unfavorable outcomes remains unclear. Using published gene-expression and dependency datasets, we searched for cell-surface protein-coding genes associated with poor survival and required for AML growth, prioritizing this class of proteins for its accessibility to biologics. This search identified CD59, a GPI-anchored protein with a canonical role in complement regulation, whose high mRNA expression correlates with adverse-risk genetics and stemness signatures. CD59 silencing impaired proliferation across genetically diverse AML cell lines, reduced leukemic burden, and extended survival in cell xenograft models. Moreover, CD59 expression was enriched on leukemic stem cells (LSCs), and its depletion impaired LSC self-renewal and primary AML engraftment in vivo while sparing normal hematopoiesis. Mechanistically, these effects reflected a non-canonical role for CD59 in sustaining Ras-MAPK signaling, whereby its loss depleted inner-leaflet phosphatidylserine and impaired Ras and c-Raf membrane recruitment and activation. rILYd4, a recombinant fragment of the bacterial toxin intermedilysin that binds and degrades CD59, recapitulated these effects and sensitized cells to venetoclax in vivo. These findings reveal CD59 as a critical regulator of Ras-MAPK signaling required for AML growth and nominate its rILYd4-mediated degradation as a therapeutic strategy.

cancer biology↗

bioRxiv2026

Exploring the functionality of market-available tools for neural recording

Low-cost and open-source neural recording systems are increasingly important for expanding access to electrophysiological research. However, many existing platforms still rely on specialized hardware or limited modularity, restricting flexibility for laboratories seeking customizable solutions. Here, we developed and evaluated a modular neural recording platform constructed entirely from commercially available components. Recordings were compared against the ground truth. The platform successfully recovered local field potential (LFP)-like waveforms in most conditions and detected spike-like activity during direct connection recordings. Principal component analysis and k-means clustering further demonstrated the ability to distinguish multiple simulated spike waveforms. Signal quality varied across configurations, with saline recordings and preamplifier integration introducing increased noise and reduced detectability. These findings demonstrate the feasibility of building affordable and modular electrophysiology systems using widely accessible hardware. Although the current implementation has limitations in sampling rate, noise performance, and in vivo validation, the presented framework provides a practical foundation for future customizable open-source neural recording.

neuroscience↗

bioRxiv2026

Aberrant oxidative metabolism selects for TET2-deficient hematopoietic stem and progenitor cells

The mechanism(s) driving selective expansion of mutant hematopoietic stem and progenitor cells (HSPC) in clonal hematopoiesis (CH) are incompletely understood. Here, we address the role of metabolism in selection for HSPC with loss of function mutations in TET2. Loss of Tet2 in murine HSPC triggers overexpression of glycolysis and oxidative phosphorylation genes and increased oxidative metabolism via an enlarged mitochondrial network. However, Tet2-deficient HSPC maintain a normal redox state. Strikingly, compound loss of the rate-limiting pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) triggers increased reactive oxygen species and impairs the fitness of Tet2-deficient HSPC. We find that aberrant oxidative metabolism is also a feature of HSPC in human CH and clonal cytopenia of unknown significance (CCUS). Overall, our data point to aberrant metabolism as a critical and conserved driver of selection in TET2-deficient CH and identify the PPP as a crucial compensatory pathway needed to maintain their selective advantage. Statement of SignificanceThis study identifies oxidative metabolism as a critical driver of selection for TET2-deficient HSPC in clonal hematopoiesis (CH). It also demonstrates that cellular redox state is a vulnerability that impairs their fitness. These insights establish targetable metabolic pathway(s) that could be exploited in the setting of TET2 mutant CH.

cancer biology↗

bioRxiv2025

Growth-promoting rhizobacteria amend the defense of strawberry plants against sequentially attacking herbivores

Plant defense systems such as induced resistance (IR; induced by herbivores) and induced systemic resistance (ISR; induced by beneficial rhizobacteria) are modulated by the same signaling pathways within plants and hence interact. ISR allows enhanced protection of aboveground plant parts against herbivores before IR induction. Both ISR and IR are systemic and may involve the production of toxic, antifeedant and/or repellent compounds, and/or reduce nutrient availability, which may in consequence affect plant usability and palatability for later arriving herbivores. The combined effects of ISR and IR on different herbivores sharing the same plant and plant performance have been rarely addressed. Here, we assessed the effects of three plant-growth-promoting rhizobacteria (PGPR), Azotobacter chroococcum, Azospirillum brasilense and Pseudomonas brassicacearum, on the defense response and physiology of strawberry plants upon sequential attack by two herbivores with different feeding modes, two-spotted spider mites Tetranychus urticae and cotton aphids Aphis gossypii. Attack of strawberry plants by spider mites and aphids adversely affected the abundance of the later arriving herbivore, mediated by the host plants defense system. First-attacking spider mites exerted much stronger adverse effects on later attacking aphids than first-attacking aphids on later attacking spider mites. In absence of PGPR inoculation, the herbivores, especially first-attacking spider mites, severely impaired host plant physiology and productivity. PGPR inoculation primed the plants defense system to attack by spider mites and aphids, allowing the plants to produce more secondary metabolites such as phenols. In consequence, the abundances of both herbivores were lower on PGPR-inoculated plants compared to chemically fertilized and control plants. Overall, our study suggests that PGPR inoculation ameliorates the plant damage caused by sequentially attacking herbivores. Additionally, the PGPRs improve the physiology and productivity, and favorably balance the nutritional state, of strawberry plants.

ecology↗

bioRxiv2025

Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex

Down syndrome is the most common genetic cause of intellectual disability and is characterized by early-onset delays in motor, cognitive, and language development. The molecular mechanisms underlying these neurodevelopmental impairments remain poorly understood. Here, we utilized single-nucleus multiomic sequencing to simultaneously profile gene expression and chromatin accessibility in the Down syndrome prefrontal cortex during early postnatal development, a critical period for synaptogenesis, neural maturation, and developmental neuroimmune interactions. Our findings reveal widespread dysregulation of chromatin accessibility and gene expression, with deficits spanning metabolic and synaptic pathways, oligodendrocyte lineage progression, and a pronounced neuroinflammatory signature. We present a molecular atlas of Down syndrome neuropathology at a critical stage of brain development, highlighting convergent neurodevelopmental and neurodegenerative pathways and informing potential targeted therapies for Down syndrome-associated neuroinflammation.

neuroscience↗

bioRxiv2025

Single-nucleus analysis reveals dysregulated oxidative phosphorylation in Down syndrome basal forebrain at birth

INTRODUCTIONBasal forebrain cholinergic neurons (BFCNs) are integral to learning, attention, and memory, and are prone to degeneration in Down syndrome (DS), Alzheimers disease, and other neurodegenerative diseases. However, the mechanisms that lead to the degeneration of these neurons are not known. METHODSSingle-nucleus gene expression and ATAC sequencing were performed on postmortem human basal forebrain from unaffected control and DS tissue samples at 0-2 years of age (n=4 each). RESULTSSequencing analysis of postmortem human basal forebrain identifies gene expression differences in DS early in life. Genes encoding proteins associated with energy metabolism pathways, specifically oxidative phosphorylation and glycolysis, and genes encoding antioxidant enzymes are upregulated in DS BFCNs. DISCUSSIONMultiomic analyses reveal that energy metabolism may be disrupted in DS BFCNs by birth. Increased oxidative phosphorylation and the accumulation of reactive oxygen species byproducts may be early contributors to DS BFCN neurodegeneration.

neuroscience↗

bioRxiv2025

Limit of detection of Raman spectroscopy using polystyrene particles from 25 to 1000 nm in aqueous suspensions

Raman spectroscopy is an analytical method capable of detecting various microorganisms and small particles. Here, we used 25-1000 nm polystyrene particles in aqueous suspensions, which are comparable in size to viral particles and viral aggregates, to determine the limit of detection of a confocal Raman microscope. We collected Raman spectra using a 785 nm wavelength laser with a power of 300 mW and a 10 s exposure time, with a 5X objective lens. We detected the most prominent peak of the polystyrene particles at 1001 cm-1, corresponding to the ring breathing mode. We established the minimum and maximum limit of detection (LODmin and LODmax) using a partial least squares (PLS) model. The LOD of the smallest size of 50 nm was identified as 7.47 x 1012 -7.64 x 1012 particle/mL, and for the largest size of 1000 nm, 6.09 x 108 -6.24 x 108 particle/mL. We demonstrated that Raman spectroscopy was non-destructive under these conditions by comparing the particle size before and after collecting Raman spectra using dynamic light scattering. Due to their size similarity to viral particles and viral aggregates, this systematic characterization of polystyrene particles provides detailed information on their Raman spectral signatures in aqueous suspensions. These findings establish a foundation for using Raman spectroscopy for the detection of small particles in aqueous suspensions and highlight its potential as a tool for real-time monitoring in vaccine manufacturing.

bioengineering↗

bioRxiv2024

Modeling vehicle collision risk for the jungle cat in the Hyrcanian forests of Iran: A guide for vehicle collision prevention

Wildlife-vehicle collisions are an important wildlife conservation challenge, especially for carnivores. As in other countries, vehicle collisions pose a major threat to carnivores in Iran. The jungle cat (Felis chaus) is a small carnivore species facing multiple threats, including habitat destruction, land use changes, and particularly vehicle collisions. We collected data on jungle cat collisions to model jungle cat-vehicle collision risk in the Hyrcanian forests of northern Iran. We also modeled the jungle cat vehicle collision risk in the study area but by creating 1 km and 5 km buffers around the roads and identified high vehicle collision risk areas within the 1 km and 5 km butters. We used the Maxent model to identify most important predictors of collision risk. Our models showed that areas in west of Golestan province, east of Mazandaran province, and in central parts of Gilan province faced highest vehicle collision risk for the jungle cat in the Hyrcanian forests. Human footprint and slope were the most important predictors of the jungle cat vehicle collision, with 48.3% and 17.2% contribution and with positive and negative correlation respectively. Results of variable importance were similar when modeling area was limited to a 5 km buffer zone around the roads. But when modeling area was limited to a 1 km buffer zone around the roads, slope became insignificant. Collisions more likely occur where vegetation grows immediately adjacent to roads, so clearing a roadside strip would reduce potential collisions. We recommend that high collision-risk areas we identified for jungle cat in the Hyrcanian forests be a focus for future monitoring and conservation planning.

ecology↗

bioRxiv2024

The Negative Effects of Smoking Cigarettes on Morphological and Histological Damages to 18 and 21 Days Mouse Embryo Liver

Smoking cigarettes can lead to morphological and histological changes in several human and animal tissues. This paper describes the effects of CS exposure on the liver, weight, and length of mouse embryos. 42 NMRI adult mice were used for mating. Pregnant female mice were categorized into 3 groups: F (filtered), NF (non-filtered), and C (controlled). Each group included 14 female mice exposed to 12 cigarettes daily; 7 mice for 18 days and 7 mice for 21 days. In addition, only the group C were exposed to ambient air. Seven mouse embryos from each group were euthanized. Their livers were fixed for histological processing. The Livers of groups F & NF as compared with group C revealed changes in cellular architecture, centrilobular veins, inflammatory cells, kupffer cells, cytoplasmic vacuolation, hepatocytes necrosis, and decreased parenchymal cellularity. The average weight of embryo, liver, and CR in F & NF significantly reduced (p<0.05 and p<0.01).

pathology↗

bioRxiv2024

AutoGaitA - Automated Gait Analysis in Python

Individual behaviours require the nervous system to execute specialised motor programs, each characterised by unique patterns of coordinated movements across body parts. Deep learning approaches for body-posture tracking have facilitated the analysis of such motor programs. However, translating the resulting time-stamped coordinate datasets into meaningful kinematic representations of motor programs remains a long-standing challenge. We developed the versatile quantitative framework AutoGaitA (Automated Gait Analysis), a Python toolbox that enables comparisons of motor programs at multiple levels of granularity and across tracking methods, species and behaviours. AutoGaitA allowed us to demonstrate that flies, mice, and humans, despite divergent biomechanics, converge on the age-dependent loss of propulsive strength, and that, in mice, locomotor programs adapt as an integrated function of both age and task difficulty. AutoGaitA represents a truly universal framework for robust analyses of motor programs and changes thereof in health and disease, and across species and behaviours.

animal behavior and cognition↗

bioRxiv2024

Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity

Dysfunctions in autophagy, a highly conserved cellular mechanism responsible for the degradation of intracellular components within lysosomes, often result in neurodegeneration. The neuroprotective effect of autophagy varies across neuronal subtypes, and the mechanisms of selective vulnerability of neurons to autophagy dysfunction are currently unknown. Utilizing a mouse model of ATG5 deficiency in inhibitory neurons and a comprehensive approach, including PET imaging, metabolomics, stable-isotope labeling studies, and live cell imaging, we establish that autophagy contributes to the survival of cerebellar Purkinje cells (PCs) by safeguarding their glycolytic activity. We show that the core autophagy protein ATG5 downregulates the levels of the glucose transporter 2 (GLUT2) during brain maturation. Autophagy-deficient PCs exhibit increased glucose uptake, along with elevated levels of glycolytic intermediates and methylglyoxal-modified proteins. We propose lysophosphatidic acid and serine as glycolytic intermediates inducing PC death and demonstrate that deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and restores their ataxic gait. Taken together, this study reveals a novel neuroprotective role of autophagy in preventing excessive glycolytic metabolism in the brain.

neuroscience↗

bioRxiv2023

Class-imbalanced Unsupervised and Semi-Supervised Domain Adaptation for Histopathology Images

In dealing with the lack of sufficient annotated data and in contrast to supervised learning, unsupervised, self-supervised, and semi-supervised domain adaptation methods are promising approaches, enabling us to transfer knowledge from rich labeled source domains to different (but related) unlabeled target domains, reducing distribution discrepancy between the source and target domains. However, most existing domain adaptation methods do not consider the imbalanced nature of the real-world data, affecting their performance in practice. We propose to overcome this limitation by proposing a novel domain adaptation approach that includes two modifications to the existing models. Firstly, we leverage the focal loss function in response to class-imbalanced labeled data in the source domain. Secondly, we introduce a novel co-training approach to involve pseudo-labeled target data points in the training process. Experiments show that the proposed model can be effective in transferring knowledge from source to target domain. As an example, we use the classification of prostate cancer images into low-cancerous and high-cancerous regions.

pathology↗

bioRxiv2022

Systematic analysis of transcriptional and epigenetic effects of genetic variation in Kupffer cells enables discrimination of cell intrinsic and environment-dependent mechanisms

Noncoding genetic variation is a major driver of phenotypic diversity but determining the underlying mechanisms and the cell types in which it acts remain challenging problems. Here, we investigate the impact of natural genetic variation provided by phenotypically diverse inbred strains of mice on gene expression and epigenetic landscapes of Kupffer cells. Analysis of gene expression in Kupffer cells and other liver cell types derived from C57BL/6J, BALB/cJ and A/J mice provided evidence for strain-specific differences in environmental factors influencing Kupffer cell phenotypes, including preferential Leptin signaling in BALB/cJ Kupffer cells. Systematic analysis of transcriptomic and epigenetic data from F1 hybrids of these mice, and transcriptomic data from strain-specific Kupffer cells engrafted into a common host enabled quantitative assessment of cis versus trans effects of genetic variation on gene expression and an estimate of cell autonomous versus non cell autonomous effects. Under homeostatic conditions, trans effects of genetic variation were dominant, with the majority of trans regulation being non cell autonomous. In contrast, strain specific responses to acutely administered LPS were primarily associated with genetic variation acting in cis to modify response elements for lineage determining and signal dependent transcription factors. Collectively, these findings reveal cell intrinsic and environmental effects of natural genetic variation on gene expression, demonstrate the use of enhancers as detectors of trans effects of genetic variation, and provide a new resource for understanding the impact of genetic variation on gene expression in Kupffer cells.

genomics↗

bioRxiv2022

A systematic scoping review of ethics of contributor role ontologies and taxonomies

Contributor Role Ontologies and Taxonomies (CROTs) provide a standard list of roles to specify individual contributions to publications. Due to the recent uptake of CROTs - the CRediT taxonomy in particular- researchers from different disciplinary backgrounds have anticipated a positive impact on ethical issues related to the attribution of credit and responsibilities. Yet, they have also voiced concerns about CROTs shortcomings and ways in which they could be misunderstood or misused and have provided suggestions to improve them. These discussions have never been collated and consolidated. To fill this gap, the current scoping review collates and explores published viewpoints about the ethics of CROTs. Ovid Medline, Scopus, Web of Science, and Google Scholar were searched. In total, 30 papers met the inclusion criteria and were subsequently analyzed using an inductive approach. We identified eight themes and 20 specific issues related to the ethics of CROTs and provided four recommendations for CROT developers: 1) Compile comprehensive instructions that explain how CROTs should be used and that note common pitfalls of employing them in practice; 2) Improve the coherence of used terms, 3) Provide translations of roles in languages other than English, and 4) Communicate a clear vision about future development plans.

scientific communication and education↗

bioRxiv2021

Knockout of Anopheles stephensi immune gene LRIM1 by CRISPR-Cas9 reveals its unexpected role in reproduction and vector competence

PfSPZ Vaccine against malaria is composed of Plasmodium falciparum (Pf) sporozoites (SPZ) manufactured using aseptically reared Anopheles stephensi mosquitoes. Immune response genes of Anopheles mosquitoes such as Leucin-Rich protein (LRIM1), inhibit Plasmodium SPZ development (sporogony) in mosquitoes by supporting melanization and phagocytosis of ookinetes. With the aim of increasing PfSPZ infection intensities, we generated an A. stephensi LRIM1 knockout line , {Delta}aslrim1 , by embryonic genome editing using CRISPR-Cas9. {Delta}aslrim1 mosquitoes had a significantly increased midgut bacterial load and an altered microbiome composition, including elimination of commensal acetic acid bacteria. The alterations in the microbiome caused increased mosquito mortality and unexpectedly, significantly reduced sporogony. The survival rate of {Delta}aslrim1 and their ability to support PfSPZ development, were partially restored by antibiotic treatment of the mosquitoes, and fully restored to baseline when {Delta}aslrim1 mosquitoes were produced aseptically. Deletion of LRIM1 also affected reproductive capacity: oviposition, fecundity and male fertility were significantly compromised. Attenuation in fecundity was not associated with the altered microbiome. This work demonstrates that LRIM1s regulation of the microbiome has a major impact on vector competence and longevity of A. stephensi. Additionally, LRIM1 deletion identified an unexpected role for this gene in fecundity and reduction of sperm transfer by males.

microbiology↗

bioRxiv2020

GeneTerpret: a customizable multilayer approach to genomic variant prioritization and interpretation

Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually scouring through a multitude of independent databases, often with the aid of several and mostly independent computational tools. To streamline the variant interpretation process, we developed GeneTerpret platform that collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in a given genome. The platform assigns quantitative validity scores to genes by query and assembly of the current genotype-phenotype data, sequence homology, molecular interactions, expression data, and animal models. The platform uses the American College of Medical Genetics (ACMG) criteria to categorize variants into five tiers (from benign to pathogenic). The platform then outputs a prioritized list of potentially causal variants/genes in a given genome for a specific case. GeneTerpret is a flexible and free platform designed to streamline the variant interpretation process through a unique interface, with improved ease, speed and accuracy. This unique integrated system provides effective validity and pathogenicity modules to assess genetic variant data and allows the user to decide which output and impact level should be considered in this process. The platform can be accessed and used online at https://geneterpret.com.

bioinformatics↗

bioRxiv2020

Noise Invariance in Inferior Colliculus Neurons is Dependant on the Input Noisy Conditions

The auditory system is extremely efficient to extract audio information in the presence of background noise. However, the neural mechanisms related to this efficiency is still greatly misunderstood, especially in the inferior colliculus (IC). In fact, while noise processing under different conditions has been investigated at the auditory cortex level, studies in the IC have been much limited. One interesting observation has been that there seems to be some degree of noise invariance in the IC in the presence of white noise. We wish to broaden this knowledge by investigating if there is a difference in the activity of neurons in the IC, when presenting noisy vocalisations with different types of noises, input signal-to-noise ratios (SNR) and signal levels. We do so using a generalized linear model (GLM), which gives us the ability to study the neural activity under these different conditions at a per neuron level. We found that non-stationary noise is the only noise type that clearly contributes to the neural activity in the IC, regardless of the SNR, input level or vocalisation type. However, when presenting white or natural stationary noises, a great diversity of responses was observed for the different conditions, where the activity of some neurons was affected by the presence of noise and the activity of others was not. Therefore, there seems to be some level of background noise invariance as early as the IC level, as reported before, however, this invariance seems to be highly dependent on the noisy conditions. New & NoteworthyThe neural mechanisms of auditory perception in the presence of background noise are still not well understood, especially in the IC. We studied neural activity in the IC when presenting noisy vocalisations using different background noise types, SNRs and input sound levels. We observed that only the non-stationary noise type clearly contributes to the neural activity in the IC. The noise invariance previously observed in the IC thus seems dependent on the noisy conditions.

neuroscience↗