Biology subjects

Karimi, S.

Publications and source records attributed to Karimi, S..

10 recordsLinked to original sources

bioRxiv2025

Investigating Alzheimers Disease Biomarkers by Applying Machine Learning Models

ObjectiveAlzheimers Disease (AD) is a debilitating neurodegenerative disorder characterized by memory loss, cognitive decline, and the accumulation of amyloid plaques and neurofibrillary tangles. This study investigates the interplay of various biomarkers and clinical features in diagnosing AD using machine learning (ML) techniques. MethodsWe analyzed data from 191 AD patients and 59 non-AD subjects, employing classifiers including Naive Bayes (NB), Random Forest (RF), Decision Tree (DT), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN). ResultsOur findings indicate that KNN, SVM, RF, and DT achieved high sensitivity (94%) and accuracy (92%), demonstrating their potential as effective diagnostic tools. Notably, significant differences in feature values between AD patients and non-AD subjects suggest that biomarker-driven approaches can enhance diagnostic precision. Key biomarkers such as neprilysin, alpha-secretase, beta-secretase, amyloid plaques and urinary formic acid emerged as critical elements. ConclusionOur results underscore the importance of selecting a targeted subset of features to streamline the diagnostic process, allowing for more efficient and cost-effective screening. While our study reveals valuable insights into AD pathology and diagnosis, future research with larger, longitudinal cohorts is essential to further elucidate these relationships and enhance our understanding of Alzheimers mechanisms, ultimately aiming for innovative therapeutic strategies.

bioinformatics↗

bioRxiv2024

DNA barcoding of passerine birds at an ornithological crossroad reveals significant East-West genetic lineage divergence

Exploring genetic diversity is essential for precise species delimitation, especially within taxonomically complex groups like passerine birds. Traditional morphological methods often fail to resolve species boundaries; however, DNA barcoding, particularly through the mitochondrial cytochrome c oxidase subunit I (COI) gene, provides a powerful alternative method for accurate species identification. This study establishes a comprehensive DNA barcode library for Iranian passerine birds, analyzing 537 COI sequences from 94 species across 23 families and 53 genera. We observed a pronounced barcode gap, with average intraspecific divergence at 0.4% and interspecific divergence at 18.6%. Notable intraspecific variation emerged in the Persian nuthatch (Sitta tephronota) and the Lesser whitethroat (Curruca curruca), while the goldfinch (Carduelis carduelis) showed limited genetic differentiation despite marked morphological distinctions. Phylogenetic analysis revealed significant east-west genetic splits in C. curruca and S. tephronota, reflecting geographic and zoogeographic boundaries of Iran. These findings demonstrate the effectiveness of DNA barcoding in elucidating biogeographic patterns, emphasizing the key role of Iran as an ornithological crossroads for avian biodiversity. Moreover, our results suggest that much of the genetic variation in the COI gene arises from synonymous mutations, highlighting the role of purifying selection in shaping mtDNA diversity across species.

zoology↗

bioRxiv2024

Brain tumor induce immunoregulatory dendritic cells in tumor draining lymph nodes that can be targeted by OX40

Brain tumors and metastases have a poor prognosis due to the unique characteristics of the central nervous system (CNS) and tumor immune microenvironment (TIME). CNS tumors exhibit limited infiltration and activation of dendritic cells (DCs) in tumor tissue and tumor-draining lymph nodes (TdLN), which regulate immune responses influenced by factors in the TIME. The immune response in the brain is significantly different from the rest of the body, and although DC subtypes have been identified in mice and humans with brain tumors or metastases, little is known how they affect the response to immunotherapy. We investigated the immunoregulatory function of cervical DCs (DC-c) compared to peripheral DCs (DC-p) in TdLN. Our analysis revealed that DC-c have unique phenotypes and promoted regulatory T cell expansion and poorly cytotoxic CD8 T cells compared to DC-p. Furthermore, we identified OX40 as a modulator of immunoregulatory DC-c function, and Batf3 knockout confirmed the essential role of DC-c in mounting an immune response to brain tumors. Additionally, the expression of markers associated with mature regulatory DCs (mregDC) in TdLN was associated with immune regulation in the CNS and the response to OX40. Our findings highlight that immunotherapy interventions can modulate DC-cs immunoregulatory function, offering an innovative approach for optimized immunotherapy against CNS malignancies.

immunology↗

bioRxiv2024

Identification of Thioredoxin1 interacting proteins in neuronal cytoskeletal organization during autophagy

Thioredoxin1 (Trx1) is a major cytoplasmic thiol oxidoreductase protein involved in redox signaling. This function is rendered by a rapid electron transfer reaction during which Trx1 reduces its substrate and itself becomes oxidized. In this reaction, Trx1 forms a transient disulfide bond with the substrate which is unstable and therefore identification of Trx1 substrates is technically challenging. This process maintains the cellular proteins in a balanced redox state and ensures cellular homeostasis. Trx1 levels are reduced in some neurodegenerative diseases; therefore, understanding the interactions between Trx1 and its substrates in neurons could have significant therapeutic implications. We utilized a transgenic mouse model expressing a Flag-tagged mutant form of Trx1 that can form stable disulfide bonds with its substrates allowing identification of the Trx1 interacting proteins. The involvement of Trx1 has been suggested in autophagy, we aimed to investigate Trx1 substrate after pharmacologic induction of autophagy in primary hippocampal neurons. Treatment of primary neurons by rapamycin, a standard autophagy inducer, caused significant reduction of neurite outgrowth and alterations in the cytoskeleton. Through immunoprecipitation and mass spectrometry, we have identified 77 Trx1 interacting proteins which were associated with a wide range of cellular functions including a major impact on cytoskeletal organization. The results were confirmed in Trx1 knocked-down cells and in nucleofected primary neurons. Our study suggests a novel role for Trx1 in regulation of neuronal cytoskeleton organization, marking the first investigation of Trx1-interacting proteins in primary neurons and confirming the multifaceted role of Trx1 in physiological and pathological states.

biochemistry↗

bioRxiv2023

Integration of spatially opposing cues by a single interneuron guides decision making in C. elegans

The capacity of animals to integrate and respond to multiple hazardous stimuli in the surroundings is crucial for their survival. In mammals, complex evaluations of the environment require large numbers and different subtypes of neurons. The nematode C. elegans avoid hazardous chemicals they encounter by reversing their direction of movement. How does the worms compact nervous system processes the spatial information and directs the change of motion? We show here that a single interneuron, AVA, receives glutamatergic excitatory signals from head sensory neurons and glutamatergic inhibitory signals from the tail sensory neurons. AVA integrates the spatially distinct and opposing cues, whose output instructs the animals behavioral decision. We further find that the differential activation of AVA from the head and tail stems from distinct anatomical localization of inhibitory and excitatory glutamate-gated receptors along the AVA process, and from different threshold sensitivities of the sensory neurons to aversive stimuli. Our results thus uncover a cellular mechanism that mediates spatial computation of nociceptive cues for efficient decision-making in C. elegans.

neuroscience↗

bioRxiv2022

Hepatocyte PPARγ contributes to the progression of non-alcoholic steatohepatitis in male and female obese mice.

Background & AimsNon-alcoholic steatohepatitis (NASH) is associated with obesity and increased expression of hepatic peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) in humans. Although we previously showed that the expression of PPAR{gamma} in hepatocytes contributes to the development NASH in lean mice, the relevance of hepatocyte PPAR{gamma} in the development of NASH associated with obesity is still poorly understood. MethodsHepatocyte PPAR{gamma} was knocked out (Pparg{Delta}Hep) after the development of high-fat diet-induced obesity in male and female mice and before NASH was induced with a high fat, cholesterol and fructose (HFCF) diet. We assessed the effect of the diets and Pparg{Delta}Hep on body composition and glucose homeostasis, as well as on the liver pathology, gene expression, and metabolome. In addition, liver biopsies from a cohort of 102 bariatric surgery patients were assessed for liver histology and gene expression. ResultsPPAR{gamma} expression, specifically PPAR{gamma}2, is mostly derived from hepatocytes and increased by high fat diets. Pparg{Delta}Hep reduced HFCF-induced NASH progression without altering steatosis. Interestingly, Pparg{Delta}Hep reduced the expression of key genes involved in hepatic fibrosis in HFCF-fed male and female mice, and collagen- stained fibrotic area in the liver of HFCF-fed male mice. In addition, transcriptomic and metabolomic data suggested that HFCF-diet regulated hepatic amino acid metabolism in a hepatocyte PPAR{gamma}-dependent manner. Specifically, Pparg{Delta}Hep increased betaine-homocysteine methyltransferase expression and reduced homocysteine levels in HFCF- fed male mice. In a cohort of 102 bariatric surgery patients, 16 cases of NASH were associated with increased insulin resistance and hepatic PPAR{gamma} expression. ConclusionsHepatocyte PPAR{gamma} expression associated with obesity could regulate methionine metabolism and the progression of fibrosis in NASH.

physiology↗

bioRxiv2022

Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans

How sensory perception is processed by the two sexes of an organism is still only partially understood. Despite some evidence for sexual dimorphism in auditory and olfactory perception, whether touch is sensed in a dimorphic manner has not been addressed. Here we find that the neuronal circuit for tail mechanosensation in C. elegans is wired differently in the two sexes and employs a different combination of sex-shared sensory neurons and interneurons in each sex. Reverse genetic screens uncovered cell- and sex-specific functions of the alpha-tubulin mec-12 and the sodium channel tmc-1 in sensory neurons, and of the glutamate receptors nmr-1 and glr-1 in interneurons, revealing the underlying molecular mechanisms that mediate tail mechanosensation. Moreover, we show that only in males, the sex-shared interneuron AVG is strongly activated by tail mechanical stimulation, and accordingly is crucial for their behavioral response. Importantly, sex reversal experiments demonstrate that the sexual identity of AVG determines both the behavioral output of the mechanosensory response and the molecular pathways controlling it. Our results present for the first time extensive sexual dimorphism in a mechanosensory circuit at both the cellular and molecular levels.

neuroscience↗

bioRxiv2021

Deploying photons for communication within neuronal networks

Deficiencies in neurotransmission lead to neurological disorders or misinterpretation of perceived threats. To restore defects in cellular communication, we developed a synthetic, photon-assisted synaptic transmission (PhAST) system. PhAST is based on luciferases and channelrhodopsins that enable the transmission of a neuronal state across space, using photons as neurotransmitters. We demonstrate the ability to overcome synaptic barriers and rescue the behavioral deficit of a genetically engineered glutamate mutant with conditional, Ca2+-triggered photon emission between two cognate neurons of the Caenorhabditis elegans nociceptive avoidance circuit. We also deploy these ingredients for asynaptic transmission between two unrelated cells in a sexually dimorphic neuronal network. Functional PhAST could sensitize otherwise poorly responsive males to touch and hence expand the behavioral repertoire. Our study, thus, establishes a powerful framework for complex photon-based communication between neurons in a living animal, that can readily be expanded to synthetic neuronal networks, organoids or non-invasive brain-machine interfaces.

synthetic biology↗

bioRxiv2020

The response of culturally important plants to experimental warming and grazing in Pakistan Himalayas

The response of wild plants towards climate warming is taxa specific, but overgrazing could also be a determining factor for the alpine ecosystems. Overgrazing and climate warming are important drivers of alpine grassland degradation worldwide. Local indigenous peoples will be the first impacted by such degradation due to impacts on animal production and the availability of local medicinal plants. Studies on plant responses to overgrazing and climate change are rarely performed to assess threats to these biological and cultural systems. Long-term observations or manipulative experiments are promising, but rarely use strategies to evaluate the sensitivity and vulnerability of such ecosystems to climatic change. We studied the combined effects of overgrazing and increased temperatures on culturally important medicinal plants of Khunjerab National Park, Pakistan. Three experimental treatments were used (control, warming through an open-top chamber, and exclusion of grazing animals vs. the control). These experimental plots were installed at different elevations (3352-4969 m) and were monitored routinely. Grazing reduced vegetation cover & biomass by 2.3% and 6.26%, respectively, but that was not significant due to the high variability among study plots. However, warming significantly increased the overall percentage cover and biomass of all target plant species, ranging from 1{+/-}0.6% in Bistorta officinalis to 18.7 {+/-} 4.9% in Poa alpina. Thus, warming may increase the availability of therapeutic plants for indigenous people while overgrazing would have deteriorating effects locally. This research illustrates that vegetation sensitivity to warming and overgrazing is likely to affect man- environment relationships, and traditional knowledge on a regional scale.

ecology↗

bioRxiv2019

Inferring punctuated evolution in the learned songs of African sunbirds

Signals used in animal communication, especially those that are learned, are thought to be prone to rapid and/or regular evolution. It has been hypothesized that the evolution of song learning in birds has resulted in elevated diversification rates, as learned song may be subject to especially rapid evolution, and song is involved in mate choice. However, we know little about the evolutionary modes of learned song divergence over timescales relevant to speciation. Here we provide evidence that aspects of the territorial songs of Eastern Afromontane sky island sunbirds Cinnyris evolve in a punctuated fashion, with periods of stasis, on the order of hundreds of thousands of years or more, broken up by strong evolutionary pulses. Stasis in learned songs is inconsistent with learned traits being subject to constant or frequent change, as would be expected if selection does not constrain song phenotypes, or if novel phenotypes are frequently advantageous. Learned song may instead follow a process resembling peak shifts on adaptive landscapes. While much research has focused on the potential for rapid evolution in bird song, our results suggest that selection can tightly constrain the evolution of learned songs over fairly long timescales. More broadly, these results demonstrate that some aspects of highly variable, plastic traits can exhibit punctuated evolution, with stasis over fairly long time periods.

evolutionary biology↗