Biology subjects

Ahmad, Z.

Publications and source records attributed to Ahmad, Z..

15 recordsLinked to original sources

bioRxiv2026

Chemogenetic Inhibition of the Ventrolateral Orbitofrontal Cortex Disrupts Prediction Error and Salience-Guided Memory-Updating at the Hippocampal Engram Level

RationaleAdaptive behavior requires revising memories when outcomes deviate from expectations. The orbitofrontal cortex (OFC) is implicated in representing outcome expectancies, but its role in memory-updating, beyond value-based learning, remains unclear. ObjectivesWe tested whether the ventrolateral OFC (VLO) contributes to hippocampal-dependent memory-updating in the Objects in Updated Locations (OUL) task, where novelty-driven exploration provides a behavioral readout consistent with successful updating of spatial information MethodsUsing inhibitory DREADDs, in male and female (Swiss Webster and C57BL/6) mice, we suppressed VLO activity during the Updating session, when new object-location information was introduced. ResultsControl mice preferentially explored the updated object-location configuration during Updating and discriminated between updated and novel object-location configurations at Test, whereas VLO-inhibited mice did not. VLO inhibition when no updating demand was present did not alter exploration of novel object-location configurations or memory for the original spatial configuration at Test. ConclusionsThese results indicate that VLO activity is selectively required when novelty must be interpreted relative to prior experience, implicating this region in evaluating change rather than detecting it. To assess hippocampal ensemble dynamics, we tagged neuronal ensembles, in the dorsal dentate gyrus (dDG) recruited during Updating, followed by quantification of overlap between Updating-tagged cells and ensembles reactivated at Test. We found that VLO inhibition reduced reactivation of Updating-tagged dDG ensembles, paralleling the behavioral impairments observed in the OUL task. These findings support a role for the VLO in hippocampal-dependent memory-updating and extend OFC models beyond reward contexts to include predictive updating of spatial memory representations. Significance StatementUsing a spatial paradigm that distinguishes detection of changed information from incorporation of that information into an updated hippocampal representation, we found that ventrolateral orbitofrontal cortex (VLO) activity is required for memory-updating when new information is present. We found behavioral deficits accompanied by impairments in hippocampal ensemble representations, indicating VLO activity is necessary for memory-updating at the hippocampal engram level. Through this mechanism, the OFC supports the flexible updating of expected outcomes when environmental conditions shift, allowing for the re-evaluation of previously learned associations. These findings extend models of orbitofrontal cortex function beyond reward-guided behavior and identify a cortical contribution to predictive spatial memory processes. Disruption of this computation may contribute to the cognitive rigidity observed in neuropsychiatric disorders.

neuroscience↗

bioRxiv2026

Biomineralized Surface-Enhanced Raman Scattering Nanotags Encode Biomolecular Identity into Machine Learning-Resolvable Plasmonic Fingerprints

Surface-enhanced Raman scattering (SERS) nanotags provide highly sensitive platforms for in vitro diagnostics but often require complex, disease-specific customization that limits clinical translation. Biomineralization, in which biomolecules mediate inorganic material synthesis, offers a versatile yet underexplored strategy for generating functional SERS nanotags. Here, we demonstrate that biomolecule-directed biomineralization of gold nanoparticles (AuNPs) using amino acids and exosomes generates distinct nano-bio interfacial architectures that encode biomolecular identity into machine learning-resolvable SERS fingerprints through modulation of plasmonic coupling and Raman reporter organization. As a proof-of-concept system, amino acid-biomineralized AuNPs were synthesized using biomolecules with diverse physicochemical properties, including differences in size, polarity, and charge. The resulting nanotags were characterized using UV-Vis spectroscopy, SERS, fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Random forest and support vector machine (SVM) models successfully differentiated amino acid-dependent SERS signatures with near-perfect classification performance. Extending this approach to a biologically complex preclinical cancer model, exosome-biomineralized AuNP nanotags were generated using exosomes derived from clinically relevant pediatric patient-derived osteosarcoma and neuroblastoma tumors. Distinct exosome-dependent spectral fingerprints enabled SVM classification with 93.9% accuracy, while Shapley Additive exPlanations (SHAP) and t-distributed stochastic neighbor embedding (t-SNE) analyses identified diagnostically relevant spectral regions and visualized clustering between tumor classes. Collectively, this work establishes biomineralization as a strategy for transforming complex biomolecular and cellular information into computationally resolvable optical fingerprints, enabling scalable and label-free diagnostic classification of patient-derived biomolecular samples.

bioengineering↗

bioRxiv2025

Preserved perception-action dissociation but altered visuomotor behaviours in healthy aging.

The two visual pathways hypothesis posits distinct brain systems for vision-for-perception and vision-for-action. While this dissociation is well-established in younger adults, its integrity in healthy aging remains unclear. To address this, younger (n = 25, range: 18-25 years) and older adults (n = 25, range: 65-95 years) completed estimation and grasping tasks in two experiments. In Experiment 1, two rectangular objects with varying lengths (40 mm and 42 mm) were placed on the "far" and "close" surfaces of a Ponzo illusion. Despite age-related changes in grasping kinematics, the perception-action dissociation persisted. The Ponzo illusion influenced estimation such that objects placed on the "far" surface were perceived as longer. In contrast, grasping was not affected by the illusion, and even showed effect in the opposite direction, with larger apertures for objects placed on the "close" surface of the illusion. Experiment 2 tested whether this reversed effect was mediated by the surface size on which the object was placed, rather than perceived distance. To this end, we removed the illusory distance cues and varied only the background surface size ("big" versus "small"). While perceptual estimations were unaffected, surface size modulated grasping in both age groups, with a stronger effect in older adults. These findings indicate that the perception-action dissociation is preserved in aging, but older adults rely more on contextual cues during action, potentially reflecting compensatory mechanisms to maintain visuomotor performance.

neuroscience↗

bioRxiv2025

Low and high frequency signatures of impaired consciousness in temporal lobe seizures

Impaired consciousness is a debilitating and unpredictable outcome of mesial temporal lobe seizures whose mechanisms to date remain unclear. Moreover, questions about the relationship between impaired consciousness and lateralization, hemispheric spread and electrophysiological characteristics of seizures are yet to be answered. To address these gaps, we conducted in-depth investigation of behavioral and intracranial EEG data from 186 mesial temporal lobe seizures of 51 patients with intractable mesial temporal lobe epilepsy. We found that bilateral mesial temporal spread of seizures is not a necessary condition for impaired consciousness, although seizures with bilateral mesial temporal involvement were significantly more likely to have impaired consciousness than unilateral seizures. Contrary to prior belief, we found no relationship between the onset side (left vs. right temporal lobe or language dominant vs. non-dominant lobe) of seizures and the probability of impaired consciousness. Lastly, we established that widespread increases in slow-wave activity (delta band) in extratemporal cortical areas, as well as increases in fast activity (beta band) in the temporal lobes were both robust markers of seizures with impaired consciousness and could predict ictal impairment with up to 86% accuracy. Our findings shed new light on networks that underlie impaired consciousness in temporal lobe epilepsy and may help guide deep brain stimulation of such systems (e.g. via thalamic nuclei) as a potential intervention to improve consciousness during seizures.

neuroscience↗

bioRxiv2025

Stretchable, hair-compatible, and long-term stable wearable EEG system

Electroencephalography (EEG) is a cornerstone in both neuroscience research and clinical diagnostics. However, conventional EEG monitoring faces hardware limitations, particularly its adaptability and stability. Headsets either require complicated wiring or do not have enough stretchability and wearability to comply with the diverse head anthropometry and hair conditions of the user population. Additionally, there is an inherent tradeoff between wet and dry electrodes in capturing high-fidelity signals from hair-covered scalp regions while ensuring continuous and long-term recording quality. Here, we present a Mesh-integrated, Stretchable, and Hair-compatible EEG system engineered to overcome these limitations. By incorporating a kirigami-inspired mesh design and stretchable eutectic Gallium-Indium interconnects, MindStretcH adapts to various head sizes and allows for easy wearing and removal. Moreover, its uniquely designed porous, conical, soft 3D-printed mold, embedded with hydrogel electrodes, effectively penetrates hair layers to deliver low impedance and sustained signal integrity with minimal discomfort. We validate MindStretcH through offline and online EEG-based brain-computer interface tasks over a month, demonstrating its exceptional stability in continuous monitoring and dynamic applications. These results mark a promising advance toward non-invasive neural interfaces in both clinical and everyday use.

bioengineering↗

bioRxiv2024

LIFERING, an E3 ligase, targets the acyl-CoA dehydrogenase-like protein IBR3, for ubiquitination and coordinates cell proliferation and cell death upon DNA damage

Plants rapidly respond to environmental changes to ensure an optimal balance between growth and survival with intact genome. Here, we show that a DNA damage response gene, which we named LIFERING, is under the direct and independent regulation of ATM/ATR-SOG1 and RBR pathways. We demonstrate that LIFERING upon DNA damage plays an essential role in maintaining the balance between cell proliferation and cell death. Downstream of RBR, it is required to maintain proliferation, and in response to DNA damaging agents it initiates a cell death accompanied by rapid elongation and differentiation of the transit amplifying cells in the root meristem. LIFERING is a RING-between-RING E3 ligase; its ligase activity is dependent on the Cys392 residue located in the BRcat domain, responsible for the coordination of zinc ion binding. Using proximity labelling, we identified the acyl-CoA dehydrogenase-like protein IBR3, which is involved in the conversion of indole-3-butyric acid (IBA) to indole-3-acetic acid (IAA), as one of its targets. We provide evidence that IBR3 is ubiquitinated at several Lys residues in the presence of LIFERING. Our findings show that LIFERING rapidly responds to DNA damage and via ubiquitination of IBR3, is likely to be involved in the regulation of free-auxin level, indicating a link between DNA damage response and auxin regulation in the root.

plant biology↗

bioRxiv2024

JUNB O-GlcNAcylation-mediated promoter accessibility of metabolic genes modulates distinct epithelial lineage in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with substantial unmet medical needs. While aberrant epithelial remodelling is a key factor in IPF progression, the molecular mechanisms behind this process remain elusive. Using a patient-derived 3D distal airway epithelial organoid model, we successfully recapitulate important IPF features, including the emergence of aberrant KRT5+/COL1A1+ basal cells and a metabolic shift towards increased O-linked {beta}-N-acetylglucosamine (O-GlcNAc) levels. Consistent with this, single-cell analysis of accessible chromatin reveals an increased chromatin accessibility in these aberrant basal cells, particularly at JUNB motif-enriched promoter regions of metabolic genes. O-GlcNAcylation shapes JUNB function and promotes a pro-fibrotic response to chronic injury, leading to aberrant epithelial remodelling. Site-specific deletion of O-GlcNAcylation on JUNB attenuates the metaplastic differentiation of basal cells, thereby aiding in the restoration of the alveolar lineage. Together, these data establish a novel link between metabolic dysregulation, mediated by the O-GlcNAc-JUNB axis, and bronchiolization in IPF, offering new therapeutic strategies to treat this fatal disease.

cell biology↗

bioRxiv2024

A 3D whole-face movement analysis system to uncover underlying physiology in mice

Facial expressions and movements, from a subtle and ephemeral grimace, to vigorous and rapid chewing, offer direct insights into the moment-to-moment change of neural and physiological processes. Mice, with discernible facial responses and evolutionarily conserved mammalian facial movement control circuits, provide an ideal model to unravel the link between facial movement and underlying physiological states. However, existing frameworks lack the spatial or temporal resolution to sensitively track all movements of the mouse face, due to its small and conical form factor. We introduce Cheese3D, a computer vision system that captures high-speed 3D motion of the entire mouse face (including ears, eyes, whisker pad, and jaw, while covering both sides of the face) using a calibrated six-camera array. The interpretable framework extracts dynamics of anatomically-meaningful 3D facial features in absolute world units at sub-millimeter precision. The precise face-wide motion data generated by Cheese3D provides clear physiological insights, as shown by proof-of-principle experiments predicting time under general anesthesia from changing facial patterns, inferring tooth and muscle anatomy from fast ingestion motions across the entire face, measuring minute differences in movements evoked by brainstem stimulation, and relating neural activity to spontaneous facial movements, including expressive features only measurable in 3D (e.g., angles of ear motion). Cheese3D can serve as a discovery tool that renders subtle mouse facial movements highly interpretable as a readout of otherwise hidden internal states.

animal behavior and cognition↗

bioRxiv2024

Stem rot affects the structure of rhizosphere microbiome in Berseem Clover (Trifolium alexandrinum)

Rhizosphere microbiome plays an essential role in maintaining plant health and productivity. Fungal and bacterial diseases may affect the rhizosphere-associated microbial communities and overall structure of plant microbiome. Here, we studied the effect of stem rot of berseem clover on the bacterial and fungal communities associated with the rhizosphere. We analyzed the rhizosphere-associated bacterial and fungal microbiome from healthy and infected berseem clover collected from three sampling sites by using 16S rRNA and ITS based Illumina sequencing metabarcoding approach. Microbiome analysis showed that healthy plants had higher bacterial and fungal diversity as compared to stem rot infected plants. At the genus level, bacterial genera Rhizobium and Comamonas were more abundant in healthy plants while Pantoea was more abundant in infected plants and fungal genera Sclerotinia, Fusarium and Cladorrhinum were more abundant in infected plants while Microdochium and Cladosporium were distinctively abundant in healthy Berseem. Functional characterization of bacterial and fungal microbiomes revealed that bacterial communities from infected plants showed more abundance of bacteria with functions replication and repair, enzyme families and biosynthesis of other secondary metabolites as compared to healthy plant microbiome and decreased in fungal groups including arbuscular mycorrhiza and soil saprotrophs and an increase in plant saprotrophs and fungal parasite-plant pathogens. This study provides comprehensive information about the structure and composition of bacterial and fungal communities associated with the berseem clover rhizosphere that could be utilized for future research on the control of stem rot of berseem clover.

plant biology↗

bioRxiv2024

A comprehensive stroke risk assessment by combining atrial computational fluid dynamics simulations and functional patient data

Stroke, a major global health concern often rooted in cardiac dynamics, demands precise risk evaluation for targeted intervention. Current risk models, like the CHA2DS2-VASc score, often lack the granularity required for personalized predictions. In this study, we present a nuanced and thorough stroke risk assessment by integrating functional insights from cardiac magnetic resonance (CMR) with patient-specific computational fluid dynamics (CFD) simulations. Our cohort, evenly split between control and stroke groups, comprises eight patients. Utilizing CINE CMR, we compute kinematic features, revealing smaller left atrial volumes for stroke patients. The incorporation of patient-specific atrial displacement into our hemodynamic simulations unveils the influence of atrial compliance on the flow fields, emphasizing the importance of LA motion in CFD simulations and challenging the conventional rigid wall assumption in hemodynamics models. Standardizing hemodynamic features with functional metrics enhances the differentiation between stroke and control cases. While standalone assessments provide limited clarity, the synergistic fusion of CMR-derived functional data and patient-informed CFD simulations offers a personalized and mechanistic understanding, distinctly segregating stroke from control cases. Specifically, our investigation reveals a crucial clinical insight: normalizing hemodynamic features based on ejection fraction fails to differentiate between stroke and control patients. Differently, when normalized with stroke volume, a clear and clinically significant distinction emerges and this holds true for both the left atrium and its appendage, providing valuable implications for precise stroke risk assessment in clinical settings. This work introduces a novel framework for seamlessly integrating hemodynamic and functional metrics, laying the groundwork for improved predictive models, and highlighting the significance of motion-informed, personalized risk assessments.

bioengineering↗

bioRxiv2021

The Epiallelic Nature of Mouse rDNA

BackgroundRibosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this variation impacts epigenetic states and expression of the rDNA has thus far not been performed. ResultsUsing a combination of long- and short-read sequencing, we establish that 45S rDNA units in the C57BL/6J mouse strain exist as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. DNA methylation dynamics at these haplotypes are dichotomous and life-stage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during ageing only. On the other hand, individual rDNA units in human show limited evidence of genetic haplotypes, and hence little discernible correlation between genetic and epigenetic states. However, in both species, adjacent units show similar epigenetic profiles, and the overall epigenetic state at rDNA is strongly positively correlated with total rDNA copy number. Analysis of different mouse inbred strains reveals that in some strains, such as 129S1/SvImJ, rDNA copy number is only approximately 150 copies per diploid genome and DNA methylation levels are <5%. ConclusionsOur work demonstrates that rDNA-associated genetic variation has a considerable influence on rDNA epigenetic state and consequently rRNA expression outcomes. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases.

genomics↗

bioRxiv2021

Unilateral Resection of Both Cortical Visual Pathways Alters Action but not Perception

The human cortical visual system consists of two major pathways, a ventral pathway that subserves perception and a dorsal pathway that subserves visuomotor control. These pathways follow dissociable developmental trajectories, and, accordingly, might be differentially susceptible to neurodevelopmental disorders or injuries. Previous studies have found that children with cortical resections of the ventral visual pathway retain largely normal visuoperceptual abilities. Whether visually guided actions, supported by computations carried out by the dorsal pathway, follow a similar pattern remains unknown. To address this question, we examined visuoperceptual and visuomotor behaviors in a pediatric patient, TC, who underwent a cortical resection that included portions of the left ventral and dorsal pathways. We collected data when TC used her right and left hands to perceptually estimate the width blocks that varied in width and length, and, separately, to grasp the same blocks. TCs perceptual estimation performance was comparable to that of controls, independent of the hand used. In contrast, relative to controls, she showed reduced visuomotor sensitivity to object shape and this was more evident when she grasped the objects with her contralesional right hand. These results provide evidence for a striking difference in the reorganization profiles of the two visual pathways. This difference supports the notion that the two pathways exhibit differential susceptibility to neurodevelopmental disorders.

neuroscience↗

bioRxiv2020

Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α

Obesity is associated with elevated levels of TNF- and proinflammatory CD11c monocytes /macrophages. TNF- mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since neutral sphingomyelinase 2 (nSMase2; product of the sphingomyelin phosphodiesterase 3 gene, SMPD3) is a key enzyme for ceramide production involved in inflammation, we investigated whether nSMase2 contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-. In this study, we demonstrate that the disruption of nSMase activity in monocytes/macrophages either by chemical inhibitor GW4869 or small interfering RNA (siRNA) against SMPD3 results in defects in the TNF- mediated expression of CD11c. Furthermore, blockage of nSMase in monocytes/macrophages inhibited the secretion of inflammatory mediators IL-1b and MCP-1. In contrast, inhibition of acid SMase (aSMase) activity did not attenuate CD11c expression or secretion of IL-1b and MCP-1. TNF--induced phosphorylation of JNK, p38 and NF-{kappa}B was also attenuated by the inhibition of nSMase2. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of nSMase2. SMPD3 was elevated in PBMCs from obese individuals and positively corelated with TNF- gene expression. These findings indicate that nSMase2 acts, at least in part, as a master switch in the TNF- mediated inflammatory responses in monocytes/macrophages.

immunology↗

bioRxiv2020

Characterization Of Yellow Root Cassava And Food Products: Investigation Of Cyanogenic Glycosides And Pro-Vitamin A

ObjectiveCyanide is a highly toxic compound, and the consumption of products containing cyanide is of singificant public health concern. In contrast, {beta}-carotene possesses essential nutritional attributes related to human health, therefore the characterisation and quanfication of both compounds in food products is both fundamental and necessary. This investigation sought to identify the cyanide and {beta}-carotene levels in two flours produced from the roots of two varieties of cassava (Manihot esculenta crantz), namely UMUCASS-38 (TMS 01/1371) and NR 8082, and their associated food products. ResultsThe fresh tuber, raw flour and food products were analysed for levels of residual cyanide and {beta}-carotene using standard analytical methods. The cyanide content of NR 8082 (18.01{+/-}0.01 ppm) and UMUCASS 38 (17.02{+/-}0.02 ppm) flours were significantly higher (p < 0.05) than the residual cyanide levels determined in the cookies (10.00{+/-}0.00 ppm) and cake (7.10{+/-}0.14 ppm). The levels of {beta}-carotene determined in the sample varied significantly (p < 0.05). The highest levels of {beta}-carotene (6.53{+/-}0.02 {micro}g/g) were determined in raw roots of UMUCASS 38 while NR 8082 levels of {beta}-carotene were 1.12{+/-}0.02 {micro}g/g. Processing the roots into flour reduced the {beta}-carotene content to 4.78{+/-}0.01 {micro}g/g and 0.76{+/-}0.02 {micro}g/g in UMUCASS 38 and NR8082 flours, respectively. Cookies and cake produced from flour derived from the UMUCASS 38 variety had 2.15{+/-}0.01 {micro}g/g and 2.84{+/-}0.04 {micro}g/g of {beta}-carotene, respectively.

biochemistry↗

bioRxiv2018

Flux Balance Analysis Identifies Distinct NADPH Production Strategies Across NCI 60 Cancer Cell Lines

Flux Balance Analysis is a linear mathematical procedure which determines the set of reaction fluxes to produce a maximum flux of a reaction of interest. In this study, a core cancer model developed by Zielinski et al. 2017 is constrained by a set of 59 cancer cell type specific uptake and secretion rates. Optimizing for cell type specific biomass objective reactions and examining serine flux distributions reveals variability in production of NADPH. In many cell lines, production of NADPH is correlated to biosynthetic demand, however, outliers exist that produce excess NADPH beyond that of biomass demand. These outliers are first characterized by their NADPH production strategy (pentose phosphate pathway or a combination of One Folate Cycle and Malic Enzyme) and then the factors responsible for the different NADPH production strategies are identified. Results indicate that pentose phosphate pathway (PPP) producing NADPH cell lines had reprogrammed tricarboxylic acid cycle metabolism to meet the demand for decreased flux through glycolytic enzymes, while one folate cycle and malic enzyme (OFC + ME) producing NADPH cell lines had higher threonine, tyrosine and serine uptake.

bioengineering↗