Biology subjects

Khan, E.

Publications and source records attributed to Khan, E..

7 recordsLinked to original sources

bioRxiv2026

Hidden Markov Modeling Reveals Altered Functional Network Dynamics in Multiple Sclerosis

Purpose: Multiple sclerosis (MS) is a neurodegenerative and demyelinating disease of the central nervous system. Recent evidence suggests that localized gray matter atrophy in MS may be involved in distributed functional brain networks. However, the dynamic trajectory of functional network alterations in MS remains unclear. The current study extends prior network-mediated findings and aims to investigate the dynamic functional connectivity (dFC) and energetic landscape across an atrophy-prone network in MS. Methods: Twenty MS participants and twenty healthy controls (HC) underwent resting-state fMRI. The atrophy-based functional network (AFN) model was implemented, and time series from atrophy-prone regions were fit to a 12-state hidden Markov model. Each functional network state, a recurring pattern of activity across the AFN, was characterized by the AFN regions with the strongest activation. The states were then grouped into two metastates. Dynamic functional network metrics were compared between groups by permutation testing and correlated with disability and cognition. The energetic landscape of the network was mapped with a pairwise maximum-entropy model. Temporal irreversibility was also measured, which defines the arrow-of-time asymmetry of network dynamics. Results: People with MS showed lower occupancy of state 1, which peaked on the right middle frontal and anterior cingulate cortex. Occupancy and mean lifetime were higher in states 3 and 10 (p < 0.05). In state 3, cortical activity was below the network average, and state 10 peaked on the postcentral gyrus. At the metastate level, MS participants spent more time in metastate M1 and less in M2 (p = 0.04). Within the MS group, a longer interval between visits to state 3 was associated with greater disability (r = 0.57), and a higher switching rate in state 10 with poorer verbal fluency (r = -0.50). The energetic landscape was similar between groups. Temporal irreversibility was lower in MS, mainly across subcortical connections. Conclusion: MS participants dwelled longer in specific dFC states of the AFN, while the rate of transition between states did not differ from healthy controls. Dynamic functional network metrics were associated with disability and cognitive performance and may serve as functional correlates of clinical impairment. The states were similar between groups, whereas the directed drive between states was lower across subcortical connections. This pattern suggests altered network dynamics rather than altered network architecture in MS. Findings from this study characterize the functional network dynamics of neurodegeneration in MS, which may inform future development of network-based approaches for monitoring disease progression.

neuroscience↗

bioRxiv2026

Genome Assembly of the Iconic Samba Mahsuri Delineates Locus-specific Population Structure within Indica Rice

High-quality reference genomes enable detailed analysis of structural variation and its consequences for genome organization in crops. Here, we present a chromosome-scale genome assembly of Oryza sativa cv. Samba Mahsuri (SM), an elite Indian mega rice variety cultivated for its grain and cooking quality. Using PacBio HiFi sequencing in combination with Illumina reads and Bionano optical mapping, we generated a [~]395 Mb assembly (SMv1.0) with 97.7% BUSCO completeness. A robust annotation framework identified 31,138 evidence-guided protein-coding gene models alongside 59,152 ab initio predictions. Comparative genomic analyses revealed extensive macrosynteny with established rice reference genomes, while uncovering pronounced locus-specific sequence and structural polymorphisms. Notably, a complex inversion-match-inversion (IMI) configuration on chromosome 6 differentiates SM from the japonica reference Nipponbare, but not from the indica reference R498. Population-scale analyses of 533 cultivated and 4 wild rice accessions demonstrate that genetic variation within the IMI region produces a markedly sharper and more coherent population structure than is observed in flanking regions or genome-wide, including tight subpopulation-based clustering and segregation of alternative IMI configurations within indica rice. Together, these results establish SMv1.0 as a robust chromosome-scale reference genome sequence for rice and demonstrate how large structural polymorphisms can shape locus-specific patterns of relatedness that diverge from genome-wide ancestry. Significance StatementWe present a high-quality chromosome-scale genome sequence of the elite Indian rice variety Samba Mahsuri (SM), which, to the best of our knowledge, represents the first chromosome-scale reference genome from Indian rice germplasm assembled using a map-based method. Using this reference to analyze population-scale genotyping data from 533 cultivated and four wild rice accessions reveals markedly tighter population clustering within a megabase-scale inversion (IMI) region, than at the whole-genome scale, along with a pronounced split within indica rice that is independent of genome-wide ancestry.

plant biology↗

bioRxiv2025

Evidence of spinal cord comparator modules for rapid corrections of movements

Successful movement requires continuous adjustments in response to changes in internal and external environments. To do so, neural circuits continuously compare efference copies of motor commands with sensory feedback to respond to sensory prediction errors. Some responses need to be very fast, indicating that they likely occur within spinal cord circuits. Here, we describe spinal cord circuits involving dI3 neurons, showing that they receive multimodal sensory inputs and direct efferent copies from both Renshaw cells and motor neurons. We further show that they form connections to motor pools. Reducing dI3 neuronal activity diminished stumbling responses, as did disrupting Renshaw cell circuits, providing evidence for a comparator role of dI3 neurons for online corrections. Together, our findings reveal a pivotal role for dI3 neurons functioning as comparators of efference copies and external sensory feedback to mediate rapid corrections of ongoing movements.

neuroscience↗

bioRxiv2025

Cell size regulation in bacteria: a tale of old regulators with new mechanisms

Successful proliferation of bacteria requires the coordination of multiple cellular events. The precise coordination between the replication of the chromosome with cell growth and division is essential for daughter cells to inherit an intact copy of the genome with the appropriate cell size. However, the molecular mechanisms that temporally and spatially integrate these essential processes have remained elusive in the field. Using the model system C. crescentus, we uncovered a previously unrecognized role for the conserved chromosome replication initiator DnaA in regulating cell growth and division dynamics. Through mutant analyses, transcriptional profiling, biochemical and high-resolution imaging, our data demonstrate that DnaA modulates cell size through direct transcriptional activation of enzymes involved in cell wall biosynthesis. We identify a conserved cell wall biosynthetic enzyme, MurD, as a key downstream effector and demonstrate its unexpected ability to restrict cell size. Both in vivo and in vitro analyses revealed that the transcriptional regulation of murD requires the ATP-bound form of DnaA, the same nucleotide-bound form required for initiating chromosome replication. These findings highlight how bacteria leverage the conserved nucleotide-dependent switch, DnaA-ATP, to temporally orchestrate spatially distinct processes ensuring accurate progression of the cell cycle.

microbiology↗

bioRxiv2022

BBIBP-CorV (Sinopharm) vaccination- induced immunity is affected by age, gender and prior COVID-19 and activates responses to spike and other antigens

Long-term solutions against SARS-CoV-2 infections require understanding of immune protection induced by different vaccine COVID-19 formulations. We investigated humoral and cellular immunity induced by Sinopharm (BBIBP-CorV) in a region of high SARS-CoV-2 seroprevalence. Levels of IgG antibodies to SARS-CoV-2 spike protein and its receptor-binding domain (RBD) were determined 24-weeks. Cellular immunity was investigated using a commercially available IFN-{gamma} release assay to SARS-CoV-2 spike (Ag1 and 2) and extended genome antigens (Ag3). Increasing IgG seropositivity to Spike protein and RBD was observed post-vaccination. Seropositivity was reduced in those over 50 years and raised in females and those with prior COVID-19. After 20 weeks post-vaccination, only one third of participants had positive T cell responses to SARS-CoV-2 antigens. Prior COVID-19 impacted IFN{gamma} responses, with reactivity enhanced in those infected earlier. The frequency of IFN{gamma} responses was highest to extended genome antigen set. Overall, BBIBP-CorV- induced antibody responses were impacted by age, gender and prior COVID-19. Cellular immunity was present in a limited number of individuals after 20 weeks but was enhanced by prior infection. This suggests the need for booster vaccinations in older individuals. BBIBP-CorV-induced cellular activation is broader than to spike, requiring further study to understand how to monitor vaccine effectiveness.

immunology↗

bioRxiv2021

Structural and functional characterization of Rv0792c from Mycobacterium tuberculosis: identifying small molecule inhibitors against GntR protein.

In order to adapt in host tissues, microbial pathogens regulate their gene expression through an array of transcription factors. Here, we have functionally characterized Rv0792c, a GntR homolog from M. tuberculosis. In comparison to the parental strain, {Delta}Rv0792c mutant strain of M. tuberculosis was compromised for survival upon exposure to oxidative stress, cell wall agents and infection in guinea pigs. RNA-seq analysis revealed that Rv0792c regulates the expression of genes that are involved in stress adaptation and virulence of M. tuberculosis. Solution small angle X-ray scattering (SAXS) data steered model building confirmed that the C-terminal region plays a pivotal role in dimer formation. Systematic evolution of ligands by exponential enrichment resulted in identification of ssDNA aptamers that can be used as a tool to identify small molecule inhibitors targeting Rv0792c. Using SELEX and SAXS data based modelling, we identified residues essential for the DNA binding activity of Rv0792c and I-OMe-Tyrphostin as an inhibitor of Rv0792c aptamer binding activity. Taken together, we provide a detailed shape-function characterization of GntR family of transcription factors from M. tuberculosis. To the best of our knowledge, this is the first study that has resulted in the identification of small molecule inhibitors against GntR family of transcription factors from bacterial pathogens.

microbiology↗

bioRxiv2021

Non-invasive imaging of gene expression and protein secretion dynamics in living mice

The topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities.

cell biology↗