Biology subjects

Parmar, R.

Publications and source records attributed to Parmar, R..

10 recordsLinked to original sources

bioRxiv2026

The anti-dyskinetic and the anti-parkinsonian effects of sub-anesthetic ketamine are also present in female preclinical models

Biological sex is an important determinant of neuropharmacological response, yet females remain underrepresented in preclinical studies of Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). We previously demonstrated that sub-anesthetic ketamine reduces established LID, attenuates dyskinesia development, and produces anti-parkinsonian effects in male unilateral 6-hydroxydopamine (6-OHDA) rat models. However, whether these therapeutic effects extend to females remained unknown. Here, we evaluated the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine in female Sprague-Dawley rats using the attenuation and established models of LID. In the attenuation paradigm, unilateral 6-OHDA-lesioned females received repeated L-DOPA administration with either ketamine (20 mg/kg, i.p.; 10-h dosing paradigm) or vehicle. Ketamine significantly attenuated the progressive development of dyskinesia, indicating that early intervention modified the trajectory of LID expression. In the established LID paradigm, ketamine produced robust significant acute reductions in abnormal involuntary movements (AIMs) after dyskinesia had fully developed, and these significant effects persisted for up to 49 days following treatment, demonstrating sustained suppression of dyskinesia severity. To determine whether ketamine altered therapeutic motor function, forelimb adjusting steps testing was performed in female unilateral 6-OHDA rats. Ketamine did not impair L-DOPA-mediated motor improvement suggesting compatibility with the gold standard medication. Ketamine was also by itself associated with significantly improved stepping performance during ketamine treatment conditions, indicating acute anti-parkinsonian motor benefit. Together, these findings demonstrate that the anti-dyskinetic and anti-parkinsonian effects of ketamine extend to female preclinical models and strengthen the translational rationale for repurposing sub-anesthetic ketamine as a potential therapeutic strategy for individuals with LID.

neuroscience↗

bioRxiv2026

Dyskinesia induced by a dopamine 2 receptor-like agonist, but not a dopamine 1 receptor-like agonist, is blocked by sub-anesthetic ketamine

L-DOPA remains the most effective symptomatic treatment for Parkinson's disease, but chronic administration is frequently complicated by L-DOPA-induced dyskinesia (LID). Our prior work has established that sub-anesthetic ketamine can reduced LID acutely and has a long-lasting neuroplastic effect. This study tested whether low-dose ketamine reduces dyskinesia induced specifically by dopamine D2R-like or D1R-like receptor activation. Male Sprague Dawley rats were primed with daily L-DOPA to establish dyskinesia and then challenged with quinpirole, a D2R-like receptor agonist, or SKF-81297, a D1R-like receptor agonist, to induce abnormal involuntary movements (AIMs). After stable AIM baselines were established, animals received agonist plus vehicle or agonist plus ketamine. Limb, axial, and orolingual AIMs were scored on the acute treatment day (D0) and after washout on D4 and D7. Quinpirole and SKF-81297 reliably produced stable total LAO AIM scores following L-DOPA priming. Ketamine significantly reduced only quinpirole-induced, but not SKF-81297-induced, total AIMs compared with vehicle on D0, demonstrating an acute anti-dyskinetic effect. This reduction persisted after washout, with ketamine-treated animals continuing to show significantly lower AIMs on D4 and D7. Time-course analyses further showed reduced AIMs expression across the post-quinpirole observation period on D0 and at multiple time points on D7. These findings demonstrate that ketamine suppresses quinpirole-induced dyskinesia in L-DOPA-primed male rats and suggest that D2R-like receptor-mediated or indirect pathway-related mechanisms, but not direct pathway-related mechanisms, may contribute to ketamine's anti-dyskinetic effects. Together, these results extend prior work on ketamine by linking its sustained anti-dyskinetic effects to dyskinesia driven by D2R-like receptor stimulation in vivo.

neuroscience↗

bioRxiv2026

Bacteroides intestinalis-Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

Insufficient dietary fiber intake is closely linked to gut microbiome dysfunction and increased risk of noncommunicable diseases. Synergistic synbiotics, pairing defined microbes with their dietary substrates, offer a precise strategy to restore microbiome function. Here, we show that pairing the human colonic commensal Bacteroides intestinalis with insoluble wheat arabinoxylan (inWAX) yields pronounced metabolic and anti-inflammatory benefits. Using mono-associated gnotobiotic mice and high-fat diet-induced obese mice, we demonstrate that this synbiotic enhances resistance to intestinal inflammation and improves glucose homeostasis. Mechanistically, this synbiotic increases production of 6-hydroxylated bile acids with anti-diabetic and anti-steatotic effects. It also promotes microbial transformation of phenolic compounds and redirects protein metabolism toward neuroactive metabolites. These metabolic shifts are accompanied by transcriptional remodeling in the colon, spleen and liver, involving induction of genes essential for circadian rhythm, lipid metabolism, immune defense, and bile acid 6-hydroxylation. Notably, Y chromosome-linked genes associated with epigenetic regulation and protein turnover are also induced, suggesting a potential sex-specific response to synbiotics. Together, our findings establish a mechanistic framework for targeted synbiotic interventions to combat inflammatory and metabolic disorders.

microbiology↗

bioRxiv2025

Enhancing CRISPR Education: A Plug-And-Play Framework for Teaching Gene Editing in Plant Biology

Modern molecular biology tools and technologies such as CRISPR have sped up scientific discovery. From an educational perspective, these advancements are both exciting and overwhelming. Educators shaping these future scientists face the ongoing challenge of staying compliant with the latest developments in molecular biology while finding effective ways to teach these discoveries. As the use of CRISPR gene editing technology continues to expand globally, there is an increasing need for a workforce that is both knowledgeable about its theoretical foundations and trained in its practical use. While advanced, technology-driven STEM courses have the potential to improve student retention, they are often lecture-heavy and lack intentional engagement strategies that support deeper learning. Moreover, agriculture is the second most impacted sector by this technology, yet there is a significant lack of teaching materials focused on CRISPR in plant biology. To address these gaps, we developed a framework for teaching gene editing that incorporates multiple engagement strategies beyond traditional lecture-based instruction. This framework was implemented over two semesters in an Introduction to Gene Editing course at Tennessee State University, offered to both undergraduate and graduate students enrolled in a degree in Agricultural Sciences. This manuscript outlines the various strategies used in the course including active learning, multimodal instructional approaches and experiential learning strategies that can be adopted in other classrooms to effectively teach gene editing. Survey-based results from the course indicate a measurable increase in student comfort with designing and executing CRISPR-Cas based experiments. Societal Impact StatementPlant biology lacks accessible teaching materials for CRISPR, a powerful gene-editing technology widely used to improve agriculture. We developed an engaging framework to teach CRISPR concepts to advanced undergraduates and graduate students in plant sciences, which can be readily adopted by other instructors. The approach increased self-reported confidence in students and comfort in explaining CRISPR. Since instructors often have limited time to design interactive lessons, this framework offers a ready-to-use, effective strategy that makes CRISPR more widely available in classrooms, ultimately strengthening CRISPR literacy in the future agricultural workforce.

scientific communication and education↗

bioRxiv2025

What Large Language Models Know About Plant Molecular Biology

Large language models (LLMs) are rapidly permeating scientific research, yet their capabilities in plant molecular biology remain largely uncharacterized. Here, we present MOBIPLANT, the first comprehensive benchmark for evaluating LLMs in this domain, developed by a consortium of 112 plant scientists across 19 countries. MOBIPLANT comprises 565 expert-curated multiple-choice questions and 1,075 synthetically generated questions, spanning core topics from gene regulation to plant-environment interactions. We benchmarked seven leading chat-based LLMs using both automated scoring and human evaluation of open-ended answers. Models performed well on multiple-choice tasks (exceeding 75% accuracy), although most of them exhibited a consistent bias towards option A. In contrast, expert reviews exposed persistent limitations, including factual misalignment, hallucinations, and low self-awareness. Critically, we found that model performance strongly correlated with the citation frequency of source literature, suggesting that LLM knowledge inherits the visibility distribution of the underlying scientific corpus. Consequently, models tend to be more reliable on consolidated topics and less reliable on under-cited or recently emerging ones. We also benchmarked agents equipped with web-search and additional tools in more complex tasks involving DNA sequence analysis. These agents were outperformed by domain specific models in sequence classification and regression tasks, indicating an opportunity for joint agentic systems that combine both the reasoning power of LLMs and the dedicated processing of DNA models. This understanding is key to guiding both the development of next-generation models and the informed use of current tools in the everyday work of plant researchers. MOBIPLANT is publicly available online in this link.

plant biology↗

bioRxiv2025

The vaginal microbiota, symptoms, and local immune correlates in transmasculine individuals using sustained testosterone therapy

Transmasculine individuals (assigned female at birth, masculine gender identity, TM) may use gender-affirming testosterone therapy, and some TM report adverse genital symptoms during treatment. In cis women, the vaginal microbiota is a key determinant of reproductive and sexual health outcomes; Lactobacillus-dominant communities are considered optimal, while more even, diverse, Lactobacillus-depleted microbiota are considered non-optimal. Prior studies suggest Lactobacillus deficiency in TM vaginal microbiota, but associations with symptoms and immune markers remain unclear. We launched the TransBiota study to characterize the TM vaginal microbiota, soluble mediators of local inflammation (SMI), and self-reported symptoms over three weeks. Fewer than 10% of TM possessed Lactobacillus-dominant microbiota, and most exhibited more diverse, Lactobacillus-depleted microbiota. We identified 11 vaginal microbiota community state types (tmCSTs), with Lactobacillus-dominant tmCSTs unexpectedly linked to abnormal odor and elevated IL-1. These findings indicate that Lactobacillus dominance may no longer be an optimal state for TM during gender-affirming testosterone therapy and change in clinical management is needed.

microbiology↗

bioRxiv2025

The Neovaginal Microbiota, Symptoms, and Local Immune Correlates in Transfeminine Individuals with Penile Inversion Vaginoplasty

Transfeminine people (assigned male at birth) often undergo penile inversion vaginoplasty to create vulva, a clitoris and a vaginal canal (referred to as a neovagina). After vaginoplasty, transfeminine people frequently experience gynecological concerns but their etiology is unknown due to a lack of knowledge of the neovaginal microenvironment. We characterized neovaginal microbiota and cytokines in 47 transfeminine participants. Participants self-reported sexual behaviors and symptoms, enabling correlation with bacterial (16S rRNA) and immune profiles. Four distinct clusters of co-occurring bacteria with unique immune profiles were identified. One cluster, which included Fastidiosipila, Ezakiella, and Murdochiella, was abundant, stable, and correlated with lower cytokines. Conversely, another cluster containing Howardella, Parvimonas, Fusobacterium, and Lawsonella was linked to higher cytokines. Although Lactobacillus was detected, Lactobacillus-dominance was rare. These findings underscore the need for evidence-based clinical guidelines tailored to transfeminine gynecologic care, emphasizing the vital role of the neovaginal microbiome in symptom management and sexual health.

microbiology↗

bioRxiv2022

Cytokine-expression patterns reveal coordinated immunological programs associated with persistent MRSA bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common, life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy, antibiotics often fail to resolve the infection in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and proteomic data across a well-characterized cohort of patients with persistent and resolving MRSA bacteremia outcomes. Tensor-based data integration yielded high correlative accuracy with persistence and revealed immunologic signatures shared across both the transcriptomic and proteomic datasets. We find that elevated proliferation of mature granulocytes associates with resolving bacteremia outcomes. In contrast, patients with persistent bacteremia heterogeneously exhibit correlates of granulocyte dysfunction or immature granulocyte proliferation. Collectively, these results suggest that transcriptional and proteomic correlates of persistent versus resolving bacteremia outcomes are complex and may not be disclosed by conventional modeling. However, a tensor-based integration approach can help to reveal consensus molecular mechanisms in an interpretable manner. Significance StatementWhile antibacterial therapies effectively resolve MRSA in vitro, these treatments often fail to clear MRSA bacteremia in vivo, suggesting that host-pathogen interactions are essential to persistent MRSA bacteremia. Recent studies have identified genetic, transcriptomic, and proteomic determinants of MRSA persistence. These determinants independently, however, provide insufficient mechanistic insight and it is unclear if they indicate unique or overlapping persistence mechanisms. Here, we use tensor-based decomposition to jointly analyze cytokine and transcriptomic measurements from patients with MRSA bacteremia. Results indicate that persistence mechanisms integrated across biological modalities reflect diverging mechanisms of persistent bacteremia. Ultimately, these results may help to identify future therapeutic targets for treating persistent MRSA bacteremia.

immunology↗

bioRxiv2022

Plasma Proteome Perturbation for CMV DNAemia in Kidney Transplantation

BackgroundCytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). MethodsLC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. ResultsSamples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR=0.03), and proteins enriched in the humoral (FDR=0.01) and innate immune responses (FDR=0.01). ConclusionPlasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for management of CMV infection in the immunocompromised host.

immunology↗

bioRxiv2019

The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus infectivity

Several enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions has long been known to result in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide a series of evidence to prove that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) binding and infection. First, purified CMV extracellular virions preferentially bind to sulfated longer chain HS on a glycoarray compared to a variety of unsulfated glycosaminoglycans including unsulfated shorter chain HS. Second, the fraction of glycosaminoglycans (GAG) displaying higher dp and sulfation has a larger impact on CMV titers compared to other fractions. Third, cell lines deficient in specific glucosaminyl sulfotransferases produce significantly reduced CMV titers compared to wild-type cells and virus entry is compromised in these mutant cells. Finally, cells pretreated with a peptide that specifically binds sulfated-HS produce significantly reduced virus titers compared to the control peptide treated cells. Taken together, these results highlight the significance of HS chain length and sulfation patterns in CMV attachment and infectivity. IMPORTANCEHeparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It binds to a variety of protein ligands, including cytokines, chemokines, growth factors and morphogens and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, and tumor metastasis. The molecular diversity in HS chains generates unique binding sites for specific ligands and can offer preferential binding for a specific virus over other viruses or cellular ligands. In the current study human cytomegalovirus (CMV) was found to bind preferentially to uniquely sulfated and polymerized HS. The HS mimics designed with these properties inhibited CMV infection. The results were corroborated by parallel studies in mutant mouse cells as well as using peptide inhibition. Combined together, the data suggests that CMV preferentially attaches to uniquely modified HS and thus this virus-host interaction is amenable to targeting by specifically designed HS mimics or peptides.

microbiology↗