Biomedical subjects

Rahul Singh

Publications and source records attributed to Rahul Singh.

3 recordsLinked to original sources

PubMed2026

Neuroimaging in cerebral folate deficiencies.

Cerebral folate deficiency refers to neurological disorders associated with a reduced cerebrospinal fluid (CSF) concentration of 5-methyltetrahydrofolate (5-MTHF), arising from primary defects in folate transport or metabolism, or secondarily from acquired or other inherited conditions. Clinical presentation ranges from infancy to adulthood, with manifestations including developmental delay, seizures, cognitive impairment, and neuropsychiatric symptoms. Folate plays a central role in one-carbon metabolism, requiring interaction with other B-vitamins, most notably vitamin B12, to support nucleotide synthesis, methylation reactions, and myelin production. Disruption of folate-dependent pathways contributes to the imaging findings of cerebral folate deficiencies, which include abnormal white matter, calcifications, cerebral or cerebellar atrophy, and in some cases, stroke, or stroke-like lesions. This review outlines folate biochemistry, transport mechanisms into the central nervous system, and associated genetic defects, followed by a discussion of imaging features in primary and secondary cerebral folate deficiencies. Relevant differential diagnoses, particularly cobalamin-related disorders, are also examined. Importantly, many cerebral folate deficiencies are potentially reversible with timely recognition and therapy, underscoring the important role of neuroimaging in diagnosis and follow-up of these disorders.

Humans↗

PubMed2025

MDA5 variants trade antiviral activity for protection from autoimmune disease.

Loss-of-function variants in MDA5, a key sensor of double-stranded RNA from viruses and retroelements, have been associated with protection from type 1 diabetes (T1D) in genome-wide association studies (GWAS). MDA5 loss-of-function variants have also been reported to increase the risk of inflammatory bowel disease (IBD). Whether these associations are linked or extend to other diseases remains unclear. Here, fine-mapping analysis of four large GWAS datasets shows that T1D-protective loss-of-function MDA5 variants also protect against psoriasis and hypothyroidism, while increasing the risk of IBD. The degree of autoimmune protection and IBD risk were linearly proportional. The magnitudes of the odds ratios for autoimmune protection and IBD risk were larger for rare MDA5 variants than for common variants, which were differentially expressed in different geographic populations. Our analysis suggests MDA5 genetic variants offer a direct fitness trade-off between viral clearance and autoimmune tissue damage.

Interferon-Induced Helicase, IFIH1↗

PubMed2021

Affordable oral health care: dental biofilm disruption using chloroplast made enzymes with chewing gum delivery.

Current approaches for oral health care rely on procedures that are unaffordable to impoverished populations, whereas aerosolized droplets in the dental clinic and poor oral hygiene may contribute to spread of several infectious diseases including COVID-19, requiring new solutions for dental biofilm/plaque treatment at home. Plant cells have been used to produce monoclonal antibodies or antimicrobial peptides for topical applications to decrease colonization of pathogenic microbes on dental surface. Therefore, we investigated an affordable method for dental biofilm disruption by expressing lipase, dextranase or mutanase in plant cells via the chloroplast genome. Antibiotic resistance gene used to engineer foreign genes into the chloroplast genome were subsequently removed using direct repeats flanking the aadA gene and enzymes were successfully expressed in marker-free lettuce transplastomic lines. Equivalent enzyme units of plant-derived lipase performed better than purified commercial enzymes against biofilms, specifically targeting fungal hyphae formation. Combination of lipase with dextranase and mutanase suppressed biofilm development by degrading the biofilm matrix, with concomitant reduction of bacterial and fungal accumulation. In chewing gum tablets formulated with freeze-dried plant cells, expressed protein was stable up to 3 years at ambient temperature and was efficiently released in a time-dependent manner using a mechanical chewing simulator device. Development of edible plant cells expressing enzymes eliminates the need for purification and cold-chain transportation, providing a potential translatable therapeutic approach. Biofilm disruption through plant enzymes and chewing gum-based delivery offers an effective and affordable dental biofilm control at home particularly for populations with minimal oral care access.

Biofilms↗