Biology subjects

Rahman, A. A.

Publications and source records attributed to Rahman, A. A..

4 recordsLinked to original sources

bioRxiv2025

PNPLA3 I148M Reduces Hepatic Triacylglycerol Secretion and Mitigates Left Ventricular Diastolic Dysfunction in MASH Diet Mice

Cardiovascular disease (CVD) is a leading cause of mortality among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Paradoxically, the strongest genetic risk factor for MASLD, PNPLA3-I148M, is associated with a reduced risk of CVD. The mechanisms for how PNPLA3-I148M causes MASLD and preserves cardiac health are not well understood. To further investigate cardioprotective effects of PNPLA3-I148M we expressed human WT-PNPLA3, PNPLA3-I148M or a GFP control in the livers of PNPLA3-/- mice. In agreement with prior investigations, mice expressing PNPLA3-I148M displayed greater hepatic neutral lipid accumulation on chow and a Metabolic Dysfunction-Associated Steatohepatitis (MASH) promoting diet. Changes in hepatosteatosis between the groups was not due to alterations in whole body metabolic parameters, although WT-PNPLA3 promoted greater glucose intolerance on a MASH diet. Echocardiography revealed that hearts from PNPLA3-WT mice had changes in left ventricular mass and thickness following 16-weeks of MASH, but not chow diet, which was not seen in the GFP or PNPLA3-I148M groups. Moreover, PNPLA3-WT and GFP mice had reduced E/A ratios (diastolic function), post MASH diet, which was not detected in PNPLA3-I148M mice. In addition, PNPLA3-I148M reduced hepatic secretion of TAGs under a MASH, but not chow diet. The expression of PNPLA3-I148M modified the liver lipidome, while minimal effects were observed in the heart. No differences in atherosclerotic plaque formation were observed following 24 weeks of MASH diet. These findings indicate that hepatic PNPLA3-I148M promotes hepatosteatosis yet protects against diet induced cardiac remodeling and diastolic dysfunction primarily through reductions in hepatic TAG secretion.

physiology↗

bioRxiv2025

Enterococcus faecium MBBL3 Exhibits Promising Probiotic Potential and Antimicrobial Efficacy Against Bovine Mastitis-Associated Escherichia coli and Klebsiella pneumoniae

Enterococcus faecium, a promising probiotic, combats pathogens, supports gut health, strengthens immunity, and provides a natural approach to address the escalating global challenge of antimicrobial resistance. This study aimed to investigate the genome of E. faecium MBBL3, isolated from healthy cow milk, to assess its probiotic potential and antimicrobial activity against pathogens causing bovine mastitis. The strain was analyzed through whole genome sequencing, along with in-vitro and in-silico assessments were conducted to determine its antimicrobial efficacy against bovine mastitis pathogens, Klebsiella pneumoniae MBBL2 (Kp MBBL2) and Escherichia coli MBBL4 (Ec MBBL4). The genome assembly and functional annotations uncovered many important probiotic traits in MBBL3, where genome comparison revealed its high genetic similarity with other Enterococcus strains. MBBL3 demonstrated the ability to ferment a wide range of carbohydrates and possessed 76 carbohydrate-active enzyme-related genes, including five key CAZy families namely GH73, GH18, CBM50, CE4, and AA10. It also possessed importance genes for bile salt and acid tolerance, stress resistance, and surface adhesion. Additionally, MBBL3 contained metabolite regions involved in the biosynthesis of antimicrobial compounds such as 2,4-DAPG, aborycin, enterocin NKR-5-3B, and sodorifen, and bacteriocin gene clusters for sactipeptides, Enterolysin_A, and UviB. Safety assessments indicated low pathogenic potential, while in-vitro assays demonstrated antibiotic susceptibility and suppressed the growth of Kp MBBL2 and Ec MBBL4, respectively. Its bacteriocin compound Enterolysin_A exhibited strong molecular interactions with virulence proteins of these mastitis pathogens. Therefore, the promising probiotic potential and antimicrobial efficacy of E. faecium MBBL3, especially against mastitis pathogens combined with its safety, position it as a valuable candidate for therapeutic applications. Key pointsO_LIE. faecium MBBL3 genosme showed high similarity with other species of this genera. C_LIO_LIGenetic makeup of MBBL3 revealed its ability to survival and adaptation in different niches including hosts gut. C_LIO_LIIn-vitro and in-silico study results, along with several genes linked to antimicrobials demonstrated its ability to combat against mastitis pathogens. C_LI

microbiology↗

bioRxiv2024

Actin isovariant ACT2-mediated cellular auxin homeostasis regulates lateral root organogenesis in Arabidopsis thaliana

Lateral root (LR) organogenesis is regulated by cellular flux of auxin within pericycle cells, which depends on the membrane distribution and polar localization of auxin carrier proteins. The correct distribution of auxin carrier proteins relies on the intracellular trafficking of these proteins aided by filamentous actin as a track. However, the precise role of actin in lateral root development is still elusive. Here, using vegetative class actin isovariant mutants, we revealed that loss of actin isovariant ACT8 led to an increase in lateral root formation. The distribution of auxin within pericycle cells was altered in act8 mutant, primarily due to the altered distribution of AUX1 and PIN7. Interestingly, incorporation of act2 mutant in act8 background (act2act8) effectively nullified the LR phenotype observed in act8 mutant, indicating that ACT2 plays an important role in LR development. To explore further, we investigated the possibility that the act8 mutants LR phenotype and cellular auxin distribution resulted from ACT2 overexpression. Consistent with the idea, enhanced lateral root formation, altered AUX1, PIN7 expression and auxin distribution in pericycle cells were observed in ACT2 overexpression lines. Collectively, these results suggest that actin isovariant ACT2 but not ACT8 plays a pivotal role in regulating source to sink auxin distribution during lateral root organogenesis.

developmental biology↗

bioRxiv2021

Actin isovariant ACT7 regulates root meristem development in Arabidopsis through modulating auxin and ethylene responses

Meristem is the most functionally dynamic part in a plant body. The shaping of the meristem requires constant cell division and cell elongation, which are influenced by hormones and cell cytoskeletal component, actin. Although the roles of hormones in modulating meristem development have been extensively studied, the role of actin in this process is still elusive. Using the single and double mutants of the vegetative class actin, we demonstrate that actin isovariant ACT7 plays an important role in root meristem development. In absence of ACT7, but not ACT8 and ACT2, depolymerization of actin was observed. Consistently, act7 mutant showed reduced cell division, cell elongation, and meristem length. Intracellular distribution and trafficking of auxin transport proteins in the actin mutants revealed that ACT7 specifically functions in root meristem to facilitate the trafficking of auxin efflux carriers PIN1 and PIN2, and consequently the transport of auxin. Compared with act7, act7act8 double mutant shows slightly enhanced phenotypic response and altered intracellular trafficking. The altered distribution of auxin in act7 and act7act8 affects the response of the roots to ethylene but not to cytokinin. Collectively, our results suggest that ACT7 dependent auxin-ethylene response plays a key role in controlling Arabidopsis root meristem development.

plant biology↗