Septins: Structural Insights, Functional Dynamics, and Implications in Health and Disease.

Septins are a class of proteins with diverse and vital roles in cell biology. Structurally, they form hetero-oligomeric complexes and assemble into filaments, contributing to the organization of cells. These filaments act as scaffolds, aiding in processes like membrane remodeling, cytokinesis, and cell motility.

Genotype and Phenotype of 21-Hydroxylase Deficiency: A Single Center Experience from Western India.

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency.

Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed.

Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations.

Cytoskeletal motor proteins are biological nanomachines that convert chemical energy into mechanical work to carry out various functions such as cell division, cell motility, cargo transport, muscle contraction, beating of cilia and flagella, and ciliogenesis. Most of these processes are driven by the collective operation of several motors in the crowded viscous intracellular environment. Imaging and manipulation of the motors with powerful experimental probes have been complemented by mathematical analysis and computer simulations of the corresponding theoretical models.

Far-UVC (222 nm) irradiation effectively inactivates ssRNA, dsRNA, ssDNA, and dsDNA viruses as compared to germicidal UVC (254 nm).

Ultraviolet-C (UVC) irradiation is being used as an effective approach for the disinfection of pathogenic viruses present in air, surfaces, and water. Recently, far-UVC radiation (222 nm) emitted by KrCl* (krypton-chloride) excimer lamps have been recommended for disinfecting high-risk public spaces to reduce the presence and transmission of infectious viruses owing to limited human health exposure risks as compared to germicidal UVC (254 nm). In this study, the UVC inactivation performances of individual filtered KrCl* excimer lamp (222 nm) and germicidal UVC lamp (254 nm) were determined against four viruses, bacteriophages MS2, Phi6, M13, and T4, having different genome compositions (ssRNA, dsRNA, ssDNA and dsDNA, respectively) and shapes (i.

46,XX aromatase deficiency: A single-center experience with the varied spectrum and recurrent variants, and a systematic review of hormonal parameters.

Background: Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.

Methods: Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling.

Cargo transport properties are enhanced by cylindrical microtubule geometry and elliptical contact zone on cargo surface.

Molecular motors are responsible for carrying cellular transport of various membranous vesicles or organelles along cytoskeletal tracks. Transport of cellular cargos require high forces that are generated by motors working in groups. Hence, the properties of cargo transport can be modulated by varying various parameters such as cargo size and shape, microtubule geometry, motor number and their arrangement on cargo surface.

Computer simulation reveals the effect of severing enzymes on dynamic and stabilized microtubules.

Microtubule (MT) severing enzymes Katanin and Spastin cut the MT into smaller fragments and are being studied extensively usingexperiments due to their crucial role in different cancers and neurodevelopmental disorders. It has been reported that the severing enzymes are either involved in increasing or decreasing the tubulin mass. Currently, there are a few analytical and computational models for MT amplification and severing.

Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review.

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response.

Side-chain cleavage enzyme deficiency: Systematic review and case series.

Objective: P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied.

Sliding of motor tails on cargo surface due to drift and diffusion affects their team arrangement and collective transport.

Kinesin is a microtubule-associated motor protein which works in teams to carry the cellular cargo transport. Lipid rafts on membranous cargos reorganize, causing the motors present in these areas to physically cluster. Unregulated clustering of motors leads to diseases such as Leishmaniasis, Newmann-Pick disease, etc.

Computational study of interactions of anti-cancer drug eribulin with human tubulin isotypes.

Microtubules (MTs) are widely targeted for the treatment of various types of cancer due to their essential role in cell division. MTs are polymers made of -tubulin heterodimers. These - and -tubulins have 8 and 10 different isotypes, respectively.

Luteinizing hormone β-subunit deficiency: Report of a novel LHB likely pathogenic variant and a systematic review of the published literature.

Context: Selective deficiency of β-subunit of luteinizing hormone (LHB) is a rare disease with scarce data on its characteristics.

Objectives: To describe a male with LHB deficiency and systematically review the literature.

Design And Patients: Description of a male patient with LHB deficiency and a systematic review of LHB deficiency patients published to date (10 males and 3 females) as per PRISMA guidelines.

17α-Hydroxylase/17,20-Lyase Deficiency in 46,XY: Our Experience and Review of Literature.

Context: There are more than 100 pathogenic variants in that have been identified in patients with 17α-hydroxylase/17,20-lyase deficiency (17OHD).

Objective: We aimed to describe 46,XY patients with 17OHD from our center and review the literature.

Methods: We retrospectively analyzed genetically proven index cases of 17OHD from our 46,XY disorders of sex development cohort and reviewed similar cases from the literature (n = 150).

17β hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: Our experience and a gender role-focused systematic review.

Objectives: To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency.

Patients And Design: We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17βHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17βHSD3 deficiency patients from the world literature to identify the determinants of gender role.

Results: 17βHSD3 deficiency was the third most common (6%) cause of non-dysgenetic 46,XY DSD in our cohort.

GNRH1 Variants in Congenital Hypogonadotropic Hypogonadism: Single-Center Experience and Systematic Literature Review.

Objective: As GNRH1 genotype-phenotype correlation in CHH is not well studied, we aim to describe the GNRH1 variants in our CHH cohort and present a systematic review as well as genotype-phenotype analysis of all mutation-positive cases reported in the world literature.

Design: This is a retrospective study of GNRH1 mutation-positive patients from a western Indian center. PRISMA guidelines-based PubMed search of the published literature of all GNRH1 mutation-positive patients was conducted.

Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review.

Background: Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1- hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype.

Methods: Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively.

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India.

The study aimed to analyze clinical and hormonal phenotype,and genotype in patients with genetically proven androgen insensitivity syndrome (AIS) from Western India. Index patients with pathogenic variants in the androgen receptor (AR) gene were identified from a consecutive 46,XY DSD cohort (n = 150) evaluated with clinical exome sequencing, and their genetically-proven affected relatives were also included. In sum, 15 index cases (9 complete AIS [CAIS] and 6 partial AIS [PAIS]) were identified making AIS the second most common (10%) cause of 46,XY DSD, next to 5α-reductase 2 deficiency (n = 26; 17.

Temperature-Dependent Activity of Motor Proteins: Energetics and Their Implications for Collective Behavior.

Molecular motor proteins are an extremely important component of the cellular transport system that harness chemical energy derived from ATP hydrolysis to carry out directed mechanical motion inside the cells. Transport properties of these motors such as processivity, velocity, and their load dependence have been well established through single-molecule experiments. Temperature dependent biophysical properties of molecular motors are now being probed using single-molecule experiments.

Expanding genetic spectrum and discriminatory role of steroid profiling by LC-MS/MS in 11β-hydroxylase deficiency.

Objective: To report clinical, hormonal and structural effects of CYP11B1 pathogenic variations in Indian patients with 11β-hydroxylase deficiency (11βOHD) and find hormonal criteria that accurately distinguish 11βOHD from 21α-hydroxylase deficiency (21OHD).

Design: Retrospective record review of genetically diagnosed patients with 11βOHD.

Patients And Measurements: Clinical features, hormonal parameters at diagnosis (by immunoassay) and recent follow-up of 13 genetically proven 11βOHD patients managed at our centre were retrospectively reviewed.

Homozygous p.Val89Leu plays an important pathogenic role in 5α-reductase type 2 deficiency patients with homozygous p.Arg246Gln in SRD5A2.

Objective: To evaluate the pathogenic role of a few benign variants and hypomorphic pathogenic variants in SRD5A2.

Design And Methods: We retrospectively analyzed phenotypes and genotypes in 23 Indian patients with genetically proven steroid 5α-reductase 2 (SRD5A2) deficiency. The interactions of the SRD5A2 enzymes resulting due to the most common benign variant (p.

Differential binding affinity of tau repeat region R2 with neuronal-specific β-tubulin isotypes.

Tau is a microtubule-associated protein whose C-terminal domain consisting of four repeat regions R1, R2, R3 and R4 binds to microtubules to stabilize them. In several neurodegenerative diseases, tau detaches from microtubules to form insoluble aggregates leading to tauopathy. Microtubules are made up of αβ tubulin subunits.

Reversible association with motor proteins (RAMP): A streptavidin-based method to manipulate organelle positioning.

We report the development and characterization of a method, named reversible association with motor proteins (RAMP), for manipulation of organelle positioning within the cytoplasm. RAMP consists of coexpressing in cultured cells (i) an organellar protein fused to the streptavidin-binding peptide (SBP) and (ii) motor, neck, and coiled-coil domains from a plus-end-directed or minus-end-directed kinesin fused to streptavidin. The SBP-streptavidin interaction drives accumulation of organelles at the plus or minus end of microtubules, respectively.

Delineating the interaction of combretastatin A-4 with αβ tubulin isotypes present in drug resistant human lung carcinoma using a molecular modeling approach.

Tubulin isotypes are known to regulate microtubule dynamic instability and contribute to the development of drug resistance in certain types of cancers. Combretastatin-A4 (CA-4) has a potent anti-mitotic, vascular disrupting and anti-angiogenic activity. It binds at the interface of αβ tubulin heterodimers and inhibits microtubules assembly.

Interaction of microtubule depolymerizing agent indanocine with different human αβ tubulin isotypes.

Tubulin isotypes are known to regulate the stability and dynamics of microtubules, and are also involved in the development of resistance against microtubule-targeted cancer drugs. Indanocine, a potent microtubule depolymerizing agent, is highly active against multidrug-resistant (MDR) cancer cells without affecting normal cells. It is known to disrupt microtubule dynamics in cells and induce apoptotic cell death.