Biology subjects

Mannoor, K.

Publications and source records attributed to Mannoor, K..

6 recordsLinked to original sources

bioRxiv2026

Hemodynamic-Structural Multi-Fidelity Assessment of Endovascular Flow Diversion Strategies for Cerebral Aneurysm Treatment: An Integrated Computational and Experimental Framework

Subarachnoid hemorrhage after cerebral aneurysm rupture has a 50% first-month fatality rate. Endovascular flow diversion is the primary treatment modality. However, no prior study has compared stents, coils, and the Woven Endo-Bridge hemodynamically integrating hemodynamic results with structural device behavior in one framework. An aneurysm model was reconstructed from computed tomography imaging of a patient, and computational fluid dynamics evaluated multiple hemodynamic metrics across three flow-diversion strategies. Finite element analysis assessed stent geometries with 50%, 55%, and 60% porosity in 316L stainless steel, poly-L-lactic acid, and nitinol. Universal testing machine tests validated the models with printed polylactic acid and thermoplastic polyurethane analogues. Dimensional and elastic-tube analyses tested scale equivalence between the FEA and UTM geometries and the rigid-wall CFD assumption. Patient-specific CFD confirmed a high-risk hemodynamic profile. The stent yielded the lowest peak intra-sac velocity, greatest pressure reduction, near-zero wall shear stress, the only reduction in time-averaged wall shear stress, cycle-averaged TAWSS, and the largest peak-systolic reductions in velocity, WSS, and vorticity. OSI and RRT rose for all three treated configurations, consistent with the hemodynamic signature of flow diversion. FEA reproduced the expected stiffness hierarchy (Steel > Nitinol > PLLA), and TPU was the closest surrogate for Nitinol's elastic recovery. Scaled specimens matched native-scale stiffness within 2.3%. Predicted radial distension was orders of magnitude below native wall values, supporting rigid-wall CFD. Stent-assisted diversion demonstrated the most favorable hemodynamic profile. A 50%-porosity Nitinol stent best matched target elastic mechanics, while 316L stainless steel provided the greatest resistance to radial compression.

neuroscience↗

bioRxiv2026

Structure-Based and Stability-Validated Prioritization of BACE1 Inhibitors Integrating Meta-Ensemble QSAR and Molecular Dynamics

Alzheimers disease remains a major therapeutic challenge, and no {beta}-secretase (BACE1) inhibitor has achieved clinical approval. A key limitation of prior discovery efforts is reliance on single-parameter optimization, often resulting in candidates with limited translational potential. In this study, we developed a biology-informed computational framework integrating meta-ensemble QSAR modeling, molecular docking, Protein Language Model (ESM-1b)-guided residue interaction weighting, and ADMET profiling within a normalized multi-parameter ranking scheme. Model performance was validated using cross-validation, external validation, and Y-randomization (n = 100; p = 0.009), while applicability domain analysis based on Tanimoto similarity highlighted reduced reliability for extrapolative predictions. Sensitivity analysis showed high ranking stability under moderate perturbations (Spearman {rho} = 0.998 for {+/-}10%; 0.963 for {+/-}25%), with reduced agreement under randomized weighting ({rho} = 0.821), indicating that prioritization is robust but influenced by weight selection. Screening of 16,196 compounds identified 153 predicted actives (accuracy = 0.852; ROC-AUC = 0.920), which were refined to 111 candidates and seven prioritized leads. Molecular dynamics simulations (200 ns) indicated stable binding and persistent catalytic interactions, with Mol-2 showing favorable dynamic stability and ADMET characteristics. Overall, this study presents an interpretable and quantitatively evaluated framework for multi-parameter compound prioritization, supporting more reliable virtual screening in early-stage CNS drug discovery.

bioinformatics↗

bioRxiv2026

Hematological and genetic basis of clinical heterogeneity of HemoglobinE/β-thalassemia

Patients with HbE/{beta}-thalassemia inheriting the same {beta}-globin mutations display varied clinical manifestations, the mechanism of which is only partially known. The study aimed to decipher the heterogenous basis of HbE/{beta}-thalassemia patients in more details by focusing on both hematological and genetic modifiers influencing the disease severity, which included-(i) HbF and HbE levels using Hb electrophoresis, (ii) {beta}-thalassemia mutations, (iii) anti3.7triplication using Gap-PCR, (iv) individual and cumulative effects of HbF-inducing SNPs in 4 major modifier genes, namely HBG2, BCL11A, HBSB1L_MYB intergenic-region, and HBBP1 which were genotyped using DNA sequencing and Real-time PCR-HRM methods. Accordingly, 130 diagnosed Bangladeshi patients with HbE/{beta}-thalassemia were enrolled and categorized as mild, moderate, and severe as per Mahidol scoring system. c.79G>A+IVS1_5G>C was the most predominant (73.8% of total) mutation pair across all the 3 severity groups, indicating secondary modifiers might influence the severity. Our study found both HbF and HbE protective to HbE/{beta}-thalassemia, as both were inversely related to the severity score (HbF: p<0.0001/r=-0.55; HbE: p<0.0001/r=-0.56). Four SNPs-XmnI-G{gamma}, rs2071348 (HBBP1), rs489544 and rs28384513 (HBS1L_MYB) showed significant association with the elevated HbF levels (p=0.005, 0.0001, 0.0001, 0.004 respectively). The multivariate analysis showed that the risk genotypes with single or combination of 2, 3,and 4 SNPs showed gradually increased risk [Odd Ratio (95%CI)= 2.51, 5.47, 19.5, 39.0, respectively] of less severe phenotype, suggesting that these linked SNP variants had a cumulative effect on both HbF level and clinical severity score. However, low HbE level and copresence of anti3.7triplication were found to nullify the ameliorating effect of multiple SNPs.

genetics↗

bioRxiv2023

Molecular Investigation of TSHR gene in Bangladeshi Congenital Hypothyroid patients

The disorder of thyroid gland development or thyroid dysgenesis (TH) accounts for 80-85% cases of congenital hypothyroidism (CH). Hence, the understanding of molecular etiology of TH is prerequisite. Mutations in TSHR gene is mostly associated with thyroid dysgenesis, prevent or disrupt normal development of the gland. The current study detects two nonsynonymous mutations (p.Ser508Leu, p.Asp727Glu) in transmembrane (TM)-region (Exon 10) of TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, transmembrane (TM)-region of TSHR protein is modelled by homology modeling. Transmembrane (TM)-region of TSHR protein is targeted by small molecules thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants were envisaged by molecular docking and interactions. The binding affinity of wild type protein was much higher than the mutant cases for both of the ligands (MS437 and MS438). Molecular dynamics simulates dynamic behavior of wild type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 show stable conformations in biological environments. Finally, PCA reveals structural and energy profile discrepancies. TSHR368-764MT1 exhibits much variations than TSHR368-764WT and TSHR368-764MT2, emphasizing more damaging pattern in TSHR368-764MT1. The study might be helpful to understand molecular etiology of thyroid dysgenesis (TH) exploring the mutational impact on TSHR protein to the interaction with agonists.

genetics↗

bioRxiv2020

Association of poor virus specific immunoglobulin G antibodyresponses with higher viral load is seen in Bangladeshi pregnantwomen having acute Hepatitis E Genotype 1 infection

Although Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time -quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= -0.7971, p=0.0002) and non-pregnant women (r= -0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus. Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

immunology↗

bioRxiv2020

Situation of antibiotic resistance in Bangladesh and its association with resistance genes for horizontal transfer

The study investigated the spectrum of antibiotic resistance and the associated genes for aminoglycoside, macrolide and ESBL class of antibiotics using clinical isolates. A total of 430 preserved bacterial strains (Acinetobacter baumannii, n= 20; Pseudomonas aeruginosa, n= 26; Klebsiella pneumoniae, n= 42; E.coli, n= 85; Staphylococcus aureus, n= 84; Salmonella Typhi, n= 82; Enterococcus spp., n= 27; Streptococcus pneumoniae, n= 36 and CNS, n= 28) were examined. The strains were isolated from patients admitted to various tertiary hospitals of Dhaka city between 2015 and 2019 with either acute respiratory infections, wound infections, typhoid fever or diarrhea. The isolates were reconfirmed by appropriate microbiological and biochemical methods. Antimicrobial susceptibility tests were done using Kirby-Bauer disk diffusion approach. PCR amplification using resistance gene-specific primers for aminoglycoside, macrolide and ESBL class of antibiotics was done and the amplified products were confirmed by Sanger sequencing. Of the total isolates, 53% came out as MDR with 96.6% of E. coli and 90% of Staphylococcus aureus. There was a year-wise gradual increase of MDR isolates from 2015-2018 and by 2019 the increase in MDR isolates became almost 2-fold compared to 2015. Among the five ESBL genes investigated, CTXM-1 came out as the most prevalent (63%) followed by NDM-1 (22%) and E. coli isolates were the predominant reservoir of these genes. ErmB (55%) was the most frequently detected macrolide resistance gene, whereas aac(6)-Ib (35.44%) was the most prevalent aminoglycoside resistance gene and these genes were most prevalent in E. coli and P. aeruginosa isolates, respectively. CTXM-1 and ErmB (16.66%) were the most frequent partners of coexistence followed by CTXM-1 and aac(3)-II.

microbiology↗