Biology subjects

Hadi, S.

Publications and source records attributed to Hadi, S..

4 recordsLinked to original sources

bioRxiv2025

A Myosin Nanomotor Essential for Stereocilia Maintenance Expands the Etiology of Hereditary Hearing Loss DFNB3

Cochlear hair cells transduce sound using stereocilia, and disruption to these delicate mechanosensors is a significant cause of hearing loss. Stereocilia architecture is dependent upon the nanomotor myosin 15. A short isoform (MYO15A-2) drives stereocilia development by delivering an elongation-promoting complex (EC) to stereocilia tips, and an alternatively spliced long isoform (MYO15A-1) tunes postnatal size in shorter stereocilia, which possess mechanosensitive ion channels. Disruption of these functions causes two distinct stereocilia pathologies, which underly human autosomal recessive non-syndromic hearing loss DFNB3. Here, we characterize a new isoform, MYO15A-3, that increases expression in postnatal hair cells as the developmental MYO15A-2 isoform wanes reciprocally. We show the critical EC complex is initially delivered by MYO15A-2, followed by a postnatal handover to MYO15A-3, which continues to deliver the EC. In a Myo15a-3 mutant mouse, stereocilia develop normally with correct EC targeting, but lack the EC postnatally and do not maintain their adult architecture, leading to progressive hearing loss. We conclude MYO15A-3 delivers the EC in postnatal hair cells and that the EC and MYO15A-3 are both required to maintain stereocilia integrity. Our results add to the spectrum of stereocilia pathology underlying DFNB3 hearing loss and reveal new molecular mechanisms necessary for resilient hearing during adult life.

neuroscience↗

bioRxiv2022

Genetic admixture history and forensic characteristics of Tibeto-Burman-speaking Qiang people explored via the newly developed Y-STR panel and genome-wide SNP data

Fine-scale patterns of population genetic structure and diversity of ethnolinguistically diverse populations are important for biogeographical ancestry inference, kinship testing and also for the development and validation of new kits focused on forensic personal identification. Analyses focused on forensic markers and genome-wide SNP data can provide new insights into the origin, admixture processes and forensic characteristics of targeted populations. Qiang people with a large sample size among Tibeto-Burman-speaking populations widely reside in the middle latitude of the Tibetan Plateau. However, their genetic structure and forensic features have remained uncharacterized due to the paucity of comprehensive genetic analyses. Here, we first developed and validated the AGCU-Y30 Y-STR panel, which contains slowly and moderately mutating Y-STRs, and then we conducted comprehensive population genetic analyses based on Y-STRs and genome-wide SNPs to explore the admixture history of Qiang people and their neighbours. The validated results of this panel showed that the new Y-STR kit was sensitive and robust enough for forensic applications. Haplotype diversity (HD) ranging from 0.9932 to 0.9996 and allelic frequencies ranging from 0.001946 to 0.8326 in 514 Qiang people demonstrated that all included markers were highly polymorphic in Tibeto-Burman people. Population genetic analyses based on Y-STRs (RST, FST, MDS, NJ, PCA and MJNs) revealed that the Qiang people harboured a paternally close relationship with lowland Tibetan-Yi corridor populations. Furthermore, we made a comprehensive population admixture analysis among Eurasian modern and ancient populations based on the shared alleles. We determined that the Qiang people were a genetically admixed population and showed the closest relationship with Tibetan and Neolithic Yellow River farmers. Admixture modelling showed that Qiang people shared the primary ancestry with Tibetan and was derived from North China, supporting the hypothesis of common origin between Tibetan and Qiang people.

genetics↗

bioRxiv2021

TRIOBP promotes bidirectional radial stiffness gradients within the organ of Corti

Hearing depends on complex mechanical properties of the inner ear sensory epithelium. Yet, the individual contributions of different cell types to the stiffness spectrum of the sensory epithelium have not been thoroughly investigated. Using sub-100 nanometer spatial resolution PeakForce Tapping Atomic Force Microscopy (PFT-AFM), we mapped the Youngs modulus (stiffness) of the apical surface of different cells of freshly-dissected cochlear epithelium from wild-type mice and mice lacking the F-actin bundling protein TRIOBP-5 or TRIOBP-4 and TRIOBP-5. Variants of the genes encoding human and mouse TRIOBP are associated with deafness. We show that TRIOBP deficiency affects formation of supporting cell apical phalangeal microfilaments and bundled cortical F-actin of hair cell cuticular plates, softening the apical surface of the sensory epithelium. Unexpectedly, high-resolution PFT-AFM-mapping also revealed previously unrecognized reticular lamina radial stiffness gradients of opposite orientations in wild-type supporting and hair cells. Deafness-associated TRIOBP deficiencies significantly modified these bidirectional radial stiffness gradients.

biophysics↗

bioRxiv2020

Genetic connectivity and diversity of endangered species the scalloped hammerhead shark Sphyrna lewini (Griffith & Smith 1834) population in Indonesia and Western Indian Ocean

The scalloped hammerhead shark Sphyrna lewini is an endangered species which expected to population declined worldwide including in Indonesia due to overexploited. However, there is a lack of information regarding recent population structure to promote proper management and conservation status in Indonesia. This study aimed to investigate the genetic diversity, population structure and connectivity of S. lewini population in Indonesia from three major sharks landing sites in Aceh (n= 41), Balikpapan (n= 30), Lombok (n= 29), and additional sequences retrieved from West Papua (n= 14) and Western Indian Ocean population (n= 65). Analyses of mitochondrial CO1 gene successfully identified a total of 179 sequences of S. lewini with an average 594 bp nucleotide with 40 polymorphic loci in 4 haplotypes for Indonesian population and 8 haplotypes for Western Indian Ocean. The overall values of genetic diversity in Indonesia was high (Hd= 0.7171; {pi}= 0.0126), with the highest was in Aceh (Hd= 0.6683; {pi}= 0.0198), and the lowest was in Papua (Hd= 0.1429; {pi}= 0.0005), while in Western Indian Ocean the overall value was fairly low (Hd= 0.2322; {pi}= 0.0010). The AMOVA and FST revealed three significant population subdivisions in Indonesia (FST= 0.4415; p < 0.001) with separated population for Aceh and West Papua, and a mixing population between Balikpapan and Lombok (FST= 0.044; p = 0.089), whereas relatively no significant differentiation within population in Western Indian Ocean (FST= -0.0131; p = 0.6011), and significant different level showed by Indonesian population compared with Western Indian Ocean population (FST= 0.7403; p < 0.001). The construction of haplotype network exhibited evidence of gene flow and haplotype sharing between populations. This result indicated a complex and limited connectivity population of S. lewini in Indonesia, and between Western Indian Ocean in regional scale which need co-management action across region.

molecular biology↗