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Biology subjects

Amir, M.

Publications and source records attributed to Amir, M..

4 recordsLinked to original sources

Advancing EEG Biosensing: Novel Scalable Production of Platinum-Silicon Microneedles

This study presents the development and analysis of a silicon microneedle electrode array fabricated using a streamlined, two-step approach for enhanced bio-signal recording applications. Numerical simulations with COMSOL Multiphysics were employed to optimize the microneedle array design, focusing on mechanical stability and minimizing skin-electrode impedance. Structural analysis identified needle lengths between 500 m and 700 m as optimal for mechanical robustness, with critical load factors indicating a high resistance to buckling under applied forces. Optimal needle spacing was determined to prevent inter-needle interference and ensure effective skin penetration. Proof-of-concept electroencephalography testing confirmed that the microneedles achieved reliable bio-signal recording, comparable to traditional wet electrodes, while offering advantages such as reduced preparation time and improved user comfort. This work establishes a simple and cleanroom-compatible, scalable method for fabricating platinum-coated silicon microneedle arrays, advancing the development of wearable, user-friendly biopotential monitoring devices.

bioengineering↗

Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy

-Klotho (KLA) is a type-1 membranous protein that can associate with fibroblast growth factor receptor (FGFR) to form co-receptor for FGF23. The ectodomain of unassociated KLA is shed as soluble KLA (sKLA) to exert FGFR/FGF23-independent pleiotropic functions. The previously determined X-ray crystal structure of the extracellular region of sKLA in complex with FGF23 and FGFR1c suggests that sKLA functions solely as an on-demand coreceptor for FGF23. To understand the FGFR/FGF23-independent pleiotropic functions of sKLA, we investigated biophysical properties and structure of apo-sKLA. Mass photometry revealed that sKLA can form a stable structure with FGFR and/or FGF23 as well as sKLA dimer in solution. Single particle cryogenic electron microscopy (cryo-EM) supported the dimeric structure of sKLA. Cryo-EM further revealed a 3.3[A] resolution structure of apo-sKLA that overlays well with its counterpart in the ternary complex with several distinct features. Compared to the ternary complex, the KL2 domain of apo-sKLA is more flexible. 3D variability analysis revealed that apo-sKLA adopts conformations with different KL1-KL2 interdomain bending and rotational angles. The potential multiple forms and shapes of sKLA support its role as FGFR-independent hormone with pleiotropic functions. A comprehensive understanding of the sKLA conformational landscape will provide the foundation for developing klotho-related therapies for diseases.

biophysics↗

Gut bacteria-derived serotonin promotes immune tolerance in early life

The gut microbiome promotes immune system development in early life, but the neonatal gut metabolome remains undefined. Here, we demonstrate that, distinct from adults, the neonatal mouse gut is enriched with neurotransmitters, and specific bacteria produce serotonin directly while downregulating monoamine oxidase A to limit serotonin breakdown. Serotonin inhibits mTOR activation to promote regulatory T cells and suppress T cell responses both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice leads to long-term immune tolerance toward both dietary antigens and commensal bacteria as well as alterations of the gut microbiome. Together, our study has uncovered unique microbiome-dependent mechanisms to maximize serotonin in the neonatal gut and a novel role for intestinal serotonin to promote immune tolerance in early life.

immunology↗

Structural and functional impact of non- synonymous SNPs in the CST complex subunit TEN1: Structural genomics approach

TEN1 protein is a key component of CST complex, implicated in maintaining the telomere homeostasis, and provide stability to the eukaryotic genome. Mutations in TEN1 gene have higher chances of deleterious impact; thus, interpreting the number of mutations and their consequential impact on the structure, stability and function is essentially important. Here, we have investigated the structural and functional consequences of nsSNPs in the TEN1 gene. A wide array of sequence- and structure-based computational prediction tools were employed to identify the effects of 78 nsSNPs on the structure and function of TEN1 protein and deleterious nsSNPs were identified. These deleterious or destabilizing nsSNPs are scattered throughout the structure of TEN1. However, major mutations were observed in the 1-helix (12-16) and {beta}5-strand (88-96). We further observed that mutations at C-terminal region were have higher tendency to form aggregate. In-depth structural analysis of these mutations reveals that the pathogenecity of these mutations are driven mainly through larger structural changes because of alterations in non-covalent interactions. This work provides a blue print to pinpoint the possible consequences of pathogenic mutations in the CST complex subunit TEN1.

evolutionary biology↗