Biology subjects

Fallahi, A.

Publications and source records attributed to Fallahi, A..

4 recordsLinked to original sources

bioRxiv2025

Human Skin Model from 15 GHz to 110 GHz

In the recently revised guidelines for electromagnetic safety, basic restrictions expressed in terms of the absorbed power density (APD) at frequencies higher than 6 GHz were introduced. Testing for APD compliance of wireless devices requires experimental and numerical body models or phantoms that conservatively reproduce the absorption characteristics of human skin. Previous studies of APD indicate that frequency-dependent impedance-matching effects are caused by the low-permittivity stratum corneum (SC) layer. The objective of this study is to complement previous work (Christ et al., 2020) and to develop dispersive dielectric models to represent reflection and absorption of electromagnetic fields at the surface of the skin across a frequency range up to 110 GHz. The reflection coefficient of the skin of human volunteers was measured at frequencies of 15 to 43 GHz with open waveguide probes, complementing previous data from 45 to 110 GHz (Christ et al., 2020). The volunteers represented both sexes and different age groups and occupations; measurements were made at various regions of the body. The statistical analysis of the results show that the reflection coefficient follows a normal distribution in regions where the SC is relatively thin, which permits development of a conservative skin model that covers the 95th percentile of the tested population. As expected, in regions where the SC is thicker, e.g., the palms, the reflection coefficient is not normally distributed, because the thickness of the SC depends on the mechanical stress and friction to which the hands are exposed during routine daily activities. There was no evidence of relevant differences due to sex, but there is evidence for a slight age-dependent difference. The measured data - via fitting to the numerical model - allow the derivation of two-layer dielectric dispersive models that represent absorption and reflection at the surface of the skin with known uncertainty. The proposed models can be used to conservatively demonstrate compliance with the APD limits of wireless devices operating at frequencies of up to 110 GHz in any of the 5G and 6G bands defined. HighlightsO_LIbroadband evaluation of the skin reflection coefficient with open waveguide probes; C_LIO_LIcorroboration of increased absorption of millimeter wave radiation in body regions with increased stratum corneum thickness; C_LIO_LIdispersive dielectric models representing reflection and absorption at the skin surface with known population coverage. C_LI

bioengineering↗

bioRxiv2023

TOM20 Gates PINK1 Activity And Mediates Its Tethering Of The TOM And TIM23 Translocases Upon Mitochondrial Stress

Mutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive early onset Parkinson disease (PD). PINK1 is a Ser/Thr kinase that regulates mitochondrial quality control by triggering mitophagy mediated by the ubiquitin ligase Parkin. Upon mitochondrial damage, PINK1 accumulates on the outer mitochondrial membrane (OMM) forming a high molecular weight complex with the translocase of the outer membrane (TOM). PINK1 then phosphorylates ubiquitin, which enables recruitment and activation of Parkin followed by autophagic clearance of the damaged mitochondrion. Thus, Parkin-dependent mitophagy hinges on the stable accumulation of PINK1 on the TOM complex. Yet, the mechanism linking mitochondrial stressors to PINK1 accumulation and whether the translocases of the inner membrane (TIMs) are also involved, remain unclear. Herein, we demonstrate that mitochondrial stress induces the formation of a PINK1-TOM-TIM23 supercomplex in human cultured cell lines, dopamine neurons, and midbrain organoids. Moreover, we show that PINK1 is required to stably tether the TOM to TIM23 complexes in response to stress, such that the supercomplex fails to accumulate in cells lacking PINK1. This tethering is dependent on an interaction between the PINK1 NT-CTE module and the cytosolic domain of the Tom20 subunit of the TOM complex, the disruption of which, by either designer or PD-associated PINK1 mutations, inhibits downstream mitophagy. Together, the findings provide key insight into how PINK1 interfaces with the mitochondrial import machinery, with important implications for the mechanisms of mitochondrial quality control and PD pathogenesis.

biochemistry↗

bioRxiv2022

Messenger-RNA Modification Standards and Machine Learning Models Facilitate Absolute Site-Specific Pseudouridine Quantification

Enzyme-mediated chemical modifications to mRNA are important for fine-tuning gene expression, but they are challenging to quantify due to low copy number and limited tools for accurate detection. Existing studies have typically focused on the identification and impact of adenine modifications on mRNA (m6A and inosine) due to the availability of analytical methods. The pseudouridine ({Psi}) mRNA modification is also highly abundant but difficult to detect and quantify because there is no available antibody, it is mass silent, and maintains canonical basepairing with adenine. Nanopores may be used to directly identify {Psi} sites in RNAs using a systematically miscalled base, however, this approach is not quantitative and highly sequence dependent. In this work, we apply supervised machine learning models that are trained on sequence-specific, synthetic controls to endogenous transcriptome data and achieve the first quantitative {Psi} occupancy measurement in human mRNAs. Our supervised machine learning models reveal that for every site studied, different signal parameters are required to maximize {Psi} classification accuracy. We show that applying our model is critical for quantification, especially in low-abundance mRNAs. Our engine can be used to profile {Psi}-occupancy across cell types and cell states, thus providing critical insights about physiological relevance of {Psi} modification to mRNAs.

genomics↗

bioRxiv2021

Unidirectional Single-File Transport of Full-Length Proteins Through a Nanopore

Nanopore sensors could revolutionize single-molecule proteomics by providing a means for identification of known proteins through fingerprinting or by de novo sequencing. However, the complex chemical and physical properties of proteins present multiple challenges to the conventional nanopore sensing method, predominantly, the single-file threading of a protein chain into a nanopore and its transport through it. Herein we describe a general approach for realizing unidirectional transport of full-length proteins through nanopores. We show that the combination of a chemically resistant biological nanopore platform and a high concentration guanidinium chloride buffer enables protein unfolding and unidirectional transport through a pore, propelled by an electroosmotic effect that largely owes to the guanidinium chloride presence. The uniform and slow (~10 {micro}s/amino acid) single-file transport, when combined with supervised machine learning of the electrical current signatures obtained, allows us to use to discern the protein threading orientation and identity. In conjunction with a method for tail-modification of native proteins and higher-resolution nanopores, our approach could offer a path towards direct single-molecule protein fingerprinting without the requirement of a motor enzyme.

biophysics↗