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Rahimi, M.

Publications and source records attributed to Rahimi, M..

8 recordsLinked to original sources

Context-dependent determinants of CRISPR-Cas9 editing efficiency revealed through cross-species endogenous editing analysis

Accurate prediction of CRISPR-Cas9 guide RNA (gRNA) editing efficiency remains limited, particularly outside human systems, where models trained on exogenous human datasets show poor generalization. We analyzed Cas9 efficiency and repair outcomes using novel endogenous editing data from four human cell types, two tomato cell types, and cells from giant river prawn and black soldier fly. While integrating publicly available predictors via ensemble frameworks improved performance, our analysis revealed hundreds of novel features affecting activity. Crucially, dominant features related to sites competition for gRNA, and local geometric properties varied across systems, highlighting the strong context dependence of Cas9 efficiency and arguing against a universal model. Interestingly, codon usage bias-based features also emerged as informative predictors, as they are proxies for chromatin accessibility. In contrast, trends in repair outcomes remained conserved. This work provides essential resources for more generalizable CRISPR guide design.

synthetic biology↗

In vitro study of chemical compositions and antibacterial activity of Lorestan endemic plant, Pistacia atlantica leaf hydroalcoholic extract against cariogenic bacteria

Background and objectivesThe use of medicinal plants has been considered as an adjunctive treatment to prevent and control dental caries, alongside the mechanical removal of microbial agents. The aim of this study was to evaluate the chemical compositions and antibacterial activity of Pistacia atlantica leaf hydroalcoholic extract against standard strains of Streptococcus mutans (SM) and Lactobacillus rhamnosus (LR). Materials and MethodsThe hydroalcoholic extract of Pistacia atlantica leaves was prepared using the maceration method, and the chemical compositions were identified by a GC-MS apparatus. The antibacterial activity was assessed on the standard strains of SM and LR by measuring the mean diameter of the inhibition zone at different concentrations using the agar well diffusion method, and determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth microdilution method. Chlorhexidine (CHX) mouthwash at a concentration of 0.2% was used as the positive control group. The tests were repeated three times, and the results were analyzed using ANOVA, Tukeys Honestly Significant Difference (HSD) test, and T-test with SPSS. A significance level of P< 0.05 was considered. ResultsThe MIC of the Pistacia atlantica leaf hydroalcoholic extract for SM, LR, and CHX was 12.5, 25, and 6.25 mg/ml, respectively, and the MBC for SM, LR, and CHX was 25, 25, and 6.25 mg/ml, respectively. In the agar well diffusion method, the mean diameter of the inhibition zone at the concentration of 200 mg/ml for SM, LR, and CHX was 23.33{+/-}6.50, 19.0{+/-}1.0, and 17.33{+/-}0.57 mm, respectively. The major chemical compositions were -pinene, -bisabolene, 3-hexenol, pulegone, and {beta}-pinene, respectively. ConclusionThe leaf hydroalcoholic extract of Pistacia atlantica demonstrated antibacterial activity against SM and LR.

microbiology↗

Novel elasticity measurement techniques reveal that the C. elegans cuticle is required for physical integrity with age

Changes in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline. Previously, we found that collagens are required for insulin signaling mutants long lifespan and that overexpression of specific collagens extends wild-type lifespan. However, whether these effects on lifespan are due to mechanical changes during aging has not yet been established. Here, we have developed two novel methods to study the cuticle: we measure mechanical properties of live animals using osmotic shock (OS), and we directly perform the tensile test (TT) on isolated cuticles using microfluidic technology. Using these tools, we find that cuticle, not the muscle, is responsible for changes in stretchiness of C. elegans, and that cuticle stiffness is highly non-linear and anisotropic. We also found that collagen mutations alter integrity of the cuticle by significantly altering elasticity. Additionally, aging stiffens the cuticle under mechanical loads beyond the cuticles healthy stretched state. Measurements of elasticity showed that long-lived daf-2 mutants were considerably better at preventing progressive mechanical changes with age. These tests of C. elegans biophysical properties suggest that the cuticle is responsible for their resilience.

biophysics↗

pH-dependent polymorphism of the structure of SARS-CoV-2 nsp7

The solution structure of SARS-CoV-2 nonstructural protein 7 (nsp7) at pH 7.0 has been determined by NMR spectroscopy. nsp7 is conserved in the coronavirinae subfamily and is an essential co-factor of the viral RNA-dependent RNA polymerase for active and processive replication. Similar to the previously deposited structures of SARS-CoV-1 nsp7 at acidic and basic conditions, SARS-CoV-2 nsp7 has a helical bundle folding at neutral pH. Remarkably, the 4 helix shows gradual dislocation from the core 2-3 structure as pH increases from 6.5 to 7.5. The protonation state of residue H36 contributes to the change of nsp7s intramolecular interactions, and thus, to the structural variation near-neutral pH. Spin-relaxation results revealed that all three loop regions in nsp7 possess dynamic properties associated with this structural variation.

biochemistry↗

Analyzing the Perceptual Attributes of Electro-tactile Stimuli as Function of Various Signal Properties

This study is designed to determine the proper electrical signals that induce various perceptual qualities. These perceptions are chosen from a wide range of feelings, comfort and even surface qualities such as smoothness or flatness. The goal is to derive the relationship between the electrical signal properties (i.e. voltage, frequency and duty cycle) and the perceived qualities which are understood by human observers and reveal any pattens in their reports. A total of 144 measurements are collected from 8 participants. The results are analyzed using numerous statistical methods. In the end, the governing factors are identified and a signal with specific properties is is determined for each of the perception qualities. A great number of plots are included in this study to facilitate the process of choosing the appropriate signal for each factor.

bioinformatics↗

Printed Texts Tracking and Following for a Finger-Wearable Electro-Braille System Through Opto-electrotactile Feedback

This paper presents our recent development on a portable and refreshable text reading and sensory substitution system for the blind or visually impaired (BVI), called Finger-eye. The system mainly consists of an opto-text processing unit and a compact electro-tactile based display that can deliver text-related electrical signals to the fingertip skin through a wearable and Braille-dot patterned electrode array and thus delivers the electro-stimulation based Braille touch sensations to the fingertip. To achieve the goal of aiding BVI to read any text not written in Braille through this portable system, in this work, a Rapid Optical Character Recognition (R-OCR) method is firstly developed for real-time processing text information based on a Fisheye imaging device mounted at the finger-wearable electrotactile display. This allows real-time translation of printed text to electro-Braille along with natural movement of users fingertip as if reading any Braille display or book. More importantly, an electro-tactile neuro-stimulation feedback mechanism is proposed and incorporated with the R-OCR method, which facilitates a new opto-electrotactile feedback based text line tracking control approach that enables text line following by user fingertip during reading. Multiple experiments were designed and conducted to test the ability of blindfolded participants to read through and follow the text line based on the opto-electrotactile-feedback method. The experiments show that as the result of the opto-electrotactile-feedback, the users were able to maintain their fingertip within a 2mm distance of the text while scanning a text line. This research is a significant step to aid the BVI users with a portable means to translate and follow to read any printed text to Braille, whether in the digital realm or physically, on any surface.

bioinformatics↗

A toolbox for studying cortical physiology in primates

Lesioning and neurophysiological studies have facilitated the elucidation of cortical functions and mechanisms of functional recovery following injury. Clinical translation of such studies is contingent on their employment in non-human primates (NHPs), yet tools for monitoring and modulating cortical physiology are incompatible with conventional NHP lesioning techniques. To address these challenges, we developed a toolbox demonstrated in seven macaques. We introduce the photothrombotic method to induce focal cortical lesions alongside a quantitative model for the design of lesion profiles based on experimental needs. Large-scale ([~]5 cm2) vascular and neural dynamics can be monitored and lesion induction can be validated in vivo with optical coherence tomography angiography and our electrocorticographic array, the latter of which also enables testing stimulation-based interventions. By combining optical and electrophysiological techniques in NHPs, we can enhance our understanding of cortical functions, investigate functional recovery mechanisms, integrate physiological and behavioral findings, and develop treatments for neurological disorders.

neuroscience↗

Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression

Sequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNA-Seq analysis on these same cancers and used copy number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection - where the percentage of replicating cells per clone is higher than expected - indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology. SIGNIFICANCEWe conducted a massively parallel DNA sequencing analysis on a set of gastric cancer cell lines and a primary gastric tumor in combination with a joint single cell RNA-Seq analysis. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection where the percentage of replicating cells per clone is higher than expected indicating ongoing tumor evolution. Our study demonstrates that combining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.

genomics↗