Biology subjects

Rashidi, S.

Publications and source records attributed to Rashidi, S..

3 recordsLinked to original sources

bioRxiv2026

Integrative Proteomic Analysis Implicates Inhibition of Intracellular Protein Trafficking in Therapy-Induced Migrastasis in Prostate Cancer

BackgroundDysregulated cell migration leading to metastasis remains the primary cause of cancer-related mortality. It has been challenging to understand how cells regulate migration. We have previously created the first selective inhibitor of cell migration, KBU2046. Here, we use it as a probe to identify regulatory processes. MethodsMetastatic and primary human prostate cancer cells were treated for different times and at different concentrations with KBU2046. Immunofluorescent microscopy examined protein localization in cells. Label-free mass spectrometry (MS) was performed on total cell proteins, Tandem Mass Tag (TMT) labeling MS was used on membrane fractions, and temporal phosphoproteomic profiling. Results were analyzed with a suite of bioinformatic tools. ResultsKBU2046-induced migrastasis is associated with the accumulation of activated integrin {beta}1 into focal adhesions. Whole-cell proteomics demonstrated suppression of processes that mediate intracellular protein trafficking and increases in mitochondrial energy-generation signatures. Evaluation of the membrane fraction identified increases in membrane repair and maintenance processes and decreases in those that drive motility. Temporal- and concentration-dependent phosphoproteomic profiling revealed that KBU2046 initiates a dynamic, cascading sequence of transient signaling waves rather than a static block. ConclusionsKBU2046-induced migrastasis appears to operate through spatial decoupling rather than structural degradation. By restricting the intracellular trafficking machinery required for receptor recycling, KBU2046 limits focal adhesion turnover, providing a correlative framework to inhibit metastatic dissemination independent of direct cytotoxicity. O_FIG O_LINKSMALLFIG WIDTH=122 HEIGHT=200 SRC="FIGDIR/small/736165v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1efd74dorg.highwire.dtl.DTLVardef@1202106org.highwire.dtl.DTLVardef@581ed3org.highwire.dtl.DTLVardef@14fdcfb_HPS_FORMAT_FIGEXP M_FIG Graphic Abstract C_FIG

cancer biology↗

bioRxiv2024

Personalized tDCS targeting visual motion area V5 modulates smooth pursuit initiation

Transcranial direct current stimulation (tDCS) for the modulation of ongoing eye movements provides an ideal model for investigating sensorimotor integration. Within neural networks subserving smooth pursuit eye movements, visual motion area V5 is a core hub to integrate visual motion information with oculomotor control. Here, we applied personalized tDCS explicitly targeting individual V5 in healthy human participants using algorithmic optimization informed by functional magnetic resonance imaging and combined electro- and magnetencephalography. We hypothesized subtle modulation of sensorimotor integration during pursuit and assessed the gain by personalized tDCS targeting V5, compared to personalized tDCS targeting the frontal eye field, as well as conventional normative tDCS over V5. Indeed, pursuit initiation was specifically delayed during personalized cathodal tDCS targeting right V5 indicating the involvement of distinct functional subregions of V5 in the initial sensorimotor integration of visual motion information with pursuit eye movements, but not the maintenance of ongoing pursuit. The results were well-controlled by anodal and sham tDCS, different pursuit tasks, finite-element simulations of individual electric fields, and by two additional control experiments, one that applied personalized tDCS targeting frontal eye field and another that applied normative tDCS over V5. Importantly, in contrast to personalized tDCS targeting FEF and normative tDCS over V5, personalized tDCS targeting V5 effectively modulated pursuit by adapting electric fields to individual anatomical and functional V5 properties. Our results provide evidence for the specific involvement of area V5 in sensorimotor integration during pursuit initiation and the ability of (targeted) tDCS to specifically introduce subtle modulation of the brain network underlying smooth pursuit eye movements. Further, our results indicate the potential of personalized tDCS to alter behavior as the main aspect of interest in human neuromodulation.

neuroscience↗

bioRxiv2020

Evaluation of the tyrosine and dopamine serum level in experimental infected BALB/c mice with chronic toxoplasmosis

BackgroundToxoplasma parasite alters the transduction of neurotransmitter signals and leads to changes in the level of brain neurotransmitters including tyrosine and dopamine, so, behavior changes can occur in infected hosts. Based on this concept, this study was conducted for evaluation of the tyrosine and dopamine serum level in infected mice with chronic toxoplasmosis. Materials and methodsToxoplasma gondii (Prugniaud strain II) was injected intra-peritoneal into BALB/c mice to induce chronic toxoplasmosis. Modified agglutination test (MAT), polymerase chain reaction (PCR), and microscopic methods were conducted to confirm the induction of chronic toxoplasmosis. The infected mice sera were separated at days 40, 50, 60, 70, and 80 for evaluation of tyrosine and dopamine serum level using High-performance Liquid Chromatography (HPLC). ResultsMicroscopic methods confirmed the formation of the Toxoplasma cysts in mice tissues. Inducing chronic toxoplasmosis is also confirmed by MAT, PCR and histological methods. HPLC results indicated a decrease in serum tyrosine level at days 40 in infected mice in comparison to control and the levels were too low to be measured at other times. However, a significantly high serum dopamine level was observed that gradually increased after parasite inoculation. ConclusionsNo detection of tyrosine level in most of the sample groups is probably related to the very low concentration of tyrosine in sera. However, low concentration of tyrosine at days 40 and increase of dopamine in most of the sample groups suggests the production of dopamine from tyrosine due to the presence of Toxoplasma in infected mice.

microbiology↗