Biology subjects

Sha, M.

Publications and source records attributed to Sha, M..

7 recordsLinked to original sources

bioRxiv2025

Brain Preparedness for Active Forgetting: Cortisol Awakening Response Proacts Prefrontal Control Over Hippocampal-Striatal Circuitry

Stress-related psychiatric pathologies (e.g., rumination in depression, intrusive memories in PTSD) involve impaired inhibitory control over emotional memories and disrupted cortisol circadian rhythms. However, how these mechanisms interact to support adaptive forgetting remains unclear. Here, by integrating multi-modal neuroendocrine profiling with fMRI-based memory suppression in 90 participants, we demonstrate that the cortisol awakening response (CAR)--a circadian surge priming the brain for daily demands--proactively and selectively enhances suppression of recently acquired but not overnight-consolidated emotional memories. This time-dependent facilitation manifests through dual neural mechanisms: Robust CAR broadly amplifies dorsolateral prefrontal cortex (dlPFC) engagement during suppression attempts and specifically strengthens top-down dlPFC control over hippocampal-striatal circuits exclusively for recent traces. Our findings bridge circadian biology, systems neuroscience, and clinical psychopathology to establish CAR as a neuroendocrine preparedness mechanism that proactively configures adaptive forgetting circuits across sleep-wake cycles, thereby informing circadian-based interventions for stress disorders.

neuroscience↗

bioRxiv2023

C4 induces pathological synaptic loss by impairing AMPAR trafficking.

During development, activation of the complement pathway, an extracellular proteolytic cascade, results in microglia-dependent synaptic elimination via complement receptor 3 (CR3). Here, we report that decreased connectivity caused by overexpression of C4 (C4-OE), a schizophrenia-associated gene, is CR3 independent. Instead, C4-OE triggers GluR1 degradation through an intracellular mechanism involving endosomal trafficking protein SNX27, resulting in pathological synaptic loss. Moreover, the connectivity deficits associated with C4-OE were rescued by increasing levels of SNX27, linking excessive complement activity to an intracellular endolysosomal recycling pathway affecting synapses.

neuroscience↗

bioRxiv2023

REVEALS: An Open Source Multi Camera GUI For Rodent Behavior Acquisition

Understanding the rich behavioral data generated by mice is essential for deciphering the function of the healthy and diseased brain. However, the current landscape lacks effective, affordable, and accessible methods for acquiring such data, especially when employing multiple cameras simultaneously. We have developed REVEALS (Rodent BEhaVior Multi-camErA Laboratory AcquiSition), a graphical user interface (GUI) written in python for acquiring rodent behavioral data via commonly used USB3 cameras. REVEALS allows for user-friendly control of recording from one or multiple cameras simultaneously while streamlining the data acquisition process, enabling researchers to collect and analyze large datasets efficiently. We release this software package as a stand-alone, open-source framework for researchers to use and modify according to their needs. We describe the details of the GUI implementation, including the camera control software and the video recording functionality. We validate results demonstrating the GUIs stability, reliability, and accuracy for capturing and analyzing rodent behavior using DeepLabCut pose estimation in both an object and social interaction assay. REVEALS can also be incorporated into other custom pipelines to analyze complex behavior, such as MoSeq. In summary, REVEALS provides an interface for collecting behavioral data from one or multiple perspectives that, combined with deep learning algorithms, will allow the scientific community to discover and characterize complex behavioral phenotypes to understand brain function better.

neuroscience↗

bioRxiv2021

Target Enrichment Enhances the Sensitivity of Sanger Sequencing for BRAF V600 Mutation Detection

BRAF is a serine/threonine protein kinase whose mutations lead to unregulated cell growth and cause different types of cancers. Since V600E is a major BRAF mutation and V600E detection as a companion diagnostic test (CDx) is stipulated in the labeling of the BRAF V600 inhibitors. Traditional Sanger sequencing cannot accurately detect mutations lower than 15% variant allele frequency (VAF) due to its limited sensitivity. Here we applied our patented XNA molecular clamping technology to modify Sanger sequencing template preparation by enriching the mutation population. We found that the use of our mutation-enriched template enhanced the analytical sensitivity of Sanger sequencing to 0.04% VAF. The method is verified to detect V600E, V600K, and V600R mutants and is validated for the known BRAF mutation status in clinical samples. Our streamlined protocol can be used for easy validation of the highly sensitive target-enrichment method for detecting BRAF V600 mutations using Sanger sequencing in clinical labs. In addition to BRAF V600 mutations, this method can be extended to the detection of other clinically important actionable mutations for cancer diagnostics.

molecular biology↗

bioRxiv2021

Positive and Neutral Updating Reconsolidate Aversive Episodic Memories via Different Routes

Aversive memories are long-lasting and prone to have adverse effects on our emotional wellbeing and mental health. Yet, how to remedy the maladaptive effects of aversive memories remains elusive. Using memory reactivation and emotional updating manipulations, we investigated how positive and neutral emotion updates aversive memories for reconsolidation in humans. We found that positive updating after reactivation was equivalent to neutral updating in altering true memories of the aversive story, but introduced more false memory. Moreover, an additional 12 hours of sleep reconsolidation did not further enlarge true memory differences, but attenuated the effect of reactivation and updating on false memory. Interestingly, the neutral rather than the positive updating reduced the emotional arousal of the aversive memory 24 hours later. Our findings provide novel insights into real-world therapeutic applications regarding how updating with positive and neutral emotion may reshape aversive memories, especially when taking wake- and sleep-filled reconsolidation into account.

neuroscience↗

bioRxiv2020

Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients

BackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients. MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed. ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs. ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

cancer biology↗

bioRxiv2019

The Manganese Salt (MnJ) Functions as A Potent Universal Adjuvant

Aluminum adjuvants have been used for a century in various vaccines due to its ability to potentiate humoral immunity and safety records since 1920s. Manganese is an essential micronutrient required for diverse biological activities in cells. We previously found that Mn2+ is a strong type I-interferon stimulator activating the cGAS-STING pathway. Herein we report that a colloidal manganese salt (MnJ) is a potent adjuvant to induce both humoral and cellular immune responses, particularly CTL activation. When administrated intranasally, MnJ was also a strong mucosal adjuvant, inducing high levels of IgA antibodies. MnJ strongly promoted dendritic cell maturation and antigen-specific T cell activation. Interestingly, IL-1/-18 induction and release by Mn2+-activated ASC-mediated inflammasomes were not observed. MnJ showed great adjuvant effects to all tested antigens including inactivated viruses, recombinant proteins and peptides by either intramuscular or intranasal immunization. These findings may have implications in developing potent but safe Mn2+-containing vaccines.

immunology↗