Neurons distribute synaptic inputs across their dendritic tree. In layer 2/3 pyramidal cells of primary visual cortex, spines on distal dendrites share somatic orientation preference but have receptive fields displaced in retinotopic space, which supports tuning to visual edges. However, it is not known how synaptic plasticity rules can lead to specialization of tuning properties […]
OncoMORPHIA: An Integrated Web Platform for Interactive 3D Visualization and Functional Annotation of Cancer Mutations
Summary: The rapid accumulation of cancer genomic data across repositories such as ClinVar, cBioPortal, and the TCGA Pan-Cancer Atlas has created an urgent need for integrated tools that allow researchers to explore mutations in their structural and clinical context without requiring specialized bioinformatics expertise. Here we present OncoMORPHIA, a free, browser-based web platform that unifies […]
Several multiple sequence alignment perturbation methods enhance AlphaFold3 sampling of alternative protein states
Protein function often involves multiple conformational states. Several multiple sequence alignment-perturbing strategies, including stochastic subsampling, clustering, and column masking, have been shown to enhance AlphaFold2 (AF2) sampling of alternative protein states. Here, we evaluate these strategies on AlphaFold3 (AF3) and compare their performance with the BioEmu Boltzmann sampling model on 107 proteins with multiple experimentally […]
Decoupled calcium homeostasis and signaling associated with cytoskeletal instability in YWHAG R132C induced pluripotent stem cell-derived cortical neurons
YWHAG Syndrome (Developmental and Epileptic Encephalopathy 56, DEE56) is an ultra- rare childhood epilepsy associated with neurodevelopmental delays, with no therapeutic intervention available. Multiple de novo mutations in the YWHAG gene, encoding for the 14-3-3gamma protein, have been identified as causative for YWHAG Syndrome. 14-3-3gamma interacts with various targets, including major neurodevelopmental signaling proteins such […]
Human TBC1 domain-containing kinase is a class I multidomain pseudokinase
TBCK-related encephalopathy (TBCKE) is a neurodevelopmental disorder associated with biallelic mutations in TBCK. Despite the increasing number of reported cases worldwide, the biochemical and biophysical properties of TBCK remain unclear, hindering molecular understanding of its role in disease. Here, we present the successful expression, purification, and biochemical characterization of full-length human TBCK produced in Spodoptera […]
Prefrontal Mechanisms of Rule Learning
Rule learning is associated with lasting changes in prefrontal activity. However, experiments typically focus on learning a single set of rules or task, and there remains a significant gap regarding how related mechanisms may reflect behavioral improvements in different contexts, especially when examining across different tasks and modalities. We therefore recorded single units from chronic […]
Beyond the mean: genetic control of gene expression fidelity and dispersion
For decades, molecular biologists have interpreted gene regulation through measurements of mean gene expression, because they could not resolve regulatory variation among individual cells. The advent of single-cell genomics has now made that variation measurable, revealing pervasive differences in gene expression among apparently similar cells. Whether this variation mainly reflects stochastic noise or an informative […]
Basic Region Variants of the MAX b-HLH-LZ preferentially form heterodimers with the MYC b-HLH-LZ to bind the E-box, rather than binding as homodimers.
The MYC associated factor X (MAX) is the heterodimeric partner of the MYC paralogs (MYC, MYCN and MYCL). When deregulated, high level of the MYC paralogs contribute to all aspects of tumorigenesis and tumor growth. MAX can also heterodimerize with the MXD proteins, MNT and MGA. Heterodimerization and sequence specific DNA binding to the E-Box […]
Molecular surveillance of Falciparum malaria in Rwanda: Shifts in parasite prevalence and risk factors between the 2014/15 and 2019/20 Rwanda Demographics and Health Surveys
Rwanda is a malaria endemic country and a focal point for emerging Plasmodium falciparum artemisinin partial resistance (ART-R). While Demographic and Health Surveys (DHS) provide both national and province-level representative data, malaria testing in Rwandan DHS (RDHS) studies has been limited to a subset of adult women and children under 5 years using RDT and/or […]
Systemic and tumor intrinsic expansion of FCRL5 expressing B cells associates with poor response to Bacillus Calmette-Guerin immunotherapy in patients with non-muscle invasive bladder cancer
Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy remains the standard treatment for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), yet more than half of the patients do not respond and experience recurrence or progression. BCG induced humoral immune responses remain poorly defined in patients with NMIBC. Building upon our previous findings showing the pathogenic role of […]
Socotra Cormorants in the Arabian Gulf represent a large, but isolated population with low genetic diversity
The Socotra Cormorant (Phalacrocorax nigrogularis) is a threatened seabird endemic to the coastal areas of the Arabian Gulf and the Arabian Sea, two regions separated by the Strait of Hormuz. Conserving threatened species requires clear delineation of population boundaries and the evaluation of genetic diversity. However, information on population structure and genetic variation, necessary for […]
Gallium induces cytotoxicity through disruption of DNA synthesis rather than ferroptosis
Background: Gallium (Ga) is a promising anti-tumor agent; however, its precise molecular targets in osteosarcoma remain debated. While current paradigms largely attribute its toxicity to reactive oxygen species (ROS) and ferroptosis, understanding its true mechanism is essential for overcoming therapeutic resistance. This highlights the need for interdisciplinary approaches, such as metabolomics, to unveil novel vulnerabilities […]