2026-09-06Molecular architecture and assembly of the human RNA DegradosomeThe PNPase exoribonuclease interacts with the SUV3 helicase to form the human RNA Degradosome responsible for processive mitochondrial RNA turnover and quality control. Although structural data reveals the trimeric PNPase architecture along with the monomeric and dimeric states o
2026-09-06A High-Throughput Assay to Identify Specific Nascent Chain Inhibitors"Undruggable" proteins without surface-accessible binding sites pose significant challenges to target-based drug discovery. Innovative approaches are needed to tackle these proteins. One promising strategy is targeting them in their nascent chain form at the ribosome, w
2026-09-06Divergent nitrogen transition pathways during global agricultural developmentReactive nitrogen (N) inputs underpin global food production, but increasing protein provision while limiting agricultural N pressure remains a major sustainability challenge. Here, we analyzed changes in N use, cropland N surplus and protein supply across 130 countries from 1992
2026-09-06HSPD1 promotes neuroblastoma by augmenting MYCN expressionMYCN amplification is associated with poor outcomes in neuroblastoma (NB). MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells. While the contrib
2026-09-06Mitochondrial protein import couples proteostasis failure to mitochondrial permeabilizationProteostasis failure is a hallmark of stress and disease, yet how it compromises mitochondrial integrity remains unclear. Here, we identify mitochondrial protein import as a critical pathway linking proteostasis failure to mitochondrial injury. We show that Raptinal, previously c
2026-09-06Cell cycle control of chromatin creates a therapeutic window for epigenetic therapy in tumorsThe relationship between cell cycle length and differentiation competence is well established in developmental biology, particularly in embryonic stem cells, where a short G1 phase maintains pluripotency and G1 lengthening permits lineage commitment. Whether this principle operat
2026-09-06A Multi-Omics Study of Cognitive Resilience to Alzheimer's DiseaseAlzheimers disease (AD) is the most severe form of dementia. While significant efforts have been made to identify AD risk factors and develop therapeutics, much less attention has been given to neurobiological factors and molecular signatures associated with cognitive resilience.
2026-09-06Differential LncRNA expression profile in the plasma of preeclampsia and normal pregnanciesBackground: Early detection of preeclampsia with noninvasive and reliable biomarkers is the foremost step for minimizing adverse effects during pregnancy. However, none maternal serum analyte evaluated so far is sufficiently accurate to allow recommending their routine use. Metho
2026-09-06The Adhesion GPCR Flamingo-Like 1 (FMIL-1) Directs Synapse Formation in a Nociceptive CircuitThe species-specific anatomy of nervous systems suggests that circuit architecture is largely encoded by genetic blueprints. In C. elegans, PVD nociceptive neurons synapse with PVC and AVA interneurons to drive escape responses to noxious stimuli. We used fluorescent markers for
2026-09-06A two-signal, two-receiver signalling system: Snake mobbing in the Arabian babblerMobbing is a collective antipredator behaviour in which animals approach and harass a threat while coordinating signals to alert conspecifics, recruit allies, or deter predators. In group-living Arabian babblers (Argya squamiceps), snake mobbing relies on two signals that differ
2026-09-06Immune Aging is an Independent Risk Factor for Cardiovascular DiseaseCardiovascular disease remains the leading cause of mortality, yet current clinical predictors miss substantial disease-risk. While the immune system contributes to this residual risk, its complexity has hindered broadly applicable, clinically scalable metrics of immune-state. He
2026-09-06Comparison of the Distribution of Fitness Effects Across PrimatesThe distribution of fitness effects (DFE) of mutations is a key determinant of both the efficacy of natural selection and the genetic load of populations. It also provides an indirect summary of the underlying fitness landscape, so the extent to which the DFE is conserved across
2026-09-06Elements of Olfactory Intelligence in DrosophilaThe ability to make the world of odorants intelligible is a key capability of the Drosophila olfactory system that we shall call olfactory intelligence. Characterizing the functional logic of the Drosophila early olfactory system that makes the natural world of odorants intelligi
2026-09-06SynTEF1 restores the functional disease phenotype of SCA27B in an hiPSC-derived neuronal modelSpinocerebellar Ataxia 27B (SCA27B), caused by a deep-intronic GAA repeat expansion in the first intron of the FGF14 gene, is one of the most frequent genetic ataxias. Its underlying disease mechanisms remain largely unknown, and disease-modifying therapies targeting upstream pro
2026-09-06PanScreen: A Comprehensive Approach to Off-Target Liability AssessmentDrug development projects are getting increasingly more expensive while their success rate is stagnating. Safety issues attributed to off-target binding represent a major reason for the failure of new drugs. Besides desired on-target binding, small molecules may interact with off
2026-09-07Maternal health factors driving breastfeeding success: an evidence triangulation frameworkDespite well-established benefits to mothers and children, breastfeeding rates fall short of WHO recommendations world-wide. Breastfeeding is a highly complex behaviour, affected by known system-level barriers and less well-established individual-level factors. We aimed to inform
2026-09-07A Comparative Study in Surgical AI: Potential and Limitations of Data, Compute, and ScalingRecent Artificial Intelligence (AI) models have matched or exceeded human experts in several benchmarks of biomedical task performance, but multi-modal benchmarks involving surgery in particular are often missing from prominent medical benchmark suites (specifically, those requir
2026-09-07Sex and gender differences in OCD: A scoping review and a two subtypes hypothesisThis scoping review explores sex and gender differences in obsessive-compulsive disorder (OCD) as reported in the literature between 2009 and 2026. A comprehensive PubMed search was conducted without restrictions, using terms related to sex, gender, and OCD. 8,394 articles were s
2026-09-06Performance of protein panels is inflated across many biomarker studiesData leakage is a prevalent yet underappreciated flaw in biomarker discovery studies. Through simulation and real-world proteomic data, we demonstrate that typical pipelines are broadly susceptible to this issue, producing inflated performance estimates, poor generalization, and
2026-09-06MAP3K7 Loss of Function Causes Dilated CardiomyopathyBackground and Aims: Dilated cardiomyopathy (DCM) is a genetically heterogeneous cause of heart failure and sudden cardiac death. Many patients remain without a molecular diagnosis. MAP3K7 encodes TAK1, a serine/threonine kinase important for cardiac homeostasis. MAP3K7 variants
2026-09-06A Valid and Reliable Virtual Reality Tool for Assessment of Arm Nonuse Post-StrokeIntroduction: Approximately 40-80% of individuals post-stroke fail to use their paretic arm despite sufficient capacity, a phenomenon known as arm nonuse. This behavior arises from an interaction between cognitive and motor factors, necessitating evaluation approaches that captur
2026-09-06Global Adoption of openEHR Clinical Data Repositories: A Vendor and Community SurveyThe openEHR standard provides an open, vendor-neutral architecture for clinical data repositories (CDRs), yet its real-world deployment has not been systematically documented. We conducted a dual-perspective survey combining a vendor survey of openEHR CDR providers with a communi
2026-09-05Endoscopic versus Shunt Treatment of Hydrocephalus in InfantsHydrocephalus primarily affects infants under one year of age. The traditional treatment for hydrocephalus is
cerebrospinal fluid (CSF) shunt. Life-time complications of CSF shunts are high and expensive, with annual
hospital charges of nearly $2.0 billion, accounting for 3.1% of
2026-09-05Mexican Teachers Cohort Study: Genetics and Cognitive FunctionThis is a resubmission of a U01 application for the “Alzheimer’s Disease Sequencing Project (ADSP) Follow- Up Study 2.0: The Diverse Population Initiative” (PAR-21-212). The overall goals are to: (i) contribute nearly 20,000 GWAS and 5000 whole genome sequences to ADSP from parti
2026-09-05Consortium for Advancing Management and Prevention of Cancer in People with HIVThe mission of the AIDS Malignancy Consortium (AMC) is to investigate through clinical trials new
treatment and prevention interventions and study the pathobiology of malignancies and their precursors in people
living with human immunodeficiency virus (PLWH) in the United States
2026-09-05Regulation of Proteasome ActivityPROJECT SUMMARY / ABSTRACT
The focus of my laboratory’s efforts is the proteasome, the protease that degrades ubiquitin-protein
conjugates. That the proteasome is the central activity within the ubiquitin-proteasome system (UPS) was known
from the time the UPS was charted, but i
2026-09-05Bacterial Survival in Fluctuating Environments: Stochastic Switches, Recombination, and MemoryProject Summary
Bacteria employ a large repertoire of responses and strategies to survive under different types of
environmental stress and metabolic fluctuations. Changes in carbon sources cause cells to turn on specific
metabolic genes, which are later repressed when those sour
2026-09-04The Harvard Chan Education Program in Cancer Prevention and ControlThe Harvard Education Program in Cancer Prevention and Control, in its 30th year, is a dynamic transdisciplinary collaboration that brings together the extensive expertise of the Harvard T.H. Chan School of Public Health, the Dana-Farber Cancer Institute and Dana-Farber/Harvard C
2026-09-04Targeting the immune synapse for programmable cellular functionPROJECT ABSTRACT
Early successes in the field of immunotherapy have demonstrated the ability to treat disease by influencing
immune cell signaling. However, our ability to control immune signaling and the emergent immune response
remains limited. The immune synapse can be thought
2026-09-04Elucidating the network design principles of biological signal processingProject Summary
Cells live in diverse environments and cellular communities, from the cells in our bodies to single-celled
organisms surviving in the soil. To navigate these complex environments, cells must be able to sense and
respond to a variety of signals. This is done throug
2026-09-04Disc-Facet Crosstalk During Spinal Degeneration and RepairThe anterior intervertebral disc and posterior diarthrodial facet joints form what is referred to the three-joint
complex of the spine, working in concert to resist large magnitude axial loads and constrain range of motion to
non-injurious levels. Degenerative pathology in both s
2026-09-04An improved low-endotoxin Clean Genome E. coli strain for production of biological productsAbstract
E. coli has played a vital role in the production of recombinant proteins and plasmid DNA (pDNA) for therapeutic
use since the advent of the biopharmaceutical industry. E. coli remains the workhorse in the production of
heterologous proteins and pDNA because of its short
2026-09-04Imaging Biomarkers of Freezing of Gait Response to Deep Brain StimulationFreezing of gait (FOG) is a common and debilitating manifestation of advanced Parkinson’s disease (PD) for
which there are limited treatment options. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is
effective in approximately half of patients with FOG (PwF), and i
2026-09-04New TREM-1 therapy for inflammatory bowel diseaseProject Summary/Abstract
Inflammatory bowel disease (IBD) involves chronic inflammation of the gastrointestinal (GI) tract and
includes ulcerative colitis (UC) and Crohn's disease (CD). Annually, over 1.5 million people in the United
States suffer from IBD with the annual fin
2026-09-04Metabolic Basis of Disease - Phase 2Project Summary:
The overall goal of this Phase 2 COBRE is to facilitate the growth of young intellectual talent and strengthen and enhance the scientific infrastructure that will promote biomedical research discoveries that will enhance our understanding of the metabolic aspects
2026-09-04De novo designed Ras tools to uncover the mechanisms underlying drug resistanceThe Ras family of proteins contain four major isoforms, and altogether these proteins are constitutively activated
in a third of cancers. In the past decade, inhibitors to mutant Ras (RasG12C) have been developed, but most
patients administered RasG12C inhibitors (RasG12Ci) relap
2026-09-04Chronic Alcohol Consumption Dysregulates Lung Hyaluronic AcidPROJECT SUMMARY/ABSTRACT:
Alcohol use disorder (AUD), which affects over 26 million people aged 21 years+ in the US, increases
the risk for pneumonia by 2-4-fold, resulting in high healthcare costs due to comorbidities and hospitalizations.
Lung macrophages are critical for inna
2026-09-04Research Training Program in Disease-Oriented Neuroscience (R25)SUMMARY
This Research Training Program in Disease Oriented Neuroscience is designed to facilitate the transition between graduate training and a research-based career in neurology and neurosurgery. R25 program trainees receive career mentoring from experienced clinician scientist
2026-09-04Integrated Multiomics Diagnostics at the Point of Care for Healthy LivingAbstract
Timely cancer diagnosis remains a major public health challenge, particularly in communities with limited clinical access, including rural areas, military bases, and urban health deserts. These populations face disproportionate delays in diagnosis due to structural barri
2026-09-04Interplay between common and rare variants associated with schizophreniaPROJECT SUMMARY
Genetic architecture of schizophrenia shows that both rare loss-of-function variants with large effect sizes and
common variation with small effect sizes contribute to schizophrenia risk. Traditionally, these two sets of
variation in the opposite allelic spectrum
2026-09-04Advancing Actionability in Oncology: Enhanced Detection of Head and Neck Cancer RecurrenceProject Summary
Head and neck cancer (HNC) remains a significant cause of mortality, with patient survival drastically
declining once recurrence advances beyond local disease. This SBIR Fast Track proposal seeks to
develop a fully automated, high-throughput assay that isolates ex
2026-09-04Audiom: Developing an Indoor Non-Visual Mapping SystemProject Abstract
The proposed project aims to address the significant challenges faced by the 12 million blind and low
vision individuals (BLVIs) in the U.S. in orienting and analyzing complex indoor spaces. Current solutions have
“blank” maps. To overcome these limitations, thi
2026-09-04Modulating ER stress-induced lipotoxicity to ameliorate mitochondrial myopathyMyopathy is one of the most common manifestations of mitochondrial diseases. Although genetic
and bioenergetic causes of oxidative phosphorylation (OxPhos) impairment are well established,
there is a limited understanding of the metabolic drivers of muscle degeneration. This know
2026-09-04UniProt: AI-Driven Scaling of Protein Knowledge for Biomedical ResearchProject Summary
The mission of UniProt is to support biomedical research by providing a stable, comprehensive, richly and
accurately annotated reference knowledgebase of protein sequences and functional information. Proteins
are an essential bridge between human genotypes and phe
2026-09-04Neural basis of structure learning for value inference in the orbitofrontal cortexAll animals live in structured environments. Learning the statistical structure of the environment can thus offer
survival benefit to animals. Understanding how the brain learns and infers the structure of the environment is
critical for elucidating the mechanisms underlying deci
2026-09-08A Study of Teduglutide in Chinese Adults With Short Bowel SyndromeThe main aim of the study is to assess how well teduglutide works over 24 weeks in Chinese adult participants with short bowel syndrome (SBS) who need parenteral support and to see how much it can reduce the amount of parenteral support and understand how the body absorbs, proces
2026-09-08Phase 1 Study of GC1130A in Patients With Sanfilippo Syndrome Type A (MPS IIIA)The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of recombinant human heparan N-sulfatase (rhHNS, GC1130A) administered via intracerebroventricular access device in patients with Sanfilippo Syndrome Type A (MPS III
2026-09-08A Phase 1/2 Study of VX-522 in Participants With Cystic Fibrosis (CF)The purpose of this study is to evaluate the safety, and tolerability and efficacy of VX-522 in participants 18 years of age and older with cystic fibrosis and a cystic fibrosis transmembrane conductance regulator (CFTR) genotype not responsive to CFTR modulator therapy.
2026-09-08ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple SclerosisMS is a chronic inflammatory and degenerative disease of the central nervous system (CNS) affecting more than 120,000 people in the UK.and 2.5 million people worldwide.
Without disease modifying treatment (DMT),the majority of people with MS (pwMS) will develop significant disab
2026-09-08Ibrutinib + R-CHOP Followed by Ibrutinib MaintenanceThis is a prospective, multicenter, single arm, phase II trial in patients with ≥ 18 and \<65 years with poor-prognosis (IPI ≥ 2) and newly diagnosed ABC-DLBCL.
Aim of the study is to assess the efficacy and the safety of R-CHOP in combination with ibrutinib for 6 cycles foll
2026-09-08Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPCThis study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.
2026-09-08A Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination ImmunotherapyThis study will help determine whether 2 doses of the combination (ipilimumab + nivolumab) is sufficient for patients with early benefit compared to the usual way of trying to give 4 doses. If patients do not show early benefit after 2 doses, patients will be able to continue wit