Publications

Adseverin is a Ca^(2+)-dependent, actin severing protein that promotes fusion of osteoclast precursors in osteoclast formation. Currently it is not understood how actin severing activity is regulated in osteoclastogenesis. Mass spectrometry of adseverin immunoprecipitates from osteoclasts showed that adseverin associated with Serpin D1. Purified Serpin D1 interacted with adseverin in vitro in a Ca^(2+)-dependent manner. Ca^(2+) increased actin severing by ~2-fold. Cells that differentiated into...

Pleiotropic and monotonic effects of gene dosage are central to understanding comorbidities in developmental pediatric and psychiatric disorders, yet the underlying biological processes are not well characterized. Here we develop a functional burden analysis to investigate the association of all protein-coding copy-number variants, genome-wide, with 43 complex traits in approximately 500,000 UK Biobank participants. We test variant associations disrupting 172 tissue or cell-type gene sets,...

Studies on schizophrenia-associated rare copy number variants (CNVs) have predominantly focused on people of European (EUR) ancestry. Here we present a rare CNV study of schizophrenia in East Asian (EAS) populations, comprising 20,903 cases and 23,258 controls. We observed a significantly elevated genome-wide rare CNV burden in EAS cases compared with controls. Cross-population comparisons showed largely consistent rare CNV effects on schizophrenia risk. In the EAS sample, we identified nine...

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences...

CONCLUSIONS: While opioid-limiting laws were not associated with meaningful reductions in opioid prescribing among Medicaid-enrolled adult survivors of childhood cancer overall, notable declines were observed among subgroups with potentially higher pain care needs.

Autism spectrum disorder (ASD; MIM 209850) is reported to vary globally from 0.01% in East Asian populations to 4.36% in certain Australian cohorts. Despite high heritability estimates (61-94%), the genetic architecture underlying ASD susceptibility remains poorly characterized across diverse populations, as most genomic studies have initially focused on individuals of European ancestry. To investigate ancestry-specific genetic contributions to ASD, we analyzed whole-genome sequencing data from...

This Letter presents the first evidence of the simultaneous production of two Z bosons and one photon with the ATLAS detector at the Large Hadron Collider. The measurement is performed using the full Run-2 dataset, recorded from 2015 to 2018, of proton-proton collisions at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 140 fb^{-1}. The fully leptonic final state with four leptons and one photon is analyzed, pp→ZZγ→ℓ^{+}ℓ^{-}ℓ^{'+}ℓ^{'-}γ with ℓ,ℓ^{'}=e or μ. This...

Eating disorders-including anorexia nervosa (AN), bulimia nervosa and binge-eating disorder-are clinically distinct but exhibit symptom overlap and diagnostic crossover. Genomic analyses have mostly examined AN. Here we conducted a genomic meta-analysis of case-control studies of binge-eating behavior (BE; 39,279 cases, 1,227,436 controls), alongside analyses of AN (24,223 cases, 1,243,971 controls) and its subtypes (all European ancestries). We identified six BE-associated loci, including loci...

Prostate cancer follows a long and heterogeneous disease course with incompletely understood aetiology¹. Here we dissect the mutational processes shaping the genomes of 959 donors from the Pan Prostate Cancer Group and assess their clinical relevance. By integrating de novo extracted single-base substitution, insertion-deletion and copy-number signatures with six novel complex structural variant signatures, we identify eight integrated mutational footprints (IMFs) that collectively explain the...

The inactivation of tumour suppressor genes is a key step in cancer development, and is usually achieved by homozygous loss. In prostate cancer, however, large genomic regions are often hemizygously lost, which complicates the identification of putative tumour suppressors in these regions. Here, we develop Epi2Hit, an integrative computational method that leverages whole genome sequencing, epigenomic profiling and gene expression to identify biallelic inactivation of tumour suppressor genes...

Gangstalking is a persecutory belief system espoused by targeted individuals who report being followed, monitored, harassed, or otherwise persecuted by groups of people in their community, often through the coordinated efforts of the government, law enforcement agencies, and strangers. Although the alleged harassment can take the form of conventional stalking, stereotypical gangstalking claims often include added victimization by street theater and directed energy weapons, along with...

Joint modeling of longitudinal data and time-to-event data have been extended to accommodate multilevel data structures. In dental studies, data often exhibit a multilevel hierarchy: each patient has multiple teeth, and one or more biomarkers are measured repeatedly over time for each tooth. In addition to biomarker measurements, the time to tooth loss may vary differently between patients as some patients are more susceptible to tooth loss, conditional on other risk factors. In this paper, we...

Bipolar disorder's (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in...

Microvascular inflammation and endothelial injury, triggered by interferon-gamma (IFNγ), are hallmarks of antibody-mediated rejection (ABMR), the leading cause of premature kidney allograft loss. Glomerular extracellular matrix (ECM) remodeling and endothelial caveolae formation are important aspects of chronic ABMR. We found galectin-1, an immunomodulatory protein that interacts with the ECM, to be increased in the glomeruli of patients with ABMR, while its gene (LGALS1) expression was...

Proton beam radiotherapy (PBRT) offers dosimetric advantages over intensity-modulated radiation therapy (IMRT), but prospective randomized data in the postoperative unilateral head and neck cancer setting remain limited. We conducted a multicenter, randomized phase II trial comparing PBRT and IMRT for patients with resected, well-lateralized head and neck cancers requiring unilateral adjuvant radiotherapy. Adults were randomized 1:1 to receive PBRT or IMRT to 60 Gy (relative biological...

Delayed C5 nerve palsy (C5NP) is a well-known complication of cervical spine surgery and is usually characterized by a benign course with spontaneous improvement over time. While patients-and surgery-specific risk factors have been identified, there is no unifying mechanism to explain the pathogenesis of this condition. The attention toward previous hypotheses faded in favor of a modern multifactorial model integrating anatomic susceptibility, biomechanical, and physiologic changes. Future...

Unlike the well-known charge-carrier kinetics in traditional photocatalysis, a knowledge gap remains regarding the photo-kinetic effects in heterogeneous photothermal catalysis. Conventionally, light is mainly regarded as a source of charge carriers and localized heating, yet how these light-induced effects alter intrinsic reaction kinetics, particularly the rate-determining step (RDS), remains unclear. Here, we provide direct kinetic evidence that illumination tunes the RDS in an archetypal...

MOTIVATION: The canonical vocabulary of twenty amino acids limits the chemical space available to proteins and peptides. Expanding this vocabulary to hundreds of non-canonical amino acids (ncAAs) allows the engineering of proteins with novel function and activity, and is of particular interest for therapeutic peptides such as macrocycles, where ncAAs can improve proteolytic stability, membrane permeability and immunogenicity. However, existing structure-based design tools either cannot model...

This Letter reports on the first evidence of inclusive Higgs-boson production at high transverse momentum in the bb[over ¯] final state, reconstructed in a single large-radius jet. The results are based on proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider at a center-of-mass energies of 13 and 13.6 TeV, corresponding to a total integrated luminosity of 301 fb^{-1}. The study profits from the large background suppression provided by the use of a new...

Compound-specific isotope analysis (CSIA) is widely used to verify in situ biodegradation of organic contaminants. Chloroanilines are persistent groundwater pollutants known to undergo reductive dechlorination under environmental conditions, yet their isotope fractionation remains unclear. This study reports multi-element isotopic fractionation (ε) associated with reductive dechlorination of 2,3-dichloroaniline (2,3-DCA) and 2-chloroaniline (2-CA) using a Dehalobacter-dominated enrichment...