The ADAMTS (a disintegrin and metalloproteinase with thrombospondin type-1 motifs) metalloprotease family comprises 19 members, and they play critical roles in development, angiogenesis and coagulation. These enzymes are also pivotal in the turnover of extracellular matrix proteins in various tissues, and their dysregulation has been linked to diseases such as arthritis, atherosclerosis, cancer and inflammation. These secreted zinc metalloproteases are composed of multiple domains and are...

Inactivating mutations in BAP1 (BRCA1-associated protein 1) are prevalent in many aggressive cancers of high global concern, including cholangiocarcinoma, mesothelioma, uveal melanoma, and renal cell carcinoma. However, research on BAP1 has been predominantly focused on single cancer types, lacking comprehensive pancancer studies that could uncover universal molecular mechanisms and therapeutic vulnerabilities. Our pancancer study uses K-ε-GG ubiquitin remnant motif pulldown coupled with mass...

The obesity epidemic is associated with significant healthcare and economic burdens. Pharmacological administration of the endocrine hormone fibroblast growth factor 21 (FGF21) increases energy expenditure and reverses obesity. However, the central targets and neural pathways for these metabolic benefits remain elusive. Here, we demonstrate that β-klotho (KLB)-expressing neurons in the hindbrain, specifically the nucleus of the solitary tract (NTS) and area postrema (AP), are both necessary and...

There exist numerous conflicting heuristic models to explain Zipf's law, which is an empirical inverse frequency power law that is ubiquitous in biological, social, and other natural phenomena characterized by complex system dynamics. Given its applicability in diverse systems, it should be possible to derive it as a model-free signature of self-organized criticality. This is what we do in this present paper by proposing a new law f x ∝ x - e / 3 , which is based on information-theoretic...

Pursuing replicability - independent evidence for previous claims - is important for creating generalizable knowledge^(1,2). Here we attempted replications of 274 claims of positive results from 164 quantitative papers published from 2009 to 2018 in 54 journals in the social and behavioural sciences. Replications were high powered on average to detect the original effect size (median of 99.6%), used original materials when relevant and available, and were peer reviewed in advance through a...