National Institute of Diabetes and Digestive and Kidney Diseases

Distinct Plasma Proteomic Signatures Distinguish MASLD From Non‐Steatotic Individuals but Not From MetALD

ABSTRACT Background and Aims Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease, yet accurate early detection remains challenging. A particular diagnostic obstacle is distinguishing MASLD from metabolic dysfunction and alcohol‐rel...

Structural insight into the activation of adenosine A2AR/A2BR by the dual-agonist MRS3997

Abstract A 1 R, A 2A R, A 2B R, and A 3 R adenosine receptors comprise a G protein-coupled receptor (GPCR) subfamily that regulates many bodily processes. Subtype-selective agonists potentially treat inflammatory and ischemic conditions. The dual A 2A R/A 2B R agonist MRS3997 pro...

Invisible but not inaccessible—Revealing transient oligomers formed by intrinsically disordered proteins with solution NMR and complementary methods

Intrinsically disordered proteins (IDPs) are often readily characterized as soluble monomers, whereas their biological and pathological roles frequently involve transient, heterogeneous, or sparsely populated oligomers. Such assemblies are often described as ‘invisible’ but invis...

An amygdaloreticular pathway promotes motor programs of ingestion

Despite internal cues signaling fullness, animals can continue eating when motivated by context or palatability. The neural pathways and signals enabling the override of these fullness cues remain unclear. Here, we examine a collateralized amygdaloreticular network, focusing on c...

High rates of transition to immune active disease in a cohort of strictly defined immune tolerant patients with chronic hepatitis B: results from the RADICAL consortium

Background Patients with immune tolerant (IT) chronic hepatitis B (CHB) have high viral loads, minimal inflammation and minimal fibrosis. Nevertheless, the benign nature of this phase and the need for antiviral therapy remain controversial. Objective We explored the natural histo...

Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation

Oncogenic KRAS and NRAS mutations are common in hematologic malignancies, but how they signal is less well characterized than in carcinomas. To uncover novel RAS biology and potential therapeutic vulnerabilities, we employed a multi-omics screening approach in multiple myeloma to...

Rethinking Complement in Homeostasis and Disease

The complement system, traditionally viewed as a central component of immune defense, is now recognized to play diverse roles in morphogenesis, tissue regeneration, cellular metabolism, and intercellular communication. This expanded perspective highlights the spatially distribute...

Proliferative control of the saccular-stage developing mouse lung requires the histone methylation activity of KMT2D

KMT2D, the histone methyltransferase and core component of the COMPASS/MLL4 complex, has been implicated in developmental diseases such as Kabuki Syndrome, interstitial lung disease, and congenital diaphragmatic hernia, with clear links to pediatric pulmonary disorders. Despite t...