The gut microbiome is the vast, diverse ecosystem of microorganisms that inhabits the human intestines and provides numerous essential functions for the host. One such key role is the metabolism of primary bile acids that are biosynthesized in the host liver into a plethora of secondary bile acids produced by gut bacteria. These metabolites serve […]
Identification of first-in-class small molecule potential inhibitor of GDF15
Background Growth Differentiation Factor 15 (GDF15), a mitokine implicated in stress response, has been associated with numerous diseases, particularly cancer cachexia. Many approaches, including monoclonal antibodies and peptide antagonists, have been implemented to inhibit GDF15 activity. It is currently unknown whether it is possible to inhibit GDF15 using small organic molecules (SOMs). Methods A structure-based […]
The Mycobacterium tuberculosis Ku C-terminus orchestrates LigD activity through domain-specific interactions
Bacterial non-homologous end joining (NHEJ) is a key DNA double-strand break (DSB) repair pathway that relies on the Ku-LigD complex to alleviate genomic instability. The Mycobacterium tuberculosis Ku C-terminal region has previously been highlighted for its role in both LigD recruitment to DNA DSBs and stimulation of LigD ligase activity. However, it remains unclear how […]
Going Against the Grain: Investigating the C4 Wheat Hypothesis with Spatial Transcriptomics
The possibility of a C4 photosynthetic pathway present in the developing grain of wheat, a C3 plant, has been the source of scientific debate. Wheat is critical to food security and may benefit greatly from the biological advantages conferred by C4 photosynthesis under heat and drought stress. Therefore, significant research has gone towards engineering wheat […]
Dpp and Immune Response Pathways Factors Mediate Paracrine Induction of Senescent Cells in Drosophila
Transition toward senescence is a cellular response to different stressors like ionizing radiation, telomere shortening or oncogene activation. This phenomenon is evolutionarily conserved across species, from insects to humans. Senescent cells (SCs) permanently withdraw from the cell cycle and undergo a series of physiological changes, most notably the acquisition of a robust secretory activity characterized […]
AutoSTED: An automated workflow for STED super-resolution imaging of cell nuclei
The traditional microscopy workflow involves manual selection of objects one after the other. This is not only time consuming, but inevitably introduces human bias. Here, we describe a workflow, AutoSTED for identification of cell nuclei on wide-field fluorescence images and subsequent automated imaging of these nuclei at super-resolution by Stimulated Emission Depletion (STED) microscopy. We […]
In Situ Photoactivated Hydrogel Adhesive Dressings for Post Colon Polypectomies (PolypCures)
Colon polypectomy is a widely performed endoscopic procedure that reduces the incidence of colorectal cancer but leaves exposed colonic wounds susceptible to bleeding, perforation, and infection. The current standard of wound care, mechanical clips, is limited by technical complexity, high cost, and poor efficacy for large (> 2 cm in diameter) or difficult-to-access lesions. Here, […]
Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling
SH2 domains are critical mediators of cellular signaling, although the molecular mechanisms by which they bind their phosphopeptide ligands remain incompletely understood. We investigate the atomic mechanisms underlying both healthy regulation and dysregulation of the human protein tyrosine phosphatase SHP2, a key regulator of cellular signaling. While most pathogenic mutations cluster near the PTP/N-SH2 interface, […]
Microglia and its P2RY12 Receptors Regulate Seizure Severity
Microglia have emerged as possible regulators of seizures with previous approaches employed being insufficiently selective of microglial-specific contributions. To more definitely determine microglial roles in seizure severity, we used the recently developed genetic microglial-deficient Csf1rDeltaFIRE/DeltaFIRE (FIRE KO) mouse model. In this model, mice lack microglia but retain brain border associated macrophages (BAMs). Using two experimental […]
Molecular basis of noncanonical complement C3 activation by histamine
For fifty years the tick-over mechanism has been considered responsible for priming the activation of the complement system’s alternative pathway through the reaction of a nucleophilic water molecule with C3 yielding C3(H2O), even though the exclusivity of this role has been challenged by the existence of extrinsic proteases that can cleave circulating C3 into C3b. […]