Comparative analysis and directed protein evolution yield an improved degron technology with minimal basal degradation, rapid inducible depletion, and faster recovery of target proteins.

Biological mechanisms are inherently dynamic, requiring precise and rapid gene manipulation for effective characterization. Traditional genetic perturbation tools such as siRNA and CRISPR knockout operate on timescales that render them unsuitable for exploring dynamic processes or studying essential genes, where chronic depletion can lead to cell death. Here, we compared four major inducible degron systems-dTAG, HaloPROTAC, and two auxin-inducible degron (AID) tools-in human pluripotent stem cells.

Homonymous hemi-macular atrophy in multiple sclerosis.

Background: Retrograde trans-synaptic degeneration (TSD) following retro-chiasmal pathology, typically retro-geniculate in multiple sclerosis (MS), may manifest as homonymous hemi-macular atrophy (HHMA) of the ganglion cell/inner plexiform layer (GCIPL).

Objective: To determine the frequency, association with clinical outcomes, and retinal and radiological features of HHMA in people with MS (PwMS).

Methods: In this cross-sectional study, healthy controls (HC) and PwMS underwent retinal optical coherence tomography scanning.

A novel deep learning approach to identify embryo morphokinetics in multiple time lapse systems.

The use of time lapse systems (TLS) in In Vitro Fertilization (IVF) labs to record developing embryos has paved the way for deep-learning based computer vision algorithms to assist embryologists in their morphokinetic evaluation. Today, most of the literature has characterized algorithms that predict pregnancy, ploidy or blastocyst quality, leaving to the side the task of identifying key morphokinetic events. Using a dataset of N = 1909 embryos collected from multiple clinics equipped with EMBRYOSCOPE/EMBRYOSCOPE+ (Vitrolife), GERI (Genea Biomedx) or MIRI (Esco Medical), this study proposes a novel deep-learning architecture to automatically detect 11 kinetic events (from 1-cell to blastocyst).

Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN.

Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 Glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated to both C3G and primary Immunoglobulin-associated Membranoproliferative Glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN.