Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.

Planetary Health Diet Index Trends and Associations with Dietary Greenhouse Gas Emissions, Disease Biomarkers, Obesity, and Mortality in the United States (2005-2018).

Background: Diet plays a vital role in human health and environmental effects. Monitoring diet quality and its relationship to both health and environment are essential for policy making.

Objectives: This study aimed to analyze trends in the Planetary Health Diet Index (PHDI) and its associations with daily greenhouse gas emissions from food (GHG), disease-related biomarkers, anthropometric measurements, obesity, and all-cause mortality in the US population.

The other health care system in Germany: care for people without health insurance.

Background: A large number of people in Germany have no health insurance. Their access to the official healthcare system is significantly more difficult or impossible. Charitable institutions try to provide medical care and create parallel healthcare structures.

Neuro-cognitive multilevel causal modeling: A framework that bridges the explanatory gap between neuronal activity and cognition.

Explaining how neuronal activity gives rise to cognition arguably remains the most significant challenge in cognitive neuroscience. We introduce neuro-cognitive multilevel causal modeling (NC-MCM), a framework that bridges the explanatory gap between neuronal activity and cognition by construing cognitive states as (behaviorally and dynamically) causally consistent abstractions of neuronal states. Multilevel causal modeling allows us to interchangeably reason about the neuronal- and cognitive causes of behavior while maintaining a physicalist (in contrast to a strong dualist) position.

Key determinants of the dual clamp/activator function of Complexin.

Complexin determines magnitude and kinetics of synchronized secretion, but the underlying molecular mechanisms remained unclear. Here, we show that the hydrophobic face of the amphipathic helix at the C-terminus of Complexin II (CpxII, amino acids 115-134) binds to fusion-promoting SNARE proteins, prevents premature secretion, and allows vesicles to accumulate in a release-ready state in mouse chromaffin cells. Specifically, we demonstrate that an unrelated amphipathic helix functionally substitutes for the C-terminal domain (CTD) of CpxII and that amino acid substitutions on the hydrophobic side compromise the arrest of the pre-fusion intermediate.