Biology subjects

Haeusler, S.

Publications and source records attributed to Haeusler, S..

3 recordsLinked to original sources

bioRxiv2026

The COPI coatomer influences LDL receptor activity, hepatic lipid storage, and apoB secretion

BackgroundDecreased hepatic removal of low density lipoproteins (LDL) and increased apolipoprotein B (apoB) production cause hypercholesterolemia, a major causal risk factor of atherosclerotic cardiovascular disease (ASCVD). By a genome-wide siRNA screen, we previously identified subunits of the Coat protein I (COPI) complex to limit LDL uptake into Huh-7 hepatocarcinoma cells. MethodsThese findings were validated by targeted in vitro experiments as well as genetic association studies in humans and three mouse models with mutated or disrupted COPI genes. ResultsSilencing of COPA, COPB1, COPB2, ARCN1, COPG1, and COPZ1 in Huh-7 cells resulted in decreased uptake of LDL and aberrant glycosylation and altered cell surface abundance of the LDL receptor (LDLR) as well as increased apoB secretion and cellular lipid storage. Single nucleotide polymorphisms of ARCN1 were associated with lower ARCN1 expression and higher levels of LDL-cholesterol (LDL-C). Rare variants of COPA and COPG1 were enriched among patients with LDL-C > 5 mmol/L. Patients and mice carrying other rare immunopathogenic missense variants of COPA and COPG1 did not present with elevated plasma levels of LDL-C, while hepatic knockdown of murine Copg1 increased the concentrations of non-HDL-cholesterol in plasma and triglycerides in the liver. ConclusionsThe COPI coatomer regulates LDLR activity and apoB secretion as well as lipid content of liver cells. Loss of function of some variants of COPI genes are associated with higher LDL-C levels.

cell biology↗

bioRxiv2023

Mechanism of high energy efficiency of carbon fixation by sulfur-oxidizing symbionts revealed by single-cell analyses and metabolic modeling

In chemosynthetic symbioses between marine invertebrates and autotrophic sulfur-oxidizing bacteria the symbionts feed their host by producing organic compounds from CO2 using reduced sulfur compounds as an energy source. One such symbiosis, the gutless marine worm Olavius algarvensis harbors at least five bacterial symbionts of which four have the genetic potential for an autotrophic metabolism. In this study we combined single-cell analyses of CO2 fixation, CO2 release and bulk uptake, with measurements of O2 respiration, sulfur content, and polyhydroxyalkanoate content, as well as mathematical modelling to investigate how energy derived from sulfur oxidation drives carbon fluxes within the symbiosis and between the holobiont and its habitat. We found that under aerobic conditions without external energy sources only the primary symbiont, Ca. Thiosymbion algarvensis, fixed carbon. This symbiont relied on internal sulfur storage for energy production. Our model showed that the apparent efficiency of carbon fixation driven by sulfur oxidation in the symbiosis was higher than thermodynamically feasible if only stored sulfur was considered as source of energy and reducing equivalents. The model and additional calculations showed that reducing equivalents must be derived from a different source than energy. We identified the large amounts of polyhdroxyalkanoate stored by the symbiont as the likely source of reducing equivalents for carbon fixation in the symbiont which boosts the yield of sulfur-driven carbon fixation. The model also showed that heterotrophic carbon fixation by host tissue is not negligible and has to be considered when assessing transfer of carbon from the symbionts to the host.

microbiology↗

bioRxiv2020

Distributed coding of stimulus magnitude across the rodent prefrontal cortex

As we interact with the external world, we judge magnitudes from sensory information. The estimation of magnitudes has been characterized in primates, yet it is largely unexplored in non-primate species. Here, we show that gerbils that solve a time-interval reproduction task display primate-like magnitude estimation characteristics, most prominently a systematic overestimation of small stimuli and an underestimation of large stimuli, often referred to as regression effect. We investigated the underlying neural mechanisms by recording from medial prefrontal cortex and show that the majority of neurons respond either during the measurement or the reproduction of a time-interval. Cells that are active during both phases display distinct response patterns. We categorize the neural responses into multiple types and demonstrate that only populations with mixed responses can encode the bias of the regression effect. These results reveal the organizing neural principles of magnitude estimation a process important to higher cognitive functions.

neuroscience↗