Biology subjects

Bohm, C.

Publications and source records attributed to Bohm, C..

4 recordsLinked to original sources

bioRxiv2025

CD33 and Clusterin Interact Biophysically and Genetically to Modulate Alzheimer Risk

We report the results of structural, functional and genetic studies on the CD33 sialic acid- binding receptor that reveal how non-coding variants in CD33 alter risk for Alzheimers disease (AD). The full-length CD33M isoform, whose expression is upregulated by non-coding AD-risk alleles, preferentially forms dimers at the cell surface, where they interact with AD-related proteins (clusterin and A{beta}). This interaction induces CD33M inhibitory signalling and downregulates protective microglial functions including phagocytic removal of amyloid plaques. Human brain expression quantitative trait loci (eQTL) and causal mediation analyses confirm that quantitative interactions between CLU and CD33 genotypes modulate AD phenotypes and suggest that genotypes at these loci might be used to personalise future therapeutic approaches. Our work also highlights several other unexpected aspects of CD33 biology, including a soluble shed extracellular fragment of CD33M and a similar soluble secreted product arising from a truncating mutation in the CD33 extracellular domain (CD33M{Delta}4bp).

neuroscience↗

bioRxiv2025

Traits of Bathy Phytochromes and Application to Bacterial Optogenetics

Phytochromes are photoreceptors sensitive to red and far-red light found in a wide variety of organisms, including plants, fungi, and bacteria. Bacteriophytochromes (BphPs) can be switched between a red light-sensitive Pr state and a far-red light-sensitive Pfr state by illumination. In so-called prototypical BphPs, the Pr state functions as the thermally favoured resting state, whereas Pfr is more stable in bathy BphPs. The prototypical DrBphP from Deinococcus radiodurans has been shown to be compatible with different output module types. Even though red light regulated optogenetic tools are available, like the pREDusk system based on the DrBphP photosensory module, far-red light-modulated variants are still rare. Here, we study the underlying contributors to bathy over prototypical BphP behaviour by way of various chimeric constructs between pREDusk and representative bathy BphPs. We pinpoint shared traits of the otherwise heterogenous subgroup of bathy BphPs, and highlight the importance of the sensor-effector linker in light modulation of histidine kinase activity. Informed by these data, we introduce the far-red light-activated system "pFREDusk", based on a histidine kinase activity governed by a bathy photosensory module. With this tool, we expand the optogenetic toolbox into wavelengths of increased sample and tissue penetration.

biochemistry↗

bioRxiv2024

Reduced selection during sweeps lead to adaptive momentum on rugged landscapes

AbstractEvolutionary theory seeks to explain the remarkable diversity and adaptability of life on Earth. Current theory offers substantial explanatory power, but it overlooks important transient dynamics that are prominent only when populations are outside equilibrium, such as during selective sweeps. We identify a dynamic that we call "adaptive momentum" whereby lineages with a selective advantage can temporarily sustain more deleterious mutations. This reduction in the strength of purifying selection allows populations to explore fitness valleys that are usually too costly to enter, potentially leading to the discovery of otherwise inaccessible fitness peaks. Using mathematical and agent-based simulations, we demonstrate adaptive momentum and show how periods of disequilibrium become windows of enhanced adaptation. Genetic exploration can occur during these windows without requiring mechanisms such as changing environments or complex landscapes. Adaptive momentum provides a simple potential explanation for bursts of rapid evolution observed in nature, including in pathogens such as SARS-CoV-2 and cancers. (152 words)

evolutionary biology↗

bioRxiv2023

Functional specialization and structured representations for space and time in prefrontal cortex

Neurons in prefrontal cortex exhibit selectivity for a range of behaviorally relevant variables, such as sensory stimuli, place, time, choice, context, and category. At the population level, representations of these variables can be organized in various ways--for instance, geometrically or hierarchically. However, how selectivity for each feature is distributed across cells and how this gives rise to such population-level representational structure is unclear. To address these questions, we analyzed coding for space, time, and category in rats performing a navigational task featuring two behavioral categories, starts and goals, each consisting of multiple locations. Population activity was organized hierarchically, with neural distances between elements of a category being smaller than the distances between categories. At the single cell level, individual medial prefrontal cortex (mPFC) neurons were tuned to category and space independently, consistent with hierarchical population geometry emerging from random mixed selectivity, while neurons exhibited preferences for representing space or time across categories, consistent with functional specialization. These distinct selectivity rules across different levels of abstraction suggest that different aspects of prefrontal representations have disparate origins and may enable modularized computations across multiple behaviors and contexts.

neuroscience↗