Biology subjects

Karlsson, M.

Publications and source records attributed to Karlsson, M..

24 records · Page 2Linked to original sources

bioRxiv2020

Identification of a novel missense variant in SPDL1 associated with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite significant progress, the genetic determinants of this disease remain incompletely defined. Using next generation sequencing data from 752 individuals with sporadic IPF and 119,055 controls, we performed both variant- and gene-level analyses to identify novel IPF genetic risk factors. Our variant-level analysis revealed a novel rare missense variant in SPDL1 (NM_017785.5 p.Arg20Gln; p = 2.4 x 10-7, odds ratio = 2.87). This signal was independently replicated in the FinnGen cohort (combined p = 2.2 x 10-20), firmly associating this variant as a novel IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. Our results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.

genetics↗

bioRxiv2020

Anterior Cingulate Cortex Directs Exploration of Alternative Strategies

The ability to adjust ones behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and switching away from it to evaluate alternatives when appropriate. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that track the pressure to switch away from the ongoing strategy, and others that relate to the pursuit of alternatives. However, whether these signals underlie computations that actually underpin strategy switching, or merely reflect tracking of related variables remains unclear. Here we provide causal evidence that rodent ACC actively arbitrates between persisting with ongoing behavioral choice and switching away temporarily to re-evaluate alternatives. Furthermore, by individually perturbing distinct output pathways, we establish that the two associated computations - whether to switch away from the current choice, and the pursuit of alternatives - are segregated within ACC micro-circuitry.

neuroscience↗

bioRxiv2019

Twister3: a simple and fast microwire twister

We present Twister3, a microwire twisting machine. This device greatly increases the speed and repeatability of constructing twisted microwire neural probes (e.g. stereotrodes and tetrodes) compared to existing options. It is cheap, well documented, and all associated designs and source code are open-source. Twister3 is of interest to any lab performing twisted microwire neural recordings, for example, using tetrode drives.

neuroscience↗

bioRxiv2019

Yeast volatomes differentially effect larval feeding in an insect herbivore

Yeasts form mutualistic interactions with insects. Hallmarks of this interaction include provision of essential nutrients, while insects facilitate yeast dispersal and growth on plant substrates. A phylogenetically ancient, chemical dialogue coordinates this interaction, where the vocabulary, the volatile chemicals that mediate the insect response, remains largely unknown. Here, we employed gas chromatography-mass spectrometry (GC-MS), followed by hierarchical cluster (HCA) and orthogonal partial least square discriminant analysis (OPLS-DA), to profile the volatomes of six Metschnikowia spp., Cryptococcus nemorosus and brewers yeast Saccharomyces cerevisiae. The yeasts, which are all found in association with insects feeding on foliage or fruit, emit characteristic, species-specific volatile blends that reflect the phylogenetic context. Species-specificity of these volatome profiles aligned with differential feeding of cotton leafworm larvae Spodoptera littoralis on these yeasts. Bioactivity correlates with yeast ecology; phylloplane species elicited a stronger response than fruit yeasts, and larval discrimination may provide a mechanism for establishment of insect-yeast associations. The yeast volatomes contained a suite of insect attractants known from plant and especially floral headspace, including (Z)-hexenyl acetate, ethyl (2E,4Z)-deca-2,4-dienoate (pear ester), (3E)-4,8-dimethylnona-1,3,7-triene (DMNT), linalool, -terpineol, {beta}-myrcene or (E,E)-a-farnesene. A wide overlap of yeast and plant volatiles, notably floral scents further emphasizes the prominent role of yeasts in plant-microbe-insect relationships including pollination. The knowledge of insect-yeast interactions can be readily brought to practical application, live yeasts or yeast metabolites mediating insect attraction provide an ample toolbox for the development of sustainable insect management.\n\nIMPORTANCEYeasts interface insect herbivores with their food plants. Communication depends on volatile metabolites, and decoding this chemical dialogue is key to understanding the ecology of insect-yeast interactions. This study explores the volatomes of eight yeast species which have been isolated from foliage, flowers or fruit, and from plant-feeding insects. They each release a rich bouquet of volatile metabolites, including a suite of known insect attractants from plant and floral scent. This overlap underlines the phylogenetic dimension of insect-yeast associations, which according to the fossil record, long predate the appearance of flowering plants. Volatome composition is characteristic for each species, aligns with yeast taxonomy, and is further reflected by a differential behavioural response of cotton leafworm larvae, which naturally feed on foliage of a wide spectrum of broad-leaved plants. Larval discrimination may establish and maintain associations with yeasts and is also a substrate for designing sustainable insect management techniques.

microbiology↗

bioRxiv2018

Actomyosin-driven force patterning controls endocytosis at the immune synapse

An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules [1]. Although [2], how forces organize and mechanics has been shown to play an important role in this process impact on synapse function is unknown. We found that mechanical forces are spatio-temporally patterned at the immune synapse: global contractile forces are observed at the synapse periphery and local point-like forces are detected at its centre. The global contractile forces result from a pulsatile centripetal actomyosin flow that leads to formation of F-actin protrusions from which the central point like forces emerge. Noticeably, these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis. Accordingly, deletion of the myosin IIA gene leads to impaired B cell responses. The interplay between global and local forces governed by the actomyosin cytoskeleton therefore controls the endocytic function of the immune synapse and might constitute a more general mechanism in the physical regulation of cell-cell interactions.

cell biology↗

bioRxiv2018

A polymer probe-based system for high density, long-lasting electrophysiological recordings across distributed neuronal circuits

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to months. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track 25% of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

neuroscience↗