Investigating properties of cerebro-spinal fluid contacting cells in rodents; can they influence ependymal cell proliferation?

The spinal cord is part of the central nervous system which contributes to many physiological functions. There is a possible neurogenic niche located within the central canal of the spinal cord, within which there are a subtype of cells proliferating at baseline. These cells demonstrate plasticity via an increased rate of proliferation following spinal cord injury (SCI). Neighbouring these dividing cells are cerebro-spinal fluid contacting cells (CSFcCs) which have a poorly defined function within rodents. This study assesses properties of CSFcCs, validates a novel transgenic mouse line and uses viral tracing to demonstrate the length and direction of their extensions. It also assessed whether CSFcCs can be manipulated to influence the activity of the cells proliferating within the ependymal layer. Antibody labelling revealed CSFcCs also labelled with GCaMP6f expressed by the vesicular gamma-aminobutyric acid transporter (VGAT) promoter and a synaptic vesicle protein revealing they have the apparatus to load GABA into vesicles and release vesicular content from their terminals within the central canal (CC). They also co-labelled with an antibody to the glucagon-like peptide 1 receptor (GLP1R), offering a novel input for stimulation. Intraperitoneal injection of the GLP1R agonist liraglutide with the proliferative marker 5- ethynyl-2'-deoxyuridine (EdU) resulted in a reduced number of EdU positive cells in the ependymal cell layer (ECL), compared to mice with EdU and vehicle only injections. This suggests there is a relationship between CSFcCs and ependymal cells (EpCs) which has not previously been shown. Mice expressing cre-recombinase under control of the PKD2L1 promoter, which are shown here to be specifically expressed in CSFcCs in the CNS, were intraspinally injected with a floxed virus expressing diphtheria toxin subunit-A (DTA). There was a remarkable increase in the number of EdU+ cells around the CC in most regions of the spinal cord compared to uninjected mice or mice injected with a virus that did not express DTA. Markers of cell death indicated that the expression of DTA in CSFcCs resulted in the death of EpCs, further indicating an essential trophic relationship between these cells. This connection between CSFcCs and dividing ependymal cells (EpCs) may be utilised for therapeutic benefit in disorders of the spinal cord where modulating proliferation may be used to restore cell populations

Employee and partner surveys wave 3 of the Linked-Employer-Employee-Panel (LEEP-B3) Project (DFG – 373090005): Organizational Inequalities and Interdependencies between Capabilities in Work and Personal Life: A Study of Employees in Different Work Organizations. Technical Report

Marx C, Abendroth A, Bächmann A-C, et al. Employee and partner surveys wave 3 of the Linked-Employer-Employee-Panel (LEEP-B3) Project (DFG – 373090005): Organizational Inequalities and Interdependencies between Capabilities in Work and Personal Life: A Study of Employees in Different Work Organizations. Technical Report. Bielefeld: Univ., Fak. für Soziologie; 2020

Vascular surveillance by haptotactic blood platelets in inflammation and infection

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets

Rapid, metal-free and aqueous synthesis of imidazo[1,2-a]pyridine under ambient conditions

A novel, rapid and efficient route to imidazo[1,2-a]pyridines under ambient, aqueous and metal-free conditions is reported. The NaOH-promoted cycloisomerisations of N-propargylpyridiniums give quantitative yield in a few minutes (10 g scale). A comparison of common green metrics to current routes showed clear improvements, with at least a one order of magnitude increase in space-time-yield

Wolves in the Wolds: Late Capitalism, the English Eerie, and the Wyrd Case of ‘Old Stinker’ the Hull Werewolf

In this article, I depart from the earlier opinions of Emily Gerard, Sabine Baring-Gould, and others, who explained the disappearance of the werewolf in folklore as following the extinction of the wolf. I argue instead that British literature is distinctive in representing a history of werewolf sightings in places in Britain where there were once wolves. I draw on the idea of absence, manifestations of the English eerie, and the turbulence of England in the era of late capitalism to illuminate my analysis of the representation of contemporary werewolf sightingsPeer reviewe

CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs

Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal–neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.Peer reviewe