Search results for "genetics [Dementia]"
showing 10 items of 2993 documents
The Metabolic Building Blocks of a Minimal Cell
2020
This article belongs to the Section Evolutionary Biology.
Ancient European dog genomes reveal continuity since the Early Neolithic
2017
Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication t…
Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases
2020
13 páginas, 6 figuras, 3 tablas
Two differential binding mechanisms of FG-nucleoporins and nuclear transport receptors
2018
Summary Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an “archetypal-fuzzy” complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lowe…
rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
2018
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…
2020
Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published …
Notch and TLR signaling coordinate monocyte cell fate and inflammation
2020
AbstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of …
Beyond protein-coding genes
2019
A long non-coding RNA called lnc-NR2F1 regulates several neuronal genes, including some involved in autism and intellectual disabilities.
The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes
2017
Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensa…
Author Correction: The genetic prehistory of the Baltic Sea region.
2018
While the series of events that shaped the transition between foraging societies and food producers are well described for Central and Southern Europe, genetic evidence from Northern Europe surrounding the Baltic Sea is still sparse. Here, we report genome-wide DNA data from 38 ancient North Europeans ranging from ~9500 to 2200 years before present. Our analysis provides genetic evidence that hunter-gatherers settled Scandinavia via two routes. We reveal that the first Scandinavian farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Mesolithic Western hunter-gatherers extended to the east of the Baltic Sea, where these populations persis…