23 research outputs found
GNAS (GNAS complex locus)
Review on GNAS (GNAS complex locus), with data on DNA, on the protein encoded, and where the gene is implicated
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Reconstruction and simulation of neocortical microcircuitry
We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm3 containing âŒ31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form âŒ8 million connections with âŒ37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies
Dynamic assembly of tight junction-associated proteins ZO-1, ZO-2, ZO-3 and occludin during mouse tooth development
Tight junctions might play a role during
tissue morphogenesis and cell differentiation. In order to
address these questions, we have studied the distribution
pattern of the tight junction-associated proteins ZO-1,
ZO-2, ZO-3 and occludin in the developing mouse tooth
as a model. A specific temporal and spatial distribution
of tight junction-associated proteins during tooth
development was observed. ZO-1 appeared
discontinuously in the cell membrane of enamel organ
and dental mesenchyme cells. However, endothelial cells
of the dental mesenchyme capillaries displayed a
continuous fluorescence at the cell membrane. Inner
dental epithelium first showed an evident signal for ZO-
1 at the basal pole of the cells at bud/cap stage, but ZO-1
was accumulated at the basal and apical pole of
preameloblast/ameloblasts at late bell stage.
Surprisingly, in the incisor ZO-1 decreased as the inner
dental epithelium differentiated, and was re-expressed in
secretory and mature ameloblasts. On the contrary, ZO-2
was confined to continuous cell-cell contacts of the
enamel organ in both molars and incisors. The lateral
cell membrane of inner dental epithelial cells was
specifically ZO-2 labeled. However, ZO-3 was
expressed in oral epithelium whereas dental embryo tissues were negative. In addition, occludin was hardly
detected in dental tissues at the early stage of tooth
development, but was distributed continuously at the cell
membrane of endothelial cells of ED19.5 dental
mesenchyme. In incisors, occludin was detected at the
cell membrane of the secretory pole of ameloblasts. The
occurrence and relation during tooth development of
tight junction proteins ZO-1, ZO-2 and occludin, but not
ZO-3, suggests a combinatory assembly in tooth
morphogenesis and cell differentiation