90 research outputs found
The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology
Macrophage signaling in HIV-1 infection
The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection
Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress
Hsp70 is a highly conserved molecular chaperone critical for the folding of new and denatured proteins. While traditional models state that cells respond to stress by upregulating inducible HSPs, this response is relatively slow and is limited by transcriptional and translational machinery. Recent studies have identified a number of post-translational modifications (PTMs) on Hsp70 that act to fine-tune its function. We utilized mass spectrometry to determine whether yeast Hsp70 (Ssa1) is differentially modified upon heat shock. We uncovered four lysine residues on Ssa1, K86, K185, K354 and K562 that are deacetylated in response to heat shock. Mutation of these sites cause a substantial remodeling of the Hsp70 interaction network of co-chaperone partners and client proteins while preserving essential chaperone function. Acetylation/deacetylation at these residues alter expression of other heat-shock induced chaperones as well as directly influencing Hsf1 activity. Taken together our data suggest that cells may have the ability to respond to heat stress quickly though Hsp70 deacetylation, followed by a slower, more traditional transcriptional response
Observations of Ly Emitters at High Redshift
In this series of lectures, I review our observational understanding of
high- Ly emitters (LAEs) and relevant scientific topics. Since the
discovery of LAEs in the late 1990s, more than ten (one) thousand(s) of LAEs
have been identified photometrically (spectroscopically) at to . These large samples of LAEs are useful to address two major astrophysical
issues, galaxy formation and cosmic reionization. Statistical studies have
revealed the general picture of LAEs' physical properties: young stellar
populations, remarkable luminosity function evolutions, compact morphologies,
highly ionized inter-stellar media (ISM) with low metal/dust contents, low
masses of dark-matter halos. Typical LAEs represent low-mass high- galaxies,
high- analogs of dwarf galaxies, some of which are thought to be candidates
of population III galaxies. These observational studies have also pinpointed
rare bright Ly sources extended over kpc, dubbed
Ly blobs, whose physical origins are under debate. LAEs are used as
probes of cosmic reionization history through the Ly damping wing
absorption given by the neutral hydrogen of the inter-galactic medium (IGM),
which complement the cosmic microwave background radiation and 21cm
observations. The low-mass and highly-ionized population of LAEs can be major
sources of cosmic reionization. The budget of ionizing photons for cosmic
reionization has been constrained, although there remain large observational
uncertainties in the parameters. Beyond galaxy formation and cosmic
reionization, several new usages of LAEs for science frontiers have been
suggested such as the distribution of {\sc Hi} gas in the circum-galactic
medium and filaments of large-scale structures. On-going programs and future
telescope projects, such as JWST, ELTs, and SKA, will push the horizons of the
science frontiers.Comment: Lecture notes for `Lyman-alpha as an Astrophysical and Cosmological
Tool', Saas-Fee Advanced Course 46. Verhamme, A., North, P., Cantalupo, S., &
Atek, H. (eds.) --- 147 pages, 103 figures. Abstract abridged. Link to the
lecture program including the video recording and ppt files :
https://obswww.unige.ch/Courses/saas-fee-2016/program.cg
Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE
There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention
Can We Identify Patients with High Risk of Osteoarthritis Progression Who Will Respond to Treatment? A Focus on Biomarkers and Frailty
Guidelines and protocols for cardiovascular magnetic resonance in children and adults with congenital heart disease: SCMR expert consensus group on congenital heart disease
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