28 research outputs found
Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours
Background: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function.Methods: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents. Results: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3. Conclusion: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis
Genome-wide analyses identify common variants associated with macular telangiectasia type 2
Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 Ă 10â8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 Ă 10â17; rs715 at 2q34, P = 9.97 Ă 10â14; rs477992 at 1p12, P = 2.60 Ă 10â12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 Ă 10â6) and serine (P = 2.48 Ă 10â4) between MacTel cases and controls
Climate simulations for 1880-2003 with GISS modelE
We carry out climate simulations for 1880-2003 with GISS modelE driven by ten
measured or estimated climate forcings. An ensemble of climate model runs is
carried out for each forcing acting individually and for all forcing mechanisms
acting together. We compare side-by-side simulated climate change for each
forcing, all forcings, observations, unforced variability among model ensemble
members, and, if available, observed variability. Discrepancies between
observations and simulations with all forcings are due to model deficiencies,
inaccurate or incomplete forcings, and imperfect observations. Although there
are notable discrepancies between model and observations, the fidelity is
sufficient to encourage use of the model for simulations of future climate
change. By using a fixed well-documented model and accurately defining the
1880-2003 forcings, we aim to provide a benchmark against which the effect of
improvements in the model, climate forcings, and observations can be tested.
Principal model deficiencies include unrealistically weak tropical El Nino-like
variability and a poor distribution of sea ice, with too much sea ice in the
Northern Hemisphere and too little in the Southern Hemisphere. The greatest
uncertainties in the forcings are the temporal and spatial variations of
anthropogenic aerosols and their indirect effects on clouds.Comment: 44 pages; 19 figures; Final text accepted by Climate Dynamic
Structure of a mitochondrial fission dynamin in the closed conformation
Dynamin 1-like proteins (DNM1-L) are mechanochemical GTPases that induce membrane fission in mitochondria and peroxisomes. Their mechanism depends on conformational changes driven by nucleotide and lipid cycling. Here we show the crystal structure of a mitochondrial fission dynamin (CmDnm1) from the algae Cyanidioschyzon merolae. Unlike other eukaryotic dynamin structures, CmDnm1 is in a hinge 1 closed conformation, with the GTPase domain compacted against the stalk. Within the crystal, CmDnm1 packs as a diamond-shaped tetramer that is consistent with an inactive off-membrane state. Crosslinking, photoinduced electron transfer assays, and electron microscopy verify these structures. In vitro, CmDnm1 forms concentration-dependent rings and proteinâlipid tubes reminiscent of DNM1-L and classical dynamin with hinge 1 open. Our data provides a mechanism for filament collapse and membrane release that may extend to other dynamin family members. Additionally, hinge 1 closing may represent a key conformational change that contributes to membrane fission
The relationship between healthcare staff wellbeing and patient care: itâs not that simple
Expecting happier and healthier staff to provide better care may make intuitive sense, but this is not always the case. This chapter highlights the complexity of the relationship between healthcare staff wellbeing and patient care, and we introduce the âhappy-productive workerâ hypothesis which postulates that happy and healthy workers are more productive. Here, we initially review the evidence for this relationship among workers in various sectors and consider some of the limitations of our understanding of this association. We then examine the research looking at the links between healthcare staff wellbeing and the quality of patient care at both the individual and organisational level. This is followed by a reflection on the inconsistency of this relationship, and how measurement, moderators, and context influence the presence and strengths of this association. Finally, we consider the implications for research, practice, and policyâincluding the Healthy Healthcare concept