1,085 research outputs found
A Sphingosine-1-Phosphate Lyase Mutation Associated With Congenital Nephrotic Syndrome and Multiple Endocrinopathy.
Background: Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome, and primary adrenal insufficiency (PAI) in the majority of cases. SGPL1 encodes sphingosine-1-phosphate lyase (SGPL1) which is a major modulator of sphingolipid signaling. Case Presentation: A Pakistani male infant presented at 5 months of age with failure to thrive, nephrotic syndrome, primary adrenal insufficiency, hypothyroidism, and hypogonadism. Other systemic manifestations included persistent lymphopenia, ichthyosis, and motor developmental delay. Aged 9 months, he progressed rapidly into end stage oligo-anuric renal failure and subsequently died. Sanger sequencing of the entire coding region of SGPL1 revealed the novel association of a rare homozygous mutation (chr10:72619152, c.511A>G, p.N171D; MAF-1.701e-05) with the condition. Protein expression of the p.N171D mutant was markedly reduced compared to SGPL1 wild type when overexpressed in an SGPL1 knockout cell line, and associated with a severe clinical phenotype. Conclusions: The case further highlights the emerging phenotype of patients with loss-of-function SGPL1 mutations. Whilst nephrotic syndrome is a recognized feature of other disorders of sphingolipid metabolism, sphingosine-1-phosphate lyase insufficiency syndrome is unique amongst the sphingolipidoses in presenting with multiple endocrinopathies. Given the multi-systemic and progressive nature of this form of PAI/ nephrotic syndrome, a genetic diagnosis is crucial for optimal management and appropriate screening for comorbidities in these patients
Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries
Recommended from our members
Bi-layer pseudo-spin field-effect transistor
A bi-layer pseudo-spin field-effect transistor (BiSFET) is disclosed. The BiSFET includes a first and second conduction layers separated by a tunnel dielectric. The BiSFET transistor also includes a first gate separated from the first conduction layer by an insulating dielectric layer, and a second gate separated from the second conduction layer by an insulating layer. These conduction layers may be composed of graphene. The voltages applied to the first and/or second gates can control the peak current and associated voltage value for current flow between top and bottom conduction channels, and interlayer current voltage characteristic exhibiting negative differential resistance. BiSFETs may be used to make a variety of logic gates. A clocked power supply scheme may be used to facilitate BiSFET-based logic.Board of Regents, University of Texas Syste
Recommended from our members
ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes
Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy
Fine Particulate Matter and Lung Function among Burning-Exposed Deepwater Horizon Oil Spill Workers
BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, controlled burning was conducted to remove oil from the water. Workers near combustion sites were potentially exposed to increased fine particulate matter [with aerodynamic diameter ≤2:5 lm (PM2:5 )] levels. Exposure to PM2:5 has been linked to decreased lung function, but to our knowledge, no study has examined exposure encountered in an oil spill cleanup. OBJECTIVE: We investigated the association between estimated PM2:5 only from burning/flaring of oil/gas and lung function measured 1–3 y after the DWH disaster. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster and had lung function measured at a subsequent home visit (n = 2,316). PM2:5 concentrations were estimated using a Gaussian plume dispersion model and linked to work histories via a job-exposure matrix. We evaluated forced expiratory volume in 1 s (FEV1; milliliters), forced vital capacity (FVC; milliliters), and their ratio (FEV1/FVC; %) in relation to average and cumulative daily maximum exposures using multivariable linear regressions. RESULTS: We observed significant exposure–response trends associating higher cumulative daily maximum PM2:5 exposure with lower FEV1 (p-trend = 0:04) and FEV1/FVC (p-trend = 0:01). In comparison with the referent group (workers not involved in or near the burning), those with higher cumulative exposures had lower FEV1 [−166:8 mL, 95% confidence interval (CI): −337:3, 3.7] and FEV1/FVC (−1:7, 95% CI: −3:6, 0.2). We also saw nonsignificant reductions in FVC (high vs. referent: −120:9, 95% CI: −319:4, 77.6; p-trend = 0:36). Similar associations were seen for average daily maximum PM2:5 exposure. Inverse associations were also observed in analyses stratified by smoking and time from exposure to spirom-etry and when we restricted to workers without prespill lung disease. CONCLUSIONS: Among oil spill workers, exposure to PM2:5 specifically from controlled burning of oil/gas was associated with significantly lower FEV1 and FEV1/FVC when compared with workers not involved in burning. https://doi.org/10.1289/EHP8930
Event shapes in e+e- annihilation and deep inelastic scattering
This article reviews the status of event-shape studies in e+e- annihilation
and DIS. It includes discussions of perturbative calculations, of various
approaches to modelling hadronisation and of comparisons to data.Comment: Invited topical review for J.Phys.G; 40 pages; revised version
corrects some nomenclatur
- …