Mitochondrial Fusion: Bax to the Fussure

Mitochondria can be organized into highly interconnected networks through continuous cycles of fission and fusion. A recent study by Hoppins et al. (2011) published in Molecular Cell now suggests that Bax, more commonly known for its role in apoptosis, can promote mitochondrial fusion in a Mitofusin 2-dependent manner

Immigrants and Employer-Provided Training

Much has been written about the labour market outcomes for immigrants in their host countries, particularly with regard to earnings, employment and occupational attainment. However, much less attention has been paid to the question of whether immigrants are as likely to receive employer-provided training relative to comparable natives. As such training should be crucial in determining the labour market success of immigrants in the long run it is a critically important question. Using data from a large scale survey of employees in Ireland, we find that immigrants are less likely to receive training from employers, with immigrants from the New Member States of the EU experiencing a particular disadvantage. The immigrant training disadvantage arises in part from a failure on the part of immigrants to get employed by training-oriented firms. However, they also experience a training disadvantage relative to natives within firms where less training is provided.immigrants, employer-provided training, Ireland

Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry

Funding Information: The Martin laboratory is supported by an ERC Advanced grant (101020534, DESTRESS) as well as an Irish Research Council Advanced Laureate Award (IRCLA/2019/133). The Hollville laboratory is supported by a Royal Society Research grant (RG16955).Peer reviewedPublisher PD

The Apoptosome Pathway to Caspase Activation in Primary Human Neutrophils Exhibits Dramatically Reduced Requirements for Cytochrome c

Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the “apoptosome” as a result of the cell stress–associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell–free extracts readily supported Apaf-1–dependent caspase activation, suggesting that these cells may assemble cytochrome c–independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1–dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1–dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation

Have the log-population processes stationary and independent increments? Empirical evidence for Italy, Spain and the USA along more than a century.

We review the classical Gibrat’s process for the population of city sizes. In particular, we are interested in whether the log-population process has stationary and independent (Gibrat’s Law for cities) increments. We have tested these characteristics for the case of the municipalities of Italy and Spain and the places of USA for a time span of more than one century. The results are clear: stationarity and independence are empirically rejected by standard tests. These results open theoretically the way for the observance of other city size distributions other than the lognormal and the double Pareto lognormal, something that in fact has already happened in the literature

Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD:Results of the Study of Heart and Renal Protection (SHARP)

Background Simvastatin, 20 mg, plus ezetimibe, 10 mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown. Study Design Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial. Setting & Population 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, = 20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy). Model, Perspective, & Timeline Assessment during SHARP follow-up from the UK perspective; long-term projections. Intervention Simvastatin plus ezetimibe (2015 UK 1.19 pound per day) during 4.9 years median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK 0.05- pound 1.06 pound per day). Outcomes Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained. Results In SHARP, the proportional reductions per 1 mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from 157,060 pound in patients at low risk to 15,230 pound in those at high risk (30,500- pound 39,600 pound per QALY); and from 47,280 pound in CKD stage 3 to 28,180 pound in patients on dialysis therapy (13,000- pound 43,300 pound per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost. Limitations High-intensity statin-alone regimens were not studied in SHARP. Conclusions Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc

iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. This identified a novel protein, that we name iTAP (iRhom Tail-Associated Protein) that binds to iRhoms, enhancing the cell surface stability of iRhoms and TACE, preventing their degradation in lysosomes. Depleting iTAP in primary human macrophages profoundly impaired TNF production and tissues from iTAP KO mice exhibit a pronounced depletion in active TACE levels. Our work identifies iTAP as a physiological regulator of TNF signalling and a novel target for the control of inflammation.info:eu-repo/semantics/publishedVersio

Length versus radius relationship for ZnO nanowires grown via vapour phase transport

We model the growth of ZnO nanowires via vapour phase transport and examine the relationship predicted between the nanowire length and radius. The model predicts that the lengths of the nanowires increase with decreasing nanowire radii. This prediction is in very good agreement with experimental data from a variety of nanowire samples, including samples showing a broad range of nanowire radii and samples grown using a lithographic technique to constrain the nanowire radius. The close agreement of the model and the experimental data strongly support supporting the inclusion of a surface diffusion term in the model for the incorporation of species into a growing nanowire

The Golden Meteorite Fall: Fireball Trajectory, Orbit and Meteorite Characterization

The Golden (British Columbia, Canada) meteorite fall occurred on Oct 4, 2021 at 0534 UT with the first recovered fragment (1.3 kg) landing on an occupied bed. The meteorite is an unbrecciated, low-shock (S2) ordinary chondrite of intermediate composition, typed as an L/LL5. From noble gas measurements the cosmic ray exposure age is 25 Ma while gas retention ages are all >2 Ga. Short-lived radionuclides and noble gas measurements of the pre-atmospheric size overlap with estimates from infrasound and lightcurve modelling producing a preferred pre-atmospheric mass of 70-200 kg. The orbit of Golden has a high inclination (23.5 degs) and is consistent with delivery from the inner main belt. The highest probability (60%) of an origin is from the Hungaria group. We propose that Golden may originate among the background S-type asteroids found interspersed in the Hungaria region. The current collection of 18 L and LL chondrite orbits shows a strong preference for origins in the inner main belt, suggesting multiple parent bodies may be required to explain the diversity in CRE ages and shock states.Comment: 92 Pages, 20 Tables, 21 Figures, plus 3 appendices, accepted in Meteoritics and Planetary Science Oct 26 202

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

PURPOSE: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA. METHODS: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome. RESULTS: In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations. CONCLUSION: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered