The probable, possible, and novel functions of ERp29

The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER t

Balloon dilatation and stenting for aortic coarctation: a systematic review and meta-analysis

Background—There is no systematic assessment of available evidence on effectiveness and comparative effectiveness of balloon dilatation and stenting for aortic coarctation. Methods and Results—We systematically searched 4 online databases to identify and select relevant studies of balloon dilatation and stenting for aortic coarctation based on a priori criteria (PROSPERO 2014:CRD42014014418). We quantitatively synthesized results for each intervention from single-arm studies and obtained pooled estimates for relative effectiveness from pairwise and network meta-analysis of comparative studies. Our primary analysis included 15 stenting (423 participants) and 12 balloon dilatation studies (361 participants), including patients ≥10 years of age. Post-treatment blood pressure gradient reduction to ≤20 and ≤10 mm Hg was achieved in 89.5% (95% confidence interval, 83.7–95.3) and 66.5% (44.1–88.9%) of patients undergoing balloon dilatation, and in 99.5% (97.5–100.0%) and 93.8% (88.5–99.1%) of patients undergoing stenting, respectively. Odds of achieving ≤20 mm Hg were lower with balloon dilatation as compared with stenting (odds ratio, 0.105 [0.010–0.886]). Thirty-day survival rates were comparable. Numerically more patients undergoing balloon dilatation experienced severe complications during admission (6.4% [2.6–10.2%]) compared with stenting (2.6% [0.5–4.7%]). This was supported by meta-analysis of head-to-head studies (odds ratio, 9.617 [2.654–34.845]) and network meta-analysis (odds ratio, 16.23, 95% credible interval: 4.27–62.77) in a secondary analysis in patients ≥1 month of age, including 57 stenting (3397 participants) and 62 balloon dilatation studies (4331 participants). Conclusions—Despite the limitations of the evidence base consisting predominantly of single-arm studies, our review indicates that stenting achieves superior immediate relief of a relevant pressure gradient compared with balloon dilatation

Lunar-sourced GEO Powersats: An Integrated ISRU System

Solar power satellites (powersats) can be built almost entirely from lunar resources. When C-class asteroids are also included as ore bodies a complete powersat can be built through insitu resource utilization (ISRU) given appropriate processing and transportation technology.This article provides an in-depth overview of the technical feasibility and economic viabilityof lunar construction and operations for powersat component construction and delivery togeostationary earth orbit (GEO). Techno-economic analysis suggests a return on investmentin seven years assuming a three percent discount rate. Electrical power collected in GEO andbeamed to terrestrial receivers by the powersats can be sold as baseload power in the wholesale electricity market to generate revenue. This work presents a complete concept of operationsfrom initial rocket launches to regolith harvesting through transport to GEO. Lunarinfrastructure can be constructed of modules to optimize size and weight for launch costs.Future growth can be derived from using ISRU to build additional processing bases. A scale-up in this manner can provide 22% of the world’s energy needs by the end of a 20-year period.This work builds upon previous studies and completes the architectural description ofpredominantly lunar-sourced GEO powersats

Distributions and compound-specific isotopic signatures of sedimentary chlorins reflect the composition of photoautotrophic communities and their carbon and nitrogen sources in Swiss lakes and the Black Sea

We examined the distributions of tetrapyrrole pigments (i.e. intact chlorophylls and bacteriochlorophylls, pheopigments) as well as their compound-specific carbon and nitrogen isotopic compositions in the sediments of three Swiss lakes (Lakes Rotsee, Cadagno and Zurich) and the Black Sea to investigate the biogeochemical cycling of carbon and nitrogen mediated by phototrophic eukaryotes (algae) and bacteria. The factors controlling chlorin isotope variations are discussed and the feasibility to use chlorins as indicators for reconstructions of surface water environments is evaluated. Chlorophyll a and its derivatives including pheophytin a, a pheophytin a epimer, pyropheophytin a, 132,173-cyclopheophorbide-a-enol, chlorophyllone a as well as steryl and carotenol chlorin esters were detected in all sediments. The presence of bacteriochlorophylls e and their derivatives confirmed the presence of brown strains of green phototrophic sulfur bacteria (Chlorobiaceae; GSB) in all three lakes. In the shallower Lakes Rotsee and Cadagno, purple sulfur bacteria (Chromatiaceae; PSB) were also present as confirmed by bacteriochlorophyll a derivatives. Despite the different degrees of water column hypoxia at the studied sites, the chlorins in all sediments were attributed to rapid transformation of intact tetrapyrroles and the formation of related pheopigments.The scatter of compound-specific carbon isotopic compositions of Chl a and its derivatives resulted from different timing of pheopigment formation, likely due to the interaction of blooms of various phytoplankton communities at different times of the year and the variable degrees of carbon limitation and/or different contributions of recycled organic matter (OM). The nitrogen isotopic composition of the chloropigments mainly derived from nitrate assimilation in Lake Zurich and the Black Sea, whereas ammonium and nitrate assimilation were predominant in Lake Rotsee. In the epilimnion of the meromictic Lake Cadagno, dissolved organic nitrogen (DON) supplied to the surface water from ammonium assimilation in the chemocline may be the main nitrogen source. Phototrophic sulfur bacteria in Lakes Rotsee and Cadagno thrived mainly under dissolved organic carbon depleted conditions within the chemocline and in the hypolimnion. GSB may use predominantly ammonium and at least in Lake Cadagno also perform N2 fixation. In contrast, the nitrogen source of PSB could not be reconstructed with d15N values of bacteriochlorins, because nitrogen isotopic fractionation during BChl a synthesis seems to be almost independent of the assimilated substrate

Compound-specific carbon and nitrogen isotopic compositions of chlorophyll a and its derivatives reveal the eutrophication history of Lake Zurich (Switzerland)

© 2016 Elsevier B.V. To reconstruct the impact of eutrophication on phototrophic communities and the biogeochemical cycling of carbon and nitrogen in the surface water, we investigated the distributions and carbon and nitrogen isotopic compositions (d13C and d15N values) of chlorins in the sediments of Lake Zurich. The chlorin distributions were dominated by chlorophyll a (Chl a) and its derivatives, which reflect rapid degradation to the pheopigments in the water column and sediments of the lake. The d13C values of these sedimentary chlorins followed the historical trends of eutrophication and reoligotrophication, except in the surface sediments, which were characterised by higher relative contributions of aged, redeposited organic matter (OM). The d13C values of the sedimentary chlorins together with bulk sediment d13C values and C/N ratios indicate that the phototrophic communities in the lake used a 13C-depleted carbon source, which is mainly of aquatic origin. The d15N values of chlorins reflect the predominance of nitrate assimilating phototrophs, especially the non-N2-fixing cyanobacterium Planktothrix rubescens prevalent during sediment deposition. Shifts in d15N values of Chl a followed mostly the trends in eutrophication and reoligotrophication, but were also affected by community assemblage shifts to diatoms and/or other cyanobacteria at the end of the 19th century and during the eutrophication maximum in the 1970s.The lower d15NChl-a values in the surface sediments coincide with increasing nitrogen to phosphorus ratios and reduced water column mixing that characterise the recent reoligotrophication period and may explain the predominance of P. rubescens in Lake Zurich. In contrast, the higher contributions of laterally transported OM explains the large offset of d15N values of the pheopigments relative to Chl a, which is supported by the high radiocarbon age of the surface sediments

Quantitative Mass Spectrometry Analysis Reveals Similar Substrate Consensus Motif for Human Mps1 Kinase and Plk1

Background Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC), a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1) is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. Methodology/Principal Findings Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. Conclusions/Significance hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase

OSS (Outer Solar System): A fundamental and planetary physics mission to Neptune, Triton and the Kuiper Belt

The present OSS mission continues a long and bright tradition by associating the communities of fundamental physics and planetary sciences in a single mission with ambitious goals in both domains. OSS is an M-class mission to explore the Neptune system almost half a century after flyby of the Voyager 2 spacecraft. Several discoveries were made by Voyager 2, including the Great Dark Spot (which has now disappeared) and Triton's geysers. Voyager 2 revealed the dynamics of Neptune's atmosphere and found four rings and evidence of ring arcs above Neptune. Benefiting from a greatly improved instrumentation, it will result in a striking advance in the study of the farthest planet of the Solar System. Furthermore, OSS will provide a unique opportunity to visit a selected Kuiper Belt object subsequent to the passage of the Neptunian system. It will consolidate the hypothesis of the origin of Triton as a KBO captured by Neptune, and improve our knowledge on the formation of the Solar system. The probe will embark instruments allowing precise tracking of the probe during cruise. It allows to perform the best controlled experiment for testing, in deep space, the General Relativity, on which is based all the models of Solar system formation. OSS is proposed as an international cooperation between ESA and NASA, giving the capability for ESA to launch an M-class mission towards the farthest planet of the Solar system, and to a Kuiper Belt object. The proposed mission profile would allow to deliver a 500 kg class spacecraft. The design of the probe is mainly constrained by the deep space gravity test in order to minimise the perturbation of the accelerometer measurement.Comment: 43 pages, 10 figures, Accepted to Experimental Astronomy, Special Issue Cosmic Vision. Revision according to reviewers comment

Network-Based Prediction and Analysis of HIV Dependency Factors

HIV Dependency Factors (HDFs) are a class of human proteins that are essential for HIV replication, but are not lethal to the host cell when silenced. Three previous genome-wide RNAi experiments identified HDF sets with little overlap. We combine data from these three studies with a human protein interaction network to predict new HDFs, using an intuitive algorithm called SinkSource and four other algorithms published in the literature. Our algorithm achieves high precision and recall upon cross validation, as do the other methods. A number of HDFs that we predict are known to interact with HIV proteins. They belong to multiple protein complexes and biological processes that are known to be manipulated by HIV. We also demonstrate that many predicted HDF genes show significantly different programs of expression in early response to SIV infection in two non-human primate species that differ in AIDS progression. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of AIDS development. More generally, if multiple genome-wide gene-level studies have been performed at independent labs to study the same biological system or phenomenon, our methodology is applicable to interpret these studies simultaneously in the context of molecular interaction networks and to ask if they reinforce or contradict each other

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme