Repression of SOX6 transcriptional activity by SUMO modification

AbstractSOX6 plays key functions in several developmental processes, including neurogenesis and skeleton formation. In this report, we show that SOX6 is modified in vitro and in vivo by small ubiquitin-related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity. Furthermore, co-expression of SOX6 with SUMO2 results in the appearance of SOX6 in a punctate nuclear pattern that colocalized with promyelocytic leukemia protein, which was partially abolished by mutations in SOX6 sumoylation sites

A global Carleman estimate in a transmission wave equation and application to a one-measurement inverse problem

We consider a transmission wave equation in two embedded domains in $R^2$, where the speed is $a1 > 0$ in the inner domain and $a2 > 0$ in the outer domain. We prove a global Carleman inequality for this problem under the hypothesis that the inner domain is strictly convex and $a1 > a2$ . As a consequence of this inequality, uniqueness and Lip- schitz stability are obtained for the inverse problem of retrieving a stationary potential for the wave equation with Dirichlet data and discontinuous principal coefficient from a single time-dependent Neumann boundary measurement

The Helium and Carbon Isotope Characteristics of the Andean Convergent Margin

Subduction zones represent the interface between Earth’s interior (crust and mantle) and exterior (atmosphere and oceans), where carbon and other volatile elements are actively cycled between Earth reservoirs by plate tectonics. Helium is a sensitive tracer of volatile sources and can be used to deconvolute mantle and crustal sources in arcs; however it is not thought to be recycled into the mantle by subduction processes. In contrast, carbon is readily recycled, mostly in the form of carbon-rich sediments, and can thus be used to understand volatile delivery via subduction. Further, carbon is chemically-reactive and isotope fractionation can be used to determine the main processes controlling volatile movements within arc systems. Here, we report helium isotope and abundance data for 42 deeply-sourced fluid and gas samples from the Central Volcanic Zone (CVZ) and Southern Volcanic Zone (SVZ) of the Andean Convergent Margin (ACM). Data are used to assess the influence of subduction parameters (e.g., crustal thickness, subduction inputs, and convergence rate) on the composition of volatiles in surface volcanic fluid and gas emissions. He isotopes from the CVZ backarc range from 0.1 to 2.6 RA (n = 23), with the highest values in the Puna and the lowest in the Sub-Andean foreland fold-and-thrust belt. Atmosphere-corrected He isotopes from the SVZ range from 0.7 to 5.0 RA (n = 19). Taken together, these data reveal a clear southeastward increase in 3He/4He, with the highest values (in the SVZ) falling below the nominal range associated with pure upper mantle helium (8 ± 1 RA), approaching the mean He isotope value for arc gases of (5.4 ± 1.9 RA). Notably, the lowest values are found in the CVZ, suggesting more significant crustal inputs (i.e., assimilation of 4He) to the helium budget. The crustal thickness in the CVZ (up to 70 km) is significantly larger than in the SVZ, where it is just ∼40 km. We suggest that crustal thickness exerts a primary control on the extent of fluid-crust interaction, as helium and other volatiles rise through the upper plate in the ACM. We also report carbon isotopes from (n = 11) sites in the CVZ, where δ13C varies between −15.3‰ and −1.2‰ [vs. Vienna Pee Dee Belemnite (VPDB)] and CO2/3He values that vary by over two orders of magnitude (6.9 × 108–1.7 × 1011). In the SVZ, carbon isotope ratios are also reported from (n = 13) sites and vary between −17.2‰ and −4.1‰. CO2/3He values vary by over four orders of magnitude (4.7 × 107–1.7 × 1012). Low δ13C and CO2/3He values are consistent with CO2 removal (e.g., calcite precipitation and gas dissolution) in shallow hydrothermal systems. Carbon isotope fractionation modeling suggests that calcite precipitation occurs at temperatures coincident with the upper temperature limit for life (122°C), suggesting that biology may play a role in C-He systematics of arc-related volcanic fluid and gas emissions.Fil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: De Moor, J. M.. University of New Mexico; Estados Unidos. UNIVERSIDAD NACIONAL DE COSTA RICA (UNA);Fil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Aguilera, F.. Universidad Católica del Norte; ChileFil: Hudak, M. R.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Turner, S. J.. University of Massachussets; Estados UnidosFil: Curtice, J.. Woods Hole Oceanographic Institution; Estados UnidosFil: Seltzer, A. M.. Woods Hole Oceanographic Institution; Estados UnidosFil: Jessen, G. L.. Universidad Austral de Chile; ChileFil: Osses, E.. Universidad Austral de Chile; ChileFil: Blamey, J. M.. Universidad de Santiago de Chile; ChileFil: Amenábar, M. J.. Universidad de Santiago de Chile; ChileFil: Selci, M.. University Of Naples Federico Ii; ItaliaFil: Cascone, M.. University Of Naples Federico Ii; ItaliaFil: Bastianoni, A.. University Of Naples Federico Ii; ItaliaFil: Nakagawa, M.. Tokyo Institute Of Technology; JapónFil: Filipovich, Ruben Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bustos, Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Buongiorno, J.. Maryville College; Estados UnidosFil: Ramírez, C. J.. Servicio Geológico Ambiental (segeoam); Costa RicaFil: Rogers, T. J.. University of Tennessee; Estados UnidosFil: Lloyd, K. G.. University of Tennessee; Estados UnidosFil: Giovannelli, D.. Institute Of Marine Biological Resources And Biotechno; Itali

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

VEIN v0.2.2: an R package for bottom–up vehicular emissions inventories

Emission inventories are the quantification of pollutants from different sources. They provide important information not only for climate and weather studies but also for urban planning and environmental health protection. We developed an open-source model (called Vehicular Emissions Inventory – VEIN v0.2.2) that provides high-resolution vehicular emissions inventories for different fields of studies. We focused on vehicular sources at street and hourly levels due to the current lack of information about these sources, mainly in developing countries.The type of emissions covered by VEIN are exhaust (hot and cold) and evaporative considering the deterioration of the factors. VEIN also performs speciation and incorporates functions to generate and spatially allocate emissions databases. It allows users to load their own emission factors, but it also provides emission factors from the road transport model (Copert), the United States Environmental Protection Agency (EPA) and Brazilian databases. The VEIN model reads, distributes by age of use and extrapolates hourly traffic data, and it estimates emissions hourly and spatially. Based on our knowledge, VEIN is the first bottom–up vehicle emissions software that allows input to the WRF-Chem model. Therefore, the VEIN model provides an important, easy and fast way of elaborating or analyzing vehicular emissions inventories under different scenarios. The VEIN results can be used as an input for atmospheric models, health studies, air quality standardizations and decision making