A new transcript in the TCRB locus unveils the human ortholog of the mouse pre-Dß1 promoter

Introduction: While most transcripts arising from the human T Cell Receptor locus reflect fully rearranged genes, several germline transcripts have been identified. We describe a new germline transcript arising from the human TCRB locus. Methods: cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript. Results: The new germline transcript encoded by the human TCRB locus consists of a new exon of 103bp, which we named TRBX1 (X1), spliced with the first exon of gene segments C ss 1 or C ss 2. X1 is located upstream of gene segment D ss 1 and is therefore deleted from a V-DJ rearranged TCRB locus. The X1-C ss transcripts do not appear to code for a protein. We define their transcription start and minimal promoter. These transcripts are found in populations of mature T lymphocytes from blood or tissues and in T cell clones with a monoallelic TCRB rearrangement. In immature thymocytes, they are already detectable in CD1a(-)CD34(+)CD4(-)CD8(-) cells, therefore before completion of the TCRB rearrangements. Conclusions: The X1 promoter appears to be the ortholog of the mouse pre-D ss 1 promoter (PD ss 1). Like PD ss 1, its activation is regulated by E ss in T cells and might facilitate the TCRB rearrangement process by contributing to the accessibility of the D ss 1 locus

On the bulk isotopic composition of magnesium and silicon during the May 1998 CME: ACE/SWIMS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95217/1/grl11855.pd

An in-flight plasma diagnostic package for spacecraft with electric propulsion

The plasma diagnostics presented in this article target the plasma surrounding a spacecraft that is created by the electric thruster and its surface modifying effects. The diagnostic package includes a retarding potential analyzer, a plane Langmuir probe, and an erosion sensor. The paper describes the instrument as well as suitable test environments for mimicking the effects expected in space and shows test results. The system is to fly for the first time on the Heinrich Hertz satellite, which is scheduled to be launched in 2023. The spacecraft will be equipped with a pair of Highly Efficient Multistage Plasma Thrusters (HEMPT) and a pair of Hall thrusters for redundancy

The Lunar Lander Neutron and Dosimetry (LND) Experiment on Chang'E 4

Chang'E 4 is the first mission to the far side of the Moon and consists of a lander, a rover, and a relay spacecraft. Lander and rover were launched at 18:23 UTC on December 7, 2018 and landed in the von K\'arm\'an crater at 02:26 UTC on January 3, 2019. Here we describe the Lunar Lander Neutron \& Dosimetry experiment (LND) which is part of the Chang'E 4 Lander scientific payload. Its chief scientific goal is to obtain first active dosimetric measurements on the surface of the Moon. LND also provides observations of fast neutrons which are a result of the interaction of high-energy particle radiation with the lunar regolith and of their thermalized counterpart, thermal neutrons, which are a sensitive indicator of subsurface water content.Comment: 38 pages, submitted to Space Science Review

Animating tree colonization and growth

In the early twentieth century the woodland at Heald Brow, north-west England, was largely a tree-less pasture, but changing land management practices lead to natural tree colonization and the development of a mixed deciduous woodland with ash (Fraxinus excelsior), oak (Quercus robur), yew (Taxus baccata) and small-leaved Lime (Tilia cordata) the main components. The research focused on T. cordata due to its rarity and conservation value, and aimed to investigate the timing of its appearance, rates of reproduction by layering and the effects of competition on its longer-term survival. A small, 0.32 ha area of woodland was mapped using standard field-based survey methods and increment cores were taken to provide minimum age estimates for living stems of all species present. The spatial and temporal data generated led to the development of a new micro-GIS animation method, using ArcGIS software, that visually highlighted secondary woodland establishment and development, and gave novel insights into the competitive interactions that governed the development. Results showed T. cordata colonization in the 1940s and layering developing in the 1960s. The later appearance and rapid establishment of T. baccata with its light-excluding canopy produced high competition scores and undoubtedly restricted further development of the main T. cordata canopy aided by F. excelsior at the periphery. This animation method and associated GIS analyses have potential application in both dendrochronological, wider ecological research and in conservation management

Current strategies for quantification of estrogens in clinical research

Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment

Engineering Nano- and Microparticles to Tune Immunity

The immune system can be a cure or cause of disease, fulfilling a protective role in attacking cancer or pathogenic microbes but also causing tissue destruction in autoimmune disorders. Thus, therapies aimed to amplify or suppress immune reactions are of great interest. However, the complex regulation of the immune system, coupled with the potential systemic side effects associated with traditional systemic drug therapies, has presented a major hurdle for the development of successful immunotherapies. Recent progress in the design of synthetic micro- and nano-particles that can target drugs, deliver imaging agents, or stimulate immune cells directly through their physical and chemical properties is leading to new approaches to deliver vaccines, promote immune responses against tumors, and suppress autoimmunity. In addition, novel strategies, such as the use of particle-laden immune cells as living targeting agents for drugs, are providing exciting new approaches for immunotherapy. This progress report describes recent advances in the design of micro- and nano-particles for immunotherapies and diagnostics.National Institutes of Health (U.S.) (AI095109)National Institutes of Health (U.S.) (CA140476)United States. Dept. of Defense (Contract W81XWH-10-1-0290)United States. Dept. of Defense (Contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and Harvar

Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike