(4R)-4-(2-Allyl-2H-1,2,3-triazol-4-yl)-1,2-O-isopropyl­idene-l-threose

X-ray crystallography unequivocally confirmed the structure of the title compound, C12H17N3O4, as (4R)-4-(2-allyl-2H-1,2,3-triazol-4-yl)-1,2-O-isopropyl­idene-l-threose. The absolute configuration was determined by the use of d-glucorono-3,6-lactone as the starting material. The crystal structure consists of hydrogen-bonded chains of mol­ecules running parallel to the a axis. There are no unusual packing features

6-De­oxy-6-fluoro-d-galactose

The crystal structure unequivocally confirms the relative stereochemistry of the title compound, C6H11FO5. The absolute stereochemistry was determined by the use of d-galactose as the starting material. The compound exists as a three-dimensional O—H⋯O hydrogen-bonded network with each mol­ecule acting as a donor and acceptor for four hydrogen bonds

Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol hydro­bromide]

X-ray crystallographic analysis of the title hydro­bromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxy­lated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae) leaves. In the crystal structure, mol­ecules are linked by inter­molecular O—H⋯Br and N—H⋯Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intra­molecular O—H⋯O inter­actions occur

A mature cluster with X-ray emission at z=2.07

We report evidence of a fully established galaxy cluster at z=2.07, consisting of a ~20sigma overdensity of red, compact spheroidal galaxies spatially coinciding with extended X-ray emission detected with XMM-Newton. We use VLT VIMOS and FORS2 spectra and deep Subaru, VLT and Spitzer imaging to estimate the redshift of the structure from a prominent z=2.07 spectroscopic redshift spike of emission-line galaxies, concordant with the accurate 12-band photometric redshifts of the red galaxies. Using NICMOS and Keck AO observations, we find that the red galaxies have elliptical morphologies and compact cores. While they do not form a tight red sequence, their colours are consistent with that of a >1.3$~Gyr population observed at z~2.1. From an X-ray luminosity of .2*10^43 erg s^-1 and the stellar mass content of the red galaxy population, we estimate a halo mass of 5.3-8*10^13 Msun, comparable to the nearby Virgo cluster. These properties imply that this structure could be the most distant, mature cluster known to date and that X-ray luminous, elliptical-dominated clusters are already forming at substantially earlier epochs than previously known.Comment: 14 pages, 12 figures; accepted for publication in Astronomy & Astrophysic

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Exploring X-ray and radio emission of type 1 AGN up to z ~ 2.3

X-ray emission from AGN is dominated by the accretion disk around a SMBH. The radio luminosity, however, has not such a clear origin except in the most powerful sources where jets are evident. The origin (and even the very existence) of the local bi-modal distribution in radioloudness is also a debated issue. By analysing X-ray, optical and radio properties of a large sample of type 1 AGN up to z>2, where the bulk of this population resides, we aim to explore the interplay between radio and X-ray emission in AGN, in order to further our knowledge on the origin of radio emission, and its relation to accretion. We analyse a large (~800 sources) sample of type 1 AGN and QSOs selected from the 2XMMi X-ray source catalogue, cross-correlated with the SDSS DR7 spectroscopic catalogue, covering a redshift range from z~0.3 to z~2.3. SMBH masses are estimated from the Mg II emission line, bolometric luminosities from the X-ray data, and radio emission or upper limits from the FIRST catalogue. Most of the sources accrete close to the Eddington limit and the distribution in radioloudness does not appear to have a bi-modal behaviour. We confirm that radioloud AGN are also X-ray loud, with an X-ray-to-optical ratio up to twice that of radioquiet objects, even excluding the most extreme strongly jetted sources. By analysing complementary radio-selected control samples, we find evidence that these conclusions are not an effect of the X-ray selection, but are likely a property of the dominant QSO population. Our findings are best interpreted in a context where radio emission in AGN, with the exception of a minority of beamed sources, arises from very close to the accretion disk and is therefore heavily linked to X-ray emission. We also speculate that the RL/RQ dichotomy might either be an evolutionary effect that developed well after the QSO peak epoch, or an effect of incompleteness in small samples.Comment: Accepted for publication in A&A; 16 pages, 5 tables, 10 figures; tables 3-5 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A

Effect of Sulindac Sulfide on Metallohydrolases in the Human Colon Cancer Cell Line HT-29

Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the ApcMin/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases

The Role of DNA Barcodes in Understanding and Conservation of Mammal Diversity in Southeast Asia

Southeast Asia is recognized as a region of very high biodiversity, much of which is currently at risk due to habitat loss and other threats. However, many aspects of this diversity, even for relatively well-known groups such as mammals, are poorly known, limiting ability to develop conservation plans. This study examines the value of DNA barcodes, sequences of the mitochondrial COI gene, to enhance understanding of mammalian diversity in the region and hence to aid conservation planning.DNA barcodes were obtained from nearly 1900 specimens representing 165 recognized species of bats. All morphologically or acoustically distinct species, based on classical taxonomy, could be discriminated with DNA barcodes except four closely allied species pairs. Many currently recognized species contained multiple barcode lineages, often with deep divergence suggesting unrecognized species. In addition, most widespread species showed substantial genetic differentiation across their distributions. Our results suggest that mammal species richness within the region may be underestimated by at least 50%, and there are higher levels of endemism and greater intra-specific population structure than previously recognized.DNA barcodes can aid conservation and research by assisting field workers in identifying species, by helping taxonomists determine species groups needing more detailed analysis, and by facilitating the recognition of the appropriate units and scales for conservation planning

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences