Hydrothermal activity lowers trophic diversity in Antarctic sedimented hydrothermal vents

Sedimented hydrothermal vents are those in which hydrothermal fluid vents through sediment and are among the least studied deep-sea ecosystems. We present a combination of microbial and biochemical data to assess trophodynamics between and within hydrothermally active and off-vent areas of the Bransfield Strait (1050–1647 m depth). Microbial composition, biomass and fatty acid signatures varied widely between and within vent and non-vent sites and provided evidence of diverse metabolic activity. Several species showed diverse feeding strategies and occupied different trophic positions in vent and non-vent areas and stable isotope values of consumers were generally not consistent with feeding structure morphology. Niche area and the diversity of microbial fatty acids reflected trends in species diversity and was lowest at the most hydrothermally active site. Faunal utilisation of chemosynthetic activity was relatively limited but was detected at both vent and non-vent sites as evidenced by carbon and sulphur isotopic signatures, suggesting that the hydrothermal activity can affect trophodynamics over a much wider area than previously thought

The structure of the hydrated electron. Part 2. A mixed quantum classical molecular dynamics - embedded cluster density functional theory: single-excitation configuration interaction study

Adiabatic mixed quantum/classical molecular dynamics simulations were used to generate snapshots of the hydrated electron (e-) in liquid water at 300 K. Water cluster anions that include two complete solvation shells centered on the e- were extracted from these simulations and embedded in a matrix of fractional point charges designed to represent the rest of the solvent. Density functional theory and single-excitation configuration interaction methods were then applied to these embedded clusters. The salient feature of these hybrid calculations is significant transfer (ca. 0.18) of the excess electron's charge density into the O 2p orbitals in OH groups forming the solvation cavity. We used the results of these calculations to examine the structure of the molecular orbitals, the density of states, the absorption spectra in the visible and ultraviolet, the hyperfine coupling (hfc) tensors, and the IR and Raman spectra of the e-. The calculated hfc tensors were used to compute the EPR and ESEEM spectra for the e- that compared favorably to the experimental spectra of trapped e- in alkaline ice. The calculated vibrational spectra of the e- are consistent with the red-shifted bending and stretching frequencies observed in resonance Raman experiments. The model also accounts for the VIS and 190-nm absorption bands of the e-. Thus, our study suggests that to explain several important experimentally observed properties of the e-, many-electron effects must be accounted for.Comment: 68 pages, 12 figures + 16 more figures in the supplement (included) submitted to J Phys Chem

Local structures of free-standing AlₓGa₁ˍₓN thin films studied by extended x-ray absorption fine structure

Local structural information for the first two atomic shells surrounding Ga atoms in free standing AlₓGa₁ˍₓN alloy films has been obtained by extended x-ray absorption fine structure spectroscopy. For an AlN mole fraction ranging from 0 to 0.6, we found that the first shell Ga–N bond length had only a weak composition dependence, roughly one quarter of that predicted by Vegard’s Law. In the second shell, the Ga–Ga bond length was significantly longer than that of Ga–Al (Δ∼0.04–0.065 Å). A bond-type specific composition dependence was observed for the second shell cation–cation distances. While the composition dependence of the Ga–Ga bond length is ∼70% of that predicted by Vegard’s Law, the Ga–Al bond length was essentially composition independent. These results suggested that local strain in AlₓGa₁ˍₓN was also accommodated by lattice distortion in the Al cation sublattice.This work was supported by the Director, Office of Science, Of- fice of Basic Energy Sciences, Materials Science Division of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. The LLO work was performed at the UC Berkeley Integrated Materials Laboratory which was supported in part by the National Science Foundation. C.J.G. and M.C.R. were supported by the Australian Synchrotron Research Program, funded by the Commonwealth of Australia via the Major National Research Facilities Program. SSRL was supported by the Office of Basic Energy Sciences of the U.S. Department of Energy

Endoscopic, radiologic, and histologic healing with vedolizumab in patients with active Crohn's disease

BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111. ispartof: GASTROENTEROLOGY vol:157 issue:4 pages:1007-+ ispartof: location:United States status: publishe

Hierarchical patterning modes orchestrate hair follicle morphogenesis

Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction–diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern’s condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction–diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs