55 research outputs found
Solution Structures of the C-Terminal Domain of Cardiac Troponin C Free and Bound to the N-Terminal Domain of Cardiac Troponin I
The N-terminal domain of cardiac troponin I (cTnI) comprising residues 33−80 and lacking the cardiac-specific amino terminus forms a stable binary complex with the C-terminal domain of cardiac troponin C (cTnC) comprising residues 81−161. We have utilized heteronuclear multidimensional NMR to assign the backbone and side-chain resonances of Ca2+-saturated cTnC(81−161) both free and bound to cTnI(33−80). No significant differences were observed between secondary structural elements determined for free and cTnI(33−80)-bound cTnC(81−161). We have determined solution structures of Ca2+-saturated cTnC(81−161) free and bound to cTnI(33−80). While the tertiary structure of cTnC(81−161) is qualitatively similar to that observed free in solution, the binding of cTnI(33−80) results mainly in an opening of the structure and movement of the loop region between helices F and G. Together, these movements provide the binding site for the N-terminal domain of cTnI. The putative binding site for cTnI(33−80) was determined by mapping amide proton and nitrogen chemical shift changes, induced by the binding of cTnI(33−80), onto the C-terminal cTnC structure. The binding interface for cTnI(33−80), as suggested from chemical shift changes, involves predominantly hydrophobic interactions located in the expanded hydrophobic pocket. The largest chemical shift changes were observed in the loop region connecting helices F and G. Inspection of available TnC sequences reveals that these residues are highly conserved, suggesting a common binding motif for the Ca2+/Mg2+-dependent interaction site in the TnC/TnI complex
s-Process Abundances in Planetary Nebulae
The s-process should occur in all but the lower mass progenitor stars of
planetary nebulae, and this should be reflected in the chemical composition of
the gas which is expelled to create the current planetary nebula shell. Weak
forbidden emission lines are expected from several s-process elements in these
shells, and have been searched for and in some cases detected in previous
investigations. Here we extend these studies by combining very high
signal-to-noise echelle spectra of a sample of PNe with a critical analysis of
the identification of the emission lines of Z>30 ions. Emission lines of Br,
Kr, Xe, Rb, Ba, and Pb are detected with a reasonable degree of certainty in at
least some of the objects studied here, and we also tentatively identify lines
from Te and I, each in one object. The strengths of these lines indicate
enhancement of s-process elements in the central star progenitors, and we
determine the abundances of Br, Kr, and Xe, elements for which atomic data
relevant for abundance determination have recently become available. As
representative elements of the ``light'' and ``heavy'' s-process peaks Kr and
Xe exhibit similar enhancements over solar values, suggesting that PNe
progenitors experience substantial neutron exposure.Comment: 56 Pages, 6 figures, accepted for publication in ApJ This version
corrects missing captions in Figure 1-3 and minor typo
Resource Quantity Affects Benthic Microbial Community Structure and Growth Efficiency in a Temperate Intertidal Mudflat
Estuaries cover <1% of marine habitats, but the carbon dioxide (CO2) effluxes from these net heterotrophic systems contribute significantly to the global carbon cycle. Anthropogenic eutrophication of estuarine waterways increases the supply of labile substrates to the underlying sediments. How such changes affect the form and functioning of the resident microbial communities remains unclear. We employed a carbon-13 pulse-chase experiment to investigate how a temperate estuarine benthic microbial community at 6.5°C responded to additions of marine diatom-derived organic carbon equivalent to 4.16, 41.60 and 416.00 mmol C m−2. The quantities of carbon mineralized and incorporated into bacterial biomass both increased significantly, albeit differentially, with resource supply. This resulted in bacterial growth efficiency increasing from 0.40±0.02 to 0.55±0.04 as substrates became more available. The proportions of diatom-derived carbon incorporated into individual microbial membrane fatty acids also varied with resource supply. Future increases in labile organic substrate supply have the potential to increase both the proportion of organic carbon being retained within the benthic compartment of estuaries and also the absolute quantity of CO2 outgassing from these environments
Harmful algal blooms and eutrophication : examining linkages from selected coastal regions of the United States
Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Harmful Algae 8 (2008): 39-53, doi:10.1016/j.hal.2008.08.017.Coastal waters of the United States (U.S.) are subject to many of the major harmful algal
bloom (HAB) poisoning syndromes and impacts. These include paralytic shellfish poisoning
(PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), ciguatera
fish poisoning (CFP) and various other HAB phenomena such as fish kills, loss of submerged
vegetation, shellfish mortalities, and widespread marine mammal mortalities. Here, the
occurrences of selected HABs in a selected set of regions are described in terms of their
relationship to eutrophication, illustrating a range of responses. Evidence suggestive of
changes in the frequency, extent or magnitude of HABs in these areas is explored in the
context of the nutrient sources underlying those blooms, both natural and anthropogenic. In
some regions of the U.S., the linkages between HABs and eutrophication are clear and well
documented, whereas in others, information is limited, thereby highlighting important areas
for further research.Support was provided through the Woods Hole Center for Oceans
and Human Health (to DMA), National Science Foundation (NSF) grants OCE-9808173 and
OCE-0430724 (to DMA), OCE-0234587 (to WPC), OCE04-32479 (to MLP), OCE-0138544
(to RMK), OCE-9981617 (to PMG); National Institute of Environmental Health Sciences
(NIEHS) grants P50ES012742-01 (to DMA) and P50ES012740 (to MLP); NOAA Grants
NA96OP0099 (to DMA), NA16OP1450 (to VLT), NA96P00084 (to GAV and CAH),
NA160C2936 and NA108H-C (to RMK), NA860P0493 and NA04NOS4780241 (to PMG),
NA04NOS4780239-02 (to RMK), NA06NOS4780245 (to DWT). Support was also provided from the West Coast Center for Oceans and Human Health (to VLT and WPC), USEPA
Grant CR826792-01-0 (to GAV and CAH), and the State of Florida Grant S7701617826 (to
GAV and CAH)
NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.
Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes
Guiding principles for the development and application of solid-phase phosphorus adsorbents for freshwater ecosystems
While a diverse array of phosphorus (P)-adsorbent materials is currently available for application to freshwater aquatic systems, selection of the most appropriate P-adsorbents remains problematic. In particular, there has to be a close correspondence between attributes of the P-adsorbent, its field performance, and the management goals for treatment. These management goals may vary from a rapid reduction in dissolved P to address seasonal enrichments from internal loading, targeting external fluxes due to anthropogenic sources, or long term inactivation of internal P inventories contained within bottom sediments. It also remains a challenge to develop new methods and materials that are ecologically benign and cost-effective. We draw on evidence in the literature and the authors’ personal experiences in the field, to summarise the attributes of a range of P-adsorbent materials. We offer 'guiding principles' to support practical use of existing materials and outline key development needs for new materials
A framework for human microbiome research
A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies
Structure, function and diversity of the healthy human microbiome
Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in
part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273
to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander;
U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.;
U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.;
R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.;
R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to
D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and
R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.;
R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was
supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves
and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang,
F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J.
V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.);
DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research;
U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and
R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and
D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research
Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF
DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US
Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL
Laboratory-Directed Research and Development grant 20100034DR and the US
Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research
Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career
Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe
J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by
the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial
Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of
Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis
of the HMPdata was performed using National Energy Research Scientific Computing
resources, the BluBioU Computational Resource at Rice University
Surface rupture of multiple crustal faults in the 2016 Mw 7.8 Kaikōura, New Zealand, earthquake
Multiple (>20
>20
) crustal faults ruptured to the ground surface and seafloor in the 14 November 2016 M w
Mw
7.8 Kaikōura earthquake, and many have been documented in detail, providing an opportunity to understand the factors controlling multifault ruptures, including the role of the subduction interface. We present a summary of the surface ruptures, as well as previous knowledge including paleoseismic data, and use these data and a 3D geological model to calculate cumulative geological moment magnitudes (M G w
MwG
) and seismic moments for comparison with those from geophysical datasets. The earthquake ruptured faults with a wide range of orientations, sense of movement, slip rates, and recurrence intervals, and crossed a tectonic domain boundary, the Hope fault. The maximum net surface displacement was ∼12 m
∼12 m
on the Kekerengu and the Papatea faults, and average displacements for the major faults were 0.7–1.5 m south of the Hope fault, and 5.5–6.4 m to the north. M G w
MwG
using two different methods are M G w
MwG
7.7 +0.3 −0.2
7.7−0.2+0.3
and the seismic moment is 33%–67% of geophysical datasets. However, these are minimum values and a best estimate M G w
MwG
incorporating probable larger slip at depth, a 20 km seismogenic depth, and likely listric geometry is M G w
MwG
7.8±0.2
7.8±0.2
, suggests ≤32%
≤32%
of the moment may be attributed to slip on the subduction interface and/or a midcrustal detachment. Likely factors contributing to multifault rupture in the Kaikōura earthquake include (1) the presence of the subduction interface, (2) physical linkages between faults, (3) rupture of geologically immature faults in the south, and (4) inherited geological structure. The estimated recurrence interval for the Kaikōura earthquake is ≥5,000–10,000 yrs
≥5,000–10,000 yrs
, and so it is a relatively rare event. Nevertheless, these findings support the need for continued advances in seismic hazard modeling to ensure that they incorporate multifault ruptures that cross tectonic domain boundaries
Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
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