The cytosolic glutathione transferase (cytGST) superfamily comprises more than 13,000 nonredundant sequences found throughout the biosphere. Their key roles in metabolism and defense against ...oxidative damage have led to thousands of studies over several decades. Despite this attention, little is known about the physiological reactions they catalyze and most of the substrates used to assay cytGSTs are synthetic compounds. A deeper understanding of relationships across the superfamily could provide new clues about their functions. To establish a foundation for expanded classification of cytGSTs, we generated similarity-based subgroupings for the entire superfamily. Using the resulting sequence similarity networks, we chose targets that broadly covered unknown functions and report here experimental results confirming GST-like activity for 82 of them, along with 37 new 3D structures determined for 27 targets. These new data, along with experimentally known GST reactions and structures reported in the literature, were painted onto the networks to generate a global view of their sequence-structure-function relationships. The results show how proteins of both known and unknown function relate to each other across the entire superfamily and reveal that the great majority of cytGSTs have not been experimentally characterized or annotated by canonical class. A mapping of taxonomic classes across the superfamily indicates that many taxa are represented in each subgroup and highlights challenges for classification of superfamily sequences into functionally relevant classes. Experimental determination of disulfide bond reductase activity in many diverse subgroups illustrate a theme common for many reaction types. Finally, sequence comparison between an enzyme that catalyzes a reductive dechlorination reaction relevant to bioremediation efforts with some of its closest homologs reveals differences among them likely to be associated with evolution of this unusual reaction. Interactive versions of the networks, associated with functional and other types of information, can be downloaded from the Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu).
REFERENCE UPPER-AIR OBSERVATIONS FOR CLIMATE Bodeker, G. E.; Bojinski, S.; Cimini, D. ...
Bulletin of the American Meteorological Society,
01/2016, Letnik:
97, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The three main objectives of the Global Climate Observing System (GCOS) Reference Upper-Air Network (GRUAN) are to provide long-term high-quality climate records of vertical profiles of selected ...essential climate variables (ECVs), to constrain and calibrate data from more spatially comprehensive global networks, and to provide measurements for process studies that permit an in-depth understanding of the properties of the atmospheric column. In the five years since the first GRUAN implementation and coordination meeting and the printing of an article (Seidel et al.) in this publication, GRUAN has matured to become a functioning network that provides reference-quality observations to a community of users.
This article describes the achievements within GRUAN over the past five years toward making reference-quality observations of upper-air ECVs. Milestones in the evolution of GRUAN are emphasized, including development of rigorous criteria for site certification and assessment, the formal certification of the first GRUAN sites, salient aspects of the GRUAN manual and guide to operations, public availability of GRUAN’s first data product, outcomes of a network expansion workshop, and key results of scientific studies designed to provide a sound scientific foundation for GRUAN operations.
Two defining attributes of GRUAN are 1) that every measurement is accompanied by a traceable estimate of the measurement uncertainty and 2) that data quality and continuity are maximized because network changes are minimized and managed. This article summarizes how these imperatives are being achieved for existing and planned data products and provides an outlook for the future, including expected new data streams, network expansion, and critical needs for the ongoing success of GRUAN.
The introduction of carbon nanotubes (CNTs) into nonconducting polymers has been observed to yield orders of magnitude increases in conductivity at very low concentrations of CNTs. These low ...percolation concentrations have been attributed to both the formation of conductive networks of CNTs within the polymer and to a nanoscale effect associated with the ability of electrons to transfer from one CNT to another known as electron hopping. In the present work, a micromechanics model is developed to assess the impact of the effects of electron hopping and the formation of conductive networks on the electrical conductivity of CNT-polymer nanocomposites. The micromechanics model uses the composite cylinders model as a nanoscale representative volume element where the effects of electron hopping are introduced in the form of a continuum interphase layer, resulting in a distinct percolation concentration associated with electron hopping. Changes in the aspect ratio of the nanoscale representative volume element are used to reflect the changes in nanocomposite conductivity associated with the formation of conductive networks due to the formation of nanotube bundles. The model results are compared with experimental data in the literature for both single- and multi-walled CNT nanocomposites where it is observed that the model developed is able to qualitatively explain the relative impact of electron hopping and nanotube bundling on the nanocomposite conductivity and percolation concentrations.
Aliment Pharmacol Ther 31, 1051–1063
Summary
Background Evidence increasingly implicates obesity as an independent risk factor for different cancers. We examined such evidence for hepatocellular ...carcinoma.
Aim To review the effect of increased levels of body mass index on hepatocellular carcinoma risk.
Methods We reviewed systematically the literature examining the association between increased body mass index and hepatocellular carcinoma risk. For each identified study, relevant data were extracted and appraised.
Results Ten cohort studies (>90 million person‐years), one nested case‐control study (244 cases) and two case‐control studies (494 cases) were identified. Of the cohort studies, 75% of person‐years related to North Americans, 15% to East Asians, and 10% to Europeans. Three cohort studies adjusted for alcohol consumption, only one cohort study adjusted for hepatitis infection status. Seven cohort studies found a positive association between obesity (body mass index ≥30 kg/m2) and hepatocellular carcinoma risk (relative risks ranging from 1.4 to 4.1); two reported no association; and one reported a significant inverse association for a population subgroup (relative risk = 0.7, 95% confidence interval: 0.5–0.9).
Conclusion Although most studies did not adjust for confounders and most data relate to a single world region, the overall evidence is suggestive of an increased hepatocellular carcinoma risk in obese and overweight individuals.
Significance Here, we examine the activity profile of the haloalkanoic acid dehalogenase (HAD) superfamily by screening a customized library against >200 enzymes from a broad sampling of the ...superfamily. From this dataset, we can infer the function of nearly 35% of the superfamily. Overall, the superfamily was found to show high substrate ambiguity, with 75% of the superfamily utilizing greater than five substrates. In addition, the HAD members with the least amount of structural accessorization of the Rossmann fold were found to be the most specific, suggesting that elaboration of the core domain may have led to increased substrate range of the superfamily.
Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process.
Osteoarthritis of the hip (OA) is a common degenerative disorder of the joint cartilage that presents a major public health problem worldwide. While intrinsic risk factors (e.g, body mass and ...morphology) have been identified, external risk factors are not well understood. In this systematic review, the evidence for workload as a risk factor for hip OA is summarized and used to derive recommendations for prevention and further research.
Epidemiological studies on workload or occupation and osteoarthritis of the hip were identified through database and bibliography searches. Using pre-defined quality criteria, 30 studies were selected for critical evaluation; six of these provided quantitative exposure data.
Study results were too heterogeneous to develop pooled risk estimates by specific work activities. The weight of evidence favors a graded association between long-term exposure to heavy lifting and risk of hip OA. Long-term exposure to standing at work might also increase the risk of hip OA.
It is not possible to estimate a quantitative dose-response relationship between workload and hip OA using existing data, but there is enough evidence available to identify job-related heavy lifting and standing as hazards, and thus to begin developing recommendations for preventing hip OA by limiting the amount and duration of these activities. Future research to identify specific risk factors for work-related hip OA should focus on implementing rigorous study methods with quantitative exposure measures and objective diagnostic criteria.
The month-to-month variability of tropical temperatures is larger in the troposphere than at Earth's surface. This amplification behavior is similar in a range of observations and climate model ...simulations and is consistent with basic theory. On multidecadal time scales, tropospheric amplification of surface warming is a robust feature of model simulations, but it occurs in only one observational data set. Other observations show weak, or even negative, amplification. These results suggest either that different physical mechanisms control amplification processes on monthly and decadal time scales, and models fail to capture such behavior; or (more plausibly) that residual errors in several observational data sets used here affect their representation of long-term trends.
Effective elastic properties for carbon nanotube reinforced composites are obtained through a variety of micromechanics techniques. Using the in-plane elastic properties of graphene, the effective ...properties of carbon nanotubes are calculated utilizing a composite cylinders micromechanics technique as a first step in a two-step process. These effective properties are then used in the self-consistent and Mori–Tanaka methods to obtain effective elastic properties of composites consisting of aligned single or multi-walled carbon nanotubes embedded in a polymer matrix. Effective composite properties from these averaging methods are compared to a direct composite cylinders approach extended from the work of Z. Hashin and B. Rosen 1964. The elastic moduli of fiber-reinforced materials. Journal of Applied Mechanics 31, 223–232 and R. Christensen and K. Lo 1979. Solutions for effective shear properties in three phase sphere and cylinder models. Journal of the Mechanics and Physics of Solids 27, 315–330. Comparisons with finite element simulations are also performed. The effects of an interphase layer between the nanotubes and the polymer matrix as result of functionalization is also investigated using a multi-layer composite cylinders approach. Finally, the modeling of the clustering of nanotubes into bundles due to interatomic forces is accomplished herein using a tessellation method in conjunction with a multi-phase Mori–Tanaka technique. In addition to aligned nanotube composites, modeling of the effective elastic properties of randomly dispersed nanotubes into a matrix is performed using the Mori–Tanaka method, and comparisons with experimental data are made.
In this paper we examine the optical sources of noise that degrade high-performance microwave photonic links. In particular, we study the residual phase noise due to laser frequency fluctuations and ...the detector nonlinearity on microwave signals transmitted on an optical fiber, or generated in the opto-electronic oscillator (OEO). Based on experimental findings, we identify a significant reduction of the relative intensity noise of the laser if the received optical power saturates the photodiode. Furthermore, we suggest the use of a semiconductor optical amplifier in saturation as yet another means to reduce the phase noise induced by laser intensity fluctuations. We also identify the use of multiple photodetectors to reduce the influence of associated 1/f noise, which adds to the phase noise of a transmitted microwave signal, and is the ultimate limitation to the phase noise of the high-performance OEO. Reduction of noise that is due to optical interferences is also addressed.
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