CEP-1347 (KT7515) promotes neuronal survival at dosages that inhibit activation of the c-Jun amino-terminal kinases (JNKs)
in primary embryonic cultures and differentiated PC12 cells after trophic ...withdrawal and in mice treated with 1-methyl-4-phenyl
tetrahydropyridine. In an effort to identify molecular target(s) of CEP-1347 in the JNK cascade, JNK1 and known upstream regulators
of JNK1 were co-expressed in Cos-7 cells to determine whether CEP-1347 could modulate JNK1 activation. CEP-1347 blocked JNK1
activation induced by members of the mixed lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and
leucine zipper kinase). The response was selective because CEP-1347 did not inhibit JNK1 activation in cells induced by kinases
independent of the MLK cascade. CEP-1347 inhibition of recombinant MLK members in vitro was competitive with ATP, resulting in IC 50 values ranging from 23 to 51 n m , comparable to inhibitory potencies observed in intact cells. In addition, overexpression of MLK3 led to death in Chinese
hamster ovary cells, and CEP-1347 blocked this death at doses comparable to those that inhibited MLK3 kinase activity. These
results identify MLKs as targets of CEP-1347 in the JNK signaling cascade and demonstrate that CEP-1347 can block MLK-induced
cell death.
Purpose To evaluate effects of two behavioral weight-loss interventions (in-person, remote) on health-related quality of life (HRQOL) compared to a control intervention. Methods Four hundred and ...fifty-one obese US adults with at least one cardiovascular risk factor completed five measures of HRQOL and depression: MOS SF-12 physical component summary (PCS) and mental component summary; EuroQoL-5 dimensions single index and visual analog scale; PHQ-8 depression symptoms; and PSQI sleep quality scores at baseline and 6 and 24 months after randomization. Change in each outcome was analyzed using outcome-specific mixed-effects models controlling for participant demographic characteristics. Results PCS-12 scores over 24 months improved more among participants in the in-person active intervention arm than among control arm participants (P < 0.05, ES = 0.21); there were no other statistically significant treatment arm differences in HRQOL change. Greater weight loss was associated with improvements in most outcomes (P < 0.05 to < 0.0001). Conclusions Participants in the in-person active intervention improved more in physical function HRQOL than participants in the control arm did. Greater weight loss during the study was associated with greater improvement in all PRO except for sleep quality, suggesting that weight loss is a key factor in improving HRQOL.
Radiation testing of electronics for the CMS endcap muon system Bylsma, B.; Cady, D.; Celik, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2013, Letnik:
698
Journal Article
Recenzirano
Odprti dostop
The electronics used in the data readout and triggering system for the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) particle accelerator at CERN are exposed to high ...radiation levels. This radiation can cause permanent damage to the electronic circuitry, as well as temporary effects such as data corruption induced by Single Event Upsets. Once the High Luminosity LHC (HL-LHC) accelerator upgrades are completed it will have five times higher instantaneous luminosity than LHC, allowing for detection of rare physics processes, new particles and interactions. Tests have been performed to determine the effects of radiation on the electronic components to be used for the Endcap Muon electronics project currently being designed for installation in the CMS experiment in 2013. During these tests the digital components on the test boards were operating with active data readout while being irradiated with 55MeV protons. In reactor tests, components were exposed to 30 years equivalent levels of neutron radiation expected at the HL-LHC. The highest total ionizing dose (TID) for the muon system is expected at the innermost portion of the CMS detector, with 8900rad over 10 years. Our results show that Commercial Off-The-Shelf (COTS) components selected for the new electronics will operate reliably in the CMS radiation environment.
Complete Genome Sequence of Caulobacter crescentus Nierman, William C.; Feldblyum, Tamara V.; Laub, Michael T. ...
Proceedings of the National Academy of Sciences - PNAS,
03/2001, Letnik:
98, Številka:
7
Journal Article
Recenzirano
Odprti dostop
The complete genome sequence of Caulobacter crescentus was determined to be 4,016,942 base pairs in a single circular chromosome encoding 3,767 genes. This organism, which grows in a dilute aquatic ...environment, coordinates the cell division cycle and multiple cell differentiation events. With the annotated genome sequence, a full description of the genetic network that controls bacterial differentiation, cell growth, and cell cycle progression is within reach. Two-component signal transduction proteins are known to play a significant role in cell cycle progression. Genome analysis revealed that the C. crescentus genome encodes a significantly higher number of these signaling proteins (105) than any bacterial genome sequenced thus far. Another regulatory mechanism involved in cell cycle progression is DNA methylation. The occurrence of the recognition sequence for an essential DNA methylating enzyme that is required for cell cycle regulation is severely limited and shows a bias to intergenic regions. The genome contains multiple clusters of genes encoding proteins essential for survival in a nutrient poor habitat. Included are those involved in chemotaxis, outer membrane channel function, degradation of aromatic ring compounds, and the breakdown of plant-derived carbon sources, in addition to many extracytoplasmic function sigma factors, providing the organism with the ability to respond to a wide range of environmental fluctuations. C. crescentus is, to our knowledge, the first free-living α-class proteobacterium to be sequenced and will serve as a foundation for exploring the biology of this group of bacteria, which includes the obligate endosymbiont and human pathogen Rickettsia prowazekii, the plant pathogen Agrobacterium tumefaciens, and the bovine and human pathogen Brucella abortus.
BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program ...(MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.
Pseudomonas fluorescens Pf-5 is a plant commensal bacterium that inhabits the rhizosphere and produces secondary metabolites that suppress soilborne plant pathogens. The complete sequence of the ...7.1-Mb Pf-5 genome was determined. We analyzed repeat sequences to identify genomic islands that, together with other approaches, suggested P. fluorescens Pf-5's recent lateral acquisitions include six secondary metabolite gene clusters, seven phage regions and a mobile genomic island. We identified various features that contribute to its commensal lifestyle on plants, including broad catabolic and transport capabilities for utilizing plant-derived compounds, the apparent ability to use a diversity of iron siderophores, detoxification systems to protect from oxidative stress, and the lack of a type III secretion system and toxins found in related pathogens. In addition to six known secondary metabolites produced by P. fluorescens Pf-5, three novel secondary metabolite biosynthesis gene clusters were also identified that may contribute to the biocontrol properties of P. fluorescens Pf-5.
Summary
Background
Behavioural weight loss programs are effective first‐line treatments for obesity and are recommended by the US Preventive Services Task Force. Gaining an understanding of ...intervention components that are found helpful by different demographic groups can improve tailoring of weight loss programs. This paper examined the perceived helpfulness of different weight loss program components.
Methods
Participants (n = 236) from the active intervention conditions of the Practice‐based Opportunities for Weight Reduction (POWER) Hopkins Trial rated the helpfulness of 15 different components of a multicomponent behavioural weight loss program at 24‐month follow‐up. These ratings were examined in relation to demographic variables, treatment arm and weight loss success.
Results
The components most frequently identified as helpful were individual telephone sessions (88%), tracking weight online (81%) and coach review of tracking (81%). The component least frequently rated as helpful was the primary care providers' general involvement (50%). Groups such as older adults, Blacks and those with lower education levels more frequently reported intervention components as helpful compared with their counterparts.
Discussion
Weight loss coaching delivered telephonically with web support was well received. Findings support the use of remote behavioural interventions for a wide variety of individuals.
Methanotrophs are ubiquitous bacteria that can use the greenhouse gas methane as a sole carbon and energy source for growth, thus playing major roles in global carbon cycles, and in particular, ...substantially reducing emissions of biologically generated methane to the atmosphere. Despite their importance, and in contrast to organisms that play roles in other major parts of the carbon cycle such as photosynthesis, no genome-level studies have been published on the biology of methanotrophs. We report the first complete genome sequence to our knowledge from an obligate methanotroph, Methylococcus capsulatus (Bath), obtained by the shotgun sequencing approach. Analysis revealed a 3.3-Mb genome highly specialized for a methanotrophic lifestyle, including redundant pathways predicted to be involved in methanotrophy and duplicated genes for essential enzymes such as the methane monooxygenases. We used phylogenomic analysis, gene order information, and comparative analysis with the partially sequenced methylotroph Methylobacterium extorquens to detect genes of unknown function likely to be involved in methanotrophy and methylotrophy. Genome analysis suggests the ability of M. capsulatus to scavenge copper (including a previously unreported nonribosomal peptide synthetase) and to use copper in regulation of methanotrophy, but the exact regulatory mechanisms remain unclear. One of the most surprising outcomes of the project is evidence suggesting the existence of previously unsuspected metabolic flexibility in M. capsulatus, including an ability to grow on sugars, oxidize chemolithotrophic hydrogen and sulfur, and live under reduced oxygen tension, all of which have implications for methanotroph ecology. The availability of the complete genome of M. capsulatus (Bath) deepens our understanding of methanotroph biology and its relationship to global carbon cycles. We have gained evidence for greater metabolic flexibility than was previously known, and for genetic components that may have biotechnological potential.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The 3.31-Mb genome sequence of the intracellular pathogen and potential bioterrorism agent, Brucella suis, was determined. Comparison of B. suis with Brucella melitensis has defined a finite set of ...differences that could be responsible for the differences in virulence and host preference between these organisms, and indicates that phage have played a significant role in their divergence. Analysis of the B. suis genome reveals transport and metabolic capabilities akin to soil/plant-associated bacteria. Extensive gene synteny between B. suis chromosome 1 and the genome of the plant symbiont Mesorhizobium loti emphasizes the similarity between this animal pathogen and plant pathogens and symbionts. A limited repertoire of genes homologous to known bacterial virulence factors were identified.
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