202 research outputs found
Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy
Lipid accumulation in skeletal muscle results in dysregulation of protein meta- bolism and muscle atrophy. We previously reported that treating C2C12 myo- tubes with palmitate (PA), a saturated fatty acid, increases the overall rate of proteolysis via activation of the ubiquitin-proteasome and autophagy systems; co-treatment with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents the PA-induced responses. Others have reported that PA induces endoplasmic reticulum (ER) stress which initiates the unfolded pro- tein response (UPR), a collective group of responses that can lead to activa- tion of caspase-mediated proteolysis and autophagy. Presently, we tested the hypothesis that DHA protects against PA-induced ER stress/UPR and its atro- phy-related responses in muscle cells. C2C12 myotubes were treated with 500 lmol/L PA and/or 100 lmol/L DHA for 24 h. Proteins and mRNA asso- ciated with ER stress/UPR, autophagy, and caspase-3 activation were evalu- ated. PA robustly increased the phosphorylation of protein kinase R (PKR)- like ER kinase (PERK) and eukaryotic initiation factor 2a (eIF2a). It also increased the mRNAs encoding activating transcription factor 4 (ATF4), spliced X-box binding protein 1 (XBP1s), C/EBP homologous protein (CHOP), and autophagy-related 5 (Atg5) as well as the protein levels of the PERK target nuclear factor erythroid 2-related factor (Nrf2), CHOP, and cleaved (i.e., activated) caspase-3. Co-treatment with DHA prevented all of the PA-induced responses. Our results indicate that DHA prevents PA- induced muscle cell atrophy, in part, by preventing ER stress/UPR, a process that leads to activation of caspase-mediated proteolysis and an increase in expression of autophagy-related genes
Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition andMetabolism (ISRNM)
Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. in addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.Abbott NutritionShireAbbot Renal NutritionBaxter HealthcareKarolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Solna, SwedenUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilVanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37212 USAUniv Calif Irvine, Med Ctr, Harold Simmons Ctr, Div Nephrol & Hypertens, Orange, CA USAUniv Calif Davis, Dept Internal Med, Davis, CA 95616 USAUniv Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USABaylor Coll Med, Dept Med, Div Nephrol, Houston, TX 77030 USAEmory Univ, Sch Med, Div Renal, Dept Med, Atlanta, GA 30306 USAAtlanta Dept Vet Affairs Med Ctr, Res Serv, Decatur, GA 30033 USAUniv Wurzburg, Div Nephrol, Dept Internal Med, D-97070 Wurzburg, GermanyUniv Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R ChinaVrije Univ Amsterdam Med Ctr, Dept Nephrol, Amsterdam, NetherlandsUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilWeb of Scienc
Search for Neutral Higgs Bosons in Events with Multiple Bottom Quarks at the Tevatron
The combination of searches performed by the CDF and D0 collaborations at the
Fermilab Tevatron Collider for neutral Higgs bosons produced in association
with b quarks is reported. The data, corresponding to 2.6 fb-1 of integrated
luminosity at CDF and 5.2 fb-1 at D0, have been collected in final states
containing three or more b jets. Upper limits are set on the cross section
multiplied by the branching ratio varying between 44 pb and 0.7 pb in the Higgs
boson mass range 90 to 300 GeV, assuming production of a narrow scalar boson.
Significant enhancements to the production of Higgs bosons can be found in
theories beyond the standard model, for example in supersymmetry. The results
are interpreted as upper limits in the parameter space of the minimal
supersymmetric standard model in a benchmark scenario favoring this decay mode.Comment: 10 pages, 2 figure
Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-
We report the first observation of the baryonic flavor-changing neutral
current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a
statistical significance of 5.8 Gaussian standard deviations. This measurement
uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV
collected by the CDF II detector at the Tevatron collider. The total and
differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We
find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}.
We also report the first measurement of the differential branching ratio of B_s
-> phi mu+ mu- using 49 signal events. In addition, we report branching ratios
for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let
Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set
We present a search for the standard model Higgs boson produced in
association with a W boson in sqrt(s) = 1.96 TeV p-pbar collision data
collected with the CDF II detector at the Tevatron corresponding to an
integrated luminosity of 9.45 fb-1. In events consistent with the decay of the
Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a
neutrino, we set 95% credibility level upper limits on the WH production cross
section times the H->bb branching ratio as a function of Higgs boson mass. At a
Higgs boson mass of 125 GeV/c2 we observe (expect) a limit of 4.9 (2.8) times
the standard model value.Comment: Submitted to Phys. Rev. Lett (v2 contains clarifications suggested by
PRL
Search for the standard model Higgs boson decaying to a pair in events with no charged leptons and large missing transverse energy using the full CDF data set
We report on a search for the standard model Higgs boson produced in
association with a vector boson in the full data set of proton-antiproton
collisions at TeV recorded by the CDF II detector at the
Tevatron, corresponding to an integrated luminosity of 9.45 fb. We
consider events having no identified charged lepton, a transverse energy
imbalance, and two or three jets, of which at least one is consistent with
originating from the decay of a quark. We place 95% credibility level upper
limits on the production cross section times standard model branching fraction
for several mass hypotheses between 90 and . For a Higgs
boson mass of , the observed (expected) limit is 6.7
(3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let
Search for the standard model Higgs boson decaying to a bb pair in events with two oppositely-charged leptons using the full CDF data set
We present a search for the standard model Higgs boson produced in
association with a Z boson in data collected with the CDF II detector at the
Tevatron, corresponding to an integrated luminosity of 9.45/fb. In events
consistent with the decay of the Higgs boson to a bottom-quark pair and the Z
boson to electron or muon pairs, we set 95% credibility level upper limits on
the ZH production cross section times the H -> bb branching ratio as a function
of Higgs boson mass. At a Higgs boson mass of 125 GeV/c^2 we observe (expect) a
limit of 7.1 (3.9) times the standard model value.Comment: To be submitted to Phys. Rev. Let
Inference of Co-Evolving Site Pairs: an Excellent Predictor of Contact Residue Pairs in Protein 3D structures
Residue-residue interactions that fold a protein into a unique
three-dimensional structure and make it play a specific function impose
structural and functional constraints on each residue site. Selective
constraints on residue sites are recorded in amino acid orders in homologous
sequences and also in the evolutionary trace of amino acid substitutions. A
challenge is to extract direct dependences between residue sites by removing
indirect dependences through other residues within a protein or even through
other molecules. Recent attempts of disentangling direct from indirect
dependences of amino acid types between residue positions in multiple sequence
alignments have revealed that the strength of inferred residue pair couplings
is an excellent predictor of residue-residue proximity in folded structures.
Here, we report an alternative attempt of inferring co-evolving site pairs from
concurrent and compensatory substitutions between sites in each branch of a
phylogenetic tree. First, branch lengths of a phylogenetic tree inferred by the
neighbor-joining method are optimized as well as other parameters by maximizing
a likelihood of the tree in a mechanistic codon substitution model. Mean
changes of quantities, which are characteristic of concurrent and compensatory
substitutions, accompanied by substitutions at each site in each branch of the
tree are estimated with the likelihood of each substitution. Partial
correlation coefficients of the characteristic changes along branches between
sites are calculated and used to rank co-evolving site pairs. Accuracy of
contact prediction based on the present co-evolution score is comparable to
that achieved by a maximum entropy model of protein sequences for 15 protein
families taken from the Pfam release 26.0. Besides, this excellent accuracy
indicates that compensatory substitutions are significant in protein evolution.Comment: 17 pages, 4 figures, and 4 tables with supplementary information of 5
figure
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