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Book umami proteins from tilapia reduce chin as well as molecular docking for the taste receptor T1R1/T1R3.
9 years; 54.4% women; main cancer types were of digestive organs (26.6%), breast (21.6%) and lung cancer (21.2%). Cognitive impairment was present in 181 (17.3%) at baseline and associated with worse self-reported tiredness, drowsiness, appetite, and depression. Reliability (ICC) and validity (associations with HrQoL) were similar between people with/without cognitive impairment across the nine symptoms, except breathlessness which showed a weaker relation to HrQoL in patients with cognitive impairment. Findings were robust in sensitivity analyses and after controlling for potential confounders. CONCLUSION In advanced cancer, self-report of nine major symptoms was reliable and valid also in people with mild to moderate cognitive impairment. TRIAL REGISTRATION ClinicalTrials.gov database (No. NCT01362816). PURPOSE To evaluate the effect of hyperthermia (HT) combined with concurrent radiochemotherapy (RCT) and treatment related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS This study was conducted between 2009 and 2013 in CC patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV. The patients were randomly assigned into two treatment groups RCT and RCT plus hyperthermia (RCHT) group. 5-year survival, treatment related toxicity and other prognostic factors were evaluated. RESULTS 373 patients completed treatment and were analyzed by per protocol (PP) analysis. The 5-year overall survival (OS) in RCHT group (81.9%) was better than that in RCT group (72.3%) and the log-rank test showed statistically significant difference between the two groups (p=0.040). Univariate and multivariate COX regression analysis for 5-year OS showed statistically significant difference (p=0.043, p=0.045, respectively). The 5-year local relapse-free survival (LRFS) in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the two groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and relatively poor prognosis in univariate and multivariate analysis. CONCLUSION The study confirmed that HT combined to RCT yielded a better 5-year OS in CC. Acute or late toxicity was similar between RCT and RCHT group. Clinical stage (FIGO) and tumor size were independent prognostic factor in CC. BACKGROUND Escherichia coli cells contain a homolog of presumed 5-keto-4-deoxyuronate isomerase (KduI) from pectin-degrading soil bacteria, but the catalytic activity of the E. coli protein (o-KduI) was never demonstrated. METHODS The known three-dimensional structure of E. coli o-KduI was compared with the available structures of sugar-converting enzymes. Based on the results of this analysis, sugar isomerization activity of recombinant o-KduI was tested against a panel of D-sugars and their derivatives. RESULTS The three-dimensional structure of o-KduI exhibits a close similarity with Pyrococcus furiosus cupin-type phosphoglucose isomerase. In accordance with this similarity, o-KduI was found to catalyze interconversion of glucose-6-phosphate and fructose-6-phosphate and, less efficiently, conversion of glucuronate to fructuronate. o-KduI was hexameric in crystals but represented a mixture of inactive hexamers and active dimers in solution and contained a tightly bound Zn2+ ion. Dilution, substrate binding and Zn2+ removal shifted the hexamer ⇆ dimer equilibrium to the dimers. CONCLUSIONS Our findings identify o-KduI as a novel phosphosugar isomerase in E. coli, whose activity may be regulated by changes in oligomeric structure. GENERAL SIGNIFICANCE More than 5700 protein sequences are annotated as KduI, but their enzymatic activity has not been directly demonstrated. E. coli o-KduI is the first characterized member of this group, and its enzymatic activity was found to be different from the predicted activity. LOXO-292 purchase V.BACKGROUND Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The AA wwC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the AA wwC basepair stacks on Sheared wobble GU WWC basepairs. METHODS We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical AA wwC basepair stacked on GU WWC basepair. RESULTS We noticed stable structures of GAG motif with specifically negative Shear of the AA basepair but stabilities of the other motifs were not found with AA wwC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, AA wwCGU WWC and AA wwCUG WWC reveal that viable orientation of AAGU prefers one of the H-bonding modes with negative Shear, supported by crystal structure database. The AAUG dinucleotide, however, prefers structure with only positive Shear. CONCLUSIONS The quantum chemical calculations explain why MD simulations of GAG sequence motif only appear stable. In the cases of the GAU and UAG motifs "tug of war" situation between positive and negative Shears of AA wwC basepair induces conformational plasticity. GENERAL SIGNIFICANCE We have projected comprehensive reason behind the promiscuous nature of AA wwC basepair which brings occasional structural plasticity. Brown adipose tissue (BAT) plays a critical role in lipid metabolism and may protect from hyperlipidemia; however, its beneficial effect appears to depend on the ambient temperature of the environment. In this study, we investigated the effects of uncoupling protein 1 (UCP1) deficiency on lipid metabolism, including the pathophysiology of hyperlipidemia, in apolipoprotein E knockout (APOE-KO) mice at a normal (23 °C) and thermoneutral (30 °C) temperature. Unexpectedly, UCP1 deficiency caused improvements in hyperlipidemia, atherosclerosis, and glucose metabolism, regardless of an increase in hepatic lipid deposition, in Ucp1/Apoe double-knockout (DKO) mice fed a high-fat diet at 23 °C, with BAT hyperplasia and robust browning of inguinal white adipose tissue (IWAT) observed. Proteomics and gene expression analyses revealed significant increases in many proteins involved in energy metabolism and strong upregulation of brown/beige adipocyte-related genes and fatty acid metabolism-related genes in browned IWAT, suggesting an induction of beige fat formation and stimulation of lipid metabolism in DKO mice at 23 °C.
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