Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes

Purpose G lioblastoma (GB) is the most frequent brain tumor. Despite recent improvement in therapeutic strategies, the prognosis of GB remains poor. Growth hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH have been successfully applied for experimental treatment of different types of tumors. The expression profile of GHRH receptor, its main splice variant SV1 and GHRH have not been investigated in human GB tissue samples. Methods We examined the expression of GHRH, fulllength pituitary-type GHRH receptor (pGHRHR), its functional splice variant SV1 and non-functional SV2 by RTPCR in 23 human GB specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR. Correlations between clinico-pathological parameters and gene expressions were analyzed. Results E xpression of GHRH was found to be positive in 61.9 % of samples. pGHRH receptor was not expressed in our sample set, while SV1 could be detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of samples, significant EGFR over-expression or PTEN under-representation could be detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down-regulation occurred together. Survival was significantly poorer in tumors lacking GHRH expression. This worse prognosis in GHRH negative group remained significant even if SV1 was also expressed. Conclusion Our study shows that GHRH and SV1 genes expressed in human GB samples and their expression patterns are associated with poorer prognosis

An evolutionary and structural characterization of mammalian protein complex organization

Background: We have recently released a comprehensive, manually curated database of mammalian protein complexes called CORUM. Combining CORUM with other resources, we assembled a dataset of over 2700 mammalian complexes. The availability of a rich information resource allows us to search for organizational properties concerning these complexes. Results: As the complexity of a protein complex in terms of the number of unique subunits increases, we observed that the number of such complexes and the mean non-synonymous to synonymous substitution ratio of associated genes tend to decrease. Similarly, as the number of different complexes a given protein participates in increases, the number of such proteins and the substitution ratio of the associated gene also tend to decrease. These observations provide evidence relating natural selection and the organization of mammalian complexes. We also observed greater homogeneity in terms of predicted protein isoelectric points, secondary structure and substitution ratio in annotated versus randomly generated complexes. A large proportion of the protein content and interactions in the complexes could be predicted from known binary protein-protein and domain-domain interactions. In particular, we found that large proteins interact preferentially with much smaller proteins. Conclusions: We observed similar trends in yeast and other data. Our results support the existence of conserved relations associated with the mammalian protein complexes

Adiponectin, leptin, and IGF-1 are useful diagnostic and stratification biomarkers of NAFLD

[EN] Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p<0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.CR was funded by FEDER through the COMPETE program and by national funds through Fundação para a Ciência e a Tecnologia (PTDC/MED-FAR/29097/2017—LISBOA-01- 0145-FEDER-029097) and by European Horizon 2020 (H2020- MSCA-RISE-2016-734719). This work was also supported by Fundação para a Ciência e Tecnologia (PD/BD/135467/2017) and Portuguese Association for the Study of Liver/MSD 2017. JB was funded by Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008), co-financed by Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation (HR17-00601), Fundación Científica de la Asociación Española Contra el Cáncer, and European Horizon 2020 (ESCALON project: H2020-SC1-BHC-2018-2020)

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p &lt; 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p &lt; 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p &lt; 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p &lt; 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p &lt; 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p &lt; 0.01).Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis

Cognition, Emotion and Behavior in Children with Tourette’s Syndrome and Children with ADHD-Combined Subtype—A Two-Year Follow-Up Study

Objective This two-year follow-up study investigates the course of and association among measures of cognitive control, focused attention, decision-making and symptom severity (anxiety, depression and behavior) in children and adolescents with Tourette’s Syndrome (TS) or Attention-Deficit/Hyperactivity Disorder-Combined subtype (ADHD-C). Method 19 children with TS, 33 with ADHD-C, and 50 typically developing children (TDC) were examined with a battery of psychometric measures and rating forms at baseline and two-years later. Results All three groups improved likewise in measures of cognitive control over time, whereas only the TDC improved in focused attention. The group of children with TS with comorbidities performed more similar to the children with ADHD-C in cognitive control at T1 and T2, whereas the children with TS without comorbidities performed more similar to the TDC in cognitive control at T1 and T2. In the decision-making task, the children with TS (with or without comorbidities) preferred a safer strategy in selecting advantageous choices than the children with ADHD-C and the TDC at T2. Children with TS and children with ADHD-C showed higher symptoms of anxiety and depression and more problems with emotional control compared with TDC at both time points. Finally, children with ADHD-C self-reported more depression symptoms than those with TS at both assessments. For the TS group, safer decision-making was related to better emotional control, and this relationship was stronger for the TS subgroup without comorbidities. Conclusion This study emphasizes the importance of addressing symptoms of anxiety and depression in children with TS or ADHD-C, identifying the effect of comorbidities in children with TS, and that children with TS or ADHD-C likely differ in their sensitivity to reinforcement contingencies

Oxidation of ammonia by iron, manganese and nickel oxides – Implications on NOx formation in chemical-looping combustion

We report an experimental evaluation of NH3 oxidation over three types of oxygen carrier materials under conditions relevant for chemical-looping combustion. The active metal and the oxidation state of the oxygen carrier is crucial to NO formation from NH3. Although, the carriers tested were equally efficient in terms of CO oxidation they differed from 0 to 6000 ppm of NO in the off-gas. The nickel based carrier produced the lowest amounts of NO and the manganese based the most. The sensitivity to the oxidation state also differed between the materials. The results stress that NO formation should be consider in the choice of oxygen carrier material as well as in the design of chemical looping-combustion systems

Influence of color, shape and damages on consumer preferences and perceived sensory attributes on sub-optimal apples

Sustainable food production and consumption are key elements today. About one third of food produced for human consumption is wasted. Consumers are responsible for the largest amount of food waste throughout the supply chain; part of this is indirect by e.g. discarding food products already in the store. The unwillingness to purchase and consume sub-optimal food products is thought to be an important cause of food waste; however, the reasons behind it are still insufficiently studied. Our research addresses the question of how combinations of color, shape and damage of apples influence consumer preferences and perceived sensory attributes. Based on a cubic design of visual appearance (color (red-to-green); shape (normal-to-odd); damage (none-to-damage) with a total of eight combinations ranging from optimal to suboptimal in all three dimensions, a total of 130 participants (68% women and 32% men), participated in a laboratory study where an image for each apple type from the design was presented in a blind tasting session (peeled and sliced apples). Sensory perception was evaluated by thirteen flavor and texture attributes on a 7-point scale. Liking was evaluated on a 7-point hedonic scale. The results showed a significant difference between the optimal apple and apples with shape and damage imperfections. Further, the optimal apple was perceived sweeter, crispier and less bitter than all other apples. The optimal apple had higher liking score, significantly different from the apples which all had a sub-optimal shape. This means that an odd shape had a negative effect on liking. A linear regression analysis showed that odd shaped apples were perceived as mainly earthy and bitter. Hence, visual sub-optimality, even presented to consumers in images, have an effect on how an apple is perceived and liked where an odd shape has larger negative impact than color and damage. COSU

Acute hepatitis A virus infection in Turkey

Anti-HAV IgM positive serum samples from acute phase hepatitis A patients from various areas in Turkey were tested for viral RNA by RT-PCR (reverse transcriptase polymerase chain reaction), using primer pairs from two different regions of the HAV genome. The PCR products amplified from both genomic regions underwent phylogenetic analyses. A comparison of the regions showed the same genotyping results, and the RT-PCR-2 in the 5'NCR demonstrated greater sensitivity compared to RT-PCR-1 in the VP1-P2A region. The majority of the isolates belonged to genotype IB and are related closely to each other; however, two isolates related even more strongly to the HAV HM175 strain. Two (n = 37) RT-PCR positive sera were classified under genotype IA. A surprising finding emerged for the mean levels of serum transaminases AST and ALT: higher levels were found in patients under 10 years of age compared to older patients. Anti-HAV IgM levels were determined quantitatively and, in addition, the HAV-RNA genome equivalents were ascertained by real time RT-PCR. No evidence was found for an association between viral load and the higher transaminase levels in the younger group. J. Med Virol. 80.785-790, 2008. (C) 2008 Wiley-Liss, Inc