Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice

Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancerrelated pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARα challenge demonstrated the dysregulation of PPARα signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21’s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver

Faster HIV-1 Disease Progression among Brazilian Individuals Recently Infected with CXCR4-Utilizing Strains

Introduction: Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus's co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression. Methods: A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/mu L. Results: Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4,350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4.350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4.350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype. Conclusions: Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.Brazilian Program for STD and AIDSBrazilian Program for STD and AIDSMinistry of Health [914/BRA/3014-UNESCO/Kallas]Ministry of HealthSao Paulo City Health DepartmentSao Paulo City Health Department [2004-0.168.922-7/Kallas]Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/15856-9/Diaz]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian Ministry of EducationBrazilian Ministry of Educatio

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

Alpha feto-protein (AFP) is a major plasma protein produced by the yolk sac and the liver during the fetal period. During the second trimester of pregnancy, APF and βhCG serum concentrations are commonly used for screening Down syndrome. AFP deficiency is rare (estimated to be 1/105 000 newborns) and only one sequence alteration has previously been reported in the AFP gene. We report a new mutation in exon 5 of the AFP gene, leading to a total absence of AFP on 2nd-trimester maternal serum screening for Down syndrome, confirmed on the amniotic fluid. Despite this, fetal development and birth were normal. After PCR-amplification, the whole AFP gene was sequenced. The new mutation was a guanine to adenine transition in position 543 creating a premature stop codon in position 181. In order to search for eventual modifications of the amniotic fluid profile, proteins were separated by electrophoresis and compared with 10 normal amniotic fluids sampled at the same developmental age (18 weeks). In the amniotic fluid of our patient albumin rate was reduced whereas alpha1 and beta protein fractions were increased, suggesting that AFP deficiency may modify the distribution of protein fractions. This observation emphasizes the complex molecular mechanisms of compensation of serum protein deficiency. Studies on other families with AFP deficiency are necessary to confirm this observation

Cross-cultural perception and power dynamics across changing organizational and national contexts:Curaçao and the Netherlands

In this article we study the role of power and power differences in cross-cultural perception. We do so by way of exploratory case studies in the Internal Revenue Service (IRS) and the police in the Netherlands and Curacao. We demonstrate how cross-cultural perception between two specific ethnic groups, European Dutch and African Curacaoans, changes depending on the amount of power imbalance in the various organizational and national contexts. With this article, we follow the call for research on the impact of power dynamics on cross-cultural perception, an approach that goes beyond the traditional, dimensional approach that is prevalent in organization literature