Biotechnological production of γ-decalactone, a peach like aroma, by Yarrowia lipolytica

The request for new flavourings increases every year. Consumer perception that everything natural is better is causing an increase demand for natural aroma additives. Biotechnology has become a way to get natural products. γ-Decalactone is a peach-like aroma widely used in dairy products, beverages and others food industries. In more recent years, more and more studies and industrial processes were endorsed to cost-effect this compound production. One of the best-known methods to produce -decalactone is from ricinoleic acid catalyzed by Yarrowia lipolytica, a generally regarded as safe status yeast. As yet, several factors affecting -decalactone production remain to be fully understood and optimized. In this review, we focus on the aromatic compound -decalactone and its production by Y. lipolytica. The metabolic pathway of lactone production and degradation are addressed. Critical analysis of novel strategies of bioprocess engineering, metabolic and genetic engineering and other strategies for the enhancement of the aroma productivity are presented.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684)

Palmitoylation Regulates Epidermal Homeostasis and Hair Follicle Differentiation

Palmitoylation is a key post-translational modification mediated by a family of DHHC-containing palmitoyl acyl-transferases (PATs). Unlike other lipid modifications, palmitoylation is reversible and thus often regulates dynamic protein interactions. We find that the mouse hair loss mutant, depilated, (dep) is due to a single amino acid deletion in the PAT, Zdhhc21, resulting in protein mislocalization and loss of palmitoylation activity. We examined expression of Zdhhc21 protein in skin and find it restricted to specific hair lineages. Loss of Zdhhc21 function results in delayed hair shaft differentiation, at the site of expression of the gene, but also leads to hyperplasia of the interfollicular epidermis (IFE) and sebaceous glands, distant from the expression site. The specific delay in follicle differentiation is associated with attenuated anagen propagation and is reflected by decreased levels of Lef1, nuclear β-catenin, and Foxn1 in hair shaft progenitors. In the thickened basal compartment of mutant IFE, phospho-ERK and cell proliferation are increased, suggesting increased signaling through EGFR or integrin-related receptors, with a parallel reduction in expression of the key differentiation factor Gata3. We show that the Src-family kinase, Fyn, involved in keratinocyte differentiation, is a direct palmitoylation target of Zdhhc21 and is mislocalized in mutant follicles. This study is the first to demonstrate a key role for palmitoylation in regulating developmental signals in mammalian tissue homeostasis

Host Specialization and Dispersal in Avian Haemosporidians

In order to be able to understand the ecological and evolutionary processes involved in the emergence of infectious diseases, one needs to comprehend how parasites arrive at new geographical areas and how they manage to maintain viable populations and even expand their ranges. We discuss host specificity in avian haemosporidians and how encounter and compatibility filters affect the dispersal of avian haemosporidians, and how these filters affect avian haemosporidian assemblages at different spatial and evolutionary scales. There are at least three important barriers to the dispersal of avian haemosporidians: (i) geographic barriers, (ii) environmental barriers, and (iii) interspecies barriers. In this chapter, we discuss the factors involved in these barriers and their effects on the structure of avian haemosporidian assemblages. Host specificity plays an important role in parasite dispersal, and in the case of avian haemosporidians that are vector-borne parasites, it needs to be evaluated both at the vector and bird host levels. Understanding the effects of these factors on host–vector–parasite dynamics is important to unravel the dispersal and diversification mechanisms of avian haemosporidians. We end this chapter reviewing host specialization in avian haemosporidians of tropical regions, discussing the mechanisms involved in the dispersal and specialization of these parasites and point out important research gaps that need attention

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation

eNOS polymorphism associated with metabolic syndrome in children and adolescents

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We investigated whether genetic polymorphisms in the endothelial nitric oxide (eNOS) gene ((TC)-C-786 in the promoter region, Glu298Asp in exon 7, and 4b/4a in intron 4) or eNOS haplotypes are associated with metabolic syndrome (MetS) in obese children and adolescents. We studied 242 subjects: 108 healthy (controls), 64 normotensive obese, and 70 obese children and adolescents with MetS. Genotypes were determined by Taqman(A (R)) allele discrimination assay and real-time polymerase chain reaction (PCR), and PCR followed by fragment separation by electrophoresis. We compared the distribution of eNOS genotypes, alleles, and haplotypes in the three groups of subjects. The CC genotype for the (TC)-C-786 polymorphism was more common in the MetS group than in the control group (OR = 3.27; CI 1.81-9.07; P 0.00625; P for significance after correction for multiple comparisons). Our findings suggest that while eNOS haplotypes are not relevant, the CC genotype for the (TC)-C-786 polymorphism is associated with MetS in obese children and adolescents. Further studies examining interactions of eNOS haplotypes with environmental factors and other genetic markers are warranted.37241671155160Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)IMEPEN Foundation at Juiz de ForaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Effect of metabolic syndrome risk factors and MMP-2 genetic variations on circulating MMP-2 levels in childhood obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Matrix metalloproteinase-2 is involved in the development of the adipose tissue, and associated with cardiovascular diseases. Metabolic risk factors (MRFs) and functional polymorphisms in the MMP-2 gene may affect its expression and activity. We investigated whether traditional MRFs and two MMP-2 gene polymorphisms (C-1306T; rs243865, and C-735T; rs2285053) affect circulating MMP-2 levels in children and adolescents, and whether MMP-2 polymorphisms and/or haplotype are associated with susceptibility to childhood obesity. We studied 114 healthy controls, 43 obese, and 83 obese with a parts per thousand yen3 MRFs children and adolescents. Genotypes were determined by Taqman allele discrimination assay and real-time PCR. Plasma MMP-2 was measured using zymography. We found positive correlations between MMP-2 concentrations and mean blood pressure in all children and adolescents group (r = 0.132; P < 0.05) and in obese children and adolescents (r = 0.247; P < 0.01). We found that the CC genotype for the C-1306T polymorphism was more common in subjects with higher MMP-2 concentrations in controls (P = 0.003) and in the obese group (P = 0.013). The CT genotype (OR = 0.40; P < 0.01) and the T allele (OR = 0.48; P < 0.01) for the C-735T polymorphism were less common in obese children and adolescents than in controls. The haplotypes distribution did not show significant differences between control and obese (P > 0.05). Ours findings show that blood pressure is associated with circulating MMP-2 concentrations, and that the CC genotype for the C-1306T polymorphism was more common subjects (controls and obese) with higher MMP-2 concentrations, whereas the CT genotype and the T allele for the C-735T polymorphism are less common in obesity.40326972704Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)IMEPEN Foundation at Juiz de ForaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Adiponectin associates positively with nitrite levels in children and adolescents

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)OBJECTIVE: To compare the circulating levels of adiponectin and nitric oxide (NO) bioavailability in eutrophic, eutrophic hypertensive, obese, and obese hypertensive children and adolescents, and to assess whether adiponectin is associated with increased NO bioavailability in these children and adolescents. METHODS: We studied 129 eutrophic, 8 eutrophic hypertensive, 91 obese, and 44 obese hypertensive children and adolescents in this cross-sectional study. Adiponectin concentrations were measured in plasma samples by enzyme-linked immunosorbent assay. To assess NO bioavailability, nitrite concentrations were measured in whole-blood samples by chemiluminescence. Multiple linear regression analysis was carried out to assess the effects of adiponectin on NO bioavailability. RESULTS: We found no significant differences in nitrite levels among groups (P>0.05). The obese hypertensive group had the lowest adiponectin levels among groups (P<0.05). Additionally, obese subjects had lower adiponectin levels than eutrophic individuals (P<0.05). A multiple linear regression analysis showed that NO bioavailability was positively associated with adiponectin concentrations (P<0.05). CONCLUSIONS: Our findings suggest that adiponectin increases NO bioavailability in children and adolescents. Further studies are needed to assess the cardiovascular protective role for this adipokine in childhood obesity.375740743Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)(14−24) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children. We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay.We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P>0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P<0.05). Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood3616975FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPNão te