Cortical Morphology Differences in Subjects at Increased Vulnerability for Developing a Psychotic Disorder: A Comparison between Subjects with Ultra-High Risk and 22q11.2 Deletion Syndrome

IntroductionSubjects with 22q11.2 deletion syndrome (22q11DS) and subjects with ultra-high risk for psychosis (UHR) share a risk of approximately 30% to develop a psychotic disorder. Studying these groups helps identify biological markers of pathophysiological processes involved in the development of psychosis. Total cortical surface area (cSA), total cortical grey matter volume (cGMV), cortical thickness (CT), and local gyrification index (LGI) of the cortical structure have a distinct neurodevelopmental origin making them important target markers to study in relation to the development of psychosis.Results22q11DS subjects had lower total cSA and total cGMV compared to UHR and HC subjects. The 22q11DS subjects showed bilateral lower LGI in the i) prefrontal cortex, ii) precuneus, iii) precentral gyrus and iv) cuneus compared to UHR subjects. Additionally, lower LGI was found in the left i) fusiform gyrus and right i) pars opercularis, ii) superior, and iii) inferior temporal gyrus in 22q11DS subjects compared to HC. In comparison to 22q11DS subjects, the UHR subjects had lower CT of the insula. For both risk groups, positive symptom severity was negatively correlated to rostral middle frontal gyrus CT.ConclusionA shared negative correlation between positive symptom severity and rostral middle frontal gyrus CT in UHR and 22q11DS may be related to their increased vulnerability to develop a psychotic disorder. 22q11DS subjects were characterised by widespread lower degree of cortical gyrification linked to early and postnatal neurodevelopmental pathology. No implications for early neurodevelopmental pathology were found for the UHR subjects, although they did have distinctively lower insula CT which may have arisen from defective pruning processes during adolescence. Implications of these findings in relation to development of psychotic disorders are in need of further investigation in longitudinal studies.     

Genetic and QTL analysis of maize tassel and ear inflorescence architecture

Maize (Zea mays L.) ear inflorescence architecture is directly relevant to grain yield components, and tassel architecture is relevant to hybrid seed production. The objectives of this study were to (1) determine heritabilities and correlations of a comprehensive set of tassel and ear inflorescence architecture traits in a set of (Illinois Low Protein×B73) B73 S₁ families, (2) identify chromosomal positions of QTL affecting tassel and ear architecture, and (3) identify possible candidate genes associated with these QTL. For tassel traits, the number of detected QTL ranged from one to five, and explained between 6.5 and 35.9% of phenotypic variation. For ear traits, the number of detected QTL ranged from one to nine and phenotypic variation explained by those QTL varied between 7.9 and 53.0%. We detected QTL for tassel architecture traits that required calculation of ratios from measured traits. Some of these calculated traits QTL were detected in regions that did not show QTL for the measured traits, suggesting that calculation of ratios may reveal developmentally relevant patterns of tassel architecture. We detected a QTL on chromosome 7 for tassel branch number near the gene ramosa1 (ra1), which is known to control tassel branch number, making ra1 a candidate gene for tassel branch number. We detected QTL for several traits on chromosomes 6, 8, and 9, where no inflorescence architecture genes have been mapped, thus providing initial information towards new gene discovery for control of inflorescence architecture.     

Growth and fermentation characteristics of new selected strains of Saccharomyces at high temperatures and high cell densities

Maintenance of high cell viability was the main characteristic of our new strains of thermotolerant Saccharomyces. Total sugar conversion to ethanol was observed for sugarcane juice fermentation at 38-40 degrees C in less than 10 h and without continuous aeration of the culture. Invertase activity differed among the selected strains and increased during fermentation but was not dependent on cell viability. Invertase activity of the cells and optimum temperature for growth, as well as velocity of ethanol formation, were dependent on medium composition and the type of strain used. At high sugarcane syrup concentrations, the best temperature for ethanol formation by strain 781 was 35 degrees C. Distinct differences among the velocities of ethanol production using selected strains were also observed in sugarcane syrup at 35-38 degrees C.     

New Therapeutic Approach: Diphenyl Diselenide Reduces Mitochondrial Dysfunction in Acetaminophen-Induced Acute Liver Failure

The acute liver failure (ALF) induced by acetaminophen (APAP) is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe)₂], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe)₂ to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe)₂ to the N-acetylcysteine (NAC) during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg), (PhSe)₂ (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)₂ or APAP+NAC, where the (PhSe)₂ or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation) and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe)₂. The effectiveness of (PhSe)₂ was similar at a lower dose than NAC. In summary, (PhSe)₂ provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.     

BYC, an atypical aspartic endopeptidase from Rhipicephalus (Boophilus) microplus eggs

An aspartic endopeptidase was purified in our laboratory from Rhipicephalus (Boophilus) microplus eggs [Logullo, C., Vaz, I.S., Sorgine, M.H., Paiva-Silva, G.O., Faria, F.S., Zingali, R.B., De Lima, M.F., Abreu, L., Oliveira, E.F., Alves, E.W., Masuda, H., Gonzales, J.C., Masuda, A., and Oliveira, P.L., 1998. Isolation of an aspartic proteinase precursor from the egg of a hard tick, Rhipicephalus (Boophilus) microplus. Parasitology 116, 525–532]. Boophilus yolk cathepsin (BYC) was tested as component of a protective vaccine against the tick, inducing a significant immune response in cattle [da Silva, V.I., Jr., Logullo, C., Sorgine, M., Velloso, F.F., Rosa de Lima, M.F., Gonzales, J.C., Masuda, H., Oliveira, P.L., and Masuda, A., 1998. Immunization of bovines with an aspartic proteinase precursor isolated from Rhipicephalus (Boophilus) microplus eggs. Vet. Immunol. Immunopathol. 66, 331–341]. In this work, BYC was cloned and its primary sequence showed high similarity with other aspartic endopeptidases. In spite of this similarity, BYC sequence shows many important differences in relation to other aspartic peptidases, the most important being the lack of the second catalytic Asp residue, considered to be essential for the catalysis of this class of endopeptidases. When we determined BYC cleavage specificity by LC-MS, we found out that it presents a preference for hydrophobic residues in P1 and P1' in accordance to most aspartic endopeptidases. Also, when analyzed by circular dicroism, BYC presented high β sheet content, also a characteristic of aspartic endopeptidases. On the other hand, although both native and recombinant BYC are catalytically active, they present a very low specific activity, what seems to indicate that this peptidase will digest its natural substrate, vitellin, very slowly. We speculate that such a slow Vn degradative process might constitute an important strategy to preserve egg protein content to the hatching larvae.     

Sporotrichosis: An Emerging Neglected Opportunistic Infection in HIV-Infected Patients in Rio de Janeiro,Brazil

Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic.A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections.HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens.     

Melanocortin‐1 receptor (MC1R) genotypes do not correlate with size in two cohorts of medium‐to‐giant congenital melanocytic nevi

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R, such as p.V92M and loss‐of‐function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium‐to‐giant CMN patients from Spain (N = 113) and from France, Norway, Canada, and the United States (N = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss‐of‐function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case–control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non‐UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development.     

New strategy to apply perfluorodecalin as an oxygen carrier in lipase production: minimisation and reuse

A novel strategy for the production of lipase by Bacillus sp. ITP-001 in a stirred tank fermenter using perfluorodecalin (PFD) was studied. Firstly, a response surface methodology 2² with three central points was employed to optimise the effect of agitation speed and aeration rate in lipase production. According to the response from the experimental designs, 300 rpm (revolutions per minute) and 0.5 vvm (air volume/liquid volume per minute) were found to provide the best condition (lipolytic activity: LA = 3,140.76 U mL^?1). Then, the influence of PFD concentration on the fermentation process was evaluated. Incorporation of PFD at all concentrations above 1 % had no statistically significant influence on lipase production, that is, the previous optimisation allowed the reduction of the amount of PFD added besides increasing lipase production. Furthermore, PFD could be used in three sequential fermentations without altering the statistical production of lipase, reducing by 67 % the cost of PFD addition.