TROY (TNFRSF19) is overexpressed in advanced glial tumors and promotes glioblastoma cell invasion via Pyk2-Rac1 signaling

A critical problem in the treatment of malignant gliomas is the extensive infiltration of individual tumor cells into adjacent brain tissues. This invasive phenotype severely limits all current therapies, and to date, no treatment is available to control the spread of this disease. Members of the tumor necrosis factor (TNF) ligand superfamily and their cognate receptors regulate various cellular responses including proliferation, migration, differentiation, and apoptosis. Specifically, the TNFRSF19/TROY gene encodes a type I cell surface receptor that is expressed on migrating or proliferating progenitor cells of the hippocampus, thalamus, and cerebral cortex. Here, we show that levels of TROY mRNA expression directly correlate with increasing glial tumor grade. Among malignant gliomas, TROY expression correlates inversely with overall patient survival. In addition, we show that TROY overexpression in glioma cells activates Rac1 signaling in a Pyk2-dependent manner to drive glioma cell invasion and migration. Pyk2 coimmunoprecipitates with the TROY receptor, and depletion of Pyk2 expression by short hairpin RNA interference oligonucleotides inhibits TROY-induced Rac1 activation and subsequent cellular migration. These findings position aberrant expression and/or signaling by TROY as a contributor, and possibly as a driver, of the malignant dispersion of glioma cells.     

Malassezia Intra-Specific Diversity and Potentially New Species in the Skin Microbiota from Brazilian Healthy Subjects and Seborrheic Dermatitis Patients

Malassezia yeasts are part of the resident cutaneous microbiota, and are also associated with skin diseases such as seborrheic dermatitis (SD). The role these fungi play in skin diseases and why they are pathogenic for only some individuals remain unclear. This study aimed to characterize Malassezia microbiota from different body sites in healthy and SD subjects from Brazil. Scalp and forehead samples from healthy, mild SD and severe SD subjects were collected. Non-scalp lesions from severe SD patients were also sampled. 5.8S rDNA/ITS2 amplicons from Malassezia sp. were analyzed by RFLP and sequencing. Results indicate that Malassezia microbiota did not group according to health condition or body area. Phylogenetic analysis revealed that three groups of sequences did not cluster together with any formally described species, suggesting that they might belong to potential new species. One of them was found in high proportions in scalp samples. A large variety of Malassezia subtypes were detected, indicating intra-specific diversity. Higher M. globosa proportions were found in non-scalp lesions from severe SD subjects compared with other areas, suggesting closer association of this species with SD lesions from areas other than scalp. Our results show the first panorama of Malassezia microbiota in Brazilian subjects using molecular techniques and provide new perspectives for further studies to elucidate the association between Malassezia microbiota and skin diseases.     

Mapping of DNA Sex-Specific Markers and Genes Related to Sex Differentiation in Turbot (Scophthalmus maximus)

Production of all-female populations in turbot can increase farmer's benefits since sexual dimorphism in growth in this species is among the highest within marine fish, turbot females reaching commercial size 3-6?months earlier than males. Puberty in males occurs earlier than in females, which additionally slows their growth. Thus, elucidating the mechanisms of sex determination and gonad differentiation is a relevant goal for turbot production. A ZZ/ZW sex determination mechanism has been suggested for this species, and four sex-related quantitative trait loci (QTL) were detected, the major one located in linkage group (LG) 5 and the three minor ones in LG6, LG8, and LG21. In the present work, we carried out a linkage analysis for several sex-related markers: (1) three anonymous sex-associated RAPD and (2) several candidate genes related to sex determination and gonad differentiation in other species (Sox3, Sox6, Sox8, Sox9, Sox17, Sox19, Amh, Dmrta2, Cyp19a, Cyp19b). We focused our attention on their co-localization with the major and minor sex-related QTL trying to approach to the master sex-determining gene of this species. Previously described growth-related QTL were also considered since the association observed between growth and sex determination in fish. Amh, Dmrta2, and one RAPD were located in LG5, while Sox9 and Sox17 (LG21), Cyp19b (LG6), and a second RAPD (LG8) co-mapped with suggestive sex-related QTL, thus supporting further analyses on these genes to elucidate the genetic basis of this relevant trait for turbot farming.     

Multi-generation genomic prediction of maize yield using parametric and non-parametric sparse selection indices

Genomic prediction models are often calibrated using multi-generation data. Over time, as data accumulates, training data sets become increasingly heterogeneous. Differences in allele frequency and linkage disequilibrium patterns between the training and prediction genotypes may limit prediction accuracy. This leads to the question of whether all available data or a subset of it should be used to calibrate genomic prediction models. Previous research on training set optimization has focused on identifying a subset of the available data that is optimal for a given prediction set. However, this approach does not contemplate the possibility that different training sets may be optimal for different prediction genotypes. To address this problem, we recently introduced a sparse selection index (SSI) that identifies an optimal training set for each individual in a prediction set. Using additive genomic relationships, the SSI can provide increased accuracy relative to genomic-BLUP (GBLUP). Non-parametric genomic models using Gaussian kernels (KBLUP) have, in some cases, yielded higher prediction accuracies than standard additive models. Therefore, here we studied whether combining SSIs and kernel methods could further improve prediction accuracy when training genomic models using multi-generation data. Using four years of doubled haploid maize data from the International Maize and Wheat Improvement Center (CIMMYT), we found that when predicting grain yield the KBLUP outperformed the GBLUP, and that using SSI with additive relationships (GSSI) lead to 5–17% increases in accuracy, relative to the GBLUP. However, differences in prediction accuracy between the KBLUP and the kernel-based SSI were smaller and not always significant.Subject terms: Quantitative trait, Genetic models     

Chromosome Banding and 18S rDNA in situ Hybridization Analysis of Seven Species of the Family Achiridae (Teleostei: Pleuronectiformes)

Achiridae is an important family of the order Pleuronectiformes widely distributed in North, Central, and South America with freshwater and marine species. In the present study cytogenetic analyses comprising conventional and molecular techniques were carried out in seven species of this family. The following diploid numbers (2n) and fundamental numbers (FN) were obtained: Achirus declivis 2n = 34, FN = 52; Achirus lineatus 2n = 40, FN = 66; Catathyridium jenynsi 2n = 40 and FN = 50; Gymnachirus nudus 2n = 36 and FN = 50; Hypoclinemus mentalis 2n = 38 and FN = 54; Trinectes paulistanus 2n = 42 and FN = 52; and Trinectes sp. 2n = 38 and FN = 54. All species presented a single nucleolar organizer region (NOR) bearing chromosome pair and C-band positive segments mainly distributed at the pericentromeric position. The wide variation observed in chromosome number and FN suggests the occurrence of larger chromosome rearrangements in the family Achiridae if compared with other families of the same order.     

Topographical analysis of Schizolobium parahyba chymotrypsin inhibitor (SPCI) by atomic force microscopy

Atomic Force Microscopy (AFM) has been a useful tool for molecular surface analysis and to estimate topographical properties of proteins. Here we report a topographical study of a chymotrypsin inhibitor from Schizolobium parahyba seeds (SPCI) by AFM. The underlying structure of SPCI oligomers has been resolved in nanometer order resolution. SPCI oligomerize in hexagonal, ellipsoid, comet, pyramidal, and "Z" shaped. The hexagonal was the most observed oligomer shape.     

Molecular underpinnings of the early brain developmental response to differential feeding in the honey bee Apis mellifera

Brain differential morphogenesis in females is one of the major phenotypic manifestations of caste development in honey bees. Brain diphenism appears at the fourth larval phase as a result of the differential feeding regime developing females are submitted during early phases of larval development. Here, we used a forward genetics approach to test the early brain molecular response to differential feeding leading to the brain diphenism observed at later developmental phases. Using RNA sequencing analysis, we identified 53 differentially expressed genes (DEGs) between the brains of queens and workers at the third larval phase. Since miRNAs have been suggested to play a role in caste differentiation after horizontal and vertical transmission, we tested their potential participation in regulating the DEGs. The miRNA-mRNA interaction network, including the DEGs and the royal- and worker-jelly enriched miRNA populations, revealed a subset of miRNAs potentially involved in regulating the expression of DEGs. The interaction of miR-34, miR-210, and miR-317 with Takeout, Neurotrophin-1, Forked, and Masquerade genes was experimentally confirmed using a luciferase reporter system. Taken together, our results reconstruct the regulatory network that governs the development of the early brain diphenism in honey bees.     

CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women

Background

The current concept of overweight/obesity is most likely related to a combination of increased caloric intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target individuals at high risk of developing obesity have been largely proposed because of the increasing number of overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL-17, and BMP-2.

Results

Plasma mediators increased in all overweight and obese individuals, with the exception of BMP-2 in the elderly group, whereas CXCL16 levels were shown to differentiate overweight and obese individuals. Overweight and/or obese middle-aged and elderly individuals presented with high LDL, triglycerides, and glycemia levels. Anthropometric parameters indicating increased-cardiovascular risk were positively correlated with CXCL-16, BMP-2, and IL-17 levels in overweight and obese middle-aged and elderly individuals.

Conclusion

This study provides evidence that CXCL-16, IL-17, and BMP-2 are potential plasma indicators of inflammatory status in middle-aged and elderly women; therefore, further investigation of obesity-related comorbidities is recommended. CXCL16, in particular, could be a potential marker for middle-aged and elderly individuals transitioning from eutrophic to overweight body types, which represents an asymptomatic and dangerous condition.