Big cat genomes reveal a history of interspecies admixture and adaptive evolution of genes underlying development and sensory perception.

BackgroundThe genus Paracoccidioides comprises human thermal dimorphic fungi, which cause paracoccidioidomycosis (PCM), an important mycosis in Latin America. Adaptation to environmental conditions is key to fungal survival during human host infection. The adaptability of carbon metabolism is a vital fitness attribute during pathogenesis.Methodology/Principal FindingsThe fungal pathogen Paracoccidioides spp. is exposed to numerous adverse conditions, such as nutrient deprivation, in the human host. In this study, a comprehensive response of Paracoccidioides, Pb01, under carbon starvation was investigated using high-resolution transcriptomic (RNAseq) and proteomic (NanoUPLC-MSE) approaches. A total of 1,063 transcripts and 421 proteins were differentially regulated, providing a global view of metabolic reprogramming during carbon starvation. The main changes were those related to cells shifting to gluconeogenesis and ethanol production, supported by the degradation of amino acids and fatty acids and by the modulation of the glyoxylate and tricarboxylic cycles. This proposed carbon flow hypothesis was supported by gene and protein expression profiles assessed using qRT-PCR and western blot analysis, respectively, as well as using enzymatic, cell dry weight and fungus-macrophage interaction assays. The carbon source provides a survival advantage to Paracoccidioides inside macrophages.Conclusions/SignificanceFor a complete understanding of the physiological processes in an organism, the integration of approaches addressing different levels of regulation is important. To the best of our knowledge, this report presents the first description of the responses of Paracoccidioides spp. to host-like conditions using large-scale expression approaches. The alternative metabolic pathways that could be adopted by the organism during carbon starvation can be important for a better understanding of the fungal adaptation to the host, because systems for detecting and responding to carbon sources play a major role in adaptation and persistence in the host niche.

AimsTo describe the abundance of major phyla and some genera in the gut microbiota of individuals according to dietary habits and examine their associations with inflammatory markers, insulin resistance, and cardiovascular risk profile.MethodsA total of 268 non-diabetic individuals were stratified into groups of dietary types (strict vegetarians, lacto-ovo-vegetarians, and omnivores). The taxonomic composition and phylogenetic structure of the microbiota were obtained through the analysis of the 16S rRNA gene. Samples were clustered into operational taxonomic units at 97% similarity using GreenGenes 13.5 database. Clinical, biochemical, and circulating inflammatory markers were compared by ANOVA or Kruskal–Wallis test.ResultsThe sample (54.2% women, mean age 49.5 years) was composed of 66 strict vegetarians, 102 lacto-ovo-vegetarians and 100 omnivores. Considering the entire sample, the greatest abundant phyla were Firmicutes (40.7 ± 15.9%) and Bacteroidetes (39.5 ± 19.9%), and no difference in abundances was found between individuals with normal and excess weight. Stratifying by dietary types, the proportion of Firmicutes was lower and of Bacteroidetes was higher in strict vegetarians when compared to lacto-ovo-vegetarians and omnivores. At the genus level, strict vegetarians had a higher Prevotella abundance and Prevotella/Bacteroides ratio than the other groups. They also had a lower proportion of Faecalibacterium than lacto-ovo-vegetarians, and both vegetarian groups had higher proportions than did omnivores. Succinivibrio and Halomonas from the Proteobacteria phylum were overrepresented in omnivores. The omnivorous group showed higher values of anthropometric data, insulin, HOMA-IR, and a worse lipid profile. Inflammatory markers exhibited a gradual and significant increase from the vegetarians and lacto-ovo-vegetarians to the omnivorous group.ConclusionsThere are differences in gut microbiota composition of individuals with distinct dietary habits, who differ according to their inflammatory and metabolic profiles. Based on the findings relative to bacteria abundances and on their recognized actions in the metabolism, we suggest that exposure to animal foods may favor an intestinal environment which could trigger systemic inflammation and insulin resistance-dependent metabolic disorders.

Zantedeschia aethiopica is an evergreen perennial plant cultivated worldwide and commonly used for ornamental and medicinal purposes including the treatment of bacterial infections. However, the current understanding of molecular and physiological mechanisms in this plant is limited, in comparison to other non-model plants. In order to improve understanding of the biology of this botanical species, RNA-Seq technology was used for transcriptome assembly and characterization. Following Z. aethiopica spathe tissue RNA extraction, high-throughput RNA sequencing was performed with the aim of obtaining both abundant and rare transcript data. Functional profiling based on KEGG Orthology (KO) analysis highlighted contigs that were involved predominantly in genetic information (37%) and metabolism (34%) processes. Predicted proteins involved in the plant circadian system, hormone signal transduction, secondary metabolism and basal immunity are described here. In silico screening of the transcriptome data set for antimicrobial peptide (AMP) –encoding sequences was also carried out and three lipid transfer proteins (LTP) were identified as potential AMPs involved in plant defense. Spathe predicted protein maps were drawn, and suggested that major plant efforts are expended in guaranteeing the maintenance of cell homeostasis, characterized by high investment in carbohydrate, amino acid and energy metabolism as well as in genetic information.

Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM). PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects and limited efficacy; therefore, there is an inevitable and urgent medical need for the development of new antifungal drugs. In the present study, we evaluated the transcriptional profile of Paracoccidioides lutzii exposed to argentilactone, a constituent of the essential oil of Hyptis ovalifolia. A total of 1,058 genes were identified, of which 208 were up-regulated and 850 were down-regulated. Cell rescue, defense and virulence, with a total of 26 genes, was a functional category with a large number of genes induced, including heat shock protein 90 (hsp90), cytochrome c peroxidase (ccp), the hemoglobin ligand RBT5 (rbt5) and superoxide dismutase (sod). Quantitative real-time PCR revealed an increase in the expression level of all of those genes. An enzymatic assay showed a significant increase in SOD activity. The reduced growth of Pbhsp90-aRNA, Pbccp-aRNA, Pbsod-aRNA and Pbrbt5-aRNA isolates in the presence of argentilactone indicates the importance of these genes in the response of Paracoccidioides spp. to argentilactone. The response of the P. lutzii cell wall to argentilactone treatment was also evaluated. The results showed that argentilactone caused a decrease in the levels of polymers in the cell wall. These results suggest that argentilactone is a potential candidate for antifungal therapy.

The prevalence of gestational diabetes mellitus (GDM) is a global public health concern. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. This study analyzes the gut microbiota composition in each trimester of weight-matched women with and without GDM and examines possible bacterial genera associations with GDM. This study followed 56 pregnant women with GDM and 59 without admitted to the outpatient clinic during their first/second or third trimester of gestation. They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological sample collection, and molecular profiling of fecal microbiota. Women with GDM were older and had a higher number of pregnancies than normal-tolerant ones. There was no difference in alpha diversity, and the groups did not differ regarding the overall microbiota structure. A higher abundance of Bacteroides in the GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with one-hour post-challenge plasma glucose and a negative correlation between Enterococcus and two-hour plasma glucose levels were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. The gut microbiota composition was not dependent on the presence of GDM weight-matched women throughout gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may therefore encourage a deeper understanding of physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.

Stingrays commonly cause human envenoming related accidents in populations of the sea, near rivers and lakes. Transcriptomic profiles have been used to elucidate components of animal venom, since they are capable of providing molecular information on the biology of the animal and could have biomedical applications. In this study, we elucidated the transcriptomic profile of the venom glands from two different freshwater stingray species that are endemic to the Paraná-Paraguay basin in Brazil, Potamotrygon amandae and Potamotrygon falkneri. Using RNA-Seq, we identified species-specific transcripts and overlapping proteins in the venom gland of both species. Among the transcripts related with envenoming, high abundance of hyaluronidases was observed in both species. In addition, we built three-dimensional homology models based on several venom transcripts identified. Our study represents a significant improvement in the information about the venoms employed by these two species and their molecular characteristics. Moreover, the information generated by our group helps in a better understanding of the biology of freshwater cartilaginous fishes and offers clues for the development of clinical treatments for stingray envenoming in Brazil and around the world. Finally, our results might have biomedical implications in developing treatments for complex diseases.

Iron is an essential micronutrient for almost all organisms, including fungi. Usually, fungi can uptake iron through receptor-mediated internalization of a siderophore or heme, and/or reductive iron assimilation (RIA). Traditionally, the RIA pathway consists of ferric reductases (Fres), ferroxidase (Fet3) and a high-affinity iron permease (Ftr1). Paracoccidioides spp. genomes do not present an Ftr1 homolog. However, this fungus expresses zinc regulated transporter homologs (Zrts), members of the ZIP family of membrane transporters that are able in some organisms to transport zinc and iron. A 2,3,5-triphenyltetrazolium chloride (TTC)-overlay assay indicates that both Pb01 and Pb18 express a ferric reductase activity; however, 59Fe uptake assays indicate that only in Pb18 is this activity coupled to a reductase-dependent iron uptake pathway. In addition, Zrts are up-regulated in iron deprivation, as indicated by RNAseq and qRT-PCR using Pb01 transcripts. RNAseq strategy also demonstrated that transcripts related to siderophore uptake and biosynthesis are up-regulated in iron-deprived condition. The data suggest that the fungus could use both a non-classical RIA, comprising ferric reductases and Fe/Zn permeases (Zrts), and siderophore uptake pathways under iron-limited conditions. The study of iron metabolism reveals novel surface molecules that could function as accessible targets for drugs to block iron uptake and, consequently, inhibit pathogen's proliferation.