Evidence for the fixation of gene duplications by positive selection in \u3ci\u3eDrosophila\u3c/i\u3e

Gene duplications play a key role in the emergence of novel traits and in adaptation. But despite their centrality to evolutionary processes, it is still largely unknown how new gene duplicates are initially fixed within populations and later maintained in genomes. Long-standing debates on the evolution of gene duplications could be settled by determining the relative importance of genetic drift vs. positive selection in the fixation of new gene duplicates. Using the Drosophila Global Diversity Lines (GDL), we have combined genome-wide SNP polymorphism data with a novel set of copy number variant calls and gene expression profiles to characterize the polymorphic phase of new genes. We found that approximately half of the roughly 500 new complete gene duplications segregating in the GDL lead to significant increases in the expression levels of the duplicated genes and that these duplications are more likely to be found at lower frequencies, suggesting a negative impact on fitness. However, we also found that six of the nine gene duplications that are fixed or close to fixation in at least one of the five populations in our study show signs of being under positive selection, and that these duplications are likely beneficial because of dosage effects, with a possible role for additional mutations in two duplications. Our work suggests that in Drosophila, theoretical models that posit that gene duplications are immediately beneficial and fixed by positive selection are most relevant to explain the long-term evolution of gene duplications in this species. Supplemental materials attached below

Eosinophil granule proteins involvement in acute appendicitis: an allergic disease?

Several pieces of evidence point to an allergic component as a trigger of acute appendicitis. As the Th2 immune response is characterized by eosinophil mobilization to the target organ and release of their cationic granule proteins, it is reasonable to investigate if the degranulation of eosinophils could be associated with the local injury. The primary aim of this study is to evaluate the participation of eosinophils granules proteins in acute appendicitis, both at local and systemic levels and the secondary aim is to evaluate the diagnostic accuracy of eosinophils granules proteins for the detection of acute appendicitis, as well as for distinguishing between complicated and uncomplicated acute appendicitis. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EP) are the most well-known eosinophil granule proteins. From August 2021 to April 2022, we present a prospective single-center study to evaluate the EDN, ECP, and EP concentrations simultaneously in appendicular lavage fluid (ALF) and the serum of 22 patients with acute phlegmonous appendicitis (APA), 24 with acute gangrenous appendicitis (AGA), and 14 normal controls. Concerning EDN, no differences were found between groups. ECP concentrations in ALF and serum were significantly higher in the histologically confirmed acute appendicitis compared to the control groups (p 11.41 ng/mL, with a sensitivity of 93.5%, but with a specificity for identifying appendicitis of 21.4%, good discriminative power (AUC = 0.880). For EP, the optimal cut-off was >93.20 ng/mL, with a sensitivity of 87%, but with a specificity of 14.3% (AUC = 0.901), excellent discriminative power. For the diagnosis of perforated AA, the discriminative power of ECP and EP serum concentrations are weak (AUC = 0.562 and AUC = 0.664, respectively). Concerning the presence of peritonitis, the discriminative power of ECP and EP serum concentrations is acceptable, respectively: AUC = 0.724 and AUC = 0.735. Serum levels of EDN (p = 0.119), ECP (p = 0.586) and EP (p = 0.08) in complicated appendicitis were similar to uncomplicated appendicitis. Serum concentrations of ECP and EP can be added to decision-making AA diagnosis. A Th2-type immune response is present in AA. These data bring forward the role of an allergic reaction in the pathogenesis of acute appendicitis.info:eu-repo/semantics/publishedVersio

Gene expression across mammalian organ development

The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified developmental stage correspondences across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs

Developmental gene expression differences between humans and mammalian models

Identifying the molecular programs underlying human organ development and how they differ from model species is key for understanding human health and disease. Developmental gene expression profiles provide a window into the genes underlying organ development and a direct means to compare them across species. We use a transcriptomic resource covering the development of seven organs to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for each human gene, the similarity of its spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat, and rabbit. We find clear associations between spatiotemporal profiles and the phenotypic manifestations of diseases. We also find that half of human genes differ from their mouse orthologs in their temporal trajectories in at least one of the organs. These include more than 200 genes associated with brain, heart, and liver disease for which mouse models should undergo extra scrutiny

Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling

Supplementary material: http://www.jimmunol.org/content/suppl/2016/11/12/jimmunol.1600584.DCSupplementalTuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ–dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling. We show that production of type I IFN by M. tuberculosis–infected macrophages induced NO synthase 2 and inhibited arginase 1 gene expression. In vivo, absence of both type I and type II IFN receptors led to strikingly increased levels of arginase 1 gene expression and protein activity in infected lungs, characteristic of alternatively activated macrophages. This correlated with increased lung bacterial burden and pathology and decreased survival compared with mice deficient in either receptor. Increased expression of other genes associated with alternatively activated macrophages, as well as increased expression of Th2-associated cytokines and decreased TNF expression, were also observed. Thus, in the absence of IFN-γ signaling, type I IFN suppressed the switching of macrophages from a more protective classically activated phenotype to a more permissive alternatively activated phenotype. Together, our data support a model in which suppression of alternative macrophage activation by type I IFN during M. tuberculosis infection, in the absence of IFN-γ signaling, contributes to host protection.This work was supported by the Fundação para a Ciência e Tecnologia, Portugal, cofunded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional, through the Fundo Europeu de Desenvolvimento Regional (PTDC/SAU-MII/101977/2008 and PTDC/BIA-BCM/102776/2008); by the Francis Crick Institute, which receives its core funding from Cancer Research U.K. (FC001126), the U.K. Medical Research Council (FC001126), and the Wellcome Trust (FC001126); by the U.K. Medical Research Council (MR/U117565642/1); and by the European Research Council (294682-TB-PATH). This work was also supported by Research Grant 2015 from the European Society of Clinical Microbiology and Infectious Diseases (to M.S.). L.M.-T. was funded by the Fundação para a Ciência e Tecnologia (SFRH/BPD/77399/2011) and the European Research Council (294682-TB-PATH). The M.S. laboratory was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e Tecnologia, Portugal, in the framework of the Institute for Research and Innovation in Health Sciences project (POCI-01-0145-FEDER-007274). M.S. is a Fundação para a Ciência e Tecnologia Associate Investigator. E.T. is a Fundação para a Ciência e Tecnologia Auxiliary Investigator

Portuguese propolis: a source of valuable bioactivities

To FEDER/COMPETE/POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013

Intake, digestibility, and ingestive behavior of sheep fed with thornless Mandacaru, cactus pear genotypes Orelha de Elefante Mexicana and Miúda

This study aimed to evaluate the intake, digestibility, and ingestive behavior of sheep fed with different species of forage cacti. Fifteen sheep (17.27kg ± 1 kg) were distributed in a completely randomized experimental design with three treatments and five replicates. The treatments were diets on a dry matter basis composed of 430.9 g kg-1 of thornless Mandacaru cactus (Cereus hildmannianus), 525.7 g kg-1 of cactus pear cv. Orelha de Elefante Mexicana (Opuntia stricta) and 492.1 g kg-1 of cactus pear cv. Miúda (Nopalea cochenillifera) in addition to Sabiá hay (Mimosa caesalpiniaefolia) (194.7 to 233.8 g kg-1), plus concentrate feed. The intake of the dry matter, organic matter, ether extract, neutral detergent fiber, total carbohydrates, non-fiber carbohydrates, total digestible nutrients and voluntary water intake in g day-1 was not differ (p > 0.05) by experimental diets. There were no differences (p > 0.05) in digestibility coefficients of the dry matter, organic matter, neutral detergent fiber, total carbohydrates, non-fiber carbohydrates, and total digestible nutrients between the experimental diets. The feeding times differed (p 0.05). The cactus Cereus and Opuntia and Nopalea have similar nutritional value in sheep’s diet

Antitumoral and antiangiogenic activity of Portuguese propolis in in vitro and in vivo models

Propolis, a natural product, has important biological properties, however, studies with Portuguese propolis are scarce. Thus, we aimed to characterize the chemical composition and the antitumoural and antiangiogenic activities of a sample from Pereiro (Portugal). The chemical profile of our propolis sample (P10.EE) is similar to the poplar propolis type. P10.EE decreased cell viability of different tumour cells, being less cytotoxic against non-tumoural cells. P10.EE decreased MDA-MB-231 and DU145 cell proliferation and migration, with cell cycle changes and increased cell death. The increased glucose consumption and lactate production in MDA-MB-231 cells is explained by an increased expression of different metabolism-related proteins. P10.EE induced a decrease in HBMEC cells total biomass and proliferation and decreased vessel sprouting in the chicken chorioallantoic membrane. Additionally, P10.EE potentiates paclitaxel effect in MDA-MB-231 and DU145 cells. Concluding, P10.EE can be a good candidate for cancer drug development since it affects different characteristics that dictate tumorigenesis.This work was supported by the Life and Health Sciences Research Institute, University of Minho, Portugal, and Fundacao para a Ciencia e Tecnologia (FCT) (SFRH/BD/5199712012 to V.M.G.), through Fundo Europeu de Desenvolvimento Regional-QREN-COMPETE, projects PTDC/AAC-CLI1098308/2008 and PTDC/AAC-CLI/11809212010 and also CERNAS (project PEst-OE/AGR/UI0681/2011)