Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries)

Maximizing the number of offspring born per female is a key functionality trait in commercial- and/or subsistence-oriented livestock enterprises. Although the number of offspring born is closely associated with female fertility and reproductive success, the genetic control of these traits remains poorly understood in sub-Saharan Africa livestock. Using selection signature analysis performed on Ovine HD BeadChip data from the prolific Bonga sheep in Ethiopia, 41 candidate regions under selection were identified. The analysis revealed one strong selection signature on a candidate region on chromosome X spanning BMP15, suggesting this to be the primary candidate prolificacy gene in the breed. The analysis also identified several candidate regions spanning genes not reported before in prolific sheep but underlying fertility and reproduction in other species. The genes associated with female reproduction traits included SPOCK1 (age at first oestrus), GPR173 (mediator of ovarian cyclicity), HB-EGF (signalling early pregnancy success) and SMARCAL1 and HMGN3a (regulate gene expression during embryogenesis). The genes involved in male reproduction were FOXJ1 (sperm function and successful fertilization) and NME5 (spermatogenesis). We also observed genes such as PKD2L2, MAGED1 and KDM3B, which have been associated with diverse fertility traits in both sexes of other species. The results confirm the complexity of the genetic mechanisms underlying reproduction while suggesting that prolificacy in the Bonga sheep, and possibly African indigenous sheep is partly under the control of BMP15 while other genes that enhance male and female fertility are essential for reproductive fitness

Leukotriene B4 mediates neutrophil migration induced by heme

Submitted by Sandra Infurna ([email protected]) on 2017-11-01T16:38:21Z No. of bitstreams: 1 liliane_alves_etal_IOC_2011.pdf: 1162327 bytes, checksum: 89a12a98540b379ce9ab4d420ff18be5 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-11-09T09:53:43Z (GMT) No. of bitstreams: 1 liliane_alves_etal_IOC_2011.pdf: 1162327 bytes, checksum: 89a12a98540b379ce9ab4d420ff18be5 (MD5)Made available in DSpace on 2017-11-09T09:53:44Z (GMT). No. of bitstreams: 1 liliane_alves_etal_IOC_2011.pdf: 1162327 bytes, checksum: 89a12a98540b379ce9ab4d420ff18be5 (MD5) Previous issue date: 2011Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia. Departamento de Farmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, brasilUniversity of Michigan. Department of Internal Medicine, Division of Pulmonary and Critical care Medicine. Ann Arbor, MI, USA.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Professor Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.High concentrations of free heme found during hemolytic events or cell damage leads to inflammation, characterized by neutrophil recruitment and production of reactive oxygen species, through mechanisms not yet elucidated. In this study, we provide evidence that heme-induced neutrophilic inflammation depends on endogenous activity of the macrophage-derived lipid mediator leukotriene B(4) (LTB(4)). In vivo, heme-induced neutrophil recruitment into the peritoneal cavity of mice was attenuated by pretreatment with 5-lipoxygenase (5-LO) inhibitors and leukotriene B(4) receptor 1 (BLT1) receptor antagonists as well as in 5-LO knockout (5-LO(-/-)) mice. Heme administration in vivo increased peritoneal levels of LTB(4) prior to and during neutrophil recruitment. Evidence that LTB(4) was synthesized by resident macrophages, but not mast cells, included the following: 1) immuno-localization of heme-induced LTB(4) was compartmentalized exclusively within lipid bodies of resident macrophages; 2) an increase in the macrophage population enhanced heme-induced neutrophil migration; 3) depletion of resident mast cells did not affect heme-induced LTB(4) production or neutrophil influx; 4) increased levels of LTB(4) were found in heme-stimulated peritoneal cavities displaying increased macrophage numbers; and 5) in vitro, heme was able to activate directly macrophages to synthesize LTB(4). Our findings uncover a crucial role of LTB(4) in neutrophil migration induced by heme and suggest that beneficial therapeutic outcomes could be achieved by targeting the 5-LO pathway in the treatment of inflammation associated with hemolytic processes

GRPR antagonist protects from drug-induced liver injury by impairing neutrophil chemotaxis and motility

Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXC chemokine receptor 2 (CXCR2) ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life-threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration, and mechanisms underlying this phenomenon. We found that acetaminophen-overdosed mice treated with GRPR antagonist had reduced DILI and neutrophil infiltration in the liver. Intravital imaging and cell tracking analysis revealed reduced neutrophil mobility within the liver. Surprisingly, GRPR antagonist inhibited CXCL2-induced migration in vivo, decreasing neutrophil activation through CD11b and CD62L modulation. Additionally, this compound decreased CXCL8-driven neutrophil chemotaxis in vitro independently of CXCR2 internalization, induced activation of MAPKs (p38 and ERK1/2) and downregulation of neutrophil adhesion molecules CD11b and CD66b. In silico analysis revealed direct binding of GRPR antagonist and CXCL8 to the same binding spot in CXCR2. These findings indicate a new potential use for GRPR antagonist for treatment of DILI through a mechanism involving adhesion molecule modulation and possible direct binding to CXCR2.status: publishe

Gerência do cuidado de enfermagem em cenários hospitalares: a construção de um conceito

Este estudo teve como objetivo construir e apresentar a definição teórica do conceito de gerência do cuidado de enfermagem em cenários hospitalares, a partir de base literária específica. Optou-se pela utilização das estratégias para construção de conceitos da Análise de Conceito, as regras de formação de conceito da Análise Arqueológica e a Análise Lexical como referencial teórico-metodológico. A operacionalização das estratégias e das regras de formação de conceito possibilitou a construção do conceito gerência do cuidado de enfermagem em cenários hospitalares. O conceito construído apresentou, em sua natureza, a capacidade de integrar dialeticamente os aspectos relativos ao saber-fazer do cuidar e gerenciar. A definição teórica do conceito Gerência do Cuidado de Enfermagem em Cenários Hospitalares deu significado ao termo, no contexto inicial de construção de uma teoria, a Gerência do Cuidado de Enfermagem em Serviços de Saúde