What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.

Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts

Risk factors for infant mortality in a municipality in southern Brazil: a comparison of two cohorts using hierarchical analysis Fatores de risco para mortalidade infantil em município do Sul do Brasil: comparação de duas coortes em análise hierarquizada

This study compared risk factors for infant mortality in 2000-2001 and 2007-2008 in Londrina, Paraná State, Brazil. Data on live births and infant deaths were linked in a single database, and a hierarchical regression model was used. Distal risk factors for infant mortality in 2000-2001 were maternal age < 20 or &#8805; 35 years and lower maternal schooling. In 2007-2008, maternal age &#8805; 35 or < 20 years were risk factors, while low schooling appeared as a protective factor. The following intermediate factors were associated with increased infant mortality in 2000-2001: multiple pregnancy, history of stillbirth, and insufficient number of prenatal visits, while cesarean delivery was a protective factor. Multiple pregnancy was the only intermediate risk factor in 2007-2008. All of the proximal factors were associated with higher infant mortality in 2000-2001, but only gestational age and 5-minute Apgar in 2007-2008. The risk factors for infant mortality changed from the first to the second cohort, which may be related to the expansion of social policies and primary care and changes in the reproductive and social patterns of Brazilian women.<br>Compararam-se fatores de risco para mortalidade infantil nos anos 2000/2001 e 2007/2008 em Londrina, Paraná, Brasil. Dados sobre nascidos vivos e óbitos infantis foram vinculados em base de dados única, e usou-se análise de regressão em modelo hierárquico. No nível distal, foram de risco para mortalidade infantil, em 2000/2001, idade materna < 20 e &#8805; 35 anos e escolaridade materna baixa. Em 2007/2008, idades maternas &#8805; 35 e < 20 anos foram de risco, enquanto escolaridade baixa, protetora. Associaram-se à maior mortalidade infantil, no nível intermediário, em 2000/2001: gestação múltipla, filhos mortos e número insuficiente de consultas pré-natal, enquanto cesariana foi fator protetor. Em 2007/2008, apenas gestação múltipla foi de risco. Todos os fatores proximais associaram-se à maior mortalidade infantil em 2000/2001 e, em 2007/2008, apenas idade gestacional e Apgar no quinto minuto. Houve mudanças nos fatores de risco para a mortalidade infantil nos biênios analisados, o que pode estar relacionado à ampliação de políticas sociais e de ações básicas de saúde, e a modificações no padrão reprodutivo e social das mulheres

Three-dimensional and stereological characterization of the human substantia nigra during aging

The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from fifteen subjects aged 50–91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p=0.04 rho=−0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN