Summary Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (Family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys1. Until the 20th century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the island of Yap in Micronesia2. Patients experienced fever, skin rash, arthralgia and conjunctivitis2. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America3. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome4,5. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKVBR) strain causes birth defects remains missing6. Here we demonstrate that the ZIKVBR infects fetuses, causing intra-uterine growth restriction (IUGR), including signs of microcephaly in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. Finally, we observed that the infection of human brain organoids resulted in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKVBR crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKVBR outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKVBR in human neurodevelopment.

ABSTRACT.-Agopian R.G., Guimarães K.P., Fernandes R.A., Silva M.V.M., Righetti M.M.S., Prisco C.R.D., Bombonato P.P. & Liberti E. A. 2016 Renal health has over the last few years called attention of veterinarians, because the chronic failure of the kidneyu is a major cause of morbidity and mortality in cats. This paper proposes biometric characterization of the kidneys from cats, Felis catus, on the macroscopic aspects (length, height, width, weight and volume), mesoscopic (height of the cortex and medulla, and their inter-relationship) and microscopic (glomerular volume) in order to establish possible differences arising from age, gender and bilateral symmetry. It where used 30 kidneys of animals from specie Felis catus (cat), 15 males and 15 females with ages between 3 months to 15 years, divided into three groups: group 1 (3-9 months), group 2 (3 -5 years) and group 3 (above 10 years). The kidneys were photographed, weighed, measured and processed for histology. The glomerular volume was obtained by stereology. The macroscopic data allowed to observe a morphometric and morphologic impartiality when compared sides, regardless of group and sex, about the length, height, width, weight and kidney volume. Significant difference was detected between males and females regardless of age for length, height, weight and volume, except for the width. There was a significant difference for all parameters considering the age: length, height, width, weight and volume. Wasnt detected signficant diferences between left and right kdney measurements of cortex, medulla and their inter-relationship, when considered bilateral symmetry. No difference was detected between males and females in mesoscopy in the cortex, medulla and cortex interrelationship cortex/medulla. Regarding age, the measurement of the height of the cortex and the interrelationship cortex/medulla showed a significant difference, but this difference was not established to the medulla of the kidney. Significant differences were found between groups, males and females, compared to the volume occupied by the glomerulus on the parenchyma renal. In all of biometric techniques there wasnt differences between right and left kidneys. The macroscopic measurements showed that males had larger kidney when compared length, height, width, weight and volume than females. The age range is directly related to the size of the kidney, which grows in all dimensions, gets heavier and with higher volume when compared young adults, and shows morphometry stability in relation to adults and senile. The renal parenchyma did not differ between the sexes, but the height of the cortex and the medulla ratio increases with age. The volume of the renal glomerulus is higher in males than in females and also increases in with the age. The kidneys showed a predominance of type I collagen in group 1 and 2, and type III collagen in group 3.