Genetic Studies Highlight the Role of TET2 and INO80 in DNA Damage Response and Kidney Disease Pathogenesis.

Genome-wide association studies (GWAS) have identified over 800 loci associated with kidney function, yet the specific genes, variants, and pathways involved remain elusive. By integrating kidney function GWAS, human kidney expression and methylation quantitative trait analyses, we identified Ten-Eleven Translocation (TET) DNA demethylase 2: TET2 as a novel kidney disease risk gene. Utilizing single-cell chromatin accessibility and CRISPR-based genome editing, we highlight GWAS variants that influence TET2 expression in kidney proximal tubule cells. Experiments using kidney-tubule-specific Tet2 knockout mice indicated its protective role in cisplatin-induced acute kidney injury, as well as chronic kidney disease and fibrosis, induced by unilateral ureteral obstruction or adenine diet. Single-cell gene profiling of kidneys from Tet2 knockout mice and TET2- knock-down tubule cells revealed the altered expression of DNA damage repair and chromosome segregation genes, notably including INO80 , another kidney function GWAS target gene itself. Remarkably both TET2- null and INO80- null cells exhibited an increased accumulation of micronuclei after injury, leading to the activation of cytosolic nucleotide sensor cGAS-STING. Genetic deletion of cGAS or STING in kidney tubules or pharmacological inhibition of STING protected TET2 null mice from disease development. In conclusion, our findings highlight TET2 and INO80 as key genes in the pathogenesis of kidney diseases, indicating the importance of DNA damage repair mechanisms.

Balance and motor coordination are not fully developed in 7 years old blind children

As crianças portadoras de deficiência visual possuem dificuldades em conhecer seu próprio corpo, objetos a sua volta e parâmetros espaciais imprescindíveis para locomoção independente. Este trabalho analisa o desenvolvimento neuropsicomotor de um grupo de crianças com deficiência visual congênita em comparação a crianças com visão normal. Avaliamos dois grupos de crianças de sete anos de idade, através do exame neurológico evolutivo (ENE). O grupo estudado era constituído de 20 crianças cegas e o grupo controle constituído de 20 crianças com visão normal, pareadas por idade e sexo. Em algumas provas, as crianças cegas foram instruídas pelo tato. As crianças portadoras de deficiência visual tiveram pior desempenho nas provas que avaliaram o equilíbrio e coordenação apendicular, quando comparadas às crianças com visão normal (p< 0,001), sugerindo que o déficit visual compromete o desenvolvimento neuropsicomotor da criança.

Balance and motor coordination are not fully developed in 7-year-old blind children.

Visually impaired children show difficulties in recognizing their own bodies, objects around then and the spatial parameters that are essential for independent movement. This study analyzes the neuro-psychomotor development of a group of congenitally visually impaired children as compared to children with normal sight. We have evaluated two groups of seven-year-olds by means of neurological evolution examination (NEE). The group studied comprised 20 blind children and the control group comprised 20 children with normal sight, and they were paired up according to age and gender. In some tests, the blind children were guided by touch. The visually impaired children performed worse in tests evaluating balance and appendage coordination compared to normal sighted children (p< 0.001), and this suggests that visual deficiency impairs children's neuro-psychomotor development.