Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage

The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has previously been shown to cause a human progeroid disorder, Néstor–Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly [ADP-ribose] polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions

Parallel Evolution of Auditory Genes for Echolocation in Bats and Toothed Whales

The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators—two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function

Processamento auditivo: comparação entre potenciais evocados auditivos de média latência e testes de padrões temporais Auditory processing: comparision between auditory middle latency response and temporal pattern tests

OBJETIVO: verificar a concordância entre os resultados da avaliação do Potencial Evocado Auditivo de Média Latência e testes de padrões temporais. MÉTODOS: foram avaliados 155 sujeitos de ambos os sexos, idade entre sete e 16 anos, com audição periférica normal. Os sujeitos foram submetidos aos testes de Padrão de Frequência e Duração e Potenciais Evocados auditivos de Média Latência. RESULTADOS: os sujeitos foram distribuídos em dois grupos: normal ou alterado para o processamento auditivo. O índice de alteração foi em torno de 30%, exceto para Potencial Evocado Auditivo de Média Latência que foi pouco menor (17,4%). Os padrões de frequência e duração foram concordantes até 12 anos. A partir dos 13 anos, observou-se maior ocorrência de alteração no padrão de frequência que no padrão de duração. Os padrões de frequência e duração (orelhas direita e esquerda) e Potencial Evocado Auditivo de Média Latência não foram concordantes. Para 7 e 8 anos a combinação padrão de frequência e duração normal / Média Latência alterado tem maior ocorrência que a combinação padrão de frequência e duração alterada / Média Latência normal. Nas demais idades, ocorreu o contrário. Não houve diferença estatística entre as faixas etárias quanto à distribuição de normal e alterado no padrão de frequência (orelhas direita e esquerda), nem para o Potencial Evocado Auditivo de Média Latência, com exceção do padrão de duração para o grupo de 9 e 10 anos. CONCLUSÃO: não houve concordância entre os resultados do Potencial Evocado Auditivo de Média Latência e os testes de padrões temporais aplicados.<br>PURPOSE: to check the concordance between the Middle Latency Response and temporal processing tests. METHODS: 155 normal hearing subjects of both genders (age group range between 7 to 16 years) were evaluated with the Pitch and Duration Pattern Tests (behavioral) and Middle Latency Response (electrophysiologic) and divided into two groups: normal and abnormal, according to their test results. RESULTS: among all subjects, 30% showed abnormality in the tests, except for the Middle Latency Response that was under 17.4%. The pitch and duration patterns (right and left ears) agreed until 12 years of age. From 13 years, there was a greater number of alteration in the pitch patterns than in the duration patterns. The pitch and duration patterns (right and left ears) and MLR did not show concordance. For the 7 and 8-year-old group, the combination pitch and duration patterns normal/abnormal Middle Latency Response had greater occurrence than the combination pitch and duration patterns abnormal / normal Middle Latency Response. For the other groups the opposite occurred. There was not statistical difference among the age groups regarding normal and abnormal results for the pitch patterns (right and left ears) and Middle Latency Response, the duration patterns showed more abnormal results for the 9, 10 years old group. CONCLUSION: it was not possible to verify concordance between the Middle Latency Response and behavioral evaluation of Frequency and Duration Patterns Test