Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

A map of the vicinity of Niagara Falls. 1857

Relief shown by hachures. Full title: A map of the vicinity of Niagara Falls drawn from actual survey for Tunis' Guide by J.H. Fairbank. "Entered according to Act of congress, in the year 1857, by W.E. Tunis," - bottom margin. Digital reproduction of folded map in "Tunis's topographical and pictorial guide to Niagara Falls". Detroit : W.E. Tunis, [1872], located in Brock University Archives and Special Collections call # SPCL F 127 N8 T9 1872. Georeferenced and modified by Map, Data and GIS Library, Brock University

SON haploinsufficiency causes impaired pre-mRNA splicing of CAKUT genes and heterogeneous renal phenotypes

Contains fulltext : 204239.pdf (Publisher’s version ) (Closed access)Although genetic testing is increasingly used in clinical nephrology, a large number of patients with congenital abnormalities of the kidney and urinary tract (CAKUT) remain undiagnosed with current gene panels. Therefore, careful curation of novel genetic findings is key to improving diagnostic yields. We recently described a novel intellectual disability syndrome caused by de novo heterozygous loss-of-function mutations in the gene encoding the splicing factor SON. Here, we show that many of these patients, including two previously unreported, exhibit a wide array of kidney abnormalities. Detailed phenotyping of 14 patients with SON haploinsufficiency identified kidney anomalies in 8 patients, including horseshoe kidney, unilateral renal hypoplasia, and renal cysts. Recurrent urinary tract infections, electrolyte disturbances, and hypertension were also observed in some patients. SON knockdown in kidney cell lines leads to abnormal pre-mRNA splicing, resulting in decreased expression of several established CAKUT genes. Furthermore, these molecular events were observed in patient-derived cells with SON haploinsufficiency. Taken together, our data suggest that the wide spectrum of phenotypes in patients with a pathogenic SON mutation is a consequence of impaired pre-mRNA splicing of several CAKUT genes. We propose that genetic testing panels designed to diagnose children with a kidney phenotype should include the SON gene