Archaic adaptive introgression in TBX15/WARS2

A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using SNP chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15

КОМПЛЕКСНАЯ ОЦЕНКА КЛИНИКО-ИНСТРУМЕНТАЛЬНЫХ ДАННЫХ ДЛЯ ОБОСНОВАНИЯ ТАКТИКИ ОПЕРАТИВНОГО ЛЕЧЕНИЯ БОЛЬНЫХ С РЕЗИСТЕНТНЫМИ ФОРМАМИ ЭПИЛЕПСИИ

Frequent epileptic seizures and side effects of drugs have a significant negative impact on the quality of life. The main goal in the treatment of such patients is not only to decrease the number of attacks and their severity, but also to improve social adaptation. Surgical treatment for some forms of pharmacoresistant epilepsy improves prognosis and enhances the quality of life of patients, and the result depends on the duration of the disease. The main task of the preoperative examination is the most accurate localization of the epileptogenic zone. In the case of proximity or the overlapping of the epileptogenic zone with functionally significant parts of the crust, additional surveys to determine the latter are conducted. The survey may be conducted using non-invasive techniques, such as MRI, functional MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT) and extracranial electrical stimulation or invasive direct electrical stimulation of the cortex.Частые эпилептические приступы и побочные эффекты применяемых препаратов могут оказывать отрицательное влияние на качество жизни. Основной целью в лечении пациентов с эпилепсией является снижение количества приступов, их тяжести, улучшение социальной адаптации. Хирургическое лечение при фармакорезистентной эпилепсии в ряде случаев позволяет снизить частоту приступов, улучшить прогноз и качество жизни пациентов. Основной задачей предоперационного обследования является максимально точное определение локализации эпилептогенной зоны. В случае близости или наложении эпилептогенной зоны на функционально значимые отделы коры проводятся дополнительные обследования с целью определения последних. В этом помогают данные, полученные с помощью неинвазивных методик, таких как МРТ, функциональная МРТ, позитронно-эмиссонная томография (ПЭТ), однофотонная эмиссионная компьютерная томография (ОФЭКТ) и экстракраниальная электростимуляция, и инвазивных путем прямой электростимуляции коры

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells

Background: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Results: Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1aα, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. Conclusions: We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state