The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold

Published version also available at http://dx.doi.org/10.1016/j.celrep.2015.03.062The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo

Outcomes in poor responders treated with in vitro fertilization/intracytoplasmic sperm injection according to bologna criteria

Purpose of the study was to evaluate the effectiveness of various approaches of artificial reproductive technologies (ART) in advanced maternal age patients with poor ovarian response (POR). Materials and methods. This is retrospective cohort study of 455 patients with POR who have undergone an IVF and embryo transfer program at from June 2016 to June 2018. Researchers evaluated pregnancy rate (PR) per embryo transferand live birth rate (LBR) per embryo transferas in vitro fertilization (IVF) outcomes. The patients fulfilled Bologna criteria were divided into 5 groups: long protocol, ant-gonadotropin-releasing hormone protocol, freeze embryos transfer without preimplantation genetic diagnostic (PGS), freeze embryos transfer with PGS, natural cycle. Results. There was no statistically significant difference in the age, Anti-Müllerian hormone level and duration of infertility between the groups. Despite different protocols of ovarian stimulation, there was no statistically significant difference in pregnancy rate in fresh cycles. At the same time, cancellation of transfer was significantly higher observed in natural cycles (p <0.001). PR and LBR were statistically significant higher in freeze embryo transfer group 29% and 12.1% vs 13.3% and 5,5% respectively (p<0.001 and p = 0.040). During the transfer of the embryo unexamined by PGS and after PGS the pregnancy rate did not differ (29.4% vs 28.2%, p <0.05), but LBR was statistically significant higher after euploid embryo transfer (8.2% without PGS vs 20.5% after PGS, p = 0.028). Conclusion. The most effective approach in patients with a poor ovarian response was cycle segmentation, cryopreservation of embryos, PGS and transfer of an euploid embryo. This category of patients requires a personalized approach to the treatment of infertility. The choice of protocol in ART program must be carried out with the full voluntary and informed consent of the patient, depending on their desires and capabilities, including financial

The Influence of Social Networks on the Formation of Motivation for Sports

Статья посвящена влиянию социальных сетей на формирование мотивации к занятиям спортом. Мотивация играет ключевую роль в успехе любого спортсмена, она стимулирует и поддерживает стремление к достижению высоких результатов и развитию своих навыков. Социальные сети могут благоприятно влиять на мотивацию спортсменов, когда необходима поддержка единомышленников.The article is devoted to the influence of social networks on the formation of motivation to play sports. Motivation plays a key role in the success of any athlete, it stimulates and supports the desire to achieve high results and develop their skills. Social networks are the place where free time is most often spent in modern reality, so they can have a beneficial effect on the motivation of athletes when the support of like-minded people is needed

Automatic structures of bounded degree revisited

The first-order theory of a string automatic structure is known to be decidable, but there are examples of string automatic structures with nonelementary first-order theories. We prove that the first-order theory of a string automatic structure of bounded degree is decidable in doubly exponential space (for injective automatic presentations, this holds even uniformly). This result is shown to be optimal since we also present a string automatic structure of bounded degree whose first-order theory is hard for 2EXPSPACE. We prove similar results also for tree automatic structures. These findings close the gaps left open in a previous paper of the second author by improving both, the lower and the upper bounds.Comment: 26 page

Digital and economic transformations for sustainable development promotion: A case of OECD countries

Digitalization, dematerialization of production and consumption, and structural shifts in the direction of service economy forming do promote to reduction of material use and sustainable development. The paper aims to investigate the role of digital, structural, economic, and social factors in sustainable development promotion in OECD countries. The paper uses the data on digital achievements, social and economic development of OECD member states from World Bank data sources for the period 2007–2018. The randomeffects GLS regression model is used, and empirical regression models to estimate the influence of key factors related to digital transformation on GDP per capita and CO2 emissions per capita are constructed. The results of the regression analysis show that using the number of Internet users as an indicator for achievement in digitalization has a positive and statistically significant influence on GDP per capita due to lower transaction costs and higher share service economy. An increase in urbanization rates (as an indicator of capital concentrations and labor specialization) by one percent promotes a GDP per capita increase of 299 USD. Also, an increase in Gini coefficient by one percentage point correlates with decrease in GDP per capita on 196 USD and the reduction of CO2 per capita by 0.12 tones due to the structural shifts in aggregate demand. Still, improvements in digital transformations have no significant environmental effect in OECD members, while processes related to urbanization, income inequalit

Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium