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steatosis in livers from all 3 groups. However, there were significantly larger and more numerous lipid droplets (LDs) in livers of MTP ASO-treated mice, whereas LDs in apoB ASO-treated livers did not differ from control ASO-treated livers ( Figure 1F). Expression of PPARγ and related target genes for LD proteins, such as Fsp27 and Plin2 (also known as Adrp), were also increased in livers from MTP ASO-but not apoB ASO-treated livers (Supplemental Figure 6).De novo hepatic lipogenesis, FA uptake, FA oxidation, and FA secretion were not different in mice treated with apoB ASO for 6 weeks. The absence of steatosis in mice treated with apoB ASO for 6 weeks, despite marked reductions in TG and apoB secretion, led us to look for compensatory changes in the other major pathways that maintain hepatic lipid homeostasis: de novo hepatic lipogenesis (DNL), FA uptake from plasma, and FA oxidation (2). Treatment with either MTP ASO or apoB ASO was associated with a general trend toward reduced expression of several lipogenic genes compared with the control ASO-treated group, but direct measurement of hepatic DNL by determining incorporation of

Erlin1 and erlin2 are highly homologous, ~ 40kDa, endoplasmic reticulum membrane proteins that assemble into a ring-shaped complex with a mass of ~2MDa. How this complex is formed is not understood, but appears to involve multiple interactions, including a coiled-coil region that mediates lower-order erlin assembly, and a short hydrophobic region, termed the “assembly domain”, that mediates higher-order assembly into ~2MDa complexes. Here we have used molecular modeling, mutagenesis and cross-linking to examine the role of the assembly domain in higher-order assembly. We find (i) that the assembly domains of erlin1 and erlin2 are amphipathic helices, (ii) that erlin1 alone and erlin2 alone can assemble into ~2MDa complexes, (iii) that higher-order assembly is strongly inhibited by point mutations to the assembly domain, (iv) that three interacting hydrophobic residues in the assembly domain and aromaticity are essential for higher-order assembly, and (iv) that while erlins1 and 2 are equally capable of forming lower-order homo- and hetero-oligomers, hetero-oligomers are the most prevalent form when erlin1 and erlin2 are co-expressed. Overall, we conclude that the ~2MDa erlin1/2 complex is composed of an assemblage of lower-order hetero-oligomers, probably heterotrimers, linked together by assembly domain hydrophobic residues.

Current local and national demographic trends have deepened the existing and formed new global demographic processes that have received a new historical reasoning that requires deep scientific research taking into account the influence of the multifactorial global dimension of the modern society development. The purpose of the article is to study the development of global demographic processes and to define the causes of their occurrence, manifestations, implications and prospects for implementation in the first half of the 21st century. The authors have identified and characterized four global demographic processes, namely population growth, migration, increase of tourism, and change in population structure. It is projected that in the 30's of the 21st century, the number and growth rates of the world population will reach the objective growth and these dynamics over the next two decades will begin to change in the direction of reducing the growth rates, which will lead to gradual stabilization, and eventually reduce the size of the world population. By the middle of the 21st century, one can observe the preservation of the growth rates of international and domestic migration, the growth of international migration flows from the South to the North and from the East to the West, the strengthening of new economically developed centers of gravity (Canada, Australia and New Zealand), the increase in migration of rural population to cities, as well as urbanization and activation of the metropolises development. The share of international tourists in comparison with the world population will be constantly increasing, and the annual growth rate of the number of international tourists will significantly depend on the world economy and may vary at the several percent level. Permanent change will occur in the age, religious-cultural and socio-economic structure of the population.

Introduction. Charcot–Marie–Tooth disease type 4D is a hereditary demyelinating neuropathy, that occurs with the high frequency in patients of Roma origin. It is characterized by early onset at the age of 2–10 years and hearing impairment, manifested by the 3rd decade of life.Aim of the study. To describe the clinical and genetic characteristics of Charcot–Marie–Tooth disease type 4D in Russian patients of Roma origin.Materials and methods. For 14 probands from unrelated families of Roma origin with a clinical diagnosis of Charcot–Marie–Tooth disease, genetic tests for the pathogenic variants c. 442C>T in the NDRG1 gene and c. 3325C>T in the SH3TC2 gene was carried out. For 8 patients with Charcot–Marie–Tooth disease type 4D, detailed clinical and electrophysiological examination was performed.Results. In 11 families of Roma origin, the c. 442C>T pathogenic variant in the NDRG1 gene in a homozygous state was detected, which accounted for 79 % all observed Roma patients with Charcot–Marie–Tooth disease. There are 12 of the 14 tested families live in the European part of Russia, 7 of them are from nearby regions. The average age of onset was 3.3 years. The first symptom in 7 of 8 patients was gait disturbances. At the time of examination (age range 6–19 years), all patients showed marked hypotrophy and weakness of the feet, lower leg, hands muscles, feet deformities, reduction or loss of tendon reflexes.Discussion. Due to the detection of only one pathogenic variant in most Russian patients of Roma origin with Charcot–Marie–Tooth disease, the knowledge of the ethnicity of a proband with early myelinopathy can significantly simplify the confirmation of the diagnosis on the molecular level.