Current driven switching of magnetic layers

The switching of magnetic layers is studied under the action of a spin current in a ferromagnetic metal/non-magnetic metal/ferromagnetic metal spin valve. We find that the main contribution to the switching comes from the non-equilibrium exchange interaction between the ferromagnetic layers. This interaction defines the magnetic configuration of the layers with minimum energy and establishes the threshold for a critical switching current. Depending on the direction of the critical current, the interaction changes sign and a given magnetic configuration becomes unstable. To model the time dependence of the switching process, we derive a set of coupled Landau-Lifshitz equations for the ferromagnetic layers. Higher order terms in the non-equilibrium exchange coupling allow the system to evolve to its steady-state configuration.Comment: 8 pages, 2 figure. Submitted to Phys. Rev.

Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients

BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therap

MODY caused by a mutation in the insulin gene

MODY10 is a rare subtype of MODY diabetes, which caused by heterozygous mutations in the insulin gene INS. There are single descriptions of families with MODY-INS or MODY10 in the literature, its clinical course is not well understood. We present a case of MODY10 in a boy with a history of diabetes mellitus (DM) in three generations (father and paternal grandmother). Proband was diagnosed with diabetes mellitus at the age of 7 years. The glycaemia at the onset of the diabetes was 10.2 mmol/l, HbA1c — 7.6%, islet cell autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADA) and islet tyrosine phosphatase 2 (IA2) antibodies (IA2) were not detected. According to the results of the oral glucose tolerance test, fasting blood glucose was 6.5 mmol/l, in 120 minutes 10.3 mmol/l, which corresponded to the diagnosis of impaired glucose tolerance. Diet with restriction of easily digestible carbohydrates was recommended, than gliclazide was added to the therapy, which the proband received for 3 years. At the age of 10, a deterioration in the parameters of carbohydrate metabolism was noted, which insulin therapy was added. Examination at the age of 12 revealed a decrease in C-peptide secretion. The child’s father has a similar phenotype — slowly progressive disorders of carbohydrate metabolism from 6 years old, from 10 years old — insulin therapy. A genetic test was provided, in the child and his father was detected a previously undescribed heterozygous mutation in the INS p.C31W. Thus, in our clinical case, MODY10 was characterized by a milder course than T1DM, but eventually leading to the development of insulin demand, which distinguishes it from the most common forms of MODY. Currently, there is no specific therapy, and the detection of a mutation in the INS gene does not affect therapeutic tactics, however, a correct genetic diagnosis makes it possible to predict the course of diabetes and provide genetic counseling to the family

Boundary Lubrication: Squeeze-out Dynamics of a Compressible 2D Liquid

The expulsion dynamics of the last liquid monolayer of molecules confined between two surfaces has been analyzed by solving the two-dimensional (2D) Navier-Stokes equation for a compressible liquid. We find that the squeeze-out is characterized by the parameter g0 ~ P0/(rho c^2), where P0 is the average perpendicular (squeezing) pressure, rho the liquid (3D) density and c the longitudinal sound velocity in the monolayer film. When g0 << 1 the result of the earlier incompressible treatment is recovered. Numerical results for the squeeze-out time, and for the time-dependence of the radius of the squeezed-out region, indicate that compressibility effects may be non-negligible both in time and in space. In space, they dominate at the edge of the squeeze-out region. In time, they are strongest right at the onset of the squeeze-out process, and just before its completion.Comment: revtex4, 6 pages, 4 figures. Published on PRB on December 31, 200

The role of specific pancreatic antibodies in the differential diagnosis of complete clinical and laboratory remission of type 1 diabetes mellitus and MODY in children

BACKGROUND: T1D is characterized by autoimmune destruction of pancreatic β-cells, which develops due to genetic and environmental risk factors. Shortly after initiating the treatment with insulin, 80% of children with T1D may require smaller doses of insulin and develop clinical and laboratory remission of the disease so called «honeymoon». The issue of whether there is a need of differential diagnosis between autoimmune DM and non-immune forms of DM raises in cases of preclinical diagnosis of T1D and laboratory remission for more than 6 months.AIM: To study the clinical, immunological, genetic characteristics of T1D remission phase and MODY in children, to determine the diagnostic criteria for T1D and MODY in children.MATERIALS AND METHODS: A single-centre, cross sectional noncontrolled comparative study of two independent cohorts. Data of 150 children examined in the Endocrinology Research Center (January 2016–June 2021). First cohort included patients with complete clinical and laboratory remission of T1D (n=36), second cohort included patients with MODY, confirmed by genetic study (n=114).RESULTS: The median age of diabetes manifestation was significantly higher in patients with T1D — 11.25 years [8.33; 13.78] than in patients with MODY — 7.5 years [4.6; 12.2] (p=0.004). In patients with T1D remission the level of glycated hemoglobin was 6.0% [5.6; 6.4], in group with MODY — 6.5% [6.2; 6.7] (p&lt;0.001). Patients with monogenic diabetes had impaired fasting glucose — 6.27 mmol/l [5.38; 6.72], while patients with remission phase had normoglycemia — 5.12 mmol/l [4.17; 5.87]. The oral glucose tolerance test was perform to all patients, two-hour glucose level did not significantly differ in two groups (p=0.08). A strong family history of diabetes in patients with MODY registered more often (93% vs. 66.7%). A positive autoantibody titer detected more often in patients with remission of T1D (77.8%) than in patients with MODY (11.4%). In addition, no more than 1 type of autoantibodies was detected in patients with MODY.CONCLUSION: Antibodies ZnT8 and IA2 showed the greatest significance for the differential diagnosis of T1D and MODY in cases with long absents of insulin requirement in children with diabetes mellitus. Genetic test is recommended in seronegative cases. If only one type of AT is detected, specialist should decide on the need to do diagnostic genetic test based on a comprehensive analysis of the patient’s clinic characteristics, including family history, manifestation and blood glucose levels

The use of Flash glucose monitoring in children with type 1 diabetes mellitus in real clinical practice

BACKGROUND: In 2018, a Frestyle Libre flash glucose monitoring system (FGM) appeared in Russia and became a potential alternative to the traditional CGM. Studies carried out to date have shown the advantages of FGM over SMBG, but only a few of them relate to real clinical practice, especially in children with type 1 diabetes.OBJECTIVE: To evaluate the efficacy of FGM in children with T1DM in relation to glycemic control indicators, the occurrence of severe hypoglycemia and diabetic ketoacidosis, as well as the satisfaction of patients and their parents with the use of FGM.MATERIALS AND METHODS: Single-center, prospective, observational cohort study. Children 4–18 years old with T1DM and HbA1c level less than 10.0% were invited to participate in the study on intensified insulin therapy (by MDI or CSII). The duration of the patient’s participation in the study was 6 months. At baseline and every 3 months thereafter, face-to-face consultations were conducted with an assessment of the general condition, HbA1c study, an assessment of glycemic indicators, progress in relation to glycemic control targets and correction of the therapy. A total of 228 patients (110 boys and 118 girls) who met the inclusion criteria were included in the study. The median age was 11.2 (8.6–14.7) years, the duration of type 1 diabetes was 3.8 (2–7.1), 136 patients received insulin therapy by CSII for 1.3 (0.8–2.6) years.RESULTS: In the general group of patients, 3 and 6 months after the start of FGM use, the HbA1c values decreased statistically significantly by 0.2%. In addition, the number of children with HbA1c &lt;7.5% increased by 6.1 and 4.9% at 3 and 6 months, respectively, but these changes were not statistically significant. The number of cases of DKA when using FGM decreased by 74%, and the number of cases of severe hypoglycemia by 83%, thus the number of episodes decreased by 4 and 6 times, respectively. Patients and / or their parents rated the ease of use and their experience with FGM on a scale from 0 (strongly agree) to 4 (strongly disagree). The majority of children and parents positively (0 or 1) assessed the convenience of installing and wearing the sensor (72.7–98.2%) using the FGM system in general (75.0–96.4%) and in comparison with the SMBG glucometer (92.3–98.2%).CONCLUSION: The installation and use of FGM is convenient and comfortable for the vast majority of children and parents, while compared to SMBG, the use of FGM is more convenient and simpler, and glucose measurement is much faster and less painful

EMF1 and PRC2 Cooperate to Repress Key Regulators of Arabidopsis Development

EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism

Feсal microbiota transplantation in the format of complex therapy in obesive siblings: clinical case

Obesity and associated metabolic diseases are often accompanied by changes in the gut microbiota leading to metagenome gene diversity decrease. Fecal microbiota transplantation (FMT) is one of the most effective methods for correcting the  intestinal microflora. FMT obtained from healthy donors has been proven to be an effective treatment of infections caused by Clostridium difficile. The use of FMT for correction of metabolic disorders is promising, however, data on its application is limited and has contradictory results. In our work, two patients (siblings) presented with obesity grade II and various types of diabetes mellitus (DM): the older brother (44 years old) with diabetes mellitus type 2 (DM 2), a younger brother (39 years old) with diabetes mellitus type 1 (DM 1). Both patients underwent FMT as part of complex antidiabetic therapy. During the course of treatment, a decrease in body weight was noted in both patients (4–5 kg for the first month of observation, then -1–2 kg per month). One year after FMT, a patient with type 2 diabetes showed a decrease in the severity of insulin resistance (IR), measured by the hyperinsulinemic euglycemic clamp test (initial M-index 2.42 mg/kg*min, after 1 year — 3.83 mg/kg* min) as well as the maintenance of satisfactory carbohydrate metabolism compensation against the diminishing the hypoglycemic therapy. In a patient with DM 1, no significant dynamics of carbohydrate exchange indices, including detected glycated hemoglobin (HbA1c), insulin dose and IR were during the observation period. Metagenomic sequencing of stool samples (n = 20) collected from both patients before and within 1 year after FMT showed no significant changes in the taxonomic profile of the microbiota at the level of microbial families. Metabolomic analysis of the composition of feces showed no directed changes in the composition of metabolites after the FMT procedure, the nature of changes within the samples from each patient during the entire study period was random. Thus, FMT had no effect on the course of DM1, but served as a starting point for weight loss and improvement glucose profile in DM2. However, convincing data confirming a causal correlation between FMT and improvement in the course of T2DM have not been obtained

E17K substitution in AKT1 in prostate cancer

Background:The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1.Methods:A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours.Results:We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer.Conclusion:The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumo

Clinical, hormonal and molecular-genetic characteristics of monogenic diabetes mellitus associated with the mutations in the <i>INS</i> gene

Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “­Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation