Nmrk2 gene is upregulated in dilated cardiomyopathy and required for cardiac function and nad levels during aging

Dilated cardiomyopathy (DCM) is a disease of multifactorial etiologies, the risk of which is increased by male sex and age. There are few therapeutic options for patients with DCM who would benefit from identification of common targetable pathways. We used bioinformatics to identify the Nmrk2 gene involved in nicotinamide adenine dinucleotde (NAD) coenzyme biosynthesis as activated in different mouse models and in hearts of human patients with DCM while the Nampt gene controlling a parallel pathway is repressed. A short NMRK2 protein isoform is also known as muscle integrin binding protein (MIBP) binding the α7β1 integrin complex. We investigated the cardiac phenotype of Nmrk2-KO mice to establish its role in cardiac remodeling and function. Young Nmrk2-KO mice developed an eccentric type of cardiac hypertrophy in response to pressure overload rather than the concentric hypertrophy observed in controls. Nmrk2-KO mice developed a progressive DCM-like phenotype with aging, associating eccentric remodeling of the left ventricle and a decline in ejection fraction and showed a reduction in myocardial NAD levels at 24 months. In agreement with involvement of NMRK2 in integrin signaling, we observed a defect in laminin deposition in the basal lamina of cardiomyocytes leading to increased fibrosis at middle age. The α7 integrin was repressed at both transcript and protein level at 24 months. Nmrk2 gene is required to preserve cardiac structure and function, and becomes an important component of the NAD biosynthetic pathways during aging. Molecular characterization of compounds modulating this pathway may have therapeutic potential

Hidden attractors in fundamental problems and engineering models

Recently a concept of self-excited and hidden attractors was suggested: an attractor is called a self-excited attractor if its basin of attraction overlaps with neighborhood of an equilibrium, otherwise it is called a hidden attractor. For example, hidden attractors are attractors in systems with no equilibria or with only one stable equilibrium (a special case of multistability and coexistence of attractors). While coexisting self-excited attractors can be found using the standard computational procedure, there is no standard way of predicting the existence or coexistence of hidden attractors in a system. In this plenary survey lecture the concept of self-excited and hidden attractors is discussed, and various corresponding examples of self-excited and hidden attractors are considered

Skeletal Muscle-Specific Ablation of γcyto-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γcyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γcyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γcyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γcyto-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests γcyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a γcyto-actin-utrophin interaction

Immunoassay for Natamycin Trace Screening: Bread, Wine and Other Edibles Analysis

The antifungal drug natamycin (NAT) is widely used in medicine and in the food industry as preservative E235 for a wide variety of foods. The risk of the development of resistance to NAT and its spread in relation to other polyene antibiotics is fraught with the emergence of incurable infections. This work is devoted to the development of an immunoassay to investigate the prevalence of NAT use for food preservation. Two immunogen designs based on tetanus toxoid, conjugated to NAT through different sites of hapten molecules, were compared in antibody generation. Assay formats using heterologous coating antigens were superior for both antibodies. The ELISA variant demonstrated the highest sensitivity (IC50 = 0.12 ng/mL), and a limit of detection of 0.02 ng/mL was selected for NAT determination. The optimized extraction procedure provided a recovery rate of 72–106% for various food matrixes with variations below 12%. Cyclodextrins, as well as NAT–cyclodextrin complex formulations, showed no interference with the quantification of NAT. One hundred and six food product brands, including baked goods, wines, beers, drinks, sauces, and yogurts, were tested to assess the prevalence of the undeclared use of NAT as a preservative. The screening examination revealed three positive yogurts with an undeclared NAT incorporation of 1.1–9.3 mg/kg

Epidemiology and clinic of Oholera 1970 in the Astrakhan region

The prognosis for cholera in the world remains unfavorable. There is a high incidence of cholera in the countries of Africa and the Caribbean, which does not exclude the possibility of importation of the infection to Russia and the recurrence of the cholera epidemic.The aim of the study was to establish the clinical and epidemiological characteristics of cholera Eltor in the Astrakhan region in 1970.A retrospective study the information sources were the medical history and results of laboratory examination of 1 246 patients with cholera in 1970 treated in the Regional infectious hospital and redeveloped during the epidemic hospitals of Astrakhan.The duration of a cholera epidemic on the territory of Astrakhan region, with mass cases of the disease, accounted for 55.0 ± 15.8 days. The infection rate of cholera of inhabitants of Astrakhan were lower compared to living in rural areas. Water infected with Cholera Vibrio was the main factor of pathogen transmission. The predominant clinical forms of cholera were mild and moderate (72%), the proportion of severe and algid forms was 28% of the total number of patients.The maximum development of cholera epidemic reached in the delta areas of Astrakhan region. The factor of the pathogen transmission was water, which contributed to the rapid increase in the number of patients. With a total number of severe and algid forms of cholera 350 (28%), in 35 (10%) patients, the disease was fatal

Mycotoxicological monitoring. Part 3. Feedstuffs from raw grain processing

The paper presents the results of mycotoxicological testing of the production batches of sunflower cake and meal, feedstuffs of soybean and wheat bran processing received from domestic processing establishments and livestock farms from 2009 to 2019. Detection and measurement of the content of fusariotoxins, including T-2 toxin, diacetoxyscirpenol, deoxynivalenol, zearalenone and fumonisins of B group, as well as alternariol, ochratoxin A, citrinin, aflatoxin B1, sterigmatocystin, cyclopiazonic acid, mycophenolic acid, ergot alkaloids and emodin was carried out by a competitive ELISA in accordance with certified procedure. The summarized results demonstrate the predominant role of alternariol in the contamination of sunflower cake and meal, as well as the frequent occurrence of T-2 toxin, ochratoxin A, citrinin, cyclopiazonic acid, sterigmatocystin, mycophenolic acid and emodin. For the main contaminants, a shift in the medians and 90% percentile towards the lower values of the average and maximum contents was observed, which indicates the possibility of their accumulation beyond the typical range. The summary and results of mycotoxicological study of wheat bran and feedstuffs of soybean processing for a complete list of 14 parameters are presented in this paper for the first time. It was found that the range of mycotoxins that can contaminate soybean meal, cake and full-fat soybean is quite wide, which is consistent with the results of the study of soybean seed mycobiota composition. It was demonstrated that soybean meal can accumulate high concentrations of mycophenolic acid – up to 1,255 μg/kg. As for the wheat bran batches, cases of contamination with diacetoxyscirpenol and the frequent occurrence of T-2 toxin, emodin and ergot alkaloids were detected. The initial monitoring data, systematized and summarized in this paper, are presented in electronic form in the section “Additional materials”. The prospects of testing of feedstuffs from processing other oilseeds, as well as from wheat and corn grain processing are discussed

Mycotoxicological monitoring. Part 1. Complete mixed feed for pigs and poultry (2009–2018)

Results of the ten-year annual mycotoxicological testing of complete mixed feeds for pigs and poultry submitted by holdings and processing establishments located in the Northwestern, Central, Southern, Volga and Ural Federal Districts are presented. Competitive ELISA tests showed that the occurrence of T-2 toxin, deoxynivalenol, zearalenon, fumonisines B, alternariol, ochratoxin A, citrinin, mycophenolic acid, ergoalkoloids and emodin was about 5% and quantities thereof varied within one or three orders; quantities of T-2 toxin, deoxynivalenol, zearalenon, fumonisines, and ochratoxin A might exceed maximum admissible levels for feed grains. Diacetoxyscirpenol, aflatoxin В1, sterigmatocystin and cyclopiazonic acid belonged to group of rare contaminants. Level of feed contamination with T-2 toxin and emodin was found to be consistently high during the said period; in some of the years occurrence of deoxynivalenol, fumonisines as well as ochra­toxin A, citrinin, mycophenolic acid and ergoalkoloids increased. In 2016–2018, mixed feed contamination with alternariol increased whereas contamination with fumonizin steadily decreased and level of zearalenon occurrence remained consistently low. Evidence for a wide occurrence of emodin known as “diarrheic factor” as well as for sporadic increase in mixed feed contamination with alternariol, citrinin, mycophenolic acid, mycotoxins having the highly dangerous toxic impact and long-term adverse effects, was detected for the first time. These data confirmed the need for their inclusion into the regulated group of substances significant for public health. General features of pig and poultry feed contamination as well as usefulness of regional surveys for intoxication risk prediction are described. Special attention is paid to the importance of the projects for creation of common information resources that could become a unique scientific basis for innovations in feed poisoning prevention. Original monitoring data systematized and summarized in the paper are given in electronic format in section Additional materials