Genetic Structure, Differentiation and Originality of Pinus sylvestris L. Populations in the East of the East European Plain

In order to carry out activities aimed at conservation and rational use of forest resources; it is necessary to study the main forest-forming plant species in detail. Scots pine (Pinus sylvestris L., Pinaceae) is mainly found in the boreal forests of Eurasia and is not so often encountered in the east of the East European Plain. The aim of the study was to study the genetic diversity, structure and differentiation of Scots pine populations in the east of the East European Plain. We studied ten populations of P. sylvestris using the Inter Simple Sequence Repeats (ISSR)-based DNA polymorphism detection method. Natural populations are demonstrated by relatively high rates of genetic diversity (He = 0.167; ne = 1.279; I = 0.253). At the same time, there is a tendency for a decrease in the genetic diversity of the studied populations of P. sylvestris from west to east. Analysis of the genetic structure shows that the studied populations are highly differentiated (GST = 0.439), the intrapopulation component accounts for about 56% of the genetic diversity. Using various algorithms for determining the spatial genetic structure, it is found that the studied populations form two groups of populations in accordance with geographic location. With the help of a genetic originality coefficient, populations with specific and typical gene pools are identified. They are recommended as sources of genetic diversity and reserves for the conservation of genetic resources of the species

Clarithromycin for community-acquired pneumonia in adults: focus on anti-inflammatory properties

Aim. To evaluate clinical efficacy, anti-inflammatory and immunomodulatory activity of clarithromycin in adults with severe community-acquired pneumonia (sCAP). Materials and methods. A prospective observational study recruited adult hospitalized patients with verified sCAP. Clarithromycin was prescribed as a component of combination antibiotic therapy (ABT) with a -lactam antibiotic (AB). The choice of -lactam AB was carried out by the attending physician in accordance with national clinical guidelines and routine practice of the medical institution. Along with assessment clinical efficacy, the dynamics of inflammatory markers in blood serum was recorded: C-reactive protein, procalcitonin (PCT), tumor necrosis factor , interleukins 1-beta (IL-1) and interleukin 6 (IL-6). The total duration of ABT was 714 days. Results. Altogether 20 patients (13 males, 7 females) aged from 18 to 84 years old were enrolled. As a result of the use of combined ABT with -lactam AB and clarithromycin, a significant decrease in the level of C-reactive protein was noted by the 35th day of therapy (from 74.6 to 14.1 mg/l). An increase in serum PCT was observed in half of the patients; during treatment, the level of PCT significantly decreased. Similar dynamics was detected for IL-6 its content in the blood serum decreased by the time of the end of ABT by 6.8 times compared with the baseline. A decrease in the level of tumor necrosis factor to the reference value was observed in most patients already in the early stages by 35 days of ABT. The majority of patients showed positive dynamics of clinical signs and symptoms with resolution of respiratory failure and other complications of sCAP. In almost half of the patients, the criteria for clinical stability were achieved in the early stages, which made it possible to switch to oral ABT. Conclusion. The results of the study are consistent with literature data indicating a rapid decrease in inflammatory markers when clarithromycin is administered to patients with sCAP. Its results can be a starting point for comparative randomized trials assessing both clinical outcomes and immunological parameters when using different classes of antibiotics for the treatment of sCAP

Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

Tetrahymena ATP synthase, an evolutionarily divergent protein complex, has a very unusual structure and protein composition including a unique Fo subunit a and at least 13 proteins with no orthologs outside of the ciliate lineage

Chemical composition and nutritive value of the feed used in dairy cow feeding in the Republic of Moldova

Information on nutritive value of locally available feed ingredients is scarce, therefore the study conducted in the laboratory of the Department “General Animal Husbandry” of the State Agrarian University of Moldova, was aimed at determining the chemical composition and nutrient content of various feeds and fodder species commonly used in the diets of dairy cow sraised in the University farm. Fodder samples, proceeding from different agricultural and ecological zones of the Republic of Moldova, were analyzed for their content of total moisture, dry matter, crude protein, fat, fiber, ash and NFE quantity and the data were compared with those available in the specialized literature. The comparative analysis showed differences in the content of a number of nutrients and large fluctuations were observed in terms of the level of oat nutrition units, energetic nutrition units and metabolizable energy contentin comparison with the data contained in normative references and used in the calculation of the nutritional value of feed and diets

The genotype‐phenotype landscape of an allosteric protein

Abstract Allostery is a fundamental biophysical mechanism that underlies cellular sensing, signaling, and metabolism. Yet a quantitative understanding of allosteric genotype‐phenotype relationships remains elusive. Here, we report the large‐scale measurement of the genotype‐phenotype landscape for an allosteric protein: the lac repressor from Escherichia coli, LacI. Using a method that combines long‐read and short‐read DNA sequencing, we quantitatively measure the dose‐response curves for nearly 105 variants of the LacI genetic sensor. The resulting data provide a quantitative map of the effect of amino acid substitutions on LacI allostery and reveal systematic sequence‐structure‐function relationships. We find that in many cases, allosteric phenotypes can be quantitatively predicted with additive or neural‐network models, but unpredictable changes also occur. For example, we were surprised to discover a new band‐stop phenotype that challenges conventional models of allostery and that emerges from combinations of nearly silent amino acid substitutions

Epidemiology of Hereditary Diseases in the Karachay-Cherkess Republic

Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in different modern open populations is important. The study presents the results of a genetic epidemiological study of hereditary diseases (HDs) in the population of the Karachay-Cherkess Republic (KChR). Clinical screening of a population of 410,367 people for the identification of HDs was conducted. The population surveyed is represented by five major ethnic groups—Karachays, Russians, Circassians, Abazins, Nogais. The study of the populations was carried out in accordance with the proprietary protocol of genetic epidemiological examination designed to identify >3500 HDs easily diagnosed during clinical examination by qualified specialists specializing in the HDs. The protocol consists of the population genetic and medical genetic sections and is intended for comprehensive population analysis based on the data on different genetic systems, including the genes of HDs, DNA polymorphisms, demographic data collected during hospital-based survey. 8950 families (with 10,125 patients) with presumably the HDs were initially identified as a result of the survey and data collection through various sources of registration (from 1156 medical workers from 163 medical institutions). A diagnosis of hereditary pathology was established in 1849 patients (from 1295 families). Two hundred and thirty nosological forms were revealed (in 1857 patients from 1295 families). The total prevalence of HDs was 1:221. Differences between populations and ethnic groups were identified: 1:350 in Russians, 1:195 in Karachays, 1:199 in Circassians, 1:218 in Abazins, 1:135 in Nogais. Frequent diseases were determined, the presence of marked genetic heterogeneity was identified during the confirmatory DNA diagnosis. To explain the reasons for the differentiation of populations by load of HD, a correlation analysis was carried out between the FST (random inbreeding) in populations and HDs load values. This analysis showed genetic drift is probably one of the leading factors determining the differentiation of KChR populations by HDs load. For the first time, the size of the load and spectrum of HDs in the populations of the KChR are determined. We have demonstrated genetic drift to be one of the main factors of the population dynamics in studied population. A significant genetic heterogeneity of HDs, both allelic and locus, was revealed in KChR

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk