DRUG RELATED NITROSOGENESIS, PHOTOCARCINOGENESIS AND ONCOPHARMACOGENESIS OF NODULAR MELANOMA: A CASE RELATED ANALYSIS CONCERNING THE POLYCONTAMINATION OF THE POLYMEDICATION WITH VALSARTAN/HYDROCHLOROTHIAZIDE AND BISOPROLOL.

Despite the fact that the pathogenesis of cutaneous melanoma is shrouded in mystery, factors that have been neglected or unnoticed until now have come to the attention in recent years, and in all likelihood, they could also be pivotal. These factors, known as nitrosamines or NDSRIs, are characterized by high carcinogenic and mutagenic potency, and some of them have demonstrated these properties to human DNA as well. Unfortunately, these ingredients also turn up as contaminants in about 300 of the most widely distributed drugs worldwide. According to the most recent literature, some of these ingredients are also identified as potent photocarcinogens, as well as human carcinogens. The intake of these carcinogens in the context of polycontamination of polymedication, has been associated for years with the occurrence of melanomas. The need for cataloguing of nitrosamines , as well as their accurate labelling on drug packaging, would help to classify them even more accurately as carcinogens affecting human DNA. We present once again a patient , who developed nodular melanoma within the context of the intake of 3 potentially nitrosamine/ NDSRIs contaminated antihypertensive drugs (valsartan/ Hydrochlorothiazide/ bisoprolol). Pathogenetic aspects concerning drug-induced nitrosogenesis, photocarcinogenesis and oncopharmacogenesis of skin cancer are discussed. Nitrosogenesis' of Cancer as concept in the medical literature has been known for decades, but in relation to other forms of human cancer. Exogenously mediated drug-mediated nitrosogenesis is a logically conditioned and newly defined concept whose significance with respect to the clinical manifestation of skin cancer is only beginning to grow.

Observation of Collider Muon Neutrinos with the SND@LHC Experiment.

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at sqrt[s]=13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb^{-1}. The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2<η<8.4, inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν_{µ} interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν_{µ} signal.

Age-related changes in cationic compositions of human cranial base bone apatite measured by X-ray energy dispersive spectroscopy (EDS) coupled with scanning electron microscope (SEM).

One of the most common scientific methods to study the chemical composition of bone matter is energy-dispersive X-ray spectroscopy (EDS). However, interpretation of the data obtained can be quite complicated and require a thorough understanding of bone structure. This is especially important when evaluating subtle changes of chemical composition, including the age-related ones. The aim of current study is to create a method of processing the obtained data that can be utilized in clinical medicine and use it to evaluate the age evolution of bone chemical composition. To achieve this goal, an elemental composition of 62 samples of cadaver compact bone, taken from the skull base (age: Me = 57.5; 21/91(min/max); Q1 = 39.5, Q3 = 73.75), was studied with EDS. We used the original method to estimate the amount of Mg2+ cations. We detected and confirmed an increase of Mg2+ cation formula amount in the bone apatite, which characterizes age-related resorption rate. Analysis of cation estimated ratio in a normative bone hydroxylapatite showed an increase of Mg2+ amount (R = 0.43, p = 0.0005). Also, Ca weight fraction was shown to decrease with age (R = - 0.43, p = 0.0005), which in turn confirmed the age-dependent bone decalcification. In addition, electron probe microanalysis (EPMA) and X-ray diffraction analysis (XRD) were performed. EDS data confirmed the EPMA results (R = 0.76, p = 0.001). In conclusion, the proposed method can be used in forensic medicine and provide additional data to the known trends of decalcification and change of density and crystallinity of mineral bone matter.

Extracellular pH and high concentration of potassium regulate the primary necrosis in the yeast Saccharomyces cerevisiae.

Extracellular pH and concentration of K+ as well as their gradient across the plasma membrane have a significant impact on the physiology of the yeast cell, but their role in cell death has not been thoroughly investigated. Here we observed that increasing extracellular pH, as well as supplementing with K+ ions had a mitigating effect on cell death in yeast occurring under several conditions. The first is sugar induced cell death (SICD), and the second is death caused by several specific gene deletions, which have been recently identified in a systematic screen. It was shown that in both cases, primary necrosis is suppressed at neutral pH. SICD was also inhibited by the protonophore dinitrophenol (DNP) and 150 mM extracellular K+, with the latter condition also benefiting survival of cell dying due to gene mutations. In the case of SICD, these effects could not be mitigated by perturbing known pH-dependent signaling pathways, and thus are likely to be realized via direct effects on the plasma membrane potential. Thus, (a)-we show that stabilization of external pH at a neutral level can suppress different types of primary necrosis, and (b)-we suggest that changes to the cellular membrane potential can play a central role in yeast cell death caused by different factors.

OPERA tau neutrino charged current interactions.

The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâ†’vτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.

Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Classification and monomer-by-monomer annotation dataset of suprachromosomal family 1 alpha satellite higher-order repeats in hg38 human genome assembly.

In the latest hg38 human genome assembly, centromeric gaps has been filled in by alpha satellite (AS) reference models (RMs) which are statistical representations of homogeneous higher-order repeat (HOR) arrays that make up the bulk of the centromeric regions. We analyzed these models to compose an atlas of human AS HORs where each monomer of a HOR was represented by a number of its polymorphic sequence variants. We combined these data and HMMER sequence analysis platform to annotate AS HORs in the assembly. This led to discovery of a new type of low copy number highly divergent HORs which were not represented by RMs. These were included in the dataset. The annotation can be viewed as UCSC Genome Browser custom track (the HOR-track) and used together with our previous annotation of AS suprachromosomal families (SFs) in the same assembly, where each AS monomer can be viewed in its genomic context together with its classification into one of the 5 major SFs (the SF-track). To catalog the diversity of AS HORs in the human genome we introduced a new naming system. Each HOR received a name which showed its SF, chromosomal location and index number. Here we present the first installment of the HOR-track covering only the 17 HORs that belong to SF1 which forms live functional centromeres in chromosomes 1, 3, 5, 6, 7, 10, 12, 16 and 19 and also a large number of minor dead HOR domains, both homogeneous and divergent. Monomer-by-monomer HOR annotation used for this dataset as opposed to annotation of whole HOR repeats provides for mapping and quantification of various structural variants of AS HORs which can be used to collect data on inter-individual polymorphism of AS.

Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam.

The OPERA experiment was designed to study ν_{µ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.

Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH. METHODS: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset. RESULTS: Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001]. CONCLUSIONS: Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.

Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To determine the association of differential leukocyte counts on admission with efficacy and safety outcomes in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: Consecutive patients with AIS receiving IVT were evaluated at two stroke centers. Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were determined during the initial 12 h of admission. Efficacy outcomes were favorable functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality. RESULTS: Among 657 IVT-treated patients with AIS, the mean age was 64 ± 14 years, 50% were female and median National Institutes of Health Stroke Scale score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte counts and NLR counts were observed in patients with 3-month FFO and FI, whereas higher counts were observed in patients who died at 3 months. The best discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%, specificity 63.1%) and leukocyte count <8100/µL (sensitivity 57.5%, specificity 55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/µL demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014) and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001). Combined neutrophil (<6800/µL) and leukocyte (<8100/µL) counts demonstrated a strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction = 0.012). CONCLUSIONS: Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

[Biomechanical Analysis of Posture and Movement Coordination in Standing Human During Trunk Bending in the Sagittal Plane].

In most motor acts to achieve a behavioral goal requires coordination of posture and movement. In this paper, such coordination is studied by the example of human trunk bending in. the sagittal plane. Such movements are difficult to study because both components of this motor act (main - bending per se, and "accessory" - posture aimed on equilibrium. maintenance) involve massive movements of body segments, which complicates separation of these components. Their separation is based on the modem ideas about the special features of the posture component as compared with the main component. It is shown that the main and posture components correspond to the move- ments along eigenvectors of the dynamic equation. These movements are unique because they demonstrate at the same time "kinematic" as well as "dynamic" synergies. They were called there- fore "natural synergies". The coordination of natural synergies is investigated in human during standing on the wide and narrow supports. It is shown that the experimentally observed coordination is close to optimal, providing minimum movement of the center of pressure. This ensures the center of pressure Position keeping inside the support area that is necessary for equilibrium maintenance.

Wild type huntingtin toxicity in yeast: Implications for the role of amyloid cross-seeding in polyQ diseases.

Proteins with expanded polyglutamine (polyQ) regions are prone to form amyloids, which can cause diseases in humans and toxicity in yeast. Recently, we showed that in yeast non-toxic amyloids of Q-rich proteins can induce aggregation and toxicity of wild type huntingtin (Htt) with a short non-pathogenic polyglutamine tract. Similarly to mutant Htt with an elongated N-terminal polyQ sequence, toxicity of its wild type counterpart was mediated by induced aggregation of the essential Sup35 protein, which contains a Q-rich region. Notably, polymerization of Sup35 was not caused by the initial benign amyloids and, therefore, aggregates of wild type Htt acted as intermediaries in seeding Sup35 polymerization. This exemplifies a protein polymerization cascade which can generate a network of interdependent polymers. Here we discuss cross-seeded protein polymerization as a possible mechanism underlying known interrelations between different polyQ diseases. We hypothesize that similar mechanisms may enable proteins, which possess expanded Q-rich tracts but are not associated with diseases, to promote the development of polyQ diseases.

Diagnostic Accuracy of Transcranial Doppler for Brain Death Confirmation: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Transcranial Doppler is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. Transcranial Doppler confirms brain death by evaluating cerebral circulatory arrest. Case series studies have generally reported good correlations between transcranial Doppler confirmation of cerebral circulatory arrest and clinical confirmation of brain death. The purpose of this study is to evaluate the utility of transcranial Doppler as an ancillary test in brain death confirmation. MATERIALS AND METHODS: We conducted a systematic review of the literature and a diagnostic test accuracy meta-analysis to compare the sensitivity and specificity of transcranial Doppler confirmation of cerebral circulatory arrest, by using clinical confirmation of brain death as the criterion standard. RESULTS: We identified 22 eligible studies (1671 patients total), dating from 1987 to 2014. Pooled sensitivity and specificity estimates from 12 study protocols that reported data for the calculation of both values were 0.90 (95% CI, 0.87-0.92) and 0.98 (95% CI, 0.96-0.99), respectively. Between-study differences in the diagnostic performance of transcranial Doppler were found for both sensitivity (I(2) = 76%; P < .001) and specificity (I(2) = 74.3%; P < .001). The threshold effect was not significant (Spearman r = -0.173; P = .612). The area under the curve with the corresponding standard error (SE) was 0.964 ± 0.018, while index Q test ± SE was estimated at 0.910 ± 0.028. CONCLUSIONS: The results of this meta-analysis suggest that transcranial Doppler is a highly accurate ancillary test for brain death confirmation. However, transcranial Doppler evaluates cerebral circulatory arrest rather than brain stem function, and this limitation needs to be taken into account when interpreting the results of this meta-analysis.

[Mitochondrial DNA Polymorphism in Different Populations of Spangled Orloff Chickens].

For the first time, the genetic diversity of the Spangled Orloff chickens was studied by analyzing the polymorphism of the hypervariable region in the D-loop of mitochondrial DNA (mtDNA). Samples for the analysis were collected at the farms ofthe All-Russia Poultry Research and Technological Institute (VNITIP), the All-Russia Institute of Farm Animal Genetics and Breeding (VNIIGRZh), and the Moscow Zoo. The D-loop partial sequences (between nucleotide positions 57 and 523) were determined according to the reference sequence of Gallus gallus spadiceus mtDNA, NC_007235 in 39 individuals obtained from these populations (GenBank Accession Nos. KM391754-KM391792). In the analyzed mtDNA fragment, a total of 20 polymorphic sites localized between positions 167 and 368, as well as at position 446, were described in Spangled Orloff chickens. One polymorphic site at position 221 (haplogroup E, haplotype ORL-2) was unique. All of the identified nucleotide changes were transition-type substitutions. Overall, based on the analysis of poly- morphic sites in the hypervariable fragment of the D-loop of Spangled Orloff chicken mtDNA, we found seven haplotypes belonging to four haplogroups (A, B, C, and E). Haplogroup E (haplotypes ORL-1, ORL-2, and ORL-3) was present in the majority of the studied individual, with the frequencies of 0.77 in the total sample and 0.47 in the VNIIGRZh farm population. Haplogroups A (haplotypes ORL-4 and ORL-7), B (ORL-6), and C (ORL-5) were found only in samples from the VNIIGRZh farm. The studied mtDNA region revealed a lower level of polymorphism in the VNITIP and Moscow Zoo populations, which only had the ORL-1 and ORL-3 haplotypes belonging to Haplogroup E, respectively. Our data suggested that the studied Spangled Orloff chicken populations differed in the composition and frequencies of mtDNA haplogroups and haplotypes.

Annotation of suprachromosomal families reveals uncommon types of alpha satellite organization in pericentromeric regions of hg38 human genome assembly.

Centromeric alpha satellite (AS) is composed of highly identical higher-order DNA repetitive sequences, which make the standard assembly process impossible. Because of this the AS repeats were severely underrepresented in previous versions of the human genome assembly showing large centromeric gaps. The latest hg38 assembly (GCA_000001405.15) employed a novel method of approximate representation of these sequences using AS reference models to fill the gaps. Therefore, a lot more of assembled AS became available for genomic analysis. We used the PERCON program previously described by us to annotate various suprachromosomal families (SFs) of AS in the hg38 assembly and presented the results of our primary analysis as an easy-to-read track for the UCSC Genome Browser. The monomeric classes, characteristic of the five known SFs, were color-coded, which allowed quick visual assessment of AS composition in whole multi-megabase centromeres down to each individual AS monomer. Such comprehensive annotation of AS in the human genome assembly was performed for the first time. It showed the expected prevalence of the known major types of AS organization characteristic of the five established SFs. Also, some less common types of AS arrays were identified, such as pure R2 domains in SF5, apparent J/R and D/R mixes in SF1 and SF2, and several different SF4 higher-order repeats among reference models and in regular contigs. No new SFs or large unclassed AS domains were discovered. The dataset reveals the architecture of human centromeres and allows classification of AS sequence reads by alignment to the annotated hg38 assembly. The data were deposited here: http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgt.customText=https://dl.dropboxusercontent.com/u/22994534/AS-tracks/human-GRC-hg38-M1SFs.bed.bz2.

[Prevalence of some modified cardiovascular risk factors among young students].

AIM: To estimate the prevalence of some modified cardiovascular risk factors (RFs) among the students of two Moscow higher education institutions to further test the technology of individual medical prevention counseling. SUBJECTS AND METHODS: A questionnaire survey was conducted among 1912 first-year students (boys and girls, mean age 17.7 years) from 2 Moscow higher education institutions to reveal physical activity levels, smoking status, alcohol abuse, and food addictions. RESULTS: Almost one third of the students (mainly girls) lead a sedentary lifestyle. The mean age at onset of smoking is 14.8 years. At the moment, the smoking students are 22% (28% of boys and 18% of girls). 12.2% of the respondents have moderate and high nicotine dependence. Most smokers demonstrate low motivation to give up smoking. The mean age for alcohol consumption is 15.8 years. 60% of the students use alcohol. There are no great differences in the drinking of alcoholic beverages between the girls and boys. 18% of the study sample students eat irregularly. Nearly 50% of the students add salt to cooked foods. 17% of the students eat too much sugar; more than 50% take sugar- and fat-laden foods. 54% of the students use vegetables and fruits insufficiently. CONCLUSION: Among all the modified cardiovascular RFs, alcohol use and irrational nutrition are most common among the students. Smoking and low physical activity are also relevant problems although these indicators among the students of Moscow are lower than among those in other regions of the Russian Federation. The found patterns call for the increased attention of the administrations of higher education institutions.

Secondary structure-stretched forms of long intron RNA products from the view point of initiation of chromosome homologs somatic pairing.

In different types of chromosome pairing (meiotic, somatic, and sister chromatids pairing) initiation stages are less elucidated. In somatic homolog pairing initiation, the long intron RNA products interference may play the essential role. The strongest somatic pairing in Drosophila melanogaster 28B1-B2 locus and its enrichment by long bi-directional transcripts prone us to analyze the pre-mRNA secondary structures. The comparison of sense (pre-mRNA) and antisense (lncRNA) portions corresponding to the lengthy introns for some others' genes loci reveals the significant correlation of stretched folding form lengths with the homologue pairing percentage. Also for 28B1-B2 locus, the most significant homologue pairing is justified by the plurality of sense and antisense RNA variants for lengthy introns. The stretched forms of long intron products with multiple stem-loop clusters widely presented for sense and antisense strands may interact by multiple loops during transcription being connected to different chromosomes and hypothetically may serve for the pairing initiation. Stretched rod-like or V-shape-like are dominating forms for the whole intron RNA products or their central portions while predominantly star-like for others intron fragments.