CRAMER: a lightweight, highly customizable web-based genome browser supporting multiple visualization instances.

SUMMARY: In recent years, the ability to generate genomic data has increased dramatically along with the demand for easily personalized and customizable genome browsers for effective visualization of diverse types of data. Despite the large number of web-based genome browsers available nowadays, none of the existing tools provides means for creating multiple visualization instances without manual set up on the deployment server side. The Cranfield Genome Browser (CRAMER) is an open-source, lightweight and highly customizable web application for interactive visualization of genomic data. Once deployed, CRAMER supports seamless creation of multiple visualization instances in parallel while allowing users to control and customize multiple tracks. The application is deployed on a Node.js server and is supported by a MongoDB database which stored all customizations made by the users allowing quick navigation between instances. Currently, the browser supports visualizing a large number of file formats for genome annotation, variant calling, reads coverage and gene expression. Additionally, the browser supports direct Javascript coding for personalized tracks, providing a whole new level of customization both functionally and visually. Tracks can be added via direct file upload or processed in real-time via links to files stored remotely on an FTP repository. Furthermore, additional tracks can be added by users via simple drag and drop to an existing visualization instance. AVAILABILITY AND IMPLEMENTATION: CRAMER is implemented in JavaScript and is publicly available on GitHub on https://github.com/FadyMohareb/cramer. The application is released under an MIT licence and can be deployed on any server running Linux or Mac OS. CONTACT: f.mohareb@cranfield.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chronic bronchitis incidence in the extended cohort of Mayak workers first employed during 1948-1982.

OBJECTIVES: This paper describes findings from the study of chronic bronchitis (CB) incidence after occupational exposure to ionising radiation among workers employed at Russian Mayak Production Association (PA) during 1948 and 1982 and followed up until 2008 based on 'Mayak Worker Dosimetry System 2008'. METHODS: Analyses were based on 2135 verified cases among 21 417 workers. Rate ratios (RR) were estimated by categorical analysis for non-radiation and radiation factors. Excess rate ratios per Gy (ERR/Gy) of external or internal exposures with adjustments via stratification on other factors were calculated. RESULTS: The interesting finding in relation to non-radiation factors was a sharp increase in the RR for CB incidence before 1960, which could be caused by a number of factors. Analyses restricted to the follow-up after 1960 revealed statistically significant associations of the CB incidence and external γ-ray radiation, ERR/Gy=0.14 (95% CI 0.02 to 0.28) having adjusted for sex, attained age, calendar period, plant, smoking status and lung α-particle dose, and internal α-particle radiation, ERR/Gy=1.14 (95% CI 0.41 to 2.18) having adjusted for sex, attained age, calendar period, plant, smoking status and lung γ-ray dose and ERR/Gy=1.19 (95% CI 0.32 to 2.53) having additionally adjusted for pre-employment occupational hazards and smoking index instead of smoking status. CONCLUSIONS: Analyses of CB incidence in the study cohort identified positive significant association with occupational exposure to radiation: however, there are no similar studies of CB incidence in relation to radiation in other cohorts to date with which a meaningful comparison of the results could be made.

[Risk of senile cataract among nuclear industry workers]. / Risk zabolevaemosti starcheskoĭ kataraktoĭ u rabotnikov predpriiatiia atomnoĭ promyshlennosti.

AIM: to assess the relative risk (RR) of senile cataract in a cohort of workers occupationally exposed to external gamma-rays over a long time period. MATERIAL AND METHODS: The RR of cataract development was studied in a cohort of nuclear workers that were first employed in 1948-1982 and followed up till the end of 2008 (n=22,377; females, 25.4%). The mean age at initial employment was 24.9 years. The mean cumulative gamma-ray dose was 0.54 Sv in males and 0.44 Sv in females. The analysis performed with EPICURE software provided RR estimates for cataract incidence in relation to a number of non-radiation and radiation factors. RESULTS: The RR of senile cataract increased with the attained age of the workers. The RR was significantly higher in males during the 2006-2008 period as compared to the 1996-2005 period. The RR was significantly higher in workers that were diagnosed with glaucoma and high myopia as compared to those that were not. The risk of senile cataract increased with the external gamma-ray dose and was the highest in workers who had formerly been exposed to doses above 2.00 Sv. The RR of senile cataract showed no dependency on sex, age at initial employment, smoking status, alcohol consumption, or diabetes mellitus. CONCLUSION: The incidence of senile cataract in the cohort under study was found to depend on both non-radiation and radiation factors.

Exonic versus intronic SNPs: contrasting roles in revealing the population genetic differentiation of a widespread bird species.

Recent years have seen considerable progress in applying single nucleotide polymorphisms (SNPs) to population genetics studies. However, relatively few have attempted to use them to study the genetic differentiation of wild bird populations and none have examined possible differences of exonic and intronic SNPs in these studies. Here, using 144 SNPs, we examined population genetic differentiation in the saker falcon (Falco cherrug) across Eurasia. The position of each SNP was verified using the recently sequenced saker genome with 108 SNPs positioned within the introns of 10 fragments and 36 SNPs in the exons of six genes, comprising MHC, MC1R and four others. In contrast to intronic SNPs, both Bayesian clustering and principal component analyses using exonic SNPs consistently revealed two genetic clusters, within which the least admixed individuals were found in Europe/central Asia and Qinghai (China), respectively. Pairwise D analysis for exonic SNPs showed that the two populations were significantly differentiated and between the two clusters the frequencies of five SNP markers were inferred to be influenced by selection. Central Eurasian populations clustered in as intermediate between the two main groups, consistent with their geographic position. But the westernmost populations of central Europe showed evidence of demographic isolation. Our work highlights the importance of functional exonic SNPs for studying population genetic pattern in a widespread avian species.

[THE IMMUNOLOGIC INDICATORS IN PATIENTS WITH CARIES OF CONTACT SURFACES OF LATERAL TEETH].

The samplings of patients aged 18-45 years with caries of contact surfaces of lateral teeth (n=18) and healthy adults aged 18-20 years with intact teeth (n=18) were examined The saliva taken in rotary vial on empty stomach in amount of 3-4 mi served as assay for analysis. To identify secretory immunoglobulin A, interleukin lß, interleukin-4 and interferon y saliva was centrifuged during 15 min under 1500 rpm. The supernatant fluid was analyzed using enzymoimmunoassay (test-systems "Vector-Best", Novosibirsk). The registration of reaction was implemented using multiscan Labsystem under wavelength 450 nm. The content of secretory immunoglobulin A was expressed in mg/l, cytokines - in pg/ml. It is demonstrated that in patients with caries average level of interleukin lß was almost two times higher (p<0.05) than analogous indicator in healthy examined patients. In healthy patients average level of interferon γ significantly (more than in 10 times) exceeded upper limit of allowable standard and was higher (p<0.05) in comparison with such in patients with caries of contact surfaces. The analysis of content of secretory immunoglobulin A in saliva established that in healthy patients average values of the given indicator were higher (p<0.05) than in patients with caries of contact surfaces of lateral teeth. The lower content of secretory immunoglobulin A and interferon y against the background of increased level of interleukin lß was detected in saliva of patients with caries of contact surfaces of lateral teeth. This occurrence can be considered as factor predisposing to development of caries process.

Online questionnaire development: using film to engage participants and then gather attitudes towards the sharing of genomic data.

How can a researcher engage a participant in a survey, when the subject matter may be perceived as 'challenging' or even be totally unfamiliar to the participant? The Genomethics study addressed this via the creation and delivery of a novel online questionnaire containing 10 integrated films. The films documented various ethical dilemmas raised by genomic technologies and the survey ascertained attitudes towards these. Participants were recruited into the research using social media, traditional media and email invitation. The film-survey strategy was successful: 11,336 initial hits on the survey website led to 6944 completed surveys. Participants included from those who knew nothing of the subject matter through to experts in the field of genomics (61% compliance rate), 72% of participants answered every single question. This paper summarises the survey design process and validation methods applied. The recruitment strategy and results from the survey are presented elsewhere.

Ensembl 2009.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

A study of the catecholaminergic systems of the lateral reticular nuclei and the serotoninergic systems of the raphe magnus in various types of analgesia.

The effects of catecholaminergic A-1 lateral reticular nuclei and serotoninergic neurons of NRM on pain reactions before and after various types of stimulation are presented. It was established that specific lesions of catecholaminergic (NE) neurons in A-1 nuclei using 6-hydroxydopamine, and of serotoninergic (5-HT) neurons of the nucleus raphe magnus using 5,7-dihydroxytryptamine caused a decrease in the respective levels of epinephrine and serotonin in the spinal cord. The baseline pain sensitivity did not change following surgery. Analgesia induced by cold swimming stress (CSS), auricular electroacupuncture (AEA) and vaginal probe (VP) was less in A-1-lesioned rats. Using stimulation of high intensity, such as CSS and VP, a decrease in pain sensitivity was determined, compared to the baseline. The AEA did not produce such an effect. The data obtained suggest that catecholaminergic systems of A-1 play an important role in pain regulation when CSS, AEA and VP are used. Other neurochemical mechanisms, as well as A-1 nuclei systems, are involved in analgesia, induced by CSS and VP. It was shown that lesion of 5-HT-ergic systems of NRM did not have any influence of antinociceptive mechanisms, when activated by AEA and VP.

Buspirone effect on the development of antinociceptive reactions.

The anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in the hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine on the test. A buspirone dose of 2 mg/kg administered to animals before foot shock, or the dose of 1.5 mg/kg before cold swimming stress, led to a significant increase in hot plate latency 1 min after stress as compared to the control. The effect of buspirone on the paw lick reaction in rats may be related to the activation of antinociceptive mechanisms and inhibition of an emotional-motivational component of the pain reaction.

The study of the central grey matter in mechanisms of different kinds of analgesia: effects of lesions.

The effect of the central grey matter (CG) on pain sensitivity has been investigated in rats. It has been demonstrated that baseline pain thresholds, tested by the hot plate method (HPM) after surgical operation, were significantly greater in CG-lesioned rats than in controls. Baseline tail flick latencies did not differ from those in the control group of animals. In the CG-lesioned rats, the latencies of pain responses, measured by the hot plate and tail flick tests after stress and auricular electroacupuncture, were significantly shorter than in the control group. The analgesia in the CG-lesioned rats after auricular electrostimulation was less than that after stress. Obtained data suggest: (1) significance of the CG in the regulation of baseline pain sensitivity, tested by different methods, is variable. CG mechanisms do not play a leading role in producing the tail flick response, whereas hind paw licking is mediated through CG-dependent mechanisms. (2) Antinociceptive effect of stress and acupuncture is mediated by the CG. (3) The role of the CG in analgesic mechanisms is greater in acupuncture than in stress. (4) Apart from the CG, other antinociceptive systems are involved in the mechanisms of stress-induced analgesia.

Alterations in rat central nervous system endorphins following transauricular electroacupuncture.

Auricular electro-stimulation (electroacupuncture) was found to produce naloxone-reversible analgesia in the rat. These behavioral effects were accompanied by significant increases in cerebrospinal fluid (CSF) levels of endorphins with concomitant decreases in the basomedial hypothalamus and medial thalamus of beta-endorphin-like immunoreactivity as well as endorphin-like radioreceptor activity. In addition, the radioreceptor assay also revealed a decrease in endorphin-like radioreceptor activity in the periaqueductal gray (PAG) matter. These results are interpreted to imply that electroacupuncture in the rat produces at least part of its analgesic action by activating central nervous system endorphinergic circuitry which results in a release and depletion of endorphins in certain brain loci and a concomitant elevation in the CSF. Hypophyseal endorphins do not appear to be involved in mediating acupuncture-induced analgesia in the rat since plasma levels of endorphins were not altered by this manipulation.

Cortical projections to the periaqueductal grey in the cat: a retrograde horseradish peroxidase study.

Stereotaxic fluid microinjections of horseradish peroxidase into different parts of the rostral and caudal periaqueductal grey (PAG) in cats have provided substantial retrograde evidence that the somatosensory cortex (I and II), frontal cortex, insular and cingular cortex are the principal sources of cortical-PAG projections. The somatosensory cortex II projects to all the regions of the rostral and caudal PAG. The frontal cortex projects to dorso-lateral quadrant of the PAG. The same projections were determined from insular and cingular cortex to PAG. The findings revealed a morphological substratum of corticofugal effects on PAG.

[Experimental research on the cellular interactions during hemopoiesis]. / Eksperimental'noe issledovanie mezhkletochnykh vzaimodeistvii pri gemopoéze.

We present a review of experimental studies performed at the Laboratory of Histogenesis of the Institute of Developmental Biology, Russian Academy of Sciences, on the problem of cell interactions during hemopoiesis. Special attention has been given to original experimental models, such as production of hemopoietic foci on underlayers of fibroblasts encapsulating a foreign body in the peritoneal cavity of rodents (after intraperitoneal transplantation of hemopoietic cells) and repopulation of ectopic hemopoietic territories under the kidney capsule of mice by syngeneic or xenogeneic hemopoietic cells. We describe the competitive interactions of genetically different hemopoietic cells after the transplantation of their mixtures to irradiated mice (multicomponent radiation chimeras). Xenogeneic and multicomponent chimeras have also been obtained in long-term bone marrow culture. We have examined characteristics of hemopoiesis on stromal cell underlayers produced by cells of various origins in vitro and then transplanted into the peritoneal cavity of irradiated mice. We discuss the results obtained and possible mechanisms of these phenomena.

[The ratio of the contents of beta-endorphin, adrenaline and noradrenaline in the hypothalamus of rats with an experimental stomach ulcer and during acupuncture]. / Sootnoshenie soderzhaniia beta-éndorfina, adrenalina i noradrenalina v gipotalamuse mozga krys pri éksperiemntal'noi iazve zheludka i akupunkture.

In white rats with experimental ulcer of the stomach, a single session of acupuncture (AP) considerably increased the contents of beta-endorphine (ED) and adrenaline (A) in the hypothalamus. Repeated AP sessions aided to a progressive decrease in the ED, A and noradrenaline (NA) levels. The AP did not change essentially the dynamics of ED, A and NA by itself. The ulcer pathology against the background of AP sessions is accompanied by a change in activity of hypothalamic systems of the ED, A and NA, and by a formation of a specific neurochemical profile changing in time.

[Changes in the content of opiate-like substances in auricular electroacupuncture anesthesia of rats]. / Izuchenie izmenenii soderzhaniia opiatpodobnykh veshchestv pri aurikuloélektroakupunkturnom obezbolivanii krys.

It was shown that auricular electro-acupuncture in rats, sufficient to induce analgesia, resulted in a significant increase of endorphins in cerebro-spinal fluid with a concomitant decrease in the basomedial hypothalamus and medial thalamus of beta-endorphin-like immunoreactivity as well as endorphin-like radioreceptor activity. In addition, the radioreceptor assay also revealed a decrease of endorphin-like radioreceptor activity in the periaqueductul gray matter. plasma levels of endorphins were not altered. Cerebro-spinal fluid contained only endogenous opiate ligand material with enkephalin-like molecular weight.

[Role of phospholipase A2 in anoxic injury to the energy-dependent functions of the mitochondria]. / Rol' fosfolipazy A2 v anoksicheskom povrezhdenii énergozavisimykh funktsii mitokhondrii.

An increase in concentration of free fatty acids was observed simultaneously with a decrease in energy dependent functions of mitochondria (oxidative phosphorylation and Ca2+-accumulating ability) after their preincubation under anoxic conditions in vitro with Ca2+ ions (11-14 nmol/mg of mitochondrial protein). Impairment of mitochondria and accumulation of fatty acids were prevented by inhibitors of phospholipase A2 from mitochondria. The anoxic impairment of mitochondria appears to be caused by Ca2+-activated phospholipase A2.

[Cation permeability of liver mitochondrial membranes during Ca+-dependent anoxic damage in vitro]. / Izuchenie kationnoi pronitsaemosti membran mitokhondrii pecheni pri Ca2+-zavisimom anoksicheskom povrezhdenii in vitro.

Ca2+ ions are responsible for impairment of oxidative phosphorylation in rat liver mitochondria under anoxia in vitro. The decrease in this function is due to inhibition of electron transport over respiratory chain and to uncoupling. The increase in membrane permeability for H+, K+ and Na+ was observed on incubation of mitochondria under anoxic condition together with Ca2+. Uncoupling of phosphorylation depends on the increased permeability of the membranes for H+. The increased permeability of membranes for Na+ and K+ under energy liberation and in presence of penetrating anions led to active swelling of organelles and to secondary (osmotic) impairment. Ca2+-activated mitochondrial phospholipase A2 appears to participate in the organelle impairment under anoxia.

[Theoretical and clinical prerequisites for the use of fragments of molar roots as abutment for dentures]. / Teoreticheskie i klinicheskie predposylki k ispol'zovaniiu fragmentov kornei moliarov v kachestve opory zubnykh protezov.

Experimental and clinical studies confirmed the possibility of using fragments of a multi-root tooth as abutment tooth for a bridge denture. When planning orthodontic treatment, choosing the abutment teeth, designing the denture, and treating the patient the orthodontist should be able to use the information on the maximum allowable loading of the fragments of resected teeth. A positive factor in utilization of the remaining tooth fragment is the ratio of clinical crown and root length, which should be inversely proportional. The study showed that retention of the morphofunctional integrity of dentition is possible when using dentures ensuring the optimum regulation stress (no higher than physiologically tolerable) in abutment tissues. Analysis of remote clinical and X-ray data showed normalization of the periodontal function of tooth fragments after tooth-sparing operations in cases when the patients were fitted with prostheses with consideration for theoretically valid methods for estimation of reserve force.