BlastR--fast and accurate database searches for non-coding RNAs.

We present and validate BlastR, a method for efficiently and accurately searching non-coding RNAs. Our approach relies on the comparison of di-nucleotides using BlosumR, a new log-odd substitution matrix. In order to use BlosumR for comparison, we recoded RNA sequences into protein-like sequences. We then showed that BlosumR can be used along with the BlastP algorithm in order to search non-coding RNA sequences. Using Rfam as a gold standard, we benchmarked this approach and show BlastR to be more sensitive than BlastN. We also show that BlastR is both faster and more sensitive than BlastP used with a single nucleotide log-odd substitution matrix. BlastR, when used in combination with WU-BlastP, is about 5% more accurate than WU-BlastN and about 50 times slower. The approach shown here is equally effective when combined with the NCBI-Blast package. The software is an open source freeware available from www.tcoffee.org/blastr.html.

Anterior ischemic optic neuropathy in eyes with optic disc drusen.

BACKGROUND: There have been anecdotal reports of anterior ischemic optic neuropathy (AION) occurring in eyes with optic disc drusen (ODD), but the clinical features of this condition have not been well characterized. OBJECTIVES: To better describe the clinical features of AION associated with ODD and to compare the clinical features of this condition with those of "garden variety" nonarteritic AION. METHODS: We reviewed the medical records of 20 patients who experienced an episode of AION in an eye with ODD. In 4 patients, both eyes were affected; thus, 24 eyes were studied. The diagnosis of ODD was made by ophthalmoscopic identification, orbital ultrasonography, or computed tomographic scanning. We recorded age, sex, vascular risk factors, symptoms, visual acuity, visual fields, and results of the follow-up examination in all patients. These findings were compared with data from previously reported series of patients with nonarteritic AION. RESULTS: Our 20 patients included 14 men and 6 women (age range, 18-69 years; mean, 49.4 years). Vascular risk factors were identified in 10 patients (50%). Three patients reported episodes of transient visual loss before their fixed deficit. The visual acuity at the initial examination was 20/60 or better in 15 (62%) of the 24 eyes; 8 had a visual acuity of 20/20. The predominant pattern of visual field loss was an altitudinal or arcuate defect in 19 (79%) and a centrocecal scotoma in 5 (21%) of the 24 eyes. There was subjective worsening of vision before the initial neuro-ophthalmic examination in 11 eyes (46%) and objective documentation of progression in 7 eyes (29%). The final visual acuity was 20/40 or better in 13 (62%) of 21 eyes and 20/200 or worse in 3 (14%) of 21 eyes. CONCLUSIONS: Our patients were strikingly similar to those with nonarteritic AION unassociated with drusen in regard to prevalence of vascular risk factors, pattern of visual field loss, and occurrence of a subsequent similar event in the fellow eye. In contrast, however, patients with ODD-AION were younger than those with nonarteritic AION, were more likely to report preceding episodes of transient visual obscuration, and enjoyed a more favorable visual outcome.

H2O the essential mix

This poster informs about the danger of dehydration caused by taking Ecstasy stating: 'Ecstasy makes you dehydrate and dancing makes you sweat, so if you're doing both sip about a pint of water an hour, have the odd sugary drink and take breaks from dancing'. It also provides contact details for the National Drugs Helpline. Tel: 0800 776600.

A topological invariant to predict the three-dimensional writhe of ideal configurations of knots and links.

We present herein a topological invariant of oriented alternating knots and links that predicts the three-dimensional (3D) writhe of the ideal geometrical configuration of the considered knot/link. The fact that we can correlate a geometrical property of a given configuration with a topological invariant supports the notion that the ideal configuration contains important information about knots and links. The importance of the concept of ideal configuration was already suggested by the good correlation between the 3D writhe of ideal knot configurations and the ensemble average of the 3D writhe of random configurations of the considered knots. The values of the new invariant are quantized: multiples of 4/7 for links with an odd number of components (including knots) and 2/7 plus multiples of 4/7 for links with an even number of components.

Prévalence des troubles de l'humeur dans la maladie de Parkinson traitée par stimulation cérébrale profonde [Prevalence of mood disorders in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation].

Subthalamic nucleus deep brain stimulation (STN-DBS) is a recognized treatment for advanced and severe forms of Parkinson's Disease. The procedure improves motor signs and often allows a reduction of the medication. The impact of the procedure on cognitive and neuropsychiatric signs of the disease is more debated and there is an international consensus for the need of a multidisciplinary evaluation of patients undergoing such programs, including a neuropsychiatric assessment. We present a review of the literature as well as the experience at our centre focused on the short and long term outcome on mood following STN-DBS.

Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?

The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the "drug addiction circuitry," an increasing amount of evidence demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.

Saccharomyces cerevisiae, a tool to study the β-oxidation through the synthesis of polyhydroxyalkanoates

Summary Polyhydroxyalkanoates (PHAs) represent a family of polyesters naturally synthesized by a wide variety of bacteria. Through their thermoplastic and elastomeric qualities, together with their biodegradable and renewable properties, they are predicted to be a good alternative to the petroleum- derived plastics. Nevertheless, as PHA production costs using bacteria fermentation are still too high, PHA synthesis within eukaryotic systems, such as plants, has been elaborated. Although the costs were then efficiently lowered, the yield of PHAs produced remained low. In this study, Saccharomyces cerevisae has been used as another eukaryotic model in order to reveal the steps which limit PHA production. These cells express the PHA synthase of Pseudomonas aeruginosa and the PHAs obtained were analyzed to understand the flux of fatty acids towards and through the peroxisomal β-oxidation core cycle, generating the main substrate of the PHA synthase. When S. cerevisiae wild-type cells are grown in a media containing glucose as carbon source as well as fatty acids, the PHA monomer composition is largely influenced by the nature of the external fatty acid used. Thus, even-chain PHA monomers are generated from oleic acid (18:1Δ9cis) and odd- chain PHA monomers are generated from heptadecenoic acid (17:1Δ. 10 cis). Moreover, PHA synthesis is dependent on the first two enzymes of the 0-oxidation core cycle, the acyl-CoA oxidase and the multifunctional enzyme enoyl-CoA hydratase II / R-3-hydroxyacyl-CoA dehydrogenase. S. cerevisiae mutant cells growing on oleic or heptadecenoic acid and deficient in either the R-3- hydroxyacyl-CoA dehydrogenase or in the 3-ketothiolase activity, the last β-oxidation cycle steps, surprisingly contained PHAs of predominantly even-chain monomers. This is also noticed in wild- type and mutants grown on glucose or raffinose, indicating that the substrate used for PHA synthesis is generated from the degradation of intracellular short- and medium-chain fatty acids by the 3- oxidation cycle. Inhibition of fatty acid biosynthesis by cerulenin blocks the synthesis of PHAs from intracellular fatty acids but still enables the use of extracellular fatty acids for polymer production. Together, these results uncovered the existence of a substantial futile cycle whereby short- and medium-chain intermediates of the cytoplasmic fatty acid biosynthetic pathway are directed towards the peroxisomal β-oxidation pathway. In this thesis, no increase of the yield of PHA produced could be obtained. But the PHA synthesis confirmed the carbon flux into and through the β-oxidation core cycle and unveiled the existence of novel mechanisms. It is thus a good tool to study in vivo the flux of carbons in S. cerevisiae cells. Résumé Les polyhydroxyalkanoates (PHAs) sont une famille de polyesters naturellement synthétisés par un grand nombre de bactéries. Ayant des propriétés de thermoplastiques, d'élastomères et étant des ressources biodégradables et renouvelables, les PHAs représentent une bonne alternative aux plastiques dérivés du pétrole. Pour pallier aux coûts considérables de la production de PHAs par fermentation bactérienne, la synthèse de PHAs par des systèmes eucaryotes telles les plantes a été élaborée. Les coûts ont ainsi efficacement été diminués, mais le rendement de PHAs produits reste faible. Dans cette étude, Saccharomyces cerevisiae a été utilisé comme autre modèle eucaryote pour révéler les étapes limitantes de la production de PHAs. Les PHAs obtenus dans les cellules exprimant la F'HA synthase de Pseudomonas aeruginosa ont été analysés afin de comprendre le flux d'acides gras vers et à travers le cycle péroxisomal de la β-oxidation, principal producteur du substrat de la PHA synthase. Lorsque la souche S. cerevisiae de type sauvage se développe dans un milieu contenant du glucose et des acides gras, la composition des monomères de PHAs est influencée par la nature des acides gras extracellulaires. Ainsi, les monomères pairs sont générés par l'acide oléique (18:1Δ9cis), tandis que les impairs le sont par l'acide heptadécénoïque (17:1Δ10cis). La synthèse de PHAs est dépendante des deux premières enzymes de la β-oxidation; l'acyl-CoA oxidase et l'enzyme multifonctionnelle enoyl-CoA hydratase II / R-3-hydroxyacyl-CoA déshydrogénase. Les souches mutantes ne possédant pas les activités de la R-3-hydroxyacyl-CoA déshydrogénase ou de la 3- ketothiolase contiennent, en présence d'acide oléique ou heptadécénoïque, des PHAs composés essentiellement de monomères pairs. Cela a également été observé en présence de glucose ou de raffinose uniquement. Le substrat utilisé pour la synthèse de PHAs a ainsi été généré par la dégradation d'acides gras intracellulaires à chaîne courte et moyenne via le cycle de la β-oxidation. L'inhibition de la synthèse d'acides gras par la cérulénine a bloqué la synthèse de PHAs par les acides gras internes. Ces résultats ont révélés l'existence d'un cycle futile par lequel des intermédiaires à chaîne courte et moyenne de la synthèse cytoplasmique d'acides gras sont dirigés vers le cycle péroxisomal de la β-oxidation. Dans cette étude, le rendement de PHAs produits reste inchangé, mais l'analyse des PHAs permet de confirmer le flux de carbones vers et à travers le cycle péroxisomal de la β-oxidation et l'existence de nouveaux méchanismes a été dévoilée. Cette synthèse s'avère être un bon outil pour étudier in vivo le flux de carbones dans les cellules de S. cerevisiae.

The cuticular hydrocarbons of the Triatoma sordida species subcomplex (Hemiptera: Reduviidae)

The cuticular hydrocarbons of the Triatoma sordida subcomplex (Hemiptera: Reduviidae: Triatominae) were ana-lysed by gas chromatography and their structures identified by mass spectrometry. They comprised mostly n-alkanes and methyl-branched alkanes with one-four methyl substitutions. n-alkanes consisted of a homologous series from C21-C33 and represented 33-45% of the hydrocarbon fraction; n-C29 was the major component. Methyl-branched alkanes showed alkyl chains from C24-C43. High molecular weight dimethyl and trimethylalkanes (from C35-C39) represented most of the methyl-branched fraction. A few tetramethylalkanes were also detected, comprising mostly even-numbered chains. Several components such as odd-numbered 3-methylalkanes, dimethylalkanes and trimethylalkanes of C37 and C39 showed patterns of variation that allowed the differentiation of the species and populations studied. Triatoma guasayana and Triatoma patagonica showed the most distinct hydrocarbon patterns within the subcomplex. The T. sordida populations from Brazil and Argentina showed significantly different hydrocarbon profiles that posed concerns regarding the homogeneity of the species. Triatoma garciabesi had a more complex hydrocarbon pattern, but it shared some similarity with T. sordida. The quantitative and qualitative variations in the cuticular hydrocarbons may help to elucidate the relationships between species and populations of this insect group.

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

OBJECTIVE Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. RESEARCH DESIGN AND METHODS This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. RESULTS sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). CONCLUSIONS High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Light-induced degradation of phyA is promoted by transfer of the photoreceptor into the nucleus.

Higher plants possess multiple members of the phytochrome family of red, far-red light sensors to modulate plant growth and development according to competition from neighbors. The phytochrome family is composed of the light-labile phyA and several light-stable members (phyB-phyE in Arabidopsis). phyA accumulates to high levels in etiolated seedlings and is essential for young seedling establishment under a dense canopy. In photosynthetically active seedlings high levels of phyA counteract the shade avoidance response. phyA levels are maintained low in light-grown plants by a combination of light-dependent repression of PHYA transcription and light-induced proteasome-mediated degradation of the activated photoreceptor. Light-activated phyA is transported from the cytoplasm where it resides in darkness to the nucleus where it is needed for most phytochrome-induced responses. Here we show that phyA is degraded by a proteasome-dependent mechanism both in the cytoplasm and the nucleus. However, phyA degradation is significantly slower in the cytoplasm than in the nucleus. In the nucleus phyA is degraded in a proteasome-dependent mechanism even in its inactive Pr (red light absorbing) form, preventing the accumulation of high levels of nuclear phyA in darkness. Thus, light-induced degradation of phyA is in part controlled by a light-regulated import into the nucleus where the turnover is faster. Although most phyA responses require nuclear phyA it might be useful to maintain phyA in the cytoplasm in its inactive form to allow accumulation of high levels of the light sensor in etiolated seedlings.

Metabolically healthy obesity: different prevalences using different criteria.

To estimate the prevalence of metabolically healthy obesity (MHO) according to different definitions. Population-based sample of 2803 women and 2557 men participated in the study. Metabolic abnormalities were defined using six sets of criteria, which included different combinations of the following: waist; blood pressure; total, high-density lipoprotein or low-density lipoprotein-cholesterol; triglycerides; fasting glucose; homeostasis model assessment; high-sensitivity C-reactive protein; personal history of cardiovascular, respiratory or metabolic diseases. For each set, prevalence of MHO was assessed for body mass index (BMI); waist or percent body fat. Among obese (BMI 30 kg/m(2)) participants, prevalence of MHO ranged between 3.3 and 32.1% in men and between 11.4 and 43.3% in women according to the criteria used. Using abdominal obesity, prevalence of MHO ranged between 5.7 and 36.7% (men) and 12.2 and 57.5% (women). Using percent body fat led to a prevalence of MHO ranging between 6.4 and 43.1% (men) and 12.0 and 55.5% (women). MHO participants had a lower odd of presenting a family history of type 2 diabetes. After multivariate adjustment, the odds of presenting with MHO decreased with increasing age, whereas no relationship was found with gender, alcohol consumption or tobacco smoking using most sets of criteria. Physical activity was positively related, whereas increased waist was negatively related with BMI-defined MHO. MHO prevalence varies considerably according to the criteria used, underscoring the need for a standard definition of this metabolic entity. Physical activity increases the likelihood of presenting with MHO, and MHO is associated with a lower prevalence of family history of type 2 diabetes.

Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway.

Deep brain stimulation (DBS) for Parkinson's disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse effects. In this study, we assessed the STN's connectivity to motor, associative, and limbic brain areas, based on structural and functional connectivity analysis of volunteer data. For the structural connectivity, we used streamline counts derived from HARDI fiber tracking. The resulting tracks supported the existence of the so-called "hyperdirect" pathway in humans. Furthermore, we determined the connectivity of each STN voxel with the motor cortical areas. Functional connectivity was calculated based on functional MRI, as the correlation of the signal within a given brain voxel with the signal in the STN. Also, the signal per STN voxel was explained in terms of the correlation with motor or limbic brain seed ROI areas. Both right and left STN ROIs appeared to be structurally and functionally connected to brain areas that are part of the motor, associative, and limbic circuit. Furthermore, this study enabled us to assess the level of segregation of the STN motor part, which is relevant for the planning of STN DBS procedures.

Let there be light in the nucleus!

Ambient light conditions trigger both developmental transitions, such as the induction of flowering, and a suite of adaptive responses, exemplified by the shade-avoidance syndrome. These responses are initiated by three families of photoreceptors that are conserved in all higher plants: the phototropins, cryptochromes and phytochromes (phyA--phyE, cry1--cry3, phot1 and phot2 in Arabidopsis). Molecular genetic studies performed mainly in Arabidopsis indicate that photon capture by these light sensors usually initiates rapid changes in the gene expression profile, leading to plant adaptation to their environment. Interestingly, numerous transcription factors are early targets of light regulation, both at the transcriptional and post-transcriptional levels.

TBS discrimine les femmes avec ostéoporose fracturaire des femmes non ostéoporotiques indépendamment de la DMO, de l'âge et de l'IMC : Etude de la cohorte Ostéo-Mobile Vaud

Introduction. - « Ostéo-Mobile Vaud » est un projet pilote visant àinformer et promouvoir les mesures générales de prévention del'ostéoporose chez les femmes vaudoises de 60 ans et plus. Son butest également d'évaluer le risque de fracture dans cette populationen associant les facteurs de risque cliniques, la mesure de la DMOpar DXA de la colonne lombaire et du fémur proximal (Hologic Discovery),la recherche des fractures vertébrales préexistantes parVFA et une appréciation de la « qualité osseuse » par TBS. Une phaseprospective de 5 ans est prévue. Le Trabecular Bone Score (TBS) estun procédé qui consiste à appliquer un traitement informatique àl'image 2D de projection de la DXA basé sur la quantification desvariations locales de niveaux de gris. Un modèle mathématiquerelie le paramètre TBS avec des paramètres de microarchitecture 3Dtels la connectivité 3D, le nombre de travées et l'espace inter-trabéculaire.Ce modèle fait de TBS une mesure indirecte de microarchitectureosseuse.Résultats. - Fin juillet 2011, 510 femmes de ± 67 ans, IMC ± 26 kg/m2,ont été évaluées. Une ou plusieurs fractures de fragilité ont été rapportéeschez 72 femmes, parmi lesquelles 39 avec fractures vertébrales.TBS diminue avec l'âge (-0.005 par année, p < 0,001) etdiminue en fonction de l'IMC (- 0,011 par kg/m2, p < 0,001). La corrélationentre TBS et la DMO de la colonne lombaire est faible(r = 0,4, p < 0,001) et un grand pourcentage de la variabilité du TBSest indépendant de la DMO (> 84%). TBS discrimine les femmes avecfractures vertébrales des femmes sans fracture vertébrale et lesfemmes avec OP clinique (fractures de fragilité) de celles sans OPclinique. Ce pouvoir discriminatif est indépendant de la DMO de lacolonne lombaire ou du T-score le plus bas, après ajustement pourl'âge et l'IMC.Odd ratio (OR, 95 % IC) pour une diminution d'une déviation standarddu TBS, ajusté pour l'âge, l'IMC et la mesure de DMO :Conclusion. - TBS représente une plus-value par rapport à la DMOdans l'appréciation du risque de fracture chez les femmes vaudoisesde 60 ans et plus.