Highly preferential association of NonF508del CF mutations with the M470 allele

AbstractBackgroundOn the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene.MethodsWe have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele.ResultsOut of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9× greater than VV subjects when F508del is excluded and 15.4× when F508del is included. In the Czech population a similar, although less pronounced, association is observed.ConclusionsBesides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

METABOLIC EFFECTS AND REPRODUCTIVE PERFORMANCES IN DAIRY COWS TREATED WITH A FUNCTIONAL FEED (NAT®W3)

The Authors investigated to correlate metabolic efficiency to reproductive performances by the administration of functional feed in high-producing dairy cattle. The trial want to study, also, the capability of laboratory diagnostic in evaluation and estimation of the reproductive capacities to select subjects to submit to reproductive praxis. Functional feed contains vitamins E, A, D3, organic-selenium, polyinsaturated fatty acids (PUFA) and a prebiotic by fermented cereals. Effects of PUFA administered were particularly investigated in lipoprotein fractions composition, in blood. Optimal relationship among LDL-cholesterol, total cholesterol and progesteron was related to best reproductive performances: in this trial. Authors can confirm this on the basis of livestock performances. Study realized during the most worm period of the year when mean daily temperature go up to 30°C. Metabolic parameters considered are linked to energetic, mineral and endocrine metabolisms. Determination were realized in blood-samples before, during, after the administration of NAT3. Bovines were fed with different addition of NAT3 (320-360 g/subj/die) for 4 months. Reproductive indices studied were: open-days and number of services per conception. Trend analysis of fertility indices demonstrated that blood levels of progesterone and blood antioxidant capability are strictly correlated and correlated also to reproductive performances. Efficacy of treatment is demonstrated by the trend of the fertility indices in the post treatment period during which indices return progressively to the pre treatment values in about 60 days: this period correspond to the lipid tissue turnover time. During these days a temporary build-up of PUFA and liposoluble vitamins was observed. Blood progesterone levels were higher (2.2 times) in correspondence of the 21st day post partum in treated subjects respect to control ( 0.18 vs 0.44 ng/l). Reproductive indexes recorded stressed that open-days varied from to . Number of services per conception was reduced from 121 to 95 at 60th day of treatment. In the next four months the value of the index settled between 90-95 days. Data obtained in this study show that administration of PUFA, antioxidants and probiotics administred in dairy cows can remodel metabolisms correlated to fertility such as progesterone, prostaglandins and prostacyclins synthesis. These evidences are stressed by trends recorded in the herd concerning values of open-days and the number of services per conception

Valutazione dell’accuratezza di DEM estratti da una stereocoppia GeoEye

Nel presente lavoro si è analizzata l’accuratezza di un Modello Digitale della Superificie (DSM) estratto da una stereocoppia GeoEye del marzo 2010 al fine di valutarne il possibile utilizzo come dato di input in modelli idraulici previsionali per studi inerenti il deflusso delle acque nel caso di esondazione di fiumi o forti precipitazioni. L’orientamento e l’estrazione del DSM sono stati eseguiti con PCI Geomatica OrthoEngine v10.3, testando la validità anche delle immagini multispettrali per ridurre le imprecisioni nella fase di matching e valutando l’accuratezza dei DSMs estratti mediante confronto sia con un modello di riferimento derivante da volo aerofotogrammetrico che con dati derivanti da rilievo GNSS, eseguito in modalità cinematica e stop&go

Pose-estimation methods for underactuated cable-driven parallel robots

Cable-Driven Parallel Robots (CDPRs) displace the end-effector (EE) by means of cables configured in a parallel fashion. When a CDPR employs fewer cables than the degrees of freedom (DoFs) of its EE, it is underactuated and underconstrained. As a result, only a limited subset of the EE DoFs can be controlled assigning specific cable lengths, and determining the EE pose through direct kinematics (DK) is unfeasible, since it also depends on mechanical equilibrium. To estimate the EE pose, then, it may be convenient to acquire and combine redundant measurements. This paper introduces a sensor fusion technique that aims at achieving the optimal estimation of the pose of a generic UACDPR. Sensor fusion is achieved by an iterative nonlinear weighted least-square algorithm, which is solved by a Gauss–Newton-like method. A novel criterion for terminating iterations, which is physically sound and straightforward to implement, is put forward. Different redundant measurements are experimentally compared, so as to show the performance of the method with different sensors involved

DAIRY COWS TREATED WITH A FUNCTIONAL FEED (NAT3): INVESTIGATION ON PUFA’S TRANSFER IN MILK AND CHEESES

In a previous trial we have demonstrated the increased content of fatty acids CLA and DHA in milk following to the administration of a functional feed NATW3(WBC 2008, Budapest). This study is to demonstrate that lower quantity of NATW3 in feed (320 g/subj./day vs 600 g/subj./day) resolves in similar results: decrease in SFA and increase in PUFA, especially cis-9 18:1, CLA and DHA. Trend of metabolic parameters was confirmed, expecially for lipidic status. The trial involved 116 high-producing dairy cows belonging to two livestocks fed with the same feed: grass family hay (especially oat hay), grass family hay silage (triticale and barley), and industrial feed. The difference concerned the way of administration of industrial feed, ad libitum and with automatic feeding system. Milk was utilized for cheesemaking. Analysis of lipid fractions stressed variations in composition , especially pointed out the transfer of PUFA in different cheeses, making their composition more suitable for a more salutistic intake. “Mozzarella": total lipids +0,96%, total proteins +1,22%, CLA (C18: 2) +118,67%, DHA (C22: 6) +27%, EPA (C20: 5) +60,00%, palmitoleic acid (C16: 1) +29,15%, decrease of stearic acid(C18: 0) --9,84%. ”Canestrato": total lipidis +0,46%, total proteins +0,66%, CLA (C18: 2) +160,42%, DHA (C22: 6) + 80,00%, EPA (C20: 5) +154,54%, palmitoleic acid (C16: 1) +39,00%, decrease of stearic acid (C18: 0) -12,73%. ”Caciocavallo": total lipids +2,48%, total proteins +0,33%, CLA (C18: 2) +58,28%, DHA (C22: 6) + 55,00%, EPA (C20: 5) +76,67%, palmitoleic acid (C16: 1) +40,12%, decrease of stearic acid (C18: 0) -11,92%

Sensitivity of the Direct Kinematics of Underactuated Cable-Driven Parallel Robots to Redundant Sensor-Measurement Errors

Underactuated cable-driven parallel robots (UACDPRs) displace a 6-degree-of-freedom end-effector (EE) with less than 6 cables. As a consequence, the EE is underconstrained and, for assigned cable lengths, the EE pose cannot be obtained from geometrical constraint equations only. In this paper, we study the performance of a direct-kinematics algorithm using redundant sensor measurements for a 4-cable UACDPR. The proposed method measures two orientation parameters of the EE besides cable lengths, in order to determine the other four pose variables, namely 3 position coordinates and one additional orientation parameter. A methodology for the computation of the sensitivity of the direct-kinematics solution to measurement errors is finally proposed

How do Bulgarian farmers spend money from direct payment \u2013 some evidences for future CAP design

This paper analyses farm household strategies and investment behaviour of Bulgarian farmers with a particular focus on the perceived effects of Common Agriculture Policy (CAP). The survey is based on a sample of 83 Bulgarian farms, carried out during 2007 by the Institute of Agricultural Economy (IAE). The farms were selected from 6 less favourite areas in the country which participate in a pilot project aiming to pre-test the effect of direct payments on different farm types. Based on this, three farm types with different specialisation (arable crops, livestock and vegetables), all implementing conventional technology were chosen. The survey includes information about farm and household structure, expectations, reaction to planned and intended investment. Direct payments are normally used in the farm with aim to cover current costs and investment expenditure

Boosting delivery of rare disease therapies: the IRDiRC Orphan Drug Development Guidebook

The International Rare Diseases Research Consortium (IRDiRC) has created a Guidebook to facilitate drug development for rare diseases by organizing available tools into a standardized framework.Functional Genomics of Muscle, Nerve and Brain Disorder