Copy number variation in the porcine genome inferred from a 60 k SNP BeadChip

Background: Recent studies in pigs have detected copy number variants (CNVs) using the Comparative Genomic Hybridization technique in arrays designed to cover specific porcine chromosomes. The goal of this study was to identify CNV regions (CNVRs) in swine species based on whole genome SNP genotyping chips. Results: We used predictions from three different programs (cnvPartition, PennCNV and GADA) to analyze data from the Porcine SNP60 BeadChip. A total of 49 CNVRs were identified in 55 animals from an Iberian x Landrace cross (IBMAP) according to three criteria: detected in at least two animals, contained three or more consecutive SNPs and recalled by at least two programs. Mendelian inheritance of CNVRs was confirmed in animals belonging to several generations of the IBMAP cross. Subsequently, a segregation analysis of these CNVRs was performed in 372 additional animals from the IBMAP cross and its distribution was studied in 133 unrelated pig samples from different geographical origins. Five out of seven analyzed CNVRs were validated by real time quantitative PCR, some of which coincide with well known examples of CNVs conserved across mammalian species. Conclusions: Our results illustrate the usefulness of Porcine SNP60 BeadChip to detect CNVRs and show that structural variants can not be neglected when studying the genetic variability in this species.

Complexation to macromolecules with a large number of sites

This paper presents an approach based on the saddle-point approximation to study the equilibrium interactions between small molecules and macromolecules with a large number of sites. For this case, the application of the Darwin–Fowler method results in very simple expressions for the stoichiometric equilibrium constants and their corresponding free energies in terms of integrals of the binding curve plus a correction term which depends on the first derivatives of the binding curve in the points corresponding to an integer value of the mean occupation number. These expressions are simplified when the number of sites tends to infinity, providing an interpretation of the binding curve in terms of the stoichiometric stability constants. The formalism presented is applied to some simple complexation models, obtaining good values for the free energies involved. When heterogeneous complexation is assumed, simple expressions are obtained to relate the macroscopic description of the binding, given by the stoichiomeric constants, with the microscopic description in terms of the intrinsic stability constants or the affinity spectrum. © 1999 American Institute of Physics.

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies.

Copy number variations and cognitive phenotypes in unselected populations

IMPORTANCE: The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE: To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS: The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES: Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS: Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1 Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P = 1.06e-04) among 248 (≥250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (≥1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P = .005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P = 1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE: Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health.

Priming psychic and conjuring abilities of a magic demonstration influences event interpretation and random number generation biases

Magical ideation and belief in the paranormal is considered to represent a trait-like character; people either believe in it or not. Yet, anecdotes indicate that exposure to an anomalous event can turn skeptics into believers. This transformation is likely to be accompanied by altered cognitive functioning such as impaired judgments of event likelihood. Here, we investigated whether the exposure to an anomalous event changes individuals' explicit traditional (religious) and non-traditional (e.g., paranormal) beliefs as well as cognitive biases that have previously been associated with non-traditional beliefs, e.g., repetition avoidance when producing random numbers in a mental dice task. In a classroom, 91 students saw a magic demonstration after their psychology lecture. Before the demonstration, half of the students were told that the performance was done respectively by a conjuror (magician group) or a psychic (psychic group). The instruction influenced participants' explanations of the anomalous event. Participants in the magician, as compared to the psychic group, were more likely to explain the event through conjuring abilities while the reverse was true for psychic abilities. Moreover, these explanations correlated positively with their prior traditional and non-traditional beliefs. Finally, we observed that the psychic group showed more repetition avoidance than the magician group, and this effect remained the same regardless of whether assessed before or after the magic demonstration. We conclude that pre-existing beliefs and contextual suggestions both influence people's interpretations of anomalous events and associated cognitive biases. Beliefs and associated cognitive biases are likely flexible well into adulthood and change with actual life events.

Evaluating the impact of filming on the number of errors committed by nursing students to determine the efficacy of simulated clinical situations

Clinic simulation as a training and knowledge method allows people experiment a real event representation with the aim of acquiring knowledge, abilities and aptitudes. The filming of the staging represents a useful tool to review the decisions taken and the actions they did, with the purpose to highlight the strengths, weaknesses and the areas for improvement. The article describes a study carried out by a group of students in second course of nursing, and it tries to evaluate if there is any influence if somebody is filming you during the clinic simulation, does it make you do more errors or not?

The present state of aragonese

How much Aragonese is still spoken remains largely an unknown quantity. Naturally, establishing the number of speakers of any variety begs the question of what speaking a language actually means, and the picture is often clouded by the political interests of particular groups, as is the case in Aragon. The strong claim to the continued widespread use of Aragonese made by such associations as the Consello d"a Fabla in Huesca is counterbalanced by that of the more reactionary, sceptical academics at the University of Saragossa, who maintain that Aragonese varieties, ignoring the Catalan of Aragon spoken right down La Franja, the transition area between Aragon and Catalonia, now only survive in certain pockets of resistance across the north of Huesca. This paper will attempt to provide a summary of the available facts and report on some of the author"s own findings during his more recent trips to Aragon. Keywords Spanish dialectology, Aragonese, standardization of Aragonese, vitality of Aragonese

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

Regional Science trends through the analysis of the main facts of the 51st ERSA Conference

The 51st ERSA Conference held in Barcelona in 2011 was one of the largest ever. By examining the characteristics of the conference, this paper identifies the main trends in Regional Science and draws on a broad array of sources of information: the delegates" demographic details, the conference program itself, a satisfaction survey conducted among delegates, a quality survey addressed to those chairing the sessions and, finally, a bibliometric database including each author signing a paper presented at the conference. We finally run a regression analysis from which we show that for ERSA delegates what matters most is quality, and this must be the direction that future conferences should move toward. Ultimately, ERSA conferences are comprehensive, all-embracing occasions, representing an ideal opportunity for regional scientists to present their work to each other and to network.

Gestió dels residus alimentaris municipals procedents de les activitats comercials del municipi de Montmeló per tal de reduir, reutilitzar i reciclar-los

En el present treball es proposa com lluitar contra el malbaratament alimentari que es genera al llarg de tota la cadena alimentària, sent aquest degut a causa d'una planificació poc adequada. L'objectiu principal és planificar i implantar un sistema de gestió per tal de recuperar l'excedent alimentari que es genera als comerços i les indústries del municipi de Montmeló, elaborant així un protocol per tal de poder redistribuir aquest aliment als sectors de la població en situacions econòmiques més precàries. Com a objectius secundaris, es pretén conscienciar, fomentar i potenciar el treball en xarxa entre els diferents agents implicats, com ara: la ciutadania, les entitats socials (Càritas Parroquial Montmeló), sector privat (establiments alimentaris del municipi, mercat municipal, indústries del sector alimentari) i el sector públic (departament de serveis socials, medi ambient, comerç i brigada municipal). A l'hora de planificar i implantar un sistema de gestió per tal de recuperar l'excedent alimentari, s'ha analitzat i valorat el camí que hi realitza, des d'on es genera fins al beneficiari final. Aquest s'ha gestionat per etapes, en les que s'han identificat els generadors, el tipus i quantitat d'aliment que malbaraten. S'ha proposat un nou sistema de recollida d'informació i les pautes que han de seguir per garantir el bon estat de l'aliment com: una taula de conservació, un protocol de funcionament, un document d'entrega i una fitxa de control de les condicions d'higiene. Per tal d'assolir una bona coordinació entre totes les parts, s'han realitzat reunions conjuntes entre els generadors, serveis socials i Càritas on s'ha acabat signant un acord de col·laboració. Entre les conclusions més rellevants cal destacar que ha servit per establir un precedent d'aprofitament alimentari al municipi de Montmeló, aconseguint alimentar a un gran nombre de famílies amb greus problemes econòmics. A més s'ha arribat a disminuir la quantitat de residus generats, amb el conseqüent estalvi de recursos econòmics i materials on s'ha recuperat un total de 5.760 Kg d'aliments aptes pel consum.

Ultrasound-guided fine-needle aspiration of thyroid nodules: assessment of the ideal number of punctures

OBJECTIVE: To determine the number of punctures in fine-needle aspiration biopsies required for a safe cytological analysis of thyroid nodules. MATERIALS AND METHODS: Cross-sectional study with focus on diagnosis. The study population included 94 patients. RESULTS: The mean age of the patients participating in the study was 52 years (standard-deviation = 13.7) and 90.4% of them were women. Considering each puncture as an independent event, the first puncture has showed conclusive results in 78.7% of cases, the second, in 81.6%, and the third, in 71.8% of cases. With a view to the increasing chance of a conclusive diagnosis at each new puncture, two punctures have showed conclusive results in 89.5% of cases, and three punctures, in 90.6% of cases with at least one conclusive result. CONCLUSION: Two punctures in fine-needle aspiration biopsies of thyroid nodules have lead to diagnosis in 89.5% of cases in the study sample, suggesting that there is no need for multiple punctures to safely obtain the diagnosis of thyroid nodules.

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Copy number variations of colorectal cancer by whole exome sequencing data

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death worldwide. About 85% of the cases of CRC are known to have chromosomal instability, an allelic imbalance at several chromosomal loci, and chromosome amplification and translocation. The aim of this study is to determine the recurrent copy number variant (CNV) regions present in stage II of CRC through whole exome sequencing, a rapidly developing targeted next-generation sequencing (NGS) technology that provides an accurate alternative approach for accessing genomic variations. 42 normal-tumor paired samples were sequenced by Illumina Genome Analyzer. Data was analyzed with Varscan2 and segmentation was performed with R package R-GADA. Summary of the segments across all samples was performed and the result was overlapped with DEG data of the same samples from a previous study in the group1. Major and more recurrent segments of CNV were: gain of chromosome 7pq(13%), 13q(31%) and 20q(75%) and loss of 8p(25%), 17p(23%), and 18pq(27%). This results are coincident with the known literature of CNV in CRC or other cancers, but our methodology should be validated by array comparative genomic hybridisation (aCGH) profiling, which is currently the gold standard for genetic diagnosis of CNV.

Conservation Laws in Cellular Automata

Conservation laws in physics are numerical invariants of the dynamics of a system. In cellular automata (CA), a similar concept has already been defined and studied. To each local pattern of cell states a real value is associated, interpreted as the “energy” (or “mass”, or . . . ) of that pattern.The overall “energy” of a configuration is simply the sum of the energy of the local patterns appearing on different positions in the configuration. We have a conservation law for that energy, if the total energy of each configuration remains constant during the evolution of the CA. For a given conservation law, it is desirable to find microscopic explanations for the dynamics of the conserved energy in terms of flows of energy from one region toward another. Often, it happens that the energy values are from non-negative integers, and are interpreted as the number of “particles” distributed on a configuration. In such cases, it is conjectured that one can always provide a microscopic explanation for the conservation laws by prescribing rules for the local movement of the particles. The onedimensional case has already been solved by Fuk´s and Pivato. We extend this to two-dimensional cellular automata with radius-0,5 neighborhood on the square lattice. We then consider conservation laws in which the energy values are chosen from a commutative group or semigroup. In this case, the class of all conservation laws for a CA form a partially ordered hierarchy. We study the structure of this hierarchy and prove some basic facts about it. Although the local properties of this hierarchy (at least in the group-valued case) are tractable, its global properties turn out to be algorithmically inaccessible. In particular, we prove that it is undecidable whether this hierarchy is trivial (i.e., if the CA has any non-trivial conservation law at all) or unbounded. We point out some interconnections between the structure of this hierarchy and the dynamical properties of the CA. We show that positively expansive CA do not have non-trivial conservation laws. We also investigate a curious relationship between conservation laws and invariant Gibbs measures in reversible and surjective CA. Gibbs measures are known to coincide with the equilibrium states of a lattice system defined in terms of a Hamiltonian. For reversible cellular automata, each conserved quantity may play the role of a Hamiltonian, and provides a Gibbs measure (or a set of Gibbs measures, in case of phase multiplicity) that is invariant. Conversely, every invariant Gibbs measure provides a conservation law for the CA. For surjective CA, the former statement also follows (in a slightly different form) from the variational characterization of the Gibbs measures. For one-dimensional surjective CA, we show that each invariant Gibbs measure provides a conservation law. We also prove that surjective CA almost surely preserve the average information content per cell with respect to any probability measure.