Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

Background: The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results: In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions: The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations.

From trade to industry. The wine production sector in the Penedès Denomination of Origin, 1940-2000

[cat] Aquest treball té com a objectiu mostrar el grau en què el sector de la producció de vi a la Denominació d'Origen Penedès ha respost als reptes que s’han plantejat tant en termes de l'oferta (de consolidació i sorgiment dels països productors fora de l'esfera europea tradicional) i de la demanda (caiguda de la el consum de vi i els nous hàbits de consum) durant la segona meitat del segle XX. El document analitza l'evolució del sector a la regió des del començament de la dècada de 1940 fins a la fi del segle. Amb la fi de la Guerra Civil de 1936-1939 el sector va haver d'afrontar una caiguda de la producció, la qual va continuar concentrant-se en la comercialització de vins tradicionals. Aquesta situació va canviar quan, a finals de la dècada de 1960, la demanda es va girar cada vegada més als vins de major qualitat embotellats. Des del punt de vista legislatiu, la resposta es va centrar en la innovació tecnològica i la reestructuració de l'empresa. Aquest període va ser testimoni de la introducció de nous equips i processos, com ara l’acer inoxidable i tancs de fermentació a temperatura controlada, amb els vins embotellats expulsant el vi a granel i la transformació dels grans magatzemistes en cellers i caves. A més, una de les principals característiques del període 1970-1985 va ser la formació dels grans conglomerats empresarials dels vins i del cava. L’entrada d'Espanya a la Unió Europea el 1986 va impulsar una acceleració d'aquest procés de transformació, deixant el sector format principalment per empreses que produeixen vins i caves, que han introduït els vins negres i varietals en la seva oferta de productes, que posseeixen moltes hectàrees de vinyes i en molts casos, que han mostrat una clara intenció de penetrar en el mercat internacional.

Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

Background: The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results: In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions: The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations.

Metal dealing at the origin of the Chordata phylum: The metallothionein system and metal overload response in Amphioxus.

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms.

Wage differentials between native and immigrant women in Spain: accounting for differences in support

Purpose: The objective of the study is to quantify the wage gap between native and immigrant women in Spain, taking into account differences in their characteristics and the need to control for common support. If immigrant women are segregated in occupations with few native women, it is important to take this into account to analyse wage differentials between both collectives. Methodology: We use microdata from the Continuous Sample of Working Histories (Muestra Continua de Vidas Laborales) on wages and other personal characteristics such as gender, country of origin, and age to apply the matching procedure and the decomposition of the wage gap along the lines of Ñopo (2008) for the analysis of wage differentials between native and immigrant women. The advantage of this procedure is that we can simultaneously estimate the common support and the mean counterfactual wage for the women on the common support (i.e., comparing native and immigrant women with similar observable characteristics). In addition, we can describe differences not only at the mean but also along the entire wage distribution. Findings: The results obtained indicate that, on average, immigrant women earn less than native women in the Spanish labour market. This wage gap is bigger when we consider immigrant women from developing countries, but our main finding is that an important part of this wage gap is related to differences in common support (i.e., immigrant women are segregated in certain jobs with low wages different from those occupied by native women). If the need to control for common support is neglected, estimates of the wage gap will be biased. Originality: Studying the case of Spain is particularly interesting because it is a country with abundant and recent immigration. Immigrant women account for more than half of the total immigrants in Spain, and unlike other host countries, they come from a highly varied range of countries, with origins as diverse as Latin America, the Maghreb and Eastern Europe. To our knowledge, no other study has explicitly focused on the analysis of the wage differential of immigrant women in the Spanish labour market by taking into account the need to control for common support. Moreover, published papers illustrating the potentiality of Ñopo"s (2008) methodology are also very scarce.

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study.

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.

On the origin of the selectivity of plasmidic H-NS towards horizontally acquired DNA: Linking H-NS oligomerization and cooperative DNA binding

The nucleoid-associated protein H-NS is a global modulator of the expression of genes associated with adaptation to environmental changes. A variant of H-NS expressed in the R27 plasmid was previously shown to selectively modulate the expression of horizontally acquired genes, with minimal effects on core genes that are repressed by the chromosomal form of H-NS. Both H-NS proteins are formed by an oligomerization domain and a DNA-binding domain, which are connected by a linker that is highly flexible in the absence of DNA. We studied DNA binding by means of oligomer-forming chimeric proteins in which domains of the chromosomal and plasmidic variants are exchanged, as well as in monomeric truncated forms containing the DNA-binding domain and variable portions of the linker. Point mutations in the linker were also examined in full-length and truncated H-NS constructs. These experiments show that the linker region contributes to DNA binding affinity and that it is a main component of the distinct DNA binding properties of chromosomal and plasmidic H-NS. We propose that interactions between the linker and DNA limit the flexibility of the connection between H- NS oligomerization and DNA binding and provide an allosteric indirect readout mechanism to detect long- range distortions of DNA, thus enabling discrimination between core and horizontally acquired DNA.

Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins

Addition of a 50 mM mixture of l-arginine and l-glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE.

Localized prostate cancer in Norway, the United States, and Spain: between-country differences of variables before treatment among patients eligible for curative treatment

Between-country differences in medical and sociodemographic variables, and patient-related outcomes (PROs) before treatment might explain published variations of side effects after radical prostatecomy (RP) or radiotherapy (RAD) for prostate cancer (PCa). This hypothesis was tested among 1908 patients from the United States, Spain, and Norway. Significant between-country differences were observed for most factors investigated before treatment. The observations should be considered in comparison of the frequency and severity of internationally published studies. Background: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to betweencountry differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. Patients and Methods: In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Results: Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Conclusion: Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literature

Determination and characterization of quinolones in foodstuffs of animal origin by CE-UV, LC-UV, LC-Fl, LC-MS and LC-MS/MS

In this work methods for the multiresidue determination of the series of quinolones include in the European regulation in food of animal origin are de veloped and validated in line with Commission Decision 2002/657/EC in terms of linearity, decision limit, capability detection, precision and stability. Mult iresidue methods were established to allow the determination of quinolones covered by EU legislation in 2377/90/EC in muscle of chicken, turkey, pig and cow, plasma of cow and pig, liver of pig and milk of cow. First an extraction step was optimized and a SPE step was applied to clean!up and preconcentrate quinolones prior to their separation by CE or LC and determination by CE!UV, LC!UV, LC!Fl, LC!MS with different ion sources (ESI ,ApCI) and different mass analyser (Q, ToF) and LC!E SI!QqQ tandem mass spectrometry. The limits of quantification obtained are always lower than Maxim um Residue Limit (MRL) established by EU for quinolones in animal products and they can be applied to the control of quinolones in foodstuffs of animal origin . Finally the proposed methods were applied to determine quinolones in samples of turkey and pig muscle, pig plasma and milk of cow. Excellent quality parameters and reduced time of analysis were obtained when LC!ESI!MS/MS is used, although the others techniques presented too satisfactory results.

Orofacial pain of cardiac origin: review literature and clinical cases

The most common types of orofacial pain originate at the dental or periodontal level or in the musculoskeletal structures. However, the patient may present pain in this region even though the source is located elsewhere in the body. One possible source of heterotopic pain is of cardiac origin. Objectives: Report two cases of orofacial pain of cardiac origin and review the clinical cases described in the literature. Study Design: Description of clinical cases and review of clinical cases. Results and conclusions: Nine cases of atypical pain of cardiac origin are recorded, which include 5 females and 4 males. In craniofacial structures, pain of cardiac origin is usually bilateral. At the craniofacial level, the most frequent location described is in the throat and jaw. Pain of cardiac origin is considered atypical due to its location, although roughly 10% of the cases of cardiac ischemia manifest primarily in craniofacial structures. Finally, the differential diagnosis of pain of odontogenic origin must be taken into account with pain of non-odontogenic origin (muscle, psychogenic, neuronal, cardiac, sinus and neurovascular pain) in order to avoid diagnostic errors in the dental practice as well as unnecessary treatments.

Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial.

BACKGROUND AND PURPOSE: Thromboxane prostaglandin receptors have been implicated to be involved in the atherosclerotic process. We assessed whether Terutroban, a thromboxane prostaglandin receptor antagonist, affects the progression of atherosclerosis, as measured by common carotid intima-media thickness and carotid plaques. METHODS: A substudy was performed among 1141 participants of the aspirin-controlled Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) trial. Common carotid intima-media thickness and carotid plaque occurrence was measured during a 3-year period. RESULTS: Baseline characteristics did not differ between Terutroban (n=592) and aspirin (n=549) treated patients and were similar as in the main study. Mean study and treatment duration were similar (28 and 25 months, respectively). In the Terutroban group, the annualized rate of change in common carotid intima-media thickness was 0.006 mm per year (95% confidence interval, -0.004 to 0.016) and -0.005 mm per year (95% confidence interval, -0.015 to 0.005) in the aspirin group. There was no statistically significant difference between the groups in the annualized rate of change of common carotid intima-media thickness (0.011 mm per year; 95% confidence interval, -0.003 to 0.025). At 12 months of follow-up, 66% of Terutroban patients had no emergent plaques, 31% had 1 to 2 emergent plaques, and 3% had ≥3 emergent plaques. In the aspirin group, the corresponding percentages were 64%, 32%, and 4%. Over time, there was no statistically significant difference in the number of emergent carotid plaques between treatment modalities (rate ratio, 0.91; 95% confidence interval, 0.77-1.07). CONCLUSIONS: Compared with aspirin, Terutroban did not beneficially affect progression of carotid atherosclerosis among well-treated patients with a history of ischemic stroke or transient ischemic attacks with an internal carotid stenosis <70%. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66157730.

Comparative genomics of Hedgehog loci in chordates and the origin of Shh regulatory novelties

The origin and evolution of the complex regulatory landscapes of some vertebrate developmental genes, often spanning hundreds of Kbp and including neighboring genes, remain poorly understood. The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32). To investigate the origin and evolution of this GRB, we sequenced and characterized the Hedgehog (Hh) loci from three invertebrate chordate amphioxus species, which share several early expression domains with Shh. Using phylogenetic footprinting within and between chordate lineages, and reporter assays in zebrafish probing >30 Kbp of amphioxus Hh, we report large sequence and functional divergence between both groups. In addition, we show that the linkage of Shh to Lmbr1 and Rnf32, necessary for the unique gnatostomate-specific Shh limb expression, is a vertebrate novelty occurred between the two whole-genome duplications.

An inertial sensor-based system for spatio-temporal analysis in classic cross-country skiing diagonal technique.

The present study proposes a method based on ski fixed inertial sensors to automatically compute spatio-temporal parameters (phase durations, cycle speed and cycle length) for the diagonal stride in classical cross-country skiing. The proposed system was validated against a marker-based motion capture system during indoor treadmill skiing. Skiing movement of 10 junior to world-cup athletes was measured for four different conditions. The accuracy (i.e. median error) and precision (i.e. interquartile range of error) of the system was below 6ms for cycle duration and ski thrust duration and below 35ms for pole push duration. Cycle speed precision (accuracy) was below 0.1m/s (0.005m/s) and cycle length precision (accuracy) was below 0.15m (0.005m). The system was sensitive to changes of conditions and was accurate enough to detect significant differences reported in previous studies. Since capture volume is not limited and setup is simple, the system would be well suited for outdoor measurements on snow.