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.

Thiopeptide antibiotics: retrospective and recent advances

Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

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.

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.

Approach to the Lower Pliocene marine-continental correlation from southern Spain. The micrommamal site of Alhaurín el Grande-1 (Málaga Basin, Betic Cordillera, Spain)

A new micromammal site at Alhaurín el Grande (Málaga, southern Spain) located above early Pliocene marine deposits allows an approach to the marine-continental correlation for this age. The early Pliocene marine filling throughout the Málaga Basin is developed in three transgressive-regressive sequences (Pl-1, Pl-2, and Pl-3 units) bounded by discontinuities. At the top of the intermediate sequence Pl-2, peaty sediments have yielded fossils of Rodentia, Lagomorpha, Insectivora, and Crocodylia. The presence of Cricetus barrieri Mein & Michaux, 1970 in combination with murids, both of primitive morphology, such as Apodemus gudrunae Van de Weerd, 1976, and more advanced forms (i.e. Occitanomys brailloni Michaux, 1969 and Stephanomys donnezani cordii Ruiz Bustos, 1986), points to an early Ruscinian age (MN 14 biozone). Based on the planktonic foraminifers, the biostratigraphic data indicate that marine sediments just below the micromammal beds belong to the MPl-2 biozone of the early Zanclean. Available paleomagnetic data from the marine sediments show that the micromammal bed must be located between the normal geomagnetic subchron C3n3n (4.89-4.80 Ma) and the subchron C3n2n (4.63-4.49 Ma), limiting the age of this site to the late part of the early Zanclean.

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.

The history of the El Niño-Southern Oscillation according to lacustrine and marine sediments

El gran impacte que El Niño - Oscil·lació del Sud (ENSO) té en la nostra societat industrialitzada ha esperonat la comunitat científica d'arreu a entendre quins són els mecanismes físics que el controlen, així com clarificar quina ha estat la seva història. El registre sedimentari de sensors naturals, com els llacs o la mar, ha permès reconstruir la història de l'ENSO. En aquest article, els autors donen una visió sintètica de la història d'aquest fenomen climàtic al llarg dels darrers quatre milions d'anys.

The history of the El Niño-Southern Oscillation according to lacustrine and marine sediments

El gran impacte que El Niño - Oscil·lació del Sud (ENSO) té en la nostra societat industrialitzada ha esperonat la comunitat científica d'arreu a entendre quins són els mecanismes físics que el controlen, així com clarificar quina ha estat la seva història. El registre sedimentari de sensors naturals, com els llacs o la mar, ha permès reconstruir la història de l'ENSO. En aquest article, els autors donen una visió sintètica de la història d'aquest fenomen climàtic al llarg dels darrers quatre milions d'anys.

Orofacial pain of cardiac origin, serial of clinical cases

Objective: To determine the clinical characteristics of the orofacial pain of cardiac origin in patients visited when doing a treadmill exercise test, at the cardiology service of the Can Ruti Hospital in Badalona (Barcelona, Spain). Study design: The sample of that study included thirty patients visiteding when doing a treadmill exercise test, at the cardiology service. The questionnaire has been asked to a sample of 30 patients. Results: Eleven of the 30 patients included in this study presented craniofacial pain before or during the cardiac seizure. The location of the pain was bilateral, non-irradiated at the mandible in all cases. The intensity of the pain was from slight to severe. The frequency of the appearance of the pain was paroxysmal in 8 cases and constant in three cases, and the duration was from a few hours to a maximum of 14 days. Discussion: The cardiac pain in craniofacial structures is usually bilateral, compared to odontogenic pain which is always unilateral. The pain of cardiac origin is considered atypical because of its location, but about the 10 % of the cases, the cardiac ischemia has its primary manifestation in orofacial structures. Conclusions: Eleven patients referred a bilateral non-irradiated mandibular pain, with intensity from slight to severe, and with a paroxystic frequency in eight cases and a constant frequency in three cases. Just one patient referred pain during the treadmill exercise test. In all cases the pain disappeared after the cardiac surgery or the administration of vasodilators.