Serotonin signaling contribution to an evolutionary success: the jaw joint of vertebrates

Serotonin (5-HT) is an ancient molecule that appeared very early during evolution, and it is present in different phyla. The 5-HT signaling system includes several G-coupled receptors and it is widely conserved in vertebrates. 5-HT is implicated in an astonishing number of biological processes and it has a key role as a morphogen in several complex networks during development before it can act as a neurotransmitter. Recent advances on how serotonin signaling can influence early development and its role in vertebrate morphogenesis come from mice and Xenopus. The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates (agnathans) represents a major event in the evolution of vertebrates. The acquisition of a jaw is assumed to have occurred after the split between gnathostomes and jawless vertebrates. A crucial question concerns what changes were introduced in the developmental patterning programme to obtain a jaw joint that is one of the most innovative inventions in the history of vertebrates. Molecular and developmental studies performed in Xenopus revealed for the first time that serotonin, through the 5-HT2B receptor signaling, is both sufficient and necessary to modulate the shape and functionality of the jaw, including the jaw joint. Accordingly, serotonin can be added to the complex interactive network of extrinsic factors that regulates mandibular arch development, thus contributing to one of the major vertebrate successes in evolution

Metal and proteomic analysis of sporadic ALS patients with common geographical origin

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder characterized by selective degeneration of both upper and lower motor neurons in the brain, brainstem, and spinal cord. This results in paralysis due to muscle weakness and atrophy, leading to death in 3-5 years. Genetic and environmental factors are involved in the pathogenesis of the disease and metals metabolism have been linked to ALS. This study enrolled seven patients and five controls (age matched, living in the same geographical area). For metal quantitation, samples of serum were analyzed by ICP-MS. For proteomic analyses, immobilized pH gradient covered the 4-10 and 3-7 pH range. Statistical analyses were carried out with Student's t-test and Artificial Neural Networks. Among the metals analyzed, As concentration resulted significantly lower in patients than in controls (p=0.007); Hg too was found in lower concentration in patients, but with a lower statistical significance (p=0.13). Higher concentration of Al in patients was detected (p=0.08). In this study, we were not able to confirm the higher concentrations of Ni and Pb in patients previously described in a smaller cohort. Our proteomics data show that APOA2 is decreased by 30% in patients with respect to controls. Furthermore, AHSG and SAP showed a significant decrease in patients with a story of more than 10 years of disease. Impaired metal homeostasis, attributable to environmental exposure, could lead to mineral overload. Besides promoting oxidative stress, metals can compete for the binding sites of metal-containing proteins, such as those containing iron-sulfur clusters. At present, no literature data link APOA2 to ALS, but the fact that its mRNA is processed by TDP43, provides a possible connection with the disease. The proteins differentially expressed belong to the group of Acute Phase Reaction proteins, possibly linking ALS to a chronic inflammation status. Further experiments are still ongoing

Dissecting Sporadic ALS in a geographical cluster of patients: a multidisciplinary study

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder that results in paralysis and leading to death in 3-5 years. Genetic and environmental factors are involved in the pathogenesis of this disease and metals metabolism has been linked to ALS. Proteomic studies are currently being performed to search for possible biomarkers. Here we present a study aimed at investigating different aspects of the disease, based on a multidisciplinary approach. The cohort of ALS patients that we analyzed includes seven patients, all originating from a common, restricted, geographical area and five matched controls. Environmental exposure is the same for all these subjects. SOD1, FUS, TDP43, C9ORF72 and APOE genotypes were evaluated. For metal quantitation, samples of serum and whole blood were analyzed by ICP-MS. For proteomic analyses, immobilized pH gradient covered the 4-10 and 3-7 pH range both in reducing and nonreducing conditions. Levels of DNA oxidation were evaluated by a comet assay. Statistical analyses were carried out with Student\u2019s t-test and Artificial Neural Networks. As concentration resulted significantly lower in patients than in controls ( Auto-CM analysis linked closely high concentrations of Al and Se to the ALS group. Levels of metals in whole blood have been correlated with levels in serum. Proteomics data show that some proteins related to Acute Phase Response (APR) and lipid homeostasis are decreased in patients. Apo\u3b54 allele is more represented in the patient\u2019s group than in controls\u2019. Impaired metal homeostasis, attributable to environmental exposure, could lead to mineral overload. Metals can compete for the binding sites of metal-containing proteins. The different expression of the APR proteins reported could be a reflection of the disease status of the subjects analyzed. Enrichment in Apo\u3b54 allele frequency in patients may provide a link between neurodegeneration and lipid metabolism disturbances

A multidisciplinary approach to study Sporadic Amyotrophic Lateral Sclerosis in patients with common geographical origin

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder, is object of intensive research as the causes are still unknown and a treatment not available yet. This project is aimed to study, with a multidisciplinary approach, a small cohort of ALS subjects with a common environmental exposure. For metal quantitation, samples of serum and whole blood were analyzed by ICP-MS. For proteomic analyses, immobilized pH gradient covered the 4-10 and 3-7 pH range. Arsenic concentration resulted significantly lower in patients than in controls. Also, Mn and Hg showed lower levels in patients. Levels of plasma APOA2 protein resulted decreased in patients with respect to controls, whereas SAMP showed a significant decrease only in the late onset group. APOA1 and TTHY also were decreased, the latter in late-onset patients. RET4 was decreased only in the early-onset group. When evaluating APOE genotype we found a 3-fold increase in the frequency of E3/E4 genotype in the patient\u2019s group. DNA oxidative stress has been evaluated through a Comet Assay. The multidisciplinary approach applied in this study allowed to dissect different aspects of ALS, often are evaluated separately and in heterogeneous cohorts of patients

Metal and proteomic analysis of sporadic ALS patients with common geographical origin

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder characterized by selective degeneration of both upper and lower motor neurons in the brain, brainstem, and spinal cord. This results in paralysis due to muscle weakness and atrophy, leading to death in 3-5 years. Genetic and environmental factors are involved in the pathogenesis of the disease and metals metabolism have been linked to ALS. This study enrolled seven patients and five controls (age matched, living in the same geographical area). For metal quantitation, samples of serum were analyzed by ICP-MS. For proteomic analyses, immobilized pH gradient covered the 4-10 and 3-7 pH range. Statistical analyses were carried out with Student's t-test and Artificial Neural Networks. Among the metals analyzed, As concentration resulted significantly lower in patients than in controls (p=0.007); Hg too was found in lower concentration in patients, but with a lower statistical significance (p=0.13). Higher concentration of Al in patients was detected (p=0.08). In this study, we were not able to confirm the higher concentrations of Ni and Pb in patients previously described in a smaller cohort. Our proteomics data show that APOA2 is decreased by 30% in patients with respect to controls. Furthermore, AHSG and SAP showed a significant decrease in patients with a story of more than 10 years of disease. Impaired metal homeostasis, attributable to environmental exposure, could lead to mineral overload. Besides promoting oxidative stress, metals can compete for the binding sites of metal-containing proteins, such as those containing iron-sulfur clusters. At present, no literature data link APOA2 to ALS, but the fact that its mRNA is processed by TDP43, provides a possible connection with the disease. The proteins differentially expressed belong to the group of Acute Phase Reaction proteins, possibly linking ALS to a chronic inflammation status. Further experiments are still ongoing

Serum metal evaluation in a small cohort of Amyotrophic Lateral Sclerosis patients reveals high levels of thiophylic species

Amyotrophic Lateral Sclerosis (ALS) has often been associated with improper/altered metal metabolism. Analysis of thiophylic metals in serum from a small and geographically restricted cohort of ALS patients indicates contents of Pb and Ni much higher in patients than in controls (Ni, 5-fold; Pb, 2-fold). Se levels are also higher in the patients\u2019 group, which has instead lower As levels than controls. Thiophylic metals may impair biogenesis of FeS clusters or substitute for iron, even in folded proteins; Se may non-functionally replace S. Thus, improper assembly/function of FeS proteins could represent another possible issue to be considered in ALS pathogenesis

Continuous Flooding or Alternate Wetting and Drying Differently Affect the Accumulation of Health-Promoting Phytochemicals and Minerals in Rice Brown Grain

Climate changes impose adoption of water-saving techniques to improve the sustainability of irrigated rice systems. This study was aimed, by a two-years side-by-side comparison, at verifying the hypothesis whether \u201cAlternate Wetting and Drying\u201d (AWD) affects the concentrations of health-related compounds and minerals in brown grains of three japonica rice (Oryza sativa L.) cvs (\u2018Baldo\u2019, \u2018Gladio\u2019, and \u2018Loto\u2019) usually grown in temperate areas in continuous flooding (CF). Due to the rotational turns in water distribution imposed by local authorities and to the weather behavior, different AWD timing and severity occurred in the two years of the study. AWD induced in both seasons yield losses in \u2018Baldo\u2019 and \u2018Gladio\u2019 but not in \u2018Loto\u2019. In the brown grains of \u2018Loto\u2019, AWD increased the concentrations of total tocols, \u3b3-oryzanol, flavonoids, and the antioxidant activity. AWD affected the concentrations of minerals, particularly increasing copper, cadmium and nickel, and decreasing manganese, arsenic and zinc. In the sensitive cultivars, \u2018Baldo\u2019 and \u2018Gladio\u2019, AWD seems to affect plant yield, rather than for severity of the dry period, for prolonged absence of ponded water that exposes plants to cooler temperatures. The selection of suitable cultivars, like \u2018Loto\u2019, tolerant to AWD-related stresses, could combine environmental, yield-related, and nutritional benefits improving the product quality

Utilização de estirpes do fungo Colletotrichum gloeosporioides no controle da Orthezia praelonga.

A cochonilha Orthezia praelonga Douglas (Hom., Ortheziidae) se constitui desde 1950 numa das maiores ameacas a citricultura brasileira. Alem das plantas cítricas, ataca vários hospedeiros cultivados e silvestres. Seu controle vem sendo realizado com uso de inseticidas altamente toxicos ou pela erradicação das árvores atacadas. Investigando seus inimigos naturais na baixada carioca-fluminense, ROBBS (1947) identificou um eficiente entomopatógeno que denominou "fungo vermelho" (Fusarium sp). Estudos posteriores realizados por outros autores reconheceram tratar-se de Colletotrichum gloeosporioides Penz., identificação recentemente confirmada pelo COMMONWEALTH MYCOLOGICAL INSTITUTE da Inglaterra.Pesquisas realizadas no CNPDA/EMBRAPA com o C. gloeosporioides de diferentes procedências resultaram na seleção de duas cepas, que demonstraram excelente colonização do inseto e exteriorização dos propagulos, em condições de laboratório e de campo. Inoculações procedidas em flores e folhas de Citrus spp. e Coffea arábica L. não revelaram qualquer reação de patogenicidade. O inoculo da estirpe de C. gloesporioides isolada de O. praelonga vem sendo aplicado por pulverizações em pomares para melhor avaliação das épocas mais adequadas a sua introdução e disseminação. Foi utilizada uma suspensão de aproximadamente 10 6 conídios/ml adicionando-se óleo mineral emulsionável a 1% v/v. O tratamento e realizado apenas em algumas árvores das reboleiras afetadas, o suficiente para a disseminação do entomopatógeno. A mortalidade verificada tem variado de 80 a 100% nos pomares tratados, de 60 a 150 dias após a pulverização

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Search for anomalies in the neutrino sector with muon spectrometers and large LArTPC imaging detectors at CERN

A new experiment with an intense ~2 GeV neutrino beam at CERN SPS is proposed in order to definitely clarify the possible existence of additional neutrino states, as pointed out by neutrino calibration source experiments, reactor and accelerator experiments and measure the corresponding oscillation parameters. The experiment is based on two identical LAr-TPCs complemented by magnetized spectrometers detecting electron and muon neutrino events at Far and Near positions, 1600 m and 300 m from the proton target, respectively. The ICARUS T600 detector, the largest LAr-TPC ever built with a size of about 600 ton of imaging mass, now running in the LNGS underground laboratory, will be moved at the CERN Far position. An additional 1/4 of the T600 detector (T150) will be constructed and located in the Near position. Two large area spectrometers will be placed downstream of the two LAr-TPC detectors to perform charge identification and muon momentum measurements from sub-GeV to several GeV energy range, greatly complementing the physics capabilities. This experiment will offer remarkable discovery potentialities, collecting a very large number of unbiased events both in the neutrino and antineutrino channels, largely adequate to definitely settle the origin of the observed neutrino-related anomalies.Comment: Contribution to the European Strategy for Particle Physics - Open Symposium Preparatory Group, Kracow 10-12 September 201