Molecular Aspects of Secretory Granule Exocytosis by Neurons and Endocrine Cells

Neuronal communication and endocrine signaling are fundamental for integrating the function of tissues and cells in the body. Hormones released by endocrine cells are transported to the target cells through the circulation. By contrast, transmitter release from neurons occurs at specialized intercellular junctions, the synapses. Nevertheless, the mechanisms by which signal molecules are synthesized, stored, and eventually secreted by neurons and endocrine cells are very similar. Neurons and endocrine cells have in common two different types of secretory organelles, indicating the presence of two distinct secretory pathways. The synaptic vesicles of neurons contain excitatory or inhibitory neurotransmitters, whereas the secretory granules (also referred to as dense core vesicles, because of their electron dense content) are filled with neuropeptides and amines. In endocrine cells, peptide hormones and amines predominate in secretory granules. The function and content of vesicles, which share antigens with synaptic vesicles, are unknown for most endocrine cells. However, in B cells of the pancreatic islet, these vesicles contain GABA, which may be involved in intrainsular signaling.' Exocytosis of both synaptic vesicles and secretory granules is controlled by cytoplasmic calcium. However, the precise mechanisms of the subsequent steps, such as docking of vesicles and fusion of their membranes with the plasma membrane, are still incompletely understood. This contribution summarizes recent observations that elucidate components in neurons and endocrine cells involved in exocytosis. Emphasis is put on the intracellular aspects of the release of secretory granules that recently have been analyzed in detail

From deceased to bioengineered graft: New frontiers in liver transplantation

none6siopenCesaretti M.; Zarzavajian Le Bian A.; Moccia S.; Iannelli A.; Schiavo L.; Diaspro A.Cesaretti, M.; Zarzavajian Le Bian, A.; Moccia, S.; Iannelli, A.; Schiavo, L.; Diaspro, A

Linking inflammation and hypertension in humans: studies in Bartter's/Gitelman's syndrome patients

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Geology of the Saint-Marcel valley metaophiolites (Northwestern Alps, Italy)

The geological map of the Saint-Marcel valley at the scale of 1:20,000 illustrates the tectonic setting of metaophiolites from the southern Aosta Valley, in the Italian side of the Western Alpine belt. The map highlights the sharp contact between the metaophiolitic basement and its metasedimentary cover, which mainly consists of quartzites, marbles, and calcschists. In spite of the Alpine tectonics, this contact is regarded as deriving from the original oceanic crust/sediments interface. Metaophiolites mostly consist of metabasalts hosting Fe\u2013Cu sulphide mineralisations, characterised by high-pressure metamorphic imprint. These rocks likely represent the shallowest portion of the Tethyan oceanic lithosphere created near the axis of the slow-spreading ridge where hydrothermal fluid circulation was active. Selected key-sections through metasediments reveal a consistent internal lithostratigraphy, in spite of the pervasive metamorphic and tectonic reworking acting during the Alpine evolution. Metasediments reflect various sedimentation episodes starting from pelagic and proximal settings to the onset of the orogenic stage. The Saint-Marcel valley metasediments thus reflect a changing in the sedimentation environments through time and space during the overall geologic evolutio

Application of next generation semiconductor-based sequencing for the identification of apis mellifera complementary sex determiner (Csd) alleles from honey dna

The complementary sex determiner (csd) gene plays an essential role in the sex determination of Apis mellifera L. Females develop only if fertilized eggs have functional heterozygous genotypes at this gene whereas males, being haploids, are hemizygous. Two identical csd alleles produce non vital males. In light of the recent decline in honey bee populations, it is therefore important to monitor the allele variability at this gene. In this study, we tested the application of next generation semiconductor-based sequencing technology (Ion Torrent) coupled with environmental honey DNA as a source of honey bee genome information to retrieve massive sequencing data for the analysis of variability at the hypervariable region (HVR) of the csd gene. DNA was extracted from 12 honey samples collected from honeycombs directly retrieved from 12 different colonies. A specifically designed bioinformatic pipeline, applied to analyze a total of about 1.5 million reads, identified a total of 160 different csd alleles, 55% of which were novel. The average number of alleles per sample was compatible with the number of expected patrilines per colony, according to the mating behavior of the queens. Allele diversity at the csd could also provide information useful to reconstruct the history of the honey

PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors

Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including formation of signalling-competent ligand-receptor complexes, their endocytosis and trafficking. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF) -activated TrkB and p75NTR in motor neurons. Here, using a proteomic approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1 knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors

A Case Study of Malignant Edema in Postpartum Mediterranean Buffaloes (Bubalus bubalis)

The paper describes for the first time four cases of postparturient malignant edema in water buffaloes due to Clostridium septicum (Cl. septicum). The study was carried out on four primiparous buffaloes that showed swelling of perineal and perivulvar areas, fever and agalactia a few hours after calving. Two of them died within 20 hours after calving. The other two developed edema in the skeletal muscles of one leg and were treated with sulfadiazine-trimethoprim for 10 days. The clinical signs completely resolved. Culture and molecular investigations identified the pathogen isolated from exudate taken from the vulva as Cl. septicum. The isolate showed multi-drug resistance. In the management of infection due to Cl. septicum, timely diagnosis and the chirurgic curettage, associated with a broad-spectrum antibiotic therapy, were found to be sufficient for the survival and recovery of the infected animals

Whole Genome Sequencing Provides Information on the Genomic Architecture and Diversity of Cultivated Gilthead Seabream (Sparus aurata) Broodstock Nuclei

The gilthead seabream (Sparus aurata) is a species of relevance for the Mediterranean aquaculture industry. Despite the advancement of genetic tools for the species, breeding programs still do not often include genomics. In this study, we designed a genomic strategy to identify signatures of selection and genomic regions of high differentiation among populations of farmed fish stocks. A comparative DNA pooling sequencing approach was applied to identify signatures of selection in gilthead seabream from the same hatchery and from different nuclei that had not been subjected to genetic selection. Identified genomic regions were further investigated to detect SNPs with predicted high impact. The analyses underlined major genomic differences in the proportion of fixed alleles among the investigated nuclei. Some of these differences highlighted genomic regions, including genes involved in general metabolism and development already detected in QTL for growth, size, skeletal deformity, and adaptation to variation of oxygen levels in other teleosts. The obtained results pointed out the need to control the genetic effect of breeding programs in this species to avoid the reduction of genetic variability within populations and the increase in inbreeding level that, in turn, might lead to an increased frequency of alleles with deleterious effects

Taking advantage from phenotype variability in a local animal genetic resource: identification of genomic regions associated with the hairless phenotype in Casertana pigs

Casertana is an endangered autochthonous pig breed (raised in south-central Italy) that is considered to be the descendant of the influential Neapolitan pig population that was used to improve British breeds in the 19th century. Casertana pigs are characterized by a typical, almost complete, hairless phenotype, even though a few Casertana pigs are normal haired. In this work, using Illumina PorcineSNP60 BeadChip data, we carried out a genome-wide association study and an FST analysis with this breed by comparing animals showing the classical hairless phenotype (n = 81) versus pigs classified as haired (n = 15). Combining the results obtained with the two approaches, we identified two significant regions: one on porcine chromosome (SSC) 7 and one on SSC15. The SSC7 region contains the forkhead box N3 (FOXN3) gene, the most plausible candidate gene of this region, considering that mutations in another gene of the same family (forkhead box N1; Foxn1 or FOXN1) are responsible for the nude locus in rodents and alopecia in humans. Another potential candidate gene, rho guanine nucleotide exchange factor 10 (ARHGEF10), is located in the SSC15 region. FOXN3 and ARHGEF10 have been detected as differentially expressed in androgenetic and senescent alopecia respectively. This study on an autochthonous pig breed contributes to shed some light on novel genes potentially involved in hair development and growth and demonstrates that local animal breeds can be valuable genetic resources for disclosing genetic factors affecting unique traits, taking advantage of phenotype variability segregating in small populations