Y418C: a novel mutation in exon 9 of the glucocerebrosidase gene of a patient with Gaucher disease creates a new Bgl I site

We report a novel mutation in exon 9 of the glucocerebrosidase gene of a patient with Gaucher disease and of Sardinian origin.     

Bayesian mapping of multiple traits in maize: the importance of pleiotropic effects in studying the inheritance of quantitative traits

Pleiotropy has played an important role in understanding quantitative traits. However, the extensiveness of this effect in the genome and its consequences for plant improvement have not been fully elucidated. The aim of this study was to identify pleiotropic quantitative trait loci (QTLs) in maize using Bayesian multiple interval mapping. Additionally, we sought to obtain a better understanding of the inheritance, extent and distribution of pleiotropic effects of several components in maize production. The design III procedure was used from a population derived from the cross of the inbred lines L-14-04B and L-08-05F. Two hundred and fifty plants were genotyped with 177 microsatellite markers and backcrossed to both parents giving rise to 500 backcrossed progenies, which were evaluated in six environments for grain yield and its components. The results of this study suggest that mapping isolated traits limits our understanding of the genetic architecture of quantitative traits. This architecture can be better understood by using pleiotropic networks that facilitate the visualization of the complexity of quantitative inheritance, and this characterization will help to develop new selection strategies. It was also possible to confront the idea that it is feasible to identify QTLs for complex traits such as grain yield, as pleiotropy acts prominently on its subtraits and as this "trait" can be broken down and predicted almost completely by the QTLs of its components. Additionally, pleiotropic QTLs do not necessarily signify pleiotropy of allelic interactions, and this indicates that the pervasive pleiotropy does not limit the genetic adaptability of plants.     

Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery

Extra-abdominal desmoid tumours are slow-growing, histologically benign tumours of fibroblastic origin with variable biologic behaviour. They are locally aggressive and invasive to surrounding anatomic structures. Magnetic resonance imaging is the modality of choice for the diagnosis and the evaluation of the tumours. Current management of desmoids involves a multidisciplinary approach. Wide margin surgical resection remains the main treatment modality for local control of the tumour. Amputation should not be the initial treatment, and function-preserving procedures should be the primary treatment goal. Adjuvant radiation therapy is recommended both for primary and recurrent lesions. Chemotherapy may be used for recurrent or unresectable disease. Overall local recurrence rates vary and depend on patient's age, tumour location and margins at resection.     

Coexisting living stromatolites and infaunal metazoans

Microbialites, bioaccretionary structures formed during the growth and metabolism of microorganisms (principally cyanobacteria) were the dominant lifeform in shallow late-Archean and Proterozoic oceans. During the Cambrian radiation of metazoan life, which began ~540 Mya, microbialite abundance and diversity further declined following a peak in the Mesoproterozoic. Notwithstanding contention, grazing and bioturbation effects of metazoans have been hypothesized as the dominant driver of modern microbialite scarcity. However, this metazoan–microbialite exclusion has not been fully explored in the few extant microbialites. Here we provide further evidence showing that living marine layered microbialites (stromatolites) coexist with a persistent assemblage of benthic macro-invertebrates, as has previously been demonstrated in some thrombolitic (clotted) microbialites. Surprisingly, these metazoans have active habits, such as burrowing, which should be expected to disrupt the layered matrix. As other studies have shown, through a network of burrows, metazoans can exploit local diurnal oxygen refugia within microbialites as well as escape predation. Our results, therefore, add novel evidence in support of the hypotheses that geologically, metazoans are not always incompatible with stromatolites, while ecologically, microbialites may act as micro-refugia for modern metazoans and historically have performed a similar inferred role in past ecosystems.     

New piperidine-based derivatives as sigma receptor ligands. Synthesis and pharmacological evaluation

The sigma receptor (σR) family has been considered mysterious for a long time. In fact, the σ2R subtype has been cloned only recently, revealing its identity as TMEM97, a NPC1-binding protein involved in cholesterol biosynthesis and implicated in the pathogenesis of cancer and neurologic disorders. With the aim of developing new chemical entities gifted with σR affinity, herein we report the design and synthesis of new piperidine-based alkylacetamide derivatives with mixed affinity towards both σ1 and σ2R subtypes.     

Variability of the immunoglobulin heavy chain constant region locus: a population study

The Immunoglobulin Heavy chain Constant region (IGHC) locus is a multigene family composed of highly homologous segments often involved in unequal crossings over that lead to deleted and duplicated haplotypes. The frequencies of these haplotypes in 558 individuals from Lombardy, Veneto, Puglia and Sardinia were determined by Pulsed Field Gel Electrophoresis (PFGE), followed by Southern blotting with four IGHC probes, and compared with those observed in 110 subjects from Piedmont. Twenty deletions and 60 duplications were characterized, all in heterozygous individuals except for 2 homozygous deletions. The differences in frequency between the five populations were not significant. The deletions/duplications involved one or more genes: GP-A2, A1-E and G4 duplications, and A1-E and GP-A2 deletions were the most common. Four new duplications are described: three, involving the genes from GP to A2, from G2 to G4, and G4, are counterparts of known deletions. The fourth duplication spans from GP to G2. A G1 deleted heterozygous individual never previously described in Italy is reported. All the rearranged haplotypes seem to be the result of unequal crossing over. The difference between the number of duplications and deletions was significant in Sardinia, Lombardy, Puglia and in the total of 668 subjects (P < 0.001). This may be due to selection or genetic drift.     

Identification of lectin binding sites in the rat brain

Lectins belong to a class of proteins or glycoproteins able to bind carbohydrates. The study reported here describes the identification of lectin-binding sites in the adult rat brain. The results indicate that among the 31 lectins utilized, eight show a specific positive reaction with neurons. Staining was also observed with other cerebral structures such as myelin, leptomeninges, choroid plexus and capillaries. Lectins are, therefore, an important histochemical tool and can be easily and reliably used for the identification of cells and cerebral structures in the adult rat brain.Abbreviations Gal galactose - Fuc fucose - Man mannose - GalNAc N-acetylgalactosamine - GlcNAc N-acetylglucosamine - NeuNAc sialic acid     

Characterisation of the serotonin efflux induced by cytosolic Ca2+ and Na+ concentration increase in human platelets.

BACKGROUND/AIM: The present study aimed at elucidating the mechanism(s) of serotonin (5-HT) efflux induced by thapsigargin from human platelets in the absence of extra-cellular Ca2+. METHODS: Efflux of pre-loaded radiolabeled serotonin was generally determined by filtration techniques. Cytosolic concentrations of Ca2+, Na+ and H+ were measured with appropriate fluorescent probes. RESULTS: 5-HT efflux from control or reserpine-treated platelets--where reserpine prevents 5-HT transport into the dense granules--was proportional to thapsigargin evoked cytosolic [Ca2+]c increase. Accordingly factors as prostacyclin, aspirin and calyculin which reduced [Ca2+]c-increase also inhibited the 5-HT efflux. Thapsigargin, which also caused a remarkable increase in cytosolic [Na+]c, promoted less 5-HT release, in parallel to lower [Na+]c and [Ca2+]c increase, when added to platelet suspensions containing low [Na+]. The Na+/H+ exchanger monensin increased the [Na+]c and induced 5-HT efflux without affecting the Ca2+ level. The 5-HT efflux induced by both [Ca2+] or [Na+]c increase did not depend on pH or membrane potential changes, whereas it decreased in the absence of extra-cellular K+, and increased in the absence of Cl- or Na+. CONCLUSION: Increases in [Ca2+]c and [Na+]c independently induce serotonin efflux through the outward directed plasma membrane serotonin transporter SERT. This event might be physiologically important at the level of capillaries or narrowed arteries where platelets are subjected to high shear stress which causes [Ca2+]c increase followed by 5-HT release which might exert vasodilatation.