The mammalian centrosome and its functional significance

Primarily known for its role as major microtubule organizing center, the centrosome is increasingly being recognized for its functional significance in key cell cycle regulating events. We are now at the beginning of understanding the centrosome’s functional complexities and its major impact on directing complex interactions and signal transduction cascades important for cell cycle regulation. The centrosome orchestrates entry into mitosis, anaphase onset, cytokinesis, G1/S transition, and monitors DNA damage. Recently, the centrosome has also been recognized as major docking station where regulatory complexes accumulate including kinases and phosphatases as well as numerous other cell cycle regulators that utilize the centrosome as platform to coordinate multiple cell cycle-specific functions. Vesicles that are translocated along microtubules to and away from centrosomes may also carry enzymes or substrates that use centrosomes as main docking station. The centrosome’s role in various diseases has been recognized and a wealth of data has been accumulated linking dysfunctional centrosomes to cancer, Alstrom syndrome, various neurological disorders, and others. Centrosome abnormalities and dysfunctions have been associated with several types of infertility. The present review highlights the centrosome’s significant roles in cell cycle events in somatic and reproductive cells and discusses centrosome abnormalities and implications in disease

Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases

Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients' Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure

Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK

Background: Biallelic mutations in TBC1-domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease. Methods: Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples. Results: A novel homozygous truncation in TBCK was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients. Conclusions: Our findings identify a novel early truncating variant in TBCK associated with a severe presentation and add muscle disease to the variability of phenotypes associated with TBCK mutations. Inconsistent genotype/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues

Cutaneous manifestations of systemic non-Hodgkin lymphomas (NHL): Study and review of literature

Systemic non-Hodgkin lymphomas are often accompanied by cutaneous manifestations, which are not always looked out for. Nevertheless, these alterations can be very important because their presence is lied to the clinical behaviour of the underlying malignancy, with an early recognition being fundamental. The aim of this study was to make order in this topic and propose a preliminary classification of the cutaneous manifestations associated with non-Hodgkin lymphomas. We performed a retrospective chart review of 62 haematological patients affected by non-Hodgkin systemic lymphomas with dermatological manifestations, who were evaluated from January 2007 to December 2011, and combined these results with a systematic review of Pub medical literature from 1937 to 2011 on this topic. A preliminary classification of these manifestations has been proposed, dividing them in specific and non-specific ones, along with a description of the clinical features and those cases observed in our department. A preliminary approach has been proposed for the study of these manifestations that could be helpful in understanding the biological behaviour and aid early recognition of a flare up in systemic non-Hodgkin lymphomas

Feasibility of local anaesthesia for varicocele correction in one-day-surgery setting. A single center experience

In this study, we compared postoperative outcomes of patients submitted to varicocele correction under general or local anesthesia at a single center

Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease

Congenital muscular dystrophies due to defects in genes encoding proteins involved in alpha-dystroglycan (alpha-DG) glycosylation are a heterogeneous group of muscle disorders variably associated with central nervous system and eye abnormalities. One of the more severe is muscle-eye-brain disease (MEB). Mutations in genes coding for proven or putative glycosyltransferases (POMT1, POM72, POMGnT1, fukutin, FKRP, and LARGE), the DPM3 gene encoding a DOL-P-Man synthase subunit, and the DAG1 gene encoding alpha-dystroglycan, have been associated with altered alpha-DG glycosylation. We report new POMGnT1 mutations and evaluate protein expression in 3 patients and 2 foetuses with variably severe MEB features. We identify two new point mutations (c.643 C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895 + 1 G>T. Our study provides further evidence that rearrangements of the POMGnT1 gene are relatively common. Importantly, if heterozygous, they can be missed on standard genomic DNA sequencing. POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression. Cerebral MRI is important for identifying MEB and alpha-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis. (C) 2012 Elsevier B.V. All rights reserved

Toxocara seroprevalence in children from a subtropical city in Argentina Prevalencia de anticuerpos anti Toxocara en niños de una ciudad subtropical de Argentina

Most studies from Argentina have focused on toxocariasis as an environmental problem of big cities, and there are no available data about children infection from small or middle-sized cities. In order to assess the prevalence of anti-Toxocara antibodies in infantile population, 206 children from Resistencia, of both sexes, aged 1-14 years old were studied by Elisa testing with E/S T. canis L2 antigens. Hematological parameters and immunoglobulin levels were determined; five days' stool samples were studied and epidemiological data were obtained by means of a questionnaire to parents. Results showed that 73% of the children had one or more dogs living at home, 57% reported geophagia and 37.9% were positive for Toxocara serology, but there was no significant difference in prevalence neither for boys and girls, nor concerning age. An increased risk of infection was observed in age groups 5-6 and 7-8 for boys, and in age groups 3-4 and 5-6 for girls.<br>La mayoría de los estudios realizados en Argentina, han enfocado a la Toxocariosis como un problema medioambiental propio de las grandes ciudades y no existen datos acerca de esta infección entre los niños de ciudades medianas o pequeñas. A fin de determinar la prevalencia de anticuerpos anti-Toxocara en la población infantil de la ciudad de Resistencia, se estudiaron 206 niños de ambos sexos, con edades comprendidas entre los 1-14 años, mediante el test de Elisa, empleando antígenos E/S de larva L2 de Toxocara canis. También se evaluaron los niveles de inmunoglobulinas séricas y los parámetros hematológicos; se efectuaron análisis coproparasitológico seriados en heces de 5 días y se recolectó información epidemiológica mediante cuestionario a los padres. Los resultados obtenidos señalan que el 73% de los niños tenían uno o mas perros viviendo en la casa, que el 57% tenían antecedentes de geofagia y que el 37.9% tenían serología positiva para Toxocara, aunque no hubo diferencias estadísticamente significativas entre varones y mujeres ni con la edad. Un mayor riesgo de contraer la infección se observó entre los grupos etarios 5-6 y 7-8 de varones y 3-4 y 5-6 de mujeres