Long-Term Survival of Human Neural Stem Cells in the Ischemic Rat Brain upon Transient Immunosuppression

Understanding the physiology of human neural stem cells (hNSCs) in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs) from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps) upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells) and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably, transplanted IhNSC-P can significantly dampen the inflammatory response in the lesioned host brain. This work further supports hNSCs as a reliable and safe source of cells for transplantation therapy in neurodegenerative disorders

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Paleoenvironmental evolution of the coastal plain of Southern Brazil: palynological data from a Holocene core in Santa Catarina State

ABSTRACT This paper presents a paleoenvironmental reconstruction from palynological analyses of a sedimentary core of Holocene age, drilled at municipality of Garopaba (Santa Catarina), Southern Brazil. A total of 46 samples was collected for palynological analyses in the 450 cm-long core PCSC-3, as also three samples for radiocarbon dating and granulometric analyses. The palynological content includes 84 taxa related to pollen grains of angiosperms (38) and gimnosperm (3), spores of pteridophyta (16) and bryophyta (2), spores of fungi (8), algae (3), acritarchs (3), dinoflagellate cysts (2) and microforaminiferal linings (1). Three specimens of acritarchs are described and illustrated in detail. Three palynological phases were defined based on changes in assemblages: Phase I, Phase II and Phase III. The Phase I is characterized as a lagoonal paleoenvironment with marine influence from the beginning of the sedimentation (5390 cal yr BP), based on occurrences of acritarchs, dinoflagellate cysts and microforaminiferal linings. The Phase II (3032 yr BP until 858 cal yr BP) also is characterized by a lagoonal paleoenvironment, however, presented decrease in percentage of marine elements and increase in freshwater algae record, suggesting less marine influence in the lagoonal body. In Phase III (last 856 years), underwater sedimentation prevailed, under swamp-like conditions

The unique nucleotide specificity of the sucrose synthase from Thermosynechococcus elongatus

Sucrose synthase catalyzes the reversible conversion of sucrose and UDP into fructose and UDP-glucose. In filamentous cyanobacteria, the sucrose cleavage direction plays a key physiological function in carbon metabolism, nitrogen fixation, and stress tolerance. In unicellular strains, the function of sucrose synthase has not been elucidated. We report a detailed biochemical characterization of sucrose synthase from Thermosynechococcus elongatus after the gene was artificially synthesized for optimal expression in Escherichia coli. The homogeneous recombinant sucrose synthase was highly specific for ADP as substrate, constituting the first one with this unique characteristic, and strongly suggesting an interaction between sucrose and glycogen metabolism.Fil: Figueroa, Carlos Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina. Loyola University Chicago; Estados UnidosFil: Asención Diez, Matías Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina. Loyola University Chicago; Estados UnidosFil: Kuhn, Misty L.. Loyola University Chicago; Estados UnidosFil: McEwen, Sheila. Loyola University Chicago; Estados UnidosFil: Salerno, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Grupo Vinculado Centro de Estudios de Biodiversidad y Biotecnología MdP- INBA; ArgentinaFil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Ballicora, Miguel A.. Loyola University Chicago; Estados Unido

Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease

Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity

Integration of geohazards into urban and land-use planning. Towards a Landslide Directive. The EuroGeoSurveys Questionnaire

Exposure to hazards is expected to increase in Europe, due to rapid population growth in urban areas and the escalation of urbanization throughout many countries. In the framework of the European Geological Surveys (EGS), the Earth Observation and Geohazards Expert Group (EOEG) has carried out a survey based enquiry regarding the integration of geohazards (earthquakes, volcanoes, landslides, ground subsidence, floods and others) into urban and land-use planning. Responses from 19 European countries and 5 regions reveal heterogeneous policies across national borders. 17% of the countries have not yet implemented any legal measures to integrate geohazards into urban and land-use plans and half of the participating countries have no official methodological guides to construct geohazard maps. Additionally, there is a scarce knowledge about real social impacts of geohazards and resulting disasters in many of the countries, although they have a significant impact on their national economies. This overview stresses the need for a common legislative framework and homogenization of the national legislations as well as mutual guidelines which adopt the principles applicable to the management of geohazards and explain the process to be followed in the production of hazard documentation. This is especially relevant in case of landslide and subsidence hazards; although those are of great importance in Europe, there are no common guidelines and practices similar to Directive 2007/60/EC on the assessment and management of flood risk. Based on their expertise, EuroGeoSurveys (EGS) have the potential to coordinate this activity in European geohazard guidelines and to promote the interaction among stakeholders