PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma

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Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons

Background. The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data. Methods. In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4-7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events. Initial and ongoing training of sites' staff were undertaken during the studies, and a data and safety monitoring board reviewed all the data during and after the studies. Results. The safety of PsA-TT was evaluated according to international standards despite obvious challenges in remote areas where these studies were conducted. These challenges included the need for uniformity of methods, timely reporting in the context of frequent communication problems, occurrence of seasonal diseases such as malaria and rotavirus diarrhea, and healthcare systems that required improvement. Conclusions. The trials of PsA-TT highlighted the value of a robust vaccine development plan and design so that lessons learned in initial studies were incorporated into the subsequent ones, initial training and periodic retraining, strict monitoring of all procedures, and continuous channel of communication with all stakeholders that enabled the application of international requirements to local settings, with high quality of dat

MAREA PROJECT : MEDISEH (Mediterranean Sensitive Habitats) specific contract no 2 (SI2.600741)

Based on the following Terms of Reference (TOR) of the content of the European Commission DG MARE request Ares (2011)665688: “Compile information supporting the identification and location of nursery areas (juveniles in their first and, if appropriate, second year of life) and spawning aggregations. This information, which is to be collated and archived in formats adequate for GIS rendering, shall refer to all the demersal and small pelagic species in the Mediterranean included in Appendix VII of Council Regulation (EC) No 199/2008 as well as for the species subject to minimum size (Council Regulation (EC) No 1967/2006-Annex III). In addition, ecological characterisation of these areas, both in terms of biological community (assemblage) and habitats therein, must be provided.” The technical tender form of the Specific Contract 2 (MEDISEH) defined the following objectives: Review of historical and current data on the locations and the status of seagrass beds, coralligenous and mäerl beds in different GSAs (Geographical Sub-Areas amending amending the Resolution GFCM/31/2007/2) all over the Mediterranean basin. Transform the information into a digitilized format within the framework of a geodatabase Review and map of all existing specific Marine Protected Areas (MPAs) in the Mediterranean area as well as areas that are under any form of national or international regulation. Identify and map suitable areas for Posidonia, coralligenous and mäerl communities by developing habitat distribution models at different spatial scales. Review and map all existing information on historical and current data of nurseries and spawning grounds of certain small pelagic (i.e., Engraulis encrasicolus, Sardina pilchardus, Scomber spp., Trachurus spp.) and demersal species (i.e., Aristaeomorpha foliacea, Aristeus antennatus, Merluccius merluccius, Mullus barbatus, Mullus surmuletus, Nephrops norvegicus, Parapenaeus longirostris, Pagellus erythrinus, Galeus melastomus, Raja clavata, Illex coindetti, Eledone cirrosa) that are included in the Data Collection Framework for the Mediterranean and subjected to minimum landing size based on Council Regulation No 1967/2006-Annex II. Analyze existing survey data and apply spatial analysis techniques in order to identify locations that are more likely to be density hot spot areas or are being more suitable for fish nurseries and spawning grounds for Engraulis encrasicolus, Sardina pilchardus, Scomber spp., Trachurus trachurus, Aristaeomorpha foliacea, Aristeus antennatus, Merluccius merluccius, Mullus barbatus, Mullus surmuletus, Nephrops norvegicus, Parapenaeus longirostris, Pagellus erythrinus, Galeus melastomus, Raja clavata, Illex coindetti, Eledone cirrosa These areas will also be characterized from an environmental and ecological perspective upon data availability. Integrate and present the aforementioned information through a Web-based GIS viewer with an associated geo-referenced database that will operate as a consulting tool for spatial management and conservation planning. Following the revision of the knowledge base, to identify gaps and suggest future research priorities. In order to meet these objectives, an expert team was composed within the MAREA Consortium from scientists with established expertise in the different topics required, and working in different areas of the Mediterranean basin. The team formed to execute the project includes the main Institutes of EU countries in the Mediterranean, all having solid reputations in the fields covered. The participating Institutes/Entities operate in the Western, Central and Eastern parts of the Mediterranean basin, and this ensures familiarity with the geographical areas that are related to the specific tendering. Moreover, a large number of scientists outside of the MAREA Consortium collaborated on a volunteer basis with data and other input. Details on the list of experts and external collaborators can be found in each Work Package in the present report. For CV details, check the MAREA expert web-site http://www.mareaproject.net/.peer-reviewe

Seagrass meadows (Posidonia oceanica) distribution and trajectories of change.

Posidonia oceanica meadows are declining at alarming rates due to climate change and human activities. Although P. oceanica is considered the most important and well-studied seagrass species of the Mediterranean Sea, to date there has been a limited effort to combine all the spatial information available and provide a complete distribution of meadows across the basin. The aim of this work is to provide a fine-scale assessment of (i) the current and historical known distribution of P. oceanica, (ii) the total area of meadows and (iii) the magnitude of regressive phenomena in the last decades. The outcomes showed the current spatial distribution of P. oceanica, covering a known area of 1,224,707 ha, and highlighted the lack of relevant data in part of the basin (21,471 linear km of coastline). The estimated regression of meadows amounted to 34% in the last 50 years, showing that this generalised phenomenon had to be mainly ascribed to cumulative effects of multiple local stressors. Our results highlighted the importance of enforcing surveys to assess the status and prioritize areas where cost-effective schemes for threats reduction, capable of reversing present patterns of change and ensuring P. oceanica persistence at Mediterranean scale, could be implemented.This study was supported and financed by the Commission of the European Union (DG MARE) within the MAREA Framework contract (Call for tenders MARE/2009/05_Lot1) through the Specific Project MEDISEH (SI2.600741): Mediterranean Sensitive Habitats, that received 568.996 euro. The opinions expressed are those of the authors of the study only and do not represent the Commission’s official position. The European Commission is thankfully acknowledged.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/srep1250

Leucine-Rich Glioma-Inactivated 1 Encephalitis: Broadening the Sphere

Background: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare entity. Its typical features are seizures, faciobrachial dystonic seizures (FBDS), cognitive impairment, and personality changes. Case report: We report the case of a 66-year-old man with an unusual presentation, consisting of two types of FBDS, one starting in the foot and the other consisting of asynchronous myoclonic and dystonic jerks of the face triggered by noise and chin stimulation. The patient displayed no personality changes or cognitive impairment. Discussion: LGI1 encephalitis is a heterogeneous disease. Many different forms of FBDS may be observed, and these seizures can be the only symptom. This type of encephalitis should be suspected in presenting very frequent episodic events with dystonic features, regardless of the part of the body affected

Highly plastic genome of Microcystis aeruginosa PCC 7806, a ubiquitous toxic freshwater cyanobacterium

Background The colonial cyanobacterium Microcystis proliferates in a wide range of freshwater ecosystems and is exposed to changing environmental factors during its life cycle. Microcystis blooms are often toxic, potentially fatal to animals and humans, and may cause environmental problems. There has been little investigation of the genomics of these cyanobacteria. Results Deciphering the 5,172,804 bp sequence of Microcystis aeruginosa PCC 7806 has revealed the high plasticity of its genome: 11.7% DNA repeats containing more than 1,000 bases, 6.8% putative transposases and 21 putative restriction enzymes. Compared to the genomes of other cyanobacterial lineages, strain PCC 7806 contains a large number of atypical genes that may have been acquired by lateral transfers. Metabolic pathways, such as fermentation and a methionine salvage pathway, have been identified, Conclusion Microcystis aeruginosa PCC 7806 appears to have adopted an evolutionary strategy relying on unusual genome plasticity to adapt to eutrophic freshwater ecosystems, a property shared by another strain of M. aeruginosa (NIES-843). Comparisons of the genomes of PCC 7806 and other cyanobacterial strains indicate that a similar strategy may have also been used by the marine strain Crocosphaera watsonii WH8501 to adapt to other ecological niches, such as oligotrophic open oceans.

Geographic Structuring of the Plasmodium falciparum Sarco(endo)plasmic Reticulum Ca2+ ATPase (PfSERCA) Gene Diversity

Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. To collect baseline pfserca sequence information before field deployment of Artemisinin-based Combination therapies that may select mutant parasites, we conducted a sequence analysis of 100 isolates from multiple sites in Africa, Asia and South America. Coding sequence diversity was large, with 29 mutated codons, including 32 SNPs (average of one SNP/115 bp), of which 19 were novel mutations. Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. The PfSERCA functional domains were very well conserved, with non synonymous mutations located outside the functional domains, except for the S769N mutation associated in French Guiana with elevated IC50 for artemether. The S769N mutation is located close to the hinge of the headpiece, which in other species modulates calcium affinity and in consequence efficacy of inhibitors, possibly linking calcium homeostasis to drug resistance. Genetic diversity was highest in Senegal, Brazil and French Guiana, and few mutations were identified in Asia. Population genetic analysis was conducted for a partial fragment of the gene encompassing nucleotide coordinates 87-2862 (unambiguous sequence available for 96 isolates). This supported a geographic clustering, with a separation between Old and New World samples and one dominant ancestral haplotype. Genetic drift alone cannot explain the observed polymorphism, suggesting that other evolutionary mechanisms are operating. One possible contributor could be the frequency of haemoglobinopathies that are associated with calcium dysregulation in the erythrocyte

Interleukin-7 Influences FOXP3+CD4+ Regulatory T Cells Peripheral Homeostasis

Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance

The Global Stratotype Sections and Points for the bases of the Selandian (Middle Paleocene) and Thanetian (Upper Paleocene) stages at Zumaia, Spain

The global stratotype sections and points for the bases of the Selandian (Middle Paleocene) and Thanetian (Upper Paleocene) stages have been defined in the coastal cliff along the Itzurun Beach at the town of Zumaia in the Basque Country, northern Spain. In the hemipelagic section exposed at Zumaia the base of the Selandian Stage has been placed at the base of the Itzurun Formation, ca. 49 m above the Cretaceous/ Paleogene boundary. At the base of the Selandian, marls replace the succession of Danian red limestone and limestone-marl couplets. The best marine, global correlation criterion for the basal Selandian is the second radiation of the important calcareous nannofossil group, the fasciculiths. Species such as Fasciculithus ulii, F. billii, F. janii, F. involutus, F.pileatus and F. tympaniformis have their first appearance in the interval from a few decimetres below up to 1.1 m above the base of the Selandian. The marker species for nannofossil Zone NP5, F. tympaniformis, first occurs 1.1 m above the base. Excellent cyclostratigraphy and magnetostratigraphy in the section creates further correlation potential, with the base of the Selandian occuring 30 precession cycles (630 kyr) above the top of magnetochron C27n. Profound changes in sedimentology related to a major sea-level fall characterize the Danian-Selandian transition in sections along the margins of the North Atlantic. The base of the Thanetian Stage is placed in the same section ca. 78 m above the Cretaceous/Paleogene boundary. It is defined at a level 2.8 m or eight precession cycles above the base of the core of the distinct clay-rich interval associated with the Mid-Paleocene Biotic Event, and it corresponds to the base of magnetochron C26n in the section. The base of the Thanetian is not associated with any significant change in marine micro-fauna or flora. The calcareous nannofossil Zone NP6, marked by the first occurrence of Heliolithus kleinpelli starts ca. 6.5 m below the base of the Thanetian. The definitions of the global stratotype points for the bases of the Selandian and Thanetian stages are in good agreements with the definitions in the historical stratotype sections in Denmark and England, respectively

The future of dialects: Selected papers from Methods in Dialectology XV

Traditional dialects have been encroached upon by the increasing mobility of their speakers and by the onslaught of national languages in education and mass media. Typically, older dialects are “leveling” to become more like national languages. This is regrettable when the last articulate traces of a culture are lost, but it also promotes a complex dynamics of interaction as speakers shift from dialect to standard and to intermediate compromises between the two in their forms of speech. Varieties of speech thus live on in modern communities, where they still function to mark provenance, but increasingly cultural and social provenance as opposed to pure geography. They arise at times from the need to function throughout the different groups in society, but they also may have roots in immigrants’ speech, and just as certainly from the ineluctable dynamics of groups wishing to express their identity to themselves and to the world. The future of dialects is a selection of the papers presented at Methods in Dialectology XV, held in Groningen, the Netherlands, 11-15 August 2014. While the focus is on methodology, the volume also includes specialized studies on varieties of Catalan, Breton, Croatian, (Belgian) Dutch, English (in the US, the UK and in Japan), German (including Swiss German), Italian (including Tyrolean Italian), Japanese, and Spanish as well as on heritage languages in Canada