A sequential protocol combining dual neuroanatomical tract-tracing with the visualization of local circuit neurons within the striatum

We describe here an experimental approach designed to aid in the identification of complex brain circuits within the rat corpus striatum. Our aim was to characterize in a single section (i) striatal thalamic afferents, (ii) striatopallidal projection neurons and (iii) striatal local circuit interneurons. To this end, we have combined anterograde tracing using biotinylated dextran amine and retrograde neuroanatomical tracing with Fluoro-Gold. This dual tracing protocol was further implemented with the visualization of different subpopulations of striatal interneurons. The subsequent use of three different peroxidase substrates enabled us to unequivocally detect structures that were labeled within a three-color paradigm

Thalamic innervation of the direct and indirect basal ganglia pathways in the rat: Ipsi- and contralateral projections

The present study describes the thalamic innervation coming from the rat parafascicular nucleus (PF) onto striatal and subthalamic efferent neurons projecting either to the globus pallidus (GP) or to the substantia nigra pars reticulata (SNr) by using a protocol for multiple neuroanatomical tracing. Both striatofugal neurons targeting the ipsilateral SNr (direct pathway) as well as striatal efferent neurons projecting to the ipsilateral GP (indirect pathway) were located within the terminal fields of the thalamostriatal afferents. In the subthalamic nucleus (STN), both neurons projecting to ipsilateral GP as well as neurons projecting to ipsilateral SNr also appear to receive thalamic afferents. Although the projections linking the caudal intralaminar nuclei with the ipsilateral striatum and STN are far more prominent, we also noticed that thalamic axons could gain access to the contralateral STN. Furthermore, a small number of STN neurons were seen to project to both the contralateral GP and PF nuclei. These ipsi- and contralateral projections enable the caudal intralaminar nuclei to modulate the activity of both the direct and the indirect pathway

A Pragmatic Assessment of Government Support for Organic Agriculture in Ireland

Drawing on a pragmatic approach, this paper provides an analysis of governmental support for organic farming in Ireland. There are varying levels of encouragement and programmes provided to farmers in their conversion from conventional to organic production, and in their maintenance of organic production. Support policies vary across regions and are linked to European Union legislation, thus it is challenging to document the many types of support in place. This research investigates relevant technical, financial, and policy support available to organic farmers in Ireland. This exploratory study develops an assessment of Ireland within eight key categories of organic agricultural support: leadership, policy, research, technical support, financial support, marketing and promotion, education and information, and future developments. Information and data from the Irish Department of Agriculture, Fisheries and Food (DAFF), the Irish Agriculture and Food Development Authority (Teagasc), and other governmental and semi-governmental agencies were utilized to assess the level of support in each category. Following the pragmatic approach, this assessment provides key findings which allow policymakers, organizations and citizens to better understand the current situation and set a path for the future development of organic farming in Ireland

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

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Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

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