Title Participants "White matter integrity in brain networks relevant to anxiety and depression : evidence from the human connectome project dataset" "Nele De Witte, Sven Müller" "The HUPO Brain Proteome project wish list : summary of the 9th HUPO BPP Workshop 9-10 January 2008, Barbados" "Michael Hamacher, Martin Eisenacher, Florian Tribl, Christian Stephan, Katrin Marcus, Tanja Hardt, Jens Wiltfang, Lennart Martens, Dominic Desiderio, Howard Gutstein, Young Mok Park, Helmut E Meyer" "The Human Brain Proteome Project (HUPO BPP) aims at advancing knowledge and the understanding of neurodiseases and aging with the purpose of identifying prognostic and diagnostic biomarkers, as well as to push new diagnostic approaches and medications. The participating groups meet in semi-annual workshops to discuss the progress, as well as the needs, within the field of proteomics. The 9(th) HUPO BPP workshop took place in Barbados from 9-10 January, 2008. Discussing the future HUPO BPP Roadmap, the attendees drafted the so called HUPO BPP wish list containing timelines, suggestions and missions. This wish list will be updated. regularly and will serve as a guideline for the next phase." "Stem-cell-derived human microglia transplanted into mouse brain to study human disease" "Nicola Fattorelli, Ivana Geric, Bart De Strooper" "Microglia are critically involved in complex neurological disorders with a strong genetic component, such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia. Although mouse microglia can recapitulate aspects of human microglia physiology, they do not fully capture the human genetic aspects of disease and do not reproduce all human cell states. Primary cultures of human microglia or microglia derived from human induced pluripotent stem cells (PSCs) are difficult to maintain in brain-relevant cell states in vitro. Here we describe MIGRATE (microglia in vitro generation refined for advanced transplantation experiments, which provides a combined in vitro differentiation and in vivo xenotransplantation protocol to study human microglia in the context of the mouse brain. This article details an accurate, step-by-step workflow that includes in vitro microglia differentiation from human PSCs, transplantation into the mouse brain and quantitative analysis of engraftment. Compared to current differentiation and xenotransplantation protocols, we present an optimized, faster and more efficient approach that yields up to 80% chimerism. To quantitatively assess engraftment efficiency by flow cytometry, access to specialized flow cytometry is required. Alternatively, the percentage of chimerism can be estimated by standard immunohistochemical analysis. The MIGRATE protocol takes ~40 d to complete, from culturing PSCs to engraftment efficiency assessment." "Analysis of the experimental detection of central nervous system-related genes in human brain and cerebrospinal fluid datasets" "Michael Mueller, Juan Antonio Vizcaíno, Philip Jones, Richard Côté, David Thorneycroft, Rolf Apweiler, Henning Hermjakob, Lennart Martens" "Large-scale and high-throughput proteomics experiments of specific samples provide substantial amounts of identified proteins and peptides, which increasingly find their way into centralized, public data repositories. These data typically have potential beyond the analyses performed by the original authors, and can therefore provide considerable added value by being reused for specific, unexplored enquiries. We here reanalyze two CNS-related proteomics datasets, one from the HUPO's Brain Proteome Project, and one from a comprehensive analysis of cerebrospinal fluid in light of the expression of specific splice isoforms from CNS-related genes. We also evaluate the empirically observed peptides of interest against predictions of their proteotypic character." "The Developing Human Connectome Project Neonatal Data Release" "Daan Christiaens" "The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed." "White-matter connectivity between face-responsive regions in the human brain" "Markus Gschwind, Gilles Pourtois, Sophie Schwartz, Dimitri Van de Ville, Patrik Vuilleumier" "New approach methods to improve human health risk assessment of thyroid hormone system disruption-a PARC project" "Louise Ramhøj, Marta Axelstad, Yoni Baert, Ana I Cañas-Portilla, Frédéric Chalmel, Lars Dahmen, Antonio De La Vieja, Bertrand Evrard, Ann-Cathrin Haigis, Timo Hamers, Kim Heikamp, Henrik Holbech, Patricia Iglesias-Hernandez, Dries Knapen, Lorna Davida P. Marchandise, Jane E Morthorst, Nikolai Georgiev Nikolov, Ana C V E Nissen, Michael Oelgeschlaeger, Kostja Renko, Vera Rogiers, Gerrit Schüürmann, Evelyn Stinckens, Mette H Stub, Monica Torres-Ruiz, Majorie Van Duursen, Tamara Vanhaecke, Lucia Vergauwen, Eva Bay Wedebye, Terje Svingen" "Current test strategies to identify thyroid hormone (TH) system disruptors are inadequate for conducting robust chemical risk assessment required for regulation. The tests rely heavily on histopathological changes in rodent thyroid glands or measuring changes in systemic TH levels, but they lack specific new approach methodologies (NAMs) that can adequately detect TH-mediated effects. Such alternative test methods are needed to infer a causal relationship between molecular initiating events and adverse outcomes such as perturbed brain development. Although some NAMs that are relevant for TH system disruption are available-and are currently in the process of regulatory validation-there is still a need to develop more extensive alternative test batteries to cover the range of potential key events along the causal pathway between initial chemical disruption and adverse outcomes in humans. This project, funded under the Partnership for the Assessment of Risk from Chemicals (PARC) initiative, aims to facilitate the development of NAMs that are specific for TH system disruption by characterizing in vivo mechanisms of action that can be targeted by in embryo/in vitro/in silico/in chemico testing strategies. We will develop and improve human-relevant in vitro test systems to capture effects on important areas of the TH system. Furthermore, we will elaborate on important species differences in TH system disruption by incorporating non-mammalian vertebrate test species alongside classical laboratory rat species and human-derived in vitro assays." "Call for participation in the neurogenetics consortium within the Human Variome Project" "Andrea Haworth, Lars Bertram, Paola Carrera, Marc Cruts, Karen Nuytemans, et al." "The rate of DNA variation discovery has accelerated the need to collate, store and interpret the data in a standardised coherent way and is becoming a critical step in maximising the impact of discovery on the understanding and treatment of human disease. This particularly applies to the field of neurology as neurological function is impaired in many human disorders. Furthermore, the field of neurogenetics has been proven to show remarkably complex genotype-to-phenotype relationships. To facilitate the collection of DNA sequence variation pertaining to neurogenetic disorders, we have initiated the Neurogenetics Consortium under the umbrella of the Human Variome Project. The Consortiums founding group consisted of basic researchers, clinicians, informaticians and database creators. This report outlines the strategic aims established at the preliminary meetings of the Neurogenetics Consortium and calls for the involvement of the wider neurogenetic community in enabling the development of this important resource." "C-terminal TMEM106B fragments in human brain correlate with disease-associated TMEM106B haplotypes" "Cristina Teixeira Vicente, Jolien Perneel, Sarah Wynants, Bavo Heeman, Marleen Van den Broeck, Matt Baker, Simon Cheung, Júlia Faura Llorens, Ian R.A. Mackenzie, Rosa Rademakers" "Transmembrane protein 106B (TMEM106B) is a tightly regulated glycoprotein predominantly localized to endosomes and lysosomes. Genetic studies have implicated TMEM106B haplotypes in the development of multiple neurodegenerative diseases with the strongest effect in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), especially in progranulin (GRN) mutation carriers. Recently, cryo-electron microscopy (cryo-EM) studies showed that a C-terminal fragment (CTF) of TMEM106B (AA120-254) forms amyloid fibrils in the brain of patients with FTLD-TDP, but also in brains with other neurodegenerative conditions and normal aging brain. The functional implication of these fibrils and their relationship to the disease-associated TMEM106B haplotype remain unknown. We performed immunoblotting using a newly developed antibody to detect TMEM106B CTFs in the sarkosyl-insoluble fraction of post-mortem human brain tissue from patients with different proteinopathies (n = 64) as well as neuropathologically normal individuals (n = 10) and correlated the results with age and TMEM106B haplotype. We further compared the immunoblot results with immunohistochemical (IHC) analyses performed in the same study population. Immunoblot analysis showed the expected ∼30 kDa band in the sarkosyl-insoluble fraction of frontal cortex tissue in at least some individuals with each of the conditions evaluated. Most patients with GRN mutations showed an intense band representing TMEM106B CTF whereas in most neurologically normal individuals it was absent or much weaker. In the overall cohort, the presence of TMEM106B CTFs correlated strongly with both age (rs = 0.539, P " "Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo" "Ira Espuny-Camacho, Kimmo A. Michelsen, David Gall, Michele Giugliano, et al." "The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair."