A Comprehensive Resource for Induced Pluripotent Stem Cells from Patients with Primary Tauopathies.

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

“Crocodiles in the corridors” : security vetting, race and Whitehall, 1945 – 1968

In July 2018, the UK’s Intelligence & Security Committee issued a report into diversity and inclusion across the intelligence and security community. The picture the report painted was far from satisfactory; in short, Britain’s intelligence agencies did not ‘fully reflect the ethnic make-up of modern Britain’. The report argued that Britain’s spy agencies – MI5, SIS (or MI6) and GCHQ – should improve black, Asian and ethnic minority recruitment, highlighting areas for improvement, especially around the vetting of recruits. This problem stems from the post-war Cold War 'security state' and the development of security-vetting programmes from the 1940s, aiming to protect Whitehall from Soviet spies and 'fellow travellers' to those with so-called 'character defects' - drink, drugs and homosexuality. But this 'security state' also saw the newly emerging multicultural Britain as a major threat. The so-called 'Windrush Generation' of migrants from the Caribbean, and migration from the Indian subcontinent and Africa, forever changed the social complexion of Britain, but posed significant questions for security officials. What was Britishness? With first or second generation migrants entering the civil service, who was a 'UK eye' and what access to secret information should they have? To what extent was discrimination justifiable to protect state secrets, and how should officials respond to new legislation such as the Race Discrimination Act? As this article shows, new entrants to the civil service faced deeply engrained prejudices, and questions over their loyalty to Britain. As late as the 1960s (and beyond), 'coloured' members of the civil service were rejected from secret posts across government, including the Ministry of Defence and intelligence and security services, especially MI5 and GCHQ, with discrimination on ‘security’ grounds justified by the landmark 1968 Race Relations Act, which barred race discrimination for housing and employment elsewhere

The Human Cell Atlas.

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

COPD May Increase the Incidence of Refractory Supraventricular Arrhythmias Following Pulmonary Resection for

Purpose: This study investigated the association of COPD and postoperative cardiac arrhythmias, specifically supraventricular tachycardia (SVT), as well as mortality in patients undergoing pulmonary resection for non-small cell lung cancer (NSCLC). Methods: A retrospective chart review of 244 patients who had undergone lung resection for NSCLC at Indiana University Hospital between 1992 and 1997 was undertaken. COPD, which was defined as an FEV 1 of < 70 % predicted and an FEV 1/FVC ratio of < 70 % based on the results of a preoperative pulmonary function test (PFT), was diagnosed in 78 of the 244 patients (COPD group). In the remaining 166 patients, the results of preoperative PFTs did not meet these criteria (non-COPD group). Both groups were otherwise well-matched with respect to multiple variables, including age, comorbid conditions, extent of pulmonary resection, and final pathologic stage. The incidence of cardiac arrhythmias and operative mortality were compared between the two groups using univariate and multivariate analysis. Results: Seventy-six patients (31.9%) experienced new onsets of postoperative SVT, with 58 of these patients (76.3%) demonstrating atrial fibrillation. The COPD group had a 58.7 % incidence of SVT (n � 44) compared to a 27.0 % incidence (n � 44) in the non-COPD group (p < 0.0 0 1)