Acta Neuropathol

pinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Engrafted maternal T cells in human severe combined immunodeficiency: evidence for a Th2-phenotype and for a potential role of apoptosis on the restriction of T-cell receptor variable beta segment usage.

Engraftment of transplacentally derived maternal T lymphocytes in infants with severe combined immuno- deficiency (SCID) is caused by lack of rejection of the HLA-mismatched maternal T cells by the recipient\u2019s immune system. Although the engrafted T cells express surface activation markers, they are anergic.1 Restriction of T-cell receptor variable (TCRV-) segment use has been demonstrated in engrafted maternal T cells,2, 3 but it remains to be explained how it occurs. The high IgE levels and eosinophilia typical of Omenn\u2019s syndrome, a SCID characterized by the emergence of a limited number of autoreactive endog- enous T-cell clones, has been attributed to the TH2 phenotype of these cells.4 However, little is known about the TH phenotype of engrafted maternal T cells in other patients with SCID with elevated serum IgE levels and eosinophilia. In one such patient described here, the engrafted maternal T cells had a predomi- nantly TH2 phenotype and a restricted pattern of TCRV-beta gene use. In addition, evidence was obtained suggesting that the latter phenomenon might result from apoptosis

Change Detection Tools

In this chapter a wide range of change detection tools is addressed. They are grouped into methods suitable for optical and multispectral data, synthetic aperture radar (SAR) images, and 3D data. Optical and multispectral methods include unsupervised approaches, supervised and knowledge-based approaches, pixel-based and object-oriented approaches, multivariate alteration detection, hyperspectral approaches, and approaches that deal with changes between optical images and existing vector data. Radar methods include constant false-alarm rate detection, adaptive filtering, multi-channel segmentation (an object-oriented approach), hybrid methods, and coherent change detection. 3D methods focus on tools that are able to deal with 3D information from ground based laser-ranging systems, LiDAR, and elevation models obtained from air/space borne optical and SAR data. Highlighted applications are landcover change, which is often one of the basic types of information to build analysis on, monitoring of nuclear safeguards, third-party interference close to infrastructures (or borders), and 3D analysis. What method to use is dependent on the sensor, the size of the changes in comparison with the resolution, their shape, textural properties, spectral properties, and behaviour in time, and the type of application. All these issues are discussed to be able to determine the right method, with references for further readin