Genetics of subcortical vascular dementia

AbstractSubcortical vascular dementia or cerebral small vessel disease is a common cause of disability in the elderly. On magnetic resonance imaging the disease is manifested as white matter lesions, lacunes and microbleeds. Its etiology is complex, with age and hypertension as established risk factors. The heritability of white matter lesions is constantly high over different populations. Linkage studies identified several loci for these lesions however no genes responsible for the linkage signals had been identified so far. Results from genetic association studies using the candidate gene approach support the role of APOE, the renin–angiotensin system, as well as the Notch3 signaling pathway in the development of subcortical vascular dementia. The recent genomegenome wide association study on white matter lesions identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoints to possible novel mechanisms leading to these lesions

Hardware cryptographic support of IBM z Systems for OpenSSH in RHEL 7.2 and SLES 12 SP1

Abstract This article summarizes our experiences with the configuration and usage of OpenSSH using hardware cryptographic support of IBM z Systems. We report our findings in the areas of performance and throughput improvement. Our positive experience indicates that you should make use of this capability when using OpenSSH

A Revolution Whose Time Has Come? The Win?Win of Quantitative Participatory Approaches and Methods

This article explores the potential presented by quantitative participatory methods (QPMs) and approaches for agricultural monitoring and evaluation and impact assessment. Pioneering examples indicate that QPMs can be ‘win?win’, with gains to farmers through their own analysis, action and voice, and to scientists and other non?farming professionals through the accuracy, relevance, scope and timeliness of the information and insights they generate. To realise their potential requires professional, academic, institutional and personal commitment and change

White Matter Lesion Progression: Genome-Wide Search for Genetic Influences

White matter lesion (WML) progression on magnetic resonance imaging (MRI) is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Economic and employment implications of a carbon market for integrated farm forestry and biodiverse environmental plantings

Many studies have predicted, at a national scale, the economic viability of new forestry plantings to contribute to mitigation of greenhouse gas emissions in Australia's cleared agricultural lands. Such predictions are highly uncertain given: (i) differences in site quality, management regimes and planting geometries (belt versus block configurations) result in rates of sequestration that are highly variable at regional scales and (ii) uncertainties in carbon accounting methods in future carbon markets. Here we examined the economics of three case studies (two of farm forestry and one of biodiverse environmental plantings) to address these issues. There was significant variation in economic viability both between and within case studies (average coefficient of variation of 39%) as a result of differences in site quality, management regime and planting geometries. We conclude that if carbon offset investment targets marginal land (i.e. areas of farms of lowest productivity), carbon prices required for economic viability are <$18t CO 2-e, even at a relatively high discount rate of 8%. Although regional employment generated per hectare tends to be less than many existing agricultural enterprises, any jobs generated from use of this low productivity land for carbon forestry would be additional. Economic viability was generally greatest for 3-4 row belt farm forestry plantings because of increased growth, particularly in areas of relatively high rainfall. Supplementary payments may therefore be needed to make biodiverse environmental plantings competitive in areas of lower rainfall and thus less profitability

Uncertainties in the effectiveness of biological control of stem borers under different climate change scenarios in Eastern Africa

Climate change (CC) is expected to significantly affect biodiversity and ecosystem services. Adverse impacts from CC in the Global South are likely to be exacerbated by limited capacities to take adequate adaptation measures and existing developmental challenges. Insect pests today are already causing considerable yield losses in agricultural crop production in East Africa. Studies have shown that insects are strongly responding to CC by proliferation, shift in distribution, and by altering their phenology, which is why an impact on agriculture can be expected. Biological control (BC) has been proposed as an alternative measure to sustainably contain insect pests, but few studies predict its efficacy under future CC. Using the species maximum entropy modeling (Maxent) approach, we predict the current and future distribution of three important lepidopteran stem borer pests of maize in Eastern Africa, i.e., Busseola fusca (Fuller, 1901), Chilo partellus (Swinhoe, 1885), and Sesamia calamistis (Hampson, 1910), and two parasitoids that are currently used for BC, i.e., Cotesia flavipes (Cameron, 1891) and Cotesia sesamiae (Cameron, 1906). Based on these potential distributions and data collected during household surveys with local farmers in Kenya and Tanzania, also future maize yield losses are predicted for a business-as-usual scenario and a sustainable development scenario. We found that BC of the stem borer pests by C. flavipes and C. sesamiae will be less effective under more severe CC resulting in a reduced ability to curb maize yield losses caused by the stem borers. These results highlight the need to adapt BC measures to future CC to maintain its potential for environmentally friendly pest management strategies. The findings of this research are thus of particular relevance to policymakers, extension officers, and farmers in the region and will aid the adaptation of smallholder agricultural practices to the impacts of CC.Peer reviewe