Inter-community and on-farm asymmetric organic matter allocation patterns drive soil fertility gradients in a rural Andean landscape

Soil fertility in agricultural landscapes is driven by complex interactions between natural and anthropogenic processes, with organic matter (OM) inputs playing a critical role. Asymmetric allocation patterns of these resources among communities and within individual farms can lead to soil fertility gradients. However, the drivers and consequences of such patterns in different socioecological contexts remains poorly documented and understood. The objective of this study was to address this gap by assessing asymmetric OM allocation patterns and the associated consequences for soil fertility management in three indigenous communities located in the Central Ecuadorian Andes. We found that both distance from homestead and perception of fertility were associated with asymmetric OM allocation patterns to fields as well as with soil fertility gradients within farms. For example, soil organic carbon (SOC), total nitrogen (N), available phosphorus (P), and exchangeable potassium (K) all decreased with distance from the homestead, while SOC, total N, and available P were positively correlated with a farmer's perception of soil fertility. We note that these fertility gradients remained even in the case of increased farm-level OM inputs. Overall OM allocation patterns differed significantly among communities and were associated with significant differences in soil fertility, with the highest levels of available P and exchangeable K found in the community with the highest OM inputs. The results of this study indicate the importance of asymmetric OM allocation patterns encountered at different scales, both within farms and among neighboring communities, in rural Andean landscapes and their significant interactions with soil fertility gradients.</p

Wearable wireless inertial measurement for sports applications

The advent of MEMS inertial sensors has reduced the size, cost and power requirements of 6 Degrees-of-Freedom inertial measurement systems to a level where their use can be considered for wearable wireless monitoring devices. Many applications for such Wearable Wireless Inertial Measurement Units exist in the area of sports and sports science. Such a system would be critical in providing data for the analysis of the kinematic motion data of an athlete - to characterise a player’s technique or track progress and provide accurate, quantitative feedback to player and coach in near real time. A small, lightweight and low power device with the ability to sense the full range of human motion at a high sampling rate is required for such applications. It must also be robust, well sealed and comfortable to wear. Further development and miniaturisation of such devices coupled with progress in energy scavenging may lead to their use in other areas and their near ubiquity, with the potential to be embedded within clothes, buildings, materials, objects and people for health monitoring, location tracking and other purpose

Controversies Surrounding Renal Denervation:Lessons Learned From Real-World Experience in Two United Kingdom Centers

Renal denervation (RDN) is a therapy that targets treatment‐resistant hypertension (TRH). The Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity) HTN‐1 and Symplicity HTN‐2 trials reported response rates of >80%; however, sham‐controlled Symplicity HTN‐3 failed to reach its primary blood pressure (BP) outcome. The authors address the current controversies surrounding RDN, illustrated with real‐world data from two centers in the United Kingdom. In this cohort, 52% of patients responded to RDN, with a 13±32 mm Hg reduction in office systolic BP (SBP) at 6 months (n=29, P=.03). Baseline office SBP and number of ablations correlated with office SBP reduction (R=−0.47, P=.01; R=−0.56, P=.002). RDN appears to be an effective treatment for some patients with TRH; however, individual responses are highly variable. Selecting patients for RDN is challenging, with only 10% (33 of 321) of the screened patients eligible for the study. Medication alterations and nonadherence confound outcomes. Adequate ablation is critical and should impact future catheter design/training. Markers of procedural success and improved patient selection parameters remain key research aims

Common Polymorphisms at the <i>CYP17A1 </i>Locus Associate With Steroid Phenotype:Support for Blood Pressure Genome-Wide Association Study Signals at This Locus

Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency &gt;0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects

Functional filter for whole genome sequencing data identifies HHT and stress-associated non-coding SMAD4 polyadenylation site variants >5kb from coding DN

Acknowledgments: This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The work was cofounded by the National Institute for Health Research Imperial Biomedical Research Centre, the D’Almeida Charitable Trust, and Imperial College Healthcare NHS Trust. AA was supported by Prince Sultan Military Medical City, Saudi Arabia. MAA was supported by the National Institutes of Health (grant R35HL140019). The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. We thank the National Health Service staff of the UK Genomic Medicine Centres and the participants for their willing participation; the Genomics England Clinical Research Interface team, specifically Susan Walker, for separately reviewing bam file variant sequences; Charlotte Bevan, Michael Hubank and Santiago Vernia for helpful discussions and manuscript review; and our academic and public partners within the NIHR Imperial BRC’s Social Genetic and Environmental Determinants of Health (SGE) theme. We specifically thank the presented families for confirmation of their clinical phenotypes and consent to share in this manuscript. The views expressed are those of the authors and not necessarily those of funders, the NHS, the NIHR, or the Department of Health and Social Care.Peer reviewedPublisher PD

Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies

To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1×10$^{−6}$. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10$^{−83}$) and the phospholamban (PLN) gene (P = 1.9×10$^{−29}$). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death

Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation:Meta-Analysis of Three Genome-Wide Association Studies

To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P&#60;1×10&lt;sup&gt;−6&lt;/sup&gt;. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10&lt;sup&gt;−83&lt;/sup&gt;) and the phospholamban (PLN) gene (P = 1.9×10&lt;sup&gt;−29&lt;/sup&gt;). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.00