Reduced endothelin-1– and nitric oxide–mediated arteriolar tone in hypertensive renal transplant recipients

Reduced endothelin-1– and nitric oxide–mediated arteriolar tone in hypertensive renal transplant recipients.BackgroundThe prevalence of hypertension is high in renal transplant recipients. It has been suggested that calcineurin inhibitors (CI) contribute to the development of post-transplant hypertension by stimulating endothelin (ET-1)-mediated and/or reducing nitric oxide (NO)-mediated vascular tone.MethodsWe tested this hypothesis using 2 groups of renal transplant recipients [normotensive patients without a need for antihypertensive medication (Normo-Tx), and hypertensive patients requiring antihypertensives (Hyper-Tx)] in the presence of CI-based immunosuppression. In addition, we studied matched control subjects (C). BQ 123 (ET-A receptor antagonist), BQ123 + BQ788 (ET-A/B-receptor antagonist), ET-1, L-NMMA (NO-synthase inhibitor), acetylcholine (ACH; endothelium-dependent vasodilator), glyceroltrinitrate (GTN, NO donor), and norepinephrine (NE, endothelium-independent vasoconstrictor) were infused into the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography.ResultsEndothelium-independent vasomotion in response to GTN and NE was similar in all groups. Vascular responses to selective and combined blockade of ET receptors in both Normo-Tx and Hyper-Tx did not exceed those of C. In fact, we observed a significantly lower increase in FBF after BQ 123 (P = 0.03), as well as after BQ 123/788 (P = 0.03) in Hyper-Tx compared with Normo-Tx. This was associated with an increased vascular sensitivity to exogenous ET-1 in Hyper-Tx compared with Normo-Tx (P = 0.04). Vasoconstriction after L-NMMA was reduced in Hyper-Tx compared with Normo-Tx (P = 0.015), while the response to ACH was reduced in both groups of Tx patients to a similar degree (P = 0.005 vs. C).ConclusionOur results do not support a major role for the vascular endothelin system in the hypertension of renal transplant recipients, whereas deficient baseline NO production may be a contributing factor

Using mobile sensing data to assess stress: Associations with perceived and lifetime stress, mental health, sleep, and inflammation

Background Although stress is a risk factor for mental and physical health problems, it can be difficult to assess, especially on a continual, non-invasive basis. Mobile sensing data, which are continuously collected from naturalistic smartphone use, may estimate exposure to acute and chronic stressors that have health-damaging effects. This initial validation study validated a mobile-sensing collection tool against assessments of perceived and lifetime stress, mental health, sleep duration, and inflammation. Methods Participants were 25 well-characterized healthy young adults (Mage = 20.64 years, SD = 2.74; 13 men, 12 women). We collected affective text language use with a custom smartphone keyboard. We assessed participants’ perceived and lifetime stress, depression and anxiety levels, sleep duration, and basal inflammatory activity (i.e. salivary C-reactive protein and interleukin-1β). Results Three measures of affective language (i.e. total positive words, total negative words, and total affective words) were strongly associated with lifetime stress exposure, and total negative words typed was related to fewer hours slept (all large effect sizes: r = 0.50 – 0.78). Total positive words, total negative words, and total affective words typed were also associated with higher perceived stress and lower salivary C-reactive protein levels (medium effect sizes; r = 0.22 – 0.32). Conclusions Data from this initial longitudinal validation study suggest that total and affective text use may be useful mobile sensing measures insofar as they are associated with several other stress, mental health, behavioral, and biological outcomes. This tool may thus help identify individuals at increased risk for stress-related health problems

AERO & VISTA: Demonstrating HF Radio Interferometry with Vector Sensors

AERO (Auroral Emission Radio Observer) and VISTA (Vector Interferometry Space Technology using AERO) are recently selected NASA HTIDeS CubeSat missions for terrestrial auroral science and radio interferometric technology demonstration. The AERO and VISTA CubeSats both host vector sensing antenna systems providing advanced electromagnetic capabilities. Together, they will provide the first in-space demonstration of interferometric imaging, beamforming, and nulling using electromagnetic vector sensors at low frequencies (100 kHz –15 MHz). A key goal of the joint missions’ technology demonstration is to validate theoretical sensor performance modeling indicating that interferometric arrays composed of vector sensors will be able to maintain sensitivity even in the presence of terrestrial interference. If validated in flight, this capability would relax the requirement that space-based low frequency interferometers be placed far from the Earth (e.g. lunar orbit), and the closer communications range will significantly increase the data volume returned from space-based radio telescope systems. The two-spacecraft AERO+VISTA mission will address the auroral science goals of AERO (Erickson et al. 2018, SSC18) while adding three additional technology demonstration goals enabled by the second CubeSat, VISTA

Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution

Challenges and opportunities for quantifying roots and rhizosphere interactions through imaging and image analysis

The morphology of roots and root systems influences the efficiency by which plants acquire nutrients and water, anchor themselves and provide stability to the surrounding soil. Plant genotype and the biotic and abiotic environment significantly influence root morphology, growth and ultimately crop yield. The challenge for researchers interested in phenotyping root systems is, therefore, not just to measure roots and link their phenotype to the plant genotype, but also to understand how the growth of roots is influenced by their environment. This review discusses progress in quantifying root system parameters (e.g. in terms of size, shape and dynamics) using imaging and image analysis technologies and also discusses their potential for providing a better understanding of root:soil interactions. Significant progress has been made in image acquisition techniques, however trade-offs exist between sample throughput, sample size, image resolution and information gained. All of these factors impact on downstream image analysis processes. While there have been significant advances in computation power, limitations still exist in statistical processes involved in image analysis. Utilizing and combining different imaging systems, integrating measurements and image analysis where possible, and amalgamating data will allow researchers to gain a better understanding of root:soil interactions

Circulating markers of extracellular matrix remodelling in severe COVID-19 patients

Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients. Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Network Positions and the Probability of Being Acquired: An Empirical Analysis in the Biopharmaceutical Industry

This paper examines the relationship between the firm's direct ties, its inter-firm network prominence and its likelihood of being acquired. The authors argue that firm's direct ties and prominence enhance the firm's visibility and signal its quality – and thus foster the firm's likelihood of being acquired. However, higher levels of direct ties and prominence, by providing access to resources and the firm's status, respectively, increase the firm's ability to remain independent and thus reduce its likelihood of being acquired. Thus, the authors posit the overall relation as an inverted U-shaped. Furthermore, they show that, for firms that undergo an initial public offering, the aforementioned relation becomes much weaker. The hypotheses are empirically tested in the biopharmaceutical industry and important theoretical and managerial implications are discussed

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals

BACKGROUND: The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent. AIMS: To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers. SUBJECTS AND METHODS: We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20–47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities. RESULTS: Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function. CONCLUSION: TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function