Human serum metabolic profiles are age dependent

Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging

Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport

Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction

Laparoscopic nephrectomy outside gerota fascia and en bloc ligation of the renal hilum for management of inflammatory renal diseases

ABSTRACT Objectives This study aims to improve laparoscopic nephrectomy techniques for inflammatory renal diseases (IRD) and to reduce complications. Materials and Methods Thirty-three patients underwent laparoscopic nephrectomy for IRD, with a method of outside Gerota fascia dissection and en-bloc ligation and division of the renal pedicle. Operative time, blood loss, complications, analgesia requirement, post-operative recovery of intestinal function and hospital stay were recorded. The degrees of perinephric adhesion were classified based on the observation during operation and post-operative dissection of the specimen, and the association of different types of adhesion with the difficulty of the procedures was examined. Results Among 33 cases, three were converted to hand-assisted laparoscopy, and one was converted to open surgery. Mean operative time was 99.6±29.2min, and blood loss was 75.2±83.5 mL. Postoperative recovery time of intestinal function was 1.6±0.7 days and average hospital stay was 4.8±1.4 days. By classification and comparison of the perinephric adhesions, whether inflammation extending beyond Gerota fascia or involving renal hilum was found to be not only an important factor influencing the operative time and blood loss, but also the main reason for conversion to hand-assisted laparoscopy or open surgery. Conclusions In laparoscopic nephrectomy, outside Gerota fascia dissection of the kidney and en-bloc ligation of the renal pedicle using EndoGIA could reduce the difficulty of procedure and operative time, with satisfactory safety and reliability. Inflammation and adhesion extending beyond Gerota fascia or involving renal hilum is an important predictor of the difficulty related to laparoscopic nephrectomy for IRD

Evaluation of headphone phase equalization on sound reproduction

Headphone equalization can help to deliver high perceptual sound quality. The headphone-to-eardrum transfer function (HETF) equalization can be used to control magnitude and phase responses of headphones. Magnitude equalization is still elusive on how to set a preferred target response while phase equalization is an important but overlooked method. Here the targets of magnitude equalization and phase equalization on headphone reproduction were evaluated through objective and subjective experiments. The objective evaluation shows that the linearity of phase response is important for the decay speed of the corresponding transient response. The subjective experiments show that the target of a linear phase response, but not a flat magnitude response, is able to significantly improve headphone reproduction quality in sound clarity

Changes in Stream Flow and Their Relationships with Climatic Variations and Anthropogenic Activities in the Poyang Lake Basin, China

The Poyang Lake Basin has been suffering from severe water problems such as floods and droughts. This has led to great adverse impacts on local ecosystems and water resource utilization. It is therefore important to understand stream flow changes and their driving factors. In this paper, the dynamics of stream flow and precipitation in the Poyang Lake Basin between 1961 and 2012 were evaluated with the Mann–Kendall test, Theil–Sen approaches, Pettitt test, and Pearson’s correlation. Stream flow was measured at the outlets of five major tributaries of Poyang Lake, while precipitation was recorded by fourteen meteorological stations located within the Poyang Lake Basin. Results showed that annual stream flow of all tributaries and the precipitation over the study area had insignificant (P > 0.1) temporal trends and change points, while significant trends and shifts were found in monthly scale. Stream flow concentration indices (SCI) at Waizhou, Meigang, and Wanjiabu stations showed significant (P < 0.05) decreasing trends with change points emerging in 1984 at Waizhou and 1978 at Wanjiabu, while there was no significant temporal trend and change point detected for the precipitation concentration indices (PCI). Correlation analysis indicated that area-average stream flow was closely related to area-average precipitation, but area-average SCI was insignificantly correlated with area-average PCI after change point (1984). El Niño/Southern Oscillation (ENSO) had greater impacts on stream flow than other climate indices, and La Niña events played a more important role in stream flow changes than EI Niño. Human activities, particularly in terms of reservoir constructions, largely altered the intra-annual distribution of stream flow but its effects on the amount of stream flow were relatively low. Results of this study provided a useful reference to regional water resource management and the prevention of flood and drought disasters

Laparoscopic nephrectomy outside gerota fascia and en bloc ligation of the renal hilum for management of inflammatory renal diseases

<div><p>ABSTRACT Objectives This study aims to improve laparoscopic nephrectomy techniques for inflammatory renal diseases (IRD) and to reduce complications. Materials and Methods Thirty-three patients underwent laparoscopic nephrectomy for IRD, with a method of outside Gerota fascia dissection and en-bloc ligation and division of the renal pedicle. Operative time, blood loss, complications, analgesia requirement, post-operative recovery of intestinal function and hospital stay were recorded. The degrees of perinephric adhesion were classified based on the observation during operation and post-operative dissection of the specimen, and the association of different types of adhesion with the difficulty of the procedures was examined. Results Among 33 cases, three were converted to hand-assisted laparoscopy, and one was converted to open surgery. Mean operative time was 99.6±29.2min, and blood loss was 75.2±83.5 mL. Postoperative recovery time of intestinal function was 1.6±0.7 days and average hospital stay was 4.8±1.4 days. By classification and comparison of the perinephric adhesions, whether inflammation extending beyond Gerota fascia or involving renal hilum was found to be not only an important factor influencing the operative time and blood loss, but also the main reason for conversion to hand-assisted laparoscopy or open surgery. Conclusions In laparoscopic nephrectomy, outside Gerota fascia dissection of the kidney and en-bloc ligation of the renal pedicle using EndoGIA could reduce the difficulty of procedure and operative time, with satisfactory safety and reliability. Inflammation and adhesion extending beyond Gerota fascia or involving renal hilum is an important predictor of the difficulty related to laparoscopic nephrectomy for IRD.</p></div

Research challenges on gully erosion control in EU and China

Trabajo presentado en la EGU General Assembly (Annual Meeting of the European Geosciences Union), celebrada online deñ 4 al 8 de mayo de 2020.Gully erosion is a soil degradation process widely present across the world. Permanent gullyerosion has usually soil erosion rates one order of magnitude higher than hillslope water erosionin conventional agriculture, e.g. 2.1 vs 0.6 mm year-1 (Castillo and Gómez, 2016). It remains a majorprocess of soil degradation worldwide. This work attempts to investigate recent trends of published research on gully erosion in relationto gully erosion control since 2000. A review in Web of Science (core collection, 2000-19 by title)reported 401 documents, produced mainly in the European Union (52.1%), China (22.7%), USA(16.0%) and Australia (8.7%). Approximately 17% of all these articles covered restoration or controlof gully erosion as their main topic. When screened most of these 68 articles deal with specificsituations and techniques with a limited number devoted to a comparative review of effectivenessof different techniques, one of the few exceptions was Liu et al. (2019a). To provide perspective,there were a similar proportion of articles devoted to the study of gully erosion processes, a and amuch larger number of articles devoted to the description of gully development and erosion ratesin specific situations. It is apparent that the subject of gully erosion control is not a dominant onein the scientific indexed literature. This review was complemented with an analysis in WOCAT(WOCAT, 2019), a comprehensive international databases of soil conservation technologies. Itshowed with 27 entries of gully erosion restoration techniques over a total of 1098 descriptions(2.5% approximately). This might be explained, partially, because most of the information on gullyerosion control appears in documents outside scientific, or technical, international databases,many times in local languages. Overall, two of the major barriers frequently noted bystakeholders, particularly farmers, for effective gully erosion control, their high costs and thecomplexity of controlling expansion of very large gullies (e.g. Liu et al.2019b) are not major majorsubjects in the international scientific literature on gullies in the last decades

Relaxant Action of Plumula Nelumbinis Extract on Mouse Airway Smooth Muscle

The traditional herb Plumula Nelumbinis is widely used in the world because it has many biological activities, such as anti-inflammation, antioxidant, antihypertension, and butyrylcholinesterase inhibition. However, the action of Plumula Nelumbinis on airway smooth muscle (ASM) relaxation has not been investigated. A chloroform extract of Plumula Nelumbinis (CEPN) was prepared, which completely inhibited precontraction induced by high K+ in a concentration-dependent manner in mouse tracheal rings, but it had no effect on resting tension. CEPN also blocked voltage-dependent L-type Ca2+ channel- (VDCC-) mediated currents. In addition, ACh-induced precontraction was also completely blocked by CEPN and partially inhibited by nifedipine or pyrazole 3. Besides, CEPN partially reduced ACh-activated nonselective cation channel (NSCC) currents. Taken together, our data demonstrate that CEPN blocked VDCC and NSCC to inhibit Ca2+ influx, resulting in relaxation of precontracted ASM. This finding indicates that CEPN would be a candidate of new potent bronchodilators