Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Myocardial changes in incident haemodialysis patients over 6-months:an observational cardiac magnetic resonance imaging study

Patients commencing on haemodialysis (HD) have an increased risk of cardiovascular events in the first year after starting HD compared to those patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal myocardial strain predict mortality. There may be changes in the myocardium of incident HD patients over a 6-month period of HD which may explain changes in cardiovascular risk. We used CMR to consider changes in LV mass, myocardial strain and T1 mapping. We examined changes in pre-dialysis highly sensitive troponin T. 33 patients undergoing HD for <12 months were recruited. Participants underwent CMR at baseline and after 6-months of standard care. 6-months of HD was associated with reduction in LV mass index (Baseline: 78.8 g/m2 follow up: 69.9 g/m2, p = <0.001). LV global longitudinal strain also improved (Baseline: −17.9%, follow up: −21.6%, p = <0.001). Change in T1 time was not significant (Baseline septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In incident HD patients, 6-months of HD was associated with improvements in LV mass, strain and troponin. These findings may reflect improvement in known cardiac tissue abnormalities found in patients over the first year of HD

System of crop intensification for more productive, resource-conserving, climate-resilient, and sustainable agriculture: experience with diverse crops in varying agroecologies

With continually increasing demand for food accompanied by the constraints of climate change and the availability and quality of soil and water, the world’s farmers are challenged to produce more food per hectare with less water, and with fewer agrochemical inputs if possible. The ideas and methods of the system of rice intensification which is improving irrigated rice production are now being extended/adapted to many other crops: wheat, maize, finger millet, sugarcane, tef, mustard, legumes, vegetables, and even spices. Promoting better root growth and enhancing the soil’s fertility with organic materials are being found effective means for raising the yields of many crop plants with less water, less fertilizer, reduced seeds, fewer agrochemicals, and greater climate resilience. In this article, we review what is becoming known about various farmer-centred innovations for agroecological crop management that can contribute to agricultural sustainability. These changes represent the emerging system of crop intensification, which is being increasingly applied in Asian, African, and Latin American countries. More research will be needed to verify the efficacy and impact of these innovations and to clarify their conditions and limits. But as no negative effects for human or environmental health have been identified, making these agronomic options more widely known should prompt more investigation and, to the extent justified by results, utilization of these methodologies

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Principles of cartilage tissue engineering in TMJ reconstruction

Diseases and defects of the temporomandibular joint (TMJ), compromising the cartilaginous layer of the condyle, impose a significant treatment challenge. Different regeneration approaches, especially surgical interventions at the TMJ's cartilage surface, are established treatment methods in maxillofacial surgery but fail to induce a regeneration ad integrum. Cartilage tissue engineering, in contrast, is a newly introduced treatment option in cartilage reconstruction strategies aimed to heal cartilaginous defects. Because cartilage has a limited capacity for intrinsic repair, and even minor lesions or injuries may lead to progressive damage, biological oriented approaches have gained special interest in cartilage therapy. Cell based cartilage regeneration is suggested to improve cartilage repair or reconstruction therapies. Autologous cell implantation, for example, is the first step as a clinically used cell based regeneration option. More advanced or complex therapeutical options (extracorporeal cartilage engineering, genetic engineering, both under evaluation in pre-clinical investigations) have not reached the level of clinical trials but may be approached in the near future. In order to understand cartilage tissue engineering as a new treatment option, an overview of the biological, engineering, and clinical challenges as well as the inherent constraints of the different treatment modalities are given in this paper

Consistency analysis of metabolic correlation networks

<p>Abstract</p> <p>Background</p> <p>Metabolic correlation networks are derived from the covariance of metabolites in replicates of metabolomics experiments. They constitute an interesting intermediate between topology (i.e. the system's architecture defined by the set of reactions between metabolites) and dynamics (i.e. the metabolic concentrations observed as fluctuations around steady-state values in the metabolic network).</p> <p>Results</p> <p>Here we analyze, how such a correlation network changes over time, and compare the relative positions of metabolites in the correlation networks with those in established metabolic networks derived from genome databases. We find that network similarity indeed decreases with an increasing time difference between these networks during a day/night course and, counter intuitively, that proximity of metabolites in the correlation network is no indicator of proximity of the metabolites in the metabolic network.</p> <p>Conclusion</p> <p>The organizing principles of correlation networks are distinct from those of metabolic reaction maps. Time courses of correlation networks may in the future prove an important data source for understanding these organizing principles.</p

Sensitive Spectroscopic Detection of Large and Denatured Protein Aggregates in Solution by Use of the Fluorescent Dye Nile Red

The fluorescent dye Nile red was used as a probe for the sensitive detection of large, denatured aggregates of the model protein β-galactosidase (E. coli) in solution. Aggregates were formed by irreversible heat denaturation of β-galactosidase below and above the protein’s unfolding temperature of 57.4°C, and the presence of aggregates in heated solutions was confirmed by static light scattering. Interaction of Nile red with β-galactosidase aggregates led to a shift of the emission maximum (λmax) from 660 to 611 nm, and to an increase of fluorescence intensity. Time-resolved fluorescence and fluorescence correlation spectroscopy (FCS) measurements showed that Nile red detected large aggregates with hydrodynamic radii around 130 nm. By steady-state fluorescence measurements, it was possible to detect 1 nM of denatured and aggregated β-galactosidase in solution. The comparison with size exclusion chromatography (SEC) showed that native β-galactosidase and small aggregates thereof had no substantial effect on the fluorescence of Nile red. Large aggregates were not detected by SEC, because they were excluded from the column. The results with β-galactosidase demonstrate the potential of Nile red for developing complementary analytical methods that overcome the size limitations of SEC, and can detect the formation of large protein aggregates at early stages

Worldwide variations in artificial skyglow

Despite constituting a widespread and significant environmental change, understanding of artificial nighttime skyglow is extremely limited. Until now, published monitoring studies have been local or regional in scope, and typically of short duration. In this first major international compilation of monitoring data we answer several key questions about skyglow properties. Skyglow is observed to vary over four orders of magnitude, a range hundreds of times larger than was the case before artificial light. Nearly all of the study sites were polluted by artificial light. A non-linear relationship is observed between the sky brightness on clear and overcast nights, with a change in behavior near the rural to urban landuse transition. Overcast skies ranged from a third darker to almost 18 times brighter than clear. Clear sky radiances estimated by the World Atlas of Artificial Night Sky Brightness were found to be overestimated by ~25%; our dataset will play an important role in the calibration and ground truthing of future skyglow models. Most of the brightly lit sites darkened as the night progressed, typically by ~5% per hour. The great variation in skyglow radiance observed from site-to-site and with changing meteorological conditions underlines the need for a long-term international monitoring program

Enhanced Hippocampal Long-Term Potentiation and Fear Memory in Btbd9 Mutant Mice

Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS