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Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates the function of membrane proteins. Here, the authors map lysine acetylation predominantly in membrane-interaction regions in peripheral membrane proteins and show with three candidate proteins how lysine acetylation is a regulator of membrane protein function.

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal activity. Overall, we observed a pronounced, long-lasting, and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons also exhibiting periods of hyperexcitability during the recovery phase. These results provide the first experimental evidence of the effects of cTBS on single neurons in awake behaving monkeys, shedding new light on the reasons underlying cTBS variability.

Abstract The neural mechanisms underlying the effects of continuous Theta-Burst Stimulation (cTBS) in humans are poorly understood. Animal studies can clarify the effects of cTBS on individual neurons, but behavioral evidence is necessary to demonstrate the validity of the animal model. We investigated the behavioral effect of cTBS applied over parietal cortex in rhesus monkeys performing a visually-guided grasping task with two differently sized objects, which required either a power grip or a pad-to-side grip. We used Fitts’ law, predicting shorter grasping times (GT) for large compared to small objects, to investigate cTBS effects on two different grip types. cTBS induced long-lasting object-specific and dose-dependent changes in GT that remained present for up to two hours. High-intensity cTBS increased GTs for a power grip, but shortened GTs for a pad-to-side grip. Thus, high-intensity stimulation strongly reduced the natural GT difference between objects (i.e. the Fitts’ law effect). In contrast, low-intensity cTBS induced the opposite effects on GT. Modifying the coil orientation from the standard 45-degree to a 30-degree angle induced opposite cTBS effects on GT. These findings represent behavioral evidence for the validity of the nonhuman primate model to study the neural underpinnings of non-invasive brain stimulation.

Olive oil byproducts show differences according to the olive oil extraction systems, which are called olive mill solid wastes, olive oil wastewater and olive oil wastewater sludge. Three different kinds of composts, including two-phase and three-phase olive mill solid wastes, and olive oil wastewater sludge were produced with separated dairy manure, poultry manure, and straw. The composts obtained from two-phase and three-phase olive mill solid wastes and olive oil wastewater sludge were named as two-phase, three-phase, and water sludge composts, respectively. They were separately enriched by rock phosphate and potassium salt. These composts were mixed with peat in a ratio of 0%, 25%, 50%, 75%, and 100% (v/v). Tomato seeds were sown in all mixtures on 3 February 2016. All the seeds were sown into 2 trays and each plug included 2 replicates. The trays were left in a germination room for 3 days, then moved to a heated greenhouse which is specialized for growing seedlings, and the seedlings were grown there for 3 weeks. The results showed that increasing compost ratios in the growing medium and also the enrichment of the growing medium increased organic matter content, electrical conductivity, and macro and micro nutrient concentrations. The germination period lasted longer with increasing compost ratios. The shoot length was lower at a compost ratio of over 50% excluding water sludge compost, which reacted to over 75%. The highest plant dry weights were obtained in the plants grown on the media with compost ratios of 50%, 25%, and 25% for water sludge compost, enriched two-phase compost, and enriched three-phase compost, respectively. We concluded that the composts obtained from two-phase and three-phase olive mill solid wastes and olive oil waste water sludge can be used without any need of enrichment and a ratio of 25% was found appropriate in most of the measured properties.

OBJECTIVE:To gain insights into the problems of dual sensory impaired older adults in long-term care. Insights into these problems are essential for developing adequate policies which address the needs of the increasing population of dual sensory impaired older adults in long-term care. METHODS:A qualitative study was conducted in parallel with a cluster randomized controlled trial. Dual sensory impaired older adults in the intervention group (n = 47, age range 82-98) were invited by a familiar nurse to identify the problems they wanted to address. Data were taken from the semi-structured intervention diaries in which nurses noted the older adults' verbal responses during a five-month intervention period in 17 long-term care homes across the Netherlands. The data were analyzed using descriptive statistics and qualitative content analysis based on the Grounded Theory. FINDINGS:The 47 dual sensory impaired older adults identified a total of 122 problems. Qualitative content analysis showed that the older adults encountered participation problems and problems controlling what happens in their personal environment. Three categories of participation problems emerged: (1) existential concerns of not belonging or not being able to connect with other people, (2) lack of access to communication, information and mobility, and (3) the desire to be actively involved in care delivery. Two categories of control-in-personal-space problems emerged: (1) lack of control of their own physical belongings, and (2) lack of control regarding the behavior of nurses providing daily care in their personal environment. CONCLUSIONS:The invasive problems identified indicate that dual sensory impaired older adults experience great existential pressures on their lives. Long-term care providers need to develop and implement policies that identify and address these problems, and be aware of adverse consequences of usual care, in order to improve dual sensory impaired residents' autonomy and quality of life.

In this paper, we demonstrate an improvement in the accuracy of a low-cost smart temperature sensor, by measurement of the nonlinear curvature correction at multiple temperature references. The sensors were positioned inside a climate chamber and connected outside to a micro-controller via a network cable. The chamber temperature was increased systematically over a wide range from −20 °C to 55 °C. A set of calibration curves was produced from the best fitting second-order polynomial curves for the offset in temperature between the sensor and reference. An improvement in accuracy of ±0.15 °C is with respect to the mentioned temperature range, compared to the significantly higher value reported of ±0.5 °C by the manufacturer for similar conditions. In summary, we demonstrate a significant improvement in the calibration of a low-cost, smart sensor frequently used in research and academic projects over a useful range of temperatures.

To complete their life cycle waterbirds rely on patchily distributed and often ephemeral wetlands along their migration route in a vast unsuitable matrix. However, further loss and degradation of remaining wetland habitats might lead to a configuration and size of stopovers that is no longer sufficient to ensure long-term survival of waterbird populations. By identifying optimal conservation targets to maintain overall habitat availability en route, we can accommodate an as yet absent functional connectivity component in larger management frameworks for migratory waterbirds, such as the Ramsar Convention and the EU Natura 2000 Network. Using a graph-based habitat availability metric (Equivalent Connected Area) we determine the functional connectivity of wetland networks for seven migratory waterbirds with divergent habitat requirements. Analyses are performed at two spatial extents both spanning the Mediterranean Sea and centered around Greece (Balkan-Cyrenaica and Greece-Cyrenaica). We create species-specific suitable habitat maps and account for human disturbance by species-specific disturbance buffers, based on expert estimates of Flight Initiation Distances. At both spatial extents we quantitatively determine the habitat networks' overall functional connectivity and identify wetland sites that are crucial for maintaining a well-connected network. We show that the wetland networks for both spatial extents are relatively well connected and identify several wetland sites in Greece and Libya as important for maintaining connectivity. The application of disturbance buffers results in wetland site-specific reduction of suitable habitat area (0.90-7.36%) and an overall decrease of the network's connectivity (0.65-6.82%). In addition, we show that the habitat networks of a limited set of species can be combined into a single network which accounts for their autoecological requirements. We conclude that targeted management in few but specific wetland complexes could benefit migratory waterbird populations. Deterioration of these vital wetland sites in Greece and Libya will have disproportionate consequences to the waterbird populations they support.

In conventional injection-moulding processes high flow and cooling velocities affect the morphological and tribological properties of microparts when compared to macroscopic parts. A novel mould technology with dynamic CO 2 -tempering is targeted with an enhanced understanding of the temperature time behaviour of morphology during the setting phase which fundamentally dominates the structure formation. The scope of this paper is to provide an understanding of the processing temperature's influence, in this context mould temperature, on the morphological and tribological properties of injection-moulded microparts. Furthermore, the characteristics of tribological testing conditions in microparts should be identified with regard to optimized testing methods. Results indicate that the tribological properties of microparts are mainly influenced by nature of the skin near layers, which can be greatly improved through the application of mould temperatures close to the crystallisation temperature. Additionally, a tribological testing method is adapted for a correct and high solution of the running-in and stationary phase in order to identify the effects of the skin layer on the wear behaviour.

In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

Background: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).Methods and Results: A total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02).Conclusion: Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM. [ABSTRACT FROM AUTHOR]

This study sought to investigate the prevalence of systolic dysfunction using global longitudinal strain (GLS) and its prognostic value in relatives of dilated cardiomyopathy (DCM) patients that had normal left ventricular ejection fraction (LVEF). DCM relatives are advised to undergo cardiac assessment including echocardiography, irrespective of the genetic status of the index patient. Even though LVEF is normal, the question remains whether this indicates absence of disease or simply normal cardiac volumes. GLS may provide additional information regarding (sub)clinical cardiac abnormalities and thus allow earlier disease detection. A total of 251 DCM relatives and 251 control subjects with a normal LVEF (≥55%) were screened. Automated software measured the GLS on echocardiographic 2-, 3-, and 4-chamber views. The cutoff value for abnormal strain was >−21.5. Median follow-up was 40 months (interquartile range: 5 to 80 months). Primary outcome was the combination of death and cardiac hospitalization. A total of 120 relatives and 83 control subjects showed abnormal GLS (48% vs. 33%, respectively; p < 0.001). Abnormal GLS was independently associated with DCM relatives and cardiovascular risk factors, rather than genetic mutations. Subjects with abnormal GLS had more frequent cardiac hospitalizations and a higher mortality as compared with subjects with normal GLS (hazard ratio: 3.29; 95% confidence interval: 1.58 to 6.87; p = 0.001). Additionally, follow-up LVEF was measured in a subset of relatives, and it decreased significantly in those with abnormal as compared with normal GLS (p = 0.006). Relatives of DCM patients had a significantly higher prevalence of systolic dysfunction detected by GLS despite normal LVEF compared with control subjects, independent of age, sex, comorbidities, and genotype. Abnormal GLS was associated with LVEF deterioration, cardiac hospitalization, and death. [ABSTRACT FROM AUTHOR]

In this study, some physical, biochemical and antioxidative properties and mineral compositions of the newly developed six grape varieties (Saruhanbey, Manisa Sultam, Sultan 1, Sultan 7, Altm Sultani and Ki~mi~ as control) and selected seven clones (Osmanca 39, Razak1 6, Pembe Gemre 9, Ĭpek 4, Çal Karasi 1-2-10) were determined. Total phenolic content and flavonoid ranged from 128 to 1501 mg/100 g and 38 to 544 mg/100 gin DW, respectively. Expectedly, their amounts in the seeded grape samples were higher than seedless samples. The highest values were observed in the Ĭpek 4 and the lowest in the Manisa Sultani and Sultan 7, respectively. Pembe Gemre 9 had the lowest anthocyanin content with 9.27 mg/100 g among all samples. The vitamin C changed between 21.34 and 63.21 mg/100 g in the samples. The differences between the samples with respect to DPPH and ABTS inhibitions, TEAC and EC50 values were statistically significant. Ĭpek 4 and Çal Karas1 1-2-10 clones indicated the higher antioxidant activity than others. The N, P, K, Ca and Mg minerals were the most abundant elements in all investigated grape samples. [ABSTRACT FROM AUTHOR]

BACKGROUND: Inflammatory cardiomyopathy (infl-CMP) is characterized by increased cardiac inflammation in the absence of viruses, ischemia, valvular disease, or other apparent causes. Studies addressing the efficacy of immunosuppressive therapy in patients with infl-CMP are sparse. This study retrospectively investigates whether immunosuppressive agents on top of heart failure therapy according to current guidelines improves cardiac function and long-term outcome in patients with infl-CMP. METHODS AND RESULTS: Within the Innsbruck and Maastricht Cardiomyopathy Registry, a total of 209 patients fulfilled the criteria for infl-CMP using endomyocardial biopsy (≥14 infiltrating inflammatory cells/mm2). A total of 110 (53%) patients received immunosuppressive therapy and 99 (47%) did not. To correct for potential selection bias, 1:1 propensity score matching was used on all significant baseline parameters, resulting in a total of 90 patients per group. Baseline characteristics did not significantly differ between both patient groups, reflecting optimal propensity score matching. After a median follow-up of 31 (15--47) months, immunosuppressive therapy resulted in an improved long-term outcome (eg, heart transplantation--free survival) as compared with standard heart failure therapy alone (Log-rank P=0.043; hazard ratio, 0.34 [95% CI, 0.17--0.92]) and in a significant larger increase of left ventricular ejection fraction after a mean of 12 months follow-up, as compared with patients receiving standard heart failure treatment only (12.2% versus 7.3%, respectively; P=0.036). CONCLUSIONS: To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation-- free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial. [ABSTRACT FROM AUTHOR]