Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition,Driving Impaired Ca2+ Handling and Arrhythmogenesis

Phospholamban (PLN), a key modulator of Ca²⁺-homeostasis, inhibits sarcoplasmic reticulum (SR) calcium-ATPase (SERCA2a) and regulates cardiac contractility. The human PLN mutation R14del has been identified in arrhythmogenic cardiomyopathy patients worldwide and is currently extensively investigated. In search of the molecular mechanisms mediating the pathological phenotype, we examined PLN-R14del associations to known PLN-interacting partners. We determined that PLN-R14del interactions to key Ca²⁺-handling proteins SERCA2a and HS-1-associated protein X-1 (HAX-1) were enhanced, indicating the super-inhibition of SERCA2a’s Ca²⁺-affinity. Additionally, histidine-rich calcium binding protein (HRC) binding to SERCA2a was increased, suggesting the inhibition of SERCA2a maximal velocity. As phosphorylation relieves the inhibitory effect of PLN on SERCA2a activity, we examined the impact of phosphorylation on the PLN-R14del/SERCA2a interaction. Contrary to PLN-WT, phosphorylation did not affect PLN-R14del binding to SERCA2a, due to a lack of Ser-16 phosphorylation in PLN-R14del. No changes were observed in the subcellular distribution of PLN-R14del or its co-localization to SERCA2a. However, in silico predictions suggest structural perturbations in PLN-R14del that could impact its binding and function. Our findings reveal for the first time that by increased binding to SERCA2a and HAX-1, PLN-R14del acts as an enhanced inhibitor of SERCA2a, causing a cascade of molecular events contributing to impaired Ca²⁺-homeostasis and arrhythmogenesis. Relieving SERCA2a super-inhibition could offer a promising therapeutic approach for PLN-R14del patients.     

Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells

The two crucial cellular insults that take place during cerebral ischemia are the loss of oxygen and loss of glucose, which can both activate a cascade of events leading to neuronal death. In addition, the toxic overactivation of neuronal excitatory receptors, leading to Ca²⁺ overload, may contribute to ischemic neuronal injury. Brain ischemia can be simulated in vitro by oxygen/glucose deprivation, which can be reversible by the re-establishment of physiological conditions. Accordingly, we examined the effects of glucose deprivation on the PI3K/Akt survival signaling pathway and its crosstalk with HIF-1α and Ca²⁺ homeostasis in SH-SY5Y human neuroblastoma cells. It was found that glucose withdrawal decreased HIF-1α protein levels even in the presence of the ischemia-mimicking CoCl_2. On the contrary, and despite neuronal death, we identified a strong activation of the master pro-survival kinase Akt, a finding that was also confirmed by the increased phosphorylation of GSK3, a direct target of p-Akt. Remarkably, the elevated Ca²⁺ influx recorded was found to promptly trigger the activation of Akt, while a re-addition of glucose resulted in rapid restoration of both Ca²⁺ entry and p-Akt levels, highlighting the plasticity of neurons to respond to ischemic challenges and the important role of glucose homeostasis for multiple neurological disorders.     

The role of personal resources in the job demands-resources model.

This study examined the role of three personal resources (self-efficacy, organizational-based self-esteem, and optimism) in the Job Demands-Resources (JD-R) model. The authors hypothesized that personal resources (1) moderate the relationship between job demands and exhaustion, (2) mediate the relationship between job resources and work engagement, and (3) relate to how employees perceive their work environment and well-being. Hypotheses were tested among 714 Dutch employees. Results showed that personal resources did not offset the relationship between job demands and exhaustion. Instead, personal resources mediated the relationship between job resources and engagement/exhaustion and influenced the perception of job resources. The implications of these findings for the JD-R model are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Third‐Order Nonlinear Optical Response of Gold‐Island Films

Films of gold nanoscaled islands with thicknesses ranging between 0.5 and 15 nm were prepared by thermal evaporation onto untreated and aminosilane‐pretreated glass substrates. Post‐deposition annealing was found to modify the morphological characteristics of the islands (e.g., average island area and height, inter‐island distance, etc.), resulting in changes of the localized surface plasmon resonance (SPR) characteristics and, therefore, modifying the nonlinear optical (NLO) response of the films. The NLO response of both unannealed and annealed (20 h at 200 °C) films was studied by means of the optical Kerr effect (OKE), using 35 ps, 532 nm laser excitation, while measurements performed by means of the Z‐scan technique allowed for the determination of both the nonlinear refraction and absorption characteristics of the films. The results are discussed and compared with other reports.     

Study of the dyeing properties of saffron and ultrafiltrated saffron powders,as colourants for natural and synthetic fibres

There is a noticeable growing interest in the use of natural dyes in contemporary textile dyeing, motivated by the requirements imposed, in favour of environmental prosperity. The use of natural dyes reduces significantly both the energy requirements and the environmental impact of the process. In the present work natural and synthetic fibres were dyed with the dyestuff isolated from Crocus sativus L., after aqueous extraction of the dried stigmas of the plant. Additionally, part of the powder was purified by using ultrafiltration technology. The saffron extract and the ultrafiltrated saffron retentate were used to dye cotton, wool, nylon and polyester, in various depths of shade and temperatures. Both saffron and ultrafiltrated saffron successfully dyed not only the natural substrates, but also the synthetic ones, while higher dyeing temperatures produced level dyeing with all substrates used. Ultrafiltrated saffron powder produced brighter and much stronger dyeing to the original saffron powder, due to the elimination of extraction by-products. Isothermal adsorptions for both colourants were performed on all substrates in order to investigate their adsorption mechanism. It was found that saffron and ultrafiltrated saffron follow a Freundlich-type adsorption isotherm on cotton, wool and nylon which is a typical mechanism for a planar-directed dye of big molecular weight. Nernst-type adsorption was found to occur on polyester which again is typical for the adsorption of disperse dyes on polyester. Thus, saffron can be claimed as a universal dye, able to successfully dye natural and synthetic substrates.     

Abnormality segmentation in brain images via distributed estimation

The aim of this paper is to introduce a novel semisupervised scheme for abnormality detection and segmentation in medical images. Semisupervised learning does not require pathology modeling and, thus, allows high degree of automation. In abnormality detection, a vector is characterized as anomalous if it does not comply with the probability distribution obtained from normal data. The estimation of the probability density function, however, is usually not feasible due to large data dimensionality. In order to overcome this challenge, we treat every image as a network of locally coherent image partitions (overlapping blocks). We formulate and maximize a strictly concave likelihood function estimating abnormality for each partition and fuse the local estimates into a globally optimal estimate that satisfies the consistency constraints, based on a distributed estimation algorithm. The likelihood function consists of a model and a data term and is formulated as a quadratic programming problem. The method is applied for automatically segmenting brain pathologies, such as simulated brain infarction and dysplasia, as well as real lesions in diabetes patients. The assessment of the method using receiver operating characteristic analysis demonstrates improvement in image segmentation over two-group analysis performed with Statistical Parametric Mapping (SPM).     

Confronting workplace exposure to chemicals with LCA: examples of trichloroethylene and perchloroethylene in metal degreasing and dry cleaning

Life-Cycle Assessment (LCA) aims to assess all environmental impacts "from cradle to grave". Nevertheless, existing methods for Life-Cycle Impact Assessment (LCIA) generally do not consider impacts from chemical exposure at the workplace. This is a severe drawback, because neglecting occupational health effects may result in product or process optimizations at the expense of workers' health. We adapt an existing LCIA method to consider occupational health effects from the use of perchloroethylene (PCE) and trichloroethylene (TCE) in dry cleaning and metal degreasing. The results show that, in applications such as metal degreasing and dry cleaning, long-term (steady-state) concentrations at the workplace are up to 6 orders of magnitude higher than ambient air levels. Legal threshold values may be exceeded, depending on machine technology, size, and surrounding working conditions. The impact from workplace exposure to the total human-toxicity potential of the complete life cycle of PCE and TCE (including use, production, and disposal) is accordingly high. We therefore conclude that occupational health effects need to be considered in LCA to prevent overlooking key environmental-health impacts in LCA.