Pro-contractile effects of perivascular fat in health and disease.

Perivascular adipose tissue (PVAT) is now recognised as an active player in vascular homeostasis. Expansion of PVAT in obesity and the possible role of PVAT in vascular dysfunction has attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediators, for instance angiotensin peptides, reactive oxygen species, chemokines and cytokines. The secretory profile of PVAT is altered by obesity, hypertension and other cardiovascular diseases, leading to imbalance between its pro-contractile and anti-contractile effects. PVAT adipocytes represent an important source of the mediators, but infiltrating immune cells may become more important under conditions of hypoxia and inflammation. This review describes recent advances on the effects of PVAT on vascular tone regulation, highlighting the evidence for a pro-contractile action in health and disease. The role of the endothelium, vascular smooth muscle, immune cells and probably perivascular nerves in PVAT function is also discussed

Advanced load-shift system: an experimental validation of the ac-dc converter as shunt active power filter

This paper presents a load-shift system with advanced functionalities to interface the power grid (PG). When compared with the conventional approach, an advanced load-shift system (aLSS) permits the compensation of power quality (PQ) problems for the grid-side, namely problems related to current harmonics, current imbalance, and power factor. The proposed aLSS is composed by a bidirectional ac-dc converter to interface the PG and by a bidirectional dc-dc converter to interface an energy storage system (ESS). Since the main innovation is related with the PG interface, the focus of this work is on the analysis of the ac-dc converter, which is based on a three-phase four-leg converter. A theoretical study and the details concerning the control algorithm are presented and discussed along the paper. A laboratory prototype of the proposed aLSS was developed and the details of implementation are described in the paper. Experimental results obtained with the developed prototype prove that the aLSS contributes for the technology progress in this area, validating a new concept of operation concerning the PQ on the PG side.This work has been supported by FCT – Fundação para a Ciência e Tecnologia with-in the Project Scope: UID/CEC/00319/2019. This work has been supported by the FCT Project QUALITY4POWER PTDC/EEI-EEE/28813/2017, and by the FCT Project newERA4GRIDs PTDC/EEI-EEE/30283/2017

Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Health-related quality of life in Huntington’s Disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s Disease health-related quality of life questionnaire (HDQoL)

Huntington’s disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient–proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient–proxy pairs completed the Huntington’s disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy–patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies’ ratings were at a similar level to patients’ self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients’ self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient’s disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients’ self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient–proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report