Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution

In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells. In contrast, we show that TRAK2-mediated retrograde mitochondrial transport is Miro1-dependent. Interestingly, we find that Miro is critical for recruiting and stabilising the mitochondrial myosin Myo19 on the mitochondria for coupling mitochondria to the actin cytoskeleton. Moreover, Miro depletion during PINK1/Parkin-dependent mitophagy can also drive a loss of mitochondrial Myo19 upon mitochondrial damage. Finally, aberrant positioning of mitochondria in Miro1/2 double-knockout cells leads to disruption of correct mitochondrial segregation during mitosis. Thus, Miro proteins can fine-tune actin- and tubulin-dependent mitochondrial motility and positioning, to regulate key cellular functions such as cell proliferation

A naturalistic inquiry on the impact of interventions aiming to improve health and the quality of life in the community

The goal of this study is to identify and describe variables contributing to the efficiency of health promotion interventions, and to assess whether these variables can serve as reliable and early indicators of the success of such interventions. The study sample includes 44 interventions selected through a network of key informants from five cities--Liverpool, Sandwell, Vienna, Pula, and Rijeka--by using a chain technique. Data on each intervention are collected through an in-depth interview with a program leader, the collection of project-related documents, and on-site observation. Qualitative analysis of data performed with content analysis and computer-assisted free-text analysis reveals different characteristics of interventions depending on whether they are initiated by the city government sector, health-care system, or citizens sector (independent of the city or country). The assessment of the efficiency of these three groups of interventions also differs because of varying features, scope (activity potentials) and impact they are able to accomplish. We have identified ways in which the efficiency of all three groups of interventions can be improved. The efficiency of the interventions within the city sector can be increased through an improved process of delegation to other sectors, higher involvement of user groups, and higher receptivity and organizational flexibility. The efficiency of the interventions within the citizens sector can be improved through professional, organizational, and financial support. Support from the professional community is important for citizens sector interventions in confirming the importance of the problem they address and legitimizing the actions they propose and undertake.Community Health promotion research Impact assessment Program evaluation Qualitative methods

Cardiac Magnetic Resonance in Hypertensive Heart Disease: Time for a New Chapter

Hypertension is one of the most important cardiovascular risk factors, associated with significant morbidity and mortality. Chronic high blood pressure leads to various structural and functional changes in the myocardium. Different sophisticated imaging methods are developed to properly estimate the severity of the disease and to prevent possible complications. Cardiac magnetic resonance can provide a comprehensive assessment of patients with hypertensive heart disease, including accurate and reproducible measurement of left and right ventricle volumes and function, tissue characterization, and scar quantification. It is important in the proper evaluation of different left ventricle hypertrophy patterns to estimate the presence and severity of myocardial fibrosis, as well as to give more information about the benefits of different therapeutic modalities. Hypertensive heart disease often manifests as a subclinical condition, giving exceptional value to cardiac magnetic resonance as an imaging modality capable to detect subtle changes. In this article, we are giving a comprehensive review of all the possibilities of cardiac magnetic resonance in patients with hypertensive heart disease

Cardiac Magnetic Resonance in Hypertensive Heart Disease: Time for a New Chapter

Hypertension is one of the most important cardiovascular risk factors, associated with significant morbidity and mortality. Chronic high blood pressure leads to various structural and functional changes in the myocardium. Different sophisticated imaging methods are developed to properly estimate the severity of the disease and to prevent possible complications. Cardiac magnetic resonance can provide a comprehensive assessment of patients with hypertensive heart disease, including accurate and reproducible measurement of left and right ventricle volumes and function, tissue characterization, and scar quantification. It is important in the proper evaluation of different left ventricle hypertrophy patterns to estimate the presence and severity of myocardial fibrosis, as well as to give more information about the benefits of different therapeutic modalities. Hypertensive heart disease often manifests as a subclinical condition, giving exceptional value to cardiac magnetic resonance as an imaging modality capable to detect subtle changes. In this article, we are giving a comprehensive review of all the possibilities of cardiac magnetic resonance in patients with hypertensive heart disease

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field