Roles of the DYRK Kinase Pom2 in Cytokinesis, Mitochondrial Morphology, and Sporulation in Fission Yeast

Pom2 is predicted to be a dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) related to Pom1 in Schizosaccharomyces pombe. DYRKs share a kinase domain capable of catalyzing autophosphorylation on tyrosine and exogenous phosphorylation on serine/threonine residues. Here we show that Pom2 is functionally different from the well-characterized Pom1, although they share 55% identity in the kinase domain and the Pom2 kinase domain functionally complements that of Pom1. Pom2 localizes to mitochondria throughout the cell cycle and to the contractile ring during late stages of cytokinesis. Overexpression but not deletion of pom2 results in severe defects in cytokinesis, indicating that Pom2 might share an overlapping function with other proteins in regulating cytokinesis. Gain and loss of function analyses reveal that Pom2 is required for maintaining mitochondrial morphology independently of microtubules. Intriguingly, most meiotic pom2Δ cells form aberrant asci with meiotic and/or forespore membrane formation defects. Taken together, Pom2 is a novel DYRK kinase involved in regulating cytokinesis, mitochondrial morphology, meiosis, and sporulation in fission yeast

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Oddziaływania procesorów fotowoltaicznych na środowisko atmosferyczne

A scale of impact of photovoltaic processors on atmospheric environment is analyzed in the paper. A photovoltaic power plant with the installed capacity of 1 MWp was the study object. The assessment was performed in accordance with the LCA methodology using the Eco-indicator 99 method. Although photovoltaics is considered a fully environmentally friendly energy source method. Although photovoltaics is considered a fully environmentally friendly energy friendly energy source method. Although photovoltaics is considered a fully environmentally friendly energy the photovoltaic power plant during its life cycle emits harmful substances to the atmosphere in an amount equal to the impact made by ca. 15 average Europeans within one year.Analizowano wielkości oddziaływania procesorów fotowoltaicznych na środowisko atmosferyczne. Badanym obiektem była elektrownia fotowoltaiczna o mocy zainstalowanej 1 MWp. Oceny dokonano zgodnie z zasadami analizy LCA, przy wykorzystaniu metody Ekowskaźnik 99. Chociaż fotowoltaika uważana jest za przyjazne dla środowiska źródło energii, to jednak rozpatrywana elektrownia w swoim cyklu życia emituje do atmosfery szkodliwe substancje na poziomie równym wpływowi wywieranemu przez ok. 15 przeciętnych Europejczyków w ciągu roku

Application of life cycle models in the assessment of destructiveness of a wind power plant rotor. Part I. Theoretical bases

W pracy dokonano przeglądu literatury odnoszącej się do oceny środowiskowej recyklingu zespołów roboczych elektrowni wiatrowej, opartej na modelowaniu LCA. Scharakteryzowano pojęcie destrukcyjności obiektów technicznych, omówiono główne założenia oceny cyklu życia (LCA) oraz przedstawiono wybrane modele oceny wpływu, a mianowicie Eko wskaźnik 99 {Eco-indicator 99), CED {Cumulative Energy Demand) oraz IPCC {IPCC 2007 GWP 100a (Intergovernmental Panel on Climate Change, Global Warming Potential, 100 years).The paper presents a literature survey relating to the environmental assessment of recycling of wind power plant units, based on the LCA modeling. Destructiveness of technical objects is characterized, main assumptions of the life cycle assessment (LCA) are discussed and selected models assessing the impact, namely: Eco-indicator 99, CED (Cumulative Energy Demand) and IPCC (IPCC 2007 GWP 100a - Intergovernmental Panel on Climate Change, Global Warming Potential, 100 years) are presented