The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

Prohibitin ring complexes in the mitochondrial inner membrane regulate cell proliferation as well as the dynamics and function of mitochondria. Although prohibitins are essential in higher eukaryotes, prohibitin-deficient yeast cells are viable and exhibit a reduced replicative life span. Here, we define the genetic interactome of prohibitins in yeast using synthetic genetic arrays, and identify 35 genetic interactors of prohibitins (GEP genes) required for cell survival in the absence of prohibitins. Proteins encoded by these genes include members of a conserved protein family, Ups1 and Gep1, which affect the processing of the dynamin-like GTPase Mgm1 and thereby modulate cristae morphogenesis. We show that Ups1 and Gep1 regulate the levels of cardiolipin and phosphatidylethanolamine in mitochondria in a lipid-specific but coordinated manner. Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells. We propose that prohibitins control inner membrane organization and integrity by acting as protein and lipid scaffolds

Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae

Due to its genetic tractability and increasing wealth of accessible data, the yeast Saccharomyces cerevisiae is a model system of choice for the study of the genetics, biochemistry, and cell biology of eukaryotic lipid metabolism. Glycerolipids (e.g., phospholipids and triacylglycerol) and their precursors are synthesized and metabolized by enzymes associated with the cytosol and membranous organelles, including endoplasmic reticulum, mitochondria, and lipid droplets. Genetic and biochemical analyses have revealed that glycerolipids play important roles in cell signaling, membrane trafficking, and anchoring of membrane proteins in addition to membrane structure. The expression of glycerolipid enzymes is controlled by a variety of conditions including growth stage and nutrient availability. Much of this regulation occurs at the transcriptional level and involves the Ino2–Ino4 activation complex and the Opi1 repressor, which interacts with Ino2 to attenuate transcriptional activation of UASINO-containing glycerolipid biosynthetic genes. Cellular levels of phosphatidic acid, precursor to all membrane phospholipids and the storage lipid triacylglycerol, regulates transcription of UASINO-containing genes by tethering Opi1 to the nuclear/endoplasmic reticulum membrane and controlling its translocation into the nucleus, a mechanism largely controlled by inositol availability. The transcriptional activator Zap1 controls the expression of some phospholipid synthesis genes in response to zinc availability. Regulatory mechanisms also include control of catalytic activity of glycerolipid enzymes by water-soluble precursors, products and lipids, and covalent modification of phosphorylation, while in vivo function of some enzymes is governed by their subcellular location. Genome-wide genetic analysis indicates coordinate regulation between glycerolipid metabolism and a broad spectrum of metabolic pathways

Distribution problems and their implementation in Excel

Tato práce se zabývá dopravním kontejnerovým problémem a obecným přiřazovacím, které jsou součástí distribučních úloh. Kotejnerový dopravní problém ma rozsáhle využití v praxi hlavně v odvětví logistiky a obecný přiřazovací problém je základem pro distribuční úlohy s mnoha možnými modifikacemi. V první části se práce věnuje pojmu lineární programováni, dále konkrétne distribučním úlohám. Druhá část je věnovaná implementaci těchto typových úloh do rozhraní MS Excel a Visual Basic. Cílem práce je seznámit čitatele s lineárnim programovánim, poukázat na jeho praktické využití a využít tyto poznatky pro implementaci v rozhraní VBA vytvořením aplikace.This work is focused on container transhipment problem and general assingment problem which are parts of distribution problems. Container transhipment problem has large use in praxis, especially in logistics branch and general assingment problem is basis for distribution problems and has many possible modifications. In first part, the aim of work is term of linear pogramming, next specifically distribution problems. Second part is dedicated to implementation of these typical problems into workspace of MS Excel and Visual Basic. The goal of this work is to familiarize the reader with aspects of linear programing, show the practical use and use these knowledge for implementation into VBA workspace by developing an application.Táto práca sa zaoberá dopravným kontajnerovým problémom a obecným priraďovacím problémom, ktoré sú súčasťou distribučných úloh. Kontajnerový dopravný problém má rozsiahle využitie v praxi najmä v odvetví logistiky a obecný priraďovací problém je základom pre distribučne úlohy s mnoho možnými modifikáciami. V prvej časti sa práca venuje pojmu lineárne programovanie, ďalej konkrétne distribučným úlohám. Druhá časť je venovaná implementácii týchto typových úloh do rozhrania MS Excel a Visual Basic. Cieľom práce je zoznámiť čitateľa s lineárnym programovaním, poukázať na jeho praktické využitie a využiť tieto poznatky pre implementáciu v rozhraní VBA vytvorením aplikácie

Application of simulation models in project management

V organizacích nabízejících elektronické služby existuje neustálý tlak na inovace stávajících produktů, tvorbu nových služeb nebo implementaci regulatorních požadavků. Každý dodávaný software probíhá procesem testování v testovacím prostředí, který odhaluje a napravuje nedostatky dodávky. Cílem práce je namodelovat proces testování softwaru a odhadnout vhodný počet lidských zdrojů v průběhu testování pomocí simulačního modelu. Doba pro testování je omezena a na konci testovacího období je dodávka ověřována, zdali je v dostačené kvalitě pro zavedení softwaru do provozu pro klienty. Pro ověření kvality jsou v práci vydefinována akceptační kritéria, která se na konci simulačního běhu vyhodnocují. Další experimenty se věnují změnám parametrů procesu a jejich vlivu na pravděpodobnost akceptace dodávky projektu.Organizations which are focused on electronic services are subject to constant pressure for innovations of current products, creation of new services and implementation of regulatory requirements. Every software delivery passes through testing process in testing environment, which unveils and fixes delivery bugs. Goal of this work is to create a model of this process and suggest appropriate amount of human resources required for completion of testing process with help of simulation modelling. Testing period is limited with ending point in time, in which current testing status of delivery is evaluated in terms of sufficient quality for software deployment into environment used by clients. Acceptance criteria are defined for quality evaluation, which are evaluated on finish of simulation run. Model is also subject to changes in process parameters and theirs impact on probability of delivery being accepted

DYNAMIC ROUTING OF IP TRAFFIC BASED ON QOS PARAMETERS

ABSTRAC