41 research outputs found
Immunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase
No full textInfection response and other immunity-linked genes (ILGs) were first named in Caenorhabditis elegans-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in C. elegans. RNAi targeting of the ADP-ribosylation factor arf-1, which disrupts the Golgi and secretory function, also activates ILGs. Low PC limits ARF-1 function, suggesting a mechanism for ILG activation via lipid metabolism, as part of a membrane stress response acting outside the ER. RNAi of selected ILGs uncovered defects in the secretion of two GFP reporters and the accumulation of a pathogen-responsive complement C1r/C1s, Uegf, Bmp1 (CUB) domain fusion protein. Our data argue that up-regulation of some ILGs is a coordinated response to changes in trafficking and may act to counteract stress on secretory function
Low Phosphatidylcholine Conditions Induce a Golgi Stress Response to Stabilize Intracellular Trafficking
No full textMembranes form the outer boundaries of cells and their organelles. Certain organelles, such as the endoplasmic reticulum (ER) and Golgi apparatus, are functionally defined by the structure and composition of their membranes. Dysfunction in the structure or function of membrane-defined organelles results in activation of stress responses to stabilize and restore the organelles. The ER stress response is associated with pathologies due to metabolic dysfunction, and as such constitute a public health concern. However, the Golgi stress response, a nascent field of study, has not been as extensively investigated. Altering levels of the membrane phospholipid phosphatidylcholine (PC) results in inactivation of a key intracellular trafficking enzyme ARF-1/ARF1. ARF proteins facilitate intracellular trafficking, and ARF-1/ARF1 enable trafficking from the Golgi apparatus to the ER. In this study I investigated whether altered levels of PC and impaired COPI retrograde intracellular trafficking could be linked to Golgi stress.
Using Caenorhabditis elegans and human HepG2 cells as models, I have shown that perturbing either COPI retrograde intracellular trafficking or production of PC affects the morphology of the Golgi apparatus while the ER is spared. Because the structure of the Golgi apparatus is essential in maintaining proper function of the organelle, this means that inhibited retrograde intracellular trafficking as well as low PC results in Golgi stress. Furthermore, I have observed that there is an increased expression of WARF-1/ARF4 under these conditions. Additionally, I determined that WARF-1 likely compensates for loss of ARF-1 function. Lastly, my data indicates that upregulation of warf-1/ARF4 is dependent on the transcription factors LET-607/CREB3L1. These results indicate that Golgi stress induces increased expression of the trafficking enzymes WARF-1/ARF4 to stabilize intracellular trafficking.Interdisciplinary Graduate Program2025-06-1
MOTIVASI PENGARANG YANG TERKANDUNG DALAM CERPEN CARMEN KARYA KEZIA ALAIA
No full textEmmanuel, Christofer. 2019. “Author’s Motivation in Carmen’s Short Story Written by Kezia Alaia”. Bachelor Program of Indonesian Literature, Semarang, Faculty of Humanities, Diponegoro University. Supervisor I Prof. Dr.
Mudjahirin Thohir, M.A., Supervisor II Drs. M. Hermintoyo, M.Pd.,
A short story tittled Carmen written by Kezia Alaia, is about a human who is struggling inside and desperate. Another uniqueness is how Kezia write the story, when she tells about a relationship between two human being when they try to understand live, in the night with current Jakarta as background.
This study uses the note-taking technique, which is a way to obtain data using written sources. While the note-taking technique is a follow-up technique carried out by the researcher when applying the refer method.
This study aims to identify the intrinsic elements in Carmen's short stories. Then to find Kezia Alaia's motivation in producing her work that describe human life in an era of urbanization in Carmen's short stories. This research can be used as a reference in understanding and interpreting the sociology of literature related to the author and its relationship with the social life of the community.
The results showed that, beside physiological needs, Kezia was more likely want to express feelings and anxiety, so that when Kezia finished her write, she could re-read and then recall her life history in the past. However, Kezia did not consume her own work, she wanted the community to understand the anxiety, and get the message implied and explicit as a reflection for the reader.
Keywords: Intrinsic. Motivation. Sociology of Literature
Hypertension - The interaction with the metabolic load and the influence of age and gender
No full textMaster Thesis, Programme in medicine, 2013
TITLE: Hypertoni – samspelet med metabolbelastning och påverkan av ålder och kön. AUTHOR: Christofer Håkansson
Department of molecular and clinical medicine Institution of medicine Sahlgrenska Academy,
University of Gothenburg, Sweden
Introduction
In Sweden approximately 1,8 million people (almost 20 % of the population)
suffer from hypertension. Hypertension is an important riskfactor for
cardiovascular disease (CVD). Further CVD affects women later in life compared
to men.
Aim
The aim was to study the interaction between blood pressure and metabolic
factors such as body mass index and waist-circumference. Moreover we aimed
to evaluate the impact of gender and age on this interaction. Additionally we
also wanted to examine the effects of blood pressure on the cardiovascular
structure and function in gender and age-perspective.
Methods
This is a descriptive observational study with 162 individuals recruited from
observational investigations. Metabolic variables and blood pressure have been
measured in all subjects and echocardiographic measurements and
investigation of peripheral arterial function has also been performed.
Results
Mean age of the population was 56 years and 80 % of the population was 50
years or older. There were 52 % women in the study. 60 % were non-smokers
and 53 % had a mean 24-hour systolic blood pressure (SABPM) over 125 mm
Hg. We found significant correlations between 24-hour systolic blood pressure
and age, BMI, waist-measurement, septum-thickness, left ventricular mass, left
ventricular mass index, deceleration time, intima media-thickness and pulse
wave velocity in men, but in women only septum-thickness and augmentation
index correlated significantly with SABPM . Conclusions
Our results suggest that middle aged men are more vulnerable to the effects of
blood pressure on cardiovascular function and structure and further that
metabolic factors associated with obesity and visceral fat influence blood
pressure more in men than in age matched women
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Study of Inhibitory Properties of Small Molecule Compounds on Histone Deacetylases
No full textHistones can undergo modifications, which regulate the accessibility of DNA. Modifications such as acetylation alter the epigenetic landscape, which regulates the expression of genes. Epigenetic regulations have been linked to important developmental stages of cardiovascular development. Because of their large clutch sizes, and transparent embryos, zebrafish are a useful for studying the effect of compounds believed to be epigenetic regulators. The aim of this project was to screen a library of small molecule compounds on zebrafish, for their effect on cardiovascular development. The library was screened on zebrafish, and thereafter analyzed by in vitro and in vivo assays. It was determined that six of these compounds had varying inhibitory properties on HDAC enzymes
CON 371, mechanical and plumbing systems - OER project materials
No full textThis document contains materials collected developed for the course CON 371 for the OER project funded by the Colorado OER Council Grant (AY 2019-20).Document includes: OER proposal, lesson slides and in-class exercises.Funded by the Colorado Open Educational Resources (OER) Grant 2018-2019
GPCR structures in drug design, emerging opportunities with new structures
No full textAbstractIn recent years, GPCR targets from diverse regions of phylogenetic space have been determined. This effort has culminated this year in the determination of representatives of all major classes of GPCRs (A, B, C, and F). Although much of the now well established knowledge on GPCR structures has been known for some years, the new high-resolution structures allow structural insight into the causes of ligand efficacy, biased signaling, and allosteric modulation. In this digest the structural basis for GPCR signaling in the light of the new structures is reviewed and the use of the new non-class A GPCRs for drug design is discussed
Genom Stanley Kubricks lins
No full textA auteur analysis of Stanley Kubrick with a intermedial focus. The paper explores the directors evolution from still photography to movies, and tries to find similarities between the two on both a aestetich level as well as in the way they are made. The purpose is to find out if Kubricks eye for detail and his perfectionism came during his work in films or if it's been with him all along. The author compares a number of Stanley Kubricks photographs to his movies in an effort to answer these questions
Delivery Reliability and Public Procurement - A Case Study on a Healthcare Provider
No full textAssuring delivery reliability is a vital part for any organisation in a supply chain, and in few cases could the consequences of a failed delivery be as dire as they would in the case of a healthcare provider. However, delivery reliability is not a well-studied subject within the context of public healthcare procurement. The aim of this thesis has been to identify the factors that affect delivery reliability with regards to the purchasing function and how these could be applied to the case organisation. The author identified five factors that affect delivery reliability with regards to purchasing. These are the purchasing process, supplier management, risk management, the power balance between the supplier and buyer and metrics. This is a multiple case-study where the author used five different procurements as cases. The data was gathered from interviews, one for each case and one interview that focused on the organisation as a whole. The cases were then compared to each other and to the established theory from a literature review, resulting in a gap analysis. From there general conclusions were drawn regarding how the case organisation could improve their work in delivery reliability with regards to purchasing. These conclusions have to do with the importance of data handling, supplier management, risk management, handling power imbalances and the purchasing process. Specifically, Region Skåne should work more with proactive expediting, evaluations, risk management, supplier management, power imbalances with their supplier, more process-oriented work in general and finally data and IT solutions. The hope is that other similar organisations can find lessons here as well
Zapiski historyczne gdańszczanina Eberharda Böttichera (1554-1617). Addenda et corrigenda
No full textHistorische Aufzeichnungen des Danzigers Eberhard Bötticher (1554-1617)Addenda et corrigendaZusammenfassung2013 erschien die von Christofer Herrmann und Edmund Kizik erstellte Edition der Chronik der Marienkirche in Danzig (Historisches Kirchen-Register), die 1616 von Eberhard Bötticher niedergeschrieben worden war. Erst nach der Veröffentlichung dieser Edition stieß ich im Bestand Bibliotheca Archivi (Sign. 300, R/Ce, 30) des Staatsarchivs Danzig auf einen Band, der die sorgfältig geführten Aufzeichnungen Böttichers aus den Jahren 1595-1600 enthält. Diese wurden in der bisherigen Forschung nicht benutzt, weshalb dies mit dem vorliegenden Beitrag nachgeholt werden soll. Bei den Aufzeichnungen handelt es sich nicht um die Fortsetzung des Tagebuchs Böttichers. Der Autor berichtet hier vor allem über die Verhandlungen zwischen dem Stadtrat, der Schöffenbank und den Vertretern wohlhabender Bürger. Sie betreffen verschiedene Probleme wirtschaftlich-rechtlicher, religiöser und politischer Natur. Diese Notizen, die Bötticher auch bei der Abfassung seines Kirchen-Registers benutzt hatte, stellen eine wertvolle Quelle für das Selbstverständnis von Bürgern dar, die sich am Ende des 16. Jahrhunderts in das politische Leben Danzigs einbringen wollten. Historical notes of Eberhard Bötticher (1554-1617) of GdańskAddenda et corrigendaAbstractIn 2013 an edition of the chronicle of St. Mary’s Church in Gdańsk (Historisches Kirchen Register) – originally written by Eberhard Bötticher in 1616 – was published by Christofer Herrmann and Edmund Kizik. After it appeared, I accidentally found in the State Archive in Gdańsk (shelf number 300, R/Cc, 30) a volume containing systematic notes made by Bötticher for the years 1595-1600. So far, they have not been used by scholars. Those note are not a continuation of Bötticher’s diary. The author concentrates on relating the negotiations between the city council, the city bench and representatives of wealthy burghers. The notes, which were used by Bötticher for writing his Kirchen Register, are a valuable source for reconstructing the attitudes of burghers attempting to enter the political life of Gdańsk at the end of the sixteenth century.In 2013 an edition of the chronicle of St. Mary’s Church in Gdańsk (Historisches Kirchen Register) – originally written by Eberhard Bötticher in 1616 – was published by Christofer Herrmann and Edmund Kizik. After it appeared, I accidentally found in the State Archive in Gdańsk (shelf number 300, R/Cc, 30) a volume containing systematic notes made by Bötticher for the years 1595-1600. So far, they have not been used by scholars. Those note are not a continuation of Bötticher’s diary. The author concentrates on relating the negotiations between the city council, the city bench and representatives of wealthy burghers. The notes, which were used by Bötticher for writing his Kirchen Register, are a valuable source for reconstructing the attitudes of burghers attempting to enter the political life of Gdańsk at the end of the sixteenth century
