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Enzymatic Characterization of a Human Acyltransferase Activity
Akihiko Ozawa, Richard B. Speaker, Iris Lindberg
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005426
Abstract: Background Non-histone protein acylation is increasingly recognized as an important posttranslational modification, but little is known as to the biochemical properties of protein serine acylating enzymes. Methodology/Principal Findings We here report that we have identified a metal-stimulated serine octanoyltransferase activity in microsomes from human erythroleukemic (HEL) cells. The HEL acylating enzyme was linear with respect to time and protein, exhibited a neutral pH optimum (stimulated by cobalt and zinc), and inhibited by chelating reagents. Hydroxylamine treatment removed most, but not all, of the attached radioactivity. A salt extract of microsomal membranes contained the major portion of enzyme activity, indicating that this acyltransferase is not an integral membrane protein. Sucrose density fractionation showed that the acyltransferase activity is concentrated in the endoplasmic reticulum. In competition experiments, the acyltransferase was well inhibited by activated forms of fatty acids containing at least eight to fourteen carbons, but not by acetyl CoA. The zinc-stimulated HEL acyltransferase did not octanoylate proenkephalin, proopiomelanocortin, His-tagged proghrelin, or proghrelin lacking the amino-terminal His-tag stub of Gly-Ala-Met. The peptides des-acyl ghrelin and ACTH were also not acylated; however, des-acyl ghrelin containing the N-terminal tripeptide Gly-Ala-Met was acylated. Mutagenesis studies indicated a requirement for serine five residues from the amino terminus, reminiscent of myristoyl transferase, but not of ghrelin acylation. However, recombinant myristoyl transferase could not recapitulate the hydroxylamine sensitivity, zinc-stimulation, nor EDTA inhibition obtained with HEL acyltransferase, properties preserved in the HEL cell enzyme purified through four sequential chromatographic steps. Conclusions/Significance In conclusion, our data demonstrate the presence of a zinc-stimulated acyltransferase activity concentrated in the endoplasmic reticulum in HEL cells which is likely to contribute to medium-chain protein lipidation.
Identification of a Small Molecule That Selectively Inhibits Mouse PC2 over Mouse PC1/3: A Computational and Experimental Study
Austin B. Yongye, Mirella Vivoli, Iris Lindberg, Jon R. Appel, Richard A. Houghten, Karina Martinez-Mayorga
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056957
Abstract: The calcium-dependent serine endoproteases prohormone convertase 1/3 (PC1/3) and prohormone convertase 2 (PC2) play important roles in the homeostatic regulation of blood glucose levels, hence implicated in diabetes mellitus. Specifically, the absence of PC2 has been associated with chronic hypoglycemia. Since there is a reasonably good conservation of the catalytic domain between species translation of inhibitory effects is likely. In fact, similar results have been found using both mouse and human recombinant enzymes. Here, we employed computational structure-based approaches to screen 14,400 compounds from the Maybridge small molecule library towards mouse PC2. Our most remarkable finding was the identification of a potent and selective PC2 inhibitor. Kinetic data showed the compound to be an allosteric inhibitor. The compound identified is one of the few reported selective, small-molecule inhibitors of PC2. In addition, this new PC2 inhibitor is structurally different and of smaller size than those reported previously. This is advantageous for future studies where structural analogues can be built upon.
An internet-based intervention program for supporting families with prematurely born infants  [PDF]
Birgitta Lindberg, Kerstin ?hrling
Open Journal of Nursing (OJN) , 2012, DOI: 10.4236/ojn.2012.22012
Abstract: The purpose of this paper was to describe the development, planning and implementing of an internet-based intervention program for providing support to families with prematurely born infants. During the families initial stay at home with their infant; families were given access to use of videoconference system from their home to have contact with staff at the neonatal unit, via direct link, throughout twenty-four hours. This program successfully ended, and video-conferencing is incorporated as a tool to support families after coming home. Probably, a variety of factors has contributed to make this program successful, as for example user friendliness and the close collaboration between researchers and staff at the neonatal unit. In conclusion, Information and Communication Technology (ICT) must be taken into consideration in developing upcoming care, thereby making possible a program to extend accessibility to health care.
Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice
Charles R Farber, James Chitwood, Sang-Nam Lee, Ricardo A Verdugo, Alma Islas-Trejo, Gonzalo Rincon, Iris Lindberg, Juan F Medrano
BMC Genetics , 2008, DOI: 10.1186/1471-2156-9-34
Abstract: Through a combination of DNA microarray analysis and quantitative PCR we identified a strong expression quantitative trait locus (eQTL) regulating Scg5 expression in two mouse chromosome 2 congenic strains and three additional F2 intercrosses. More importantly, the eQTL was coincident with a body weight QTL in congenic mice and Scg5 expression was negatively correlated with body weight in two of the F2 intercrosses. Analysis of haplotype blocks and genomic sequencing of Scg5 in high (C3H/HeJ, DBA/2J, BALB/cByJ, CAST/EiJ) and low (C57BL/6J) expressing strains revealed mutations unique to C57BL/6J and possibly responsible for the difference in mRNA abundance. To evaluate the functional consequence of Scg5 overexpression we measured the pituitary levels of 7B2 protein and PCSK2 activity and found both to be increased. In spite of this increase, the level of pituitary α-MSH, a PCSK2 processing product, was unaltered.Together, these data support a role for Scg5 in the modulation of body weight.Body weight, as with all complex traits, is partially regulated by the coordinate action of individual genes. One common approach for dissecting the genetics of growth is the mapping of quantitative trait loci (QTL). In the last decade numerous human and mouse growth QTL have been identified [1]; however, while this progress is important, few if any of the loci have been unequivocally resolved to the effects of a single quantitative trait gene (QTG).Several studies involving many different mouse inbred strains have demonstrated an enrichment of growth and obesity QTL on chromosome 2 [2,3]. In our laboratory, we have developed a number of genomic resources with the goal of discerning the molecular basis of chromosome 2 QTL segregating between the C57BL/6J (B6), C57BL/6J-hg/hg (HG) and CAST/EiJ (CAST) strains [4,5]. These include two congenic strains, B6.CAST-(D2Mit329-D2Mit457)N(6) (B62D) and HG.CAST-(D2Mit329-D2Mit457)N(6) (HG2D), constructed by introgressing an identical congenic
Functional Consequences of a Novel Variant of PCSK1
Lindsay A. Pickett, Michael Yourshaw, Valeria Albornoz, Zijun Chen, R. Sergio Solorzano-Vargas, Stanley F. Nelson, Martín G. Martín, Iris Lindberg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055065
Abstract: Background Common single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity. Methodology/Principal Findings A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3. Conclusion/Significance Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted.
Verklig fiktion om virtuell verklighet – Litteraturundervisningens utmaning
Ylva Lindberg
L?ring og Medier , 2009,
Abstract: F ljande text utg r fr n fr gorna varf r och hur humaniora ska integrera ny teknik. I detta fall belyses mer specifikt hur svensk mnet och litteraturundervisningen kan anknyta till den teknologi som virtuella tredimensionella v rldar via internet uppvisar. I den f rsta delen av artikeln refereras till ett f rs k att anv nda den virtuella v rlden Second Life i en kurs i litteraturvetenskap. Sedan beskrivs de n ra samband som finns mellan litteratur och teknik. D refter f ljer en argumentation som vill visa p varf r just virtuella v rldar r betydelsefulla f r litteraturvetenskapen. Konklusionen r att digitala universum kan vara ett verktyg d r teknik och litteratur kan m tas p lika villkor, utan att den ena eller den andra dominerar teoretiskt. I den andra delen utforskas rent allm nt m jligheterna att f rnya svensk mnet och litteraturundervisningen genom aktuell informations- och kommunikationsteknologi, IKT, och mer specifikt genom virtuella v rldar, som i sig rymmer en stor del av n mnda tekniker. H r fokuseras framf r allt p grundskolan, men ven p h gre studier. Mot bakgrund av den senaste debatten kring litteraturkanon, grundskolans kursplaner, samt svensk mnets konception diskuteras vilken plats som finns i undervisningen f r IKT och ett studium av virtuella v rldar. Den centrala fr gan kretsar ven h r kring hur det litter ra och humanistiska perspektivet kan m ta det tekniskt naturvetenskapliga och vice versa. I tredje delen ges en mycket kortfattad forsknings versikt som syftar till att belysa hur man b de i litteraturvetenskapliga och tekniska forskningssammanhang under de senaste ren diskuterat f rh llandet mellan litteraturvetenskap och teknik, men ven mellan teknik och andra konstformer, s som bildkonsten. I den sista och fj rde delen presenteras n gra romaner som utspelar sig i den virtuella v rlden Second Life eller i en digital milj som r mycket lik denna. I denna del presenteras olika argument f r att teknik p detta s tt kan integreras i mnet genom litteraturl sning. Avsnittet g r en analys av romanerna Notre seconde vie (2008) av Alain Monnier och ANIMA: A Novel about Second Life (2007) av avataren Dalian Hansen, d r exempel tas fram som kan knyta an till svensk mnets tre konceptioner - litteraturhistoria, spr kliga f rdigheter och erfarenhetspedagogik - samt till litteracitet och s rskilt till digital litteracitet.
‘The next step’ – alumni students' views on their preparation for their first position as a physician
Ola Lindberg
Medical Education Online , 2010, DOI: 10.3402/meo.v15i0.4884
Abstract: Background: Although medical programmes are often thoroughly evaluated, these evaluations more seldom include workplace points of view. The present study focuses on how well a Swedish medical programme was judged to prepare students for work as a physician. Methods: Thirty-two competences in physicians'work were identified through interviews. A subsequent questionnaire was completed by 123 programme alumni who had worked for 1–2 years in different parts of the country. Alumni were asked to rate the importance of each competence, their self-assessed competence as well as how these competences were addressed during their medical training. Results: The subsequent analysis identified areas where their training programme, according to the alumni, failed to prepare them satisfactorily. Problem areas included competences in clinical skills, handling stressful situations and in applied rather than foundational knowledge about common symptoms and diseases. Conclusion: Despite extensive practical training, medical education still faces some problems in the transition from education to work.
I det nya m ngspr kiga Sverige
Inger Lindberg
Utbildning & Demokrati : Tidsskrift f?r Didaktik och Utbildningspolitik , 2009,
Abstract: In the new multilingual Sweden. In this article, global as well as local aspects of language dominance are considered in a discussion of the role of language for social equity, integration, democracy in today’s Sweden. In this respect, the dual role of Swedish – as a minority language globally and majority language locally – is considered, in particular for the implementation of Swedish language policy. On 1 July 2009, a new Language Act entered into force based on current language policy which includes objectives to ensure everyone’s access to the Swedish language and to safeguard the position of Swedish as the main language in Sweden. The Language Act is a result of increasing impact of English and wide-spread multilingualism in the Swedish society in the early 21st century. The need for initiatives to preserve linguistic diversity and promote multilingualism is addressed in a provision contained in the Language Act, in which the right for everyone who has a mother tongue other than Swedish is to be given the opportunity to develop and use their mother tongue is secured. The present article takes a critical look at some of the questions raised by the Language Act with special relevance for issues of education, democracyand integration in postmodern, multilingual Sweden.
Portfolio optimization when expected stock returns are determined by exposure to risk
Carl Lindberg
Mathematics , 2009, DOI: 10.3150/08-BEJ163
Abstract: It is widely recognized that when classical optimal strategies are applied with parameters estimated from data, the resulting portfolio weights are remarkably volatile and unstable over time. The predominant explanation for this is the difficulty of estimating expected returns accurately. In this paper, we modify the $n$ stock Black--Scholes model by introducing a new parametrization of the drift rates. We solve Markowitz' continuous time portfolio problem in this framework. The optimal portfolio weights correspond to keeping $1/n$ of the wealth invested in stocks in each of the $n$ Brownian motions. The strategy is applied out-of-sample to a large data set. The portfolio weights are stable over time and obtain a significantly higher Sharpe ratio than the classical $1/n$ strategy.
Evaluation of process management of postpartum hemorrhage due to uterine atony  [PDF]
Iris Holzer, Rainer Lehner
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.37093

Objective: To evaluate the management process and the guidelines for management of postpartum hemorrhage due to uterine atony at the General Hospital Vienna, Medical University Vienna. Material and Methods: A retrospective analysis was carried out on all 24 cases of postpartum hemorrhage due to uterine atony with an estimated blood loss of more than 800 mL, in which standardized guidelines were obtained. We included all women who gave birth at the General Hospital of Vienna, the Medical University Vienna, during the period from January 1st 2003 and December 31st 2009 and who suffered blood loss 800 mL at minimum due to uterine atony. Results: The guidelines were in use for 14% - 71%. The average blood loss of the 24 cases with uterine atony was 1342 mL. Conclusion: The management process of postpartum hemorrhage due to uterine atony deviates from the hospital’s guidelines in many cases.

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