Die Regierungsreform im Bund : in kleinen Schritten und auf einem engen Pfad, Inkrementalismus und Pfadabhängigkeit

Die Bestrebungen für eine Regierungsreform in der Schweiz lassen sich weit zurückverfolgen, sie führten aber zu keinen weitreichenden Ände-rungen betreffend das Regierungsorgan. Hauptsächliche Folgen waren Verwaltungsreformen. Schrittweise oder inkrementalistische Änderungen sind feststellbar. Sie betreffen die sogenannte Organisationsgewalt, die Bundeskanzlei, die Führungsstäbe, vor allem aber die Staatssekretärinnen und Staatssekre-täre. Die Leitplanken und die Zusatzbotschaft aus dem Jahr 2010 des Bun-desrates für eine Regierungsreform richten sich nach den Ergebnissen des Beitrages nach inkrementalistischen Entwicklungen aus. Mit der Verlängerung der Amtsdauer der Bundespräsidentin oder des Bundes-präsidenten könnte zudem ein neuer Entwicklungspfad begründet wer-den. Dem aktuellen Reformanstoss werden auf Grund der verwendeten Erklärungsansätze erhöhte Chancen zugemessen. Les efforts pour une réforme du gouvernement en Suisse remontent loin, mais ils n'ont pas abouti à des modifications de longue portée concernant l'organe gouvernemental. Les résultats principaux étaient des réformes de l'administration. Des modifications graduelles ou incrémentales sont détectables. Elles concernent le pouvoir d'organisation, la Chancellerie fédérale, les états-majors, mais surtout les secrétaires d'État. Les axes principaux et le message additionnel pour une réforme du gouvernement sont orientés vers les développements incrémentales constatés selon les recherches effectuées. L'allongement de la durée de fonction du président de la Confédération pourrait en plus constituer un nouveau chemin du développement. L'impulsion actuelle pour une réforme a des chances élevées d'aboutir selon les essais d'explication.

Breast cancer and melanoma cell line identification by FTIR imaging after formalin-fixation and paraffin-embedding.

Over the past few decades, Fourier transform infrared (FTIR) spectroscopy coupled to microscopy has been recognized as an emerging and potentially powerful tool in cancer research and diagnosis. For this purpose, histological analyses performed by pathologists are mostly carried out on biopsied tissue that undergoes the formalin-fixation and paraffin-embedding (FFPE) procedure. This processing method ensures an optimal and permanent preservation of the samples, making FFPE-archived tissue an extremely valuable source for retrospective studies. Nevertheless, as highlighted by previous studies, this fixation procedure significantly changes the principal constituents of cells, resulting in important effects on their infrared (IR) spectrum. Despite the chemical and spectral influence of FFPE processing, some studies demonstrate that FTIR imaging allows precise identification of the different cell types present in biopsied tissue, indicating that the FFPE process preserves spectral differences between distinct cell types. In this study, we investigated whether this is also the case for closely related cell lines. We analyzed spectra from 8 cancerous epithelial cell lines: 4 breast cancer cell lines and 4 melanoma cell lines. For each cell line, we harvested cells at subconfluence and divided them into two sets. We first tested the "original" capability of FTIR imaging to identify these closely related cell lines on cells just dried on BaF2 slides. We then repeated the test after submitting the cells to the FFPE procedure. Our results show that the IR spectra of FFPE processed cancerous cell lines undergo small but significant changes due to the treatment. The spectral modifications were interpreted as a potential decrease in the phospholipid content and protein denaturation, in line with the scientific literature on the topic. Nevertheless, unsupervised analyses showed that spectral proximities and distances between closely related cell lines were mostly, but not entirely, conserved after FFPE processing. Finally, PLS-DA statistical analyses highlighted that closely related cell lines are still successfully identified and efficiently distinguished by FTIR spectroscopy after FFPE treatment. This last result paves the way towards identification and characterization of cellular subtypes on FFPE tissue sections by FTIR imaging, indicating that this analysis technique could become a potential useful tool in cancer research.

The role of microRNAs in the development of type 2 diabets

Pancreatic ß cells are highly specialized endocrine cells located within the islets of Langerhans in the pancreas. Their main role is to produce and secrete insulin, the hormone essential for the regulation of glucose homeostasis and body's metabolism. Diabetes mellitus develops when the amount of insulin released by ß cells is not sufficient to cover the metabolic demand. In type 1 diabetes (5-10% of diagnoses) insulin deficiency is caused by the autoimmune destruction of pancreatic ß cells. Type 2 diabetes (90% of diagnoses) results from a genetic predisposition and from the presence of adverse environmental conditions. The combination of these factors reduces insulin sensitivity of peripheral target tissues, causes impairment in ß-cell function and can lead to partial loss of ß cells. The development of novel therapeutic strategies for the treatment of diabetes necessitates the comprehension of the cellular processes involved in dysfunction and loss of ß cells. My thesis was focused on the involvement in the physiopathological processes leading to the development of diabetes of a class of small regulatory RNA molecules, called microRNAs (miRNAs) that post- transcriptionally regulate gene expression. Global miRNA profiling in pancreatic islets of two animal models of diabetes, the db/db mice and mice that were fed a high fat diet (HFD), characterized by obesity and insulin resistance, led us to identify two groups of miRNAs displaying expression changes under pre-diabetic and diabetic conditions. Among the miRNAs already upregulated in pre-diabetic db/db mice and HFD mice, miR- 132 was found to have beneficial effects on pancreatic ß cell function and survival. Indeed, mimicking the upregulation of miR-132 in primary pancreatic islet cells and ß-cell lines improved glucose- induced insulin secretion and favored survival of the cells upon exposure to pro-apoptotic stimuli such as palmitate and cytokines. MiR-132 was found to exert its action by enhancing the expression of MafA, a transcription factor essential for ß-cell function, survival and identity. On the other hand, up-regulation of miR-199a-5p and miR-199a-3p was detectable only in the islets of diabetic db/db mice and resulted in impaired insulin secretion and sensitization of the cells to apoptosis. MiR-199a- 5p was found to decrease insulin secretion by inducing the expression of granuphilin, a potent inhibitor of ß cell exocytosis. In contrast, miR-199a-3p was demonstrated to directly target and reduce the expression of two key ß-cell genes, mTOR and cMET, resulting in impaired ß-cell adaptation to metabolic demands and loss by apoptosis. Our findings suggest that miRNAs are important players in the onset of type 2 diabetes. MiRNA expression is adjusted in pancreatic ß cells exposed to a diabetogenic environment. These changes initially concern miRNAs responsible for adaptive processes aimed at compensating the onset of insulin resistance, but later such changes can be overlapped by modifications in the level of several additional miRNAs that favor ß-cell failure and the onset of type 2 diabetes.

The Child Welfare Decategorization Program, August 2010

This Handbook is designed to outline the purposes, goals, structure, and operational procedures for Iowa’s Child Welfare Decategorization Program. The Handbook incorporates experiences gained since the inception of Decategorization in 1987. As with any initiative that began on a pilot basis, Decategorization has been an evolving program in which parameters and procedures have undergone modifications to achieve the desired results. The Handbook serves as a guidebook for implementation and operation of Decategorization and a means of communicating information on program parameters and procedures. Purposes of Decategorization of child welfare and juvenile justice funding is an initiative intended to establish systems of delivering human services based upon client needs to replace systems based upon a multitude of categorical funding programs and funding sources, each with different service definitions and eligibility requirements. Decategorization is designed to redirect child welfare and juvenile justice funding to services which are more preventive, family centered, and community-based in order to reduce use of restrictive approaches that rely on institutional, out-of home, and out-of-community care.

Chirurgie du diabète: provocation ou réalité [Surgery for diabetes: challenge or reality?]

Bariatric surgery techniques can usually increase either sensitivity or insulin resistance, acting on three different levels: decrease of food intake, malabsorption and modifications of entero-insulaire axis activity. This latter is taken into account in order to develop a new protocol to obtain diabetes remission without important weight loss and nutritional deficiencies. Preliminary results are interesting but they come from very short time studies with few patients. Moreover, complications rate is at present very high. Knowing better gastrointestinal mechanisms of diabetes control and especially incretins role is absolutely necessary before identifying surgery as a true metabolic treatment.

Soil fertility, nutrition and yield of maize and barley with gypsum application on soil surface in no-till

Annual crop yield and nutrition have shown differentiated responses to modifications in soil chemical properties brought about by gypsum application. The aim of this study was to evaluate the effect of gypsum application rates on the chemical properties of a Latossolo Bruno (Clayey Oxisol), as well as on the nutrition and yield of a maize-barley succession under no-till. The experiment was set up in November 2009 in Guarapuava, Parana, Brazil, applying gypsum rates of 0.0, 1.5, 3.0, 4.5, and 6.0 Mg ha-1 to the soil surface upon sowing maize, with crop succession of barley. Gypsum application decreased the levels of Al3+ and Mg2+ in the 0.0-0.1 m layer and increased soil pH in the layers from 0.2-0.6 m depth. Gypsum application has increased the levels of Ca2+ in all soil layers up to 0.6 m, and the levels of S-SO4(2-) up to 0.8 m. In both crops, the leaf concentrations of Ca and S were increased while Mg concentrations have decreased as a function of gypsum rates. There was also an effect of gypsum rates on grain yield, with a quadratic response of maize and a linear increase for barley. Yield increases were up to 11 and 12 % in relation to control for the maximum technical efficiency (MTE) rates of 3.8 and 6.0 Mg ha-1 of gypsum, respectively. Gypsum application improved soil fertility in the profile, especially in the subsurface, as well as plant nutrition, increasing the yields of maize and barley.

State of Iowa Long-Term Economic Recovery Strategy Prepared for the Economic Development Administration, U.S. Department of Commerce, October 2010

The Rebuild Iowa Office (RIO) continues to coordinate the state‘s recovery effort from the storms, tornadoes and floods of 2008. Much has been accomplished since the Office‘s last quarterly report was issued in July 2010. State funding has been disbursed to help Iowans with unmet needs and housing. Local governments and entities are utilizing millions of federal dollars so thousands of disaster-impacted homeowners can be offered a buyout. More infrastructure projects are under construction and new neighborhoods are being built with mitigation efforts in mind. However, as Iowa continues to celebrate many successes along the road to recovery, it must also address the numerous challenges that are encountered along the path. Recovering from the state‘s largest disaster must be looked at as a marathon, not a sprint. Over the past three months, the RIO has especially remained focused on helping small business owners impacted by the 2008 disasters. Many disaster-affected businesses have reopened their doors, however their debt load continues to be overwhelming and many still struggle with the timeliness of the disbursement of funds. This report describes how programs and recent modifications are working to assist recovering businesses. This report contains updates on housing progress while outlining the complexities behind certain programs and the bottlenecks communities are facing due to strict federal guidelines for implementation. This following pages also describe how Iowa is implementing Smart Planning principles, publicizing flood awareness through outreach efforts and preparing a blueprint for the state to follow when future disasters occur. As always, the RIO recognizes and thanks the countless leaders and front-line workers from local, regional, state and federal government, businesses, non-profit organizations and private citizens that have provided input, support and leadership. Their dedication to Iowa‘s disaster recovery has made the plans and projects on the following pages possible.

Pulse wave analysis aortic pressure . distole should also be considered

La rigidité anormalement haute des artères à grande conductance est un marqueur de l'augmentation du risque cardiovasculaire et est typiquement retrouvée chez les patients diabétiques ou hypertendus. Ces vaisseaux deviennent plus rigides avec l'âge, expliquant la haute prévalence d'hypertension systolique chez les personnes âgées. Cette rigidification agit sur la pression sanguine de plusieurs façons. Notamment la fonction windkessel est gênée, menant à l'augmentation de la pression systolique et de la pression puisée, la diminution de la pression diastolique, et ainsi à l'augmentation de la postcharge ventriculaire gauche associée à une probable diminution de la perfusion coronarienne. De plus, la propagation des ondes de pression le long de l'arbre vasculaire est accélérée, de sorte que les ondes réfléchies générées au site de décalage d'impédance atteignent l'aorte ascendante plus tôt par rapport au début de l'éjection ventriculaire, aboutissant à une augmentation de la pression systolique centrale, ce qui n'arriverait pas en présence de vaisseaux moins rigides. Dans ce cas, au contraire, les ondes de pression antérogrades et réfléchies voyages plus lentement, de sorte que les ondes de réflexion tendent à atteindre l'aorte centrale une fois l'éjection terminée, augmentant la pression diastolique et contribuant à la perfusion coronarienne. La tonométrie d'applanation est une méthode non invasive permettant l'évaluation de la forme de l'onde de pression au niveau l'aorte ascendante, basée sur l'enregistrement du pouls périphérique, au niveau radial dans notre étude. Nous pouvons dériver à partir de cette méthode un index d'augmentation systolique (sAIX) qui révèle quel pourcentage de la pression centrale est du aux ondes réfléchies. Plusieurs études ont montré que cet index est corrélé à d'autres mesures de la rigidité artérielle comme la vitesse de l'onde de pouls, qu'il augmente avec l'âge et avec les facteurs de risques cardiovasculaires, et qu'il est capable de préciser le pronostic cardiovasculaire. En revanche, peu d'attention a été portée à l'augmentation de la pression centrale diastolique due aux ondes réfléchies (dAIX). Nous proposons donc de mesurer cet index par un procédé d'analyse développé dans notre laboratoire, et ce dans la même unité que l'index systolique. Etant donné que les modifications de la paroi artérielle modulent d'une part la vitesse de l'onde de pouls (PWV) et d'autre part le temps de voyage aller-retour des ondes de pression réfléchies aux sites de réflexion, toute augmentation de la quantité d'énergie réfléchie atteignant l'aorte pendant la systole devrait être associée à une diminution de l'énergie arrivant au même point pendant la diastole. Notre étude propose de mesurer ces deux index, ainsi que d'étudier la relation de l'index d'augmentation diastolique (dAIX) avec la vitesse de propagation de l'onde de pouls (PWV) et avec le rythme cardiaque (HR), ce dernier étant connu pour influencer l'index d'augmentation systolique (sAIX) . L'influence de la position couchée et assise est aussi étudiée. Les mesures de la PWV et des sAIX et dAIX est réalisée chez 48 hommes et 45 femmes âgées de 18 à 70 ans, classés en 3 groupes d'âges. Les résultats montrent qu'en fonction de l'âge, le genre et la position du corps, il y a une relation inverse entre sAIX et dAIX. Lorsque PWV et HR sont ajoutés comme covariables à un modèle de prédiction comprenant l'âge, le genre et la position du corps comme facteurs principaux, sAIX est directement lié à PWV (p<0.0001) et inversement lié à HR (p<0.0001). Avec la même analyse, dAIX est inversement lié à PWV (p<0.0001) et indépendant du rythme cardiaque (p=0.52). En conclusion, l'index d'augmentation diastolique est lié à la rigidité vasculaire au même degré que l'index d'augmentation systolique, alors qu'il est affranchi de l'effet confondant du rythme cardiaque. La quantification de l'augmentation de la pression aortique diastolique due aux ondes réfléchies pourrait être une partie utile de l'analyse de l'onde de pouls.

Growth decrease in Alpine whitefish: investigating the relative contribution of fishing induced selection and environmental change and its implication for conservation measures

La pression exercée par les activités humaines menace pratiquement tous les écosystèmes aquatiques du globe. Ainsi, sous l'effet de divers facteurs tels que la pollution, le réchauffement climatique ou encore la pêche industrielle, de nombreuses populations de poissons ont vu leurs effectifs chuter et divers changements morphologiques ont été observés. Dans cette étude, nous nous sommes intéressés à une menace particulière: la sélection induite par la pêche sur la croissance des poissons. En effet, la génétique des populations prédit que la soustraction régulière des individus les plus gros peut entraîner des modifications rapides de certains traits physiques comme la croissance individuelle. Cela a par ailleurs été observé dans de nombreuses populations marines ou lacustres, dont les populations de féras, bondelles et autres corégones des lacs suisses. Toutefois, malgré un nombre croissant d'études décrivant ce phénomène, peu de plans de gestion en tiennent compte, car l'importance des effets génétiques liés à la pêche est le plus souvent négligée par rapport à l'impact des changements environnementaux. Le but premier de cette étude a donc été de quantifier l'importance des facteurs génétiques et environnementaux. Dans le premier chapitre, nous avons étudié la population de palée du lac de Joux (Coregonus palaea). Nous avons déterminé les différentiels de sélection dus à la pêche, c'est-à-dire l'intensité de la sélection sur le taux de croissance, ainsi que les changements nets de croissance au cours du temps. Nous avons observé une baisse marquée de croissance et un différentiel de sélection important indiquant qu'au moins 30% de la diminution de croissance observée était due à la pression de sélection induite par la pêche. Dans le deuxième chapitre, nous avons effectué les mêmes analyses sur deux espèces proches du lac de Brienz (C. albellus et C. fatioi) et avons observé des effets similaires dont l'intensité était spécifique à chaque espèce. Dans le troisième chapitre, nous avons analysé deux autres espèces : C. palaea et C. confusus du lac de Bienne, et avons constaté que le lien entre la pression de sélection et la diminution de croissance était influencé par des facteurs environnementaux. Finalement, dans le dernier chapitre, nous avons étudié les effets potentiels de différentes modifications de la taille des mailles des filets utilisés pour la pêche à l'aide de modèles mathématiques. Nous concluons que la pêche a un effet génétique non négligeable (et donc peu réversible) sur la croissance individuelle dans les populations observée, que cet effet est lié à la compétition pour la nourriture et à la qualité de l'environnement, et que certaines modifications simples de la taille des mailles des filets de pêche pourraient nettement diminuer l'effet de sélection et ainsi ralentir, voir même renverser la diminution de croissance observée.

Council Bluffs Interstate System Improvements Project Pottawatomie County, Iowa and Douglas County, Nebraska Project Number: IM-029-3(62)54-13-78, November 2004

The Iowa Department of Transportation (Iowa DOT), Nebraska Department of Roads (NDOR), and the Federal Highway Administration (FHWA) are proposing to improve the interstate system around Council Bluffs with improvements extending across the Missouri River on I-80 to east of the I-480 interchange in Omaha, Nebraska, see Figure 1-1. The study considers long-term, broad-based transportation improvements along I-80, I-29, and I-480, including approximately 18 mainline miles of interstate and 14 interchanges (3 system1, 11 service), that would add capacity and correct functional issues along the mainline and interchanges and upgrade the I-80 Missouri River Crossing. These improvements, once implemented, would bring the segments of I-80 and I-29 up to current engineering standards and modernize the roadway to accommodate future traffic needs. In 2001, Iowa DOT and FHWA initiated the Council Bluffs Interstate System (CBIS) Improvements Project. The agencies concluded that the environmental study process would be conducted in two stages; that is, a tiered approach would be applied. The project is being conducted pursuant to the National Environmental Policy Act (NEPA) regulations issued by the Council on Environmental Quality (CEQ), 40 Code of Federal Regulations (CFR) Part 1502.20, and FHWA 23 CFR Part 771.111, that permit tiering for large, complex NEPA studies. Tier 1 is an examination of the overall interstate system improvement needs, including a clear explanation of the area’s transportation needs, a study of alternatives to satisfy them, and broad consideration of potential environmental and social impacts. The Tier 1 evaluation is at a sufficient level of engineering and environmental detail to assist decision makers in selecting a preferred transportation strategy. Tier 1 includes preparation of a draft and final Environmental Impact Statement (EIS) that would disclose the potential environmental and social effects (evaluated at a planning level that considers a variety of conceptual designs) of the proposed improvements. The final EIS will conclude with a Record of Decision (ROD) that states the preferred plan for improvements to be implemented. Essentially, the Tier 1 document will establish the planning framework for the needed improvements. Because the scope of the overall system improvements is large, the interstate improvements would be implemented as a series of individual projects that fit into the overall planning framework. The Tier 1 Area of Potential Impact, which is discussed in detail in Section 4 is an alternative that considers a combination of the most reasonable concepts that have been developed, buffered by approximately 100 or more feet to ensure that any Tier 2 design modifications would remain inside the outer boundary.

Metabolic role of aquaglyceroporin 9 in astrocytes

Aim: Aquaglyceroporin-9 (AQP9) is a member of the Aquaporin channel family involved in water flux through plasma membranes and exhibits the distinctive feature of also being permeable to glycerol and monocarboxylates. AQP9 is detected in astrocytes and catecholaminergic neurons.1 However, the presence of AQP9 in the brain is now debated after a recent publication claiming that AQP9 is not expressed in the brain.2 Based on our results,3 we have evidence of the presence of AQP9 in the brain and we further hypothesize that AQP9 plays a functional role in brain energy metabolism. Methods: The presence of AQP9 in brain of OF1 mice was studied by RT-PCR and immunohistochemistry. To address the role of AQP9 in brain, we used commercial siRNA against AQP9 to knockdown its expression in 2 cultures of astrocytes from two distinct sources (from differentiated stem cells4 and primary astrocyte cultures). After assessment of the decrease of AQP9, glycerol uptake was measured using [H3]-glycerol. Then, modifications of the astrocytic energy metabolism was evaluated by measurement of glucose consumption, lactate release5 and evaluation of the mitochondrial activity by MTT staining. Results: AQP9 is expressed in astrocytes of OF1 mouse brain (mRNA and protein levels). We also showed that AQP9 mRNA and protein are present in cultured astrocytes. Four days after AQP9 siRNA application, the level of expression is significantly decreased by 76% compared to control. Astrocytes with AQP9 knockdown exhibit a 23% decrease of glycerol uptake, showing that AQP9 is a glycerol channel in cultured astrocytes. In parallel, astrocytes with AQP9 knockdown have a 155% increase of their glucose consumption without modifications of lactate release. Moreover, considering the observed glucose consumption increase and the absence of proliferation induction, the significant MTT activity increase (113%) suggests an increase of oxidative metabolism in astrocytes with AQP9 knockdown. Discussion: The involvement of AQP9 in astrocyte energy metabolism adds a new function for this channel in the brain. The determination of the role of AQP9 in astrocytes provides a new perspective on the controversial expression of AQP9 in brain. We also suggest that AQP9 may have a complementary role to monocarboxylate transporters in the regulation of brain energy metabolism.

Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.

Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating the inflammatory response by mediating leukocyte tethering and rolling on adherent leukocytes. In this study, we have examined the effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding. The functional importance of these modifications was determined by analyzing soluble L-selectin binding and leukocyte rolling on CHO cells expressing various glycoforms of PSGL-1 or mutant PSGL-1 targeted at N-terminal Thr or Tyr residues. Simultaneous expression of core-2 beta1,6-N-acetylglucosaminyltransferase and fucosyltransferase VII was required for optimal L-selectin binding to PSGL-1. Substitution of Thr-57 by Ala but not of Thr-44, strongly decreased L-selectin binding and leukocyte rolling on PSGL-1. Substitution of Tyr by Phe revealed that PSGL-1 Tyr-51 plays a predominant role in mediating L-selectin binding and leukocyte rolling whereas Tyr-48 has a minor role, an observation that contrasts with the pattern seen for the interactions between PSGL-1 and P-selectin where Tyr-48 plays a key role. Molecular modeling analysis of L-selectin and P-selectin interactions with PSGL-1 further supported these observations. Additional experiments showed that core-2 O-glycans attached to Thr-57 were also of critical importance in regulating the velocity and stability of leukocyte rolling. These observations pinpoint the structural characteristics of PSGL-1 that are required for optimal interactions with L-selectin and may be responsible for the specific kinetic and mechanical bond properties of the L-selectin-PSGL-1 adhesion receptor-counterreceptor pair.

Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila

Background: The trithorax group (trxG) and Polycomb group (PcG) proteins are responsible for the maintenance of stable transcriptional patterns of many developmental regulators. They bind to specific regions of DNA and direct the post-translational modifications of histones, playing a role in the dynamics of chromatin structure.Results: We have performed genome-wide expression studies of trx and ash2 mutants in Drosophila melanogaster. Using computational analysis of our microarray data, we have identified 25 clusters of genes potentially regulated by TRX. Most of these clusters consist of genes that encode structural proteins involved in cuticle formation. This organization appears to be a distinctive feature of the regulatory networks of TRX and other chromatin regulators, since we have observed the same arrangement in clusters after experiments performed with ASH2, as well as in experiments performed by others with NURF, dMyc, and ASH1. We have also found many of these clusters to be significantly conserved in D. simulans, D. yakuba, D. pseudoobscura and partially in Anopheles gambiae.Conclusion: The analysis of genes governed by chromatin regulators has led to the identification of clusters of functionally related genes conserved in other insect species, suggesting this chromosomal organization is biologically important. Moreover, our results indicate that TRX and other chromatin regulators may act globally on chromatin domains that contain transcriptionally co-regulated genes.

Biomarker analysis of stored blood products: emphasis on pre-analytical issues.

Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking.

Proteomic analysis of Intercept-treated platelets.

In the past decades, transfusion medicine has been driven by the quest for increased safety against transfusion-transmitted infections, mainly by better donor selection and by the development of improved serological and nucleic-acid-based screening assays. Recently, pathogen reduction technologies became available and started to be implemented in several countries, with the primary goal to fight against bacterial contamination of blood products, a rare but dramatic event against which there was no definitive measure. Though pathogen reduction technologies represent a quantum leap in transfusion safety, the biomedical efficacy of platelet concentrates (PCs) treated with various pathogen reduction techniques has been recently questioned by clinical studies. Here, a gel-based proteomic analysis of PCs (n=5), Intercept-treated or untreated, from pooled buffy-coat (10 donors per PC) at Days 1, 2 and 8, shows that the Intercept process that is the most widespread pathogen reduction technique to date, has relatively low impact on the proteome of treated platelets: the process induces modifications of DJ-1 protein, glutaredoxin 5, and G(i)alpha 2 protein. As for the impact of storage, chloride intracellular channel protein 4 (CLIC4) and actin increased independently of Intercept treatment during storage. Whereas alteration of the DJ-1 protein and glutaredoxin 5 points out an oxidative stress-associated lesion, modification of G(i)alpha2 directly connects a possible Intercept-associated lesion to haemostatic properties of Intercept-treated platelets. This article is part of a Special Issue entitled: Integrated omics.