Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures

OBJECTIVE: The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. METHODS: Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. RESULTS: Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. CONCLUSION: The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker.

Autonomic and cardiovascular effects of acute high altitude exposure after myocardial infarction and in normal volunteers

High sympathetic tone creates a significant risk for ventricular arrhythmias and sudden death, which can especially affect patients after a myocardial infarction (MI) when exercising in a hypoxic environment.

Erhaltung der Umwelt

Die Volksinitiative „Grüne Wirtschaft“ der Grünen Partei Schweiz kam erfolgreich zustande. – Nach unbenutztem Verstreichen der Referendumsfrist zur Revision des CO2-Gesetzes zog das überparteiliche Initiativ-Komitee sein Volksanliegen „für ein gesundes Klima“ zugunsten des in Kraft tretenden Gegenvorschlags zurück. – Zum Erreichen des im Kyoto-Protokoll vorgeschriebenen CO2-Reduktionsziels unterzeichnete der Bundesrat ein Zusatzabkommen mit der Stiftung Klimarappen. – Die im Vorjahr beschlossene Revision des Gewässerschutzgesetzes sowie die entsprechende Verordnung waren ausschlaggebend für die Einreichung zahlreicher Standesinitiativen. – Aufgrund einer Motion wird die Ausgabe von Wegwerf-Plastiksäcken an Ladentheken zukünftig verboten. – Das Parlament beschloss die Ratifikation der Europäischen Landschaftskonvention.

NETWORK TOPOLOGY IN HUMAN PROTEIN INTERACTION DATA PREDICTS FUNCTIONAL ASSOCIATION

High-throughput assays, such as yeast two-hybrid system, have generated a huge amount of protein-protein interaction (PPI) data in the past decade. This tremendously increases the need for developing reliable methods to systematically and automatically suggest protein functions and relationships between them. With the available PPI data, it is now possible to study the functions and relationships in the context of a large-scale network. To data, several network-based schemes have been provided to effectively annotate protein functions on a large scale. However, due to those inherent noises in high-throughput data generation, new methods and algorithms should be developed to increase the reliability of functional annotations. Previous work in a yeast PPI network (Samanta and Liang, 2003) has shown that the local connection topology, particularly for two proteins sharing an unusually large number of neighbors, can predict functional associations between proteins, and hence suggest their functions. One advantage of the work is that their algorithm is not sensitive to noises (false positives) in high-throughput PPI data. In this study, we improved their prediction scheme by developing a new algorithm and new methods which we applied on a human PPI network to make a genome-wide functional inference. We used the new algorithm to measure and reduce the influence of hub proteins on detecting functionally associated proteins. We used the annotations of the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as independent and unbiased benchmarks to evaluate our algorithms and methods within the human PPI network. We showed that, compared with the previous work from Samanta and Liang, our algorithm and methods developed in this study improved the overall quality of functional inferences for human proteins. By applying the algorithms to the human PPI network, we obtained 4,233 significant functional associations among 1,754 proteins. Further comparisons of their KEGG and GO annotations allowed us to assign 466 KEGG pathway annotations to 274 proteins and 123 GO annotations to 114 proteins with estimated false discovery rates of <21% for KEGG and <30% for GO. We clustered 1,729 proteins by their functional associations and made pathway analysis to identify several subclusters that are highly enriched in certain signaling pathways. Particularly, we performed a detailed analysis on a subcluster enriched in the transforming growth factor β signaling pathway (P<10-50) which is important in cell proliferation and tumorigenesis. Analysis of another four subclusters also suggested potential new players in six signaling pathways worthy of further experimental investigations. Our study gives clear insight into the common neighbor-based prediction scheme and provides a reliable method for large-scale functional annotations in this post-genomic era.

CT dose and image quality in the last three scanner generations.

AIM To compare the computed tomography (CT) dose and image quality with the filtered back projection against the iterative reconstruction and CT with a minimal electronic noise detector. METHODS A lung phantom (Chest Phantom N1 by Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation, the Definition Flash and the Definition Edge (all from Siemens, Erlangen, Germany). The scan parameters were identical to the Siemens presetting for THORAX ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100, 50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were reconstructed using classic filtered back projection. Iterative reconstruction (SAFIRE, level 3) was performed for the two other scanners. A Stellar detector was used with the Somatom Definition Edge. The CT doses were represented by the dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast, noise and subjective image quality were recorded by two different radiologists with 10 and 3 years of experience in chest CT radiology. To determine the average dose reduction between two scanners, the integral of the dose difference was calculated from the lowest to the highest noise level. RESULTS When using iterative reconstruction (IR) instead of filtered back projection (FBP), the average dose reduction was 30%, 52% and 80% for bone, soft tissue and air, respectively, for the same image quality (P < 0.0001). The recently introduced Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and 70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose reduction was larger at lower dose levels. With the same radiation dose, an average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by changing from FBP to IR and from IR to Sd, respectively. For the same contrast to noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was produced for IR and Sd, respectively. For the same subjective image quality, the dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd, respectively. CONCLUSION This study showed an average dose reduction between 27% and 70% for the new Stellar detector, which is equivalent to using IR instead of FBP.

Hypertensive nephropathy treatment by heart-protecting musk pill: a study of anti-inflammatory therapy for target organ damage of hypertension.

This study was designed to investigate the protective effect of the heart-protecting musk pill (HMP) on inflammatory injury of kidney from spontaneously hypertensive rat (SHR). Male SHRs aged 4 weeks were divided into SHR model group, HMP low-dosage group (13.5 mg/kg), and HMP high-dosage group (40 mg/kg). Age-matched Wistar-Kyoto rats were used as normal control. All rats were killed at 12 weeks of age. Tail-cuff method and enzyme-linked immunosorbent assay were used to determine rat systolic blood pressure and angiotensin II (Ang II) contents, respectively. Renal inflammatory damage was evaluated by the following parameters: protein expressions of inflammatory cytokines, carbonyl protein contents, nitrite concentration, infiltration of monocytes/macrophages in interstitium and glomeruli, kidney pathological changes, and excretion rate of urinary protein. HMP did not prevent the development of hypertension in SHR. However, this Chinese medicinal compound decreased renal Ang II content. Consistent with the change of renal Ang II, all the parameters of renal inflammatory injury were significantly decreased by HMP. This study indicates that HMP is a potent suppressor of renal inflammatory damage in SHR, which may serve as a basis for the advanced preventive and therapeutic investigation of HMP in hypertensive nephropathy.

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats.

BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC). METHODS: The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. RESULTS: Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% +/- 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% +/- 5.9% after 2.5 mg/kg MPD, and 56.5% +/- 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among these brain areas. CONCLUSION: These results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.

Legal Implications of the Use of Export Taxes in Addressing Carbon Leakage: Competing Border Adjustment Measures

The prevailing uncertainties about the future of the post-Kyoto international legal framework for climate mitigation and adaptation increase the likelihood of unilateral trade interventions that aim to address climate policy concerns, as exemplified by the controversial European Union initiative to include the aviation industry in its emissions trading system. The emerging literature suggests that border carbon adjustment (BCA) measures imposed by importing countries would lead to substantial legal complications in relation to World Trade Organization law and hence to possible trade disputes. Lack of legal clarity on BCAs is exacerbated by potential counter or pre-emptive export restrictions that exporting countries might impose on carbon-intensive products. In this context, this paper investigates the interface between legal and welfare implications of competing unilateral BCA measures. It argues that carbon export taxes will be an inevitable part of the future climate change regime in the absence of a multilateral agreement. It also describes the channels through which competing BCAs may lead to trade conflicts and political complications as a result of their distributional and welfare impacts at the domestic and global levels.

Does ‘better’ discounting lead to ‘worse’ outcomes in long-run decisions? The dilemma of hyperbolic discounting

The shortcomings of conventional discounting, especially in the context of long-run environmental problems, have been extensively discussed in the literature. Recently, hyperbolic discounting, i. e. discounting at declining instead of constant discount rates, has attracted a lot of interest among both scientists and politicians. Although there are compelling arguments for employing hyperbolic discounting, there are also pitfalls, which have to be pointed out. In this paper I show that the problem of time-inconsistency, an inherent characteristics of hyperbolic discounting, leads to a potential clash between economic efficiency and intergenerational equity. As an example, I refer to the weak progress in the controlling of greenhouse gas emissions under the Kyoto protocol. As the problem of time-inconsistency cannot be solved on economic grounds alone, there is a need for an intergenerational moral commitment.

Common target genes of palatal and gingival fibroblasts for EMD: the microarray approach.

BACKGROUND AND OBJECTIVE Connective tissue grafts are frequently applied, together with Emdogain(®) , for root coverage. However, it is unknown whether fibroblasts from the gingiva and from the palate respond similarly to Emdogain. The aim of this study was therefore to evaluate the effect of Emdogain(®) on fibroblasts from palatal and gingival connective tissue using a genome-wide microarray approach. MATERIAL AND METHODS Human palatal and gingival fibroblasts were exposed to Emdogain(®) and RNA was subjected to microarray analysis followed by gene ontology screening with Database for Annotation, Visualization and Integrated Discovery functional annotation clustering, Kyoto Encyclopedia of Genes and Genomes pathway analysis and the Search Tool for the Retrieval of Interacting Genes/Proteins functional protein association network. Microarray results were confirmed by quantitative RT-PCR analysis. RESULTS The transcription levels of 106 genes were up-/down-regulated by at least five-fold in both gingival and palatal fibroblasts upon exposure to Emdogain(®) . Gene ontology screening assigned the respective genes into 118 biological processes, six cellular components, eight molecular functions and five pathways. Among the striking patterns observed were the changing expression of ligands targeting the transforming growth factor-beta and gp130 receptor family as well as the transition of mesenchymal epithelial cells. Moreover, Emdogain(®) caused changes in expression of receptors for chemokines, lipids and hormones, and for transcription factors such as SMAD3, peroxisome proliferator-activated receptor gamma and those of the ETS family. CONCLUSION The present data suggest that Emdogain(®) causes substantial alterations in gene expression, with similar patterns observed in palatal and gingival fibroblasts.

Printed Narrative: The Festival Books for Archduke Ernest of Austria from Brussels and Antwerp 1594

Workshop „The Narrative in Eastern and Western Art“, Graduate School of Letters, Kyoto, 2-5 December 2013 Abstract by Ivo Raband, University of Berne Printed Narrative: The Festival Books for Ernest of Austria from Brussels and Antwerp 1594 During the early modern period the medium of the festival book became increasingly more important as an object of ‘political narration’ throughout Europe. Focusing on Netherlandish examples from the sixteenth and seventeenth centuries, my talk will focus on the festival books printed for the Joyous Entries of Archduke Ernest of Austria (1553–1595). Ernest was appointed Governor General of the Netherlands by King Philipp II in 1593, being the first Habsburg Prince to reside in Brussels since 30 years. In Brussels and Antwerp, the Archduke was greeted with the traditional Blijde Imkomst, Joyous Entry, which dates back to the fourteenth century and was a necessity to actually become the sovereign of Brabant and Antwerp and to uphold the privileges of the cities. Decorated with ephemeral triumphal arches, stages, and tableaux vivants, both cities welcomed Ernest and, at the same time, demonstrated their civic self-assurance and negotiated their statuses. In honor of these events of civic power, the city magistrates commissioned festival books. These books combine a Latin text with a description of the events and the ephemeral structures, including circa 30 engravings and etchings. Being the only visual manifestation of the Joyous Entries, the books became important representational objects. The prints featured in festival books will be my point of departure for discussing the importance of narrative political prints and the concept of the early modern festival book as a ‘political object’. By comparing the prints from Ernest’s entries with others from the period between 1549 and 1635, I will show how the prints became as important as the event itself. Thus, I want to pose the question of whether it would have been possible to substitute a printed version of the event for the actual ceremony.