Prevalence and Clinical Features of Isolated Clinical Hypertension and Dipping Profile in a Large Cohort of Untreated Hypertensive Subjects

Aim: To examine the prevalence and clinical features of isolated clinical hypertension (ICH) and the dipping patterns in a large cohort of untreated hypertensive subjects form the Spanish ABPM registry

VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.

It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT) produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. DESIGN Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. RESULTS We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1alpha, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARgamma1/gamma2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. CONCLUSION Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new fat has acquired in research in relation to adipogenesis and angiogenesis.

FGF21 signalling pathway and metabolic traits - genetic association analysis.

Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol - LDL-C, HDL-cholesterol - HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q<0.5. Of these, only one FGFR2 polymorphism (rs2071616) showed replicated association with LDL-C in both CoLaus (P=0.009) and men from GerMIFS (P=0.017). The direction of allelic effect of rs2071616 upon LDL-C was consistent in all examined populations. These data show that common genetic variations in FGFR2 may be associated with LDL-C in subjects of white European ancestry.

GENCODE: the reference human genome annotation for The ENCODE Project.

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

The Multiscenario Multienvironment BioSecure Multimodal Database (BMDB)

A new multimodal biometric database designed and acquired within the framework of the European BioSecure Network of Excellence is presented. It is comprised of more than 600 individuals acquired simultaneously in three scenarios: 1) over the Internet, 2) in an office environment with desktop PC, and 3) in indoor/outdoor environments with mobile portable hardware. The three scenarios include a common part of audio/video data. Also, signature and fingerprint data have been acquired both with desktop PC and mobile portable hardware. Additionally, hand and iris data were acquired in the second scenario using desktop PC. Acquisition has been conducted by 11 European institutions. Additional features of the BioSecure Multimodal Database (BMDB) are: two acquisitionsessions, several sensors in certain modalities, balanced gender and age distributions, multimodal realistic scenarios with simple and quick tasks per modality, cross-European diversity, availability of demographic data, and compatibility with other multimodal databases. The novel acquisition conditions of the BMDB allow us to perform new challenging research and evaluation of eithermonomodal or multimodal biometric systems, as in the recent BioSecure Multimodal Evaluation campaign. A description of this campaign including baseline results of individual modalities from the new database is also given. The database is expected to beavailable for research purposes through the BioSecure Association during 2008.

No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach.

AIMS/HYPOTHESIS: Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes. METHODS: We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association. RESULTS: The genetic score showed a linear association with uric acid levels, with a difference of 12.2 μmol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p = 0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 μmol/l. CONCLUSIONS/INTERPRETATION: Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.

Independent Living Program, Winter 2006

LENORE'S STORY Lenore Barnes began losing vision in her early eighties due to macular degeneration. In her mid-eighties she quit driving and purchased a CCTV. Her vision continued to decrease, and while the CCTV remained helpful it was of diminishing benefit.

Disegni come documento e disegni come monumento : Giovanni Ciampini, Sebastiano Resta e la fortuna del Medioevo artistico nella Roma di Bellori

La tesi di Dottorato, condotta in accordo di colutela tra l'Università di Roma Tor Vergata e l'UNIL di Losanna, ha affrontato l'analisi di un gruppo di undici disegni custodia presso la National Gallery of Scotland di Edimburgo, copie di alcuni dei più significativi mosaici medioevali delle chiese di Roma, ricostruendone la genesi, quindi le vicende legate alla committenza, e il percorso collezionistico. I disegni scozzesi, oggetto di un importante articolo di Julian Gardner pubblicato sul Burlington Magatine nel 1973, furono commissionati intorno agli anni Settanta del XVII secolo dall'antiquario romano Giovanni Giustino Ciampini (1633-1698) in connessione alla stesura della sua opera di erudizione più avvertita e famosa: i Vetera Mommenta in' quibus praecipue Musiva Opera, sacrarum, profanan,mque, Aedìum structura, ac nonnulli antiqui ritus dissertationibus iconìbusque illustrantur. La composizione dei Vetera Mommenta - un'opera riccamente illustrata che nasce per rispondere alle esigenze della ideologia della Chiesa di Roma in un momento di rinnovata crisi del sistema - impone a Ciampini di porsi da un lato nella prospettiva della più alta tradizione antiquaria cinque e seicentesca, di cui recupera i metodi di lettura e di analisi applicati allo studio delle monete e dei monumenti antichi interpretati quali prove per la ricostruzione storica, e dall'altra, come è emerso dalle mie ricerche, lo pone immediatamente in contatto con gli avamposti del più moderno metodo di indagine storica e filologica applicato alle fonti e ai documenti della storia ecclesiastica, inaugurato dall'ambiente bollandista e inaurino. I monumenti paleocristiani e medioevali assumono in quest'ottica lo status di 'fatti incontestabili', le fonti primarie attraverso le quali Ciampini ricuce le tappe salienti della storia della Chiesa, da Costantino fino al XV secolo. Nel 1700 le copie di Edimburgo arrivano nelle mani del mercante e connoisseur milanese il padre oratoriano Sebastiano Resta (1635-1714), di stanza a Roma presso la Chiesa Nuova della Vallicella dal 1660, che decide di rilegarle tutte insieme in un volume da donare al suo maggiore acquirente e patrono, il vescovo di Arezzo Giovanni Matteo Marchetti. Come spiega Resta in alcune sue lettere, il presente avrebbe dovuto costituire insieme una curiosità ed offrire un confronto: infatti «le copie delli mosaici di Roma che erano di Monsignor Ciampini» - afferma Resta - avrebbero mostrato al Marchetti «le maniere di que' tempi gottici, barbari e divoti de cristiani e [fatto] spiccare i secoli seguenti». Questa indagine infatti ha fatto riemergere aspetti della precoce attenzione di Sebastiano Resta per l'arte dei "secoli bassi", mai debitamente affrontata dagli studi. E' infatti sulla scorta di una profonda conoscenza dei testi della letteratura artistica, e in connessione alla esplosione vivacissima della controversia Malvasia/Baldinucci sul primato del risorgere delle arti in Toscana, che Sebastiano a partire dagli anni Ottanta del Seicento comincia a meditare sul Medioevo artistico con il fine di spiegare l'evoluzione del linguaggio tecnico e formale che ha condotto alla perfezione dell'atte moderna. In questa prospettiva ι disegni del XIV e XV secolo che egli riuscì ad intercettare sul mercato valgono quali testimonianze delle maniere degli artefici più antichi e sono imbastiti nei molteplici album che Resta compone nel rispetto della successione cronologica dei presunti autori, e ordinati in base alle scuole pittoriche di pertinenza. La tesi permette perciò di descrivere nelle loro diverse specificità: da un lato il modo dei conoscitori come Resta, interessati nell'opera al dato stilistico, con immediate e sensibili ricadute sul mercato, e disposti anche con passione a ricercare i documenti relativi all'opera in quanto pressati dall'urgenza di collocarla nella sequenza cronologica dello sviluppo del linguaggio formale e tecnico; dall'altro gli antiquari come Ciampini e come Bianchini, per i quali le opere del passato valgono come prove irrefutabili della ricostruzione storica, e divengono quindi esse stesse, anche nel loro statuto di copia, documento della stona. Sono due approcci che si manifestano nel Seicento, e talvolta in una medesima persona, come mostra il caso anche per questo cruciale di Giovati Pietro Bellori, ma che hanno radici cinquecentesche, di cui i protagonisti di queste vicende sono ben consapevoli: e se dietro Resta c'è palesemente Vasari, dietro Ciampini e soprattutto Bianchini c'è la più alta tradizione antiquaria del XVI secolo, da Antonio Augustin a Fulvio Orsini.

Rules or consequences? The role of ethical mindsets in moral dynamics

Recent research on the dynamics of moral behavior has documented two contrastingphenomena - moral consistency and moral balancing. Moral balancing refers to thephenomenon whereby behaving (un)ethically decreases the likelihood of doing so againat a later time. Moral consistency describes the opposite pattern - engaging in(un)ethical behavior increases the likelihood of doing so later on. Three studies supportthe hypothesis that individuals' ethical mindset (i.e., outcome-based versus rule-based)moderates the impact of an initial (un)ethical act on the likelihood of behaving ethicallyin a subsequent occasion. More specifically, an outcome-based mindset facilitates moralbalancing and a rule-based mindset facilitates moral consistency.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.