Association of circulating levels of MMP-8 with mortality from respiratory disease in patients with rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA

A Small Genomic Region Containing Several Loci Required for Gastrulation in Drosophila

Genetic screens in Drosophila designed to search for loci involved in gastrulation have identified four regions of the genome that are required zygotically for the formation of the ventral furrow. For three of these, the genes responsible for the mutant phenotypes have been found. We now describe a genetic characterization of the fourth region, which encompasses the cytogenetic interval 24C3-25B, and the mapping of genes involved in gastrulation in this region. We have determined the precise breakpoints of several existing deficiencies and have generated new deficiencies. Our results show that the region contains at least three different loci associated with gastrulation effects. One maternal effect gene involved in ventral furrow formation maps at 24F but could not be identified. For a second maternal effect gene which is required for germ band extension, we identify a candidate gene, CG31660, which encodes a G protein coupled receptor. Finally, one gene acts zygotically in ventral furrow formation and we identify it as Traf4

Chest wall syndrome among primary care patients: a cohort study

BACKGROUND: The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS). METHODS: Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome. RESULTS: Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients. CONCLUSION: CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration

Computational Analysis of the Spatiotemporal Coordination of Polarized PI3K and Rac1 Activities in Micro-Patterned Live Cells

Polarized molecular activities play important roles in guiding the cell toward persistent and directional migration. In this study, the polarized distributions of the activities of phosphatidylinositol 3-kinase (PI3K) and the Rac1 small GTPase were monitored using chimeric fluorescent proteins (FPs) in cells constrained on micro-patterned strips, with one end connecting to a neighboring cell (junction end) and the other end free of cell-cell contact (free end). The recorded spatiotemporal dynamics of the fluorescent intensity from different cells was scaled into a uniform coordinate system and applied to compute the molecular activity landscapes in space and time. The results revealed different polarization patterns of PI3K and Rac1 activity induced by the growth factor stimulation. The maximal intensity of different FPs, and the edge position and velocity at the free end were further quantified to analyze their correlation and decipher the underlying signaling sequence. The results suggest that the initiation of the edge extension occurred before the activation of PI3K, which led to a stable extension of the free end followed by the Rac1 activation. Therefore, the results support a concerted coordination of sequential signaling events and edge dynamics, underscoring the important roles played by PI3K activity at the free end in regulating the stable lamellipodia extension and cell migration. Meanwhile, the quantification methods and accompanying software developed can provide a convenient and powerful computational analysis platform for the study of spatiotemporal molecular distribution and hierarchy in live cells based on fluorescence images

Progress and prospects toward our understanding of the evolution of dosage compensation

In many eukaryotic organisms, gender is determined by a pair of heteromorphic sex chromosomes. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to restore expression levels of X-linked genes relative to autosomes accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation mechanisms. This review focuses on evolutionary aspects of dosage compensation, in light of recent advances in comparative and functional genomics that have substantially increased our understanding of the molecular mechanisms of dosage compensation and how it evolved. We review processes involved in sex chromosome evolution, and discuss the dynamic interaction between Y degeneration and the acquisition of dosage compensation. We compare mechanisms of dosage compensation and the origin of dosage compensation genes between different taxa and comment on sex chromosomes that apparently lack compensation mechanisms. Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes

Restricting Dosage Compensation Complex Binding to the X Chromosomes by H2A.Z/HTZ-1

Dosage compensation ensures similar levels of X-linked gene products in males (XY or XO) and females (XX), despite their different numbers of X chromosomes. In mammals, flies, and worms, dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in one sex resulting in a change in gene expression from the affected X chromosome(s). In mammals and flies, dosage compensation is associated with specific histone posttranslational modifications and replacement with variant histones. Until now, no specific histone modifications or histone variants have been implicated in Caenorhabditis elegans dosage compensation. Taking a candidate approach, we have looked at specific histone modifications and variants on the C. elegans dosage compensated X chromosomes. Using RNAi-based assays, we show that reducing levels of the histone H2A variant, H2A.Z (HTZ-1 in C. elegans), leads to partial disruption of dosage compensation. By immunofluorescence, we have observed that HTZ-1 is under-represented on the dosage compensated X chromosomes, but not on the non-dosage compensated male X chromosome. We find that reduction of HTZ-1 levels by RNA interference (RNAi) and mutation results in only a very modest change in dosage compensation complex protein levels. However, in these animals, the X chromosome–specific localization of the complex is partially disrupted, with some nuclei displaying DCC localization beyond the X chromosome territory. We propose a model in which HTZ-1, directly or indirectly, serves to restrict the dosage compensation complex to the X chromosome by acting as or regulating the activity of an autosomal repellant

Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study

Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that plays important roles in immunity and inflammation. Some studies have suggested that polymorphism in the TGFB1 gene is associated with heart disease in the general population. The purpose of the present study was to determine whether common single-nucleotide polymorphisms (SNP) in the TGFB1 gene are associated with ischaemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and to investigate the influence of smoking on any association

Reaktioaika identiteetin valehtelun paljastajana maahantulon yhteydessä

Tutkimuksen tavoitteena oli selvittää, voidaanko identiteetin valehtelua paljastaa reaktioajan perusteella. Lähtökohtana aiheen valinnalle oli matkustajaliikenteen turvallisuusuhkien li-sääntyminen ja toisaalta rajavalvontamenetelmien automatisoituminen. Nykyään edellytetään yhä enemmän älykkäitä automatisoituja ratkaisuja turvallisuusuhkien paljastamiseksi samalla kun viranomaisten resursseja vähennetään. Rikollisten profilointi ja identiteetin valehtelun paljastaminen suuresta matkustajavirrasta on haasteellista matkustajamäärien kasvaessa. Tutkimuksen viitekehyksessä käsiteltiin ihmisen käyttäytymisen moninaisuutta kuten identiteetin muodostumista, tunteita ja muistia. Toisena keskeisenä aiheena tarkasteltiin valehtelua ja sen paljastamiseen liittyviä menetelmiä ja vaikeuksia. Tutkimuksen keskeisenä osana oli luoda merkityskartta jokaiselle koehenkilölle. Merkityskartalla tarkoitetaan tässä tutkimuksessa henkilön lapsuuden ja nuoruuden aikaisia emotionaalisesti merkitseviä muistoja, jotka voivat liittyä henkilöihin, paikkoihin, tavaroihin ja tapahtumiin. Identiteetin valehtelua ei ole aiemmin tutkittu henkilökohtaisiin emotionaalisiin muistoihin perustuen. Tutkimus toteutettiin kolmessa vaiheessa. Ensimmäinen vaihe oli haastattelukysymysten laa-timinen, haastattelu merkityskartan luomista varten ja merkityskartan luominen. Toinen vaihe käsitti valeidentiteetin luomisen ja koehenkilöiden valmistamisen kokeeseen. Kolmas vaihe sisälsi identiteettikokeen valmistelun ja identiteettikokeen. Tutkimuksen haastatteluvaiheeseen osallistui 30 koehenkilöä, joista 22 oli naisia ja 8 miehiä. Näistä näyttelijäopiskelijoita oli 10 ja muita opiskelijoita 20. Lopullisessa kokeessa koehenkilöitä oli 22, joista 16 oli naisia ja 6 miehiä, sekä näistä näyttelijäopiskelijoita oli 6. Koehenkilöiden keski-ikä oli 24 vuotta 6 kuukautta. Koehenkilöt haastateltiin yksitellen, jonka jälkeen jokaiselle luotiin merkityskartta. Koevaihetta varten luotiin sekä oikean että valeidentiteetin osiot. Oikea identiteetti rakentui jokaisen omasta merkityskartasta ja valeidentiteetti keksittiin ja se oli sama kaikille. Valeidentiteetti lähetettiin koehenkilöille sähköpostilla ja heitä pyydettiin opettelemaan se ulkoa. Reaktioaikaa mittaavassa kokeessa koehenkilöt vastasivat sekä oikeaa että valeidentiteettiä koskeviin kysymyksiin, joita kokeessa oli 26 kappaletta kummassakin identiteettiosiossa. Haastatteluaineisto litteroitiin sanatarkasti ja analysoitiin laadullisesti. Identiteettikokeen vastausten reaktioajat käsiteltiin määrällisesti. Reaktioajoista laskettiin keskiarvot ja reaktioaikoja verrattiin t-testeillä. Tutkimuksen tuloksista selviää, että vastausten reaktioaika kolmeen kysymykseen on tilastollisesti erittäin merkitseviä ja kahteen kysymykseen tilastollisesti merkitseviä. Nämä kysymykset liittyivät perheeseen ja tärkeisiin henkilöihin sekä lapsuuden kokemuksiin. Tutkimus osoittaa, että tilastollisesti merkitseviä eroavaisuuksia voidaan löytää totta puhuvan ja valehtelijan välillä, kun esitetään emotionaalisia kysymyksiä lapsuuteen ja perheeseen liittyen. Siten sensitiivisen aivoalueen emotionaalinen aktivointi voi paljastaa identiteetin valehtelijan nopeampana reaktioaikana. Tutkimustuloksia voidaan hyödyntää, kun kehitetään älykkäitä maahantulon valvontajärjestelmiä. Tutkimusta voidaan laajentaa liittämällä koevaiheeseen aivokuvantaminen, jonka avulla selvitetään, aktivoituvatko aivojen eri alueet esitettäessä oikeaan ja valeidentiteettiin liittyviä emotionaalisesti latautuneita kysymyksiä.The purpose of this study was to investigate whether identity deception can be detected on the basis of response time. Increased security threats in passenger traffic and the automation of border surveillance systems were motivating factors in carrying out this experiment. As the authorities’ operational resources decrease, more and more intelligent automatic solutions are required in order to expose security threats. The profiling of criminals and the detection of identity deception from growing passenger traffic is challenging. The theoretical part of this study focused on matters related to the complexity of human behaviour such as how identity is formed, emotions and memory. Another essential topic was deception, including how it is detected and the difficulties involved in detection. An important part of this study was to develop a Mean Map for each subject. By Mean Map we mean in this study emotional memories associated with persons, places, belongings and happenings during the subject’s childhood and youth. Similar identity deception research into personal emotional memories has not been conducted before. The study was carried out in three phases. The first phase consisted of drafting interview questions, the interview and the creation of the Mean Map. The second phase comprised the creation of a false identity and the subject´s preparation for the experiment. The third phase consisted of the preparation of the identity experiment as well as the experiment itself. Altogether 30 subjects took part in the interview phase of which 22 were women and 8 men. Out of the 30 subjects 10 were acting students. 22 subjects participated in the experiment, 16 of whom were women and 6 men as well as 6 acting students. The mean age was 24 years and 6 months. All subjects were interviewed one by one after which a Mean Map was created. For the experiment phase a true and false identity were formed. The true identity was based on the subject’s Mean Map. The false identity was made up and it was the same for all the subjects. The false identity was sent via email and the subjects were asked to learn it by heart. During the experiment that measured the response time, the subjects answered questions concerning true and false identity. There were 26 questions in both identity roles and the order was chosen randomly. The interviews were written literally and they were analysed qualitatively. The response times of the experiment phase were analysed quantitatively. The mean response time was calculated and they were compared with a T-test. The findings of this study demonstrated significant differences between the true and false period when emotional questions concerning childhood are presented. There were five answers in which response times were of significance. The questions regarding family, important persons and experiences were found to be meaningful. Thus emotional activation of sensitive brain areas can detect identity deception with a faster response time. The results of this study can be utilised when developing intelligent control systems that can be used at the point of entry. The study can be expanded by an experiment using functional Magnetic Resonance Imaging in order to investigate whether different brain areas will be activated when presenting emotional charged questions regarding true and false identity