Filifactor alocis - involvement in periodontal biofilms

<p>Abstract</p> <p>Background</p> <p>Bacteria in periodontal pockets develop complex sessile communities that attach to the tooth surface. These highly dynamic microfloral environments challenge both clinicians and researchers alike. The exploration of structural organisation and bacterial interactions within these biofilms is critically important for a thorough understanding of periodontal disease. In recent years, <it>Filifactor alocis</it>, a fastidious, Gram-positive, obligately anaerobic rod was repeatedly identified in periodontal lesions using DNA-based methods. It has been suggested to be a marker for periodontal deterioration. The present study investigated the epidemiology of <it>F. alocis </it>in periodontal pockets and analysed the spatial arrangement and architectural role of the organism in <it>in vivo </it>grown subgingival biofilms.</p> <p>Results</p> <p>A species-specific oligonucleotide probe, FIAL, was designed and evaluated. A total of 490 subgingival plaque samples were submitted to PCR and subsequent dot blot hybridization to compare the prevalence of <it>F. alocis </it>in patients suffering from generalized aggressive periodontitis (GAP), chronic periodontitis (CP), and control subjects resistant to periodontitis. Moreover, a specially designed carrier system was used to collect <it>in vivo </it>grown subgingival biofilms from GAP patients. Subsequent topographic analysis was performed using fluorescence in situ hybridization.</p> <p>While the majority of patients suffering from GAP or CP harboured <it>F. alocis</it>, it was rarely detected in the control group. In the examined carrier-borne biofilms the organism predominantly colonized apical parts of the pocket in close proximity to the soft tissues and was involved in numerous structures that constitute characteristic architectural features of subgingival periodontal biofilms.</p> <p>Conclusions</p> <p><it>F. alocis </it>is likely to make a relevant contribution to the pathogenetic structure of biofilms accounting for periodontal inflammation and can be considered an excellent marker organism for periodontal disease.</p

The P-Loop Domain of Yeast Clp1 Mediates Interactions Between CF IA and CPF Factors in Pre-mRNA 3′ End Formation

Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3′ end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5′ RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3′ end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3′ end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3′ endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3′ end formation

Effekt av en mobilapplikasjon på holdning til og etterlevelse av legemiddelbehandling hos pasienter med ulcerøs kolitt.

Hensikt: Hensikten med denne studien var å undersøke effekten av en mobilapplikasjon på holdning til og etterlevelse av legemiddelbehandling hos pasienter med ulcerøs kolitt (UC) ved Gastromedisinsk poliklinikk og Medisinsk dagpost, Oslo universitetssykehus (OUS), Ullevål. Metode: Pasienter over 18 år med minst ett års varighet av diagnostisert UC, som håndterte legemidler selv og hadde en smarttelefon, ble invitert til å teste mobilapplikasjonen Applev med blant annet påminnelser for legemiddelinntak. Spørreskjemaene BMQ (beliefs about medicines questionnaire) og MARS-5 (medication adherence report scale) ble benyttet for måling av henholdsvis holdninger til og etterlevelse av legemiddelbehandling før og etter bruk av Applev. I tillegg til ble sykdomsmarkører for UC og modifisert Mayo-skår for evaluering av sykdomsaktivitet sammenlignet før og etter implementering av applikasjonen. Resultat: Det ble inkludert 16 pasienter, men tre av disse ble ekskludert i ettertid da de ikke møtte opp til kontroll etter bruk av mobilapplikasjonen. Median alder i studiepopulasjonen var 36 år (spredning 22-64 år). Median antall påminnelser var 58 per pasient i utprøvingsperioden, som varierte fra 28 dager til 40 dager. Antall påminnelser varierte fra to om dagen til en påminnelse annenhver uke avhengig type preparat og behandling. Det ble ikke påvist noen statistisk signifikant forskjell i holdningsvariabelen nødvendighet-bekymring (medianverdi 4 etter vs. 5 før; P=0.7) eller andel pasienter med høy etterlevelse (62 % etter vs. 46 % før; P=0.7) etter bruk av Applev. Det ble heller ikke påvist noen statistisk signifikant forskjell i forandringer av sykdomsmarkører eller modifisert Mayo-skår. Konklusjon: Studien viste ingen signifikant forbedring i holdning til eller etterlevelse av legemiddelbehandling blant pasienter med UC etter bruk av mobilapplikasjonen Applev. Det ble imidlertid observert en høyere andel av pasienter med høy etterlevelse etter bruk av Applev, noe som kan indikere at en positiv effekt på etterlevelse kan oppnås ved bruk av mobilapplikasjoner. Flere og større studier med et lengre tidsperspektiv må gjennomføres på pasienter med kroniske lidelser for å belyse dette nærmere

Henrici Linckens/ D. in alma Noricorum Universitate Pand. Prof. Publ. & Facult. Iurid. h.t. Decani, Discursus Academicus De Matrimonio, Lege Salica Contracto, Germanice Von der Vermählung zur lincken Hand : Occasione Text. II. Feud. XXIX. Ventilationi publicae propositus / Respondente Antonio Christophoro Hübnero, Kittinga-Franco. Mens. April. A. 1676.

HENRICI LINCKENS/ D. IN ALMA NORICORUM UNIVERSITATE PAND. PROF. PUBL. & FACULT. IURID. H.T. DECANI, DISCURSUS ACADEMICUS DE MATRIMONIO, LEGE SALICA CONTRACTO, GERMANICE VON DER VERMÄHLUNG ZUR LINCKEN HAND : OCCASIONE TEXT. II. FEUD. XXIX. VENTILATIONI PUBLICAE PROPOSITUS / RESPONDENTE ANTONIO CHRISTOPHORO HÜBNERO, KITTINGA-FRANCO. MENS. APRIL. A. 1676. Henrici Linckens/ D. in alma Noricorum Universitate Pand. Prof. Publ. & Facult. Iurid. h.t. Decani, Discursus Academicus De Matrimonio, Lege Salica Contracto, Germanice Von der Vermählung zur lincken Hand : Occasione Text. II. Feud. XXIX. Ventilationi publicae propositus / Respondente Antonio Christophoro Hübnero, Kittinga-Franco. Mens. April. A. 1676. (1) Titelblatt (1) Prooemium. (3) Caput I. (7) Cap. II. (25) Cap. III. (46

Comparison of Three Low-Molecular-Weight Fluorescent Probes for Measuring Free Zinc Levels in Cultured Mammary Cells

Free zinc is a critical regulator in signal transduction and affects many cellular processes relevant to cancer, including proliferation and cell death. Acting as a second messenger, altered free intracellular zinc has fundamental effects on regulating enzymes such as phosphatases and caspases. Therefore, the determination of free intracellular zinc levels is essential to assess its influence on the signaling processes involved in cancer development and progression. In this study, we compare three low-molecular-weight fluorescent probes, ZinPyr-1, TSQ, and FluoZin-3, for measuring free zinc in different mammary cell lines (MCF10A, MCF7, T47D, and MDA-MB-231). In summary, ZinPyr-1 is the most suitable probe for free Zn quantification. It responds well to calibration based on minimal fluorescence in the presence of the chelator TPEN (N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine) and maximal fluorescence by saturation with ZnSO4, resulting in the detection of free intracellular zinc in breast cancer subtypes ranging from 0.62 nM to 1.25 nM. It also allows for measuring the zinc fluxes resulting from incubation with extracellular zinc, showing differences in the zinc uptake between the non-malignant MCF10A cell line and the other cell lines. Finally, ZinPyr-1 enables the monitoring of sub-cellular distributions by fluorescence microscopy. Altogether, these properties provide a basis for the further exploration of free zinc in order to realize its full potential as a possible biomarker or even therapeutic target in breast cancer

The prevalence of the metabolic syndrome and associated cardiovascular complications in adult-onset GHD during GH replacement: a KIMS analysis

Background: Adult-onset growth hormone deficiency (AO-GHD) is associated with an increased prevalence of the metabolic syndrome (MetS). Aim: To determine the effect of GH replacement on the prevalence of MetS in AO-GHD and to study the impact of MetS on the incidence of cardiovascular events during GH replacement. Patients and methods: 1449 AO-GHD patients (males 48.9%; mean age 48.9 ± 12.8 year) were retrieved from KIMS (Pfizer International Metabolic Database). The prevalence of MetS (using International Diabetes Federation criteria) and its components were calculated at baseline and after one year of GH replacement. The relative risk to develop cardiovascular events according to the presence of MetS at baseline was assessed in another group of 3282 patients after prolonged GH replacement. Results: The prevalence of MetS was 46.9% at baseline and 48.2% after one year of GH replacement (P = NS). The percentage of patients with abnormal waist circumference decreased significantly (80.3 vs 77.4%; P < 0.001), but impaired glucose metabolism (17.1 vs 23.3%; P < 0.001) increased and HDL cholesterol (48.2 vs 50.9%; P = 0.011) decreased. Switch from MetS to NoMS (18.5%) and from NoMS to MetS (18.8%) occurred. All patients showed a significant and comparable amelioration of quality of life. During seven years of GH replacement patients with MetS had a 66% higher risk (P = 0.0016) to develop a new coronary disease compared to NoMS. Conclusion: MetS prevalence remains unchanged in AO-GHD during one year of GH replacement whereas its components are differentially affected. Besides GH replacement, consequent pharmacotherapy of all risk factors and endorsement of lifestyle intervention appears to be of uttermost importance together with early GHD diagnosis to prevent cardiovascular disease during prolonged treatment