Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy

Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein-and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age + HRT-related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17 beta-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17 beta-estradiol, fat-, glucose-and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature

Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas similar to 30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.Tweetable abstract Methylation status of a polymorphically imprinted gene, VTRNA2-1/nc886, is stable in human populations (48 cohorts, n > 30,000) and in somatic tissues, except in cerebellum and skeletal muscle. Twin data suggest it may already be established in the oocyte.</p

The Older Finnish Twin Cohort – 45 Years of Follow-up

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes

Kromogeenisten maljojen käyttö virtsaviljelyssä

virtsatieinfektion aiheuttaa tavallisesti potilaan suolistosta peräisin oleva gramnegatiivinen sauvabakteeri ja joskus grampositiivinen kokkibakteeri. Virtsatieinfektioiden tavanomaisin aiheuttaja on E.coli. Virtsaviljelyn avulla saadaan selvillle infektion aiheuttanut bakteeri ja sille antibioottiherkkyydet. Kromogeenisella maljalla tarkoitetaan elatusainetta, joka sisältää väriä muodostavia yhdisteitä eli kromogeeneja. Värinmuodostus perustuu spesifiseen entsyymi-substraatti-reaktioon, jonka seurauksena syntyy värillinen bakteeripesäke. Tutkimuksessamme vertailemme eri valmistajien chromagareita toisiinsa sekä HUSLAB kliinisen mikrobiologian vastuualueen bakteriologian osaston virtsaviljelydiagnostiikkaan. 53 näytettä viljeltiin kahdeksalle eri kromogeeniselle maljalle ja CLED-maljalle. Kasvun määrää ja pesäkemorfologiaa tarkasteltiin maljoilta silmämääräisesti. Maljojen spesifisyyttä tutkittiin vertailemalla maljoilta saatuja tuloksia toisiinsa. Sensitiivisyyttä tutkittiin laimennossarjan avulla. Kromogeenisilta maljoilta saatujen tulosten vastaavuutta vertailtiin HUSLAB bakteriologian osaston virtsaviljelydiagnostiikkaan. Tutkimuksemme perusteella pesäkemorfologiassa ja kasvun määrässä ei ollut havaittavissa suuria eroja kromogeenisten maljojen välillä. Värireaktiot toimivat odotetulla tavalla ja bakteerikasvu oli maljoilla lähes yhtä runsasta. Kromogeenisten maljojen spesifisyydessä ei ollut havaittavissa suuria eroavaisuuksia, sillä maljat löysivät virtsatieinfektioiden aiheuttajat lähes yhtä hyvin. Sensitiivisyyttä tutkittaessa laimennossarjalla chromagareiden välille syntyi pieniä eroja. Pääasiassa kromogeenisilta maljoilta saadut tulokset vastasivat hyvin virtsaviljelydiagnostiikasta saatuja tuloksia. Tutkimuksemme perusteella voidaan todeta, että kromogeenisista maljoista on apua virtsaviljelydiagnostiikassa ja niiden käyttö voisi nopeuttaa vastauksen saamista potilaalle. Chromagareiden käyttöönotto vaatisi kuitenkin hyvää perehdytystä henkilökunnalle HUSLAB bakteriologian osastolla, sekä terveysasemilla ja sairaaloissa, joissa maljan esimmäinen tarkastelu tapahtuu

Gating of proton and water transfer in the respiratory enzyme cytochrome c oxidase

The membrane-bound enzyme cytochrome c oxidase is responsible for cell respiration in aerobic organisms and conserves free energy from O(2) reduction into an electrochemical proton gradient by coupling the redox reaction to proton-pumping across the membrane. O(2) reduction produces water at the bimetallic heme a(3)/Cu(B) active site next to a hydrophobic cavity deep within the membrane. Water molecules in this cavity have been suggested to play an important role in the proton-pumping mechanism. Here, we show by molecular dynamics simulations that the conserved arginine/heme a(3) Δ-propionate ion pair provides a gate, which exhibits reversible thermal opening that is governed by the redox state and the water molecules in the cavity. An important role of this gate in the proton-pumping mechanism is supported by site-directed mutagenesis experiments. Transport of the product water out of the enzyme must be rigidly controlled to prevent water-mediated proton leaks that could compromise the proton-pumping function. Exit of product water is observed through the same arginine/propionate gate, which provides an explanation for the observed extraordinary spatial specificity of water expulsion from the enzyme

Health-related quality of life and pelvic floor dysfunction in advanced-stage ovarian cancer survivors: associations with objective activity behaviors and physiological characteristics

Purpose: Little is known about the relationship between health-related quality of life (HRQoL), pelvic floor dysfunction (PFD), and modifiable lifestyle and physiological factors for ovarian cancer survivors (OCS). The primary aim of the study was to compare post-treatment advanced-stage OCS with age-matched controls on measures of HRQoL and PFD. The secondary aim was to examine associations between HRQoL, PFD, objective activity behaviors, physical function, and body composition in OCS. Methods: Twenty advanced-stage OCS and 20 controls completed questionnaires assessing HRQoL (SF-36) and PFD (Australian Pelvic Floor Questionnaire), and underwent objective assessments of activity behavior (7-day accelerometry), physical function (400-m walk, repeated chair rise, 6-m usual-pace walk, one-repetition maximum chest press, and single-leg extension), and body composition (dual-energy x-ray absorptiometry). Results: Compared to controls, OCS had worse physical HRQoL (− 4.3 median difference, p = 0.013), but equivalent self-reported PFD, indicated by combined bladder, bowel, and pelvic organ prolapse symptoms (0.89 mean difference, p = 0.277). In OCS, physical HRQoL was significantly negatively associated with PFD (r = 0.468, p = 0.043). Decreased physical HRQoL and increased PFD were significantly associated with less moderate-to-vigorous physical activity in ≥ 10-min bouts (ρ = 0.627, p = 0.003; ρ = − 0.457, p = 0.049), more sedentary time (r = − 0.449, p = 0.047; r = 0.479, p = 0.038), and slower 400-m walk time (ρ = − 0.565, p = 0.022; ρ = 0.504, p = 0.028). Conclusions: Post-treatment advanced-stage OCS have decreased physical HRQoL, which is associated with modifiable factors such as worse PFD, less moderate-to-vigorous physical activity, more sedentary time, and decreased objective physical function. This highlights the need for ongoing supportive care and multidisciplinary interventions after first-line ovarian cancer treatment