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"en": "Abstract Background Carbonic anhydrase related proteins (CARPs) VIII, X and XI functionally differ from the other carbonic anhydrase (CA) enzymes. Structurally, they lack the zinc binding residues, which are important for enzyme activity of classical CAs. The distribution pattern of the CARPs in fetal brain implies their role in brain development. In the adult brain, CARPs are mainly expressed in the neuron bodies but only weaker reactivity has been found in the astrocytes and oligodendrocytes. Altered expression patterns of CARPs VIII and XI have been linked to cancers outside the central nervous system. There are no reports on CARPs in human astrocytomas or oligodendroglial tumors. We wanted to assess the expression of CARPs VIII and XI in these tumors and study their association to different clinicopathological features and tumor-associated CAs II, IX and XII. Methods The tumor material for this study was obtained from surgical patients treated at the Tampere University Hospital in 1983â 2009. CARP VIII staining was analyzed in 391 grade I-IV gliomas and CARP XI in 405 gliomas. Results CARP VIII immunopositivity was observed in 13% of the astrocytomas and in 9% of the oligodendrogliomas. Positive CARP XI immunostaining was observed in 7% of the astrocytic and in 1% of the oligodendroglial tumor specimens. In our study, the most benign tumors, pilocytic astrocytomas, did not express CARPs at all. In WHO grade II-IV astrocytomas, CARPs were associated with molecular events related to more benign behavior, which was the case with CARP VIII in oligodendrogliomas and oligoastrocytomas as well. Conclusions The study observations suggest that the CARPs play a role in tumorigenesis of diffusively infiltrating gliomas. Furthermore, the molecular mechanisms beneath the cancer promoting qualities of CARPs have not yet been discovered. Thus, more studies concerning role of CARPs in oncogenesis are needed."
},
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}
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"en": "Abstract Background Wound healing of retinal pigment epithelium (RPE) is a complex process that may take place in common age-related macular degeneration eye disease. The purpose of this study was to evaluate whether wounding and wound healing has an effect on Ca2+ dynamics in human embryonic stem cell (hESC)-RPEs cultured different periods of time. Methods The 9-day-cultured or 28-day-cultured hESC-RPEs from two different cell lines were wounded and the dynamics of spontaneous and mechanically induced intracellular Ca2+ activity was measured with live-cell Ca2+ imaging either immediately or 7Â days after wounding. The healing time and speed were analyzed with time-lapse bright field microscopy. The Ca2+ activity and healing speed were analysed with image analysis. In addition the extracellular matrix deposition was assessed with confocal microscopy. Results The Ca2+ dynamics in hESC-RPE monolayers differed depending on the culture time: 9-day-cultured cells had higher number of cells with spontaneous Ca2+ activity close to freshly wounded edge compared to control areas, whereas in 28-day-cultured cells there was no difference in wounded and control areas. The 28-day-cultured, wounded and 7-day-healed hESC-RPEs produced wide-spreading intercellular Ca2+ waves upon mechanical stimulation, while in controls propagation was restricted. Most importantly, both wave spreading and spontaneous Ca2+ activity of cells within the healed area, as well as the cell morphology of 28-day-cultured, wounded and thereafter 7-day-healed areas resembled the 9-day-cultured hESC-RPEs. Conclusions This acquired knowledge about Ca2+ dynamics of wounded hESC-RPE monolayers is important for understanding the dynamics of RPE wound healing, and could offer a reliable functionality test for RPE cells. The data presented in here suggests that assessment of Ca2+ dynamics analysed with image analysis could be used as a reliable non-invasive functionality test for RPE cells."
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"en": "Abstract Background Advances in mass spectrometry have accelerated biomarker discovery in many areas of medicine. The purpose of this study was to compare two mass spectrometry (MS) methods, isobaric tags for relative and absolute quantitation (iTRAQ) and sequential window acquisition of all theoretical fragment ion spectra (SWATH), for analytical efficiency in biomarker discovery when there are multiple methodological constraints such as limited sample size and several time points for each patient to be analyzed. Methods A total of 140 tear samples were collected from 28 glaucoma patients at 5 time points in a glaucoma drug switch study. Samples were analyzed with iTRAQ and SWATH methods using NanoLC-MSTOF mass spectrometry. Results We discovered that even though iTRAQ is faster than SWATH with respect to analysis time per sample, it loses in sensitivity, reliability and robustness. While SWATH analysis yielded complete data of 456 proteins in all samples, with iTRAQ we were able to quantify 477 proteins in total but on average only 125 proteins were quantified in a sample. 283 proteins were common in the datasets produced by the two methods. Repeatability of the methods was assessed by calculating percent relative standard deviation (% RSD) between replicate MS analyses: SWATH was more repeatable (56% of proteins"
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"en": "Abstract Background Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes."
},
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{
"id": "be28a2ad-4020-40c5-82f4-cc90fbb15b97",
"url": "http://www.yso.fi/onto/okm-tieteenala/ta1184",
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"pref_label": {
"en": "Genetics, developmental biology, physiology",
"fi": "Genetiikka, kehitysbiologia, fysiologia",
"sv": "Genetik, utvecklingsbiologi, fysiologi"
}
},
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"url": "http://www.yso.fi/onto/okm-tieteenala/ta318",
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"pref_label": {
"en": "Medical biotechnology",
"fi": "Lääketieteen bioteknologia",
"sv": "Medicinsk bioteknologi"
}
}
],
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"issued": "2018-07-17",
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],
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}
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"title": {
"en": "Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6"
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