Epigenetic X chromosome inactivation

Inaktivacija X kromosoma je složeni epigenetički proces koji dovodi do utišavanja jednog od dva X kromosoma u somatskim stanicama ženki sisavaca s ciljem kompenzacije doze X vezanih gena među spolovima. Glavnu ulogu u ovom procesu ima Xic regija na X kromosomu. Ona sadrži XIST gen s kojeg se transkribira glavni signal za utišavanje - nekodirajući Xist RNA transkript. Proces utišavanja X-kromosoma se odvija u nekoliko koraka i obuhvaća uzajamnu interakciju nekodirajućih molekula RNA Xist i Tsix, različitih modifikacije histona, metilacije DNA, i drugih mehanizama u regulaciji transkripcije gena. Prilikom inaktivacije X kromosom se pakira u kompaktnu kromatinsku strukturu koja se održava kroz daljnje stanične diobe. Dva oblika inaktivacije X kromosoma su nasumični i utisnuti. Prilikom utisnutog načina inaktivacije X kromosoma za utišavanje je uvijek predodređen X kromosom naslijeđen od oca, dok se prilikom nasumične inaktivacije mehanizmima brojanja i izbora nasumično odabire bilo majčinski ili očinski kromosom za inaktivaciju. Točnije, pomoću blokirajućeg faktora, na jednom od X kromosoma se onemogućava inaktivacija, dok se preostali X kromosom(i) inaktivira(ju) kako bi se postigao omjer jednog aktivnog X kromosoma po diploidnom setu autosoma u stanici. Utisnuta inaktivacija se odvija kod tobolčara te u izvanembrionalnom tkivu placentalnih sisavaca, dok se u stanicama embrija placentalnih sisavaca odvija nasumična inaktivacija.X chromosome inactivation is a complex epigenetic process that leads to silencing of one of two X chromosomes in somatic cells of female mammals in order to compensate dosage of X-related genes between the sexes. Major role in this process belongs to Xic region of X chromosome. It contains the XIST gene from which the main signal that drives silencing is transcribed - noncoding Xist RNA transcript. Implementation of silencing occurs in several steps and involves the mutual interaction of non-coding antisense RNA Xist and Tsix, DNA methylation, histone modifications, and other mechanisms for regulation of transcription. The result is condensation of the X chromosome and formation of compact chromatin structure that is maintained through further cell division. Two forms of X chromosome inactivation are random inactivation and imprinted inactivation. In the imprinted mode the X chromosome inherited from the father is predisposed for silencing, while in the random mode mechanism of counting and choice randomly selects either the maternal or paternal chromosome for inactivation. Specifically, by using a blocking factor on one of the X chromosomes, it prevents its inactivation, while the remaining X chromosome(s) inactivate in order to achieve a ratio of one active X per diploid set of autosomes in cell. Imprinted inactivation occurs in marsupials and extra-embryonic placental mammalian tissues, whereas in cells of placental mammalian embryos random inactivation occurs

Cortico-ponto-cerebellar pathway in rats. An anatomical study of the somatosensory cortical input to the cerebellum

Cortico-ponto-cerebellar pathway is one of the major subcortical pathways linking sensory cortical areas with distant motor regions of the brain. In this thesis I focus on the projections from the primary somatosensory cortex in order to understand the principles in the organisation of this pathway in rats. Primary somatosensory cortex in rats contains aggregates of granule cells in layer IV, named "barrels" by Woolsey and Van der Loos (1970). There are about 32 whiskers and an equal number of large cortical barrels within the posteromedial barrel subfield (PMBSF) in the primary somatosensory cortex. In addition to its cortical representation the peripheral organisation of the whiskers is replicated in other stations within the afferent pathway, the trigeminal nuclei and the thalamus. This organisation is easily identified both anatomically and physiologically. Therefore rat somatosensory system can serve as a model system to study sensory-motor integration. I mapped terminals from small regions of the primary somatosensory cortex of rats (within and surrounding the PMBSF) in the pontine nuclei using the anterograde tracers Phaseolus vulgaris leucoagglutinin, biocytin and biotinilated dextran-amine. The results demonstrate that cells in layer Vb of all the cortical barrels project to the ipsilateral pons. Most barrel columns terminate within the same set of pontine nuclei with slight medio-lateral shifts in their termination zones. The most rostral, smaller barrel columns and the cortical regions representing intervibrissal fur project bilaterally. This dichotomy is not present in corticotectal projections. Both small and large barrel columns as well as the less granular zones of the somatosensory cortex project to the deep layers of the ipsilateral superior colliculus. Retrograde tracing with fluorescent latex beads demonstrated that at least 70% of layer Vb cells in the primary somatosensory cortex in rats send collaterals to the deep layers of the superior colliculus and the pontine nuclei. Pontine nuclei project as mossy fibres onto the cerebellar cortex. These projections are predominantly contralateral but there are also ipsilateral mossy fibre terminals. Some pontine cells in cats are known to send axons that collateralise within the cerebellar white matter and supply the ipsilateral as well as the contralateral cerebellar cortex (Rosina and Provini, 1982). The experiments in the third chapter were designed to analyse whether and to what extent the axons of the pontine cells in rats, which receive somatosensory cortical inputs related to the whiskers, bifurcate. Whisker sensitive patches in lobules VII, IX and Crus I of the cerebellar cortex were injected with differently coloured fluorescent beads. Both sides of pontine nuclei contained large numbers of retrogradely labelled cells, a small percentage of which was double labelled

Epigenetic X chromosome inactivation

Inaktivacija X kromosoma je složeni epigenetički proces koji dovodi do utišavanja jednog od dva X kromosoma u somatskim stanicama ženki sisavaca s ciljem kompenzacije doze X vezanih gena među spolovima. Glavnu ulogu u ovom procesu ima Xic regija na X kromosomu. Ona sadrži XIST gen s kojeg se transkribira glavni signal za utišavanje - nekodirajući Xist RNA transkript. Proces utišavanja X-kromosoma se odvija u nekoliko koraka i obuhvaća uzajamnu interakciju nekodirajućih molekula RNA Xist i Tsix, različitih modifikacije histona, metilacije DNA, i drugih mehanizama u regulaciji transkripcije gena. Prilikom inaktivacije X kromosom se pakira u kompaktnu kromatinsku strukturu koja se održava kroz daljnje stanične diobe. Dva oblika inaktivacije X kromosoma su nasumični i utisnuti. Prilikom utisnutog načina inaktivacije X kromosoma za utišavanje je uvijek predodređen X kromosom naslijeđen od oca, dok se prilikom nasumične inaktivacije mehanizmima brojanja i izbora nasumično odabire bilo majčinski ili očinski kromosom za inaktivaciju. Točnije, pomoću blokirajućeg faktora, na jednom od X kromosoma se onemogućava inaktivacija, dok se preostali X kromosom(i) inaktivira(ju) kako bi se postigao omjer jednog aktivnog X kromosoma po diploidnom setu autosoma u stanici. Utisnuta inaktivacija se odvija kod tobolčara te u izvanembrionalnom tkivu placentalnih sisavaca, dok se u stanicama embrija placentalnih sisavaca odvija nasumična inaktivacija.X chromosome inactivation is a complex epigenetic process that leads to silencing of one of two X chromosomes in somatic cells of female mammals in order to compensate dosage of X-related genes between the sexes. Major role in this process belongs to Xic region of X chromosome. It contains the XIST gene from which the main signal that drives silencing is transcribed - noncoding Xist RNA transcript. Implementation of silencing occurs in several steps and involves the mutual interaction of non-coding antisense RNA Xist and Tsix, DNA methylation, histone modifications, and other mechanisms for regulation of transcription. The result is condensation of the X chromosome and formation of compact chromatin structure that is maintained through further cell division. Two forms of X chromosome inactivation are random inactivation and imprinted inactivation. In the imprinted mode the X chromosome inherited from the father is predisposed for silencing, while in the random mode mechanism of counting and choice randomly selects either the maternal or paternal chromosome for inactivation. Specifically, by using a blocking factor on one of the X chromosomes, it prevents its inactivation, while the remaining X chromosome(s) inactivate in order to achieve a ratio of one active X per diploid set of autosomes in cell. Imprinted inactivation occurs in marsupials and extra-embryonic placental mammalian tissues, whereas in cells of placental mammalian embryos random inactivation occurs

Microbial mats as shelter microhabitat for amphipods in an intermittent karstic spring

Microbial mats represent complex communities where cyanobacteria and diatoms as key organisms provide shelter for diverse assemblages of aquatic invertebrates, like the small stygophilous amphipod Synurella ambulans. Studies addressing such communities in the karst springs have rarely examined springheads, and have ignored intermittent springs. During high flow conditions the stygophilic crustaceans are flushed to the surface of a temporary stream Krčić where microbial mats prevent their drift and enables their successful retreat into underground in the periods of drought. The objective of this study was to characterize the microbial mat community of the Krčić Spring as a shelter for S. ambulans during strong current and high water level. Representative samples for diatom and cyanobacterial species identification and composition, as well as the fresh mat material for potential animal activity and cyanobacterial phylogenetic analysis were collected. The most dominant diatom was Achnanthidium minutissimum, whilst Fragilaria capucina, Meridion circulare, Navicula cryptocephala and Nitzschia palea had abundance greater than 0.5%. Morphological observations of cyanobacteria revealed that Phormidium favosum was the most dominant, with Hydrocoleum muscicola as a subdominant. Cyanobacterial phylogenetic relationship revealed two distinct clusters: (i) "Phormidium cluster", confirming morphological observations in both winter and spring samples, and (ii) "Wilmottia cluster", a first report for Croatia and found exclusively in the winter sample. Laboratory observations revealed a small stygophilic amphipod S. ambulans, hiding and feeding inside the pockets of fresh microbial mat. The intermittent Krčić Spring as a predator-free and competitor-free ecosystem provides a spatiotemporal conformity between microbial mat and stygophilous amphipod

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results

Impact of general practice endorsement on the social gradient in uptake in bowel cancer screening

This is a summary of independent research funded by the National Institute for Health. Research (NIHR)’s Programme Grants for Applied Research Programme (RP-PG-0609–10106

The Position of the Croatian Society of Hypertension on the Observed Increase in Risk of Non-melanoma Skin Cancer Associated with Hydrochlorothiazide Treatment

Upravni odbor Hrvatskoga društva za hipertenziju na svojoj elektroničkoj sjednici održanoj 12. prosinca 2018. raspravljao je o opaženom povećanom riziku za nastanak nemelanomskih karcinoma kože povezanom s liječenjem hidroklorotiazidom i pripremio sljedeće mišljenje. Zaključci 1. Rizik od nemelanomskoga karcinoma kože i usnica veći je u bolesnika liječenih hidroklorotiazidom nego što je u osoba koje nisu liječene ovim lijekom. Rizik se povećava s duljinom trajanja liječenja, tj. s kumulativnom dozom. 2. Mehanizam karcinogenosti hidroklorotiazida temelji se na fotosenzitivnosti. UV zračenje dovodi do disocijacije kloridnoga dijela molekule lijeka, čime se stvara pretpostavka za sintezu slobodnih radikala kisika i posljedično oštećenje molekule DNK. 3. Korist od primjene hidroklorotiazida veća je od rizika. 4. Omjer koristi i rizika napose je veći u starijih i teže bolesnih osoba. 5. Bolesnik mora biti informiran o postojećem riziku. 6. Bolesnik mora biti informiran o postojećoj alternativnoj terapiji koja je na raspolaganju u Hrvatskoj. 7. Svaki liječnik mora u svakoga pojedinog bolesnika procijeniti omjer koristi i rizika te nakon razgovora s bolesnikom odlučiti nastavlja li terapiju hidroklorotiazidom ili se odlučuje za postojeću alternativu. 8. Svim bolesnicima, a napose bolesnicima koji su liječeni hidroklorotiazidom, treba preporučiti uporabu adekvatne fotoprotekcije i redovito provjeravanja pojave ili promjena na koži

Self-Management education for adults with poorly controlled epILEpsy (SMILE (UK)): a randomised controlled trial protocol

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.National Institute for Health Research Health Technology Assessment Programme; reference 09/165/01

ACTION OF IONIZING RADIATION AND PROTECTION AGAINST IONIZING RADIATION

U završnom radu objasnit će se ionizirajuće zračenje, njegovo djelovanje i otkriće, vrste zračenja te širenje zračenja kroz tvar. Opisuje kako izračunati broj atomskih jezgri koje će se s vremenom raspasti, učinke zračenja na ljudsko tijelo i moguće štete od ionizirajućeg zračenja.In the final paper, ionizing radiation, its action and discovery, types of radiation through matter will be explained. It describes how to calculate the number of atomic nuclei that will decay over time, the effects of radiation on the human body and possible harm from ionizing radiation