Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes

Background: CCHCR1 (Coiled Coil alpha-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centiosomal piotein, as well as a component of cytoplasmic piocessmg bodies (P-bodies) that regulate mRNA turnovel. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings, it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants. Results: The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though seveial similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies. Conclusions: CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and division. The piesent findings may explain the previous inconsistent obseivations about the functions of CCHCR1.Peer reviewe

The Psoriasis Risk Allele HLA-C*06 : 02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis

Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Immunochip single-nucleotide polymorphism (SNP) array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. More than 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (odds ratio [OR], 3.7 to 4.7; P = 4.9 x 10(-6) to 5.7 x 10(-6)). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (P = 4.8 x 10(-4); OR, 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*57:01, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis (P = 3.2 x 10(-4); OR, 6.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.Peer reviewe

Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis

Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.Peer reviewe

CCHCR1 Is Up-Regulated in Skin Cancer and Associated with EGFR Expression

Peer reviewe

Centrosomal Localization of the Psoriasis Candidate Gene Product, CCHCR1, Supports a Role in Cytoskeletal Organization

Peer reviewe

NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis

Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional, and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5'-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls, and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6, and IFI16 are upregulated in psoriatic epidermis, and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.Peer reviewe

Microbe-host interplay in atopic dermatitis and psoriasis

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.Peer reviewe

Käännä luovuudelle toinenkin poski : hiusalan ammattilaisten koulutusasenteisiin vaikuttaminen

Kouluttautuminen ja asiantuntijana kehittyminen ovat asioita, joita yhteiskunnassamme arvostetaan ja tavoitellaan. Niiden tavoitteluun liittyy vahvasti sosiaalista painetta, joka kumpuaa henkilön sisäisestä kehittymisen halusta sekä yhteiskuntamme luomasta suorituspaineesta. Opinnäytetyön lähtökohtaisena tavoitteena oli kehittää hiusalan kouluttautumista lisäämällä kampaajien koulutusaktiivisuutta sekä sitouttamalla heitä maahantuontiyritykseen. Keinoja tavoitteen täyttymiseksi etsittiin ja kehitettiin luovan ongelmanratkaisun avulla. Uuden kehittämistä ja luovuutta ihannoidaan ja niitä varten kehitetään monenlaisia työkaluja. Olemme kuitenkin ihmisinä erilaisia, joten valmiiden luovuustyökalujen käyttäminen ei tuo esiin henkilön aitoa luovuutta. Oman luovuuden etsiminen ja siihen luottaminen ovat suuressa roolissa tässä kehittämisprosessissa. Työ on monikerroksinen ja se kertoo tekijöiden haastavasta luovuusmatkasta, asiantuntijuuden kehittymisestä sekä kauneudenhoitoalan maahantuontiyrityksen tarjoaman kouluttautumisen kehittämisestä. Työn toiminnallisessa osuudessa haettiin teemahaastattelun avulla hiljaista tietoa kampaajien kouluttautumiskäyttäytymiseen vaikuttavista tekijöistä. Hiljaista tietoa tutkimalla asenne nousi suurimmaksi vaikuttajaksi koulutusten antoisuuden kokemisessa ja koulutuksiin osallistumispäätöksen tekemisessä. Syventymällä asenteiden vaikutuksiin löytyi henkilön ulkopuolelta tuleva tarve kouluttautua: yhteiskunnan luoma koulutuspaine. Näiden kouluttautumiseen vaikuttavien tekijöiden löydyttyä alkuperäinen idea eräänlaisesta koulutuspassista kehittyi uudeksi ideaksi. Syntyi uudenlainen asenteisiin vaikuttava kouluttautumisfoorumi internetissä. Foorumi toteutettiin Facebookissa ja se suunniteltiin tukemaan positiivista asennemuutosta kouluttautumista kohtaan.Education and development as an expert in one’s field are appreciated and pursued in oursociety. Reaching for these goals is strongly associated with social pressure that evolves from one‘s inner urge for development and from the pressure to perform set by our society. The original goal of this thesis was to develop education in the hair industry by increasing the hairdressers‘ urge for further education and by engaging them in an import company. The ways of achieving these goals were searched and developed by creative problem solving. Developing something innovation and creativity are idealized, and for those purposes many tools are being developed. However, as people, we are all different, so the existing tools for creativity do not actually bring out one‘s own creativity. Finding one‘s own creativity and trusting it play important roles in this development process. This thesis offers multilayered insight into the authors’ challenging journey in creativity, their development as experts and the development of education offered by an import company in the beauty care business. The functional part of this thesis was to gather the so called silent information by a theme interview about factors that affect the hairdressers‘ educational behavior. By studying that silent information, the authors discovered that the attitude of the hairdressers was the biggest influence in how beneficial they thought that their further education was and also when making the decision to participate in further education. When the authors studied the effects of attitudes in greater depth, they found a need of further education coming from outside the individual: the pressure for further education set by the society. After discovering the factors that influence one‘s further education, the original idea of an education pass developed as a whole new idea. A new internet educational forum which aims at influencing one‘s attitudes was born. The forum was executed on Facebook and it was designed for supporting the positive attitude adjustment towards further education

Koodausta koululaisten kanssa: koodikoulun suunnittelu ja toteutus Sanginsuun alakoululla

Opinnäytetyömme aiheena oli koodikoulun järjestäminen Sanginsuun alakoululla. Sanginsuun koulu sijaitsee Oulussa, ja siellä opiskelee 25 oppilasta. Toimeksiannon opinnäytetyöhön saimme koulun vanhempaintoimikunnalta. Tutkimuksessamme perehdyimme ensin pedagogiikkaan ja ohjelmoinnin käsitteisiin. Lisäksi perehdyttiin Scratch -ohjelmointiympäristöön, joka valittiin koodikoulun toteutusvälineeksi. Toteutuksessa painotimme livekoodausta ja vertaisoppimista, kuten parikoodausta, ja otimme huomioon opetussuunnitelman suositukset ohjelmoinnista. Tavoitteenamme oli herättää lasten mielenkiinto ohjelmointiin ja tietotekniikkaan ohjelmoinnin opetuksessa toimiviksi havaittuja metodeja sekä pelillistä ja leikillistä oppimista hyödyntäen. Opinnäytetyömme pääpainopiste oli koodikoulun suunnittelu, toteutus ja palautteen kerääminen. Ohjelmoinnin opetuksessa on olennaista mukauttaa opetus oppilaiden tarpeisiin ja tarjota käytännön työkaluja ja resursseja. Tulevaisuudessa opetuksen tulisi korostaa yhteistoiminnallista oppimista, käytännön projektien merkitystä ja teknologian hyödyntämistä. Lapsilta saamamme palautteen perusteella koodikoulun tavoitteessa onnistuttiin, sillä oppilailta keräämämme palaute oli yksimielisen positiivista. Useampi lapsi myös toivoi vapaassa palautteessa ohjelmoinnin opetusta jatkossakin