The Making and Reflecting of Gender Identities in the Czech Gaming Comunities of Selected MMORPG Games

V práci budou analyzovány způsoby a formy utváření i recepce a přebírání genderových identit v předem definovaných MMORPG herních světech v kontextu české herní komunity. Zkoumáni budou podrobeny zejména herní dispozitivy jednotlivých postav a herních možností s cílem definovat podmíněnost daných elementů herního světa kulturou a autorským vstupem tvůrčích týmů. Dále budou analyzovány konkrétní formy utváření genderových identit v herních světech v samotných hrách, ale i imerze genderové identity postav do reálného světa hráčů. Za tímto účelem bude provedena detailní analýza streamovacích platforem, herních fór a video kanálů. Cílem je stanovit mírů přebírání, ale i subverze genderových normativů v prostředí herní komunity a vzájemnou míru vlivu prolínání herního a mimo-herního světa v kontextu genderové problematiky.The work will analyze ways and forms of shaping as well as reception and gender identity takeover in pre-defined MMORPG gaming worlds in the context of the Czech gaming community. In particular, the game layouts of individual characters and game possibilities will be examined in order to define the conditionality of given elements of the game world by culture and the authorinput of creative teams. Furthermore, the specific forms of shaping gender identities in the gaming worlds in the games themselves will be analysed, as well as the immerization of gender identity of the characters into the real world of the players. To this end, a detailed analysis of streaming platforms, gaming forums and video channels will be carried out. The aim is to establish the rates of takeover, but also the subversion of gender normatives in the environment of the gaming community and the degree of interplay between the passing of the gaming and non-gaming worlds in the context of gender issues.Fakulta filozofickáPředstavení diplomové práce: téma, hypotéza, cíl, metody. Seznámení s posudkem vedoucího DP. Seznámení s posudkem oponentky DP. Reakce uchazečky.  Závěrečná rozprava.Dokončená práce s úspěšnou obhajobo

Metoda UV-metrického a pH-metrického stanovení disociačních konstant ionizovatelných léčiv: Valsartan

Valsartan is used for treating high blood pressure, congestive heart failure and to increase the chances of living longer after a heart attack and to reduce the mortality rate for people with left ventricular dysfunction following a heart attack. Regression analysis of the pH-spectra with REACTLAB and of the pH-titration curve with ESAB determined two close consecutive dissociation constants. MARVIN and ACD/Percepta predicted two protonation sites. In water a soluble anion L2- forms two sparingly soluble species LH-, LH2. Although adjusted pH less affected the spectral changes in the chromophore, pK(a1)(T) = 3.70 +/- 0.12, pK(a2)(T) = 4.82 +/- 0.08 at 25 degrees C and pK(a1)(T) = 3.44 +/- 0.08, pK(a2)(T) = 4.67 +/- 0.02 at 37 degrees C in an aqueous phosphate buffer were determined. By regression analysis of potentiometric pH-titration curves and pK(a1)(T)= 3.51 +/- 0.01, pK(a2)(T) = 4.63 +/- 0.01, at 25 degrees C and pKT(a1) = 3.44 +/- 0.03, pK(a2)(T) = 4.51 +/- 0.03 at 37 degrees C in an aqueous medium were estimated. Positive enthalpy values Delta H-0(pK(a1)) = 10.33 kJ.mol(-1), Delta H-0(pK(a2)) = 17.70 kJ.mol(-1) showed that the dissociation process was endothermic. The standard state Gibbs energy changes are Delta G(0)(pK(a1)) = 20.03 kJ.mol(-1), Delta G(0)(pK(a2)) = 26.43 kJ.mol(-1) at 25 degrees C and the Delta S-0 at 25 degrees C and 37 degrees C are (Delta S-0(pK(a1)) = - 32.56 J.K-1.mol(-1), Delta S-0(pK(a2)) = - 29.26 J.K-1.mol(-1) at 25 degrees C and Delta S-0(pK(a1)) = - 30.01 J.K-1.mol(-1), Delta S-0(pK(a2)) = - 25.92 J.K-1.mol(-1) at 37 degrees C. [GRAPHICS] .Valsartan se používá k léčbě vysokého krevního tlaku, srdečního selhání a ke zvýšení šance na život déle po infarktu a snížení úmrtnosti lidí s dysfunkcí levé komory po infarktu. Regresní analýzou bylo stanoveno pH spektrum s REACTLAB a křivka titrace pH s ESAB pak dvě úzké po sobě jdoucí disociační konstanty. MARVIN a ACD / Percepta předpovídaly dvě protonační místa. Ve vodě rozpustný anion L2− tvoří dva řídce rozpustné druhy LH-, LH2. Nastavená hodnota pH méně ovlivnila spektrální změny v chromoforu, pKTal = 3,70 ± 0,12, pKTa2 = 4,82 ± 0,08 při 25 ° C a pKTal = 3,44 ± 0,08, pKTa2 = 4,67 ± 0,02 při 37 ° C ve vodném roztoku fosfátového pufru. Regresní analýzou potenciometrické křivky byly odhadnuty z pH-titrace pKTa1 = 3,51 ± 0,01, pKTa2 = 4,63 ± 0,01 při 25 ° C a pKTal = 3,44 ± 0,03, pKTa2 = 4,51 ± 0,03 při 37 ° C ve vodném médiu. Pozitivní hodnoty entalpie ΔH0 (pKa1) = 10,33 kJ · mol − 1, ΔH0 (pKa2) = 17,70 kJ · mol −1 ukázaly, že disociační proces byl endotermický. Standardní energetické změny Gibbs jsou ΔG0 (pKa1) = 20,03 kJ · mol − 1, ΔG0 (pKa2) = 26,43 kJ · mol − 1 při 25 ° C a ΔS0 při 25 ° C a 37 ° C jsou (ΔS0 (pKa1) = - 32,56 J · K − 1 · mol − 1, ΔS0 (pKa2) = - 29,26 J · K − 1 · mol − 1 při 25 ° C a ΔS0 (pKa1) = - 30,01 J · K-1 · mol-1, ΔS0 (pKa2) = - 25,92 J · K-1 · mol-1 při 37 ° C

TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial–Mesenchymal Transition and Invasiveness

Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli (Apc) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells. We found that Trop2 is produced early after Apc inactivation and its expression is associated with the transcription of genes involved in epithelial–mesenchymal transition, the regulation of migration, invasiveness, and extracellular matrix remodeling. A functionally similar group of genes was also enriched in TROP2-positive cells from human CRC samples. To decipher the driving mechanism of TROP2 expression, we analyzed its promoter. In human cells, this promoter was activated by β-catenin and additionally by the Yes1-associated transcriptional regulator (YAP). The regulation of TROP2 expression by active YAP was verified by YAP knockdown in CRC cells. Our results suggest a possible link between aberrantly activated Wnt/β-catenin signaling, YAP, and TROP2 expression

Comparison of currently used gene panels for tTMB calculation [30, 31] with our panel (LMB_TMB1).

Comparison of currently used gene panels for tTMB calculation [30, 31] with our panel (LMB_TMB1).</p

List of referring centres.

Background and aimGene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis.Patients and methodsBoth paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families.ResultsWES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations.ConclusionOur findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.</div

Antibodies.

Background and aimGene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis.Patients and methodsBoth paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families.ResultsWES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations.ConclusionOur findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.</div

Molecular findings, family with JAM1 deficiency.

Background and aimGene defects contribute to the aetiology of intrahepatic cholestasis. We aimed to explore the outcome of whole-exome sequencing (WES) in a cohort of 51 patients with this diagnosis.Patients and methodsBoth paediatric (n = 33) and adult (n = 18) patients with cholestatic liver disease of unknown aetiology were eligible. WES was used for reassessment of 34 patients (23 children) without diagnostic genotypes in ABCB11, ATP8B1, ABCB4 or JAG1 demonstrable by previous Sanger sequencing, and for primary assessment of additional 17 patients (10 children). Nasopharyngeal swab mRNA was analysed to address variant pathogenicity in two families.ResultsWES revealed biallelic variation in 3 ciliopathy genes (PKHD1, TMEM67 and IFT172) in 4 clinically unrelated index subjects (3 children and 1 adult), heterozygosity for a known variant in PPOX in one adult index subject, and homozygosity for an unreported splice-site variation in F11R in one child. Whereas phenotypes of the index patients with mutated PKHD1, TMEM67, and PPOX corresponded with those elsewhere reported, how F11R variation underlies liver disease remains unclear. Two unrelated patients harboured different novel biallelic variants in IFT172, a gene implicated in short-rib thoracic dysplasia 10 and Bardet-Biedl syndrome 20. One patient, a homozygote for IFT172 rs780205001 c.167A>C p.(Lys56Thr) born to first cousins, had liver disease, interpreted on biopsy aged 4y as glycogen storage disease, followed by adult-onset nephronophthisis at 25y. The other, a compound heterozygote for novel frameshift variant IFT172 NM_015662.3 c.2070del p.(Met690Ilefs*11) and 2 syntenic missense variants IFT172 rs776310391 c.157T>A p.(Phe53Ile) and rs746462745 c.164C>G p.(Thr55Ser), had a severe 8mo cholestatic episode in early infancy, with persisting hyperbilirubinemia and fibrosis on imaging studies at 17y. No patient had skeletal malformations.ConclusionOur findings suggest association of IFT172 variants with non-syndromic cholestatic liver disease.</div

Variants detected by initial Sanger sequencing in 60 excluded patients.

Variants detected by initial Sanger sequencing in 60 excluded patients.</p

STROBE statement—checklist of items that should be included in reports of observational studies.

STROBE statement—checklist of items that should be included in reports of observational studies.</p

Nasopharyngeal swab expression of cholestasis and ciliopathy genes.

Nasopharyngeal swab expression of cholestasis and ciliopathy genes.</p