• MeSH
• Anthelmintics MeSH
• Cestoda drug effects   MeSH
• Levamisole administration & dosage   MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH

• MeSH
• HIV Infections therapy   immunology   MeSH
• Dose-Response Relationship, Immunologic MeSH
• Immune Tolerance MeSH
• Papillomaviridae MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• dermatovenerologie
• alergologie a imunologie

• MeSH
• Insulin blood   MeSH
• Blood Proteins chemistry   MeSH
• Publication type
• Academic Dissertation MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biochemie

F1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, the Prdm9 gene, intersubspecific homeology of Mus musculus musculus and Mus musculus domesticus autosomes, and the X-linked Hstx2 locus. Hstx2 modulates the extent of Prdm9-dependent meiotic arrest and harbors two additional factors responsible for intersubspecific introgression-induced oligospermia (Hstx1) and meiotic recombination rate (Meir1). To facilitate positional cloning and to overcome the recombination suppression within the 4.3 Mb encompassing the Hstx2 locus, we designed Hstx2-CRISPR and SPO11/Cas9 transgenes aimed to induce DNA double-strand breaks specifically within the Hstx2 locus. The resulting recombinant reduced the Hstx2 locus to 2.70 Mb (chromosome X: 66.51-69.21 Mb). The newly defined Hstx2 locus still operates as the major X-linked factor of the F1 hybrid sterility, and controls meiotic chromosome synapsis and meiotic recombination rate. Despite extensive further crosses, the 2.70 Mb Hstx2 interval behaved as a recombination cold spot with reduced PRDM9-mediated H3K4me3 hotspots and absence of DMC1-defined DNA double-strand-break hotspots. To search for structural anomalies as a possible cause of recombination suppression, we used optical mapping and observed high incidence of subspecies-specific structural variants along the X chromosome, with a striking copy number polymorphism of the microRNA Mir465 cluster. This observation together with the absence of a strong sterility phenotype in Fmr1 neighbor (Fmr1nb) null mutants support the role of microRNA as a likely candidate for Hstx2.

• MeSH
• X Chromosome genetics   MeSH
• Histone-Lysine N-Methyltransferase genetics   MeSH
• Homologous Recombination MeSH
• Meiosis MeSH
• MicroRNAs genetics   MeSH
• Genes, Modifier * MeSH
• Infertility, Male genetics   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Polymorphism, Genetic * MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Adjuvants, Immunologic MeSH
• Warts therapy   MeSH
• Immunologic Factors MeSH
• Papillomavirus Infections immunology   MeSH
• Vulvar Diseases epidemiology   MeSH
• Publication type
• Collected Work MeSH

• Conspectus
• Gynekologie. Porodnictví
• NML Fields
• gynekologie a porodnictví
• infekční lékařství

Aktinická keratóza (AK) je dysplastická lézia, ktorá je indukovaná ultrafialovým žiarením, vyvíja sa prevažne u pacientov so svetlou pokožkou. V súčasnosti je považovaná mnohými autormi za skvamocelulárny karcinóm (SCC) in situ s potenciálom progredovať do invazívneho SCC. Incidencia vývoja aktinických keratóz stúpa u kaukazskej rasy s vekom, blízkosťou k rovníku a zamestnaním vonku. V liečbe existuje množstvo ablatívnych i neablatívnych terapeutických modalít. Významnou neablatívnou liečebnou možnosťou sa v posledných rokoch javí imikvimód – agonista „toll- like“ receptorov, ktorý je účinným, bezpečným a pacientom akceptovaným vonkajším liečivom na aktinické keratózy.

Actinic keratosis (AK) is is a dysplastic UV light-induced lesion, develops mostly in fair-skinned patients. Currently considered by many authors as a squamous cell carcinoma (SCC) in situ, and has the potential to progress to invasive SCC. The incidence of actinic keratosis in caucasians increases with age, proximity to the equator and outdoor occupation. In the treatment, nummerous ablative and non ablative therapeutic approaches exist. Imiquimod –agonist of toll-like receptors is an effective, safe and acceptable for patient, is considered to be a significant non ablative external therapeutic approach for AK in the recent years.

• MeSH
• Keratosis, Actinic etiology   drug therapy   MeSH
• Aminoquinolines therapeutic use   MeSH
• Humans MeSH
• Toll-Like Receptors agonists   therapeutic use   MeSH
• Ultraviolet Rays adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.

• MeSH
• Apoptosis MeSH
• Epigenesis, Genetic * MeSH
• Epithelial-Mesenchymal Transition MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Mutation MeSH
• Mice MeSH
• Primitive Streak embryology   MeSH
• Germ Layers embryology   physiology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In the recent genome-wide association study the polymorphisms of annexin A11 (ANXA11) gene were associated with susceptibility to sarcoidosis. Beside the replication of this finding and analysis of local ANXA11 expression in bronchoalveolar lavage cells, we wondered whether 'leading' ANXA11 rs1049550 (R230C) variant might also be related to the clinical manifestation of sarcoidosis. The study included 245 Czech patients with sarcoidosis and 254 healthy control subjects. The frequency of ANXA11(*)T allele was significantly lower in patients with sarcoidosis (35%) compared with controls (42%, P=0.04, odds ratio=0.77). Furthermore, ANXA11(*)T allele was less frequent in patients with the infiltration of lung parenchyma by comparison with those with isolated hilar lymphadenopathy (P=0.01). In line with the previous observation, ANXA11 mRNA expression was not deregulated in sarcoidosis and was independent from rs1049550 variant. In conclusion, ANXA11 rs1049550 single nucleotide polymorphism is the susceptibility marker in sarcoidosis, at least in Caucasians. Its role as a disease modifier should be independently replicated.

• MeSH
• Annexins genetics   metabolism   MeSH
• Biomarkers MeSH
• Genome-Wide Association Study MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Granuloma genetics   MeSH
• Polymorphism, Single Nucleotide MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Diseases genetics   pathology   MeSH
• RNA, Messenger biosynthesis   MeSH
• Lung pathology   MeSH
• Lung Diseases genetics   MeSH
• Sarcoidosis genetics   metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Adjuvants, Immunologic MeSH
• Biomedical Research MeSH
• Polysaccharides MeSH

JAK 2-V617F mutation causes myeloproliferative neoplasms (MPNs) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis. At diagnosis, patients with PV already exhibited iron deficiency, whereas patients with ET had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with an N542-E543del mutation in exon 12 (E12). At baseline, on a control diet, all JAK2-mutant mouse models with a PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2-V617F mutant mice with an ET-like phenotype had normal iron stores comparable with that of wild-type (WT) mice. On a low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with a PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the premegakaryocyte-erythrocyte progenitors, which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment for patients with PV.

• MeSH
• Iron Deficiencies * MeSH
• Thrombocythemia, Essential * genetics   MeSH
• Phenotype MeSH
• Hemoglobins genetics   MeSH
• Janus Kinase 2 genetics   MeSH
• Mutation MeSH
• Myeloproliferative Disorders * drug therapy   genetics   diagnosis   MeSH
• Mice MeSH
• Polycythemia Vera * genetics   MeSH
• Iron MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH