The Evolution of Satellite III DNA Subfamilies among Primates

We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16–23 million years ago (MYA) and the more recent group 1 sequences emerging ∼4.5 MYA. We also show the relative order of emergence of each group 2 subfamily in the various primate species. Our results show that each SatIII subfamily is an independent evolutionary unit, that the rate of evolution is not uniform between species, and that the evolution within a species is not uniform between chromosomes

Housing Demand in the Polish Peoples’ Republic

Although historians and social scientists devoted considerable attention to issues related to housing in the Polish Peoples’ Republic era, many problems still need further research. The crucial problem of the paper is to find an answer to the question: what did Poles have to do in the period between 1944/45 and 1989 in order to obtain housing? The answer given is the effect of several years of primary source research which encompassed archival material of assorted types and origins

Deep molecular response after 3rd-line dasatinib treatment in patient with chronic myelogenous leukemia in chronic phase

Niepowodzenie terapii imatynibem (IM) u chorych na przewlekłą białaczkę szpikową (CML) w fazie przewlekłej jest wskazaniem do rozpoczęcia terapii 2. linii inhibitorami kinazy tyrozynowej II generacji. Niestety, u części z nich ponownie obserwuje się objawy nietolerancji/nieskuteczności TKI II generacji. W pracy przedstawiono przypadek chorego na CML w fazie przewlekłej z opornością na IM, u którego w trakcie leczenia nilotynibem stwierdzono wystąpienie objawów toksyczności hematologicznej (małopłytkowość 3. stopnia wg CTCAE), a następnie oporności mutacyjnej (H396P KD BCR-ABL1). Na podstawie przewidywanego profilu skuteczności TKI II generacji in vitro zdecydowano o dalszym leczeniu dazatynibem w dawce 100 mg/raz/dobę doustnie. Całkowitą odpowiedź cytogenetyczną uzyskano po 6 miesiącach, a większą odpowiedź molekularną — po 9 miesiącach leczenia. W kolejnych miesiącach obserwowano stałą poprawę jakości odpowiedzi molekularnej. W ocenie przeprowadzonej w czerwcu 2014 roku potwierdzono uzyskanie głębokiej odpowiedzi molekularnej. Co więcej, potwierdzono jej utrzymywanie się w kolejnych ocenach.Imatinib (IM) therapy failure in patients with chronic myelogenous leukemia (CML) in the chronic phase is an indication for second-line treatment with second generation of tyrosine kinase inhibitors (2nd generation of TKI). Unfortunately, the symptoms of therapy intolerance/failure are observed in part of them. We present a case of CML patient in chronic phase with IM-resistance in whom hematologic toxicity was observed during nilotinib treatment (thrombocytopenia grade 3 acc. CTCAE), as well as the symptoms of mutational TKI-resistance (H396P KD BCR-ABL) thereafter. On the basis of 2nd generation of TKI efficacy in vitro profile, a decision about dasatinib therapy in a dose of 100 mg orally daily was undertaken. Complete cytogenetic response was obtained after 6 months, and major molecular response after 9 months of therapy. A follow-up revealed continuous improvement in quality of molecular response. In June 2014 deep molecular response was obtained. Moreover, their persistence during consecutive months was also confirmed

Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas

Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients.Methylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level.The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients.Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling.The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas

Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors

Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p p FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development.</p

Diagnosis of myelodysplastic syndromes in Poland: Polish Adult Leukemia Group (PALG) 2021 recommendations

Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic diseases of the hematopoietic cells manifested by ineffective hematopoiesis and a tendency to transform into acute myeloid leukemia. MDS should be considered in the differential diagnosis of cytopenia, especially in the elderly. This article presents the recommendations of MDS experts of the Polish Adult Leukemia Group (PALG) for the diagnosis of myelodysplastic syndromes. We present current classifications and prognostic indices, as well as diagnostic examinations recommended for MDS: cytological, histopathological, immunophenotypic, cytogenetic and molecular tests. The aim of the study is to implement up-to-date knowledge about myelodysplastic syndromes into routine clinical practice, from the diagnosis of cytopenia to the specific diagnosis and prognosis in MDS patients.  Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic diseases of the hematopoietic cells manifested by ineffective hematopoiesis and a tendency to transform into acute myeloid leukemia. MDS should be considered in the differential diagnosis of cytopenia, especially in the elderly. This article presents the recommendations of MDS experts of the Polish Adult Leukemia Group (PALG) for the diagnosis of myelodysplastic syndromes. We present current classifications and prognostic indices, as well as diagnostic examinations recommended for MDS: cytological, histopathological, immunophenotypic, cytogenetic and molecular tests. The aim of the study is to implement up-to-date knowledge about myelodysplastic syndromes into routine clinical practice, from the diagnosis of cytopenia to the specific diagnosis and prognosis in MDS patients.

The rhythms of Piotr Cieplak’s theater

Wydział Filologii Polskiej i Klasycznej: Katedra Dramatu, Teatru i WidowiskPraca jest próbą podważenia widocznych w rozważaniach krytyków tendencji do etykietowania Piotra Cieplaka jako artysty-Proteusza: czyli artysty nieustannie zmieniającego techniki, formy i konwencje inscenizacyjne, a także czerpiącego z różnych, niespójnych inspiracji i proponującego coraz to inne typy teatru. Przyznając, że teatr Piotra Cieplaka jest rzeczywiście różnorodny, usiłuję pokazać, że to różnorodność nieprzypadkowa, lecz podporządkowana wpisanemu w twórczość Cieplaka światopoglądowi i wynikającej z niego wizji roli i zadań teatru. Innymi słowy jest to różnorodność, którą rządzą rytmy – tematyczne i estetyczne. Główne rytmy tematyczne w teatrze Cieplaka to moim zdaniem nowoczesność i Biblia. Pierwszy objawia się nieustannym przywoływaniem przez reżysera „donosów rzeczywistości”, drugi – pokazywaniem „obrotów rzeczy”, czyli sytuacji i doświadczeń znanych już z Biblii, i nieustannie powracających w różnych konfiguracjach i wariantach. Analizując te dwa rytmy w teatrze Cieplaka usiłuję na tej podstawie zdiagnozować Cieplakową wizję rytmu ludzkiego życia. Jednocześnie pokazuję, że to właśnie ta wizja determinuje „kształty” teatru Cieplaka i uzasadnia ich nieustanną zmienność. W zmienności tej również dostrzegam pewne rytmy, które – jak się okazuje – nie tylko ilustrują wpisany w teatr Cieplaka światopogląd, ale odzwierciedlają też przemiany zachodzące we współczesnym teatrze – zwłaszcza w zakresie rozumienia realizmu. Analizując je, usiłuję zdiagnozować, jak Cieplak definiuje cele i zadania teatru funkcjonującego w „płynnej nowoczesności”. Charakter teatru Cieplaka jest moim zdaniem ściśle powiązany z okolicznościami, w jakich funkcjonuje. Przestawiając rytmy teatru Cieplaka chcę pokazać reżysera jako artystę na wskroś nowoczesnego, ale przyjmującego wobec nowoczesności specyficzną postawę.This doctoral thesis is an attempt to undermine the trend in the critics' tendency for classifying Piotr Cieplak as an artist-Proteus that means the artist who is constantly evolving techniques, forms and conventions of staging, as well as drawing on different, inconsistent inspiration and proposing ever changing types of theater. While acknowledging that the Piotr Cieplak's theater is really diverse, I will also show that this variety is of non-accidental character and is an inscription of Cieplak's worldview and his vision of the role and tasks of the theater. In other words, it is the diversity which is governed by certain rhythms - thematic as well as aesthetic. The main theme rhythms in Cieplak's theater are in my opinion modernity and the Bible. The first one is revealed by constant director's evocations to "denunciations of reality ", the second is presented by showing the human life "fate turn-outs ", that is, situations and experiences already presented in the Bible and continually recurring in various configurations and variants. By analyzing these two rhythms in Cieplak's theater I am trying to define his vision of human life rhythm . Simultaneously I am proving that this vision itself determines the "shapes" of Cieplak's theater and justifies their constant volatility. In this variation I also notice a certain rhythm, which as it turns out not only illustrates Cieplak's theater beliefs, but also reflects the changes taking place in the contemporary theater - especially in the understanding of realism. By analyzing them, I am trying to diagnose how Cieplak defines the objectives and tasks of the theater which is functioning in a "liquid modernity". The nature of Cieplak's theater is in my opinion closely related to the circumstances in which it operates. Changing Cieplak's rhythms of the theater I would like to present him as a thoroughly modern artist having a host-specific attitude towards modernity though