Ocena związku polimorfizmów genów kodujących wybrane cytokiny z występowaniem porodu przedwczesnego w populacji kobiet polskich

Summary Objective: Recent studies suggest that preterm delivery might be conditioned genetically. The main aim of this study was to examine the relationship between spontaneous preterm delivery (PTD) and the carriage of polymorphic genes that code the following cytokines: interleukin-1β [IL1β (+3953C>T)], interleukin-6 promoter [IL6 (-174G>C)], tumour necrosis factor-α promoter [TNFα (-308G>A)] and interleukin-1 receptor antagonist (IL1RN) in the population of Polish women. Methods: A case-control study. 125 Caucasian women were examined, among them 62 cases and 63 controls. Case subjects were defined as those who had a delivery at less than 366 weeks of gestation due to either preterm premature rupture of membranes or preterm labour while control subjects gave birth at term. Detailed demographic, medical and obstetric data based on structured questionnaire and medical record were collected. Maternal venous blood samples were collected after the delivery and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL) techniques for the presence of each of the allelic variants. Logistic regression model was used to compute odds ratio and its 95% confidence intervals. Results: Women that carried IL1RN*2 were found to be at an increased risk of preterm delivery OR=2.75(95%CI:1.02-4.13). No correlation between IL-1β, IL-6 and TNF-α gene polymorphisms and the risk of PTD was found. Coincidence of IL1RN polymorphism (genotype IL1RN*1/ IL1RN*2, IL1RN*1/ IL1RN*3, IL1RN*2/ IL1RN*3) with IL-6 promoter polymorphism (genotype GG, GC) multiplied the risk of preterm delivery OR=3.02(95%CI: 1.00-8.91). Conclusions: Maternal carriage of the IL1RN*2 allele appears to be associated with an elevated risk of preterm delivery in the population of Polish women. Coincidence of IL1RN*2 with at least one copy of IL-6 allele G might increase the risk of preterm delivery even further.Streszczenie Cel pracy: Ostatnie doniesienia wskazują, że wystąpienie porodu przedwczesnego może mieć uwarunkowania genetyczne. Celem pracy była ocena zależności między nosicielstwem polimorficznych alleli następujących genów: interleukiny-1β [IL1β (+3953C>T)], promotora genu interleukiny-6 [IL6 (-174G>C)], promotora genu czynnika martwicy nowotworów-α [TNFα (-308G>A)] oraz antagonisty receptora interleukiny-1 (IL1RN) a ryzykiem wystąpienia porodu przedwczesnego w populacji polskich kobiet. Materiał i metody: Do badania zakwalifikowano 125 kobiet rasy kaukaskiej. Grup´ badana stanowiły 62 kobiety, które urodziły przed 36+6 tygodniem trwania ciąży w wyniku przedwczesnego pęknięcia błon płodowych przed terminem lub spontanicznej czynności skurczowej macicy. Grupę porównawczą stanowiły 63 kobiety, które urodziły w terminie. Na podstawie standaryzowanego kwestionariusza oraz dokumentacji medycznej zebrano szczegółowe dane demograficzne, medyczne i położnicze. DNA izolowano z krwi żylnej pobranej od matek po porodzie. Polimorfizm genów oceniono stosując metod´ analizy restrykcyjnej (PCR-RFLP – polymerase chain reaction-restriction fragment length polymorphism). Ilorazy szans oraz ich 95% przedziały ufności obliczono przy użyciu modelu regresji logistycznej. Wyniki: Nosicielki IL1RN*2 cechowały się zwiększonym ryzykiem wystąpienia porodu przedwczesnego OR=2,75 (95%CI:1,02-4,13). Nie stwierdzono zależności pomiędzy występowaniem polimorfizmu genów kodujących IL-1β, IL-6 i TNF-α a ryzykiem urodzenia wcześniaka. Współwystępowanie polimorficznych alleli genu IL1RN (genotyp IL1RN*1/ IL1RN*2, IL1RN*1/ IL1RN*3, IL1RN*2/ IL1RN*3) z polimorficznymi allelami promotora genu IL-6 (genotyp: GG, GC) zwiększało ryzyko wystąpienia porodu przedwczesnego OR=3,02(95%CI: 1,00-8,91). Wnioski: Nosicielstwo allela 2 intronu 2 genu antagonisty receptora interleukiny-1 (IL1RN*2) związane jest ze zwiększonym ryzykiem występowania porodu przedwczesnego w populacji kobiet polskich. Jednoczesne występowanie IL1RN*2 oraz co najmniej jednego allela G genu interleukiny-6 dodatkowo zwiększa ryzyko przedwczesnego zakończenia ciąży

Ocena ekspresji cykliny E w rozrostach i raku błony śluzowej trzonu macicy u kobiet po menopauzie

Objectives: The aim of present study was to determine expression of cyclin E in endometrial hyperplasia without atypia, atypical endometrial hyperplasia and endometrial cancers in comparison with expression of cyclin E in atrophic endometrium of postmenopausal women. We have also estimated relationship between cyclin E expression and prognostic factors for endometrial cancer such as: histological type, cancer stage and histological grade. Material and methods: 154 women were enrolled into study. Women were divided into 4 groups. The first group consist of 38 women with endometrial hyperplasia without atypia, the second group consist of 18 women with atypical endometrial hyperplasia. The third group comprise 62 women with endometrial cancer and the forth 36 women with atrophic endometrium. Cyclin E expression was estimated in formalin-fixed, paraffin-embedded tissues obtained from enrolled women with the use of immunohistochemical techniques. We estimated labelling index (LI) – the number of cells that stained for cyclin E in relation to all cells at the certain field of view. Results: Medians of labelling indices of cyclin E in atrophic endometrium, endometrial hyperplasia with atypia, atypical endometrial hyperplasia end endometrial cancer were 13,7%, 34,7%, 62%, 72,2% respectively. These differences were statistically significant. In our study we haven’t found relationship between cyclin E expression and histological type of tumour (p=0,186), cancer stage (p=0,186) and histological grade (p=0,539). Conclusions: In the carcinogenesis of endometrial tumours in postmenopausal women there is a progressive disorder in mechanisms regulating cell cycle. It seems impossible to use cyclin E as prognostic factor for endometrial cancer.Cel pracy: Celem pracy była ocena ekspresji cykliny E w rozrostach endometrium bez atypii komórkowej, w rozrostach endometrium z atypią komórkową oraz w rakach endometrium, w porównaniu do ekspresji cykliny E w endometrium atroficznym u kobiet po menopauzie. Dodatkowo oceniliśmy zależność między ekspresją cykliny E a czynnikami prognostycznymi w raku endometrium takimi jak: typ histologiczny nowotworu, stopień klinicznego zaawansowania wg FIGO oraz stopień zróżnicowania histologicznego. Materiał i metody: Do badania zakwalifikowano 154 kobiety podzielone na 4 grupy. Do pierwszej grupy włączono 38 kobiet z rozrostem endometrium bez atypii, do drugiej 18 kobiet z rozrostem endometrium z atypią, do trzeciej 62 kobiety z rakiem endometrium, a do czwartej 36 kobiet z endometrium atroficznym. Ekspresję cykliny E oceniono w utrwalonych w formalinie, zatopionych w parafinie preparatach endometrium uzyskanych od badanych kobiet przy użyciu metod immunohistochemicznych. Oceniono indeks komórkowy (LI - labelling index) – liczbę komórek wykazujących ekspresję cykliny E w stosunku do wszystkich komórek w danym polu widzenia Wyniki: Mediany indeksów komórkowych cykliny E w endometrium atroficznym, rozroście endometrium bez atypii, rozroście endometrium z atypią oraz raku endometrium wynosiły odpowiednio 13,7%, 34,7%, 62%, 72,2%. Różnice te były istotne statystycznie. W pracy nie wykazaliśmy zależności między nasileniem ekspresji cykliny E, a typem histologicznym nowotworu (p=0,186), stopniem klinicznego zaawansowania wg FIGO (p=0,186) oraz stopniem zróżnicowania histologicznego guza (p=0,539). Wnioski: W procesie rozwoju nowotworu błony śluzowej trzonu macicy u kobiet po menopauzie dochodzi do stopniowego zaburzenia mechanizmów regulujących cykl komórkowy. Ocena ekspresji cykliny E nie może być wykorzystana jako czynnik prognostyczny w raku endometrium

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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The evolution of thecideide microstructures and textures: traced from Triassic to Holocene

Thecideide brachiopods are an anomalous group of invertebrates. In this study, we discuss the evolution of thecideide brachiopods from the Triassic to the Holocene and base our results and conclusions on microstructure and texture measurements gained from electron backscatter diffraction (EBSD). In fossil and Recent thecideide shells, we observe the following mineral units: (1) nanometric to small granules; (2) acicles; (3) fibres; (4) polygonal crystals; and (5) large roundish crystals. We trace for thecideide shells the change of mineral unit characteristics such as morphology, size, orientation, arrangement and distribution pattern. Triassic thecideide shells contain extensive sections formed of fibres interspersed with large, roundish crystals. Upper Cretaceous to Pleistocene thecideide hard tissues consist of a matrix of minute to small grains reinforced by acicles and small polygonal crystals. Recent thecideide species form their shell of mineral units that show a wide range of shapes, sizes and arrangements. We find from Late Triassic to Recent a gradual decrease in mineral unit size, regularity of mineral unit morphology and orientation and the degree of calcite co‐orientation. While crystallite co‐orientation is the highest for fibrous microstructures, it is strikingly low for taxa that form their shell out of nanogranular to acicular mineral units. Our results indicate that Upper Jurassic species represent transitional forms between ancient taxa with fibrous shells and Recent forms that construct their shells of acicles and granules. We attribute the observed changes in microstructure and texture to be an adaptation to a different habitat and lifestyle associated with cementation to hard substrates

Thick brachiopod shell concentrations from prodelta and siliciclastic ramp in a Tortonian Atlantic–Mediterranean strait (Miocene, Guadix Basin, southern Spain)

Carbonate production by brachiopods in shallow-water habitats is generally expected to be not sufficiently high and temporally persistent to allow them to form very thick and densely packed shell concentrations. The formation of thick brachiopod concentrations requires long-term persistence of populations with high density of individuals, and such circumstances are assumed to be rare especially during the Cenozoic. However, here we show that the large-sized brachiopod Terebratula terebratula, the most common species in benthic assemblages with epifaunal bivalves and irregular echinoids, formed several decameter- to meter-thick, densely packed concentrations in shallow siliciclastic, high-energy environments, in a seaway connecting the Atlantic Ocean with the Mediterranean Sea during the Latest Tortonian (Late Miocene, Guadix Basin, southern Spain). This brachiopod formed (1) meter-scale, thick, parautochthonous concentrations in a prodelta setting and (2) thin, mainly allochthonous, tide- and storm-reworked concentrations in megaripples and dunes. The abundance of brachiopods at the spatial scale of the Guadix Basin seems to be mainly related to intermediate levels of sedimentation rate and current velocity because abundance and thickness of shell concentrations decline both (1) in onshore direction towards delta foresets with high sedimentation rate generated by debris flows and (2) in offshore direction with increasing levels of tide- and storm-induced substrate instability. Although brachiopods in dune and megaripple deposits are more fragmented, disarticulated, and sorted, and have a higher pedicle/brachial valve ratio than in prodelta deposits, taphonomic damage is still relatively high in prodelta deposits. Terebratula terebratula thus formed thick concentrations in spite of that disintegration processes were relatively intense along the whole depositional gradient. Therefore, population dynamic of this species was probably characterized by production maxima that were comparable to some Cenozoic molluscs in terms of their productivity potential to form thick shell concentrations in shallow subtidal environments. We suggest that temporal changes in brachiopod carbonate production have a significant spatial and phylogenetic component because multiple large-sized species of the family Terebratulidae, which underwent radiation during the Cenozoic, attained high abundances and formed shell concentrations in temperate regions.This research was supported by project CGL2009-07830/BTE and financed by the Spanish Ministry of Education and Science (MEC), the European Fund of Regional Development (FEDER), and Research Group RNM-200 of the Junta de Andalucía. A. Tomašových was supported by the Slovak Research and Development Agency (APVV-0248-07 and 0644-10), the Slovakian Scientific Grant Agency (VEGA 2/0068/11), and the National Science Foundation (DEB 0919451)