Neuroendocrine neoplasms and somatostatin receptor subtypes expression

Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course — from benign biological potential to recurrences and rapidly progressive disease. Somatostatin analogs that bind to somatostatin receptor are part of the therapy; detection and evaluation of activation of somatostatin receptor subtypes are part of the process of new therapy induction. When using RT-PCR method and immunohistochemistry, it is possible to detect more than two SSTR subtypes in majority or all neuroendo­crine neoplasms regardless tumor origin. Generally with some exceptions, from the viewpoint of tumor grade — apart the site of origin, there is a tendency to decrease the percentage of SSTRs expression; 100% (G1, 2)–85.7% (G3) for SSTR 1; 81.8% (G1, 2)–61.9% (G3) for SSTR 2; 54.5% (G1, 2)–52.4% (G3) for SSTR 3; 9% (G1, 2)–4.8% (G3) for SSTR 5. Different studies indi­cate significant differences in the expression of SSTR 1 and 2A and 2B between NEC G3 small cell type and non-small cell type. Further research on SSTRs expression in NEN could serve as base to development and improvement of somatostatin analogs’ pharmacotherapy in patients with unsatisfactory course

Annotation, submission and screening of repetitive elements in Repbase: RepbaseSubmitter and Censor

BACKGROUND: Repbase is a reference database of eukaryotic repetitive DNA, which includes prototypic sequences of repeats and basic information described in annotations. Updating and maintenance of the database requires specialized tools, which we have created and made available for use with Repbase, and which may be useful as a template for other curated databases. RESULTS: We describe the software tools RepbaseSubmitter and Censor, which are designed to facilitate updating and screening the content of Repbase. RepbaseSubmitter is a java-based interface for formatting and annotating Repbase entries. It eliminates many common formatting errors, and automates actions such as calculation of sequence lengths and composition, thus facilitating curation of Repbase sequences. In addition, it has several features for predicting protein coding regions in sequences; searching and including Pubmed references in Repbase entries; and searching the NCBI taxonomy database for correct inclusion of species information and taxonomic position. Censor is a tool to rapidly identify repetitive elements by comparison to known repeats. It uses WU-BLAST for speed and sensitivity, and can conduct DNA-DNA, DNA-protein, or translated DNA-translated DNA searches of genomic sequence. Defragmented output includes a map of repeats present in the query sequence, with the options to report masked query sequence(s), repeat sequences found in the query, and alignments. CONCLUSION: Censor and RepbaseSubmitter are available as both web-based services and downloadable versions. They can be found at (RepbaseSubmitter) and (Censor)

Molecular Profile of Barrett's Esophagus and Gastroesophageal Reflux Disease in the Development of Translational Physiological and Pharmacological Studies

Barrett's esophagus (BE) is a premalignant condition caused by gastroesophageal reflux disease (GERD), where physiological squamous epithelium is replaced by columnar epithelium. Several in vivo and in vitro BE models were developed with questionable translational relevance when implemented separately. Therefore, we aimed to screen Gene Expression Omnibus 2R (GEO2R) databases to establish whether clinical BE molecular profile was comparable with animal and optimized human esophageal squamous cell lines-based in vitro models. The GEO2R tool and selected databases were used to establish human BE molecular profile. BE-specific mRNAs in human esophageal cell lines (Het-1A and EPC2) were determined after one, three and/or six-day treatment with acidified medium (pH 5.0) and/or 50 and 100 µM bile mixture (BM). Wistar rats underwent microsurgical procedures to generate esophagogastroduodenal anastomosis (EGDA) leading to BE. BE-specific genes (keratin (KRT)1, KRT4, KRT5, KRT6A, KRT13, KRT14, KRT15, KRT16, KRT23, KRT24, KRT7, KRT8, KRT18, KRT20, trefoil factor (TFF)1, TFF2, TFF3, villin (VIL)1, mucin (MUC)2, MUC3A/B, MUC5B, MUC6 and MUC13) mRNA expression was assessed by real-time PCR. Pro/anti-inflammatory factors (interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, tumor necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor) serum concentration was assessed by a Luminex assay. Expression profile in vivo reflected about 45% of clinical BE with accompanied inflammatory response. Six-day treatment with 100 µM BM (pH 5.0) altered gene expression in vitro reflecting in 73% human BE profile and making this the most reliable in vitro tool taking into account two tested cell lines. Our optimized and established combined in vitro and in vivo BE models can improve further physiological and pharmacological studies testing pathomechanisms and novel therapeutic targets of this disorder

The activity of Bodzanta of Kosowice of the Szeliga coat of arms as the archbishop of Gniezno

Bodzanta z Kosowic herbu Szeliga wzbudza wśród historyków bardzo skrajne opinie – od wytrawnego gracza politycznego i dobrego administratora do człowieka nieporadnego o chwiejnych poglądach politycznych. Negatywny obraz tej postaci stworzył Jan z Czarnkowa, który w swojej kronice ukazał w złym świetle arcybiskupa gnieźnieńskiego Bodzantę. Tak różne opinie na temat tej osoby zainspirowały mnie do podjęcia próby zbadania działalności arcybiskupa w latach 1382–1388, a szczególnie w okresie po wojnie domowej w Wielkopolsce. Artykuł obejmuje okres od momentu nominacji Bodzanty na stanowisko arcybiskupa do jego śmierci. Głównym założeniem tekstu jest podważenie opinii Janka z Czarnkowa o Bodzancie – człowieku szkodzącemu polskiemu Kościołowi. Dotychczasowy stan badań na temat arcybiskupa ogranicza się do skrupulatnego opracowania jego działań politycznych podczas wojny domowej w Wielkopolsce. W artykule przede wszystkim kładę nacisk na działalność prawno-gospodarczą arcybiskupa, która miała miejsce po zakończeniu narracji Kroniki Jana z Czarnkowa. Szczególnie wartościowa jest analiza pomijanego do tej pory dokumentu dotyczącego konfliktu Bodzanty i Władysława Opolczyka z roku 1387 oraz opracowanie działalności prawno-gospodarczej arcybiskupa. Głównym celem artykułu jest zebranie i uporządkowanie informacji o działalności Bodzanty z Kosowic w latach 1382–1388. Staram się także ukazać relacje łączące arcybiskupa z monarchami ówczesnej Europy. Istotne jest także pokazanie znaczenia aktywności zwierzchnika polskiego Kościoła w rozwijaniu zniszczonej domeny arcybiskupiej. Wydaje się, że dopiero takie spojrzenie na działalność bohatera tego artykułu pozwala na wyciągnięcie obiektywnych wniosków dotyczących jego urzędowania na arcybiskupstwie.Bodzanta of Kosowice of the Szeliga coat of arms raises extreme opinions among historians - from an experienced political player and a good administrator to an awkward man of shaky poitical views. Bodzanta's negative image was created by Jan of Czarnków, who presented him in a negative light in his Chronicle. Such differing opinions have inspired the author of the article to attempt to examine the activity of the archbishop in the years 1382-1338, particularly after the civil war in Greater Poland. The article covers the period from the nomination of Bodzanta as archbishop until his death and its main aim is to undermine the opinion of Jan of Czarnków about Bodzanta being harmful for the Polish church. The current state of research on the archbishop’s activity is limited to a detailed description of his political activities during the civil war in Greater Poland. The article emphasizes the legal and economic activity of the archbishop, which took place after the events presented in the Chronicle of Jan of Czarnków. The author finds particularly valuable his analysis of the document so far overlooked regarding the conflict between Bodzanta and Władysław Opolczyk from 1387 and the description of the legal and economic activity of the archbishop. The main purpose of the article is to collect and organize information on the activities of Bodzanta from Kosowice in the years 1382–1388. The article also attempts to show the relationship between the archbishop and the monarchs of Europe at that time. It is also important to show the significance of the activity of the head of the Polish Church in developing the destroyed archbishop's domain. It seems that only such a perspective at the activities of the archbishop allows to draw objective conclusions regarding his office