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Prezentowany tekst to relacja Krzysztofa Koszlagi, nauczyciela z ponad pięćdziesięcioletnim stażem oraz jednego z czołowych działaczy NSZZ „Solidarność” Oświaty i Wychowania, wraz z komentarzem naukowym. Narracja ukazuje funkcjonowanie szkolnictwa w PRL w latach 1969–1989, a także wpływ zachodzących w tym okresie zmian społeczno-politycznych na pracę nauczyciela i relacje z uczniami. Podstawą zamieszczonego tekstu jest wywiad pogłębiony przeprowadzony ze świadkiem historii, opatrzony wstępem zawierającym dane biograficzne autora relacji oraz opis projektu naukowego, w ramach którego przeprowadzony został wywiad, wraz z uwzględnieniem zastosowanych metod badawczych.

New pharmacological approaches that target orexin receptors (OXRs) are being developed to treat sleep disorders such as insomnia and narcolepsy, with fewer side effects than existing treatments. Orexins are neuropeptides that exert excitatory effects on postsynaptic neurons via the OXRs, and are important in regulating sleep/wake states. To date, there are three FDA-approved dual orexin receptor antagonists for the treatment of insomnia, and several small molecule oral OX2R (OXR type 2) agonists are in the pipeline for addressing the orexin deficiency in narcolepsy. To find new hypnotics and psychostimulants, rodents have been the model of choice, but they are costly and have substantially different sleep patterns to humans. As an alternative model, zebrafish larvae that like humans are diurnal and show peak daytime activity and rest at night offer several potential advantages including the ability for high throughput screening. To pharmacologically validate the use of a zebrafish model in the discovery of new compounds, we aimed in this study to evaluate the functionality of a set of known small molecule OX2R agonists and antagonists on human and zebrafish OXRs and to probe their effects on the behavior of zebrafish larvae. To this end, we developed an in vitro IP-One Homogeneous Time Resolved Fluorescence (HTRF) immunoassay, and in vivo locomotor assays that record the locomotor activity of zebrafish larvae under physiological light conditions as well as under dark-light triggers. We demonstrate that the functional IP-One test is a good predictor of biological activity in vivo. Moreover, the behavioral data show that a high-throughput assay that records the locomotor activity of zebrafish throughout the evening, night and morning is able to distinguish between OXR agonists and antagonists active on the zebrafish OXR. Conversely, a locomotor assay with alternating 30 min dark-light transitions throughout the day is not able to distinguish between the two sets of compounds, indicating the importance of circadian rhythm to their pharmacological activity. Overall, the results show that a functional IP-one test in combination with a behavioral assay using zebrafish is well-suited as a discovery platform to find novel compounds that target OXRs for the treatment of sleep disorders.

The article discusses the errors of the electronic measuring apparatus built at AFIT using the FAM-C and FDM-A methods, dedicated to monitoring the technical condition of aircraft power units. The basic components and variants of the use of the built electronic apparatus are presented: the optimization of the selection of construction parameters and the change of the error level in the selection of various types of construction of a given system. The influence of external factors on errors of the measuring system was also described, including changes in the amplitude of the electrical power generator output signal and the influence of the carrier frequency depending on the phase configuration of the measuring system. The method of comprehensive checking of electronic measuring equipment for FAM-C and FDM-A methods in laboratory conditions was presented.

Synaptic vesicle glycoprotein 2A (SV2A) regulates action potential-dependent neurotransmitter release and is commonly known as the primary binding site of an approved anti-epileptic drug, levetiracetam. Although several rodent knockout models have demonstrated the importance of SV2A for functional neurotransmission, its precise physiological function and role in epilepsy pathophysiology remains to be elucidated. Here, we present a novel

This paper aims at sketching cultural portrayals of the Ukrainian city Odessa and the Bosnian capital, Sarajevo, with reference to their current socio-political situation. Cultural visions of both places not only tend to have a lot in common, paradoxically due to the differences that they share but also the ones present in various texts of culture. Thus, both cities can boast their own myths. The symbolic space is approached among others through the prism of Vladimir Toporov’s theory. The city perceived by some researchers as a metaphor of culture functions as a kind of laboratory that fixates social and cultural changes emerging within the society on the microscopic scale. In addition, the current geopolitical situation of those places is mentioned with its war/conflict aftermath that contributes to certain city image.

Marta Siekierska, TRAGEDIA HOLOKAUSTU ORAZ ŻYDOWSKIE MIEJSCA PAMIĘCI NA UKRAINIE W POWIEŚCI J. S. FOERA WSZYSTKO JEST ILUMINACJĄ. „PORÓWNANIA” 1 (24), 2019. T. XXIV, S. 135-145. ISSN 1733-165X. Cel niniejszego artykułu stanowi próba analizy powieści, skoncentrowana na relacjach zachodzących między formą i językiem utworu a traumą historyczną, jakiej doświadczają bohaterowie. Specyficzna konstrukcja oraz język, który wykorzystuje w powieści autor, przekładają się na nowatorski sposób przetworzenia historii oraz tematu Zagłady. Tekst prezentuje również obecny w powieści pejzaż polsko-ukraińskiego pogranicza, wytyczanego przez historyczne, metafizyczne oraz kulturowe granice. Analizie i interpretacji zostaje poddana obecna w utworze bogata symbolika, uwypuklająca wymiar znaczącej nieobecności zgładzonej społeczności oraz wymownej luki, białego miejsca pamięci, która po nich pozostała.

Protein aggregation is an underappreciated mechanism that may contribute to the loss- and oncogenic-gain-of-function of mutant tumor suppressors such as p53 and axin. In the present study, we describe amyloid-like aggregation behaviour of the second most frequently mutated tumor suppressor in human cancer, PTEN. In silico analysis revealed a particularly high aggregation vulnerability for this protein, which was corroborated by in vitro aggregation assays. In cultured tumor cells, we found that under stress conditions, PTEN readily undergoes amyloid-like aggregation as a result of mutation. However, we also show that severe dysregulation of protein homeostasis may lead to aggregation of wild-type PTEN. These observations were supported by a small survey of patient-derived uterine tumor tissues, which found that more than 25% of tumors analyzed displayed wild-type PTEN aggregation. Finally, in an exploratory clinical study we found that PTEN aggregation status was correlated with a decline in clinical outcome. Our findings establish that the tumor suppressor PTEN is highly aggregation-prone and our work suggests that protein aggregation might be an underestimated but prevalent component of cancer cell biology.

The paper aims to demonstrate the Clinic's and own research in the treatment of major salivary gland tumors.In the years 2013-2019, there were 95 salivary gland surgeries, including 45 performed in women (47.36%) aged between 24 and 82 and in 50 men (52.64%) aged 29 to 86. Diagnostics of major salivary glands included: patient history, otolaryngological examination, ultrasound and fine needle aspiration (BACC) (of tumor), laboratory tests (morphology, CRP) and computed tomography (CT) or magnetic resonance imaging (MRI) to accurately assess salivary glands, location of lesion and lymph nodes prior to elective surgery. Research results: In the analyzed material patients with major salivary gland tumors were most frequently operated on at the age of 61-70 (34.7%) and 51-60 years (23.2%). Most patients with tumors were hospitalized in the last 4 years between 2016-2019, which accounted for 77.8% of all operated cases. Among the operated lesions, benign neoplasms and tumors occurred in 93.7%, of which the most frequent findings in histopathological examination were Warthin tumor in 50.5%, and multiform adenoma in 26.3%. The remaining tumors and benign neoplasms constituted only 16.9% and were observed in isolated cases, including eosinophilic adenoma, lymphoepithelial cyst, myoepithelial adenoma, lipofibrosarcoma, congestive cyst, air cyst, tubular adenoma, basal cell carcinoma, cyst with squamous metaplasia features, vascular malformation. Malignant salivary gland tumors were found in 6.3%, including the following malignant tumors were revealed histopathologically: adenocarcinoma, mucoepidermal carcinoma, acinocellular carcinoma, epithelialmyoepithelial carcinoma, ductal carcinoma.The majority of operated salivary gland tumors were benign (93.7%), of which the most common histopathologically were: Warthin tumor (50.5%) and multiform adenoma (26.3%), while malignant tumors occurred in 6.3%. Tumors were localized mainly in the parotid gland in as many as 93.7% cases, of which the most common localization concerned the superficial lobe in 56.8%. The most frequent surgical technique used in the Clinic was extracapsular dissection of the tumor in 88.4%, and other methods were used rarely.

Enterobius vermicularis is a cosmopolitan parasite of large intestine. Enterobius vermicularis infection is found mostly in closed human communities such as kindergartens, nurseries and orphanages. The aim of the study was to evaluate the frequency of E. vermicularis in preschool children from Wielkopolska Voivodeship. In addition, the aim was to determine the relationships between the gender of children, place of residence and the occurrence of enterobiasis and to define the most common symptoms of enterobiasis in infected children. There were 145 children (84 girls and 61 boys) aged 3-6 who attended kindergartens in Wielkopolskie voivodeship. Swabs from the anus area was used according to Graham’s method. The frequency of E. vermicularis infection in the studied children was 7.6%. There were no relationships between the gender of participants as well as the place of residence and the frequency of E. vermicularis infection. There was no relationship between the occurrence of symptoms of enterobiasis and E. vermicularis infection. The examination showed that the half of studied children infected with E. vermicularis had no symptoms of infection. Enterobiasis is the most common parasitosis in preschool and early childhood children. The prevalence of enterobiasis in humans is correlated with socio-environmental factors. On the basis of the presented study, it was found that in order to control the E. vermicularis infection, it would be necessary to regularly educate parents about the risks of parasitic diseases and to teach children the principles of hygiene from a young age.

Development of RNA-based technologies relies on the ability to detect, manipulate, and modify RNA. Efficient, selective and scalable covalent modification of long RNA molecules remains a challenge. We report a chemical method for modification of RNA 3'-end based on previously unrecognized superior reactivity of N-substituted ethylenediamines in reductive amination of periodate-oxidized RNA. Using this method, we obtained fluorescently labelled or biotinylated RNAs varying in length (from 3 to 2000 nt) and carrying different 5' ends (including m7G cap) in high yields (70-100% by HPLC). The method is scalable (up to sub-milligrams of mRNA) and combined with label-facilitated HPLC purification yields highly homogeneous products. The combination of 3'-end labelling with 5'-end labelling by strain-promoted azide-alkyne cycloaddition (SPAAC) afforded a one-pot protocol for site-specific RNA bifunctionalization, providing access to two-colour fluorescent RNA probes. These probes exhibited fluorescence resonance energy transfer (FRET), which enabled real-time monitoring of several RNA hydrolase activities (RNase A, RNase T1, RNase R, Dcp1/2, and RNase H). Dually labelled mRNAs were efficiently translated in cultured cells and in zebrafish embryos, which combined with their detectability by fluorescent methods and scalability of the synthesis, opens new avenues for the investigation of mRNA metabolism and the fate of mRNA-based therapeutics. ispartof: NUCLEIC ACIDS RESEARCH vol:50 issue:1 ispartof: location:England status: published

BACKGROUND: Epilepsy is a chronic neurological condition, with over 30% of cases unresponsive to treatment. Zebrafish larvae show great potential to serve as an animal model of epilepsy in drug discovery. Thanks to their high fecundity and relatively low cost, they are amenable to high-throughput screening. However, the assessment of seizure occurrences in zebrafish larvae remains a bottleneck, as visual analysis is subjective and time-consuming. NEW METHOD: For the first time, we present an automated algorithm to detect epileptic discharges in single-channel local field potential (LFP) recordings in zebrafish. First, candidate seizure segments are selected based on their energy and length. Afterwards, discriminative features are extracted from each segment. Using a labeled dataset, a support vector machine (SVM) classifier is trained to learn an optimal feature mapping. Finally, this SVM classifier is used to detect seizure segments in new signals. RESULTS: We tested the proposed algorithm both in a chemically-induced seizure model and a genetic epilepsy model. In both cases, the algorithm delivered similar results to visual analysis and found a significant difference in number of seizures between the epileptic and control group. COMPARISON WITH EXISTING METHODS: Direct comparison with multichannel techniques or methods developed for different animal models is not feasible. Nevertheless, a literature review shows that our algorithm outperforms state-of-the-art techniques in terms of accuracy, precision and specificity, while maintaining a reasonable sensitivity. CONCLUSION: Our seizure detection system is a generic, time-saving and objective method to analyze zebrafish LPF, which can replace visual analysis and facilitate true high-throughput studies. ispartof: Journal of Neuroscience Methods vol:287 pages:13-24 ispartof: location:Netherlands status: published

Plants accumulate a family of hydrophobic polymers known as polyprenols, yet how they are synthesized, where they reside in the cell, and what role they serve is largely unknown. Using Arabidopsis thaliana as a model, we present evidence for the involvement of a plastidial cis-prenyltransferase (AtCPT7) in polyprenol synthesis. Gene inactivation and RNAi-mediated knockdown of AtCPT7 eliminated leaf polyprenols, while its overexpression increased their content. Complementation tests in the polyprenol-deficient yeast ∆rer2 mutant and enzyme assays with recombinant AtCPT7 confirmed that the enzyme synthesizes polyprenols of ∼55 carbons in length using geranylgeranyl diphosphate (GGPP) and isopentenyl diphosphate as substrates. Immunodetection and in vivo localization of AtCPT7 fluorescent protein fusions showed that AtCPT7 resides in the stroma of mesophyll chloroplasts. The enzymatic products of AtCPT7 accumulate in thylakoid membranes, and in their absence, thylakoids adopt an increasingly “fluid membrane” state. Chlorophyll fluorescence measurements from the leaves of polyprenol-deficient plants revealed impaired photosystem II operating efficiency, and their thylakoids exhibited a decreased rate of electron transport. These results establish that (1) plastidial AtCPT7 extends the length of GGPP to ∼55 carbons, which then accumulate in thylakoid membranes; and (2) these polyprenols influence photosynthetic performance through their modulation of thylakoid membrane dynamics.

Poradnik powstał w odpowiedzi na potrzeby matek i ojców, którzy cierpią z powodu problemu alkoholowego swoich dorosłych dzieci. Warto podkreślić, że to właśnie rodzice są uczestnikami i świadkami swoistej „kariery” alkoholowej swojego dziecka, a przez to sami przeżywają całą gamę negatywnych emocji, trudności czy dylematów. W publikacji zamieszczono krótkie opisy ilustrujące konkretne sytuacje, zdarzenia czy historie osób, które doświadczały kryzysów związanych z nadużywaniem alkoholu przez dorosłe dziecko. Autorki stopniowo odsłaniają i wyjaśniają problematykę nie tylko samego uzależnienia, lecz także przygotowują czytelnika krok po kroku do wprowadzania w życie różnych form pomocy zarówno wobec własnej osoby, jak i dorosłego dziecka z problemem alkoholowym. Zadanie „Wspieranie badań naukowych w obszarze problemów wynikających z używania alkoholu” finansowane ze środków Narodowego Programu Zdrowia na lata 2016–2020

Celem artykulu jest opisanie trudności związanych z funkcjonowaniem w bliskim związku uczuciowym, jakich doświadczają dorosle dzieci z rodzin rozwiedzionych. Analiza przeprowadzonych wywiadow wskazuje, ze narratorzy doświadczali trudności w radzeniu sobie z rozwodem rodzicow, co mialo swoje odzwierciedlenie przede wszystkim w budowaniu bliskich relacji uczuciowych z plcią przeciwną. Problemy te w najwiekszej mierze odnosily sie do sfery emocjonalnej, a wiązaly sie z brakiem zaufania, lekiem o przyszlośc i trwalośc związku, nieumiejetnością wyrazania i okazywania uczuc, niskim poczuciem wlasnej wartości i niską samooceną oraz z deprywacją wewnetrznej potrzeby bezpieczenstwa.

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies., tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

Cel – W artykule przedstawiono zmiany wprowadzone rozporządzeniem Ministra Finansow z 4 września 2015 roku w sprawie audytu wewnetrznego oraz informacji o pracy i wynikach tego audytu w porownaniu z zapisami zastepowanego rozporządzenia Ministra Finansow z 1 lutego 2010 roku w sprawie przeprowadzania i dokumentowania audytu wewnetrznego. Nowe przepisy obowiązują od 1 stycznia 2016 roku i wprowadzają istotne zmiany do pracy audytora wewnetrznego w jednostkach sektora finansow publicznych. Celem artykulu jest ocena kierunku zmian na tle dotychczasowych rozwiązan oraz analiza poszczegolnych zapisow rozporządzenia pod kątem celowości i spojności z innymi regulacjami. Metodologia badania – Analiza porownawcza, wnioskowanie logiczne. Wynik – Wskazano najwazniejszych zmiany wprowadzone rozporządzeniem Ministra Finansow z 4 września 2015 roku oraz kontrowersje związane z niektorymi wprowadzonymi rozwiązaniami, ktore mogą wplywac na niezaleznośc pracy audytora oraz są niespojne z innymi regulacjami (instrukcja kancelaryjna). Analiza wskazuje na niejasności i koniecznośc wypracowania przez audytorow wlaściwych procedur. Oryginalnośc/wartośc – W artykule przeanalizowano zmiany w obszarze audytu wewnetrznego wprowadzone rozporządzeniem Ministra Finansow z 4 września 2015 roku. Zmiany zostaly opisane i ocenione na tle wcześniejszych regulacji. Analiza zapisow rozporządzenia wskazuje na problemy z interpretacją niektorych zapisow i trudności w jednolitym stosowaniu wspomnianych przepisow z powodu ich niejednoznaczności.

Badanie dotyczyło wpływu mimicznego sprzężenia zwrotnego na subiektywną percepcję zmęczenia. Przebadano 75 studentów (19 – 26 lat). Badani wypełniali dwukrotnie polską adaptację skali FAS, przed i po wykonaniu zadania eksperymentalnego, polegającego na przyjęciu określonej postawy ciała oraz mimiki. W badaniu utworzono 2 grupy eksperymentalne i 1 grupę kontrolną, różniące się pod względem wykonywanego zadania. Zmienną zależną stanowiło zmęczenie, a niezależną rodzaj mimiki. Założono, że u osób które przyjmą zmęczony wyraz twarzy subiektywna ocena percepcji zmęczenia wzrośnie. Hipoteza nie została potwierdzona. Jednocześnie potwierdza to odporność wyników testu FAS na chwilowe zmiany percepcji zmęczenia i adekwatność tego narzędzia.

Introduction: Hepatitis C virus (HCV) infection is a worldwide problem and hepatitis, which is its natural unfavourable course, is still a challenge for hepatologist. At present, standards of treatment are changing from combined therapy with interferon alpha (IFN-α) and ribavirin to new antiviral drugs. The current classification divides interferon induced thyroid diseases (IITD) into two groups: autoimmune (Hashimoto disease, Graves disease, positive antithyroid autoantibodies in euthyroid patients) and non-autoimmune (destructive thyroiditis, non-autoimmune hypothyroidism). A common complication of cytokine therapy is the induction of antithyroid autoantibodies de novo without thyroid dysfunction. During therapeutic regimens combined with ribavirin, destructive thyroiditis with typical biphasic course is more common than in IFN-α monotherapy. Clinically, overt pathologies often have discrete symptoms, which cause diagnostic and therapeutic dilemmas. Aims: The aim of this study was to estimate IITD occurrence, to find risk factors for IITD development. Material and methods: The study group consisted of 66 patients treated for HCV infection. Before and during antiviral therapy, hormonal (TSH, fT4, fT3), immunological (thyroid autoantibodies), ultrasonographic and genetic (HLA-A2) parameters were evaluated. Results: Hormonal disturbances were detected in 24.2% of patients; however, 43.9% of patients had positive thyroid autoantibodies (de novo) without hormonal imbalance. Multivariate analysis revealed the following: female sex, elevated TSH level, occurrence of anti-TPO autoantibodies (TPO-Ab), and increased blood velocity in thyroid arteries are risk factors for IITD development. In conclusion: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 μU/mL), positive TPO-Ab and increased blood velocity in thyroid arteries.

Epilepsy is a neurological disease that affects more than 70 million people worldwide and is characterized by the presence of spontaneous unprovoked recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail to control seizures in 30% of patients due to drug resistance. Hence, safer and more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures naturally present in most plants and consumed daily with no adverse effects reported. These structures have shown activity in several seizure and epilepsy animal models through allosteric modulation of GABAA receptors, but also via potent anti-inflammatory action in the brain. As such, dietary flavonoids offer an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability. It has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, thereby dramatically enhancing metabolic stability and membrane transport, facilitating absorption and highly increasing bioavailability. Since no scientific data is available regarding the use of methylated flavonoids in the fight against epilepsy, we studied naringenin (NRG), kaempferol (KFL), and three methylated derivatives, i.e., naringenin 7-O-methyl ether (NRG-M), naringenin 4′,7-dimethyl ether (NRG-DM), and kaempferide (4′-O-methyl kaempferol) (KFD) in the zebrafish pentylenetetrazole (PTZ) seizure model. We demonstrate that the methylated flavanones NRG-DM and NRG-M are highly effective against PTZ-induced seizures in larval zebrafish, whereas NRG and the flavonols KFL and KFD possess only a limited activity. Moreover, we show that NRG-DM is active in two standard acute mouse seizure models, i.e., the timed i.v. PTZ seizure model and the 6-Hz psychomotor seizure model. Based on these results, NRG-DM is proposed as a lead compound that is worth further investigation for the treatment of generalized seizures and drug-resistant focal seizures. Our data therefore highlights the potential of methylated flavonoids in the search for new and improved ASDs.

Tuberous sclerosis complex (TSC) is a rare, genetic disease caused by loss-of-function mutations in either TSC1 or TSC2. Patients with TSC are neurologically characterized by the presence of abnormal brain structure, intractable epilepsy and TSC-associated neuropsychiatric disorders. Given the lack of effective long-term treatments for TSC, there is a need to gain greater insight into TSC-related pathophysiology and to identify and develop new treatments. In this work we show that homozygous tsc2(-/-) mutant zebrafish larvae, but not tsc2(+/-) and WT larvae, display enlarged brains, reduced locomotor behavior and epileptiform discharges at 7dpf. In addition, we pharmacologically validated the TSC model by demonstrating the dramatic rescue effect of pericardially injected rapamycin, a well-known mTOR inhibitor, on selected behavioral read-outs and at the molecular level. By means of trancriptome profiling we also acquired more insight into the neuropathology of TSC, and as a result were able to highlight possible new treatment targets. The gene expression profiles of WT and tsc2(+/-) larvae revealed 117 differentially expressed genes (DEGs), while between WT and tsc2(-/-) larvae and tsc2(+/-) and tsc2(-/-) larvae there were 1414 and 1079 DEGs, respectively. Pathway enrichment analysis from the WT and tsc2(-/-) DEGs, identified 14 enriched pathways from the up-regulated genes and 6 enriched pathways from the down-regulated genes. Moreover, genes related to inflammation and immune response were up-regulated in the heads of tsc2(-/-) larvae, in line with the findings in human brain tissue where inflammatory and immune responses appear to be major hallmarks of TSC. Taken together, our phenotypic, transcriptomic and pharmacological analysis identified the tsc2(-/-) zebrafish as a preclinical model that mirrors well aspects of the human condition and delineated relevant TSC-related biological pathways. The model may be of value for future TSC-related drug discovery and development programs. [Abstract copyright: Copyright © 2017. Published by Elsevier Inc.]

Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.

The article examines the process of longing for Odessa-Mama on the basis of Michale Boganim’s Odessa…Odessa!, Liev Schreiber’s Everything is illuminated and Sergey Ursulyak’s Liquidation. In this paper particular attention is devoted to the terms Odessan myth and Odessan text that are key elements of analysed movies and contribute to the nostalgic portrayal of Odessa.

Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore the functional relevance of CHD2 haploinsufficiency in an in vivo model system, we knocked down chd2 in zebrafish by using targeted morpholino antisense oligomers. chd2-knockdown larvae exhibited altered locomotor activity, and the epileptic nature of this seizure-like behavior was confirmed by field-potential recordings that revealed epileptiform discharges similar to seizures in affected persons. Both altered locomotor activity and epileptiform discharges were absent in appropriate control larvae. Our study provides evidence that de novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures. publisher: Elsevier articletitle: De Novo Loss-of-Function Mutations in CHD2 Cause a Fever-Sensitive Myoclonic Epileptic Encephalopathy Sharing Features with Dravet Syndrome journaltitle: The American Journal of Human Genetics articlelink: http://dx.doi.org/10.1016/j.ajhg.2013.09.017 content_type: article copyright: Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. ispartof: American Journal Of Human Genetics vol:93 issue:5 pages:967-975 ispartof: location:United States status: published

Zebrafish, a small vertebrate model well-known in developmental biology, is now widely recognized as an important organism for modeling human diseases. Particularly, in the past decade, zebrafish has emerged as a novel and promising model in the field of epilepsy and drug discovery. In this chapter, we aim to give a comprehensive overview of the success and potential of zebrafish epilepsy research. We describe zebrafish models of epilepsy and epileptic seizures generated by various pharmacological and genetic manipulations, with a focus on current methods to monitor and characterize seizure-related activities. Moreover, future perspectives in zebrafish epilepsy modeling and epilepsy research are highlighted. Finally, we discuss challenges and strategies for further translational research in zebrafish epilepsy field.

Plants accumulate a family of hydrophobic polymers known as polyprenols, yet how they are synthesized, where they reside in the cell, and what role they serve is largely unknown. Using

Introduction The rapid development of modern imaging techniques, has led to an increase in accidentally discovered adrenal masses without clinically apparent hormonal abnormalities. Such tumours have been termed “incidentalomas”. The diagnostic work-up in patients with adrenal incidentalomas is aimed at the determination of hormonal activity of the tumour and identification of patients with potentially malignant tumours. The aim of our study was a retrospective analysis of selected clinical characteristics and hormonal studies in accidentally discovered adrenal tumours. Material and methods Fourty hundred sixty-three patients with serendipitously discovered adrenal masses, diagnosed and treated in the Department of Endocrinology and Internal Diseases, Medical University of Gdansk as well as in the affiliated Endocrinology Clinic between 1993 and October of 2009 were included in the analysis. Out of all patients, 245 were referred for adrenalectomy. Results We found that clinically “silent” tumours often demonstrate subclinical hormonal activity. In our report, increased 24-h urinary excretion of cortisol correlated positively with tumour size (p < 0.001). Moreover, a statistical relationship was demonstrated between tumour size and serum cortisol concentration assessed in the 1 mg dexamethasone suppression test (p < 0.001). Increased values of dehydroepiandrosterone/dehydroepiandrosterone sulphate were more often found in malignant than in benign tumours (p < 0.01). Urinary concentrations of 17-ketosteroids correlate positively with diagnosis of adrenocortical cancer (p = 0.02). Conclusions We found that clinically “silent” tumours often demonstrate subclinical hormonal activity (subclinical Cushing syndrome, subclinical pheochromocytoma, low-symptomatic adrenocortical cancer).

In the earthworm Dendrobaena veneta, anterior parts of body were removed at segment 6 and 20 days after decerebration the ovary ultrastructure of these specimens was examined. Numerous changes in oocytes, including shrunk ooplasm, changes in shape, damage of microvilli and oocyte sheath, as well as occurrence ER whorls made it impossible for oocytes to complete oogenesis and caused their degeneration. Similarly, dramatic degenerative changes occurred in Golgi complexes and ER in trophocytes, which might result in disturbances of vitellogenesis. Decerebration deprived the earthworm of neurosecretion (gonadotropins), which resulted in oogenesis distortion. The obtained results were discussed with the results of previous experiment. Then the ovary ultrastructure was described in the individuals maintained in Cd contaminated soil for 20 days. The results in both experiments proved very similar. It may be assumed that cadmium might affect oogenesis in D. veneta in indirect way by suppressing neurosecretion synthesis and its release.

A methodology, an application scenario and a new system enabling collaborative distributed design have been presented. The system based on Tool Registration and Management Services (TRMS) constitutes the core of the engineering collaborative infrastructure that has been deployed in the distributed design of intellectual property (IP) components. The system assures information security (including user authorization, data and transfer encrypting), communication through firewalls, remote administration of users and tools, and some support for distributed inter-organization workflows.

Cadmium effects on the supra- and subpharyngeal ganglia, neurosecretion and RNA content in the neurosecretory cells were tested in earthworms Dendrobaena veneta exposed to 10 and 50 mg Cd kg(-1) in soil after 20 days of the experiment. Accumulation of cadmium in the ganglia of nervous system was also measured using AAS method. Cadmium was accumulated in the nervous system. The accumulated amount was proportional to Cd soil concentration and the exposure time. A considerable fall in neurosecretion and RNA content in the neurosecretory cells and neurosecretion in the neuropile (the axons) of both tested ganglia was induced by 50 mg Cd kg(-1). It seemed that neurosecretion synthesis and its axonal transport could be suppressed. Cadmium caused degenerative changes as vacuolization of the neurosecretory cells and neuropile in both tested ganglia.

Authors report a case of a 52-year-old woman after struma ovarii with chronic lymphocytic inflammation excision. Finally thyroxin treatment was started and patient's hypothyroidism symptoms diminished.Struma ovarii is a type of mature teratoma in which thyroid tissue forms the main component. In most cases struma ovarii is composed of normal thyroid tissue while lymphocytic thyroiditis in struma ovarii occurs very rarely. The authors report a case of a 52-year-old woman after ovarian tumor excision. In histopatholgical examination struma ovarii with chronic lymphocytic inflammation was diagnosed. Additional studies revealed a typical ultrasonographic picture of Hashimoto disease in the thyroid gland and an increased concentration of thyroglobulin antibodies. A final diagnosis of Hashimoto disease was confirmed. Initially, thyroid gland function was normal but 11 months after surgery, supplementation therapy with thyroxin was administered. In this case, an early diagnosis of Hashimoto disease resulted from excision of struma ovarii with chronic lymphocytic inflammation. It induced early thyroxin treatment and allowed to reduce hypothyroidism symptoms.

Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

User interfaces for geospatial information are the tools by which users interact with and explore that information. The provision of appropriate interface tools for exploiting the potential of cont...

Febrile seizures affect 2–4% of all children (Berg et al., 2013) and have a strong genetic component. (Eckhaus et al., 2013) Mutations in three main genes SCN1A, SCN1B , GABRG2 (Escayg et al., 2000; Wallace et al., 1998; Wallace et al., 2001) have been described to cause febrile seizures with or without epilepsy. In the present study, we identified mutations in the gene STX1B encoding syntaxin-1B (Sudhof, 2013) which are associated with both febrile seizures and epilepsy. Syntaxin-1B plays an important role at the synapse as it is involved in the composition of the SNARE complex which mediates vesicle fusion at the membrane. The protein has two important domains. One is the so called H abc , which is located at the N-terminus. The second important domain is the SNARE domain at the C-terminus of the protein. Both domains are crucial for folding and binding in the SNARE complex in which, SNAP25 and synaptobrevin are also involved (Zhou et al., 2013). The identification of STX1B mutations was done by a combination of a linkage analysis and whole-exome/genome sequencing in two independent large pedigrees (Lerche et al., 2001; Weber et al., 2008). That approach revealed co-segregating STX1B mutations predicting an early truncation or an in-frame insertion/deletion which were located in the H abc and probably and most likely lead to an early truncation of the protein. Subsequently, we screened a cohort of 449 familial or sporadic cases and identified three additional nonsense or missense mutations in STX1B . One of the detected mutations even occurred de novo . These three mutations are located in the SNARE domain of the protein. Furthermore, a de novo microdeletion encompassing STX1B was identified by an array comparative genomic hybridization (CGH). To investigate the functional consequences at the protein level, we used an in vivo zebrafish model. To simulate the truncated state of the protein we established a stx1b knockdown. By field potential analyses of zebrafish larvae we were able to record seizure-like behavior and epileptiform discharges. Furthermore, we observed that increased temperature led to more frequent and longer discharges in the knockdown larvae. Beside the truncating mutations we also investigated one of the missense mutations. For this approach we chose the mutation which showed least genetic evidence. However, we also observed a decrease of epileptiform activity and discharges. We were further able to rescue the phenotype by wildtype syntaxin-1B. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes and give further evidence for epilepsy to be a "synaptopathy".

Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore the functional relevance of CHD2 haploinsufficiency in an in vivo model system, we knocked down chd2 in zebrafish by using targeted morpholino antisense oligomers. chd2-knockdown larvae exhibited altered locomotor activity, and the epileptic nature of this seizure-like behavior was confirmed by field-potential recordings that revealed epileptiform discharges similar to seizures in affected persons. Both altered locomotor activity and epileptiform discharges were absent in appropriate control larvae. Our study provides evidence that de novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures.

Hyperhomocysteinaemia is an independent risk factor for premature atherosclerotic vascular disease and venous thrombosis. Hypothyroidism is associated with mild hyperhomocysteinaemia. The aim of the present study was to assess plasma total homocysteine (tHcy) and its determinants (folate, cobalamin) in hyperthyroid patients before and after treatment.Thirty hyperthyroid and thirty healthy premenopausal women were studied. The hyperthyroid patients were investigated in the untreated state and again after restoration of euthyroidism. The levels of homocysteine, folate, cobalamin, and thyroid stimulating hormone (TSH), free thyroxine (fT(4)), free triiodothyronine (fT(3)), and renal function were measured before and after treatment.In hyperthyroidism, tHcy was lower than in the control group. The serum level of folate was higher and serum cobalamin was lower in the hyperthyroid state. Following antithyroid drug therapy, tHcy significantly increased and folate decreased. The level of cobalamin remained unchanged. Univariate analysis in the hyperthyroid group indicated that tHcy significantly negatively correlated only with fT(3).Lower homocysteine levels in hyperthyroid state can be explained by the influence of thyroid hormone. High level of folate is only partially responsible for these changes.

The electronic atlas is a new form of cartographic presentation and can be defined as an atlas developed for use primarily on electronic media. The electronic atlas is one product of an Electronic Mapping System (EMS), which is a system for the development and/or the use of electronic maps. This paper considers the major characteristics of electronic atlases and electronic mapping systems. A brief review of the development of electronic atlases is followed by a detailed description of their characteristics using the Electronic Atlas of Canada as an example. -from Authors

The Internet provides increasing opportunities for accessing information and on-line services. The government of Canada is restructuring its services to take advantage of this medium. While web-based mapping has been a reality for several years, production of maps for people with special needs poses new challenges, as additional accessibility requirements have to be met. This chapter focuses on web-based tactile and audio-tactile maps for blind and visually impaired users developed within the Mapping for the Visually Impaired project carried out at the Mapping Services Branch in collaboration with other government departments, such as Industry Canada and Transport Canada, conducted within the Canadian Government On-Line initiative (GOL). The GOL — Persons with Disabilities Online — portal involves partnerships among several departments to implement websites specifically tailored to provide information and services for people with special needs, their families, caregivers and service providers. The Mapping for the Visually Impaired (MVI) website is an integral part of this broader initiative providing tactile maps for education, mobility training, transportation and tourism. Moreover, the Web-4-All project carried out by Industry Canada in cooperation with the University of Toronto will further facilitate the development of new interfaces and innovative ways of sharing spatial information, to facilitate learning and improve mobility for blind and visually impaired people. This chapter will discuss users’ needs, present types of maps, which have been incorporated into the Mapping for the Visually Impaired website, and elaborate on theoretical and technical issues when producing and distributing tactile and audio-tactile maps on the Internet.

Bone Hematopoietic Stem Cell Transplantation (HSCT) following high-dose chemo- and radiotherapy became treatment of choice in various numbers of hematological and hereditary or acquired immune disorders. Protocols preparing to allogenic transplantation have a few aims: eradication of neoplastic disease, suppression of defense system of recipient (reduction of transplant rejection), preparation of bone marrow microenvironment to implantation donor's cells. Chemotherapy is combined with acute side effects as nausea, vomiting, diarrhea, hair loss, mucositis, and hemorrhagic cystitis. Late toxic effects also appear, it require prolonged observation and care. Among them most common is dysfunction of thyroid and gonads in adults and growth inhibition in children. The aim of this study was prospective evaluation of thyroid function in adults with autologous and allogeneic BMT or HSCT following myeloablative chemotherapy.23 patients (16 females and 7 males) treated in Department of Hematology and Transplantology Medical University of Gdańsk were included. Average age was 34.3 years with range from 17-50 years. Each patient had endocrinological interview, physical examination of thyroid, TSH level assessment and ultrasonographic thyroid volume measurement before HSCT Identical control examinations were performed in third and twenty month after transplantation. TSH level and thyroid volume were tested for significant differences before and after transplantation using paired t-tests. A P-value of0.05 was considered statistically significant.12 months after HSCT following myeloablative chemotherapy we noted on average decrease in volume of thyroid from 17,5 ml to 13.5 ml (females to 9.7 ml). This difference was statistically significant with p = 0.002. Also 12 months after the procedure progressive rise in TSH level was noted from 2.0 mU/l to 3.2 mU/l. Nevertheless this tendency was not statistically significant with p = 0.08.We suggest control of TSH, fT4 level and thyroid ultrasound examination at least twice--before and 12 months after transplantation. Myeloablative chemotherapy before HSCT may cause early (after 3 months) hypothyroidism--it may last one year after procedure. In case of high TSH level we suggest individually adapted L-thyroxine replacement therapy.

Clinically silent adrenal masses (incidentaloma) are incidentally discovered lesions when noninvasive imaging methods (ultrasonography--USG, computer tomography--CT, magnetic resonance imaging--MRI) are performed for the reason other than known or suspected adrenal disease. Most of studies report the prevalence of adrenal incidentaloma range between 1 and 10% in radiological series.Between 1993 and 03.2004 we observed 198 patients with incidentalomas of adrenal glands (144 females--72.7% and 54 males--27.3%).After endocrinological evaluation, 164 patients were qualified for surgery. In 119 (72.5%) cases open adrenalectomy was performed, and in 45 (27.5%) laparoscopic adrenalectomy was done. Adrenocortical adenoma was diagnosed in 54.9%, adrenal hyperplasia in 8.5%, adrenal carcinoma in 6.7%, pheochromocytoma in 12.9% (in 3.1% of all cases malignant pheochromocytoma was diagnosed), in 4.9% others malignant tumors (primary or metastatic), in 4.9% adrenal cysts and in 7.1% other rare adrenal pathologies were found.All malignancies were found in tumors with the diameter over 3 cm. In tumors with diameter over 6 cm malignant cases were found in 70.8%.

A 50-year-old woman, who presented with progressive androgenization, central obesity and severe hypertension, was initially suspected to have an adrenal virilizing tumor. Her serum testosterone level was in the male range (9.3-11.6 ng/ml) and was not suppressed with dexamethasone. Although no pathological abdominal or pelvic mass was detected, total hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination revealed a theca-cell tumor of the right ovary. Postoperatively the testosterone level returned to normal and the patient had regression of virilism. Our case illustrates that a virilizing ovarian tumor can be small and elude imaging studies, but may be detected by means of well-considered clinical management.

Decision makers need access to heterogeneous, interdependent and meaningful information to obtain an understanding of the geospatial conditions for informed decision making and analysis of various options for situation assessment. Hypermedia concepts and visualization can facilitate the integration of large amounts of multi-source datasets and provide customized representations of filtered georeferenced data to enable the decision makers to explore and understand various spatial solutions without requiring advanced knowledge of geospatial technologies and systems. A specific application of decision making is the collaborative geospatial decision making, which is based on real-time data sharing, coordinated data access and synchronization between multiple geographically dispersed participants. The roles of hypermedia, visualization and geocollaboration are explored and case studies are presented to support decisions for city planning via interactive mapping, urban planning scenarios, and understanding urban sprawl over time. Two systems are discussed. The in-house developed Dynamic Visualization System (DVS), which dynamically hyperlinks to web map servers, and the GeoConference, a commercial real-time Internet-based geospatial collaborative conference system.

Safety concerns and economic, environmental, scientific, and sustainable development issues require the monitoring and assessment of the various changes that occur in the geographical space. For knowledgebased decision-making and management approaches, spatial change can be better understood through representations, which enhance the cognitive eye-brain process. Work conducted in multiple programs of the Earth Sciences Sector (ESS), Natural Resources Canada is presented. This work aims to develop effective visualization of time-dependent spatial information to assist in the communication and understanding of the various geographic phenomena. Initially, elements and approaches for the effective cartographic representation of spatial changes are discussed. Subsequently, principles for the visualization of change and various modes for change representation are given along with the current web-based technological developments and trends. The visualization concepts and techniques discussed are demonstrated using several examples.

The structure of the ovary and the type of oogenesis were determined in the earthworm Dendrobaena veneta (Oligochaeta, Haplotaxida, Lumbricidae) with histological, electron-microscopic and immunocytochemical methods. In this species the ovary is of the alimentary, nutrimentary type because it contains oocytes and the nurse cells (trophocytes). The ovarian stroma is built by somatic cells, the processes of which are connected to each other via numerous desmosomes. The somatic cells and their processes envelop the germ cells tightly and play a supportive role. Oogonia, oocytes and trophocytes are arranged in distinct zones in the ovary. Trophocytes form chains of cells, which are interconnected by intercellular bridges. Numerous microtubules are located within the latter. The oocytes are distally arranged in the ovary. Vitellogenesis involves both auto- and heterosyntheses. The results obtained were compared with the reports on oogenesis in other representatives of Annelida.

The paper presents a new approach towards large system design in distributed teams based on a workflow technology. The techniques applied introduce interoperability among design tools across computing platforms and organization borders. They result in an improved quality of wide area engineering collaboration. After a short discussion about selected aspects of the applied workflow technology from an electronic design engineers' perspective, an Internet-based distributed design process of IP components with emphasis on specific elements of microprocessor designs is introduced. As an example, we present a workflow that enables integration and interoperability of selected IP design tasks, represented as parallel and serial sets of the workflow activities. The workflows that were employed in the design process had been developed for the purpose of design task integration in the pan-European project E-Colleg. They can be effectively adopted by distributed teams working on multiple sites, multiple platforms for remote project management.

The paper concerns a configurable soft core of the 8051 /spl mu/C implemented in VHDL. The main goal of efforts undertaken during design of the core was the full compatibility with the industrial standards 80C51 and 80C52 on the instruction and timing levels. It doesn't limit flexibility of the core's architecture, which can be easily optimized according to the current design constraints. The configuration capabilities of the core are grouped in a configuration package. That approach allows for separation from the indigenous part of the core, which remains untouched by a user and can be encoded in order to hide the VHDL code. Inside the configuration package there are several constants. Assigning values to them, a user has the opportunity to determine the core's structure (types of functional modules used in the core), RAM and ROM sizes, the instruction set, number of interrupted sources, number of execution cycles for division and multiplication, etc. The core is independent of the CPU peripheral modules (e.g. timer/counters, I/O ports, UART, etc.) due to a SFR bus. Peripherals are accessed by the use of special function registers. The upper half of available addresses of the internal RAM is just reserved for them. Hence the communication between the CPU and SFRs is carried out in the same way as in the case of memory cells. The core has been proven on silicon. It was applied in the smart pressure sensor chip and an 8031-compatible /spl mu/C. The compatibility with the industrial was checked on the logic verifier, where original 80C51 and 80C52 chips were applied during tests as references.