bluuebunny/crossref_metadata_2025 huggingface dataset:
Cartas privadas y actitudes lingüísticas en España y América durante los siglos XVIII y XIX. Algunos problemas en el modo de acceso al objeto de estudio
Authors: Rivas Zancarrón Manuel
Published: December 2019

Together with an oral manifestation put into practice by tradition since birth, necessity drove ordinary people to develop the ability to speak with an absence of the self, the you and the communicative situation. Initially, it was the emigration to America, promoted by the miseries of a decadent homeland, which contributed to the development of a textual genre of urgency, without literary retensions, which in later years became a sign of good education on the part of those using it. With this work, we review the methodological pitfalls that are hidden when accessing this type of object. We analyse the difficulties that might be found by researchers when facing these documents from a philological point of view and from the sociolinguistic view of the attitudes of the speakers—both implicit and explicit. The concept of “discursive tradition” will act as a methodological moderator and will allow the construction of a bridge between diachronic Sociolinguistics and Language History in the recovery of oral remains from the speech of the 18th and 19th centuries in Spain and America.
Phase IIIb Safety and Efficacy of Intravenous NEPA for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients with Breast Cancer Receiving Initial and Repeat Cycles of Anthracycline and Cyclophosphamide (AC) Chemotherapy
Authors: Schwartzberg Lee , Navari Rudolph , Clark-Snow Rebecca , Arkania Ekaterine , Radyukova Irena , Patel Kamal , Voisin Daniel , Rizzi Giada , Wickham Rita , Gralla Richard J. , Aapro Matti , Roeland Eric
Published: December 2019

Background

NEPA, a combination antiemetic of a neurokinin-1 (NK1) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5-HT3RA, palonosetron] offers 5-day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion-site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, particularly fosaprepitant in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting.

Materials and Methods

This phase IIIb, multinational, randomized, double-blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30-minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only.

Results

A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment-related AEs in both groups. There were no treatment-related injection-site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0–120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles.

Conclusion

IV NEPA was highly effective and safe with no associated hypersensitivity and injection-site reactions in patients receiving AC.
Elektroeğirme Yöntemiyle Ag Katkılı Karbon Nanoliflerin Sentezi
Authors: EVCİN Atilla , ERSOY Bahri , ÇİÇEK BEZİR Nalan
Published: December 2019

Karbon nanolifler (KNL) ve karbon nanotüpler (KNT), yüksek mukavemetli, elastik modülü, termal ve elektriksel özellikleri ve nispeten düşük yoğunlukları nedeniyle gelişmiş kompozitler için çok işlevli tek boyutlu karbon nanomalzemelerini ortaya çıkarmıştır. KNL'ler, poliakrilonitril (PAN) gibi polimerden elektroeğirme yöntemiyle türetilebilir. Elektroeğirme, mikron altı aralığında çeşitli polimerik, seramik ve kompozit nanofiberlerin üretilmesi için basit ve yüksek verimli bir yöntemdir. Bu çalışmada, gümüş katkılı KNL'ler N, N-dimetilformamid (DMF) içindeki poliakrilonitril (PAN) çözeltilerinden elektroeğrilmiştir. Elektroeğirme parametreleri 25 kV voltaj, 1 mL/sa akış hızı,6 cm iğne-toplayıcı arasındaki mesafe olarak sabitlendi. Çözeltideki PAN derişimi DMF içerisinde ağırlıkça % 8 idi. Ag katkılandırılmış PAN nanolifleri, 1 saat boyunca 250 °C'de oksidasyon ile stabilize edilmiş ve H2/N2 karışımında 30 dak boyunca 1000 °C'de karbonize edilmiştir. KNL çap dağılımı ve morfolojileri taramalı elektron mikroskop analizi ve FibraQuant 1.3 yazılımı ile değerlendirilmiştir.
Sintering Properties of Slip Casted Greek Red Mud Bodies
Authors: DEMİRKOL Nermin , SAMANCI Vildan
Published: December 2019

Red mud is a solid waste residue of
the digestion of bauxite ores with caustic soda for alumina production. There
are several red mud sources in the world. The aim of this study was to identify
the sintering conditions and technological properties of slip casted Greek red
mud bodies. Chemical analysis of used greek red mud was determined by XRF. Slip
casted samples were prepared with 40 vol. % solid content and sintered at 900,
950 and 1000 °C for 2h, seperately. Sintering and technological properties were
determined by measuring density, firing shrinkage and water absorption.
Structural characterization was carried out with scanning electron microscopy
(SEM) and X-ray diffraction studies. The best density, water absorption, firing
shrinkage values were obtained with Greek red mud body sintered at 1000°C.
Artistic glaze was applied onto the Greek red mud bodies sintered at 1000°C.
Glaze-body interaction were determined.
Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism
Authors: Köse Nuri , Yıldırım Tarık , Akın Fatih , Yıldırım Seda Elçim , Altun İbrahim
Published: December 2019

Pulmonary embolism (PE) is associated with significant morbidity and mortality. New biological markers are being investigated for estimating the prognosis of PE patients. Since PE is closely associated with inflammatory status, the neutrophil-lymphocyte (NLR), platelet-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios were suggested to be useful in predicting patient outcomes. This study aimed to evaluate the prognostic role of NLR, PLR, and LMR in PE. A total of 103 PE cases from a cardiology department were included in the study. Control group consisted of 102 patients selected from outpatient clinics other than cardiology, cardiovascular surgery, and chest diseases. We retrospectively evaluated demographic and clinical characteristics, treatments, laboratory and imaging findings, and outcomes of patients. The median follow-up of PE patients was 39 months, and the 5-year overall survival probability was 73.8%. Out of 103 patients, 20 were classified as high risk PE cases (19.4%). Thrombolytic treatment was administered to 23 patients (22.3%). Systolic pulmonary arterial pressure was measured during one year, showing a significant decrease from 51.7 ± 15.7 mmHg at admission to 26.6 ± 4.0 mmHg at first year assessment. Age (OR: 1.06, p < 0.001) and NLR (OR: 1.52, p < 0.0019) were significantly associated with the disease status. The independent prognostic factors in moderate-low and low risk PE groups were NLR (HR: 1.17, p = 0.033) and LMR (HR: 1.58, p = 0.046). In moderate-high and high risk PE patients, the independent prognostic factors were age (HR: 1.07, p = 0.014) and PLR (HR: 1.01, p = 0.046). NLR, PLR, and LMR were associated with the prognosis of PE patients. The clinical severity of PE should be considered when utilizing these markers to assess patient outcomes.
Employee Relations at Asian Subsidiaries in Hungary
Authors: Sass Magdolna , Szunomár Ágnes , Gubik Andrea , Kiran Shobha , Ozsvald Éva
Published: December 2019

Asian foreign direct investment is substantial in Hungary in regional comparison. Multinationals from China, India, Japan, and Korea are important investors in the Hungarian economy. The main aim of this article is to describe how home and host country institutions and business and management culture influence the operation of the companies in question, first of all in the various areas of human resource management. In the analysis, we rely mainly on the Varieties-of-Capitalism approach, given its emphasis on the organizational and related cultural differences that result in different types of capitalisms in the world economy. The article is based on company interviews conducted with the representatives of seven Asian subsidiaries in Hungary (1–10 interviews per company) that are operational in the automotive and/or electronics industry. Our conclusion is that management and labor relations in these companies evolve under the influence and through the interaction of related home and host country business culture, thus they contain elements of both. However, we found the clear dominance of host country impacts, which has become more pronounced over time.
Isolation and Study of Abies Bark Proanthocyanidins
Authors: Levdansky Vladimir A. , Kondrasenko Alexander A. , Levdansky Alexander V.; , Lutoshkin Maxim A.
Published: December 2019

The process of proanthocyanidins isolation from abies bark by water and water-alcohol solutions containing 5, 10, 15 and 20 % ethanol was studied for the first time. The optimal conditions providing the maximum yield of proanthocyanidins were determined experimentally. It was shown that the use of 15-20 % water-alcohol solutions allows to increase the yield of proanthocyanidins from 0.33 to 0.38 %. The composition of the obtained proanthocyanidins was studied by UV, IR, and 13C NMR spectroscopy. The obtained proanthocyanidins were transformed into colored anthocyanidins in ethanol medium in the presence of hydrochloric acid. The flavonoids cyanidin and delphinidin were isolated and identified. It was established that the obtained proanthocyanidins mainly consist of procyanidin and prodelphinidin. It was shown that proanthocyanidins obtained from abies bark, in contrast to the proanthocyanidins isolated from pine bark described in the literature, contain gallic acid residues, which is typical for proanthocyanidins isolated from various types of tea
Position of the Local Government of Commune Level in the Space of Security and Public Order
Authors: Karpiuk Mirosław
Published: December 2019

The paper addresses problems of the position of the local government of the commune level in the space of security and public order. The commune pursues tasks in this area besides other public tasks and ensuring security and public order falls within the category of fundamental tasks, the fulfilment of which requires considerable effort, including financial effort. The commune as a basic unit of local government is to respond to threats most immediately and neutralise them with its own resources and means, or if this is not possible, to prevent them from spreading. This is the main objective of the commune to be pursued in this area of running public administration.
Legado de la Antigua Grecia Respecto al Saber Filosófico del Derecho
Authors: Arenas Castrillón Jarsot
Published: December 2019

La filosofía pertenece al género de las realidades primeras y más simples – universalísimas- que no admiten una definición propiamente dicha o definición esencial. Tal definición debe hacerse por el género próximo y la diferencia específica, y en ese tipo de realidades universalísimas no se da ni uno, ni otra. Por ello, la filosofía admite tan sola una definición descriptiva o descripción. Por otra parte, la pregunta ¿qué es la filosofía? es ella misma una interpretación filosófica; así, cada sistema filosófico puede valer como una respuesta a la interpretación y también a lo que filosofía representada para la vida humana.
Violencia de Género en el Marco del Conflicto Armado y el Desplazamiento Forzado
Authors: Ortiz Marimón Janis , Ramírez Ballestero Wendy M.
Published: December 2019

El presente escrito es un análisis, de los derechos que se les fueron violados a las mujeres en el marco del conflicto armado y de los factores que incidieron en la violación de estos derechos, en especial los que violaron los derechos de la integridad sexual, señalando los conceptos esenciales para entender lo influyente y representativa que fue la violencia contra la mujer en el periodo de violencia que vivió nuestro país y el desarrollo normativo, nacional e internacional como principal influencia de antes mencionado y también el desarrollo jurisprudencial que ha permeado la temática de violencia de género y violencia contra la mujer acaecida en el contexto del conflicto interno armado colombiano.
Produtividade lexical e produções lexicográficas em uma língua sinalizada
Authors: Santos Hadassa Rodrigues
Published: December 2019

Este artigo apresenta um recorte das produções lexicográficas e terminográficas da Língua Brasileira de Sinais – Libras, emergentes no contexto acadêmico brasileiro, e os principais processos morfológicos envolvidos na expansão lexical de uma língua sinalizada. Tais processos e produtos refletem a ocorrência de neologismos coletados em espaços universitários que resultou no registro dessas novas unidades sinalizadas. Este trabalho fundamenta-se em estudos que contemplam o fenômeno da produtividade lexical com ênfase nos processos neológicos verificáveis em línguas de sinais. Apresentamos os aspectos lexicais envolvidos na formação de sinais em línguas de modalidade distinta da oral, sob o viés da Morfologia Distribuída (HALLE; MARANTZ, 1993) e os produtos lexicográficos e terminográficos produzidos em Libras na última década, e a sua importância no contexto universitário brasileiro (FARIA-NASCIMENTO, 2009; CASTRO JÚNIOR, 2014; COSTA, 2012; OLIVEIRA, 2015). Os produtos e processos observados atestam que essas línguas são plenas e vivas, ampliam-se naturalmente a fim de atender a novas necessidades comunicativas e expressivas de seus sinalizantes, a exemplo de qualquer outra língua. Pretendeu-se, com este trabalho, oferecer subsídios para a compreensão da estrutura e do funcionamento de línguas de sinais e, sob perspectiva mais abrangente, de línguas naturais.
Um novo olhar sobre as sentenças com redobro em português brasileiro
Authors: Quarezemin Sandra
Published: December 2019

O objetivo principal desta pesquisa é investigar o comportamento do sujeito e do pronome resumptivo nas sentenças com redobro do sujeito em português brasileiro (PB). A partir de evidências sintáticas, semânticas e prosódicas, será possível verificar (i) se tais construções podem ser analisadas como casos de deslocamento à esquerda; (ii) se essas sentenças caracterizam o PB como uma língua tópico proeminente; (iii) se o sujeito pré-verbal se comporta como um tópico; (iv) se o sujeito tem o mesmo comportamento do objeto deslocado com retomada pronominal; (v) se o pronome resumptivo que retoma o sujeito pré-verbal nessas construções deve ser analisado como um clítico (um núcleo) ou como um pronome fraco, ocupando a posição de especificador. A hipótese deste trabalho é a de que o pronome resumptivo pode instanciar visivelmente o núcleo da projeção funcional SubjP (RIZZI, 2005), sendo a realização lexical de Subj, atrai um constituinte compatível com o traço “sujeito da predicação” (cf. CARDINALETTI, 1997, 2004).
Falando francamente: uma leitura bakhtiniana do conceito de “inglês como língua franca” no componente curricular língua inglesa da BNCC
Authors: Duboc Ana Paula Martinez
Published: December 2019

O presente artigo visa analisar o conceito de inglês como língua franca (ILF) que fundamenta o Componente Curricular Língua Inglesa da Base Nacional Comum Curricular – Ensino Fundamental (BNCC). Para tanto, inicia com a apresentação das principais definições deste conceito polêmico e polissêmico, com ênfase para as primeiras teorizações da década de 80 no âmbito das pesquisas internacionais de modo a culminar nas recentes reconceituações na produção científica brasileira, o que chamo aqui de ILF made in Brazil, evidenciando a natureza refratária, dialogizante e heteroglóssica do signo segundo Bakhtin. Após tecer considerações acerca desses conceitos, o artigo analisa a presença do conceito de ILF no Componente Curricular Língua Inglesa da BNCC, atestando a existência de um conflito epistemológico quando texto introdutório e quadros de conteúdos são confrontados, conflito posto na medida em que a natureza fluida e situada atribuída aos recentes debates sobre ILF entra em choque com a normatividade, consenso e padronização usualmente postos por um currículo nacional comum. À moda bakhtiniana, o artigo conclui em favor da não condenação desse conflito epistemológico na medida em que nele reside o jogo de sentidos e a transformação em potencial no encontro entre professor-sujeito-intérprete e ILF-enquanto-signo, de natureza refratária, dialogizante e heteroglóssica.
Uma perspectiva pragmática para o estudo dos letramentos em periferias brasileiras
Authors: Silva Daniel Do Nascimento e
Published: December 2019

Este texto apresenta as linhas gerais de uma perspectiva pragmática para a abordagem dos letramentos em periferias brasileiras. ‘Pragmático’ aqui é entendido como aquilo que produz uma série de efeitos no mundo (conforme John L. Austin e Judith Butler) e também como prática que conjuga a tríade lei do sistema, rapidez da atividade e olhar reflexivo dos atores (conforme a abordagem da prática comunicativa de William Hanks). O artigo extrai as características de uma abordagem pragmática dos letramentos de trabalhos que problematizam e politizam a relação entre oralidade e escrita e que questionam o que conta como escrita numa sociedade. Retira essas características também de pesquisas etnolinguísticas com sistemas de escrita e de inscrição pictórica em grupos ameríndios, as quais sugerem não haver grupo humano sem um sistema convencional de grafismo. Em vista disso, a abordagem pragmática dos letramentos em periferias é, em última instância, uma forma de dialogar com pessoas que em alguma medida já escrevem, embora suas práticas não sejam legitimadas como escrita.
Mobile Youth and Belonging in the Gulf: A Study of Dubai
Authors: Hashmi Sitwat Azhar
Published: December 2019

The rapid economic growth in the Gulf Cooperation Council (GCC) region has enticed flocks of expatriates from all over the world to the region in hopes of attaining a better quality of life. These expats often migrate with their spouses and children in tow bringing to light a new challenge for the Arab world: mobile youth. This research aims to find if the journey ‘home’ (repatriation) plays a role in developing these mobile children’s sense of belonging to a ‘home’, and if so, to which ‘home’. In order to do this, the research will conduct a theoretical analysis of these mobile youth born or raised within the Gulf by analysing one-on-one structured interviews through the lens of the theory of belonging, and the study of language and culture. This research concludes that in fact, mobile youth build their sense of belonging in relation to multiple ‘homes’ and not just to their ‘adopted’ or ‘parental’ home.
Borders and the Feasibility of Rebel Conflict
Authors: Hadley Lance
Published: December 2019

Contemporary spatial research on civil conflict in Sub-Saharan Africa has largely focused on border regions as spaces of limited political and economic opportunity. These studies largely adopt approaches that present borderlands as institutionally desolate regions lacking in governance, economic opportunity and political inclusion and giving rise to the feasibility of rebel conflict. While spatial analyses focus on territorially-based capabilities, such as state power projection, they typically overlook borderlands and their territorial distinctiveness with regards to rebel capabilities. This paper specifically explores the structural effects of borders on rebel capabilities and argues that Sub-Saharan Africa’s porous borders enhance the capabilities of rebels to operate in nearby territories. I empirically test this hypothesis with a zero-inflated negative binomial model and spatially disaggregated conflict events data from the Armed Conflict Location & Event Data Project dataset mapped to the PRIO-GRID 0.5-degree x 0.5-degree geographic data structure. In total, the analysis covers 14,120 georeferenced rebel conflict events in 37 countries between 1997-2019. The results provide strong evidence that territories nearer to borders are likely to experience more battle events relative to other territories, suggesting that borderlands may enable distinct conflict-related capabilities for rebels not found elsewhere. Additionally, the model also differentiates the effects that the border may have on conflict, testing the effect of rough terrain, resources, excluded groups, and towns at the border. Of the variables tested, the results suggest that territories with border towns significantly increase the capabilities of rebels to engage in conflict and suggest a more nuanced scholarly consideration of cross-border institutions that facilitate rebel conflict.
Some Consideration on the Aesthetics of the Geopolitical Wall
Authors: Ganivet Elisa
Published: December 2019

The wall object becomes the subject of the border. The artistic interpretation enlightens us about its evolution but also of the danger of a flattening of the perception. The walled solution of a boundary reveals only the tip of the iceberg of a complex geopolitical articulation. The danger of a fantasized hyperreality, became sensationalist, it can be captured by contemporary artists and inform us of the state of the so-called globalized world.
Moving Atlas (artist portfolio)
Authors: Yen Karen
Published: December 2019

Using the language of maps, I take on the role of cartographer by tracing emotions, sensations, perceptions and the unchartered realms of my imagination associated with being a person of an ever changing diaspora. Using acrylic paints, paper collage and charcoal on canvas and paper, I rearticulate the practice of mapping by drawing from the landscapes of my memory and imagination. This allows me to temporarily orient myself in this vast world while venturing beyond the boundaries of geography to examine the contradictions between the nature of our imagination and physical boundaries.
Non-homologous DNA end joining.
Authors: Pastwa Elzbieta , Błasiak Janusz
Published: December 2019

DNA double-strand breaks (DSBs) are a serious threat for the cell and when not repaired or misrepaired can result in mutations or chromosome rearrangements and eventually in cell death. Therefore, cells have evolved a number of pathways to deal with DSB including homologous recombination (HR), single-strand annealing (SSA) and non-homologous end joining (NHEJ). In mammals DSBs are primarily repaired by NHEJ and HR, while HR repair dominates in yeast, but this depends also on the phase of the cell cycle. NHEJ functions in all kinds of cells, from bacteria to man, and depends on the structure of DSB termini. In this process two DNA ends are joined directly, usually with no sequence homology, although in the case of same polarity of the single stranded overhangs in DSBs, regions of microhomology are utilized. The usage of microhomology is common in DNA end-joining of physiological DSBs, such as at the coding ends in V(D)J (variable(diversity) joining) recombination. The main components of the NHEJ system in eukaryotes are the catalytic subunit of DNA protein kinase (DNA-PK(cs)), which is recruited by DNA Ku protein, a heterodimer of Ku70 and Ku80, as well as XRCC4 protein and DNA ligase IV. A complex of Rad50/Mre11/Xrs2, a family of Sir proteins and probably other yet unidentified proteins can be also involved in this process. NHEJ and HR may play overlapping roles in the repair of DSBs produced in the S phase of the cell cycle or at replication forks. Aside from DNA repair, NHEJ may play a role in many different processes, including the maintenance of telomeres and integration of HIV-1 genome into a host genome, as well as the insertion of pseudogenes and repetitive sequences into the genome of mammalian cells. Inhibition of NHEJ can be exploited in cancer therapy in radio-sensitizing cancer cells. Identification of all key players and fundamental mechanisms underlying NHEJ still requires further research.
Analogs of diadenosine tetraphosphate (Ap4A).
Authors: Guranowski Andrzej
Published: December 2019

This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.
PDZ domains - common players in the cell signaling.
Authors: Jeleń Filip , Oleksy Arkadiusz , Smietana Katarzyna , Otlewski Jacek
Published: December 2019

PDZ domains are ubiquitous protein interaction modules that play a key role in cellular signaling. Their binding specificity involves recognition of the carboxyl-terminus of various proteins, often belonging to receptor and ion channel families. PDZ domains also mediate more complicated molecular networks through PDZ-PDZ interactions, recognition of internal protein sequences or phosphatidylinositol moieties. The domains often form a tandem of multiple copies, but equally often such tandems or single PDZ domain occur in combination with other signaling domains (for example SH3, DH/PH, GUK, LIM, CaMK). Common occurrence of PDZ domains in Metazoans strongly suggests that their evolutionary appearance results from the complication of signaling mechanisms in multicellular organisms. Here, we focus on their structure, specificity and role in signaling pathways.
Photoreceptor guanylate cyclase variants: cGMP production under control.
Authors: Sokal Izabela , Alekseev Andrei , Palczewski Krzysztof
Published: December 2019

Changes in the Ca2+ concentration are thought to affect many processes, including signal transduction in a vast number of biological systems. However, only in few cases the molecular mechanisms by which Ca2+ mediates its action are as well understood as in phototransduction. In dark-adapted photoreceptor cells, the equilibrium level of cGMP is maintained by two opposing activities, such as phosphodiesterase (PDE) and guanylate cyclase (GC). Upon absorption of photons, rhodopsin-G-protein-mediated activation of PDE leads to a transient decrease in [cGMP] and subsequently to lowering of [Ca2+]. In turn, lower [Ca2+] increases net production of cGMP by stimulation of GC until dark conditions are re-established. This activation of GC is mediated by Ca2+ -free forms of Ca2+ -binding proteins termed GC-activating proteins (GCAPs). The last decade brought the molecular identification of GCs and GCAPs in the visual system. Recent efforts have been directed toward understanding the properties of GC at the physiological and structural levels. Here, we summarize the recent progress and present a list of topics of ongoing research.
The effect of cAMP and cGMP on the activity and substrate specificity of protein kinase A from methylotrophic yeast Pichia pastoris.
Authors: Frajnt Magdalena , Cytryńska Małgorzata , Jakubowicz Teresa
Published: December 2019

Cyclic AMP dependent protein kinase (PKA) from Pichia pastoris yeast cells was found to be activated by either cAMP or cGMP. Analogs of cAMP such as 8-chloro-cAMP and 8-bromo-cAMP were as potent as cAMP in PKA activation while N6,2'-O-dibutyryl-cAMP did not stimulate the enzyme activity. It was shown that protamine sulfate was almost equally phosphorylated in the presence of 1-2 x 10(-6)M cAMP or cGMP while other substrates such as Kemptide, ribosomal protein S6, were phosphorylated to a lower extent in the presence of cGMP. It was demonstrated that pyruvate kinase is a substrate of PKA which co-purified with the P.pastoris enzyme. Moreover, pyruvate kinase was phosphorylated by PKA in the presence of cAMP and cGMP to comparable levels.
Photodynamic effects of two water soluble porphyrins evaluated on human malignant melanoma cells in vitro.
Authors: Szurko Agnieszka , Krämer-Marek Gabriela , Wideł Maria , Ratuszna Alicja , Habdas Jan , Kuś Piotr
Published: December 2019

Two water soluble porphyrins: meso-tetra-4-N-methylpyridyl-porphyrin iodide (P1) and 5,10-di-(4-acetamidophenyl)-15,20-di-(4-N-methylpyridyl) porphyrin (P2) were synthesised and evaluated in respect to their photochemical and photophysical properties as well as biological activity. Cytotoxic and phototoxic effects were evaluated in human malignant melanoma Me45 line using clonogenic assay, cytological study of micronuclei, apoptosis and necrosis frequency and inhibition of growth of megacolonies. Both porphyrins were characterised by high UV and low visible light absorptions. Dark toxicity measured on the basis of the clonogenic assay and inhibition of megacolony growth area indicated that P1 was non-toxic at concentrations up to 50 microg/ml (42.14 microM) and P2 at concentrations up to 20 microg/ml (16.86 microM). The photodynamic effect induced by red light above 630 nm indicated that both porphyrins were able to inhibit growth of melanoma megacolonies at non-toxic concentrations. Cytologic examination showed that the predominant mode of cell death was necrosis.
A study of the influence of newly synthesized acyclonucleosides and 1,2,3,4-tetrahydroisoquinoline derivatives on deoxythymidine and deoxycytidine kinase activities in human neurofibrosarcoma and ovarian cancer.
Authors: Modrzejewska Hanna , Brzezińska Elzbieta , Dramiński Marcin , Zgit-Wróblewska Anna , Krzykowska Katarzyna , Rozpończyk Elzbieta , Greger Janusz
Published: December 2019

The influence of nine newly synthesized uracil acyclonucleosides, and 36 derivatives of 1,2,3,4-tetrahydroisoquinoline on the activity of enzymes catalysing dTMP and dGMP synthesis, on the content of dTTP and dGTP in acid soluble fraction and on the incorporation of [14C]dThd and [14C ]dGuo into DNA in tumour homogenates was studied. The influence of the compounds was studied in the cytosol from intraoperatively excised human tumours - neurofibrosarcoma and ovarian cancer. It was shown that dTMP and dGMP synthesis is inhibited competitively by 34.1+/-4.0% in both types of tumours by 0.2 mM 1-N-(3'-hydroxypropyl)-6-methyluracil (1) and 0.2 mM 1-N-(3'-hydroxypropyl)- 5,6- tetramethyleneuracil (2). The mentioned acyclonucleosides reduced the content of dTTP and dGTP in the acid soluble fraction of tumours (59.7+/-3.1% of control). 1-(4-chlorophenyl)-6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline (3), 1-(2,3-dichlorophenyl)-6,7-dihydroxy 1,2,3,4-tetrahydroisoquinoline (4) and 1-(3-methoxyphenyl)-6,7-dihydroxy 1,2,3,4-tetrahydroisoquinoline (5) at 0.2 mM concentration caused a mixed type inhibition of the synthesis of dTMP and dGMP by, on average, 33.2+/-4.4%, and reduced the content of dTTP and dGTP in the acid soluble fraction (52.6+/-3.7% of control) but were active only in the cytosol of neurofibrosarcoma. While acyclonucleosides undergo phosphorylation in the cytosol by cellular kinases, with their triphosphates being active acyclonucleoside metabolites, active 1,3,4,5-tetrahydroisoquinoline derivatives (compounds not containing a deoxyribose moiety), cannot be phosphorylated. ACN and THI derivatives which inhibit dThd and dCyd kinase activities, inhibit also the incorporation of [14C]dThd and [14C]dGuo (ACN - 50.2+/-2.7%, THI - 53.4+/-3.9% of incorporation inhibition) into tumour DNA. The obtained results point to the mechanism of uracil acyclonucleosides and 1,2,3,4-tetrahydroisoquinoline biological activity consisting in inhibiting the synthesis of DNA components.
Evidence for the presence of the Kennedy and Bremer- Greenberg pathways in Caenorhabditis elegans.
Authors: Lochnit Günter , Geyer Rudolf
Published: December 2019

Nematodes were found to synthesize phosphorylcholine-containing molecules not present in higher organisms, i.e. phosphorylcholine-substituted glycosphingolipids and (glyco)proteins. Investigations on the biosynthesis of these structures provided first biochemical evidence for the presence of the Kennedy and Bremer-Greenberg pathways in the model organism Caenorhabditis elegans.
Characterisation of Mesorhizobium huakuii cyclic beta-glucan.
Authors: Choma Adam , Komaniecka Iwona
Published: December 2019

Periplasmic and extracellular glucans of Mesorhizobium huakuii were isolated and characterized by compositional and MALDI-TOF analyses, as well as 1H and 13C NMR spectroscopy. It was shown that M. huakuii produces a cyclic beta-glucan composed entirely of nonbranched glucose chains and unmodified by nonsugar substituents. The degree of polymerisation of the cyclic oligosaccharides was estimated to be in the range from 17 to 28. The most abundant glucan molecules contained 22 glucose residues. Glucose residues within the glucan were connected by beta-(1,2) glycosidic linkages. The cyclic glucan produced by M. huakuii is quite similar to the periplasmic beta-(1,2) glucans synthesized by Agrobacterium and Sinorhizobium genera. The synthesis of beta-glucan in M. huakuii is osmoregulated and this glucan could function as an osmoprotectant in free living cells.
Signalling: basics and evolution.
Authors: Williams Robert J P
Published: December 2019

Signalling concerns the transfer of information from one body, a source, to another, a receiver in order to stimulate activity. The problem arises with the word information. It is defined as what is transferred in a sequence of things, say between people, e.g. words or signs. The idea of signalling between people is then obvious but it is not clear in cell biology. Information transfer, signalling, is required for the organisation of all cellular activity but we must ask what is transferred and how is it transmitted and received? Sometimes it is assumed that all information, i.e. organisation in a cell, is represented in the DNA sequence. This is incorrect. We shall show that the environment is a second source of information concerning material and energy. The receiving party from both DNA and the environment is general metabolism. The metabolism then signals back and sends information to both DNA and uptake from the environment. Even then energy is needed with machinery to send out all signals. This paper examines the way signalling evolved from prokaryotes through to man. In this process the environmental information received increased to the extent that finally the brain is a phenotypic as much as a genotypic organ within a whole organism. By phenotypic we mean it is organised by and interactive with information from the environment.
Endothelial NADH/NADPH-dependent enzymatic sources of superoxide production: relationship to endothelial dysfunction.
Authors: Kalinowski Leszek , Malinski Tadeusz
Published: December 2019

There is growing evidence that endothelial dysfunction, which is often defined as the decreased endothelial-derived nitric oxide (NO) bioavailability, is a crucial factor leading to vascular disease states such as hypertension, diabetes, atherosclerosis, heart failure and cigarette smoking. This is due to the fact that the lack of NO in endothelium-dependent vascular disorders contributes to impaired vascular relaxation, platelet aggregation, increased vascular smooth muscle proliferation, and enhanced leukocyte adhesion to the endothelium. During the last several years, it has become clear that reduction of NO bioavailability in the endothelium-impaired function disorders is associated with an increase in endothelial production of superoxide (O(2)(*-)). Because O(2)(*-) rapidly scavenges NO within the endothelium, a reduction of bioactive NO might occur despite an increased NO generation. Among many enzymatic systems that are capable of producing O(2)(*-), NAD(P)H oxidase and uncoupled endothelial NO synthase (eNOS) apparently are the main sources of O(2)(*-) in the endothelial cells. It seems that O(2)(*-) generated by NAD(P)H oxidase may trigger eNOS uncoupling and contribute to the endothelial balance between NO and O(2)(*-). That is maintained at diverse levels.
The contribution of uncoupling protein and ATP synthase to state 3 respiration in Acanthamoeba castellanii mitochondria.
Authors: Jarmuszkiewicz Wiesława , Czarna Małgorzata , Sluse-Goffart Claudine , Sluse Francis E
Published: December 2019

Mitochondria of the amoeba Acanthamoeba castellanii possess a free fatty acid-activated uncoupling protein (AcUCP) that mediates proton re-uptake driven by the mitochondrial proton electrochemical gradient. We show that AcUCP activity diverts energy from ATP synthesis during state 3 mitochondrial respiration in a fatty acid-dependent way. The efficiency of AcUCP in mitochondrial uncoupling increases when the state 3 respiratory rate decreases as the AcUCP contribution is constant at a given linoleic acid concentration while the ATP synthase contribution decreases with respiratory rate. Respiration sustained by this energy-dissipating process remains constant at a given linoleic acid concentration until more than 60% inhibition of state 3 respiration by n-butyl malonate is achieved. The present study supports the validity of the ADP/O method to determine the actual contributions of AcUCP (activated with various linoleic acid concentrations) and ATP synthase in state 3 respiration of A.castellanii mitochondria fully depleted of free fatty acid-activated and describes how the two contributions vary when the rate of succinate dehydrogenase is decreased by succinate uptake limitation.
DNA microarrays, a novel approach in studies of chromatin structure.
Authors: Widłak Piotr
Published: December 2019

The DNA microarray technology delivers an experimental tool that allows surveying expression of genetic information on a genome-wide scale at the level of single genes--for the new field termed functional genomics. Gene expression profiling--the primary application of DNA microarrays technology--generates monumental amounts of information concerning the functioning of genes, cells and organisms. However, the expression of genetic information is regulated by a number of factors that cannot be directly targeted by standard gene expression profiling. The genetic material of eukaryotic cells is packed into chromatin which provides the compaction and organization of DNA for replication, repair and recombination processes, and is the major epigenetic factor determining the expression of genetic information. Genomic DNA can be methylated and this modification modulates interactions with proteins which change the functional status of genes. Both chromatin structure and transcriptional activity are affected by the processes of replication, recombination and repair. Modified DNA microarray technology could be applied to genome-wide study of epigenetic factors and processes that modulate the expression of genetic information. Attempts to use DNA microarrays in studies of chromatin packing state, chromatin/DNA-binding protein distribution and DNA methylation pattern on a genome-wide scale are briefly reviewed in this paper.
Solution structure of conformationally restricted vasopressin analogues.
Authors: Trzepałka Emilia , Oleszczuk Marta , Maciejczyk Maciej , Lammek Bernard
Published: December 2019

In recent years, a massive effort has been directed towards designing potent and selective antagonists of neurohypophyseal hormones substituted at position 3. Modification of vasopressin at position 3 with 4,4'-biphenylalanine results in pharmacologically inactive analogues. Chemically, this substitution appears to vary only slightly from those previously made by us (1-Nal or 2-Nal), which afforded potent agonists of V(2) receptors. In this situation, it seemed worthwhile to study the structure of the analogues with 4,4'-biphenylalanine (BPhe) at position 3 in aqueous solution using NMR spectroscopy and total conformational analysis. This contribution is part of extensive studies aimed at understanding spatial structures of 3-substituted [Arg(8)]vasopressin analogues of different pharmacological properties. NMR data were used to calculate 3D structures for all the analogues using two methods, EDMC with the ECEPP/3 force field, and molecular dynamic with the simulated annealing (SA) algorithm. The structures obtained by the first method show a better fit between the NMR spectral evidence and the calculation for all the peptides.
Dansylated analogues of the opioid peptide [Dmt1]DALDA: in vitro activity profiles and fluorescence parameters.
Authors: Berezowska Irena , Lemieux Carole , Chung Nga N , Zelent Bogumil , Schiller Peter W
Published: December 2019

Dansylated analogues of the potent and selective micro opioid peptide agonist [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2); Dmt = 2',6'-dimethyltyrosine) were prepared either by substitution of N(beta)-dansyl-alpha,beta-diaminopropionic acid or N(epsilon)-dansyllysine for Lys(4), or by attachment of a dansyl group to the C-terminal carboxamide function via a linker. All three analogues displayed high micro agonist potency in vitro and the C-terminally dansylated one retained significant micro receptor selectivity. The three analogues showed interesting differences in their fluorescence emission maxima and quantum yields, indicating that the dansyl group in two of them was engaged in intramolecular hydrophobic interactions. These dansylated [Dmt(1)]DALDA analogues represent valuable tools for binding studies, cellular uptake and intracellular distribution studies, and tissue distribution studies.
Biological evaluation of analogues of an insect neuropeptide proctolin.
Authors: Woźnica Iwona , Szeszel-Fedorowicz Wioletta , Rosińskiand Grzegorz , Konopińska Danuta
Published: December 2019

Continuing our studies on proctolin (Arg-Tyr-Leu-Pro-Thr) we performed the synthesis and biological evaluation of 52 analogues substituted in position 2, 3, 4, and 5 of the peptide chain. The peptides were bioassayed for cardiotropic activity in vitro on Tenebrio molitor and myotropic activity on foregut of Schistocerca gregaria. Twenty analogues retained 20-80% of proctolin activity.
The mystery of reactive oxygen species derived from cell respiration.
Authors: Nohl Hans , Gille Lars , Staniek Katrin
Published: December 2019

Mitochondrial respiration is considered to provide reactive oxygen species (ROS) as byproduct of regular electron transfer. Objections were raised since results obtained with isolated mitochondria are commonly transferred to activities of mitochondria in the living cell. High electrogenic membrane potential was reported to trigger formation of mitochondrial ROS involving complex I and III. Suggested bioenergetic parameters, starting ROS formation, widely change with the isolation mode. ROS detection systems generally applied may be misleading due to possible interactions with membrane constituents or electron carriers. Avoiding these problems no conditions reported to transform mitochondrial respiration to a radical source were confirmed. However, changing the physical membrane state affected the highly susceptible interaction of the ubiquinol/bc(1) redox complex such that ROS formation became possible.
Screening of the myelin protein zero gene in patients with Charcot-Marie-Tooth disease.
Authors: Nowakowski Adam , Kochański Andrzej
Published: December 2019

The myelin protein zero gene (MPZ) coding for the most abundant protein of the peripheral myelin was shown to be mutated in Charcot-Marie-Tooth type 1B disease (CMT1B). Later on MPZ mutations have been shown in axonal type of CMT (CMT2). Recently three novel MPZ gene mutations were reported in congenital hypomyelinating neuropathy (CHN). In contrast to the previously reported studies, focused on CMT1B disease, we aimed to analyze the coding and promoter sequences of the MPZ gene in a group of patients with three CMT phenotypes i.e.: CMT1, CMT2 and CHN. Over 500 PCR products were screened by single strand conformation polymorphism analysis (SSCP) and heteroduplex analysis (HA). In one CMT2 family we founded the E56K mutation in the MPZ gene and in one CHN patient the T124K substitution was detected. In agreement with previously reported studies we conclude that MPZ gene screening should be performed for wide phenotype spectrum of CMT.
Saliva as a non-invasive material for early diagnosis
Authors: Woźniak Monika , Paluszkiewicz Czesława , Kwiatek Wojciech Maria
Published: December 2019

The proper diagnosis is a critical factor to reduce further disturbances at the early stage of the disease and plays an important role in increasing the success rate of the therapy. The traditional diagnostic tools such as biopsy or blood collection are always associated with patient’s discomfort, the possibility of infections and time-consuming procedures. This article describes the non-invasive and easily accessible saliva as a source of numerous molecular biomarkers. The salivary fluid can provide information about the pathological changes not only in the oral area but also in other parts of the body, therefore salivary tests may be promising tools for risk prediction and treatment monitoring of many disorders.
Resveratrol Attenuates Malathion Induced Damage in Some Reproductive Parameters by Decreasing Oxidative Stress and Lipid Peroxidation in Male Rats
Authors: Jalili Cyrus , Roshankhah Shiva , Salahshoor Mohammad Reza , Mohammadi Mohammad Mehdi
Published: December 2019

Objective: Malathion is the most organophosphates which capable to produce free radicals and induce disturbance on some of male reproductive parameter. Resveratrol is an herbal polyphenol and it has been beneficial antioxidant effects during short-term administration. This study was designed to evaluate the effects of Resveratrol against damage induced by Malathion to the reproductive parameter of male rats. Materials and methods: In this experimental study, 48 male rats were randomly assigned to 8 groups: normal control (saline) and Malathion control (250 mg/kg) groups; Resveratrol groups (2, 8, 20 mg/kg) and Malathion + Resveratrol (2, 8, 20 mg/kg). Treatments were administered intraperitoneally and gavage daily for 65 days. The sperm parameters, testis malondialdehyde (MDA), total antioxidant capacity (TAC), testosterone level and germinal layer height were evaluated and statistically analyzed. Results: The results displayed that the values of all parameters except MDA level (which increased) reduced significantly in the Malathion control group compared to the normal control group (p < 0.001). The Resveratrol and Resveratrol + Malathion treatments at all doses increased significantly all parameters except MDA level (which decreased) compared to the Malathion control group (p < 0.001). No significant modifications were observed in all Resveratrol groups compared to the normal control group (p > 0.05). Conclusion: Resveratrol attenuates toxic effect of Malathion on some of male reproductive parameters.