Diallyl trisulfide-induced prostate cancer cell death is associated with Akt/PKB dephosphorylation mediated by P-p66shc

PURPOSE: P66Shc, an isoform of adaptor proteins, is known to mediate various signals including those leading to apoptosis or cell proliferation. Previously, we have shown that diallyl trisulfide (DATS)-induced prostate cancer cell death was mediated by increased ROS formation. In this study, we investigated the role of p66Shc protein and its serine 36 phosphorylation in DATS induced decrease in prostate cancer cell viability (PC-3). METHODS: PC-3 prostate cancer cells were used in this study. Stable cell lines expressing p66ShcS36A or an empty vector have been obtained. Cell viability, concentration of ROS, changes in P-p66Shc and P-Akt and DNA damage were determined. RESULTS: We observed that DATS treatment increased p66Shc phosphorylation at serine 36. Importantly, the phosphorylation was abolished by JNK inhibitor SP600125. Cells expressing plasmid-encoded variant of p66ShcS36A showed much higher resistance to DATS-induced cells death. In addition to that, we observed that DATS-induced ROS formation was completely abolished in cells expressing the p66ShcS36A variant. Interestingly, SP600125 proved to prevent DATS-induced Akt inactivation. In order to confirm that the observed effect is related to phosphorylation of p66Shc, we performed experiments on a stable cell line expressing p66ShcS36A. In such cells, DATS-induced Akt dephosphorylation was significantly reduced. On the other hand, hydrogen peroxide induced Akt activation in PC-3 cells, which was abrogated in cells expressing p66ShcS36A. CONCLUSIONS: Our results uncover a novel signaling pathway with p66Shc being indispensable for DATS-induced inactivation of Akt due to hypophosphorylation

Geldanamycin and its derivatives as Hsp90 inhibitors

The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and its analogues 17AAG and 17DMAG. The therapeutic usage of geldanamycin has been limited due to its poor water solubility and severe hepatotoxicity. Therefore, its analogues, including 17AAG, 17DMAG, Tanespimycin and Retaspimycin hydrochloride, with improved pharmacokinetic profiles, have been developed

Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 whose activity is at least partly responsible for cancer development and drug resistance. On the other hand, geldanamycin induced upregulation of Hsp60 gene expression, and a simultaneous loss of hyperacetylated Hsp60 mitochondrial protein pool resulting in decreased viability and augmented cancer cell death. Hyperacetylation of Hsp60 seems to be associated with anticancer activity of geldanamycin. In light of the fact that mitochondrial dysfunction plays a critical role in the apoptotic signaling pathway, the presented data may support a hypothesis that Hsp60 can be another functional part of mitochondria-related acetylome being a potential target for developing novel anticancer strategies

Wyniki testów przetwarzania danych batymetrycznych uzyskanych z sondy GS+

A navigational chart is the primary source of information for the navigator. The main component that contributes significantly to the safety of navigation is the information on the depth of the area. A sonar, which uses acoustic waves is a device for bathymetric measurements and it measures the vertical distance between the head and the bottom or an object located at the bottom. For the purposes of the article, data was used from an interferometric sonar, which is a modification of a multi-beam sonar. Due to the very wide operating angle, it allows for simultaneous vertical data collection, similar to a typical multi-beam sonar, as well as horizontal data collection, much like a sidescan sonar. Bathymetric data is obtained not only on the basis of measurement of time, in which the acoustic wave reflected from the object returns to the receiving transducer, but also by measuring the difference between phases of the wave reaching the piezoelectric elements within a head. The paper presents the test result of bathymetric data processing obtained by the swath sonar GeoSwath+, which is trademark of GeoAcoustics. Data collected during the acquisition was subjected to filtration. For the purpose of the article, the authors used pre-filtered measurement data collected in the area of the Port of Szczecin. However, the filtered samples are large sets of data. Data reduction is a procedure meant to reduce the size of a data set to make it easier and more effective to analyze. This paper examines the capabilities of the GS+ software in the scope of reduced bathymetric data after filtration. The results of different settings are presented in the form of grids, which were then exported to the Surfer 10 software and subjected to detailed analysis.Mapa nawigacyjna jest głównym źródłem informacji dla nawigatora. Zasadniczym elementem, który wpływa na bezpieczeństwo nawigacji, jest informacja odnosząca się do głębokości morza. Urządzeniem do pomiarów batymetrycznych jest sonar. Mierzy pionową odległość pomiędzy przetwornikiem a dnem lub obiektem umieszczonym na dnie. Dla celów tego artykułu wykorzystano dane z sonaru interferometrycznego, który jest modyfikacją sonaru wielowiązkowego. Dzięki szerokiemu kątowi operacyjnemu pozwala on na symultaniczne zbieranie danych pionowych, podobnie jak typowy wielowiązkowy sonar, oraz danych poziomych, podobnie jak sonar boczny. Dane batymetryczne są uzyskiwane nie tylko na podstawie pomiaru czasu, lecz także poprzez mierzenie różnic fazowych pomiędzy elementami piezoelektrycznymi w przetworniku. Artykuł prezentuje przetwarzanie testowych danych batymetrycznych uzyskanych przez sonar GeoSwath+. Autorzy wykorzystali uprzednio przefiltrowane dane pomiarowe zebrane w rejonie Portu Szczecin. Ponieważ przefiltrowane próbki są dużymi zbiorami danych, poddano je redukcji, czyli procedurze zmniejszenia wielkości zbioru danych, aby łatwiej i efektywniej je analizować. Niniejszy artykuł bada możliwości sondy GS+ w zakresie zredukowanych danych batymetrycznych po filtracji. Wyniki różnych zestawień zostały zaprezentowane w formie siatek, które następnie eksportowano do programu Surfer 10 i poddawano szczegółowej analizie

Antioxidant properties of selected teas known as food supplements

Celem pracy była ocena właściwości przeciwutleniających oraz zawartości związków fenolowych naparów herbatek będących suplementami diety. Analizie poddano 15 herbatek ziołowych oraz ziołowoowocowych, które podzielono na 5 grup, przyjmując za kryterium deklarację wpływu odżywczego i fizjologicznego określoną przez producenta - wpływ na włosy i skórę, figurę, samopoczucie, odporność oraz energię ciała. Zakres badań obejmował: oznaczenie właściwości przeciwrodnikowych (test z rodnikiem DPPH), oznaczenie zawartości związków fenolowych (metoda Folina-Ciocalteu’a) oraz oznaczenie siły redukującej (metoda FRAP). Na podstawie przeprowadzonych badań stwierdzono, że napary herbatek wykazały zróżnicowane właściwości przeciwutleniające oraz zawartości związków fenolowych. Grupa herbat wpływających na odporność charakteryzowała się najwyższą aktywnością przeciwrodnikową, najwyższą siłą redukującą oraz najwyższą zawartością polifenoli ogółem. Wyniki badań ukazują dodatnią korelację między aktywnością przeciwutleniającą wyrażoną odsetkiem wygaszonego rodnika DPPH, siłą redukującą FRAP oraz zawartością związków fenolowych ogółem.The objective of the study was to assess the antioxidant properties and the content of phenolic compounds in tea infusions known as food supplements. 15 herbal and fruit - herbal teas were analyzed; the teas were sorted into 5 groups according to the assumed criterion: a producer declaration stating the nutritive and physiological effect of each tea on hair and skin, figure, wellness, immunity, and body energy. The range of research performed in order to achieve the objective of the study covered what follows: the determination of antiradical properties (test with a DPPH radical), the determination of the content of phenolic compounds (Folin-Ciocalteu method), and the determination of the ferric reducing antioxidant power (FRAP method). On the basis of the analysis conducted, it was found that the tea infusions had diverse antioxidant properties and diverse contents of phenolic compounds. The group of teas boosting the immune system was characterized by the highest antiradical activity, the highest ferric reducing antioxidant power, and the highest content of total polyphenolic compounds. The research results show a positive correlation between the antioxidant activity, expressed as DPPH radical scavenging activity, the reducing power FRAP, and the content of total phenolic compounds

Application of geodatabase dedicated for bathymetric data during the production of electronic navigational charts for inland shipping

Digital hydrographic products include the ENC Electronic Navigational Charts and the IENC Inland Electronic Navigational Charts used for inland shipping. The process of IENC production comprises data acquisition and editing. Each object belongs to a class specified in the applicable standards and possesses necessary attributes. IENC cells include, among others, data related to depths in a given water body. Contemporary bathymetric measuring systems allow for saving more and more data of increased quality. Examples of systems characterized by the ability to acquisition high density data are interferometer systems. The authors of this article used GeoSwath Plus 250 kHz sonar system to collect bathymetric data. Bathymetric data included in the IENC cell should be up to date, structured and easy to manage. A piece of software by the ESRI Company, also dedicated to creating hydrographic products, allows to do just that. The authors have used a specialized geodatabase during the IENC production, which made managing bathymetric data easier. The article describes an analysis of the geodatabase’s functionality during the production of electronic navigational chart for inland shipping

Using high-density bathymetric data for the production of precise ENC

Due to an increasing trend of replacing traditional paper navigational charts with electronic ones, requirements for the creation of new ENC have been steadily growing. One example is the precise electronic navigational chart, which is based on accurate mapping of topographic and hydrographic elements. Information about depth of the waters contained on the charts are crucial for the safety of navigation. During the production of precise navigational charts, bathymetric information acquired by a multi-beam sonar system (or swath-bathymetry interferometric system) is used. A multi-beam sonar system emits several signal beams from a single transducer in different directions, which allows to cover a hundred percent of the survey area. The authors of the article carried out an analysis of bathymetric data in terms of differences in their preparation for the production of precise ENC

Aspects of creation precise electronic navigational charts

W czasach rozwijającego się transportu wodnego, stawia się wymogi aby porty morskie i morsko-rzeczne przyjmowały coraz większe jednostki pływające. Zarządca portu musi spełnić warunek zachowania bezpiecznej głębokości dla wpływających statków, a kapitan lub pilot wprowadzający jednostkę na akwen portowy musi zapewnić bezpieczną nawigację na akwenie portu. Istotnym elementem mającym wpływ na bezpieczeństwo portu są mapy nawigacyjne. Dotychczas stosowane mapy papierowe, zostają stopniowo zastępowane przez elektroniczne mapy nawigacyjne (ang. ElectronicNavigationalCharts, ENC), które odpowiadają szczegółowo opisanym standardom przyjętym przez Międzynarodową Organizację Hydrograficzną (ang. International Hydrographic Organization, IHO).IHO w swoich publikacjach: S-57 oraz S-52 przedstawia format kodowania ENC oraz sposób prezentacji danych na ekranie. Standard S-44 opisuje wymagania dokładnościowe pomiarów batymetrycznych, które są nieodzownym elementem typowej mapy ENC. Do tworzenia map ENC wykorzystuje się dane z różnych źródeł, tj. pomiary terenowe, ortofotomapy, zdjęcia satelitarne, materiały historyczne oraz pomiary batymetryczne. Dane pozyskane z różnych źródeł cechują się zróżnicowaną dokładnością. Kartowanie linii brzegowej uzależnione jest od dokładności rastra i najczęściej wymaga weryfikacji terenowej przy użyciu przyrządów geodezyjnych lub systemu GPS/RTK. Dokładności przy wykonywaniu pomiarów batymetrycznych zależą nie tylko od użytego sprzętu hydroakustycznego, ale również urządzeń peryferyjnych systemu batymetrycznego, np. dokładności pozycjonowania głowicy echosondy Autorzy niniejszego opracowania przedstawili analizę powyższych standardów i ich zastosowanie dotworzenia precyzyjnych map nawigacyjnych ENC. W ramach opracowania przygotowano i opisano geobazę rozszerzoną o dodatkowe obiekty mapowe.Nowadays, while maritime spedition is still in big progress, the requierements for maritime harbours and sea-river ports are to carry out the larger vessels. It is the harobour manager obligation to ensure the safe depth for entering vessels and the master of the vessel or pilot, to maintain safety of navigation during maneuvering in harbour basins. Used, so far, paper maps are gradually replaced by the electronic navigational charts (ENC), which are corresponding with the standards described in detail by International Hydrographic Organization (IHO). In its publication: S-57 and S-52, the Organization shows the ENCs encoding format and presentation of data on the screen. S-44 Standard describes the bathymetric measurement accuracy. The bathymetry is the essential element of typical ENC charts. Creating the ENC chart requires data from various sources, such as terrestrial measurements, ortophotos, satellite images, historical information and bathymetric surveying. Each of these data has its own precision and therefore has a different accuracy. Mapping of the coastline depends on the accuracy of the raster and usually requires the verification on the land, with usage of surveying tools or GPS-RTK. Precision in bathymetric surveying generates a potential errors of accuracy, due to the use of the acoustic equipment and also bathymetric systems peripherals sensors, such a position from the GPS antenna. In this article, the authors are presenting an analysis of standards and their application in production of the precise navigational charts ENC. Within the framework of this study, the extended with additional mapping objects geodatabase were described and prepared

Sex and vaccination: Insights from female rats vaccinated with juvenile-specific proteases from Fasciola hepatica

Most animal research is less evidence-based for females, with the majority of studies conducted on males. Since immune responses vary between males and females, sexual dimorphism in immunity contributes, among other things, to sex-based differences post-vaccination. However, the issue of sex effects in animal vaccine research is rarely considered in vaccine study design. Previously, we have evaluated the efficacy of cathepsin L3 (FhCL3-1 and FhCL3-2) and B3 proteases (FhCB3) from juvenile Fasciola hepatica as vaccines against fasciolosis in male rats. Their administration resulted in reductions in liver fluke recovery in the range of 4763% when compared with an infection control group. Here, we investigated if the protective effect of vaccination with these proteins can also be observed for female rats. The data indicates females were not protected from F. hepatica infection when vaccinated with juvenile cathepsins. Only in the FhCL3-2 vaccinated group was a low, non-significant, reduction in worm burden observed (21%). Although liver fluke mean body lengths and wet weights were reduced in vaccinated animals when compared with the infection controls, these effects were adjuvant- not vaccine-induced, while for males changes in these parameters were related primarily to vaccination. Specific humoral responses throughout the study were evident; however, trends in antibody responses in females replicated trends observed previously for male humoral responses. Formerly, elevated levels of FhCL3-1 and FhCL3-2 specific IgG1 and IgG2a were suggested to be correlated with protection. Here, despite increased and clear responses of these antibodies, protection was not observed. Hence, in the present study the roles of IgG1 and IgG2 in liver fluke reduction are questionable. Results demonstrated in our study show that observations obtained in one sex are not always applicable to the other sex. Hopefully, the findings of the study will stimulate discussion of the issue of sex i

Intranasal delivery of a formulation containing stage-specific recombinant proteins of Fasciola hepatica cathepsin L5 and cathepsin B2 triggers an anti-fecundity effect and an adjuvant-mediated reduction in fluke burden in sheep

Fasciola hepatica infection continues to be a major problem in the agriculture sector, particularly in sheep and cattle. Cathepsin L and B proteases are major components of the excretory/secretory material of the parasite, and their roles in several important aspects of parasite invasion and survival has led to their use as targets in rational vaccine design. Previous studies in rats demonstrated that the use of stage-specific antigens, cathepsin B2 and cathepsin L5, as part of a multivalent vaccine, was able to confer significant protection against challenge. In the present study, recombinant versions of cathepsin L5 and cathepsin B2 produced in yeast were used in combination to vaccinate sheep. Intramuscular and intranasal forms of administration were applied, and sheep were subsequently challenged with 150 F. hepatica metacercariae. Intramuscular vaccination was able to induce a strong systemic antibody response against both antigens, but failed to confer significant protection. Conversely, no elevated antibody response was detected against the vaccine antigens following nasal vaccination; however, a reduction in parasite egg viability (>92%) and a statistically significant (p = 0.006), predominantly adjuvant-mediated reduction in worm burdens was observed