Adaptation to different types of cognitive conflict. Are there common mechanisms?

One of the functions of cognitive control is to detect difficulties in information processing and adjust the level of performance. This article presents study on confl ict adaptation in which we investigated how detection of cognitive conflict influences behaviour on a subsequent trial. In two experiments we aimed to find out whether the adjustment can be carried out across two kinds of cognitive conflicts: between competing responses and requirements of two tasks. The modified version of the flanker task in switching paradigm was used so that participants had to switch between two tasks that shared the same stimulus set. The results showed that the two kinds of confl icts did not interact with each other. Furthermore, each conflict evoked conflict adaptation, but this adaptation did not occurred across conflicts. This suggests that conflict adaptation covers a set of mechanisms functioning uniquely in one domain

Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells

Pterostilbene, a polyphenolic compound present in grapes and other fruits, has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types. We found that pterostilbene at the IC90 concentration of 44 µM inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells. Treatment with pterostilbene resulted in a transient accumulation of cells in the G0/G1-cell cycle phase followed by the S-phase arrest. Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential, phosphatidylserine externalization and internucleosomal DNA fragmentation. Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia

Plasticity of neuropeptidergic neoplasm cells in the primary and metastatic Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous carcinoma with characteristics of neuroendocrine tumor. We performed immunohistochemical analysis to demonstrate the presence of various neuropeptides within cells of MCC resected from a 75-year old woman. The cells of primary tumor of cheek were compared with the cells of regional right submandibular metastatic tumor which was found eight months later. A double- staining IHC for the pan-neuronal marker, PGP 9.5, and selected neuropeptides in the tissue material obtained from both locations was performed. Single multipolar cells in the main mass of primary tumor stained positively for PGP 9.5 and such neuropeptides as GAL, VIP, PACAP, NPY and CGRP. Moreover, we demonstrated for the first time the presence of neuropeptides in metastatic MCC cells. In the metastatic tumor, cells showing the co-localization of PGP-9.5 and neuropeptides were more numerous, mostly of oval shape, and significantly smaller than in the primary tumor. Thus, the progression of MCC may be associated with the acquisition by its cells of new morphological and biological features

Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells

Many biologically active compounds, including macromolecules that are used as various kinds of drugs, must be delivered to the interior of cell or organelles such as mitochondria or nuclei to achieve a therapeutic effect. However, very often, lipophilic cell membrane is impermeable for these molecules. A new method in the transport of macromolecules through the cell membrane is the one based on utilizing cell-penetrating peptides (CPPs). Invented 25 years ago, CPPs are currently the subject of intensive research in many laboratories all over the world. CPPs are short compounds comprising up to 30 amino acid residues, which penetrate the cell membrane but do not cause cell damage. Additionally, CPPs can transfer hydrophilic molecules (peptides, proteins, nucleic acids) which exceed their mass, and for which the cell membrane is generally impermeable. In this review, we concentrate on the cellular uptake mechanism of CPPs and a method of conjunction of CPPs to the transported molecules. We also highlight the potential of CPPs in delivering various kinds of macromolecules into cells, including compounds of therapeutic interest

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines

Introduction. Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). Material and methods. HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Results. Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5–5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. Conclusions. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells

A Novel Biosensor for Evaluation of Apoptotic or Necrotic Effects of Nitrogen Dioxide during Acute Pancreatitis in Rat

The direct and accurate estimation of nitric dioxide levels is an extremely laborious and technically demanding procedure in the molecular diagnostics of inflammatory processes. The aim of this work is to demonstrate that a stop-flow technique utilizing a specific spectroscopic biosensor can be used for detection of nanomolar quantities of NO2 in biological milieu. The use of novel compound cis-[Cr(C2O4)(AaraNH2)(OH2)2]+ increases NO2 estimation accuracy by slowing down the rate of NO2 uptake. In this study, an animal model of pancreatitis, where nitrosative stress is induced by either 3g/kg bw or 1.5 g/kg bw dose of l-arginine, was used. Biochemical parameters and morphological characteristics of acute pancreatitis were monitored, specifically assessing pancreatic acinar cell death mode, NO2 generation and cellular glutathione level. The severity of the process correlated positively with NO2 levels in pancreatic acinar cell cytosol samples, and negatively with cellular glutathione levels

Interpersonal communication in the family. Opportunities and threats

Tematem niniejszej pracy jest komunikacja w rodzinie. Poruszona jest kwestia wpływu sposobu porozumiewania się na rozwój umiejętności interpersonalnych oraz jakość życia jednostki. W pracy przedstawione są prawidłowe oraz niewłaściwe style komunikacji w trzech podsystemach rodziny: w małżeństwie, między rodzicami i dzieckiem oraz rodzeństwem.The topic of this work is family communication. The issue of the influence of the way of communication on the development of interpersonal skills and the quality of life of an individual is raised. The work presents correct and inappropriate communication styles in three subsystems of the family: marriage, between parents and child and sibling

Sirtuins - longevity enzymes?

Białka Sir, znane też jako Sir2 czy sirtuiny (sir-two-iny), tworzą rodzinę deacetylaz NAD+-zależnych. Są to ewolucyjnie konserwowane enzymy, których występowanie stwierdzono u wszystkich zbadanych organizmów eukariotycznych i wielu prokariotycznych. Sirtuiny są zaangażowane w wiele ważnych procesów biologicznych, włączając regulację transkrypcji, naprawę DNA, utrzymywanie stabilności chromosomów. Dowiedziono, że białka z rodziny Sir2 odgrywają istotną rolę w patogenezie niektórych chorób związanych z wiekiem. Zauważono, że zwiększenie aktywności tych enzymów towarzyszy ograniczeniu kalorycznemu diety i jest niezbędnym warunkiem, aby wystąpił przedłużający życie efekt głodzenia.Sir proteins, known also as Sir2 or sirtuins (sir-two-ins), form a family of NAD+-dependent deacetylases. There are evolutionarily conserved enzymes found in all investigated eukaryotic and in many prokaryotic organisms. Sirtuins are involved in many important biological processes, including transcriptional regulation, DNA repair, the maintenance of chromosome stability. It was proved, that Sir2 family of proteins plays a critical role in pathogenesis of certain age-related diseases. It was noticed, that the increase of activity of these enzymes is associated with caloric restriction and is an essential requirement for occurance of life-extending effect of starvation

Cholesterol - friend or enemy of brain?

Udział cholesterolu w patogenezie choroby Alzheimera jest zagadnieniem jak dotąd niewyjaśnionym. Wydaje się, że jest on jednym z czynników promujących odkładanie beta-amyloidu, a tym samym - tworzenie "płytek starczych". Jednak istnieją fakty, które sugerują ochronną rolę tego sterolu w rozwoju zmian chorobowych w tym schorzeniu.Cholesterol is blamed for causing Alzheimer’s disease. Yet little is known about the relationship between Alzheimer disease and cholesterol. It has been documented that cholesterol is required for beta amyloid formation. On the other hand it has been proven that cholesterol acts as protector of brain against beta amyloid deposits

Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells

Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 µM did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents