INTRODUCTION: Alzheimer's disease (AD) is a slowly progressing neurodegenerative brain disease with irreversible brain effects; it is the most common cause of dementia. With increasing age, the probability of suffering from AD increases. In this research, population growth of the European Union (EU) until the year 2080 and the number of patients with AD are modeled. AIM: The aim of this research is to predict the spread of AD in the EU population until year 2080 using a computer simulation. METHODS: For the simulation of the EU population and the occurrence of AD in this population, a system dynamics modeling approach has been used. System dynamics is a useful and effective method for the investigation of complex social systems. Over the past decades, its applicability has been demonstrated in a wide variety of applications. In this research, this method has been used to investigate the growth of the EU population and predict the number of patients with AD. The model has been calibrated on the population prediction data created by Eurostat. RESULTS: Based on data from Eurostat, the EU population until year 2080 has been modeled. In 2013, the population of the EU was 508 million and the number of patients with AD was 7.5 million. Based on the prediction, in 2040, the population of the EU will be 524 million and the number of patients with AD will be 13.1 million. By the year 2080, the EU population will be 520 million and the number of patients with AD will be 13.7 million. CONCLUSION: System dynamics modeling approach has been used for the prediction of the number of patients with AD in the EU population till the year 2080. These results can be used to determine the economic burden of the treatment of these patients. With different input data, the simulation can be used also for the different regions as well as for different noncontagious disease predictions.

• Publication type
• Journal Article MeSH

Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of Cox-2 mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.

• MeSH
• Programmed Cell Death 1 Receptor * MeSH
• CD8-Positive T-Lymphocytes * immunology   MeSH
• Squamous Cell Carcinoma of Head and Neck * etiology   immunology   MeSH
• Papillomavirus Infections * immunology   MeSH
• Humans MeSH
• Head and Neck Neoplasms MeSH
• Lymphocytes, Tumor-Infiltrating MeSH
• Check Tag
• Humans MeSH

The incorporation of histone H3 with an acetylated lysine 56 (H3K56ac) into the nucleosome is important for chromatin remodeling and serves as a marker of new nucleosomes during DNA replication and repair in yeast. However, in human cells, the level of H3K56ac is greatly reduced, and its role during the cell cycle is controversial. Our aim was to determine the potential of H3K56ac to regulate cell cycle progression in different human cell lines. A significant increase in the number of H3K56ac foci, but not in H3K56ac protein levels, was observed during the S and G2 phases in cancer cell lines, but was not observed in embryonic stem cell lines. Despite this increase, the H3K56ac signal was not present in late replication chromatin, and H3K56ac protein levels did not decrease after the inhibition of DNA replication. H3K56ac was not tightly associated with the chromatin and was primarily localized to active chromatin regions. Our results support the role of H3K56ac in transcriptionally active chromatin areas but do not confirm H3K56ac as a marker of newly synthetized nucleosomes in DNA replication.

• MeSH
• Cell Cycle genetics   physiology   MeSH
• Chromatin metabolism   MeSH
• G2 Phase genetics   MeSH
• Histones metabolism   MeSH
• HL-60 Cells MeSH
• Mass Spectrometry MeSH
• Humans MeSH
• Nucleosomes metabolism   MeSH
• DNA Replication genetics   physiology   MeSH
• S Phase genetics   MeSH
• Saccharomyces cerevisiae Proteins genetics   metabolism   MeSH
• Saccharomyces cerevisiae genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Colonies of Saccharomyces cerevisiae laboratory strains pass through specific developmental phases when growing on solid respiratory medium. During entry into the so-called alkali phase, in which ammonia signaling is initiated, 2 prominent cell types are formed within the colonies: U cells in upper colony regions, which have a longevity phenotype and activate the expression of a large number of metabolic genes, and L cells in lower regions, which die more quickly and exhibit a starvation phenotype. Here, we performed a detailed analysis of the activities of enzymes of central carbon metabolism in lysates of both cell types and determined several fermentation end products, showing that previously reported expression differences are reflected in the different enzymatic capabilities of each cell type. Hence, U cells, despite being grown on respiratory medium, behave as fermenting cells, whereas L cells rely on respiratory metabolism and possess active gluconeogenesis. Using a spectrum of different inhibitors, we showed that glycolysis is essential for the formation, and particularly, the survival of U cells. We also showed that β-1,3-glucans that are released from the cell walls of L cells are the most likely source of carbohydrates for U cells.

• MeSH
• beta-Glucans metabolism   MeSH
• Cell Wall metabolism   MeSH
• Time Factors MeSH
• Phenotype MeSH
• Fermentation * drug effects   MeSH
• Genotype MeSH
• Glycolysis * drug effects   MeSH
• Enzyme Inhibitors pharmacology   MeSH
• Culture Media chemistry   metabolism   MeSH
• Microbial Viability MeSH
• Microbiological Techniques methods   MeSH
• Colony Count, Microbial MeSH
• Saccharomyces cerevisiae Proteins genetics   metabolism   MeSH
• Saccharomyces cerevisiae drug effects   enzymology   genetics   growth & development   MeSH
• Serial Passage MeSH
• Substrate Specificity MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The role of abscisic acid (ABA) during early development was investigated in tomato seedlings. The endogenous content of ABA in particular organs was analyzed in seedlings grown in the dark and under blue light. Our results showed that in dark-grown seedlings, the ABA accumulation was maximal in the cotyledons and elongation zone of hypocotyl, whereas under blue-light, the ABA content was distinctly reduced. Our data are consistent with the conclusion that ABA promotes the growth of etiolated seedlings and the results suggest that ABA plays an inhibitory role in de-etiolation and photomorphogenesis in tomato.

• MeSH
• Etiolation * MeSH
• Hypocotyl growth & development   MeSH
• Cotyledon growth & development   MeSH
• Abscisic Acid metabolism   MeSH
• Seedlings growth & development   metabolism   MeSH
• Solanum lycopersicum growth & development   metabolism   MeSH
• Light * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Natural cytokinins as well as the majority of their synthetic derivatives show negative effects on root growth and development. Changes in morphology, primarily linked to the inhibition of the cell division in the meristematic zone, are manifested as thickening and shortening of the primary root and impaired lateral root branching. Rational design of cytokinin derivatives can partially overcome these drawbacks and reduce the negative effects. Using our database of cytokinin derivatives, we selected several aromatic cytokinin analogs with modifications at the N9 atom of the adenine moiety. We found that tetrahydropyranyl and tetrahydrofuranyl substitutions at the N9 atom led to enhanced acropetal transport of the modified cytokinin, and both derivatives also showed weak anticytokinin activity. Consequently, changes in the distribution of the active cytokinin pool together with gradual metabolic conversion of the modified cytokinin to its free form prevent root growth inhibition that limits cytokinin utilization in micropropagation techniques.

• MeSH
• Cytokinins chemistry   pharmacology   MeSH
• Plant Roots drug effects   MeSH
• Zea mays MeSH
• Culture Techniques * MeSH
• Plant Development drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Melatonin was found in the fresh water characeae Chara australis. The concentrations (~4 μg/g of tissue) were similar in photosynthesizing cells, independent of their position on the plant and rhizoids (roots) without chloroplasts. Exogenous melatonin, added at 10 μM to the artificial pond water, increased quantum yield of photochemistry of photosystem II by 34%. The increased efficiency appears to be due to the amount of open reaction centers of photosystem II, rather than increased efficiency of each reaction center. More open reaction centers reflect better functionality of all photosynthetic transport chain constituents. We suggest that melatonin protection against reactive oxygen species covers not only chlorophyll, but also photosynthetic proteins in general.

• MeSH
• Antioxidants metabolism   pharmacology   MeSH
• Chara drug effects   metabolism   MeSH
• Characeae MeSH
• Chlorophyll metabolism   MeSH
• Chloroplasts MeSH
• Photosynthesis * drug effects   MeSH
• Photosystem II Protein Complex metabolism   MeSH
• Melatonin metabolism   pharmacology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Light-Harvesting Protein Complexes metabolism   MeSH
• Electron Transport * drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In a recent addendum, Oren Tzfadia and Gad Galili (PSB 2014; 9:e26732) showed that several Arabidopsis exocyst subunits possess consensus Atg8-interacting motifs (AIMs), which may mediate their interaction with the autophagy-associated Atg8 protein, providing thus a mechanistic base for participation of exocyst (sub)complexes in autophagy. However, the bioinformatically identified AIMs are short peptide motifs that may occur by chance. We thus performed an exhaustive search in a large collection of plant exocyst-derived sequences from our previous bioinformatic study and found that AIMs are over-represented among exocyst subunits of all lineages examined, including moss and club moss, compared with a representative sample of the Arabidopsis proteome. This is consistent with the proposed exocyst AIMs being biologically meaningful and evolutionarily ancient. Moreover, among the numerous EXO70 paralogs, the monocot-specific EXO70F clade appears to be exempt from the general AIM enrichment, suggesting a modification of the autophagy connection in a subset of exocyst variants.

• MeSH
• Amino Acid Motifs MeSH
• Arabidopsis cytology   metabolism   MeSH
• Autophagy * MeSH
• Phylogeny MeSH
• Protein Subunits chemistry   metabolism   MeSH
• Plant Proteins chemistry   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Plant cells use sugars mainly as a source or store of energy and carbon skeletons for anabolic reactions and for osmotic regulation. The perception of sugars and their responses are rather complex including the heterotrimeric G protein pathway and a seven-transmembrane RGS molecule. Previously, we found that endocytosis of the 7TM-RGS leads to sustained activation of the G protein pathway in the genetic model Arabidopsis. Here we show that other plants possess similar endocytosis systems of the 7TM-RGS proteins. A phosphorylation site essential for the endocytosis is well conserved in land plant 7TM-RGS proteins. In addition, conifer and tobacco 7TM-RGS proteins are internalized in response to sugar. These results indicate a universal mechanism to activate G signaling by endocytosis in plant cells that have 7TM-RGS proteins.

• MeSH
• Arabidopsis drug effects   genetics   metabolism   MeSH
• Tracheophyta drug effects   genetics   metabolism   MeSH
• Endocytosis drug effects   genetics   MeSH
• Phosphorylation drug effects   genetics   MeSH
• Glucose pharmacology   MeSH
• Arabidopsis Proteins genetics   metabolism   MeSH
• RGS Proteins metabolism   MeSH
• Plant Proteins genetics   metabolism   MeSH
• Nicotiana drug effects   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Prezygotic interspecific crossability barrier in the genus Cucumis is related to the ploidy level of the species (cucumber (C. sativus), x = 7; muskmelon (C. melo) and wild Cucumis species, x = 12). Polyploidization of maternal plants helps hybridization among other Cucumis species by overcoming prezygotic genetic barriers. The main objective of this paper is to compare the results of several methods supporting interspecific crosses in cucumber without and with polyploidization (comparison between diploid (2x) and mixoploid (2x/4x) cucumber maternal plants). Mixoploid plants were obtained after in vivo and in vitro polyploidization by colchicine and oryzalin. Ploidy level was estimated by flow cytometry. Embryo rescue, in vitro pollination, and isolation of mesophyll protoplast were tested and compared. Positive effect of polyploidization was observed during all experiments presented by higher regeneration capacity of cultivated mixoploid cucumber embryos, ovules, and protoplasts. Nevertheless, the hybrid character of putative hybrid accessions obtained after cross in vivo and in vitro pollination was not confirmed.

• MeSH
• Biotechnology methods   MeSH
• Cucumis genetics   physiology   MeSH
• DNA Shuffling methods   MeSH
• Species Specificity MeSH
• Chromosome Duplication MeSH
• Hybridization, Genetic MeSH
• Pollination physiology   MeSH
• Ploidies MeSH
• Polyploidy MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH