Chemoresistance of glioblastoma cancer stem cells - much more complex than expected

Glioblastomas (GBM) are a paradigm for the investigation of cancer stem cells (CSC) in solid malignancies. The susceptibility of GBM CSC to standard chemotherapeutic drugs is controversial as the existing literature presents conflicting experimental data. Here, we summarize the experimental evidence on the resistance of GBM CSC to alkylating chemotherapeutic agents, with a special focus on temozolomide (TMZ). The data suggests that CSC are neither resistant nor susceptible to chemotherapy per se. Detoxifying proteins such as O6-methylguanine-DNA-methyltransferase (MGMT) confer a strong intrinsic resistance to CSC in all studies. Extrinsic factors may also contribute to the resistance of CSC to TMZ. These may include TMZ concentrations in the brain parenchyma, TMZ dosing schemes, hypoxic microenvironments, niche factors, and the re-acquisition of stem cell properties by non-stem cells. Thus, the interaction of CSC and chemotherapy is more complex than may be expected and it is necessary to consider these factors in order to overcome chemoresistance in the patient

Spectacular Role of Electron Correlation in the Hyperfine Interactions in 2D5/2^2D_{5/2} States in Alkaline Earth Ions

The low-lying n(=3,4,5)d $^2D_{5/2}$ states alkaline earth ions are of vital importance in a number of different physical applications. The hyperfine structure constants of these states are characterized by unusually strong electron correlation effects. Relativistic coupled-cluster theory has been employed to carry out {\it ab initio} calculations of these constants. The role of the all order core-polarization effects was found to be decisive in obtaining good agreement of the results of our calculations with accurate measurements. The present work is an apt demonstration of the power of the coupled-cluster method to cope with strongly interacting configurations.Comment: Submitted to Physical Review Letters, 3 figures and 5 table

OpenGM: A C++ Library for Discrete Graphical Models

OpenGM is a C++ template library for defining discrete graphical models and performing inference on these models, using a wide range of state-of-the-art algorithms. No restrictions are imposed on the factor graph to allow for higher-order factors and arbitrary neighborhood structures. Large models with repetitive structure are handled efficiently because (i) functions that occur repeatedly need to be stored only once, and (ii) distinct functions can be implemented differently, using different encodings alongside each other in the same model. Several parametric functions (e.g. metrics), sparse and dense value tables are provided and so is an interface for custom C++ code. Algorithms are separated by design from the representation of graphical models and are easily exchangeable. OpenGM, its algorithms, HDF5 file format and command line tools are modular and extendible

Conditions of the Development of Logistic Centers in Poland in the Context of European States Experiences

The article is, for the most part, the aftermath of his own examinations carried out in years 2007-2010 and concerning logistic centers development conditioning.Artykuł jest w znacznej mierze pokłosiem badań własnych autora przeprowadzonych w latach: 2007-2010 dotyczących uwarunkowań rozwoju centrów logistycznych

The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy

Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on the regulated activation of the Atg1-kinase complex. However, the underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components in vitro. We find that on assembly from its cytoplasmic subcomplexes, the Atg1-kinase complex becomes activated, enabling it to recruit and tether Atg9-vesicles. The scaffolding protein Atg17 targets the Atg1-kinase complex to autophagic membranes by specifically recognizing the membrane protein Atg9. This interaction is inhibited by the two regulatory subunits Atg31 and Atg29. Engagement of the Atg1-Atg13 subcomplex restores the Atg9-binding and membrane-tethering activity of Atg17. Our data help to unravel the mechanism that controls Atg17-mediated tethering of Atg9-vesicles, providing the molecular basis to understand initiation of autophagosome-biogenesis

Improving the Socio-emotional Well-being of the Older Generation through the Implementation of Territorial Marketing

This article is based on the analysis of the possibility of using Berkman's conceptual model of mechanism of social networks influence on human health to improve the well-being of the older generation in Russia. The emphasis is put on the development of social contacts of older people through the implementation of territorial marketing. Objective and subjective indicators of well-being of older people are directly related to the characteristics and peculiarities of the territory where they live and carry out their activities (city, region, country). In this context, marketing of territory can be regarded as an activity aimed at creating and maintaining comfortable living conditions of different age groups, taking into considerations their characteristics. Special attention is paid to the social and emotional mechanisms of social support, social influence, social inclusion, social participation, interpersonal contacts and access to resources and benefits the territory of older generation. Specificity of older adults segmentation of the region (the city) is defined. The importance of active cooperation of various age groups identified in the process of territorial segmentation of the market is particularly stressed, in terms of improving the lives of older adults

Osteoarthritis, cerebrovascular dysfunction and the common denominator of inflammation: a narrative review

© 2018 The Author(s) Objective: Population-based cohort studies suggest an association between osteoarthritis (OA) and cerebrovascular disease, yet the mechanisms underlying vascular comorbidities in OA remain unclear. The purpose of this narrative review is to discuss the literature examining inflammation in OA with a focus on physiological mechanisms, and whether overlapping mechanisms exist in cerebrovascular dysfunction. Method: A literature search was conducted in PubMed using combinations of search terms: osteoarthritis, cerebrovascular (disease/dysfunction/risk), cardiovascular (disease/dysfunction/risk), aging/ageing, inflammation, inflammatory mediators, cytokine, c-reactive protein, interleukin, advanced glycation end-products, metabolic syndrome, reactive oxidative species, cognitive impairment, (vascular-related) dementia, small cerebral vessel disease, endothelial function, blood–brain barrier, gender/sex, hypertension, peripheral vascular health, and physical activity. Reference lists of identified articles were also researched manually. Results: Overlapping inflammatory factors that may contribute to onset and progression of both OA and cerebrovascular dysfunction are presented. We describe oxidative mechanisms involving pro-inflammatory cytokines and oxidative species, advanced glycation end-products, sex hormones, microvascular dysfunction and osteoprotegerin, and their specific roles in potentially contributing to OA and cerebrovascular dysfunction. Conclusion: Synthesis of the current literature suggests future investigations may benefit from directly testing cerebrovascular hemodynamics and cognitive function in individuals with or at risk of OA to elucidate common physiological mechanisms

Particle astrophysics

The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented