The Expanding Family of Bone Marrow Homing Factors for Hematopoietic Stem Cells: Stromal Derived Factor 1 Is Not the Only Player in the Game

The α-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and homing of CXCR4+ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of these cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting SDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive lipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain extracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness of HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments and antimicrobial cationic peptides, such as cathelicidin/LL-37 or β2-defensin) as well as prostaglandin E2 (PGE2). Since all these factors are upregulated in BM after myeloblative conditioning for transplantation, a more complex picture of homing emerges that involves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis

Hallmarks of mechanochemistry: From nanoparticles to technology

The aim of this review article on recent developments of mechanochemistry (nowadays established as a part of chemistry) is to provide a comprehensive overview of advances achieved in the field of atomistic processes, phase transformations, simple and multicomponent nanosystems and peculiarities of mechanochemical reactions. Industrial aspects with successful penetration into fields like materials engineering, heterogeneous catalysis and extractive metallurgy are also reviewed. The hallmarks of mechanochemistry include influencing reactivity of solids by the presence of solid-state defects, interphases and relaxation phenomena, enabling processes to take place under non-equilibrium conditions, creating a well-crystallized core of nanoparticles with disordered near-surface shell regions and performing simple dry time-convenient one-step syntheses. Underlying these hallmarks are technological consequences like preparing new nanomaterials with the desired properties or producing these materials in a reproducible way with high yield and under simple and easy operating conditions. The last but not least hallmark is enabling work under environmentally friendly and essentially waste-free conditions (822 references).Slovak Grant Agency VEGA 2/0009/11, 2/0043/11Slovak Agency for Science and Development APVV VV-0189-10, VV-0528-11Russian Foundation for Basic Research 10-03-00942a, 12-03-00651aMinistry of Science and Higher education in Poland CUT/c-1/DS/KWC/2008-2012, PB1T09B02330, NN209145136, NN20914893

Studies of unicellular micro-organisms Saccharomyces cerevisiae by means of Positron Annihilation Lifetime Spectroscopy

Results of Positron Annihilation Lifetime Spectroscopy (PALS) and microscopic studies on simple microorganisms: brewing yeasts are presented. Lifetime of ortho - positronium (o-Ps) were found to change from 2.4 to 2.9 ns (longer lived component) for lyophilised and aqueous yeasts, respectively. Also hygroscopicity of yeasts in time was examined, allowing to check how water - the main component of the cell - affects PALS parameters, thus lifetime of o-Ps were found to change from 1.2 to 1.4 ns (shorter lived component) for the dried yeasts. The time sufficient to hydrate the cells was found below 10 hours. In the presence of liquid water an indication of reorganization of yeast in the molecular scale was observed. Microscopic images of the lyophilised, dried and wet yeasts with best possible resolution were obtained using Inverted Microscopy (IM) and Environmental Scanning Electron Microscopy (ESEM) methods. As a result visible changes to the surface of the cell membrane were observed in ESEM images.Comment: Nukleonika (2015

MHC class II complexes sample intermediate states along the peptide exchange pathway

The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR- detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII’s ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual’s MHC restricted immune response

Beam profile investigation of the new collimator system for the J-PET detector

Jagiellonian Positron Emission Tomograph (J-PET) is a multi-purpose detector which will be used for search for discrete symmetries violations in the decays of positronium atoms and for investigations with positronium atoms in life-sciences and medical diagnostics. In this article we present three methods for determination of the beam profile of collimated annihilation gamma quanta. Precise monitoring of this profile is essential for time and energy calibration of the J-PET detector and for the determination of the library of model signals used in the hit-time and hit-position reconstruction. We have we have shown that usage of two lead bricks with dimensions of 5x10x20 cm^3 enables to form a beam of annihilation quanta with Gaussian profile characterized by 1 mm FWHM. Determination of this characteristic is essential for designing and construction the collimator system for the 24-module J-PET prototype. Simulations of the beam profile for different collimator dimensions were performed. This allowed us to choose optimal collimation system in terms of the beam profile parameters, dimensions and weight of the collimator taking into account the design of the 24 module J-PET detector.Comment: 14 pages, 9 figure

Discriminative characteristics of marginalised novel psychoactive users: A transnational study

New psychoactive substances (NPS) continue to be considered as a major public health concern in many European countries. The study was implemented within the framework of a transnational project of six European countries (Germany, Hungary, Ireland, Netherlands, Poland, Portugal). Our aim here is to report on the distinct and differentiating characteristics of marginalised NPS users. Three subgroups of a total of 3023 adult NPS users (socially marginalised, night life, online community) were examined regarding their socio-demographic characteristics, substance use, and external motives towards NPS use. Poland and Hungary reported higher rates of NPS use in comparison to traditional controlled drugs. The external/contextual motives did not play a central role in the background of NPS use, the least important motives were alleged legality and non-detectability of these substances. Marginalised (defined as those accessing low threshold harm reduction services) users’ substance use patterns are different from the other two groups in terms of showing more intense and riskier drug use. The most important variables which contributed to be categorised as a marginalised NPS user were lower level education, being older, having an unfavourable labour market position and using drugs intravenously. Contextual motives did not play a decisive role in being categorised as a marginalised user when drug use pattern was controlled. These identified discriminative features of marginalised drug users should inform policy makers to develop and implement tailor-made interventions targeting this user group to successfully tackle the elevated public health concerns associated with NPS use

Searches for discrete symmetries violation in ortho-positronium decay using the J-PET detector

In this paper we present prospects for using the J-PET detector to search for discrete symmetries violations in a purely leptonic system of the positronium atom. We discuss tests of CP and CPT symmetries by means of ortho-positronium decays into three photons. No zero expectation values for chosen correlations between ortho-positronium spin and momentum vectors of photons would imply the existence of physics phenomena beyond the Standard Model. Previous measurements resulted in violation amplitude parameters for CP and CPT symmetries consistent with zero, with an uncertainty of about 10-3. The J-PET detector allows to determine those values with better precision thanks to a unique time and angular esolution combined with a high geometrical acceptance. Achieving the aforementioned is possible due to application of polymer scintillators instead of crystals as detectors of annihilation quanta.Comment: in Nukleonika 201