Spexin-expressing neurons in the magnocellular nuclei of the human hypothalamus

Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel neuropeptide spexin (SPX) within the human magnocellular hypothalamus. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. For the first time we describe SPX expressing neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the human hypothalamus using immunohistochemical and fluorescent methods, key regions involved in the mechanisms of osmotic homeostasis, energy expenditure, consummatory behaviour, reproductive processes, social recognition and stress responses. The vast majority of neurons located in both examined neurosecretory nuclei show abundant SPX expression and this may indirectly implicate a potential contribution of SPX signalling to the hypothalamic physiology in the human brain. © 2020 Elsevier B.V

Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios

The mechanisms underlying hematopoietic lineage decisions remain disputed. Lineage affiliated transcription factors (TFs) with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described to be expressed in uncommitted cell populations. This has led to the assumption that lineage choice is cell-intrinsically initiated and made by stochastic switches of randomly fluctuating cross-antagonistic TFs. However, this hypothesis was developed based on RNA expression data from snapshot and/or population average analyses. Alternative models of lineage choice can therefore not be excluded. Here, we use novel reporter mouse lines and live imaging for continuous single cell long-term quantification of PU.1 and GATA1 TF protein levels. We analyse individual hematopoietic stem cells (HSCs) throughout their differentiation into megakaryocytic/erythroid (MegE) and granulocytic/monocytic (GM) lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates GM versus MegE lineage decision making. Rather, they suggest their involvement only in executing and locking down lineage choice once made. The current prevailing model on early myeloid lineage choice will thus have to be revised

Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6–12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy

Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6–12 months) subpopulation of OVA-301 phase III randomized trial

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6–12 months platinum-free interval (PFI)] is unclear

Cardiovascular development: towards biomedical applicability: Regulation of cardiomyocyte differentiation of embryonic stem cells by extracellular signalling

Investigating the signalling pathways that regulate heart development is essential if stem cells are to become an effective source of cardiomyocytes that can be used for studying cardiac physiology and pharmacology and eventually developing cell-based therapies for heart repair. Here, we briefly describe current understanding of heart development in vertebrates and review the signalling pathways thought to be involved in cardiomyogenesis in multiple species. We discuss how this might be applied to stem cells currently thought to have cardiomyogenic potential by considering the factors relevant for each differentiation step from the undifferentiated cell to nascent mesoderm, cardiac progenitors and finally a fully determined cardiomyocyte. We focus particularly on how this is being applied to human embryonic stem cells and provide recent examples from both our own work and that of others

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Aspects of the applications of composite materials in combustion engines

The paper presents the results of investigations concerning the possibilities of application of composite materials in the construction of internal combustion engines. The total mass of the engine can be reduced by allying composite materials, which have a much higher strength than hitherto applied conventional materials. Less thermal expansion allows reducing assembly clearance between the piston and cylinder. The surface topography after the process of machining of composite materials contains hollows, which act as trays for lubricant, wear products and pollution particulates. Therefore, it is possible to reduce friction, fuel consumption, level of exhaust emission and improve the durability of engine. During the investigations, the engine piston made of aluminium matrix composite has been tested. The tests were related to the influence of surface topography of the piston skirt containing Al2O3 particles on the adsorption of lubricating oil, which facilitates lubrication in small displacement test engine. Aluminium matrix composite materials have some disadvantages, too. The most important are higher finishing costs and higher wear of the other sliding element. To reduce the finishing costs of making the suitable surface, special methods for example water jet cutting, have been worked out. To reduce the wear of the other sliding element, reinforcing spherical particles without sharp edges should be applied. Covering the tribological partner-sliding surface with a composite surface layer (e.g. Cr+Al2O3) can result in a relevant reduction of its wear

Wpływ rodzaju drogi, typu i struktury wiekowej pojazdów uczestniczących w ruchu drogowym na poziom emisji spalin

The total emission level is heavily dependent on the number of vehicles. Additionally, the type of vehicles and their age structures are very important. The structure of vehicles also depends on the type of the road. The article presents the results of calculations of the pollutants emission from the road transport. Total emission was calculated with combination of the investigation results i.e. the type of vehicles and their age structures for different types of roads. The investigations have been made for different classes of roads with different types of vehicles. The traffic line has been recorded in the same length of time. On the basis of analysis of the recorded traffic line, the number and the type of vehicles have been estimated. The classification of vehicles have been made according to the level of emission i.e. passenger cars, light duty vehicles, heavy duty vehicles, busses and others, taking into consideration the age structures of vehicles. The level of total traffic emission has been calculated on the basis of results. There has been used the Copert programme methodology. The results of the calculations have been made with combination of the type of road, the speed of vehicles, the type of vehicles and their age structure, are presented.Poziom emisji zanieczyszczeń zależy przede wszystkim od liczby pojazdów poruszających się po drodze. Dodatkowo istotne są struktury rodzajowa oraz wiekowa pojazdów. Struktura pojazdów zależy natomiast w dużym stopniu od rodzaju drogi. W pracy przedstawiono wyniki obliczeń poziomu emisji wybranych składników spalin emitowanych w ruchu drogowym. Obliczenia zostały przeprowadzone z uwzględnieniem wyników badań struktur rodzajowej i wiekowej pojazdów dla różnych typów dróg. Badania strumienia pojazdów wykonano na drogach różnej kategorii, przy różnej strukturze pojazdów. Rejestrowano strumień pojazdów w określonych odcinkach czasowych. Na podstawie analizy obrazu zarejestrowanego strumienia określono liczbę i rodzaj pojazdów. Pojazdy podzielono na kategorie według poziomu emisji, tj. samochody osobowe, samochody dostawcze, ciężarowe, autobusy i inne, uwzględniając strukturę wiekową. Na podstawie uzyskanych wyników oszacowano poziom emisji szkodliwych składników spalin. Obliczenia zostały wykonane za pomocą metodyki przyjętej w programie Copert. Przedstawiono wyniki szacunkowego poziomu emisji spalin w zależności rodzaju drogi, prędkości jazdy, struktur wiekowej i rodzajowej pojazdów

Description of the level of exhaust emission from spark ignition engines for different work conditions of engine

W pracy przedstawiono metodę obliczania objętościowej ilości poszczególnych składników spalin silnika o zapłonie iskrowym. Przeprowadzono wstępne obliczenia. Wyniki porównano z rezultatami badań emisji poszczególnych składników spalin. Obiektem badań był silnik o zapłonie iskrowym z turbodoładowaniem.This paper presents the method of calculation the amount of different ingredients of exhaust emission from spark ignition engines. The tentative calculations were made. Results of the calculations were compared with the results of the research, which were made for turbo-charged spark ignition engine