Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb

Many environmental chemicals are thought to affect brain function. It was reported that chemicals in the nasal cavity directly reach the brain through the connection between olfactory neurons and the olfactory bulb (OB). In this ‘olfactory transport,’ xenobiotics absorbed at the nasal mucosa reach the brain by bypassing some physical barriers and defenses, and thus olfactory transport is suspected to be a vulnerable mechanism of the brain against invasion threats of environmental chemicals. In this study, we focused on the neuronal toxicity of rotenone administered intranasally to mice. The results showed that the mice that were administered rotenone had attenuated olfactory functions. We also found that intranasally administered rotenone induced acute mitochondrial stress at the OB. The repeated administration of rotenone resulted in a decrease in the number of dopaminergic neurons, which are inhibitory interneurons in the OB. Taken together, our findings suggest that the inhalation of environmental toxins induces the neurodegeneration of cranial neurons through olfactory transport, and that olfactory dysfunction may be induced as an earliest symptom of neurodegeneration caused by inhaled neurotoxins.     

An anthropomorphic multimodality (CT/MRI) head phantom prototype for end-to-end tests in ion radiotherapy

With the increasing complexity of external beam therapy “end-to-end” tests are intended to cover every step from therapy planning through to follow-up in order to fulfill the higher demands on quality assurance. As magnetic resonance imaging (MRI) has become an important part of the treatment process, established phantoms such as the Alderson head cannot fully be used for those tests and novel phantoms have to be developed. Here, we present a feasibility study of a customizable multimodality head phantom. It is initially intended for ion radiotherapy but may also be used in photon therapy.As basis for the anthropomorphic head shape we have used a set of patient computed tomography (CT) images. The phantom recipient consisting of epoxy resin was produced by using a 3D printer. It includes a nasal air cavity, a cranial bone surrogate (based on dipotassium phosphate), a brain surrogate (based on agarose gel), and a surrogate for cerebrospinal fluid (based on distilled water). Furthermore, a volume filled with normoxic dosimetric gel mimicked a tumor.The entire workflow of a proton therapy could be successfully applied to the phantom. CT measurements revealed CT numbers agreeing with reference values for all surrogates in the range from 2 HU to 978 HU (120 kV). MRI showed the desired contrasts between the different phantom materials especially in T2-weighted images (except for the bone surrogate). T2-weighted readout of the polymerization gel dosimeter allowed approximate range verification.     

Retrograde TrkAIII transport from ERGIC to ER: a re-localisation mechanism for oncogenic activity

In human SH-SY5Y neuroblastoma (NB) cells, nascent immature N-glycosylated 110kDa TrkA moves rapidly from the endoplasmic reticulum (ER) to the Golgi Network (GN), where it matures into the 140kDa receptor prior to being transported to the cell surface, creating GN and cell surface pools of inactive receptor maintained below the spontaneous activation threshold by a full compliment of inhibitory domains and endogenous PTPases. In contrast, the oncogenic alternative TrkAIII splice variant is not expressed at the cell surface but re-localises to intracellular membranes, within which it exhibits spontaneous ERGIC/COPI-associated activation and oncogenic Akt signalling. In this study, we characterise the mechanism responsible for TrkAIII re-localisation. Spontaneous TrkAIII activation, facilitated by D4 IG-like domain and N-glycosylation site omission, increases spontaneous activation potential by altering intracellular trafficking, inhibiting cell surface expression and eliminating an important inhibitory domain. TrkAIII, spontaneously activated within the permissive ERGIC/COPI compartment, rather than moving in an anterograde direction to the GN exhibits retrograde transport back to the ER, where it is inactivated. This sets-up self-perpetuating TrkAIII re-cycling between the ERGIC and ER, that ensures continual accumulation above the spontaneous activation threshold of the ERGIC/COPI compartment. This is reversed by TrkA tyrosine kinase inhibitors, which promote anterograde transport of inactivated TrkAIII to the GN, resulting in GN-associated TrkAIII maturation to a 120kDa species that is degraded at the proteasome.     

Red blood cell rheology in sepsis

Changes in red blood cell (RBC) function can contribute to alterations in microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and neutrophil deformability impair the passage of these cells through the microcirculation. While the role of leukocytes has been the focus of many studies in sepsis, the role of erythrocyte rheological alterations in this syndrome has only recently been investigated. RBC rheology can be influenced by many factors, including alterations in intracellular calcium and adenosine triphosphate (ATP) concentrations, the effects of nitric oxide, a decrease in some RBC membrane components such as sialic acid, and an increase in others such as 2,3 diphosphoglycerate. Other factors include interactions with white blood cells and their products (reactive oxygen species), or the effects of temperature variations. Understanding the mechanisms of altered RBC rheology in sepsis, and the effects on blood flow and oxygen transport, may lead to improved patient management and reductions in morbidity and mortality.     

Iron uptake by rat duodenal microvillous membrane vesicles: evidence for a carrier mediated transport system

The mechanism of iron translocation from intestinal lumen to portal plasma is poorly understood. To examine these processes, uptake of Fe2+ and Fe3+ by rat duodenal microvillous membrane vesicles prepared by a Ca2+ precipitation procedure was studied. Membrane aliquots were incubated with increasing concentrations of 59FeCl3 in the presence of a one-thousand-fold molar excess of citrate or 59FeSO4 with a twenty-fold molar excess of L-ascorbic acid. After various time intervals the incubation reaction was stopped by addition of 0.1 mM FeCl3 (4 degrees C), and uptake of 59Fe was determined by a vacuum filtration assay. Initial uptake velocity of 59FeCl3 and 59FeSO4 was determined from the slope of the cumulative uptake curves, which was linear for the first 60 s. Initial uptake rates of both, 59Fe3+ and 59Fe2+ revealed an identical saturable uptake component with a Km of 19-22 nM and Vmax of 8 pmol min-1 mg protein-1. In addition, transport of Fe2+ revealed a linear unspecific uptake phase, which was predominant at high substrate concentrations. Saturable uptake of Fe2+ and Fe3+ was temperature dependent, and significantly reduced by trypsin pretreatment of the microvillous membrane vesicles, indicating the involvement of a protein in the uptake process. This suggestion was pursued by isolation of an iron binding protein from duodenal brushborder membranes. After solubilization of microvillous plasma membranes with 1% Triton X 100, affinity chromatography of the membrane protein mixture over an iron chelate gel derived from epoxy activated Sepharose and elution with 50 mM EDTA yielded a single 52,000 dalton protein. The protein co-chromatographed over an Ultro-Pac TSK G 3000SW HPLC column together with 59FeCl3 and 59FeSO4. It showed no immunologic activity to rabbit antibodies against whole rat serum or rat transferrin. Furthermore, by photoaffinity labelling technique a single iron binding protein with a molecular weight of about 52,000 dalton was identified in microvillous membranes of the rat duodenum. These data are compatible with the hypothesis that intestinal iron absorption is mediated by a specific carrier-dependent transport system.     

The Analysis of Materials Strength Used in the Construction of the Flexible Underwater Bell—Batychron

Batychron is a flexible underwater bell patented by the Gdynia Maritime University as a device used in hydro-technics engineering for underwater transport and diving while maintaining the safety of human life. This study aims to present the methods and results of strength tests and the conducted analysis of the selection of the most appropriate method of joining thermoplastic polyurethane film (TPU) and polypropylene belts for underwater use to obtain a device with a specific buoyancy force. A universal testing machine with a hydraulic drive was used for the tests. Various methods of joining polypropylene belts were tested to select the most favourable in terms of strength properties. For this purpose, two types of materials were selected: the TE324 polyester belt and the TS501_50 style belt. Various connection methods have been used: without seams; zig-zag stitch, straight cross; cross stitch, straight longitudinal; cross stitch, straight transverse, in order to select a joint with the highest strength parameters. In addition, the tensile strength of individual types of belts was tested. The methods of joining the TPU film were verified. The obtained results allowed us to determine that the strongest bond of TE324 material is a straight, longitudinal cross stitch. This is related to the load distribution in the belts tested in laboratory conditions, but also reflected in their practical application. Thanks to the results obtained, it was possible to select the optimal methods of joining (connection) and the construction of Batychron.     

Unveiling the Effect of CaF2 on the Microstructure and Transport Properties of Phosphosilicate Systems

As an effective flux, CaF₂ is beneficial in improving the fluidity of slag in the steel-making process, which is crucial for dephosphorization. To reveal the existence form and functional mechanism of CaF₂ in phosphosilicate systems, the microstructures and transport properties of CaO-SiO₂-CaF₂-P₂O₅ quaternary slag systems are investigated by molecular dynamics simulations (MD) combined with experiments. The results demonstrate that the Si-O coordination number does not vary significantly with the increasing CaF₂ content, but the P-O coordination number dramatically decreases. CaF₂ has a minor effect on the single [SiO₄] but makes the structure of the silicate system simple. On the contrary, F⁻ ions could reduce the stability of P-O bonds and promoted the transformation of [PO₄] to [PO₃F], which is beneficial for making the P element-enriched phosphate network structure more aggregated. However, the introduction of CaF₂ does not alter the tetrahedral character of the original fundamental structural unit. In addition, the results of the investigation of the transport properties show that the self-diffusion coefficients of each ion are positively correlated with CaF₂ content and arranged in the order of F⁻ > Ca²⁺ > O²⁻ ≈ P⁵⁺ > Si⁴⁺. Due to CaF₂ reducing the degree of polymerization of the whole melts, the viscosity decreases from 0.39 to 0.13 Pa·s as the CaF₂ content increases from 0% to 20%. Moreover, the viscosity of the melt shows an excellent linear dependence on the structural parameters.     

Polycrystalline PbTe:In Films on Amorphous Substrate: Structure and Physical Properties

Polycrystalline PbTe:In films on a polyimide substrate were obtained and investigated. Their structural and transport properties in a wide range of temperatures (10–300 K) were studied. The unique feature of In impurity in PbTe is the stabilization of the Fermi level (pinning effect) that allowed for the preparation polycrystalline films with the same carrier concentration. We found that heat treatment in an argon atmosphere does not change the average grain size and carrier concentration for as-grown films but greatly increases the Hall mobility and the electron mean free path. By comparing the mobility in the bulk and in the film after heat treatment, we extracted the value of the mobility that arises due to scattering at the grain boundary barriers. The ultimate goal of the present study is the development of these films in designing portable uncooled photodetectors for the mid-IR range.