Щоденники експедиційної роботи Григорія Дем'яна (Вступна стаття та підготовка текстів Василя Сокола)

The interaction between S(-II) and ferric oxides exerts a major control for the sulphur and iron cycle and in particular for the carbon and electron flow in many aquatic systems. It is regarded to be a key reaction leading ultimately to pyrite formation, the pathways still remaining unresolved. We have studied the reaction between lepidocrocite (γ-FeOOH, 21–42 mmol L−1) and dissolved S(-II) (3–9 mmol L−1) in batch experiments at pH 7 in a glove box using TEM, XRD, Mössbauer spectroscopy, and wet chemistry extraction to explore the nanocrystalline products forming at different time steps in close contact to the lepidocrocitesurface. S(0) and acid extractable Fe(II) (Fe(II)HCl) were the main products detected by wet chemistry extraction. The reaction could be divided into three steps: a rapid (<15 min) consumption of dissolved S(-II), formationof S(0) and the build-up of an Fe(II)HCl pool. Then in the absence of dissolved S(-II) concentrations of S(0) and Fe(II)HCl increased only slightly. TEM measurements revealed the occurrence of a mackinawite rim covering the lepidocrocite crystals and being separated from the lepidocrocitesurface by an interfacial magnetite layer that can be regarded as a steady state product of the interaction between lepidocrocite and mackinawite. A significant fraction of Fe(II) was formed in excess to FeS within the first 2 h. The amount of this fraction increased with decreasing ratio between dissolved S(-II) concentration and the concentration ofsurface sites, which we attributed to a kinetic decoupling of S(-II) oxidation and Fe(II) detachment from the lepidocrocitesurface. At low ratios, S(-II) seems to transfer electrons to lepidocrocite faster then stoichiometric amounts of FeS could. After 2 days Fe(II)HCl and S(0) started to decrease resulting in pyrite formation accompanied by traces of magnetite. TEM measurements indicated that mackinawite completely dissolved and precipitation of pyrite occurred dislocated from the lepidocrocitesurface. The absence of dissolved sulphide under these conditions suggest that excess Fe(II) is involved in the formationof polysulphides which are key precursors during pyrite formation. We propose that the occurrence of excess Fe(II) is a common phenomenon particularly in low sulphide – high iron environments attributing significant reactivity to ferric (hydr)oxide

Crystal growth patterns in solid solution systems:case studies on oscillatory zoning and mineral replacement reactions

Oszillierende Zonierung und Mineralverdrängungsreaktionen sind Beispiele für Kristallwachstumsmuster in Mischkristallsystemen. Beide Themenbereiche wurden mit hochauflösender Mikroanalytik und thermodynamischer Modellierung behandelt. Oszillierend zonierte Granate der Grossular-Andradit-Reihe wurden mit der analytischen Transmissions-Elektronenmikroskopie (ATEM) untersucht und der Maßstab und die Grenzflächen in der Bedeutung für die Wachstumsdynamik diskutiert. Mit Molekularsimulationen wurden die thermodynamischen Mischungseigenschaften und die Grenzflächenstabilität berechnet und in Bezug zu den natürlichen Proben gesetzt. Mineralverdrängungsmuster metamorpher Granate eines teilweise eklogitisierten Gesteins wurden mikroanalytisch mittels ATEM untersucht und in Bezug zu Reaktionsmechanismen gesetzt. Die Volumenänderung (Porosität) bei Verdrängungsreaktionen von Mischkristallen in wässriger Lösung wird als Modell vorgestellt und auf das System KBr-KCl-H2O angewandt

GILZ-mimics as novel therapeutic agents for progressive multiple sclerosis

poster abstractMultiple sclerosis (MS), a leading cause of neurological disability is an inflammatory demyelinating disease of the central nervous system (CNS). The clinical course of MS is highly variable ranging from isolated neurologic episodes to frequently relapsing or progressive disease. Currently there are no effective treatments for progressive MS. The long-term goal of this project is to evaluate a novel therapeutic strategy for progressive MS. Under physiological conditions signaling via the transcription factor, nuclear factor-kappa B (NF-κB) and glucocorticoid (GC) stimulation pathways regulate the immuno-inflammatory responses of the CNS resident glial cells. While NF-κB induces transcriptional activation, signaling via GC receptor functions to suppress immune responses. Persistent activation of NF-κB in the glial cells precipitates neuronal degeneration and axonal loss characteristic of progressive MS. Interactome analysis between the GC and NF-κB pathways suggested a novel strategy to inhibit NF-κB. Glucocorticoid-induced leucine zipper (GILZ) is a GC inducible protein that binds p65, the functionally critical subunit of NF-κB, and prevent transactivation of pathological mediators. The sites of interaction are localized to the proline rich region of the GILZ protein and the p65 transactivation domain. A 23 residue GILZ peptide prevented nuclear translocation of p65 and suppressed disease in an animal model of MS. Structurally GILZ peptide adopted polyproline type II (PPII) helical conformation, a favorable feature for drug development. The objective of this study is to optimize the lead peptide and develop drug like analogs. Specific features of the GILZ-p65 interactions were adapted in the design of over 25 GILZ analogs such that each exhibit optimum PPII helix, bind p65 transactivation domain and potentially accommodate modified residues that enhance the binding specificity with the p65. The analogs were ranked after passing through the Lipinski filter to determine the drug like properties. The top ranked analogs will be evaluated for functional efficacy

Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema.

Background and Aims: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood. Methods: A retrospective casenote review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease. Results: A combination of penile and scrotal oedema was reported at presentation in 80% of patients; 40% of patients had associated intestinal Crohn's disease. The average time from symptom onset to diagnosis was 52.7 months. Half of cutaneous biopsies contained non-caseating granulomas and 14% contained intralymphatic granulomas. In all, 72% of patients responded to oral steroids initially but recurrence was common. Complete or partial response was achieved in 60% of patients treated with azathioprine. Three of six patients responded to anti-tumour necrosis factor [TNF] therapy. A small proportion of patients required circumcision or de-bulking surgery for more debilitating disease. Conclusions: Ano-genital granulomatosis is a rare condition that presents with genital lymphoedema, and there is frequently a protracted delay in diagnosis. There is a very strong association with intestinal Crohn's disease. Genital lymphoedema associated with gastrointestinal symptoms should prompt careful evaluation to exclude both ano-genital granulomatosis and Crohn's disease

Pitch Memory in Nonmusicians and Musicians: Revealing Functional Differences Using Transcranial Direct Current Stimulation

For music and language processing, memory for relative pitches is highly important. Functional imaging studies have shown activation of a complex neural system for pitch memory. One region that has been shown to be causally involved in the process for nonmusicians is the supramarginal gyrus (SMG). The present study aims at replicating this finding and at further examining the role of the SMG for pitch memory in musicians. Nonmusicians and musicians received cathodal transcranial direct current stimulation (tDCS) over the left SMG, right SMG, or sham stimulation, while completing a pitch recognition, pitch recall, and visual memory task. Cathodal tDCS over the left SMG led to a significant decrease in performance on both pitch memory tasks in nonmusicians. In musicians, cathodal stimulation over the left SMG had no effect, but stimulation over the right SMG impaired performance on the recognition task only. Furthermore, the results show a more pronounced deterioration effect for longer pitch sequences indicating that the SMG is involved in maintaining higher memory load. No stimulation effect was found in both groups on the visual control task. These findings provide evidence for a causal distinction of the left and right SMG function in musicians and nonmusician

Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules

This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed—HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4+ T cells stimulated by autologous monocytes induced by HBsAg

Use of Precision Medicine Molecular Profiling of Baseline Tumor Specimen May Not Benefit Outcomes in Children With Relapsed or Refractory Pediatric Sarcomas

Given the poor prognosis of pediatric patients with relapsed or refractory sarcomas, discovery and implementation of innovative approaches and tools to guide therapy are urgent needs. This retrospective pilot study evaluated the impact of relapse and refractory therapies aligned with molecular characterization of biopsies collected at the time of primary diagnosis

Role of 4-1BB Ligand in Costimulation of T Lymphocyte Growth and its Upregulation on M12 B Lymphomas by cAMP

K46J B lymphomas express a T cell costimulatory activity that is not inhibited by CTLA-4Ig, anti-B7-1, anti-B7-2, anti-intercellular adhesion molecule 1 or antibodies to heat stable antigen. In this paper we report that this costimulatory activity is mediated at least in part by 4-1BB ligand, a member of the tumor necrosis factor (TNF) gene family that binds to 4-1BB, a T cell activation antigen with homology to the TNF/nerve growth factor receptor family. A fusion protein between 4-1BB and alkaline phosphatase (4-1BB-AP) blocks T cell activation by K46J lymphomas in both an antigen-specific system and with polyclonally (anti-CD3) activated T cells. 4-1BB-AP also blocks antigen presentation by normal spleen cells. When the antigen-presenting cells express B7 molecules as well as 4-1BB ligand, we find that B7 molecules and 4-1BB-AP both contribute to T cell activation. These data suggest that 4-1BB ligand plays an important role in costimulation of IL-2 production and proliferation by T cells. The B lymphoma M12 expresses low levels of 4-1BB-L but can be induced to express higher levels by treatment of the B ceils with cAMP, which also induces B7-1 and B7-2 in these cells. Thus cAMP appears to coordinately induce several costimulatory molecules on B cells

High-resolution intravital microscopy

Cellular communication constitutes a fundamental mechanism of life, for instance by permitting transfer of information through synapses in the nervous system and by leading to activation of cells during the course of immune responses. Monitoring cell-cell interactions within living adult organisms is crucial in order to draw conclusions on their behavior with respect to the fate of cells, tissues and organs. Until now, there is no technology available that enables dynamic imaging deep within the tissue of living adult organisms at sub-cellular resolution, i.e. detection at the level of few protein molecules. Here we present a novel approach called multi-beam striped-illumination which applies for the first time the principle and advantages of structured-illumination, spatial modulation of the excitation pattern, to laser-scanning-microscopy. We use this approach in two-photon-microscopy - the most adequate optical deep-tissue imaging-technique. As compared to standard two-photon-microscopy, it achieves significant contrast enhancement and up to 3-fold improved axial resolution (optical sectioning) while photobleaching, photodamage and acquisition speed are similar. Its imaging depth is comparable to multifocal two-photon-microscopy and only slightly less than in standard single-beam two-photon-microscopy. Precisely, our studies within mouse lymph nodes demonstrated 216% improved axial and 23% improved lateral resolutions at a depth of 80 µm below the surface. Thus, we are for the first time able to visualize the dynamic interactions between B cells and immune complex deposits on follicular dendritic cells within germinal centers (GCs) of live mice. These interactions play a decisive role in the process of clonal selection, leading to affinity maturation of the humoral immune response. This novel high-resolution intravital microscopy method has a huge potential for numerous applications in neurosciences, immunology, cancer research and developmental biology. Moreover, our striped-illumination approach is able to improve the resolution of any laser-scanning-microscope, including confocal microscopes, by simply choosing an appropriate detector

Assessment on the Use of High Capacity “Sn4_{4}P3_{3}”/NHC Composite Electrodes for Sodium-Ion Batteries with Ether and Carbonate Electrolytes

This work reports the facile synthesis of a Sn–P composite combined with nitrogen doped hard carbon (NHC) obtained by ball-milling and its use as electrode material for sodium ion batteries (SIBs). The “Sn$_{4}$P$_{3}$”/NHC electrode (with nominal composition “Sn$_{4}$P$_{3}$”:NHC = 75:25 wt%) when coupled with a diglyme-based electrolyte rather than the most commonly employed carbonate-based systems, exhibits a reversible capacity of 550 mAh g$_{electrode}$$^{−1}$ at 50 mA g$^{−1}$ and 440 mAh g$_{electrode}$$^{−1}$ over 500 cycles (83% capacity retention). Morphology and solid electrolyte interphase formation of cycled “Sn$_{4}$P$_{3}$”/NHC electrodes is studied via electron microscopy and X-ray photoelectron spectroscopy. The expansion of the electrode upon sodiation (300 mAh g$_{electrode}$$^{−1}$) is only about 12–14% as determined by in situ electrochemical dilatometry, giving a reasonable explanation for the excellent cycle life despite the conversion-type storage mechanism. In situ X-ray diffraction shows that the discharge product is Na$_{15}$Sn$_{4}$. The formation of mostly amorphous Na$_{3}$P is derived from the overall (electro)chemical reactions. Upon charge the formation of Sn is observed while amorphous P is derived, which are reversibly alloying with Na in the subsequent cycles. However, the formation of Sn$_{4}$P$_{3}$ can be certainly excluded