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Microscopic diffusion processes in thermotropic 5CB liquid crystals (LC) with imbedded surfactant-stabilized water microemulsions are studied using pulsed field gradient nuclear magnetic resonance (PFG NMR). The experiments are performed in a temperature range around the isotropic-nematic transition temperature of the LC. The temperature dependence of the diffusivities of the liquid crystal and surfactant molecules remains almost unchanged in the whole temperature range studied. With varying water content, the diffusivities of the surfactant molecules are found to be almost invariable, indicating that the surfactant diffusivities remain essentially unaffected by whether a microemulsion is formed or the surfactant molecules diffuse as individual species. At the same time, the formation of the microemulsion is found to be crucial for the macroscopic separation of the mixture into LC- and surfactant-rich phases. [ABSTRACT FROM AUTHOR]

Mesoporous glasses - the leaching products of phase-separated alkali borosilicate glasses - are widely used in fundamental research and practical applications. In this work, the option to control their internal mesopore structure by varying the conditions of microphase separation has been studied. Structure and transport characterization of a family of nanoporous glasses obtained under different conditions has been performed using a combination of several experimental techniques, including gas adsorption, nuclear magnetic resonance cryoporometry and diffusometry. [ABSTRACT FROM AUTHOR]

Abstract: Assessing connectivity of mesopores formed in microporous matrices is of importance for a wide range of applications. In this work we present an experimental study of the transport of n-hexane and nitrobenzene in a commercial activated carbon material containing purposefully introduced mesoporosity. The experimental results on diffusivities and activation energies for diffusion, as obtained using the pulsed field gradient technique of NMR, corroborate the information on pore architecture as resulting from adsorption isotherm measurement and unequivocally demonstrate the material-spanning continuity of the formed mesopore network, as a prerequisite for an unlimited transport enhancement in comparison with the purely microporous equivalent. [Copyright &y& Elsevier]

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for antiradiation prophylaxis and therapy in defense and medical scenarios. [ABSTRACT FROM AUTHOR]

Fluorescence lifetime imaging microscopy (FLIM) measures fluorescence decay rate at every pixel of an image. FLIM can separate probes of the same color but different fluorescence lifetimes (FL), thus it is a promising approach for multiparameter imaging. However, available GFP-like fluorescent proteins (FP) possess a narrow range of FLs (commonly, 2.3–3.5 ns) which limits their applicability for multiparameter FLIM. Here we report a new FP probe showing both subnanosecond fluorescence lifetime and exceptional fluorescence brightness (80% of EGFP). To design this probe we applied semi-rational amino acid substitutions selection. Critical positions (Thr65, Tyr145, Phe165) were altered based on previously reported effect on FL or excited state electron transfer. The resulting EGFP triple mutant, BrUSLEE (Bright Ultimately Short Lifetime Enhanced Emitter), allows for both reliable detection of the probe and recording FL signal clearly distinguishable from that of the spectrally similar commonly used GFPs. We demonstrated high performance of this probe in multiparameter FLIM experiment. We suggest that amino acid substitutions described here lead to a significant shift in radiative and non-radiative excited state processes equilibrium. [ABSTRACT FROM AUTHOR]

There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF, TNFα) is implicated in various pathophysiological processes and can be either protective, as in host defense, or deleterious, as in autoimmunity or toxic shock. To uncover the in vivo functions of TNF produced by different cell types, we generated mice with TNF ablation targeted to various leukocyte subsets. Systemic TNF in response to lipopolysaccharide was produced mainly by macrophages and neutrophils. This source of TNF was indispensable for resistance to an intracellular pathogen, Listeria, whereas T-cell-derived TNF was important for protection against high bacterial load. Additionally, both T-cell-derived TNF and macrophage-derived TNF had critical and nonredundant functions in the promotion of autoimmune hepatitis. Our data suggest that T-cell-specific TNF ablation may provide a therapeutic advantage over systemic blockade. [Copyright &y& Elsevier]

β-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine β-defensin 2 (mDF2β) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2β may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens. [ABSTRACT FROM AUTHOR]

In order to definitively ascertain the functional contribution of lymphotoxin (LT) expressed by B cells, we produced mice with the LTβ gene deleted from B cells (B-LTβ KO mice). In contrast to systemic LTβ deletion, in B-LTβ KO mice only splenic microarchitecture was affected, while lymph nodes and Peyer''s patches (PP) were normal, except for PP''s reduced size. Even though B-LTβ KO spleens retained a small number of follicular dendritic cells (FDC) which appeared to be dependent on LTβ produced by T cells, IgG responses to sheep red blood cells were markedly reduced. Thus, the organogenic function of B-LTβ is almost entirely restricted to spleen, where it supports the correct lymphoid architecture that is critical for an effective humoral immune response. [Copyright &y& Elsevier]