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91.
- 1.
- The purpose of this study was to determine if humid heat acclimation improves thermoregulatory function at the level of the eccrine sweat gland. 相似文献
92.
Human beta-defensins comprise a large number of peptides that play a functional role in the innate and adaptive immune system. Recently, clusters of new beta-defensin genes with predominant expression in testicular tissue have been discovered on different chromosomes by bioinformatics. beta-Defensins share a common pattern of three disulfides that are essential for their biological effects. Here we report for the first time the chemical synthesis of the new fully disulfide-bonded beta-defensins hBD-27 and hBD-28, and compare the results with synthetic procedures to obtain the known hBD-2 and hBD-3. While hBD-27 was readily converted into a product with the desired disulfide pattern by oxidative folding, hBD-28 required a selective protective group strategy to introduce the three disulfide bonds. The established synthetic processes were applied to the synthesis of hBD-2, which, like hBD-27, was accessible by oxidative folding, whereas hBD-3 required a selective strategy comparable to hBD-28. Experimental work demonstrated that trityl, acetamidomethyl, and t-butyl are superior to other protection strategies. However, the suitable pairwise arrangement of the protective groups can be different, as shown here for hBD-3 and hBD-28. Determination of the minimum inhibitory concentration against different bacteria revealed that hBD-27, in contrast to other beta-defensins tested, has virtually no antimicrobial activity. Compared to the other peptides tested, hBD-27 showed almost no cytotoxic activity, measured by hemoglobin release of erythrocytes. This might be due to the low positive net charge, which is significantly higher for hBD-2, hBD-3, and hBD-28. 相似文献
93.
94.
Glycodelin protein and mRNA is downregulated in human first trimester abortion and partially upregulated in mole pregnancy. 总被引:1,自引:0,他引:1
Bettina Toth Karin Roth Christiane Kunert-Keil Christoph Scholz Sandra Schulze Ioannis Mylonas Klaus Friese Udo Jeschke 《The journal of histochemistry and cytochemistry》2008,56(5):477-485
Glycodelin (Gd) is a major reproductive glycoprotein and a mediator for immunomodulatory effects directed to cellular, humoral, and innate immunity. Human pregnancy depends on a diversity of physiological processes including modulation of the maternal immunosystem. We evaluated the expression of Gd protein and mRNA in first trimester decidual tissue of normal pregnancies and spontaneous abortion and hydatidiform moles. Furthermore, in vitro experiments on endometrial cancer cells to analyze the effect of human chorionic gonadotropin (hCG) on Gd regulation were performed. In decidual tissue of abortion patients, Gd expression was significantly decreased compared with normal gestation, which was confirmed by in situ hybridization. In mole pregnancy, an upregulation of Gd in the first 8 weeks of pregnancy was present. Gd is a main product of decidual tissue in the first trimester of human pregnancy. Reduced Gd expression in abortive pregnancy could lead to an increased activation of the maternal immunosystem, thus causing rejection of the developing fetus. Moreover, Gd expression in endometrial cancer cells in vitro could be stimulated by addition of hCG. Therefore, we speculate that hCG could be one of the factors regulating Gd expression because hCG is downregulated in women with abortion and upregulated in mole pregnancy. In addition, we found a positive feedback loop in Gd and hCG expression in human pregnancy. 相似文献
95.
Fok S Domachuk P Rosengarten G Krause N Braet F Eggleton BJ Soon LL 《Biophysical journal》2008,95(3):1523-1530
The extracellular availability of growth factors, hormones, chemokines, and neurotransmitters under gradient conditions is required for directional cellular responses such as migration, axonal pathfinding, and tissue patterning. These responses are, in turn, important in disease and developmental processes. This article addresses critical barriers toward devising a chemotaxis assay that is broadly applicable for different kinds of cancer cells through the design of a microfluidic chamber that produces a steep gradient of chemoattractant. Photolithography was used to create microchannels for chemoattractant delivery, flow diversion barriers/conduits, and small outlets in the form of apertures. The 1-μm apertures were made at the active surface by uncapping a thin (1.5 μm) layer of AZ1518. This process also created a vertical conduit that diverted the flow such that it occurred perpendicularly to the active, experimental surface where the gradients were measured. The other side of the vertical conduit opened to underlying 20-μm deep channels that carried microfluidic flows of tracer dyes/growth factors. Modeled data using computational fluid dynamics produced gradients that were steep along the horizontal, active surface. This simulation mirrors empirically derived gradients obtained from the flow analyses of fluorescent compounds. The open chamber contains a large buffer volume, which prevents chemoattractant saturation and permits easy cell and compound manipulation. The technique obviates the use of membranes or laminar flow that may hinder imaging, rinsing steps, cell seeding, and treatment. The utility of the chamber in the study of cell protrusion, an early step during chemotaxis, was demonstrated by growing cancer cells in the chamber, inducing a chemoattractant gradient using compressed air at 0.7 bar, and performing time-lapse microscopy. Breast cancer cells responded to the rapidly developed and stable gradient of epidermal growth factor by directing centroid positions toward the gradient and by forming a leading edge at a speed of 0.45 μm/min. 相似文献
96.
We examined the influence of riparian vegetation on macroinvertebrate community structure in streams of the Upper Thames River
watershed in southwestern Ontario. Thirty-three μ-basins (129–1458 ha) were used to identify land cover variables that influenced
stream macroinvertebrates. Micro-basins represented the entire drainage area of study streams and were similar in stream order
(first, second) and land cover (agricultural or forest; no urban). We described the structure and composition of riparian
vegetation and benthic macroinvertebrate communities at the outflow reach. The nature of the land cover was quantified for
the stream network buffer (30 m) and the whole μ-basin. The objective of this study was to measure the magnitude and nature
of the relationship between the riparian vegetation and benthic macroinvertebrate community at the outflow reach, stream network
buffer, and whole μ-basin scales. Taxon richness (including total number of Ephemeroptera, Plecoptera, and Trichoptera taxa)
and Simpson’s diversity of the macroinvertebrate community all increased with increased tree cover in the riparian zone at
the outflow reach scale. Simpson’s equitability was lower with greater agricultural land cover in the stream network buffer.
No relationship between the macroinvertebrate community and land cover was found at the whole μ-basin scale. Analysis of the
influence of land cover on stream communities within a spatial hierarchy is important for understanding the interactions of
stream ecosystems with their adjacent landscapes. 相似文献
97.
Falck S Paavilainen VO Wear MA Grossmann JG Cooper JA Lappalainen P 《The EMBO journal》2004,23(15):3010-3019
Twinfilin and capping protein (CP) are highly conserved actin-binding proteins that regulate cytoskeletal dynamics in organisms from yeast to mammals. Twinfilin binds actin monomer, while CP binds the barbed end of the actin filament. Remarkably, twinfilin and CP also bind directly to each other, but the mechanism and role of this interaction in actin dynamics are not defined. Here, we found that the binding of twinfilin to CP does not affect the binding of either protein to actin. Furthermore, site-directed mutagenesis studies revealed that the CP-binding site resides in the conserved C-terminal tail region of twinfilin. The solution structure of the twinfilin-CP complex supports these conclusions. In vivo, twinfilin's binding to both CP and actin monomer was found to be necessary for twinfilin's role in actin assembly dynamics, based on genetic studies with mutants that have defined biochemical functions. Our results support a novel model for how sequential interactions between actin monomers, twinfilin, CP, and actin filaments promote cytoskeletal dynamics. 相似文献
98.
Functional dicer is necessary for appropriate specification of radial glia during early development of mouse telencephalon 总被引:1,自引:0,他引:1
Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1-/- dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon. 相似文献
99.
Leucocyte recruitment and molecular fortification of keratinocytes triggered by streptococcal M1 protein 下载免费PDF全文
Streptococcus pyogenes of the M1 serotype is commonly associated with invasive streptococcal infections and development of streptococcal toxic shock syndrome. The M1 protein is a powerful inducer of inflammatory responses for several human cell types, but the reason why M1 protein‐related strains is over‐represented in invasive streptococcal diseases is still not understood. This study was undertaken to investigate if soluble M1 protein can aggravate the severity of streptococcal skin infections in respect to inflammation, leucocyte recruitment, and tissue remodelling as seen in patients with cellulitis and necrotizing fasciitis. We found that HaCaT cells are able to recruit activated leucocytes when encountering M1 protein. Neither the bacterial protein nor activated leucocytes caused cell damage on HaCaT cells, instead HaCaT cells responded to the bacterial virulence factor by releasing several proteins protective against bacterial infection and leucocyte responses. However, although not cytotoxic, M1 protein completely abolished wound healing abilities of HaCaT cells. Taken together, our results demonstrate that M1 protein is a critical virulence factor that can augment streptococcal skin infection suggesting that the protein is an interesting target for drug development. 相似文献
100.
Differential toxicity of TAR DNA‐binding protein 43 isoforms depends on their submitochondrial localization in neuronal cells 下载免费PDF全文
Illari Salvatori Alberto Ferri Silvia Scaricamazza Ilaria Giovannelli Alessia Serrano Simona Rossi Nadia D'Ambrosi Mauro Cozzolino Andrea Di Giulio Sandra Moreno Cristiana Valle Maria Teresa Carrì 《Journal of neurochemistry》2018,146(5):585-597