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1.
High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans 总被引:1,自引:0,他引:1
We compared male-reproductive-tract polypeptides of Drosophila melanogaster
and D. simulans by using two-dimensional gel electrophoresis. Approximately
64% of male-reproductive-tract polypeptides were identical between two
randomly chosen isofemale lines from these two species, compared with 83%
identity for third-instar imaginal wing-disc polypeptides. Qualitatively
similar differences were found between reproductive tracts and imaginal
discs when D. sechellia was compared with D. melanogaster and with D.
simulans. When genic polymorphism was taken into account, approximately 10%
of male- reproductive-tract polypeptides were apparently fixed for
different alleles between D. melanogaster and D. simulans; this proportion
is the same as that found for soluble enzymes by one-dimensional gel
electrophoresis. Strikingly, approximately 20% of male-reproductive- tract
polypeptides of either D. melanogaster or D. simulans had no detectable
homologue in the other species. We propose that proteins of the Drosophila
male reproductive tract may have diverged more extensively between species
than have other types of proteins and that much of this divergence may
involve large changes in levels of polypeptide expression.
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2.
Ho PP Fontoura P Platten M Sobel RA DeVoss JJ Lee LY Kidd BA Tomooka BH Capers J Agrawal A Gupta R Zernik J Yee MK Lee BJ Garren H Robinson WH Steinman L 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(9):6226-6234
Targeting pathogenic T cells with Ag-specific tolerizing DNA vaccines encoding autoantigens is a powerful and feasible therapeutic strategy for Th1-mediated autoimmune diseases. However, plasmid DNA contains abundant unmethylated CpG motifs, which induce a strong Th1 immune response. We describe here a novel approach to counteract this undesired side effect of plasmid DNA used for vaccination in Th1-mediated autoimmune diseases. In chronic relapsing experimental autoimmune encephalomyelitis (EAE), combining a myelin cocktail plus IL-4-tolerizing DNA vaccine with a suppressive GpG oligodeoxynucleotide (GpG-ODN) induced a shift of the autoreactive T cell response toward a protective Th2 cytokine pattern. Myelin microarrays demonstrate that tolerizing DNA vaccination plus GpG-ODN further decreased anti-myelin autoantibody epitope spreading and shifted the autoreactive B cell response to a protective IgG1 isotype. Moreover, the addition of GpG-ODN to tolerizing DNA vaccination therapy effectively reduced overall mean disease severity in both the chronic relapsing EAE and chronic progressive EAE mouse models. In conclusion, suppressive GpG-ODN effectively counteracted the undesired CpG-induced inflammatory effect of a tolerizing DNA vaccine in a Th1-mediated autoimmune disease by skewing both the autoaggressive T cell and B cell responses toward a protective Th2 phenotype. These results demonstrate that suppressive GpG-ODN is a simple and highly effective novel therapeutic adjuvant that will boost the efficacy of Ag-specific tolerizing DNA vaccines used for treating Th1-mediated autoimmune diseases. 相似文献
3.
Cottrell DM Capers J Salem MM DeLuca-Fradley K Croft SL Werbovetz KA 《Bioorganic & medicinal chemistry》2004,12(11):2815-2824
A series of 5-thiocyanatomethyl- and 5-alkyl-3-aryl-1,2,4-oxadiazoles were synthesized and evaluated for their activity against kinetoplastid parasites. Formation of the oxadiazole ring was accomplished through the reaction of benzamidoximes with acyl chlorides, while the thiocyanate group was inserted by reacting the appropriate 5-halomethyl oxadiazole with ammonium thiocyanate. The thiocyanate-containing compounds possessed low micromolar activity against Leishmania donovani and Trypanosoma brucei, while the 5-alkyl oxadiazoles were less active against these parasites. 3-(4-Chlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4b) displayed modest selectivity for L. donovani axenic amastigote-like parasites over J774 macrophages, PC3 prostate cancer cells, and Vero cells (6.4-fold, 3.8-fold, and 9.1-fold, respectively), while 3-(3,4-dichlorophenyl)-5-(thiocyanatomethyl)-1,2,4-oxadiazole (compound 4 h) showed 30-fold selectivity against Vero cells but was not selective against PC3 cells. In a murine model of visceral leishmaniasis, compound 4b decreased liver parasitemia caused by L. donovani by 48% when given in five daily i.v. doses at 5mg/kg and by 61% when administered orally for 5 days at 50 mg/kg. These results indicate that aromatic thiocyanates hold promise for the treatment of leishmanial infections if the selectivity of these compounds can be improved. 相似文献
4.
RS Fisher 《The Journal of general physiology》1977,69(5):571-604
When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V(O), concurrent with the observations that (a) a high resistance outer barrier R(O) accounting for approximately 75 percent or more of the transcellular resistance of control skins had been penetrated and that (b) 10(-5) M amiloride and reduced [Na] outside caused the values of V(O) to increase towards means value near -130 mV while the values of percent R(O) increased to more than 90 percent. It was of relationships were the same as the values of E(1) observed in studies of the current-voltage relationships were the same as the values of E’(1) defined as the values of voltage at the inner barrier when the V(O) of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of E(1), approximately 130 mV, represent the E(Na) of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of transepithelial voltage less than E(1) the V(O) was negative. These data can be interpreted with a simple electrical equivalent circuit of the active sodium transport pathway of the frog skin that includes the idea that the outer membrane behaves as an electrical rectifier for ion transport. 相似文献
5.
Paula H Suss Luiz Guilherme A Capriglione Fabiane Barchiki Lye Miyague Danielle Jackowski Letícia Fracaro Andressa V Schittini Alexandra C Senegaglia Carmen LK Rebelatto Márcia Olandoski Alejandro Correa Paulo RS Brofman 《Experimental biology and medicine (Maywood, N.J.)》2015,240(7):969-978
The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC. 相似文献
6.
Densities of Vibrio vulnificus in the intestines of fish from the U.S. Gulf Coast. 总被引:3,自引:4,他引:3 下载免费PDF全文
Densities of Vibrio vulnificus in the intestinal contents of various finfish, oysters, and crabs and in sediment and waters of the U.S. Gulf Coast were determined by the most probable number procedure. Species were identified by enzyme immunoassay. During the winter, densities of V. vulnificus were low, and the organism was isolated more frequently from sheepshead fish than from sediment and seawater. From April to October, V. vulnificus densities were considerably higher (2 to 5 logs) in estuarine fish than in surrounding water, sediment, or nearby oysters and crustacea. Highest densities were found in the intestinal contents of certain bottom-feeding fish (10(8)/100 g), particularly those that consume mollusks and crustaceans. Densities of V. vulnificus in fish that feed primarily on plankton and other finfish were similar to those in oysters, sediment, and crabs (10(5)/100 g). V. vulnificus was found infrequently in offshore fish. The presence of high densities of V. vulnificus in the intestines of common estuarine fish may have both ecological (growth and transport) and public health (food and wound infections) implications. 相似文献
7.
Field surveys in eastern North America confirm the naturalization of Glossostigma plants at 19 localities in four states: Connecticut, New Jersey, Pennsylvania, and Rhode Island. DNA sequence analysis of individuals from 14 sampled populations identifies these nonindigenous plants as Glossostigma cleistanthum, a species native to Australia and New Zealand. These results correct prior misidentifications of North American plants as G. diandrum. The earliest North American record of G. cleistanthum (1992) is from a Ramsar tidal wetland in Connecticut. Morphological analyses demonstrate that G. cleistanthum differs from G. diandrum by its longer leaves and ability to produce both cleistogamous and chasmogamous flowers in response to ecological conditions. Glossostigma cleistanthum has a high reproductive potential and spreads rapidly within and between both artificial and natural habitats. A survey of more than 100 lakes indicated that G. cleistanthum occurs most often in waters with high clarity and low pH, alkalinity, conductivity, and phosphorous. Because of its affinity for oligotrophic conditions, this species is a particular threat to pristine natural aquatic communities, which often contain imperiled plants. 相似文献
8.
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The
repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently
diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted
to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes
and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder
may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of
extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical
aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate
with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major
histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune
B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize
the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies
in normal individuals. 相似文献
9.
EFFECTS OF HUMAN ACTIVITIES ON STRUCTURE AND COMPOSITION OF WOODY SPECIES OF THE NOKREK BIOSPHERE RESERVE OF MEGHALAYA,NORTHEAST INDIA 下载免费PDF全文
Aims Our study was conducted in the Nokrek Biosphere Reserve (NBR) in the Garo hills districts of Meghalaya, Northeast India. Our aim was to assess the effects of human activities on plant diversity,population structure and regeneration.Methods We selected a representative 1.2 hm2 stand in both the core and buffer zones of NBR. Structure and composition were determined by randomly sampling square quadrats, population structure was assessed by determining age structure, and regeneration was assessed by measuring densities of seedling, sapling and adult trees.Important findings More woody species were recorded from the core zone than the buffer zone (87 vs. 81 species), and there were a large number of tropical, temperate, and Sino-Himalayan, Burma-Malaysian and Malayan elements, primitive families and primitive genera. The trees were distributed in three distinct strata,canopy, subcanopy and sapling. Subcanopy and sapling layers had the highest species richness (81% -88% ). Lauraceae and Euphorbiaceae were the dominant families in terms of the number of species, and a large number of families were represented by single species. Most woody species (57 % - 79 % ) were contagiously distributed and had low frequency ( < 20% ). Although stand density was high in the buffer zone, its basal area was low compared to the stand in the core zone. Low similarity and high β-diversity indicate marked differences in species composition of the stands. Shannon diversity index was high in both the stands, while Simpson dominance index was low. The diameter-class distribution for dominant species revealed that the most had a large number of young individuals in their populations. Preponderance of tree seedlings, followed by a steep decline in population density of saplings and adult trees, indicated that the seedling to sapling stage was the most critical in the life cycle of the tree populations. Most species (42 % - 48 % ) had no regeneration,25 % - 35 % had good/fair regeneration, and the rest had poor regeneration or reoccurred as immigrants. 相似文献