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41.
Nuclear DNA intron sequences are increasingly used to investigate evolutionary relationships among closely related organisms. The phylogenetic usefulness of intron sequences at higher taxonomic levels has, however, not been firmly established and very few studies have used these markers to address evolutionary questions above the family level. In addition, the mechanisms driving intron evolution are not well understood. We compared DNA sequence data derived from three presumably independently segregating introns (THY, PRKC I and MGF) across 158 mammalian species. All currently recognized extant eutherian mammalian orders were included with the exception of Cingulata, Dermoptera and Scandentia. The total aligned length of the data was 6366 base pairs (bp); after the exclusion of autapomorphic insertions, 1511 bp were analyzed. In many instances the Bayesian and parsimony analyses were complementary and gave significant posterior probability and bootstrap support (>80) for the monophyly of Afrotheria, Euarchontoglires, Laurasiatheria and Boreoeutheria. Apart from finding congruent support when using these methods, the intron data also provided several indels longer than 3 bp that support, among others, the monophyly of Afrotheria, Paenungulata, Ferae and Boreoeutheria. A quantitative analysis of insertions and deletions suggested that there was a 75% bias towards deletions. The average insertion size in the mammalian data set was 16.49 bp +/- 57.70 while the average deletion was much smaller (4.47 bp +/- 14.17). The tendency towards large insertions and small deletions is highlighted by the observation that out of a total of 17 indels larger than 100 bp, 15 were insertions. The majority of indels (>60% of all events) were 1 or 2 bp changes. Although the average overall indel substitution rate of 0.00559 per site is comparable to that previously reported for rodents and primates, individual analyses among different evolutionary lineages provide evidence for differences in the formation rate of indels among the different mammalian groups.  相似文献   
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Variola virus, the causative agent of smallpox, is a member of the poxvirus family and one of the most virulent human pathogens known. Although smallpox was eradicated almost 30 years ago, it is not understood why the mortality rates associated with the disease were high, why some patients recovered, and what constitutes an effective host response against infection. As variola virus infects only humans, our current understanding of poxvirus infections comes largely from historical clinical data from smallpox patients and from animal studies using closely related viruses such as ectromelia, myxoma and monkeypox. The outcome of an infection is determined by a complex interaction between the type of immune response mounted by the host and by evasion mechanisms that the virus has evolved to subvert it. Disease pathogenesis is also a function of both host and viral factors. Poxviruses are not only cytopathic, causing host tissue damage, but also encode an array of immunomodulatory molecules that affect the severity of disease. The ability of the host to control virus replication is therefore critical in limiting tissue damage. However, in addition to targeting virus, the immune response can inadvertently damage the host to such a degree that it causes illness and even death. There is growing evidence that many of the symptoms associated with serious poxvirus infections are a result of a 'cytokine storm' or sepsis and that this may be the underlying cause of pathology.  相似文献   
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Whole extract of rhizomes of Podophyllum hexandrum has been reported earlier by our group to render whole-body radioprotection. High-altitude P. hexandrum (HAPH) was therefore fractionated using solvents of varying polarity (non-polar to polar) and the different fractions were designated as, n-hexane (HE), chloroform (CE), alcohol (AE), hydro-alcohol (HA) and water (WE). The total polyphenolic content (mg% of quercetin) was determined spectrophotometrically, while. The major constituents present in each fraction were identified and characterized using LC-APCI/MS/MS. In vitro screening of the individual fractions, rich in polyphenols and lignans, revealed several bioactivities of direct relevance to radioprotection e.g. metal-chelation activity, antioxidant activity, DNA protection, inhibition of radiation (250 Gy) and iron/ascorbate-induced lipid peroxidation (LPO). CE exhibited maximum protection to plasmid (pBR322) DNA in the plasmid relaxation assay (68.09% of SC form retention). It also showed maximal metal chelation activity (41.59%), evaluated using 2,2-bipyridyl assay, followed by AE (31.25%), which exhibited maximum antioxidant potential (lowest absorption unit value: 0.0389± 0.00717) in the reducing power assay. AE also maximally inhibited iron/ascorbate-induced and radiation-induced LPO (99.76 and 92.249%, respectively, at 2000 g/ml) in mouse liver homogenate. Under conditions of combined stress (radiation (250 Gy) + iron/ascorbate), at a concentration of 2000 g/ml, HA exhibited higher percentage of inhibition (93.05%) of LPO activity. HA was found to be effective in significantly (p < 0.05) lowering LPO activity over a wide range of concentrations as compared to AE. The present comparative study indicated that alcoholic (AE) and hydro-alcoholic (HA) fractions are the most promising fractions, which can effectively tackle radiation-induced oxidative stress.  相似文献   
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CABYR is a highly polymorphic, sperm flagellar calcium-binding protein that is tyrosine as well as serine/threonine phosphorylated during capacitation. Six alternative splice variants of human CABYR (I-VI) have previously been identified, involving two coding regions, CR-A and CR-B, separated by an intervening stop codon. It is presently unknown if proteins encoded by the predicted coding region B of CABYR are translated during spermiogenesis, where they localize, or which CABYR isoforms bind calcium. Immunofluorescent and electron microscopic studies using polyclonal antibodies generated to the recombinant c-terminal 198 aa CABYR-B localized the isoforms containing CABYR-B to the ribs and longitudinal columns of the fibrous sheath in the principal piece of the flagellum. Antisera to recombinant CABYR-A and CABYR-B proteins recognized distinct populations of CABYR isoforms encoded by either CR-A alone and/or CR-B as well as a common population of CABYR isoforms. Only the recombinant CABYR-A and not the CABYR-B bound calcium in vitro, which is consistent with the hypothesis that CABYR-A is the only form that binds calcium in sperm. These observations confirmed that, despite the presence of the stop codon in CR-A, splice variants containing CR-B are expressed during spermiogenesis and assemble into the fibrous sheath of the principal piece; however, calcium binding occurs only to those CABYR isoforms containing CABYR-A.  相似文献   
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Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.  相似文献   
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Protein kinase C (PKC) signaling can be activated rapidly by 17β-estradiol (E(2)) via nontraditional signaling in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells and is associated with tumorigenicity. Additionally, E(2) has been shown to elicit anti-apoptotic effects in cancer cells counteracting pro-apoptotic effects of chemotherapeutics. Supporting evidence suggests the existence of a membrane-associated ER that differs from the traditional receptors, ERα and ERβ. Our aim was to identify the ER responsible for rapid PKC activation and to evaluate downstream effects, such as proliferation, apoptosis, and metastasis. RT-PCR, Western blot, and immunofluorescence were used to determine the presence of ER splice variants in multiple cell lines. E(2) effects on PKC activity were measured with and without ER-blocking antibodies. Cell proliferation was determined by [(3)H]thymidine incorporation, and cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, (MTT) whereas apoptosis was determined by DNA fragmentation and TUNEL. Quantitative RT-PCR and sandwich ELISA were used to determine the effects on metastatic factors. The role of membrane-dependent signaling in cancer cell invasiveness was examined using an in vitro assay. The results indicate the presence of an ERα splice variant, ERα36, in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells, which localized to plasma membranes and rapidly activated PKC in response to E(2), leading to deleterious effects such as enhancement of proliferation, protection against apoptosis, and enhancement of metastatic factors. These findings propose ERα36 as a novel target for the development of therapies that can prevent progression of breast cancer in the primary tumor as well as during metastasis.  相似文献   
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Malarial infection during pregnancy has been associated with maternal anemia and death, abortion, still-birth and is a major cause of low birth weight, an important risk factor for infant morbidity and mortality in endemic areas. The present study was designed to delineate the oxidative stress in various organs (liver, spleen, kidney, brain and placenta) of pregnant Plasmodium berghei infected BALB/c mice. It was observed that pregnant-infected mice had higher parasitaemia than nonpregnant-infected mice. Most notably, levels of malondialdehyde (MDA), a measure of lipid peroxidation, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly higher in the liver, spleen, kidney and brain of pregnant-infected mice compared with pregnant mice. Although MDA levels were significantly higher, GSH and SOD levels remained unaltered in the placenta of pregnant-infected mice compared with pregnant mice. Furthermore, catalase activity was significantly lower in all the organs of pregnant-infected mice compared with pregnant mice. Histopathological observations in the organs clearly show the cellular and morphological alterations that may be occurring due to increased lipid peroxidation. Taken together, the data suggest that the increased severity of malarial infection during pregnancy may be due to accentuated oxidative stress.  相似文献   
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