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101.
It has been suggested that the karyotype of the marsupials derived from a low diploid number (2n = 14) which originated, through
fissions of biarmed chromosomes, the karyotypes with a higher 2n. The telomeric sequence (T2AG3)nwas in situhybridized to the chromosomes of Gracilinanus microtarsusand G. emiliae, Micoureus demeraraeand Marmosa murina, species with 2n = 14, in Monodelphissp., M. domestica, M. kunsiand M. brevicaudatawith 2n = 18, and in Lutreolina crassicaudata, Didelphis albiventris, Chironectes minimus, Philander opossumand P. frenata, all of them with 2n = 22. The probe hybridization occurred in the telomeric regions of both arms, short and long, of all
chromosomes of the complement of all individuals of all species analysed. However, in some pairs of the karyotypes of Gracilinanus microtarsusand Micoureus demerarae(with 2n = 14), and in Monodelphissp., M. domestica, M. kunsiand M. brevicaudata(2n = 18) ectopic signs of hybridization were detected proximal to the centromeres, suggesting the retention of this telomeric
sequence in the centromeric regions of some chromosomes of these species. Based on these results, it is proposed that the
karyotype of marsupials evolved from a 2n = 22 to a 2n = 14, by means of chromosomal fusions.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
102.
A.A. Paszek G.H. Flickinger L. Fontanesi C.W. Beattie G.A. Rohrer L. Alexander L.B. Schook 《Journal of molecular evolution》1998,46(1):121-126
We report the use of microsatellites (MS) to track the recent evolution of swine. Allelic frequencies for nine MS loci linked
on swine chromosome 6 (SSC6) representing four western and one Chinese swine breeds were used to estimate genetic distances
and times of breed divergence. A phylogenetic tree was constructed which partitioned into western and Meishan breed branches.
Yorkshire and Hampshire breeds exhibited the most recent divergence with a calculated distance of 391 years. The oldest divergence,
of 2,227 years, was between Meishan and Hampshire swine. Estimates of breed divergence are consistent with historical records.
Additional analysis suggests that polymorphic MS linked on a single chromosome are sufficient to determine evolutionary relationships
within a single species.
Received: 23 September 1996 / Accepted: 26 April 1997 相似文献
103.
Giuseppina Mattace Raso Claudio Pirozzi Roberta d'Emmanuele di Villa Bianca Raffaele Simeoli Anna Santoro Adriano Lama Francesca Di Guida Roberto Russo Carmen De Caro Raffaella Sorrentino Antonio Calignano Rosaria Meli 《PloS one》2015,10(5)
Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA. 相似文献
104.
Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/leucovorin and bevacizumab. 相似文献
105.
Bianca Schmid Melanie Rinas Alessia Ruggieri Eliana Gisela Acosta Marie Bartenschlager Antje Reuter Wolfgang Fischl Nathalie Harder Jan-Philip Bergeest Michael Flossdorf Karl Rohr Thomas H?fer Ralf Bartenschlager 《PLoS pathogens》2015,11(12)
Dengue virus (DENV) is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN) response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2’-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2’-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells. 相似文献
106.
107.
Christoph Schwarz Daniel A. Klaus Bianca Tudor Edith Fleischmann Thomas Wekerle Georg Roth Martin Bodingbauer Klaus Kaczirek 《PloS one》2015,10(10)
Background
Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear.Materials and Methods
This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality.Results
Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020).Conclusions
Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time.Trial Registration
ClinicalTrials.gov NCT01785212 相似文献108.
The nematode Pristionchus pacificus is of growing interest as a model organism in evolutionary biology. However, despite multiple studies of its genetics, developmental cues, and ecology, the basic life-history traits (LHTs) of P. pacificus remain unknown. In this study, we used the hanging drop method to follow P. pacificus at the individual level and thereby quantify its LHTs. This approach allowed direct comparisons with the LHTs of Caenorhabditis elegans recently determined using this method. When provided with 5×109
Escherichia coli cells ml–1 at 20°C, the intrinsic rate of natural increase of P. pacificus was 1.125 (individually, per day); mean net production was 115 juveniles produced during the life-time of each individual, and each nematode laid an average of 270 eggs (both fertile and unfertile). The mean age of P. pacificus individuals at first reproduction was 65 h, and the average life span was 22 days. The life cycle of P. pacificus is therefore slightly longer than that of C. elegans, with a longer average life span and hatching time and the production of fewer progeny. 相似文献
109.
Carolina G. Fernandes Guilhian Leipnitz Bianca Seminotti Alexandre U. Amaral Ângela Zanatta Carmen R. Vargas Carlos S. Dutra Filho Moacir Wajner 《Cellular and molecular neurobiology》2010,30(2):317-326
High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically
characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering
that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly
understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in
brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats.
We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl
oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since
the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME,
a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased
the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants.
Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites
of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to
a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with
learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that
this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy
associated with dysmyelination and leukodystrophy observed in this disorder. 相似文献
110.
O'Donnell L Panier S Wildenhain J Tkach JM Al-Hakim A Landry MC Escribano-Diaz C Szilard RK Young JT Munro M Canny MD Kolas NK Zhang W Harding SM Ylanko J Mendez M Mullin M Sun T Habermann B Datti A Bristow RG Gingras AC Tyers MD Brown GW Durocher D 《Molecular cell》2010,40(4):619-631
Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin,?a topoisomerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks. 相似文献