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81.
Principal component models for sparse functional data 总被引:5,自引:0,他引:5
82.
Leukemia is the most common pediatric malignancy, constituting more than 30% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and poor survival rates post relapse remain a challenge. Given this, more effective and innovative therapeutic strategies are needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for the regulation of several mitotic processes, have been identified as potential targets for cancer therapeutics. Elevated expression of Aurora kinases has been demonstrated in several malignancies and is associated with aberrant mitotic activity, aneuploidy and alterations in chromosomal structure and genome instability. Based on this rationale, a number of small molecule inhibitors have been formulated and advanced to human studies in the recent past. A comparative analysis of these agents in cytotoxicity and target modulation analyses against a panel of leukemia cells provides novel insights into the unique mechanisms and codependent activity pathways involved in targeting Aurora kinases, constituting a distinctive preclinical experimental framework to identify appropriate agents and combinations in future clinical studies. 相似文献
83.
Mitchell GB Sigurdson CJ O'Rourke KI Algire J Harrington NP Walther I Spraker TR Balachandran A 《PloS one》2012,7(6):e39055
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrP(CWD)) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrP(CWD) in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection. 相似文献
84.
In anti-neutrophil cytoplasmic autoantibody-associated vasculitides (AAV), several observations support a key role of T-helper
cells (CD4+ T cells) in disease pathophysiology. An expanded population of effector memory CD4+ T cells in AAV patients may contribute to tissue injury and disease progression. In addition, functional impairment of regulatory
T cells (TRegs) is reported in AAV patients. A fraction of TRegs have the capacity to differentiate into Th17 cells in the context of a proinflammatory environment. Therefore, nonfunctionality
of TRegs described in AAV patients may be caused by their conversion into IL-17-producing cells that may contribute to granulomatous
vasculitis. Further investigations directed at the plasticity of TRegs in AAV patients are warranted. 相似文献
85.
Cees GM Kallenberg Arjan Vissink Frans GM Kroese Wayel H Abdulahad Hendrika Bootsma 《Arthritis research & therapy》2011,13(1):205
In vitro and in vivo experimental data have pointed to new immunopathogenic mechanisms in primary Sj?gren's syndrome (pSS). The availability of
targeted treatment modalities has opened new ways to selectively target these mechanistic pathways in vivo. This has taught us that the role of proinflammatory cytokines, in particular TNFα, is not crucial in the immunopathogenesis
of pSS. B cells appear to play a major role, as depletion of B cells leads to restoration of salivary flow and is efficacious
for treatment of extraglandular manifestations and mucosa-associated lymphoid tissue lymphoma. B cells also orchestrate T-cell
infiltration and ductal epithelial dearrangement in the salivary glands. Gene profiling of salivary gland tissue in relation
to B-cell depletion confirms that the axis of IFNα, B-cell activating factor, B-cell activation, proliferation and survival
constitutes a major pathogenic route in pSS. 相似文献
86.
87.
We developed a new and simple method to collect sections of a whole brown rice kernel for investigation of histological properties. A single kernel of rice was dehydrated through a graded ethanol series, transferred to xylene, and embedded in paraffin. During sectioning of the blocks using a rotary microtome, we used a special adhesive tape to collect and place the sections on slides so they remained flat. The use of the adhesive tape technique combined with autofluorescence characteristics allowed us to visualize cell walls throughout an entire longitudinal or transverse section of a whole rice kernel. We obtained scanning electron microscopy images of the sections to determine section quality. 相似文献
88.
We previously identified a 66 kDa axonemal protein (Ci-Axp66.0) in sperm of the ascidian Ciona intestinalis. Here we found that Ci-Axp66.0 shows sequence similarity to the DC2 subunit of the Chlamydomonas outer arm docking complex. Analysis of secondary structure of Ci-Axp66.0 suggested that the N-terminal two-thirds of the molecule is rich in coiled coil structure, as in Chlamydomonas DC2. Immunogold localization revealed that it is located in the vicinity of outer arm dynein. Ci-Axp66.0 was partly extracted from the axonemes by a high salt solution and co-purified with outer arm dynein. This co-purification was not affected by the absence of Mg(2+) in isolation buffer, indicating that Ci-Axp66.0 is associated with outer arm dynein. These results suggest that Ci-Axp66.0 is a component of the outer arm dynein docking complex in the axonemes of Ciona sperm. 相似文献
89.
Background
Poorly preserved biological tissues have become an important source of DNA for a wide range of zoological studies. Measuring the quality of DNA obtained from these samples is often desired; however, there are no widely used techniques available for quantifying damage in highly degraded DNA samples. We present a general method that can be used to determine the frequency of polymerase blocking DNA damage in specific gene-regions in such samples. The approach uses quantitative PCR to measure the amount of DNA present at several fragment sizes within a sample. According to a model of random degradation the amount of available template will decline exponentially with increasing fragment size in damaged samples, and the frequency of DNA damage (λ) can be estimated by determining the rate of decline.Results
The method is illustrated through the analysis of DNA extracted from sea lion faecal samples. Faeces contain a complex mixture of DNA from several sources and different components are expected to be differentially degraded. We estimated the frequency of DNA damage in both predator and prey DNA within individual faecal samples. The distribution of fragment lengths for each target fit well with the assumption of a random degradation process and, in keeping with our expectations, the estimated frequency of damage was always less in predator DNA than in prey DNA within the same sample (mean λpredator = 0.0106 per nucleotide; mean λprey = 0.0176 per nucleotide). This study is the first to explicitly define the amount of template damage in any DNA extracted from faeces and the first to quantify the amount of predator and prey DNA present within individual faecal samples.Conclusion
We present an approach for characterizing mixed, highly degraded PCR templates such as those often encountered in ecological studies using non-invasive samples as a source of DNA, wildlife forensics investigations and ancient DNA research. This method will allow researchers to measure template quality in order to evaluate alternate sources of DNA, different methods of sample preservation and different DNA extraction protocols. The technique could also be applied to study the process of DNA decay. 相似文献90.
Roberto Mariotti Nicolò GM Cultrera Concepcion Muñoz Díez Luciana Baldoni Andrea Rubini 《BMC plant biology》2010,10(1):211