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51.
Background
DNA microarray technology is a powerful technique that was recently developed in order to analyze thousands of genes in a short time. Presently, microarrays, or chips, of the cDNA type and oligonucleotide type are available from several sources. The number of publications in this area is increasing exponentially. 相似文献52.
Monoclonal antibodies against chicken type V collagen: production, specificity, and use for immunocytochemical localization in embryonic cornea and other organs 总被引:6,自引:17,他引:6 下载免费PDF全文
TF Linsenmayer JM Fitch TM Schmid Zak NB E Gibney RD Sanderson R Mayne 《The Journal of cell biology》1983,96(1):124-132
Two monoclonal antibodies have been produced against chick type V collagen and shown to be highly specific for separate, conformational dependent determinants within this molecule. When used for immunocytochemical tissue localization, these antibodies show that a major site for the in situ deposition of type V is within the extracellular matrices of many dense connective tissues. In these, however, it is largely in a form unavailable to the antibodies, thus requiring a specific “unmasking” treatment to obtain successful immunocytochemical staining. The specificity of these two IgG antibodies was determined by inhibition ELISA, in which only type V and no other known collagen shows inhibition. In ELISA, mixtures of the two antibodies give an additive binding reaction to the collagen, suggesting that each is against a different antigenic determinant. That both antigenic determinants are conformational dependent, being either in, or closely associated with, the collagen helix is demonstrated by the loss of antibody binding to molecules that have been thermally denatured. The temperature at which this occurs, as assayed by inhibition ELISA, is very similar to that at which the collagen helix melts, as determined by optical rotation. This gives strong additional evidence that the antibodies are directed against the collagen. The antibodies were used for indirect immunofluorescence analyses of cryostat sections of corneas and other organs from 17 to 18-day-old chick embryos. Of all tissues examined only Bowman’s membrane gave a strong staining reaction with cryostat sections of unfixed material. Staining in other areas of the cornea and in other tissues was very light or nonexistent. When, however, sections were pretreated with pepsin dissolved in dilute HAc or, surprisingly, with the dilute HAc itself dramatic new staining by the antibodies was observed in most tissues examined. The staining, which was specific for the anti-type V collagen antibodies, was largely confined to extracellular matrices of dense connective tissues. Experiments using protease inhibitors suggested that the “unmasking” did not involve proteolysis. We do not yet know the mechanism of this unmasking; however, one possibility is that the dilute acid causes swelling or conformational changes in a type-V collagen-containing supramolecular structure. Further studies should allow us to determine whether this is the case. 相似文献
53.
54.
The evolution of different maternal investment strategies in two closely related desert vertebrates 下载免费PDF全文
Joshua R. Ennen Jeffrey E. Lovich Roy C. Averill‐Murray Charles B. Yackulic Mickey Agha Caleb Loughran Laura Tennant Barry Sinervo 《Ecology and evolution》2017,7(9):3177-3189
We compared egg size phenotypes and tested several predictions from the optimal egg size (OES) and bet‐hedging theories in two North American desert‐dwelling sister tortoise taxa, Gopherus agassizii and G. morafkai, that inhabit different climate spaces: relatively unpredictable and more predictable climate spaces, respectively. Observed patterns in both species differed from the predictions of OES in several ways. Mean egg size increased with maternal body size in both species. Mean egg size was inversely related to clutch order in G. agassizii, a strategy more consistent with the within‐generation hypothesis arising out of bet‐hedging theory or a constraint in egg investment due to resource availability, and contrary to theories of density dependence, which posit that increasing hatchling competition from later season clutches should drive selection for larger eggs. We provide empirical evidence that one species, G. agassizii, employs a bet‐hedging strategy that is a combination of two different bet‐hedging hypotheses. Additionally, we found some evidence for G. morafkai employing a conservative bet‐hedging strategy. (e.g., lack of intra‐ and interclutch variation in egg size relative to body size). Our novel adaptive hypothesis suggests the possibility that natural selection favors smaller offspring in late‐season clutches because they experience a more benign environment or less energetically challenging environmental conditions (i.e., winter) than early clutch progeny, that emerge under harsher and more energetically challenging environmental conditions (i.e., summer). We also discuss alternative hypotheses of sexually antagonistic selection, which arise from the trade‐offs of son versus daughter production that might have different optima depending on clutch order and variation in temperature‐dependent sex determination (TSD) among clutches. Resolution of these hypotheses will require long‐term data on fitness of sons versus daughters as a function of incubation environment, data as yet unavailable for any species with TSD. 相似文献
55.
Background
The discovery and mapping of genomic variants is an essential step in most analysis done using sequencing reads. There are a number of mature software packages and associated pipelines that can identify single nucleotide polymorphisms (SNPs) with a high degree of concordance. However, the same cannot be said for tools that are used to identify the other types of variants. Indels represent the second most frequent class of variants in the human genome, after single nucleotide polymorphisms. The reliable detection of indels is still a challenging problem, especially for variants that are longer than a few bases.Results
We have developed a set of algorithms and heuristics collectively called indelMINER to identify indels from whole genome resequencing datasets using paired-end reads. indelMINER uses a split-read approach to identify the precise breakpoints for indels of size less than a user specified threshold, and supplements that with a paired-end approach to identify larger variants that are frequently missed with the split-read approach. We use simulated and real datasets to show that an implementation of the algorithm performs favorably when compared to several existing tools.Conclusions
indelMINER can be used effectively to identify indels in whole-genome resequencing projects. The output is provided in the VCF format along with additional information about the variant, including information about its presence or absence in another sample. The source code and documentation for indelMINER can be freely downloaded from www.bx.psu.edu/miller_lab/indelMINER.tar.gz.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-015-0483-6) contains supplementary material, which is available to authorized users. 相似文献56.
Kono M Herrmann S Loughran NB Cabrera A Engelberg K Lehmann C Sinha D Prinz B Ruch U Heussler V Spielmann T Parkinson J Gilberger TW 《Molecular biology and evolution》2012,29(9):2113-2132
The inner membrane complex (IMC) is a unifying morphological feature of all alveolate organisms. It consists of flattened vesicles underlying the plasma membrane and is interconnected with the cytoskeleton. Depending on the ecological niche of the organisms, the function of the IMC ranges from a fundamental role as reinforcement system to more specialized roles in motility and cytokinesis. In this article, we present a comprehensive evolutionary analysis of IMC components, which exemplifies the adaptive nature of the IMCs' protein composition. Focusing on eight structurally distinct proteins in the most prominent "genus" of the Alveolata-the malaria parasite Plasmodium-we demonstrate that the level of conservation is reflected in phenotypic characteristics, accentuated in differential spatial-temporal patterns of these proteins in the motile stages of the parasite's life cycle. Colocalization studies with the centromere and the spindle apparatus reveal their discriminative biogenesis. We also reveal that the IMC is an essential structural compartment for the development of the sexual stages of Plasmodium, as it seems to drive the morphological changes of the parasite during the long and multistaged process of sexual differentiation. We further found a Plasmodium-specific IMC membrane matrix protein that highlights transversal structures in gametocytes, which could represent a genus-specific structural innovation required by Plasmodium. We conclude that the IMC has an additional role during sexual development supporting morphogenesis of the cell, which in addition to its functions in the asexual stages highlights the multifunctional nature of the IMC in the Plasmodium life cycle. 相似文献
57.
Spiros Palikyras Konstantinos Sofiadis Athanasia Stavropoulou Adi Danieli-Mackay Vassiliki Varamogianni-Mamatsi David Hörl Simona Nasiscionyte Yajie Zhu Ioanna Papadionysiou Antonis Papadakis Natasa Josipovic Anne Zirkel Aoife O'Connell Gary Loughran James Keane Audrey Michel Wolfgang Wagner Andreas Beyer Hartmann Harz Heinrich Leonhardt Grazvydas Lukinavicius Christoforos Nikolaou Argyris Papantonis 《Aging cell》2024,23(4):e14083
Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and by its paracrine effects. To address these issues, we repurposed a small molecule inhibitor, inflachromene (ICM), to induce senescence to human primary cells. Within 6 days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered a high similarity of the two states. Notably though, ICM suppresses the pro-inflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescent-like phenotype thereby allowing the study of its core regulatory program without confounding heterogeneity. 相似文献
58.
Sodam Kim Sun Young Kim John P Pribis Michael Lotze Kevin P Mollen Richard Shapiro Patricia Loughran Melanie J Scott Timothy R Billiar 《Molecular medicine (Cambridge, Mass.)》2013,19(1):88-98
High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses cytokinelike, proinflammatory properties when released extracellularly in the C23–C45 disulfide form. HMGB1 also plays a key role as a mediator of acute and chronic inflammation in models of sterile injury. Although HMGB1 interacts with multiple pattern recognition receptors (PRRs), many of its effects in injury models occur through an interaction with toll-like receptor 4 (TLR4). HMGB1 interacts directly with the TLR4/myeloid differentiation protein 2 (MD2) complex, although the nature of this interaction remains unclear. We demonstrate that optimal HMGB1-dependent TLR4 activation in vitro requires the coreceptor CD14. TLR4 and MD2 are recruited into CD14-containing lipid rafts of RAW264.7 macrophages after stimulation with HMGB1, and TLR4 interacts closely with the lipid raft protein GM1. Furthermore, we show that HMGB1 stimulates tumor necrosis factor (TNF)-α release in WT but not in TLR4−/−, CD14−/−, TIR domain-containing adapter-inducing interferon-β (TRIF)−/− or myeloid differentiation primary response protein 88 (MyD88)−/− macrophages. HMGB1 induces the release of monocyte chemotactic protein 1 (MCP-1), interferon gamma–induced protein 10 (IP-10) and macrophage inflammatory protein 1α (MIP-1α) in a TLR4- and CD14-dependent manner. Thus, efficient recognition of HMGB1 by the TLR4/MD2 complex requires CD14. 相似文献
59.
Nuclear factor kappa B-dependent activation of the antiapoptotic bfl-1 gene by the Epstein-Barr virus latent membrane protein 1 and activated CD40 receptor 总被引:3,自引:0,他引:3 下载免费PDF全文
D'Souza BN Edelstein LC Pegman PM Smith SM Loughran ST Clarke A Mehl A Rowe M Gélinas C Walls D 《Journal of virology》2004,78(4):1800-1816
60.
Raisa?Perzova Elliot?Graziano Swathi?Sanghi Caitlin?Welch Patricia?Benz Lynn?Abbott Danielle?Lalone Jordan?Glaser Thomas?Loughran William?Sheremata Bernard?J?PoieszEmail author 《Virology journal》2013,10(1):360