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1.
2.
Scott A. Kleiner 《Biology & philosophy》1999,14(1):55-63
Thomas Nickles challenges my thesis that innovative discoveries can be based on deliberately chosen problems and research strategies. He suggests that all significant innovation can be seen as such only in retrospect and that its generation must be serendipitous. Here I argue in response that significant innovations can and do often arise from self conscious critical appraisal of orthodox practice combined with regulated though speculative abductive argumentation to alternative explanatory schemata. Orthodox practice is not based upon monolithic systems of belief about the subject of inquiry. Rather major domains of scientific practice often are approached from different conceptualizations that provide grounds for critical dialectic and consilient empirical information. Abductive arguments that meet appropriate conditions of likelihood, probability and analogy are an important means of justifying allocating resources to innovative practices that have yet to produce products that can rival those of established orthodoxy. 相似文献
3.
Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
4.
Nicholas Cianciotto Terry Serwold-Davis Neal Groman Giulio Ratti Rino Rappuoli 《FEMS microbiology letters》1990,66(1-3):299-301
Chromosomal restriction fragments of Corynebacterium ulcerans and C. diphtheriae, containing an integration site for corynephages of the beta family, show homology on Southern blots. Homologous DNA in also found in the soil isolate C. glutamicum, although this strain is not susceptible to beta-corynephages. Three of these DNA fragments, one for each bacterial strain, and a fragment of gamma-corynephage DNA previously shown to contain the phage integration site, were cloned and sequenced. Alignment of the 3 bacterial sequences shows a very high degree of homology in a stretch of ca 120 nucleotides, whereas the rest of the sequences is generally non-homologous. Within this common bacterial portion, a segment of ca. 96 nucleotides (core sequence) is also highly homologous to the phage sequence. The first half (ca. 50 bp) of the core sequence is identical in all aligned sequences whereas the second half, which is largely occupied by a stem-and-loop structure, contains point mutations peculiar to each clone. The described sequences are likely to be involved in phage integration/excision processes. 相似文献
5.
6.
Thomas Jahns Alexandra Zobel Diethelm Kleiner Heinrich Kaltwasser 《Archives of microbiology》1988,149(5):377-383
Evidence for the existence of an energy-dependent urea permease was found for Alcaligenes eutrophus H16 and Klebsiella pneumoniae M5a1 by studying uptake of 14C-urea. Since intracellular urea was metabolized immediately, uptake did not result in formation of an urea pool. Evidence is based on observations that the in vivo urea uptake and in vitro urease activity differ significantly with respect to kinetic parameters, temperature optimum, pH optimum, response towards inhibitors and regulation. The K
m for urea uptake was 15–20 times lower (38 M and 13 M urea for A. eutrophus and K. pneumoniae, respectively) than the K
m of urease for urea (650 M and 280 M urea), the activity optimum for A. eutrophus was at pH 6.0 and 35°C for the uptake and pH 9.0 and 65°C for urease. Uptake but not urease activity in both organisms strongly decreased upon addition of inhibitors of energy metabolism, while in K. pneumoniae, potent inhibitors of urease (thiourea and hydroxyurea) did not affect the uptake process. Significant differences in the uptake rates were observed during growth with different nitrogen sources (ammonia, nitrate, urea) or in the absence of a nitrogen source; this suggested that a carrier is involved which is subject to nitrogen control. Some evidence for the presence of an energy-dependent uptake of urea was also obtained in Pseudomonas aeruginosa DSM 50071 and Providencia rettgeri DSM 1131, but not in Proteus vulgaris DSM 30118 and Bacillus pasteurii DSM 33.Non-standard abbreviations CCCP
Carbonylcyanide-m-chlorphenylhydrazone
- DCCD
dicyclohexylcarbodiimide
- DNP
2,4-dinitrophenole 相似文献
7.
Summary In the Gasserian ganglion and testis of the rat the endothelium of the small blood vessels has a singular appearance due to the presence of a high number of microvillous processes. These arise from the luminal surface, either individually, or in small groups. The significance of this structure is not known. It is pointed out that these vessels are particularly sensitive to cadmium intoxication.This investigation was performed during a tenure by Dr. Gabbiani of a fellowship of the Medical Research Council of Canada and was supported by the National Institutes of Health (Grant No. 5R01 HE-08794-04) and the Ministère de la Santé du Québec (projet 604-7-635).The authors wish to thank Dr. S. M. Shea for his advice in the measurement of the villi. The technical assistance of Miss Virginia Gilmore and of Mr. Eduardo Garriga is gratefully acknowledged. 相似文献
8.
Rosa Sorrentino Carlo Iannicola Sandro Costanzi Giulio Ratti Carolyn Hurley Roberto Tosi Nobuyuki Tanigaki 《Immunogenetics》1990,32(1):8-12
TR81 is a specificity closely related to or identical with DR3. In Caucasoids two amino acids, Tyr at position 26 and Arg at position 74 of HLA class II DR chains, have been found to be associated with the presence of TR81. Recently, a variant of DRBI *03 identified in American Blacks has been shown to possess Arg at position 74 but Phe at position 26. This codon combination is found to be present in four other cell lines where it still specifies the TR81 determinant. This suggests that the TR81 specificity is uniquely dependent on the presence of Arg at position 74. 相似文献
9.
Massimo Di Giulio 《Journal of molecular evolution》1997,45(6):571-578
A highly complex RNA world, as is sometimes presented in view of the widespread and diversified use of RNA enzymes, would
have encountered many difficulties in passing to a world with catalysis mediated by proteins. These difficulties can be overcome
by postulating a very early relationship between the nucleotide and the amino acid components. In particular, after asserting
that some characteristics expressed by (nucleotide) coenzymes in catalysis are easier to understand if a close and early relationship
between these coenzymes and amino acids is hypothesized, a model is presented for the origin of the enzyme–coenzyme complex.
This model is essentially based on an intermediate formed by a tRNA-like molecule covalently linked to a polypeptide. The
model attributes the majority of the catalytic role in the ribonucleoprotein world to the latter complex and thus it takes
into account the birth of the key intermediate in the origin of protein synthesis—namely, peptidyl-tRNA, which would have
otherwise been extremely difficult to select. The predictions of the model are discussed along with its robustness, using
the data derived from the study of intermediary metabolism and those from molecular biology. Finally, the appearance of the
genetic code in the late phase of the ribonucleopeptide world is discussed.
Received: 13 January 1997 / Accepted: 25 July 1997 相似文献
10.
Dr. Laura Curatolo Christine Chaponnier Maria Benedetta Donati Luciano Morasca Giulio Gabbiani 《Cell and tissue research》1982,223(3):665-673
Summary It is known that human and animal fibroblasts are able to induce the retraction of a fibrin clot. In the present study the correlation between (i) fibrinclot retractile (FCR) activity, (ii) the number of actin stress-lines in mouse fibroblasts during growth in culture, and (iii) the sensitivity of actin stress-lines to a powerful actin-depolymerizing factor (ADF), present in plasma and serum of humans and laboratory animals was investigated. Fibroblasts at early passages (2–4) were tested for these parameters at various intervals after seeding (24, 96, and 168 h). The number of actin stress-lines was progressively higher, while the sensitivity to ADF action was progressively lower in cells cultured from 24 to 168 h; the FCR capacity was significantly decreased at 168 h. These data suggest that cells containing weakly polymerized and/or stabilized actin are more active than those containing highly polymerized and/or stabilized actin in triggering fibroblast contraction. 相似文献