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121.
Human DNA polymerase nu (pol nu) is one of three A family polymerases conserved in vertebrates. Although its biological functions are unknown, pol nu has been implicated in DNA repair and in translesion DNA synthesis (TLS). Pol nu lacks intrinsic exonucleolytic proofreading activity and discriminates poorly against misinsertion of dNTP opposite template thymine or guanine, implying that it should copy DNA with low base substitution fidelity. To test this prediction and to comprehensively examine pol nu DNA synthesis fidelity as a clue to its function, here we describe human pol nu error rates for all 12 single base-base mismatches and for insertion and deletion errors during synthesis to copy the lacZ alpha-complementation sequence in M13mp2 DNA. Pol nu copies this DNA with average single-base insertion and deletion error rates of 7 x 10(-5) and 17 x 10(-5), respectively. This accuracy is comparable to that of replicative polymerases in the B family, lower than that of its A family homolog, human pol gamma, and much higher than that of Y family TLS polymerases. In contrast, the average single-base substitution error rate of human pol nu is 3.5 x 10(-3), which is inaccurate compared to the replicative polymerases and comparable to Y family polymerases. Interestingly, the vast majority of errors made by pol nu reflect stable misincorporation of dTMP opposite template G, at average rates that are much higher than for homologous A family members. This pol nu error is especially prevalent in sequence contexts wherein the template G is preceded by a C-G or G-C base pair, where error rates can exceed 10%. Amino acid sequence alignments based on the structures of more accurate A family polymerases suggest substantial differences in the O-helix of pol nu that could contribute to this unique error signature. 相似文献
122.
Beyond Reserves: A Research Agenda for Conserving Biodiversity in Human-modified Tropical Landscapes 总被引:5,自引:0,他引:5
Robin L. Chazdon Celia A. Harvey Oliver Komar Daniel M. Griffith Bruce G. Ferguson Miguel Martínez-Ramos Helda Morales Ronald Nigh Lorena Soto-Pinto Michiel van Breugel Stacy M. Philpott 《Biotropica》2009,41(2):142-153
To truly understand the current status of tropical diversity and to forecast future trends, we need to increase emphasis on the study of biodiversity in rural landscapes that are actively managed or modified by people. We present an integrated landscape approach to promote research in human-modified landscapes that includes the effects of landscape structure and dynamics on conservation of biodiversity, provision of ecosystem services, and sustainability of rural livelihoods. We propose research priorities encompassing three major areas: biodiversity, human–environment interactions, and restoration ecology. We highlight key areas where we lack knowledge and where additional understanding is most urgent for promoting conservation and sustaining rural livelihoods. Finally, we recommend participatory and multidisciplinary approaches in research and management. Lasting conservation efforts demand new alliances among conservation biologists, agroecologists, agronomists, farmers, indigenous peoples, rural social movements, foresters, social scientists, and land managers to collaborate in research, co-design conservation programs and policies, and manage human-modified landscapes in ways that enhance biodiversity conservation and promote sustainable livelihoods. 相似文献
123.
Sayós J Martínez-Barriocanal A Kitzig F Bellón T López-Botet M 《Biochemical and biophysical research communications》2004,324(2):640-647
The CD85j inhibitory receptor (also termed ILT2 or LIR-1) is a type-I transmembrane protein that belongs to the Ig superfamily and is expressed by different leukocyte lineages. The extracellular region of CD85j binds HLA class I molecules and its cytoplasmic domain displays four immunoreceptor tyrosine-based inhibition motifs (ITIM). Upon tyrosine phosphorylation CD85j recruits the SHP-1 tyrosine phosphatase, involved in negative signaling. In order to identify other molecules to which CD85j might interact with in a phosphotyrosine-dependent manner, a cDNA B-cell library was screened in a three-hybrid system in yeast using the CD85j cytoplasmic tail as bait in the presence of the Src-kinase c-fyn420, 531Y-F, 176R-Q mutant. In this system, the C-terminal Src kinase (Csk) was shown to interact with CD85j. Phosphorylation-dependent recruitment of Csk to the CD85j cytoplasmic tail was confirmed in CD85j-transfected mammalian cells by immunoprecipitation and Western blot analysis. Mutational analyses and phospho-peptide mapping suggested that the SH2 domain of Csk may preferentially bind to ITIM Y562 of CD85j; yet, mutation to phenylalanine of Y533, Y614, and Y644 also significantly reduced Csk recruitment by CD85j. Even though CD85j was detected in both anti-SHP1 and CSK immunoprecipitates, these two molecules did not co-precipitate together with CD85j. Our data support the possibility that Csk regulates the function of CD85j. 相似文献
124.
Ali C Akyildiz Lambert Speelman Harald van Brummelen Miguel A Gutiérrez Renu Virmani Aad van der Lugt Anton FW van der Steen Jolanda J Wentzel Frank JH Gijsen 《Biomedical engineering online》2011,10(1):25
Background
Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress. 相似文献125.
Sayantani Chatterjee Ling Y. Lee Rebeca Kawahara Jodie L. Abrahams Barbara Adamczyk Merrina Anugraham Christopher Ashwood Zeynep Sumer‐Bayraktar Matthew T. Briggs Jenny H. L. Chik Arun Everest‐Dass Sarah Frster Hannes Hinneburg Katia R. M. Leite Ian Loke Uwe Mginger Edward S. X. Moh Miyako Nakano Saulo Recuero Manveen K. Sethi Miguel Srougi Kathrin Stavenhagen Vignesh Venkatakrishnan Katherine Wongtrakul‐Kish Simone Diestel Peter Hoffmann Niclas G. Karlsson Daniel Kolarich Mark P. Molloy Michael H. Muders Martin K. Oehler Nicolle H. Packer Giuseppe Palmisano Morten Thaysen‐Andersen 《Proteomics》2019,19(21-22)
While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis. 相似文献
126.
127.
Melgarejo E Medina MA Sánchez-Jiménez F Urdiales JL 《The international journal of biochemistry & cell biology》2009,41(5):998-1001
Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes and macrophages to areas of inflammation. MCP-1 is a prototypical chemokine subject to coordinated regulation by immunomodulatory agents. Since MCP-1 is implicated in multiple inflammatory diseases, it is a potential target for the treatment of these disorders. In this review, we will provide background information and summarize the MCP-1 structure and signaling pathways. Its involvement in multiple diseases, such as tumour development, atherogenesis and rare autoimmune diseases is also revised. 相似文献
128.
Laccase detoxification of steam-exploded wheat straw for second generation bioethanol 总被引:3,自引:0,他引:3
Miguel Jurado Alicia Prieto ngeles Martínez-Alcal ngel T. Martínez María Jesús Martínez 《Bioresource technology》2009,100(24):6378-6384
In this work we compared the efficiency of a laccase treatment performed on steam-exploded wheat straw pretreated under soft conditions (water impregnation) or harsh conditions (impregnation with diluted acid). The effect of several enzymatic treatment parameters (pH, time of incubation, laccase origin and loading) was analysed. The results obtained indicated that severity conditions applied during steam explosion have an influence on the efficiency of detoxification. A reduction of the toxic effect of phenolic compounds by laccase polymerization of free phenols was demonstrated. Laccase treatment of steam-exploded wheat straw reduced sugar recovery after enzymatic hydrolysis, and it should be better performed after hydrolysis with cellulases. The fermentability of hydrolysates was greatly improved by the laccase treatment in all the samples. Our results demonstrate the action of phenolic compounds as fermentation inhibitors, and the advantages of a laccase treatment to increase the ethanol production from steam-exploded wheat straw. 相似文献
129.
Projects funded by International Development Research Centre (IDRC) of Canada and the European Commission have enabled the
examination of more than 3000 samples of maize collected from all regions of Costa Rica at different stages, from the growing
crop through storage to final sale, and at different water contents. Contamination with Aspergillus flavus was frequent and
about 80% of samples contained more than 20 ng aflatoxins g-1 grain. Average contamination with aflatoxins in the Brunca Region
was > 274 ng g -1 while that in other regions was < 70 ng g -1. Except in Brunca region, where it averaged 376 ng g -1, contamination
of grain from commercial sources was slightly less than of that from farms (≤15 ng g-1). It appeared that samples kept on
the cob after harvest contained almost no aflatoxin while shelled samples were frequently highly contaminated. Experiments
were therefore done in Brunca and Huetar Atlantic Regions, utilising 34 experimental maize crops to study in detail the development
of A. flavus and aflatoxin from before harvest, through postharvest treatment before drying and through storage for six months.
A. flavus was isolated more frequently from maize shelled immediately after harvest than from that kept on the cob until it
could be dried, and from more samples from the Brunca Region than from the Huetar Atlantic Region. Samples harvested with
≥18% water content often contained >70% of grains infected with A. flavus but sometimes there were few grains infected. As
found in the initial survey, more aflatoxin contamination developed in shelled maize than in that handled on the cob during
the period from harvesting to drying, especially if the delay was more than 5 days, and more in Brunca than in Huetar. Shelled
grain contained 400–800 ng aflatoxin g -1 in Brunca but <100 ng g-1 in Huetar while grain kept on the cob contained <30 ng
g-1, even with >18% water content. Incidence of Fusarium spp. exceeded 50% except where A. flavus colonized more than 80%
of grains.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
130.
The release of a potent bone-resorption inhibitor such as zoledronate from a versatile drug delivery system such as SBA 15
has been modeled. The initial and boundary conditions have been defined, together with the system parameters, including the
determination of equilibrium and transport parameters. Additionally, the experimental model of the same system has been observed
to validate the prediction here developed. This approach represents a powerful tool for the designing of mesoporous implantable
drug delivery systems because their release kinetics can be predicted in advance, and this leads to a considerable time and
resources saving. 相似文献