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41.
alpha 1-Proteinase inhibitors (alpha 1-PIs) are members of the serpin
superfamily of proteinase inhibitors, and are important in the maintenance
of homeostasis in a wide variety of animal taxa. Previous studies have
shown that in mice (genus Mus), evolution of alpha 1-PIs is characterized
by gene amplification, region-specific concerted evolution, and rapid
accumulation of amino acid substitutions. The latter occurs primarily in
the reactive center, which is the region of the alpha 1-PI molecule that
determines the inhibitor's specificity for target proteinases. The P1
residue within the reactive center, which is methionine in so-called
orthodox alpha 1-PIs and an amino acid other than methionine in unorthodox
alpha 1-PIs, is a primary determinant of inhibitor specificity. In the
present study, we find that the expression of mRNAs encoding unorthodox
alpha 1-PIs is polymorphic within Mus species, i.e., among individuals or
inbred strains. This is in striking contrast to mRNAs that encode orthodox
alpha 1-PIs, whose concentrations are relatively invariant. The
intraspecies variations in mRNA expression represent polymorphisms in the
structure of the alpha 1- PI gene family. The results, taken together with
previously described aspects of alpha 1-PI evolution, indicate that the
dissimilar levels of polymorphism exhibited by orthodox and unorthodox
alpha 1-PIs, which likely have distinct physiological functions, may
reflect different levels of selective constraint. The significance of this
finding to the evolution of gene families is discussed.
相似文献
42.
Ecosystems provide multiple services upon which humans depend. Understanding the drivers of the ecosystem functions that support these services is therefore important. Much research has investigated how species richness influences functioning, but we lack knowledge of how other community attributes affect ecosystem functioning. Species evenness, species spatial arrangement, and the identity of dominant species are three attributes that could affect ecosystem functioning, by altering the relative abundance of functional traits and the probability of synergistic species interactions such as facilitation and complementary resource use. We tested the effect of these three community attributes and their interactions on ecosystem functions over a growing season, using model grassland communities consisting of three plant species from three functional groups: a grass (Anthoxanthum odoratum), a forb (Plantago lanceolata), and a N-fixing forb (Lotus corniculatus). We measured multiple ecosystem functions that support ecosystem services, including ecosystem gas exchange, water retention, C and N loss in leachates, and plant biomass production. Species evenness and dominant species identity strongly influenced the ecosystem functions measured, but spatial arrangement had few effects. By the end of the growing season, evenness consistently enhanced ecosystem functioning and this effect occurred regardless of dominant species identity. The identity of the dominant species under which the highest level of functioning was attained varied across the growing season. Spatial arrangement had the weakest effect on functioning, but interacted with dominant species identity to affect some functions. Our results highlight the importance of understanding the role of multiple community attributes in driving ecosystem functioning. 相似文献
43.
Seegmiller A; Williams KR; Hammersmith RL; Doak TG; Witherspoon D; Messick T; Storjohann LL; Herrick G 《Molecular biology and evolution》1996,13(10):1351-1362
Internal eliminated sequences (IESs) often interrupt ciliate genes in the
silent germline nucleus but are exactly excised and eliminated from the
developing somatic nucleus from which genes are then expressed. Some long
IESs are transposons, supporting the hypothesis that short IESs are ancient
transposon relics. In light of that hypothesis and to explore the
evolutionary history of a collection of IESs, we have compared various
alleles of a particular locus (the 81 locus) of the ciliated protozoa
Oxytricha trifallax and O. fallax. Three short IESs that interrupt two
genes of the locus are found in alleles from both species, and thus must be
relatively ancient, consistent with the hypothesis that short IESs are
transposon relics. In contrast, TBE1 transposon interruptions of the locus
are allele-specific and probably the results of recent transpositions.
These IESs (and the TBE1s) are precisely excised from the DNA of the
developing somatic macronucleus. Each IES interrupts a highly conserved
sequence. A few nucleotides at the ends of each IES are also conserved,
suggesting that they interact critically with IES excision machinery.
However, most IES nucleotide positions have evolved at high rates, showing
little or no selective constraint for function. Nonetheless, the length of
each IES has been maintained (+/- 3 bp). While one IES is approximately 33
bp long, three other IESs have very similar sizes, approximately 70 bp
long. Two IESs are surrounded by direct repeats of the sequence TTCTT. No
other sequence similarities were found between any of the four IESs.
However, the ends of one IES do match the inverted terminal repeat
consensus sequence of the "TA" IESs of Paramecium. Three O. trifallax
alleles appear to have been recipients in recent conversion events that
could have been provoked by double-strand breaks associated with IES ends
subsequent to IES transposition. Our findings support the hypothesis that
short IESs evolved from ancient transposons that have lost most of their
sequences, except those necessary for precise excision during macronuclear
development.
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44.
The effect of synthetic analogues of chymostatin upon protein degradation in isolated skeletal muscle. 下载免费PDF全文
A series of peptides based on the structure of the proteinase inhibitor chymostatin were tested for their toxicity and ability to suppress protein degradation in the isolated mouse diaphragm. The inhibitory activities of the analogues were very similar, in marked contrast to their disparate abilities as inhibitors of chymotrypsin. Toxicity was determined by measurement of the rates of protein synthesis and of leakage of lactate dehydrogenase into the incubation medium. No significant toxicity was measurable at concentrations of inhibitor that were effective at suppressing proteolysis. The structural features of the chymostatin molecule may be less than optimal for suppression of proteolysis in muscle. 相似文献
45.
46.
SUMMARY Emphasis is given to the importance of wetlands and the need for a rational and multi-use approach to their development. Their occurence in the landscape is explained and a brief account is given of characteristic soils and other related features. Wetlands are widely distributed in certain landscapes and generally have high agricultural potential, especially for the production of cultivated pastures. A large proportion of the vleis in Natal have already been developed. Important principles and procedures to be considered in planning wetland development are presented. The urgent need to develop a wetland strategy, initiate appropriate research, apply effective legislation and identify wetlands in need of total protection is stressed. 相似文献
47.
Changes in predator species richness can have important consequences for ecosystem functioning at multiple trophic levels, but these effects are variable and depend on the ecological context in addition to the properties of predators themselves. Here, we report an experimental study to test how species identity, community attributes, and community structure at the herbivore level moderate the effects of predator richness on ecosystem functioning. Using mesocosms containing predatory insects and aphid prey, we independently manipulated species richness at both predator and herbivore trophic levels. Community structure was also manipulated by changing the distribution of herbivore species across two plant species. Predator species richness and herbivore species richness were found to negatively interact to influence predator biomass accumulation, an effect which is hypothesised to be due to the breakdown of functional complementarity among predators in species-rich herbivore assemblages. The strength of predator suppression of herbivore biomass decreased as herbivore species richness and distribution across host plants increased, and positive predator richness effects on herbivore biomass suppression were only observed in herbivore assemblages of relatively low productivity. In summary, the study shows that the species richness, productivity and host plant distribution of prey communities can all moderate the general influence of predators and the emergence of predator species richness effects on ecosystem functioning. 相似文献
48.
Yunan C. Janurio Jessica Eden Luan S. de Oliveira Raffaella De Pace Lucas A. Tavares Mara E. da Silva-Janurio Vinícius B. Apolloni Elise L. Wilby Randolf Altmeyer Patricia V. Burgos Sonia A.L. Corrêa David C. Gershlick Luis L.P. daSilva 《The Journal of biological chemistry》2022,298(8)
One of the hallmarks of Alzheimer’s disease is the accumulation of toxic amyloid-β (Aβ) peptides in extracellular plaques. The direct precursor of Aβ is the carboxyl-terminal fragment β (or C99) of the amyloid precursor protein (APP). C99 is detected at elevated levels in Alzheimer’s disease brains, and its intracellular accumulation has been linked to early neurotoxicity independently of Aβ. Despite this, the causes of increased C99 levels are poorly understood. Here, we demonstrate that APP interacts with the clathrin vesicle adaptor AP-1 (adaptor protein 1), and we map the interaction sites on both proteins. Using quantitative kinetic trafficking assays, established cell lines and primary neurons, we also show that this interaction is required for the transport of APP from the trans-Golgi network to endosomes. In addition, disrupting AP-1-mediated transport of APP alters APP processing and degradation, ultimately leading to increased C99 production and Aβ release. Our results indicate that AP-1 regulates the subcellular distribution of APP, altering its processing into neurotoxic fragments. 相似文献
49.
Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody™, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody™ expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody™ are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody™ vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.Key words: DNA vaccines, cancer vaccines, melanoma, CTL, helper T cells 相似文献
50.
E?BaptesteEmail author E?Susko J?Leigh D?MacLeod RL?Charlebois WF?Doolittle 《BMC evolutionary biology》2005,5(1):33