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Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer’s disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer’s disease patients perform poorly on both real space and computerized cued (allothetic) or uncued (idiothetic) recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze), and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer’s disease.  相似文献   
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The immune response to the complete streptococcal M6 protein was examined by kinetic ELISA to determine the reactivity of rabbit and human sera to M6 peptides representing 82% of the native molecule. The results revealed that rabbits immunized with purified native M6 protein or whole streptococci responded by reacting early and predominantly to one of the three sequence repeat regions of the molecule, the B-repeat, antibodies which have been shown to be non-opsonic. Antibodies to peptides representing the hypervariable N-terminal and adjacent A-repeat regions appear when opsonic antibodies are detected in the serum. Antibodies to peptides located within the conserved C-terminal half of the molecule (proximal to the cell) were restricted even after several immunizations. An examination of human sera from individuals with no recent streptococcal infection (greater than 3 yr), revealed that those sera opsonic for M6 streptococci contained antibodies reactive predominantly to the N-terminal and A-repeat regions, supporting the view that opsonic antibodies are long lived. Nonopsonic human sera to M6 streptococci exhibited a low reactivity to all peptides. However, by Western blot analysis, all human sera tested contained antibodies to the conserved region of the molecule, whereas only sera opsonic for M6 streptococci reacted with the variable region. Evidence is presented supporting the view that antibodies to the conserved regions of the M molecule may be conformation dependent.  相似文献   
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A number of proteins have been isolated from human cells on the basis of their ability to support DNA replication in vitro of the simian virus 40 (SV40) origin of DNA replication. One such protein, replication factor C (RFC), functions with the proliferating cell nuclear antigen (PCNA), replication protein A (RPA), and DNA polymerase delta to synthesize the leading strand at a replication fork. To determine whether these proteins perform similar roles during replication of DNA from origins in cellular chromosomes, we have begun to characterize functionally homologous proteins from the yeast Saccharomyces cerevisiae. RFC from S. cerevisiae was purified by its ability to stimulate yeast DNA polymerase delta on a primed single-stranded DNA template in the presence of yeast PCNA and RPA. Like its human-cell counterpart, RFC from S. cerevisiae (scRFC) has an associated DNA-activated ATPase activity as well as a primer-template, structure-specific DNA binding activity. By analogy with the phage T4 and SV40 DNA replication in vitro systems, the yeast RFC, PCNA, RPA, and DNA polymerase delta activities function together as a leading-strand DNA replication complex. Now that RFC from S. cerevisiae has been purified, all seven cellular factors previously shown to be required for SV40 DNA replication in vitro have been identified in S. cerevisiae.  相似文献   
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The industrial park of Herdersbrug (Brugge, Flanders, Belgium) comprises 92 small and medium‐sized enterprises, a waste‐to‐energy incinerator, and a power plant (not included in the study) on its site. To study the carbon dioxide (CO2) neutrality of the park, we made a park‐wide inventory for 2007 of the CO2 emissions due to energy consumption (electricity and fossil fuel) and waste incineration, as well as an inventory of the existing renewable electricity and heat generation. The definition of CO2 neutrality in Flanders only considers CO2 released as a consequence of consumption or generation of electricity, not the CO2 emitted when fossil fuel is consumed for heat generation. To further decrease or avoid CO2 emissions, we project and evaluate measures to increase renewable energy generation. The 21 kilotons (kt) of CO2 emitted due to electricity consumption are more than compensated by the 25 kt of CO2 avoided by generation of renewable electricity. Herdersbrug Industrial Park is thus CO2 neutral, according to the definition of the Flemish government. Only a small fraction (6.6%) of the CO2 emitted as a consequence of fossil fuel consumption (heat generation) and waste incineration is compensated by existing and projected measures for renewable heat generation. Of the total CO2 emission (149 kt) due to energy consumption (electricity + heat generation) and waste incineration on the Herdersbrug Industrial Park in 2007, 70.5% is compensated by existing and projected renewable energy generated in the park. Forty‐seven percent of the yearly avoided CO2 corresponds to renewable energy generated from waste incineration and biomass fermentation.  相似文献   
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Quantified were the age, growth, mortality and reproductive structure of lake sturgeon (Acipenser fulvescens) collected in the US and Canadian waters of the Namakan Reservoir. The hypotheses were tested that (i) age and growth of lake sturgeon in the Namakan Reservoir would differ by sex and reproductive stage of maturity, and (ii) that the relative strength of year‐classes of lake sturgeon in the reservoir would be affected by environmental variables. To quantify age, growth and mortality of the population, existing data was used from a multi‐agency database containing information on all lake sturgeon sampled in the reservoir from 2004 to 2009. Lake sturgeon were sampled in the Minnesota and Ontario waters of the Namakan Reservoir using multi‐filament gillnets 1.8 m high and 30–100 m long and varying in mesh size from 178 to 356 mm stretch. Reproductive structure of the lake sturgeon was assessed only during spring 2008 and 2009 using plasma testosterone and estradiol‐17β concentrations. Ages of lake sturgeon >75 cm ranged from 9 to 86 years (n = 533, mean = 36 years). A catch‐curve analysis using the 1981–1953 year classes estimated total annual mortality of adults to be 4.8% and annual survival as 95.2%. Using logistic regression analysis, it was found that total annual precipitation was positively associated with lake sturgeon year‐class strength in the Namakan Reservoir. A 10 cm increase in total annual precipitation was associated with at least a 39% increase in the odds of occurrence of a strong year class of lake sturgeon in the reservoir. Plasma steroid analysis revealed a sex ratio of 2.4 females: 1 male and, on average, 10% of female and 30% of male lake sturgeon were reproductively mature each year (i.e. potential spawners). Moreover, there was evidence based on re‐captured male fish of both periodic and annual spawning, as well as the ability of males to rapidly undergo gonadal maturation prior to spawning. Knowledge of lake sturgeon reproductive structure and factors influencing recruitment success contribute to the widespread conservation efforts for this threatened species.  相似文献   
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Predators directly impact prey populations through lethal encounters, but understanding nonlethal, indirect effects is also critical because foraging animals often face trade‐offs between predator avoidance and energy intake. Quantifying these indirect effects can be difficult even when it is possible to monitor individuals that regularly interact. Our goal was to understand how movement and resource selection of a predator (wolves; Canis lupus) influence the movement behavior of a prey species (moose; Alces alces). We tested whether moose avoided areas with high predicted wolf resource use in two study areas with differing prey compositions, whether avoidance patterns varied seasonally, and whether daily activity budgets of moose and wolves aligned temporally. We deployed GPS collars on both species at two sites in northern Minnesota. We created seasonal resource selection functions (RSF) for wolves and modeled the relationship between moose first‐passage time (FPT), a method that discerns alterations in movement rates, and wolf RSF values. Larger FPT values suggest rest/foraging, whereas shorter FPT values indicate travel/fleeing. We found that the movements of moose and wolves peaked at similar times of day in both study areas. Moose FPTs were 45% lower in areas most selected for by wolves relative to those avoided. The relationship between wolf RSF and moose FPT was nonlinear and varied seasonally. Differences in FPT between low and high RSF values were greatest in winter (?82.1%) and spring (?57.6%) in northeastern Minnesota and similar for all seasons in the Voyageurs National Park ecosystem. In northeastern Minnesota, where moose comprise a larger percentage of wolf diet, the relationship between moose FPT and wolf RSF was more pronounced (ave. across seasons: ?60.1%) than the Voyageurs National Park ecosystem (?30.4%). These findings highlight the role wolves can play in determining moose behavior, whereby moose spend less time in areas with higher predicted likelihood of wolf resource selection.  相似文献   
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