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71.
Stirling PC Bakhoum SF Feigl AB Leroux MR 《Nature structural & molecular biology》2006,13(10):865-870
Molecular chaperones have evolved diverse tertiary and quaternary structures to stabilize non-native polypeptides and facilitate their transition to the native state. Indeed, different families of chaperones lack sequence similarity, and few are represented ubiquitously in all three domains of life. Despite their discrete evolutionary paths, recent crystal structures reveal that many chaperones use seemingly convergent strategies to bind non-native proteins. This crystallographic evidence shows, or strongly suggests, that chaperones including prefoldin, Skp, trigger factor, Hsp40 and Hsp90 have clamp-like structural features used to grip substrate proteins. We explore the notion that clamp-like structures are evolutionarily favored by both ATP-dependent and ATP-independent molecular chaperones. Presumably, clamps present a multivalent binding surface ideal for protecting unstable protein conformers until they reach the native state or are transferred to another component of the folding machinery. 相似文献
72.
Premolar teeth collected from 220 adult female polar bears (Ursus maritimus) from western Hudson Bay, Canada, were examined to determine whether past reproductive events are recorded in cementum. The
widths of annular cementum growth layer groups (GLGs) were measured and compared as proportional width index (PWI) values
to correct for age and body size bias. Known reproductive states (pregnant, with cubs, or with yearlings) were used to confirm
and calibrate cementum annuli. Significant differences in PWI were observed between GLGs formed the year females were pregnant
versus when accompanied by cubs or yearlings. The probability of a female having produced a cub in adulthood was determined
by fitting a logistic regression model between the ΔPWI of females when pregnant and with their cubs. Logistic regression
of ΔPWI (β0 = −0.229, β1 = −13.465, G
2 = 46.55, df = 1, P < 0.001) correctly classified the presence or absence of cubs in 72% of GLGs. Cementum width did not vary between different
litter sizes. Observations of females with early litter loss suggests that longer periods of lactation contributes to decreased
cementum width and therefore cementum may record a minimum age of litter survival. Predictions of litter production rate (0.43 litters/female/year)
derived from cementum were similar to field observations; however, age at first parturition was underestimated by 1 year.
We conclude that patterns of cementum deposition may be useful to determine individual reproductive histories and establish
course estimates of reproductive parameters when regular field observations are not feasible. We also conclude that reproductive
parameters derived from cementum are not adequate on their own for monitoring populations which are in decline or under stress
and field observation should not be replaced under these conditions. 相似文献
73.
Stirling PC Crisp MJ Basrai MA Tucker CM Dunham MJ Spencer FA Hieter P 《Chromosoma》2012,121(3):263-275
It has been more than two decades since the original chromosome transmission fidelity (Ctf) screen of Saccharomyces cerevisiae was published. Since that time the spectrum of mutations known to cause Ctf and, more generally, chromosome instability (CIN)
has expanded dramatically as a result of systematic screens across yeast mutant arrays. Here we describe a comprehensive summary
of the original Ctf genetic screen and the cloning of the remaining complementation groups as efforts to expand our knowledge
of the CIN gene repertoire and its mutability in a model eukaryote. At the time of the original screen, it was impossible
to predict either the genes and processes that would be overrepresented in a pool of random mutants displaying a Ctf phenotype
or what the entire set of genes potentially mutable to Ctf would be. We show that in a collection of 136 randomly selected
Ctf mutants, >65% of mutants map to 13 genes, 12 of which are involved in sister chromatid cohesion and/or kinetochore function.
Extensive screening of systematic mutant collections has shown that ~350 genes with functions as diverse as RNA processing
and proteasomal activity mutate to cause a Ctf phenotype and at least 692 genes are required for faithful chromosome segregation.
The enrichment of random Ctf alleles in only 13 of ~350 possible Ctf genes suggests that these genes are more easily mutable
to cause genome instability than the others. These observations inform our understanding of recurring CIN mutations in human
cancers where presumably random mutations are responsible for initiating the frequently observed CIN phenotype of tumors. 相似文献
74.
Steven W Kembel Evan Jones Jeff Kline Dale Northcutt Jason Stenson Ann M Womack Brendan JM Bohannan G Z Brown Jessica L Green 《The ISME journal》2012,6(8):1469-1479
Buildings are complex ecosystems that house trillions of microorganisms interacting with each other, with humans and with their environment. Understanding the ecological and evolutionary processes that determine the diversity and composition of the built environment microbiome—the community of microorganisms that live indoors—is important for understanding the relationship between building design, biodiversity and human health. In this study, we used high-throughput sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and airborne bacterial communities at a health-care facility. We quantified airborne bacterial community structure and environmental conditions in patient rooms exposed to mechanical or window ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbial communities than did window-ventilated rooms. Bacterial communities in indoor environments contained many taxa that are absent or rare outdoors, including taxa closely related to potential human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relative humidity and temperature, were correlated with the diversity and composition of indoor bacterial communities. The relative abundance of bacteria closely related to human pathogens was higher indoors than outdoors, and higher in rooms with lower airflow rates and lower relative humidity. The observed relationship between building design and airborne bacterial diversity suggests that we can manage indoor environments, altering through building design and operation the community of microbial species that potentially colonize the human microbiome during our time indoors. 相似文献
75.
In this paper, we present an application of a number of tools and concepts for modeling and analyzing raw, unaveraged, and
unedited breath-by-breath oxygen uptake data. A method for calculating anaerobic capacity is used together with a model, in
the form of a set of coupled nonlinear ordinary differential equations to make predictions of the
kinetics, the time to achieve a percentage of a certain constant oxygen demand, and the time limit to exhaustion at intensities
other than those in which we have data. Speeded oxygen kinetics and increased time limit to exhaustion are also investigated
using the eigenvalues of the fixed points of our model. We also use a way of analyzing the oxygen uptake kinetics using a
plot of
vs
which allows one to observe both the fixed point solutions and also the presence of speeded oxygen kinetics following training.
A method of plotting the eigenvalue versus oxygen demand is also used which allows one to observe where the maximum amplitude
of the so-called slow component will be and also how training has changed the oxygen uptake kinetics by changing the strength
of the attracting fixed point for a particular demand. 相似文献
76.
Judith van Holten Kris Reedquist Pascale Sattonet-Roche Tom JM Smeets Christine Plater-Zyberk Margriet J Vervoordeldonk Paul P Tak 《Arthritis research & therapy》2004,6(3):R239
We investigated the therapeutic potential and mechanism of action of IFN-β protein for the treatment of rheumatoid arthritis
(RA). Collagen-induced arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice were given daily injections
of recombinant mouse IFN-β or saline for 7 days. Disease progression was monitored by visual clinical scoring and measurement
of paw swelling. Inflammation and joint destruction were assessed histologically 8 days after the onset of arthritis. Proteoglycan
depletion was determined by safranin O staining. Expression of cytokines, receptor activator of NF-κB ligand, and c-Fos was
evaluated immunohistochemically. The IL-1-induced expression of IL-6, IL-8, and granulocyte/macrophage-colony-stimulating
factor (GM-CSF) was studied by ELISA in supernatant of RA and osteoarthritis fibroblast-like synoviocytes incubated with IFN-β.
We also examined the effect of IFN-β on NF-κB activity. IFN-β, at 0.25 μg/injection and higher, significantly reduced disease
severity in two experiments, each using 8–10 mice per treatment group. IFN-β-treated animals displayed significantly less
cartilage and bone destruction than controls, paralleled by a decreased number of positive cells of two gene products required
for osteoclastogenesis, receptor activator of NF-κB ligand and c-Fos. Tumor necrosis factor α and IL-6 expression were significantly
reduced, while IL-10 production was increased after IFN-β treatment. IFN-β reduced expression of IL-6, IL-8, and GM-CSF in
RA and osteoarthritis fibroblast-like synoviocytes, correlating with reduced NF-κB activity. The data support the view that
IFN-β is a potential therapy for RA that might help to diminish both joint inflammation and destruction by cytokine modulation. 相似文献
77.
78.
79.
The anti-PM/Scl autoantibodies are known to characterize a subset of autoimmune patients with myositis, scleroderma (Scl), and the PM/Scl overlap syndrome. The major autoantigens that are recognized by anti-PM/Scl autoantibodies are designated PM/Scl-100 and PM/Scl-75. These autoantigens have been reported to associate into a large complex consisting of 11 to 16 proteins and to play a role in ribosome synthesis. Recently, it was discovered that the PM/Scl complex is the human counterpart of the yeast (Saccharomyces cerevisiae) exosome, which is an RNA-processing complex consisting of 11 3' → 5' exoribonucleases. To date, 10 human exosome components have been identified, although only some of these were studied in more detail. In this review, we discuss some recent advances in the characterization of the PM/Scl complex. 相似文献
80.