1,345 research outputs found
The Importance of DNA Repair in Tumor Suppression
The transition from a normal to cancerous cell requires a number of highly
specific mutations that affect cell cycle regulation, apoptosis,
differentiation, and many other cell functions. One hallmark of cancerous
genomes is genomic instability, with mutation rates far greater than those of
normal cells. In microsatellite instability (MIN tumors), these are often
caused by damage to mismatch repair genes, allowing further mutation of the
genome and tumor progression. These mutation rates may lie near the error
catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting
that further increasing mutation rates will destroy cancerous genomes. However,
recent results have demonstrated that DNA genomes exhibit an error threshold at
mutation rates far lower than their conservative counterparts. Furthermore,
while the maximum viable mutation rate in conservative systems increases
indefinitely with increasing master sequence fitness, the semiconservative
threshold plateaus at a relatively low value. This implies a paradox, wherein
inaccessible mutation rates are found in viable tumor cells. In this paper, we
address this paradox, demonstrating an isomorphism between the conservatively
replicating (RNA) quasispecies model and the semiconservative (DNA) model with
post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes
inactivated, the maximum viable mutation rate increases smoothly to that of a
conservatively replicating system on a transformed landscape, with an upper
bound that is dependent on replication rates. We postulate that inactivation of
post-methylation repair mechanisms are fundamental to the progression of a
tumor cell and hence these mechanisms act as a method for prevention and
destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation;
Minor error corrected; Minor changes to model syste
Hidden in plain sight: The importance of cryptic interactions in marine plankton
Here, we present a range of interactions, which we term “cryptic interactions.” These are interactions that occur throughout the marine planktonic foodweb but are currently largely overlooked by established methods, which mean large‐scale data collection for these interactions is limited. Despite this, current evidence suggests some of these interactions may have perceptible impacts on foodweb dynamics and model results. Incorporation of cryptic interactions into models is especially important for those interactions involving the transport of nutrients or energy. Our aim is to highlight a range of cryptic interactions across the plankton foodweb, where they exist, and models that have taken steps to incorporate these interactions. Additionally, it is discussed where additional research and effort is required to continue advancing our understanding of these cryptic interactions. We call for more collaboration between ecologists and modelers in order to incorporate cryptic interactions into biogeochemical and foodweb models
Climate variability, oceanography, bowhead whale distribution, and Iñupiat subsistence whaling near Barrow, Alaska
Author Posting. © Arctic Institute of North America, 2010. This article is posted here by permission of Arctic Institute of North America for personal use, not for redistribution. The definitive version was published in Arctic 63 (2010): 179-194.The annual migration of bowhead whales (Balaena mysticetus) past Barrow, Alaska, has provided subsistence hunting to Iñupiat for centuries. Bowheads recurrently feed on aggregations of zooplankton prey near Barrow in autumn. The mechanisms that form these aggregations, and the associations between whales and oceanography, were investigated using field sampling, retrospective analysis, and traditional knowledge interviews. Oceanographic and aerial surveys were conducted near Barrow during August and September in 2005 and 2006. Multiple water masses were observed, and close coupling between water mass type and biological characteristics was noted. Short-term variability in hydrography was associated with changes in wind speed and direction that profoundly affected plankton taxonomic composition. Aggregations of ca. 50–100 bowhead whales were observed in early September of both years at locations consistent with traditional knowledge. Retrospective analyses of records for 1984–2004 also showed that annual aggregations of whales near Barrow were associated with wind speed and direction. Euphausiids and copepods appear to be upwelled onto the Beaufort Sea shelf during Eor SEwinds. A favorable feeding environment is produced when these plankton are retained and concentrated on the shelf by the prevailing westward Beaufort Sea shelf currents that converge with the Alaska Coastal Current flowing to the northeast along the eastern edge of Barrow Canyon.This work was supported by NSF Grants OPPPP-0436131 to C. Ashjian (S. Braund Subcontract), OPPPP-0436110 to R. Campbell, OPPPP-0436127 to W. Maslowski, OPPPP-0436009 to C. Nicolson and J. Kruse, OPPPP-043166 to S. Okkonen, and OPPPP-0435956 to Y. Spitz, E. Sherr, and B. Sherr
Nature of the Na 20 2646-keV level and the stellar reaction rate for Ne 19 ( p ,γ ) 20 Na
Careful comparison of F20 and Na20, and available data on reactions leading to both, suggests that Jπ(2646)=3+. Other mirror identifications are indicated and quantities of astrophysical interest are calculated
p27KIP1 Deletions in Childhood Acute Lymphoblastic Leukemia
AbstractThe p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations in childhood acute lymphoblastic leukemia (ALL). As described here, fluorescence in situ hybridization (FISH) analysis of 35 primary ALL samples with cytogenetic evidence of 12p abnormalities revealed hemizygous deletions of p27KIP1 in 29 cases. Further analysis of 19 of these cases with two additional gene-specific probes from the 12p region (hematopoietic cell phosphatase, HCP and cyclin D2, CCND2) showed that p27KIP1 is located more proximally on the short arm of chromosome 12 and is deleted more frequently than either HCP or CCND2. Of 16 of these cases with hemizygous deletion of p27KIP1, only eight showed loss of HCP or CCND2, whereas loss of either of the latter two loci was uniformly associated with loss of p27KIP1. Missense mutations or mutations leading to premature termination codons were not detected in the coding sequences of the retained p27KIP1 alleles in any of the 16 ALL cases examined, indicating a lack of homozygous inactivation. By Southern blot analysis, one case of primary T-cell ALL had hemizygous loss of a single p27KIP1 allele and a 34.5-kb deletion, including the second coding exon of the other allele. Despite homozygous inactivation of p27KIP1 in this case, our data suggest that haploinsufficiency for p27KIP1 is the primary consequence of 12p chromosomal deletions in childhood ALL. The oncogenic role of reduced, but not absent, levels of p27KIP1 is supported by recent studies in murine models and evidence that this protein not only inhibits the activity of complexes containing CDK2 and cyclin E, but also promotes the assembly and catalytic activity of CDK4 or CDK6 in complexes with cyclin D
Ecological organization and succession during natural recolonization of a tropical pond
Study of in vitro and in vivo effects of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells
Structure of the mirror nuclei Be and B in a microscopic cluster model
The structure of the mirror nuclei Be and B is studied in a
microscopic and three-cluster model
using a fully antisymmetrized 9-nucleon wave function. The two-nucleon
interaction includes central and spin-orbit components and the Coulomb
potential. The ground state of Be is obtained accurately with the
stochastic variational method, while several particle-unbound states of both
Be and B are investigated with the complex scaling method.The
calculation for Be supports the recent identification for the existence of
two broad states around 6.5 MeV, and predicts the and
states at about 4.5 MeV and 8 MeV, respectively. The
similarity of the calculated spectra of Be and B enables one to
identify unknown spins and parities of the B states. Available data on
electromagnetic moments and elastic electron scatterings are reproduced very
well. The enhancement of the 1 transition of the first excited state in
Be is well accounted for. The calculated density of Be is found to
reproduce the reaction cross section on a Carbon target. The analysis of the
beta decay of Li to Be clearly shows that the wave function of Be
must contain a small component that cannot be described by the simple model. This small component can be well accounted for by extending a
configuration space to include the distortion of the -particle to
and partitions.Comment: 24 page
The Molecular Diversity of Freshwater Picoeukaryotes Reveals High Occurrence of Putative Parasitoids in the Plankton
Eukaryotic microorganisms have been undersampled in biodiversity studies in freshwater environments. We present an original 18S rDNA survey of freshwater picoeukaryotes sampled during spring/summer 2005, complementing an earlier study conducted in autumn 2004 in Lake Pavin (France). These studies were designed to detect the small unidentified heterotrophic flagellates (HF, 0.6–5 µm) which are considered the main bacterivores in aquatic systems. Alveolates, Fungi and Stramenopiles represented 65% of the total diversity and differed from the dominant groups known from microscopic studies. Fungi and Telonemia taxa were restricted to the oxic zone which displayed two fold more operational taxonomic units (OTUs) than the oxycline. Temporal forcing also appeared as a driving force in the diversification within targeted organisms. Several sequences were not similar to those in databases and were considered as new or unsampled taxa, some of which may be typical of freshwater environments. Two taxa known from marine systems, the genera Telonema and Amoebophrya, were retrieved for the first time in our freshwater study. The analysis of potential trophic strategies displayed among the targeted HF highlighted the dominance of parasites and saprotrophs, and provided indications that these organisms have probably been wrongfully regarded as bacterivores in previous studies. A theoretical exercise based on a new ‘parasite/saprotroph-dominated HF hypothesis’ demonstrates that the inclusion of parasites and saprotrophs may increase the functional role of the microbial loop as a link for carbon flows in pelagic ecosystems. New interesting perspectives in aquatic microbial ecology are thus opened
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