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1.
Genetic variation at the Major Histocompatibility Complex locus DQ beta was
analyzed in 233 beluga whales (Delphinapterus leucas) from seven
populations: St. Lawrence Estuary, eastern Beaufort Sea, eastern Chukchi
Sea, western Hudson Bay, eastern Hudson Bay, southeastern Baffin Island,
and High Arctic and in 12 narwhals (Monodon monoceros) sympatric with the
High Arctic beluga population. Variation was assessed by amplification of
the exon coding for the peptide binding region via the polymerase chain
reaction, followed by either cloning and DNA sequencing or single-stranded
conformation polymorphism analysis. Five alleles were found across the
beluga populations and one in the narwhal. Pairwise comparisons of these
alleles showed a 5:1 ratio of nonsynonymous to synonymous substitutions per
site leading to eight amino acid differences, five of which were
nonconservative substitutions, centered around positions previously shown
to be important for peptide binding. Although the amount of allelic
variation is low when compared with terrestrial mammals, the nature of the
substitutions in the peptide binding sites indicates an important role for
the DQ beta locus in the cellular immune response of beluga whales.
Comparisons of allele frequencies among populations show the High Arctic
population to be different (P < or = .005) from the other beluga
populations surveyed. In these other populations an allele, Dele-DQ
beta*0101-2, was found in 98% of the animals, while in the High Arctic it
was found in only 52% of the animals. Two other alleles were found at high
frequencies in the High Arctic population, one being very similar to the
single allele found in narwhal.
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2.
Abdollahi A Gruver BN Patriotis C Hamilton TC 《Biochemical and biophysical research communications》2003,307(1):188-197
Alteration in epidermal growth factor receptor (EGFR) family signaling is among the most frequently implicated effectors of human oncogenesis. Overexpression of members of this family of receptors has often been detected in many epithelial tumors and is believed to be associated with an overall poor prognosis in patients with cancer. Therefore, we hypothesized that identification of potential EGF target genes in normal cells will provide a basis for unbiased genetic analysis of this signaling pathway in cancer. We utilized Atlas Rat 1.2 nylon cDNA arrays (Clontech) to determine gene expression changes in normal rat ovarian surface epithelial (ROSE) cells following EGF treatment. The results indicate activation of genes involved in a wide variety of cellular mechanisms, including regulation of cell cycle and proliferation, apoptosis, and protein turnover. In addition, using an in vitro model of ovarian cancer, we demonstrated that malignant transformation of ROSE cells resulted in alteration of downstream effectors of the EGFR pathway, as exemplified by aberrant expression of p66Shc, c-Jun, c-Myc, c-Fos, Lot1, p21Cip/Waf, and cdc25A. These data suggest that knowledge of the downstream genetic lesions, which may result in loss of growth factor requirement of the affected cells, will be crucial for the selection of the EGFR pathway as an effective target for cancer therapy. 相似文献
3.
Elongation factor-1 alpha occurs as two copies in bees: implications for phylogenetic analysis of EF-1 alpha sequences in insects 总被引:5,自引:1,他引:4
We report the complete sequence of a paralogous copy of elongation factor-1
alpha (EF-1 alpha) in the honeybee, Apis mellifera (Hymenoptera: Apidae).
This copy differs from a previously described copy in the positions of five
introns and in 25% of the nucleotide sites in the coding regions. The
existence of two paralogous copies of EF-1 alpha in Drosophila and Apis
suggests that two copies of EF-1 alpha may be widespread in the
holometabolous insect orders. To distinguish between a single, ancient gene
duplication and parallel, independent fly and bee gene duplications, we
performed a phylogenetic analysis of hexapod EF-1 alpha sequences.
Unweighted parsimony analysis of nucleotide sequences suggests an ancient
gene duplication event, whereas weighted parsimony analysis of nucleotides
and unweighted parsimony analysis of amino acids suggests the contrary:
that EF-1 alpha underwent parallel gene duplications in the Diptera and the
Hymenoptera. The hypothesis of parallel gene duplication is supported both
by congruence among nucleotide and amino acid data sets and by
topology-dependent permutation tail probability (T-PTP) tests. The
resulting tree topologies are also congruent with current views on the
relationships among the holometabolous orders included in this study
(Diptera, Hymenoptera, and Lepidoptera). More sequences, from diverse
orders of holometabolous insects, will be needed to more accurately assess
the historical patterns of gene duplication in EF-1 alpha.
相似文献
4.
A Gdalyahu E Tring PO Polack R Gruver P Golshani MS Fanselow AJ Silva JT Trachtenberg 《Neuron》2012,75(1):121-132
Several models of associative learning predict that stimulus processing changes during association formation. How associative learning reconfigures neural circuits in primary sensory cortex to "learn" associative attributes of a stimulus remains unknown. Using 2-photon in vivo calcium imaging to measure responses of networks of neurons in primary somatosensory cortex, we discovered that associative fear learning, in which whisker stimulation is paired with foot shock, enhances sparse population coding and robustness of the conditional stimulus, yet decreases total network activity. Fewer cortical neurons responded to stimulation of the trained whisker than in controls, yet their response strength was enhanced. These responses were not observed in mice exposed to a nonassociative learning procedure. Our results define how the cortical representation of a sensory stimulus is shaped by associative fear learning. These changes are proposed to enhance efficient sensory processing after associative learning. 相似文献
5.
This study continues analysis from a companion paper on over 350,000 insured Swedish dogs up to 10 years of age contributing
to more than one million dog-years at risk during 1995–2000. The age patterns for total and diagnostic mortality and for general
causes of death (trauma, tumour, locomotor, heart and neurological) are presented for numerous breeds. Survival estimates
at five, eight and 10 years of age are calculated. Survival to 10 years of age was 75% or more in Labrador and golden retrievers,
miniature and toy poodles and miniature dachshunds and lowest in Irish wolfhounds (91% dead by 10 years). Multivariable analysis
was used to estimate the relative risk for general and more specific causes of death between breeds accounting for gender
and age effects, including two-way interactions. Older females had tumour as a designated cause of death more often than males
in most breeds, but not in the Bernese mountain dog. Information presented in this and the companion paper inform our understanding
of the population level burden of disease, and support decision-making at the population and individual level about health
promotion efforts and treatment and prognosis of disease events. 相似文献
6.
Aaron M Gruver Brian D Yard Campbell McInnes Changanamkandath Rajesh Douglas L Pittman 《BMC molecular biology》2009,10(1):27
Background
The homologous recombination (HR) pathway is vital for maintaining genomic integrity through the restoration of double-stranded breaks and interstrand crosslinks. The RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) are essential for this process in vertebrates, and the RAD51D paralog is unique in that it participates in both HR repair and telomere maintenance. RAD51D is also known to directly interact with the RAD51C and XRCC2 proteins. Rad51d splice variants have been reported in mouse and human tissues, supportive of a role for alternative splicing in HR regulation. The present study evaluated the interaction of the Rad51d splice isoform products with RAD51C and XRCC2 and their expression patterns. 相似文献7.
8.
Background
Movement of cells, either as amoeboid individuals or in organised groups, is a key feature of organ formation. Both modes of migration occur during Drosophila embryonic gonad development, which therefore provides a paradigm for understanding the contribution of these processes to organ morphogenesis. Gonads of Drosophila are formed from three distinct cell types: primordial germ cells (PGCs), somatic gonadal precursors (SGPs), and in males, male-specific somatic gonadal precursors (msSGPs). These originate in distinct locations and migrate to associate in two intermingled clusters which then compact to form the spherical primitive gonads. PGC movements are well studied, but much less is known of the migratory events and other interactions undergone by their somatic partners. These appear to move in organised groups like, for example, lateral line cells in zebra fish or Drosophila ovarian border cells. 相似文献9.
Hick RW Gruver AL Ventevogel MS Haynes BF Sempowski GD 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(1):169-176
The thymus is a lymphoid organ that selects T cells for release to the peripheral immune system. Unfortunately, thymopoiesis is highly susceptible to damage by physiologic stressors and can contribute to immune deficiencies that occur in a variety of clinical settings. No treatment is currently available to protect the thymus from stress-induced involution. Leptin-deficient (ob/ob) mice have severe thymic atrophy and this finding suggests that this hormone is required for normal thymopoiesis. In this study, the ability of leptin to promote thymopoiesis in wild-type C57BL/6 and BALB/c mice, as well as in leptin-deficient (ob/ob) and endotoxin-stressed (Escherichia coli LPS) mice, was determined. Leptin administration induced weight loss and stimulated thymopoiesis in ob/ob mice, but did not stimulate thymopoiesis in wild-type C57BL/6 nor BALB/c mice. In endotoxin-stressed mice, however, leptin prevented LPS-induced thymus weight loss and stimulated TCRalpha gene rearrangement. Coadministration of leptin with LPS blunted endotoxin-induced systemic corticosterone response and production of proinflammatory cytokines. Thus, leptin has a selective thymostimulatory role in settings of leptin deficiency and endotoxin administration, and may be useful for protecting the thymus from damage and augmenting T cell reconstitution in these clinical states. 相似文献
10.
Changanamkandath Rajesh Aaron M. Gruver Venkatesha Basrur Douglas L. Pittman 《Proteomics》2009,9(16):4071-4086
The RAD51 family of proteins is involved in homologous recombination (HR) DNA repair and maintaining chromosome integrity. To identify candidates that interact with HR proteins, the mouse RAD51C, RAD51D and XRCC2 proteins were purified using bacterial expression systems and each of them used to co‐precipitate interacting partners from mouse embryonic fibroblast cellular extracts. Mass spectroscopic analysis was performed on protein bands obtained after 1‐D SDS‐PAGE of co‐precipitation eluates from cell extracts of mitomycin C treated and untreated mouse embryonic fibroblasts. Profiling of the interacting proteins showed a clear bias toward nucleic acid binding and modification proteins. Interactions of four candidate proteins (SFPQ, NONO, MSH2 and mini chromosome maintenance protein 2) were confirmed by Western blot analysis of co‐precipitation eluates and were also verified to form ex vivo complexes with RAD51D. Additional interacting proteins were associated with cell division, embryo development, protein and carbohydrate metabolism, cellular trafficking, protein synthesis, modification or folding, and cell structure or motility functions. Results from this study are an important step toward identifying interacting partners of the RAD51 paralogs and understanding the functional diversity of proteins that assist or regulate HR repair mechanisms. 相似文献