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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.
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.
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3.
Srilatha Nalluri Sampa Ghoshal-Gupta Ammar Kutiyanawalla Sitaram Gayatri Byung Rho Lee Shahanawaz Jiwani Amyn M. Rojiani Mumtaz V. Rojiani 《PloS one》2015,10(9)
Tissue inhibitors of metalloproteinases (TIMPs) are multifaceted molecules that exhibit properties beyond their classical proteinase inhibitory function. Although TIMP-1 is a known inhibitor of apoptosis in mammalian cells, the mechanisms by which it exerts its effects are not well-established. Our earlier studies using H2009 lung adenocarcinoma cells, implanted in the CNS, showed that TIMP-1 overexpressing H2009 cells (HB-1), resulted in more aggressive tumor kinetics and increased vasculature. The present study was undertaken to elucidate the role of TIMP-1 in the context of apoptosis, using the same lung cancer cell lines. Overexpressing TIMP-1 in a lung adenocarcinoma cell line H2009 resulted in an approximately 3-fold increased expression of Bcl-2, with a marked reduction in apoptosis upon staurosporine treatment. This was an MMP-independent function as a clone expressing TIMP-1 mutant T2G, lacking MMP inhibition activity, inhibited apoptosis as strongly as TIMP1 overexpressing clones, as determined by inhibition of PARP cleavage. Immunoprecipitation of Bcl-2 from cell lysates also co-immunoprecipitated TIMP-1, indicative of an interaction between these two proteins. This interaction was specific for TIMP-1 as TIMP-2 was not present in the Bcl-2 pull-down. Additionally, we show a co-dependency of TIMP-1 and Bcl-2 RNA and protein levels, such that abrogating Bcl-2 causes a downregulation of TIMP-1 but not TIMP-2. Finally, we demonstrate that TIMP-1 dependent inhibition of apoptosis occurs through p90RSK, with phosphorylation of the pro-apoptotic protein BAD at serine 112, ultimately reducing Bax levels and increasing mitochondrial permeability. Together, these studies define TIMP-1 as an important cancer biomarker and demonstrate the potential TIMP-1 as a crucial therapeutic target. 相似文献
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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.
Pangkhi Medhi Ololade Olatunji Atul Nayak Chandra Teja Uppuluri Richard T. Olsson Buchi N. Nalluri Diganta B. Das 《AAPS PharmSciTech》2017,18(5):1488-1494
Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture. 相似文献
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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.
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