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91.
Background
Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies. 相似文献92.
Simmonds HA Cameron JS Goldsmith DJ Fairbanks LD Raman GV 《Nucleosides, nucleotides & nucleic acids》2006,25(9-11):1071-1075
Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early. Compliance with allopurinol treatment and diet has been as important as early recognition. Hypertension has been rigorously controlled. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide? 相似文献
93.
T. Niemeyer C. Dietz L. Fairbanks I. Schroeder-Printzen R. Henkel M. Löeffler 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1215-1219
The objective of this study was to elucidate the role of uridine for spermatozoa, since this pyrimidine nucleoside was found in millimolar concentration in human seminal plasma. Here, the degradative activity of uridine-phosphorylase [EC 2.4.2.3] and the salvage activity of uridine kinase [EC 2.7.1.48] were detected in human spermatozoa. HPLC analysis depicted the uptake of exogeneous 14C-labelled adenine, but not of uridine and of hypoxanthine, into nucleotide pools of boar spermatozoa. On addition of uridine, the computer-assisted semen analysis (CASA) of human cells revealed a reduction of the percentage of motile spermatozoa in contrast to an elevation of some velocity parameters. It is concluded that exogeneous uridine could function as suppressor for early capacitation and as a substrate for phosphorolysis, if ribose is needed, rather than to satisfy a demand for intracellular pyrimidine nucleotides. 相似文献
94.
Pluvinage B Higgins MA Abbott DW Robb C Dalia AB Deng L Weiser JN Parsons TB Fairbanks AJ Vocadlo DJ Boraston AB 《Structure (London, England : 1993)》2011,19(11):1603-1614
The complete degradation of N-linked glycans by the pathogenic bacterium Streptococcus pneumoniae is facilitated by the large multimodular cell wall-attached exo-β-D-N-acetylglucosaminidase StrH. Structural dissection of this virulence factor using X-ray crystallography showed it to have two structurally related glycoside hydrolase family 20 catalytic domains, which displayed the expected specificity for complex N-glycans terminating in N-acetylglucosamine but exhibited unexpected differences in their preferences for the substructures present in these glycans. The structures of the two catalytic domains in complex with unhydrolyzed substrates, including an N-glycan possessing a bisecting N-acetylglucosamine residue, revealed the specific architectural features in the active sites that confer their differential specificities. Inhibitors of StrH are demonstrated to be effective tools in modulating the interaction of StrH with components of the host, such as the innate immune system. Overall, new structural and functional insight into a carbohydrate-mediated component of the pneumococcus-host interaction is provided. 相似文献
95.
Laura S. Stone Jonathan P. German Kelly F. Kitto Carolyn A. Fairbanks George L. Wilcox 《PloS one》2014,9(10)
Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs). Analgesics acting at α2ARs and opioid receptors (ORs) frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C). Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic efficacy over either drug alone. These data support the utility of combination adrenergic/opioid therapy in pain management for antinociceptive efficacy with reduced side-effect liability. 相似文献
96.
Walker PL Corrigan A Arenas M Escuredo E Fairbanks L Marinaki A 《Nucleosides, nucleotides & nucleic acids》2011,30(12):1243-1247
Purine nucleoside phosphorylase (PNPase) deficiency is an autosomal recessive disorder affecting purine degradation and salvage pathways. Clinically, patients typically present with severe immunodeficiency, neurological dysfunction, and autoimmunity. Biochemically, PNPase deficiency may be suspected in the presence of hypouricemia. We report biochemical and genetic data on a cohort of seven patients from six families identified as PNPase deficient. In all patients, inosine, deoxyinosine, guanosine, and deoxyguanosine were elevated in urine, and mutation analysis revealed seven different mutations of which three were novel. The mutation c.770A>G resulted in the substitution p.His257Arg. A second novel mutation c.257A>G (p.His86Arg) was identified in two siblings and a third novel mutation, c.199C>T (p.Arg67X), was found in a 2-year-old female with delayed motor milestones and recurrent respiratory infections. A review of the literature identified 67 cases of PNPase deficiency from 49 families, including the cases from our own laboratory. PNPase deficiency was confirmed in 30 patients by genotyping and 24 disease causing mutations, including the three novel mutations described in this paper, have been reported to date. In five of the seven patients, plasma uric acid was found to be within the pediatric normal range, suggesting that PNPase deficiency should not be ruled out in the absence of hypouricemia. 相似文献
97.
Thumma SR Fairbanks RK Lamoreaux WT Mackay AR Demakas JJ Cooke BS Elaimy AL Hanson PW Lee CM 《World journal of surgical oncology》2012,10(1):75-12
ABSTRACT: BACKGROUND: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors and is associated with a dismal prognosis. The median survival after the primary diagnosis remains poor, even after multimodal treatment approaches. However, a few patients have been reported to have long term survival greater than three years. A number of studies have attempted to define factors capable of predicting long term outcomes in specific patient groups. This article reports the outcomes of a very large group of patients diagnosed with GBM, and analyzes specific prognostic factors known to influence survival in these patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) to investigate various patient-related and treatment- related factors that could influence the long term survival in patients diagnosed with glioblastoma. A total of 34,664 patients aged 20 years or older with a diagnosis of GBM during the years 1973 to 2008 were studied. Overall survival outcomes were examined with Kaplan-Meier survival analysis and Cox hazard models. RESULTS: Asian/Pacific Islanders had a better survival compared to the white population (P = <0.001). Patients diagnosed with GBM during the years 2000 to 2008 had a superior survival rate when compared with earlier decades (P = <0 .001). Statistically significant improvements in overall survival were also found for patients who received surgical resections, and adjuvant radiation treatment versus no radiation (P-values <0.001). Young age was also found to be highly predictive of improved overall survival rates when separated into age groups as well as when studied as a continuous variable. CONCLUSIONS: Clinical pretreatment and treatment factors, including young age at diagnosis, Asian/Pacific Islander ethnicity, recent year of diagnosis, surgical resection and the use of adjuvant radiation therapy favorably influence survival in patients diagnosed with glioblastoma. Trial Registration All data were obtained from the United States Surveillance Epidemiology and End Results (SEER) database. 相似文献
98.
Microsatellite polymorphisms are playing an increasingly vital role in primatological research, and are particularly useful for paternity exclusion in both wild and captive populations. Although vervet monkeys (Chlorocebus aethiops) are commonly studied in both settings, few previous studies have utilized microsatellite markers for assessing genetic variation in this species. In a pilot project to assess paternity in the UCLA-VA Vervet Monkey Research Colony (VMRC), we screened 55 commercially available human microsatellite markers chosen from a panel of 370 that have been shown to be polymorphic in baboons (Papio hamadryas). Using a standard PCR protocol, 43 (78%) loci produced amplifiable product. Of these, 14 were polymorphic and 11 were genotyped in 51 individuals, including 19 offspring and 14 potential sires. The average heterozygosity across the 11 loci was.719. In all 19 paternity cases all but one male was excluded as the true sire at two or more loci. This includes successfully distinguishing between two maternal half-sib brothers who were potential sires in most of the paternity cases. Given that the colony is descended from 54 wild-caught founders trapped between 1975 and 1987 from an introduced population on St. Kitts, West Indies, these values imply high microsatellite variability in natural vervet populations. Our results provide a panel of markers derived from the human genome that is suitable for assessing genetic variation and paternity in vervets. 相似文献
99.
Kuzoff RK; Sweere JA; Soltis DE; Soltis PS; Zimmer EA 《Molecular biology and evolution》1998,15(3):251-263
18S ribosomal RNA genes are the most widely used nuclear sequences for
phylogeny reconstruction at higher taxonomic levels in plants. However, due
to a conservative rate of evolution, 18S rDNA alone sometimes provides too
few phylogenetically informative characters to resolve relationships
adequately. Previous studies using partial sequences have suggested the
potential of 26S or large-subunit (LSU) rDNA for phylogeny retrieval at
taxonomic levels comparable to those investigated with 18S rDNA. Here we
explore the patterns of molecular evolution of entire 26S rDNA sequences
and their impact on phylogeny retrieval. We present a protocol for PCR
amplification and sequencing of entire (approximately 3.4 kb) 26S rDNA
sequences as single amplicons, as well as primers that can be used for
amplification and sequencing. These primers proved useful in angiosperms
and Gnetales and likely have broader applicability. With these protocols
and primers, entire 26S rDNA sequences were generated for a diverse array
of 15 seed plants, including basal eudicots, monocots, and higher eudicots,
plus two representatives of Gnetales. Comparisons of sequence dissimilarity
indicate that expansion segments (or divergence domains) evolve 6.4 to 10.2
times as fast as conserved core regions of 26S rDNA sequences in plants.
Additional comparisons indicate that 26S rDNA evolves 1.6 to 2.2 times as
fast as and provides 3.3 times as many phylogenetically informative
characters as 18S rDNA; compared to the chloroplast gene rbcL, 26S rDNA
evolves at 0.44 to 1.0 times its rate and provides 2.0 times as many
phylogenetically informative characters. Expansion segment sequences
analyzed here evolve 1.2 to 3.0 times faster than rbcL, providing 1.5 times
the number of informative characters. Plant expansion segments have a
pattern of evolution distinct from that found in animals, exhibiting less
cryptic sequence simplicity, a lower frequency of insertion and deletion,
and greater phylogenetic potential.
相似文献
100.
H. A. Simmonds J. S. Cameron D. J. Goldsmith L. D. Fairbanks G. Venkat Raman 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1071-1075
Renal disease is rare today in classic adult gout, and gout is rare in renal disease—especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: 1. They have been diagnosed and treated sufficiently early. 2. Compliance with allopurinol treatment and diet has been as important as early recognition. 3. Hypertension has been rigorously controlled. 4. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide? 相似文献