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61.
Anthony A. Killeen Kumud S. Sane Harry T. Orr 《The Journal of steroid biochemistry and molecular biology》1991,38(6):677-686
The gene encoding steroid 21-hydroxylase activity, P450c21B, is located in the major histocompatibility complex (MHC) class III region, in close proximity to a highly homologous pseudogene, P450c21A. Recombinations between P450c21B and P450c21A have been shown to result in deficiency of 21-hydroxylase activity, the usual cause of congenital adrenal hyperplasia (CAH). A mutant P450c21 gene from a patient with simple virilizing CAH was identified and shown to be consistent with a recombination between P450c21A and P450c21B. Sequence analysis of the mutant gene showed the recombination site to be located between the first exon and the second intron. The mutant gene encodes a leucine instead of the normal proline at codon 31. This mutation resides on a chromosome bearing the HLA-B44 serotype. A comparison of mutation associated with HLA-B44 and that normally found with the HLA-Bw47 serotype suggests that the HLA-B44 mutations are of more ancient origin. The patient's homologous chromosome has a deletion of P450c21B. Endocrinological testing therefore allows for testing of the mutant gene in genetic isolation. Such testing demonstrated that the patient was capable of producing aldosterone and retaining sodium in response to a low-sodium diet, indicating that the mutant gene encodes an enzyme with partial 21-hydroxylase activity. 相似文献
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63.
This experiment tested the hypothesis that changes in rate of reinforcement affect the rate of an internal pacemaker as suggested by the Behavioral Theory of Timing (BeT: Killeen and Fetterman, 1988). Pigeons were trained to discriminate durations of 10 s and 20 s, and then exposed to higher or lower rates of freely delivered reinforcers. When returned to the discrimination task, judgments were reliably biased in the predicted directions: those returning from a richer context judged standard durations to be longer than did those returning from a poorer context. These results validate a key assumption of BeT, and provide an explanation of how changing tempos of life bias the perception of time. 相似文献
64.
Aideen P Killeen Dermot G Morris David A Kenny Michael P Mullen Michael G Diskin Sinéad M Waters 《BMC genomics》2014,15(1)
Background
In both beef and dairy cattle, the majority of early embryo loss occurs within the first 14 days following insemination. During this time-period, embryos are completely dependent on their maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to their survival. The objective of this study was to investigate whether differences in endometrial gene expression during the mid-luteal phase of the estrous cycle exist between crossbred beef heifers ranked as either high (HF) or low fertility (LF) (following four rounds of artificial insemination (AI)) using the Affymetrix® 23 K Bovine Gene Chip.Results
Conception rates for each of the four rounds of AI were within a normal range: 70–73.3%. Microarray analysis of endometrial tissue collected on day 7 of the estrous cycle detected 419 differentially expressed genes (DEG) between HF (n = 6) and LF (n = 6) animals. The main gene pathways affected were, cellular growth and proliferation, angiogenesis, lipid metabolism, cellular and tissue morphology and development, inflammation and metabolic exchange. DEG included, FST, SLC45A2, MMP19, FADS1 and GALNT6.Conclusions
This study highlights, some of the molecular mechanisms potentially controlling uterine endometrial function during the mid-luteal phase of the estrous cycle, which may contribute to uterine endometrial mediated impaired fertility in cattle. Differentially expressed genes are potential candidate genes for the identification of genetic variation influencing cow fertility, which may be incorporated into future breeding programmes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-234) contains supplementary material, which is available to authorized users. 相似文献65.
William D. Gosling Francis E. Mayle Nicholas J. Tate Timothy J. Killeen 《Review of Palaeobotany and Palynology》2009,153(1-2):70-85
Accurate differentiation between tropical forest and savannah ecosystems in the fossil pollen record is hampered by the combination of: i) poor taxonomic resolution in pollen identification, and ii) the high species diversity of many lowland tropical families, i.e. with many different growth forms living in numerous environmental settings. These barriers to interpreting the fossil record hinder our understanding of the past distributions of different Neotropical ecosystems and consequently cloud our knowledge of past climatic, biodiversity and carbon storage patterns. Modern pollen studies facilitate an improved understanding of how ecosystems are represented by the pollen their plants produce and therefore aid interpretation of fossil pollen records. To understand how to differentiate ecosystems palynologically, it is essential that a consistent sampling method is used across ecosystems. However, to date, modern pollen studies from tropical South America have employed a variety of methodologies (e.g. pollen traps, moss polsters, soil samples). In this paper, we present the first modern pollen study from the Neotropics to examine the modern pollen rain from moist evergreen tropical forest (METF), semi-deciduous dry tropical forest (SDTF) and wooded savannah (cerradão) using a consistent sampling methodology (pollen traps). Pollen rain was sampled annually in September for the years 1999–2001 from within permanent vegetation study plots in, or near, the Noel Kempff Mercado National Park (NKMNP), Bolivia. Comparison of the modern pollen rain within these plots with detailed floristic inventories allowed estimates of the relative pollen productivity and dispersal for individual taxa to be made (% pollen/% vegetation or ‘p/v’). The applicability of these data to interpreting fossil records from lake sediments was then explored by comparison with pollen assemblages obtained from five lake surface samples.Pollen productivity is demonstrated to vary inter-annually and conforms to a consistent hierarchy for any given year: METF > SDTF > cerradão. This suggests an association between pollen productivity and basic structural characteristics of the ecosystem, i.e. closed canopy vs. open canopy vs. savannah. Comparison of modern pollen and vegetation revealed that some important floristic elements were completely absent from the pollen: Qualea and Erisma (METF), Bauhinia, Simira and Guazuma (SDTF), and Pouteria and Caryocar (cerradão). Anadenanthera was found to be abundant in both the pollen and flora of SDTF (p/v = 3.6), while Poaceae was relatively poorly represented in cerradão (0.2). Moraceae, Cecropia and Schefflera were found to be over-represented palynologically in all ecosystems. Overall, the data demonstrated that no one taxon could be used as a definitive indicator of any of the ecosystems. Instead, associations of taxa were found to be important: METF = Moraceae (> 40%), Cecropia, Hyeronima, Celtis; SDTF = Anadenanthera, Apuleia, Ferdinandusa and non-arboreal Asteraceae, Bromeliaceae, Piper and fern spores; cerradão = Poaceae, Myrtaceae, Borreria, Solanum plus Asteraceae and fern spores. Interpretation of Poaceae pollen was highlighted as problematic, with relatively low abundance in the cerradão (< 20%) in comparison to high abundance in lake environments (c. 30–50%). Re-examination of fossil pollen records from NKMNP revealed that modern vegetation associations were only established in the last few thousand years. 相似文献
66.
HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix-induced hyperpermeability of Caco-2 monolayers 总被引:5,自引:0,他引:5
Liu S Stolz DB Sappington PL Macias CA Killeen ME Tenhunen JJ Delude RL Fink MP 《American journal of physiology. Cell physiology》2006,290(4):C990-C999
High-mobility group box 1 (HMGB1), a cytokine-like proinflammatory protein, is secreted by activated macrophages and released by necrotic cells. We hypothesized that immunostimulated enterocytes might be another source for this mediator. Accordingly, Caco-2 cells or primary mouse intestinal epithelial cells (IECs) were incubated with "cytomix" (a mixture of TNF, IL-1, and IFN-) for various periods. HMGB1 in cell culture supernatants was detected by Western blot analysis and visualized in Caco-2 cells with the use of fluorescence confocal and immunotransmission electron microscopy. Caco-2 cells growing on filters in diffusion chambers were stimulated with cytomix for 48 h in the absence or presence of anti-HMGB1 antibody, and permeability to fluorescein isothiocyanate-dextran (average molecular mass, 4 kDa; FD4) was assessed. Cytomix-stimulated Caco-2 cells secreted HMGB1 into the apical but not the basolateral compartments of diffusion chambers. Although undetectable at 6 and 12 h after the start of incubation with cytomix, HMGB1 was present in supernatants after 24 h of incubation. HMGB1 secretion by Caco-2 monolayers also was induced when the cells were exposed to FSL-1, a Toll-like receptor (Tlr)-2 agonist, or flagellin, a Tlr5 agonist, but not lipopolysaccharide, a Tlr4 agonist. Cytomix also induced HMGB1 secretion by primary IECs. Cytoplasmic HMGB1 is localized within vesicles in Caco-2 cells and is secreted, at least in part, associated with exosomes. Incubating Caco-2 cells with cytomix increased FD4 permeation, but this effect was significantly decreased in the presence of anti-HMGB1 antibody. Collectively, these data support the view that HMGB1 is secreted by immunostimulated enterocytes. This process may exacerbate inflammation-induced epithelial hyperpermeability via an autocrine feedback loop. exosome; toll-like receptor; flagellin 相似文献
67.
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Pigeons pecked on three keys, responses to one of which could be reinforced after a few pecks, to a second key after a somewhat larger number of pecks, and to a third key after the maximum pecking requirement. The values of the pecking requirements and the proportion of trials ending with reinforcement were varied. Transits among the keys were an orderly function of peck number, and showed approximately proportional changes with changes in the pecking requirements, consistent with Weber's law. Standard deviations of the switch points between successive keys increased more slowly within a condition than across conditions. Changes in reinforcement probability produced changes in the location of the psychometric functions that were consistent with models of timing. Analyses of the number of pecks emitted and the duration of the pecking sequences demonstrated that peck number was the primary determinant of choice, but that passage of time also played some role. We capture the basic results with a standard model of counting, which we qualify to account for the secondary experiments. 相似文献
69.
70.
Russell TL Lwetoijera DW Knols BG Takken W Killeen GF Ferguson HM 《Proceedings. Biological sciences / The Royal Society》2011,278(1721):3142-3151
Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in phenotypic traits predict the dynamics of Anopheles gambiae sensu lato mosquitoes, the most important vectors of human malaria. Anopheles gambiae dynamics were monitored over a six-month period of seasonal growth and decline. The population exhibited density-dependent feedback, with the carrying capacity being modified by rainfall (97% wAIC(c) support). The individual phenotypic expression of the maternal (p = 0.0001) and current (p = 0.040) body size positively influenced population growth. Our field-based evidence uniquely demonstrates that individual fitness can have population-level impacts and, furthermore, can mitigate the impact of exogenous drivers (e.g. rainfall) in species whose reproduction depends upon it. Once frontline interventions have suppressed mosquito densities, attempts to eliminate malaria with supplementary vector control tools may be attenuated by increased population growth and individual fitness. 相似文献