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941.
942.
Bottom‐up processes in a declining yellow‐footed rock‐wallaby (Petrogale xanthopus celeris) population 下载免费PDF全文
Populations of large herbivores are generally considered to be food limited, escaping the regulatory effects of predation through their large body size, migratory behaviour and/or the occurrence of alternate prey species. In the Australian arid and semi‐arid zones, the availability of forage biomass is considered to be the primary driver of fluctuations in kangaroo abundance. However, little is known about the population dynamics of the smaller sympatric macropods. We examined the demographic traits of a large colony of yellow‐footed rock‐wallabies (Petrogale xanthopus celeris), following a 2‐year period of above average rainfall. The population was located within a conservation reserve that was subject to a predator control program around its perimeter and on neighbouring properties. The low predator abundance provided an opportunity to gauge the strength of bottom‐up population processes. During the two years of the study, the population declined in size by 53%, resulting from both the virtual absence of juvenile recruitment and the loss of adult wallabies. Although reproductive output was high, low pouch young and juvenile survival rates resulted in few individuals progressing into the adult population. With minimal recruitment, the rate of population decline (r = 0.77) matched the observed adult survival rate (Φ = 0.76). Despite average rainfall conditions during the study, survival rates across all age‐classes were equivalent to those reported for other rock‐wallaby populations during periods of scarcity. The reduced survival rates were attributed to low levels of forage resources, particularly around the wallabies' refuge sites, suggesting the bottom‐up regulation of the colony at high densities. The data suggest that the colony was at temporarily high abundance, following a rainfall driven pulse of recruitment. Conservation management actions for this species should focus on increasing juvenile survival rates within declining populations, through the control of feral goats (Capra hircus), rabbits (Oryctolagus cuniculus) and red foxes (Vulpes vulpes). 相似文献
943.
Angus?M?MacNicolEmail author Linda?L?Hardy Horace?J?Spencer Melanie?C?MacNicol 《BMC developmental biology》2015,15(1):15
Background
There is increasing evidence of a pivotal role for regulated mRNA translation in control of developmental cell fate transitions. Physiological and pathological stem and progenitor cell self-renewal is maintained by the mRNA-binding protein, Musashi1 through repression of translation of key mRNAs encoding cell cycle inhibitory proteins. The mechanism by which Musashi1 function is modified to allow translation of these target mRNAs under conditions that require inhibition of cell cycle progression, is unknown.Results
In this study, we demonstrate that differentiation of primary embryonic rat neural stem/progenitor cells (NSPCs) or human neuroblastoma SH-SY5Y cells results in the rapid phosphorylation of Musashi1 on the evolutionarily conserved site serine 337 (S337). Phosphorylation of this site has been shown to be required for cell cycle control during the maturation of Xenopus oocytes. S337 phosphorylation in mammalian NSPCs and human SH-SY5Y cells correlates with the de-repression and translation of a Musashi reporter mRNA and with accumulation of protein from the endogenous Musashi target mRNA, p21WAF1/CIP1. Inhibition of Musashi regulatory phosphorylation, through expression of a phospho-inhibitory mutant Musashi1 S337A or over-expression of the wild-type Musashi, blocked differentiation of both NSPCs and SH-SY5Y cells. Musashi1 was similarly phosphorylated in NSPCs and SH-SY5Y cells under conditions of nutrient deprivation-induced cell cycle arrest. Expression of the Musashi1 S337A mutant protein attenuated nutrient deprivation-induced NSPC and SH-SY5Y cell death.Conclusions
Our data suggest that in response to environmental cues that oppose cell cycle progression, regulation of Musashi function is required to promote target mRNA translation and cell fate transition. Forced modulation of Musashi1 function may present a novel therapeutic strategy to oppose pathological stem cell self-renewal.944.
Chronic mTOR inhibition in mice with rapamycin alters T,B, myeloid,and innate lymphoid cells and gut flora and prolongs life of immune‐deficient mice 下载免费PDF全文
Vincent Hurez Vinh Dao Aijie Liu Srilakshmi Pandeswara Jonathan Gelfond Lishi Sun Molly Bergman Carlos J. Orihuela Veronica Galvan Álvaro Padrón Justin Drerup Yang Liu Paul Hasty Zelton Dave Sharp Tyler J. Curiel 《Aging cell》2015,14(6):945-956
The mammalian (mechanistic) target of rapamycin (mTOR) regulates critical immune processes that remain incompletely defined. Interest in mTOR inhibitor drugs is heightened by recent demonstrations that the mTOR inhibitor rapamycin extends lifespan and healthspan in mice. Rapamycin or related analogues (rapalogues) also mitigate age‐related debilities including increasing antigen‐specific immunity, improving vaccine responses in elderly humans, and treating cancers and autoimmunity, suggesting important new clinical applications. Nonetheless, immune toxicity concerns for long‐term mTOR inhibition, particularly immunosuppression, persist. Although mTOR is pivotal to fundamental, important immune pathways, little is reported on immune effects of mTOR inhibition in lifespan or healthspan extension, or with chronic mTOR inhibitor use. We comprehensively analyzed immune effects of rapamycin as used in lifespan extension studies. Gene expression profiling found many and novel changes in genes affecting differentiation, function, homeostasis, exhaustion, cell death, and inflammation in distinct T‐ and B‐lymphocyte and myeloid cell subpopulations. Immune functions relevant to aging and inflammation, and to cancer and infections, and innate lymphoid cell effects were validated in vitro and in vivo. Rapamycin markedly prolonged lifespan and healthspan in cancer‐ and infection‐prone mice supporting disease mitigation as a mechanism for mTOR suppression‐mediated longevity extension. It modestly altered gut metagenomes, and some metagenomic effects were linked to immune outcomes. Our data show novel mTOR inhibitor immune effects meriting further studies in relation to longevity and healthspan extension. 相似文献
945.
Cátia Fernandes-Cerqueira Elena Ossipova Sunithi Gunasekera Monika Hansson Linda Mathsson Anca I. Catrina Yngve Sommarin Lars Klareskog Karin Lundberg Johan R?nnelid Ulf G?ransson Per-Johan Jakobsson 《Arthritis research & therapy》2015,17(1)
IntroductionWe have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA).MethodsThe autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP)2 using the CCPlus® ELISA kit.ResultsTwo peptides derived from the fibrinogen α chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen β chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency.ConclusionsHere we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA. 相似文献
946.
947.
Reduction in nutrient intake without malnutrition can delay ageing and extend healthy life in diverse organisms from yeast to primates. This effect can be recapitulated by genetic or pharmacological dampening of the signal through nutrient signalling pathways, making them a promising target for intervention into human ageing and age-related diseases. Here we review the current knowledge of the interactions between nutrient signalling pathways and ageing, focusing on the findings emerged in the past few years. 相似文献
948.
Bailey K Cevik V Holton N Byrne-Richardson J Sohn KH Coates M Woods-Tör A Aksoy HM Hughes L Baxter L Jones JD Beynon J Holub EB Tör M 《Molecular plant-microbe interactions : MPMI》2011,24(7):827-838
RPP5 is the seminal example of a cytoplasmic NB-LRR receptor-like protein that confers downy mildew resistance in Arabidopsis thaliana. In this study, we describe the cloning and molecular characterization of the gene encoding ATR5(Emoy2), an avirulence protein from the downy mildew pathogen Hyaloperonospora arabidopsidis isolate Emoy2. ATR5(Emoy2) triggers defense response in host lines expressing the functional RPP5 allele from Landsberg erecta (Ler-0). ATR5(Emoy2) is embedded in a cluster with two additional ATR5-like (ATR5L) genes, most likely resulting from gene duplications. ATR5L proteins do not trigger RPP5-mediated resistance and the copy number of ATR5L genes varies among H. arabidopsidis isolates. ATR5(Emoy2) and ATR5L proteins contain a signal peptide, canonical EER motif, and an RGD motif. However, they lack the canonical translocation motif RXLR, which characterizes most oomycete effectors identified so far. The signal peptide and the N-terminal regions including the EER motif of ATR5(Emoy2) are not required to trigger an RPP5-dependent immune response. Bioinformatics screen of H. arabidopsidis Emoy2 genome revealed the presence of 173 open reading frames that potentially encode for secreted proteins similar to ATR5(Emoy2), in which they share some motifs such as EER but there is no canonical RXLR motif. 相似文献
949.
Miao J Choi SE Seok SM Yang L Zuercher WJ Xu Y Willson TM Xu HE Kemper JK 《Molecular endocrinology (Baltimore, Md.)》2011,25(7):1159-1169
950.