Selective estrogen receptor modulators (SERMs), including the SERM/SERD bazedoxifene (BZA), are used to treat postmenopausal osteoporosis and may reduce breast cancer (BCa) risk. One of the most ...persistent unresolved questions regarding menopausal hormone therapy is compromised control of proliferation and phenotype because of short- or long-term administration of mixed-function estrogen receptor (ER) ligands. To gain insight into epigenetic effectors of the transcriptomes of hormone and BZA-treated BCa cells, we evaluated a panel of histone modifications. The impact of short-term hormone treatment and BZA on gene expression and genome-wide epigenetic profiles was examined in ERαneg mammary epithelial cells (MCF10A) and ERα+ luminal breast cancer cells (MCF7). We tested individual components and combinations of 17β-estradiol (E2), estrogen compounds (EC10) and BZA. RNA-seq for gene expression and ChIP-seq for active (H3K4me3, H3K4ac, H3K27ac) and repressive (H3K27me3) histone modifications were performed. Our results show that the combination of BZA with E2 or EC10 reduces estrogen-mediated patterns of histone modifications and gene expression in MCF-7ERα+ cells. In contrast, BZA has minimal effects on these parameters in MCF10A mammary epithelial cells. BZA-induced changes in histone modifications in MCF7 cells are characterized by altered H3K4ac patterns, with changes at distal enhancers of ERα-target genes and at promoters of non-ERα bound proliferation-related genes. Notably, the ERα target gene GREB1 is the most sensitive to BZA treatment. Our findings provide direct mechanistic-based evidence that BZA induces epigenetic changes in E2 and EC10 mediated control of ERα regulatory programs to target distinctive proliferation gene pathways that restrain the potential for breast cancer development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The predator satiation (PS) hypothesis of masting holds that seeding periodicity among plant populations enhances seed survival by starving granivores during low‐output periods and satiating reduced ...consumer populations during mast (high‐output) years. Although well‐studied in the northern hemisphere and in New Zealand, the PS hypothesis has received scant research attention in Australia. This is despite vegetation communities across nearly half the continent being dominated by masting species subject to high levels of seed predation (e.g. mulga Acacia aneura shrublands and spinifex Triodia spp. grasslands). Here, phenological monitoring and experimental testing of the PS hypothesis in the desert masting grass Triodia pungens (soft spinifex) occurred over 10 years at Deep Well station, central Australia. Field evidence supported the hypothesis that masting enhances seed escape from predators, as mean proportion seed survival at experimental bait stations was significantly greater during mast years (0.38 in 2012 and 0.33 in 2017) than during inter‐mast years (0.01 in 2016 and 2018). The possibility that seed decay as opposed to consumption affected results was controlled for by a deterioration experiment that indicated no significant loss of seed viability after 6‐months burial. The results support the hypothesis that masting in T. pungens is an adaptive trait related to the satiation of seed predators. However, whether masting enhances seed escape because predators are satiated at higher seed densities (i.e. masting causes a predator functional response) and/or because frequent low‐output periods reduce predator populations and make satiation more likely (i.e. a numerical predator masting response), remains unresolved. Aside from T. pungens, there are numerous other plants of the Australian arid zone that experience high levels of granivory and display masting. Seed predation may be a more important selective force acting on arid Australian plant reproduction than previously thought.
The predator satiation (PS) hypothesis holds that seeding periodicity among plant populations enhances seed escape from granivores. Although well‐studied in the northern hemisphere and in New Zealand, the PS hypothesis has received scant research attention in Australia. This study demonstrated reduced Triodia pungens seed predation during mast than inter‐mast years, suggesting that masting in this grass is an evolved reproductive syndrome driven by granivory.
A century-old tenet in physics and engineering asserts that any type of system, having bandwidth Δω, can interact with a wave over only a constrained time period Δt inversely proportional to the ...bandwidth (Δt·Δω ~ 2π). This law severely limits the generic capabilities of all types of resonant and wave-guiding systems in photonics, cavity quantum electrodynamics and optomechanics, acoustics, continuum mechanics, and atomic and optical physics but is thought to be completely fundamental, arising from basic Fourier reciprocity. We propose that this “fundamental” limit can be overcome in systems where Lorentz reciprocity is broken. As a system becomes more asymmetric in its transport properties, the degree to which the limit can be surpassed becomes greater. By way of example, we theoretically demonstrate how, in an astutely designed magnetized semiconductor heterostructure, the above limit can be exceeded by orders of magnitude by using realistic material parameters. Our findings revise prevailing paradigms for linear, time-invariant resonant systems, challenging the doctrine that high-quality resonances must invariably be narrowband and providing the possibility of developing devices with unprecedentedly high time-bandwidth performance.
Alternative stable state theory predicts that different disturbance regimes may support contrasting ecosystem states under otherwise analogous environmental conditions. In fire-prone systems, this ...theory is often invoked to explain abrupt ecotones, especially when adjacent vegetation types have contrasting flammabilities and differing tolerances to pyric perturbation. Despite being well-documented in forest-savanna transitions, unambiguous examples of fire-driven alternate stable states (FDASS) in arid systems are rare. The current study examined whether flammable spinifex (Triodia spp.) grasslands and fire-sensitive waputi (Aluta maisonneuvei subsp. maisonneuvei) shrublands in Australia’s Gibson Desert represent FDASS. Specifically, analyses of soil and topographic variables assessed whether environmental differences explain habitat zonation. To determine whether different flammabilities of Aluta and Triodia systems may perpetuate alternative states via vegetation-fire feedback processes, community-level fuelloads were quantified to provide an indirect measure of flammability. To determine the propensity for fire to trigger ‘state-shifting’, community responses to a single high-severity fire were evaluated. Habitat segregation did not relate to between-site environmental differences, and the fuel-load study indicated that the more pyrophytic community (Triodia grassland) is more flammable, and hence more likely to experience higher frequency fire-cycles. Fire was identified as a potential vector of ‘state-change’, because although both systems regenerated well after fire, Triodia reproduced more prolifically at a younger age than Aluta, and hence should tolerate shorter fire-return intervals. In the absence of between-community topographic and edaphic differences, or herbivores that consume either plant, it is likely that Aluta shrublands and Triodia grasslands represent fire-mediated alternative equilibrium states.
Understanding the mechanisms of implementation strategies (i.e., the processes by which strategies produce desired effects) is important for research to understand why a strategy did or did not ...achieve its intended effect, and it is important for practice to ensure strategies are designed and selected to directly target determinants or barriers. This study is a systematic review to characterize how mechanisms are conceptualized and measured, how they are studied and evaluated, and how much evidence exists for specific mechanisms.
We systematically searched PubMed and CINAHL Plus for implementation studies published between January 1990 and August 2018 that included the terms "mechanism," "mediator," or "moderator." Two authors independently reviewed title and abstracts and then full texts for fit with our inclusion criteria of empirical studies of implementation in health care contexts. Authors extracted data regarding general study information, methods, results, and study design and mechanisms-specific information. Authors used the Mixed Methods Appraisal Tool to assess study quality.
Search strategies produced 2277 articles, of which 183 were included for full text review. From these we included for data extraction 39 articles plus an additional seven articles were hand-entered from only other review of implementation mechanisms (total = 46 included articles). Most included studies employed quantitative methods (73.9%), while 10.9% were qualitative and 15.2% were mixed methods. Nine unique versions of models testing mechanisms emerged. Fifty-three percent of the studies met half or fewer of the quality indicators. The majority of studies (84.8%) only met three or fewer of the seven criteria stipulated for establishing mechanisms.
Researchers have undertaken a multitude of approaches to pursue mechanistic implementation research, but our review revealed substantive conceptual, methodological, and measurement issues that must be addressed in order to advance this critical research agenda. To move the field forward, there is need for greater precision to achieve conceptual clarity, attempts to generate testable hypotheses about how and why variables are related, and use of concrete behavioral indicators of proximal outcomes in the case of quantitative research and more directed inquiry in the case of qualitative research.
Five national academies of science and medicine-from Brazil, Germany, South Africa, and the United States-issued a powerful statement about air pollution's immense impacts on public health. The ...statement concluded that the evidence linking air pollution and adverse health effects is unequivocal, the costs are enormous and yet the problem is preventable. However it is insufficient to treat clean air as a policy objective. It must be regarded as a fundamental human right, related to the rights of life, health, and a safe, clean, healthy and sustainable environment. The human rights perspective changes everything, because governments have clear, legally enforceable obligations to respect, protect, and fulfill human rights.
Ongoing challenges in the swine industry, such as reduced access to antibiotics and virus outbreaks (e.g., porcine epidemic diarrhea virus, African swine fever virus), have prompted calls for ...innovative feed additives to support pig production. Medium-chain fatty acids (MCFAs) and monoglycerides have emerged as a potential option due to key molecular features and versatile functions, including inhibitory activity against viral and bacterial pathogens. In this review, we summarize recent studies examining the potential of MCFAs and monoglycerides as feed additives to improve pig gut health and to mitigate feed pathogens. The molecular properties and biological functions of MCFAs and monoglycerides are first introduced along with an overview of intervention needs at different stages of pig production. The latest progress in testing MCFAs and monoglycerides as feed additives in pig diets is then presented, and their effects on a wide range of production issues, such as growth performance, pathogenic infections, and gut health, are covered. The utilization of MCFAs and monoglycerides together with other feed additives such as organic acids and probiotics is also described, along with advances in molecular encapsulation and delivery strategies. Finally, we discuss how MCFAs and monoglycerides demonstrate potential for feed pathogen mitigation to curb disease transmission. Looking forward, we envision that MCFAs and monoglycerides may become an important class of feed additives in pig production for gut health improvement and feed pathogen mitigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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