The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the ...adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo.
There has been an explosion of interest in mindfulness-based programs (MBPs) such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy. This is demonstrated in ...increased research, implementation of MBPs in healthcare, educational, criminal justice and workplace settings, and in mainstream interest. For the sustainable development of the field there is a need to articulate a definition of what an MBP is and what it is not. This paper provides a framework to define the essential characteristics of the family of MBPs originating from the parent program MBSR, and the processes which inform adaptations of MBPs for different populations or contexts. The framework addresses the essential characteristics of the program and of teacher. MBPs: are informed by theories and practices that draw from a confluence of contemplative traditions, science, and the major disciplines of medicine, psychology and education; underpinned by a model of human experience which addresses the causes of human distress and the pathways to relieving it; develop a new relationship with experience characterized by present moment focus, decentering and an approach orientation; catalyze the development of qualities such as joy, compassion, wisdom, equanimity and greater attentional, emotional and behavioral self-regulation, and engage participants in a sustained intensive training in mindfulness meditation practice, in an experiential inquiry-based learning process and in exercises to develop understanding. The paper's aim is to support clarity, which will in turn support the systematic development of MBP research, and the integrity of the field during the process of implementation in the mainstream.
We analyze K2 light curves for 132 low-mass (1 M M* 0.1 M ) members of the 600-800 Myr old Hyades cluster and measure rotation periods ( ) for 116 of these stars. These include 93 stars with no prior ...measurements; the total number of Hyads with a known is now 232. We then combine literature binary data with Gaia DR2 photometry and astrometry to select single-star sequences in the Hyades and its roughly coeval Praesepe open cluster and derive a new reddening value of AV = 0.035 0.011 for Praesepe. Comparing the effective temperature- distributions for the Hyades and Praesepe, we find that solar-type Hyads rotate, on average, 0.4 day slower than their Praesepe counterparts. This difference indicates that the Hyades is slightly older than Praesepe: we apply a new gyrochronology model tuned with Praesepe and the Sun and find an age difference between the two clusters of 57 Myr. However, this difference decreases and eventually disappears for lower-mass stars. This provides further evidence for stalling in the rotational evolution of these stars and highlights the need for more detailed analysis of angular momentum evolution for stars of different masses and ages.
Immunity, microbiota and kidney disease Knauf, Felix; Brewer, J Richard; Flavell, Richard A
Nature reviews. Nephrology,
05/2019, Letnik:
15, Številka:
5
Journal Article
Recenzirano
The recognition that intestinal microbiota exert profound effects on human health has led to major advances in our understanding of disease processes. Studies over the past 20 years have shown that ...host components, including components of the host immune system, shape the microbial community. Pathogenic alterations in commensal microorganisms contribute to disease manifestations that are generally considered to be noncommunicable, such as inflammatory bowel disease, diabetes mellitus and liver disease, through a variety of mechanisms, including effects on host immunity. More recent studies have shed new light on how the immune system and microbiota might also drive the pathogenesis of renal disorders. In this Review, we discuss the latest insights into the mechanisms regulating the microbiome composition, with a focus both on genetics and environmental factors, and describe how commensal microorganisms calibrate innate and adaptive immune responses to affect the activation threshold for pathogenic stimulations. We discuss the mechanisms that lead to intestinal epithelial barrier inflammation and the relevance of certain bacteria to the pathogenesis of two common kidney-based disorders: hypertension and renal stone disease. Limitations of current approaches to microbiota research are also highlighted, emphasizing the need to move beyond studies of correlation to causation.
Bayesian inference methods rely on numerical algorithms for both model selection and parameter inference. In general, these algorithms require a high computational effort to yield reliable estimates. ...One of the major challenges in phylogenetics is the estimation of the marginal likelihood. This quantity is commonly used for comparing different evolutionary models, but its calculation, even for simple models, incurs high computational cost. Another interesting challenge relates to the estimation of the posterior distribution. Often, long Markov chains are required to get sufficient samples to carry out parameter inference, especially for tree distributions. In general, these problems are addressed separately by using different procedures. Nested sampling (NS) is a Bayesian computation algorithm, which provides the means to estimate marginal likelihoods together with their uncertainties, and to sample fromthe posterior distribution at no extra cost. The methods currently used in phylogenetics for marginal likelihood estimation lack in practicality due to their dependence on many tuning parameters and their inability of most implementations to provide a direct way to calculate the uncertainties associated with the estimates, unlike NS. In this article, we introduce NS to phylogenetics. Its performance is analysed under different scenarios and compared to established methods. We conclude that NS is a competitive and attractive algorithm for phylogenetic inference. An implementation is available as a package for BEAST 2 under the LGPL licence, accessible at https://github.com/BEAST2-Dev/nested-sampling.
Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required ...for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system
. Blocking either viral replication with remdesivir
or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release interleukin 1 (IL-1) and IL-18, and undergo pyroptosis, thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and the accompanying inflammatory response are necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Notably, this blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 through the production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.
In this special issue about biofactors causing cognitive impairment, we present evidence for and discuss two such biofactors. One is excess copper, causing neuronal toxicity. The other is zinc ...deficiency, causing neuronal damage. We present evidence that Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years. This leads to the conclusion that something in the developed environment is a major risk factor for AD. We hypothesize that the factor is inorganic copper, leached from the copper plumbing, the use of which coincides with the AD epidemic. We present a web of evidence supporting this hypothesis. Regarding zinc, we have shown that patients with AD are zinc deficient when compared with age‐matched controls. Zinc has critical functions in the brain, and lack of zinc can cause neuronal death. A nonblinded study about 20 years ago showed considerable improvement in AD with zinc therapy, and a mouse AD model study also showed significant cognitive benefit from zinc supplementation. In a small blinded study we carried out, post hoc analysis revealed that 6 months of zinc therapy resulted in significant benefit relative to placebo controls in two cognitive measuring systems. These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both.
Most work on plant competition intensity in general has focused on how aboveground and belowground competition for resources between plants changes with soil resource availability. In contrast, much ...work on the competitive effects of non‐native invasive species on native species has focused on other mechanisms (e.g., allelopathy and microbial changes) and has largely ignored how these effects interact with mechanisms of resource competition along productivity gradients. We examined aboveground effects of an invasive grass, Microstegium vimineum, along with soil differences between invaded and non‐invaded areas on two native perennial herbs at a productive and an unproductive oak woodland site in north Mississippi, USA. We transplanted 32 individuals each of Helianthus silphioides and Potentilla simplex from uninvaded areas into natural patches dominated by M. vimineum at each of the sites. Each transplant was randomly assigned to a pot with either native soil or soil from around M. vimineum roots. Aboveground competition was manipulated by securing M. vimineum shoots in a non‐shading position around the transplant. We monitored survival of all transplants weekly in the growing seasons of 2020 and 2021. Transplant survival of H. silphioides was lowest in M. vimineum soil at the more productive site when M. vimineum was not pinned back. Transplant survival of P. simplex was lower at the more productive site but was mostly unresponsive to pinning and soil treatments. Synthesis. Our results suggest that soil‐mediated legacy effects of an invader may reduce some native species' ability to compete for light at productive sites.
Most work on plant competition intensity has focused on how aboveground and belowground competition for resources between plants changes with soil resource availability, while work on the competitive effects of non‐native invasive species on native species has focused on non‐resource‐related mechanisms (e.g., allelopathy) and has largely ignored how these effects interact with other mechanisms of competition along productivity gradients. We examined aboveground and soil‐mediated legacy effects of an invasive grass, Japanese stilt grass, Microstegium vimineum, on two native perennial herbs at a productive and an unproductive oak woodland site in north Mississippi, USA. Transplant survival of the Ozark sunflower, Helianthus silphioides, was lowest in M. vimineum soil at the more productive site when M. vimineum was not pinned back, while transplant survival of the common cinquefoil, Potentilla simplex, was lower at the more productive site but did not show a statistically significant response to competition treatments, suggesting that soil‐mediated legacy effects of an invader have the potential to reduce some native species' ability to compete for light, especially at productive sites.
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