Retroviruses infect a broad range of vertebrate hosts that includes amphibians, reptiles, fish, birds and mammals. In addition, a typical vertebrate genome contains thousands of loci composed of ...ancient retroviral sequences known as endogenous retroviruses (ERVs). ERVs are molecular remnants of ancient retroviruses and proof that the ongoing relationship between retroviruses and their vertebrate hosts began hundreds of millions of years ago. The long-term impact of retroviruses on vertebrate evolution is twofold: first, as with other viruses, retroviruses act as agents of selection, driving the evolution of host genes that block viral infection or that mitigate pathogenesis, and second, through the phenomenon of endogenization, retroviruses contribute an abundance of genetic novelty to host genomes, including unique protein-coding genes and cis-acting regulatory elements. This Review describes ERV origins, their diversity and their relationships to retroviruses and discusses the potential for ERVs to reveal virus-host interactions on evolutionary timescales. It also describes some of the many examples of cellular functions, including protein-coding genes and regulatory elements, that have evolved from ERVs.
Recent advances in Bayesian hypothesis testing have led to the development of uniformly most powerful Bayesian tests, which represent an objective, default class of Bayesian hypothesis tests that ...have the same rejection regions as classical significance tests. Based on the correspondence between these two classes of tests, it is possible to equate the size of classical hypothesis tests with evidence thresholds in Bayesian tests, and to equate P values with Bayes factors. An examination of these connections suggest that recent concerns over the lack of reproducibility of scientific studies can be attributed largely to the conduct of significance tests at unjustifiably high levels of significance. To correct this problem, evidence thresholds required for the declaration of a significant finding should be increased to 25–50:1, and to 100–200:1 for the declaration of a highly significant finding. In terms of classical hypothesis tests, these evidence standards mandate the conduct of tests at the 0.005 or 0.001 level of significance.
A methionine-restricted diet robustly improves healthspan in key model organisms. For example, methionine restriction reduces age-related pathologies and extends lifespan up to 45% in rodents. ...However, the mechanisms underlying these benefits remain largely unknown. We tested whether the yeast chronological aging assay could model the benefits of methionine restriction, and found that this intervention extends lifespan when enforced by either dietary or genetic approaches, and furthermore, that the observed lifespan extension is due primarily to reduced acid accumulation. In addition, methionine restriction-induced lifespan extension requires the activity of the retrograde response, which regulates nuclear gene expression in response to changes in mitochondrial function. Consistent with an involvement of stress-responsive retrograde signaling, we also found that methionine-restricted yeast are more stress tolerant than control cells. Prompted by these findings in yeast, we tested the effects of genetic methionine restriction on the stress tolerance and replicative lifespans of cultured mouse and human fibroblasts. We found that such methionine-restricted mammalian cells are resistant to numerous cytotoxic stresses, and are substantially longer-lived than control cells. In addition, similar to yeast, the extended lifespan of methionine-restricted mammalian cells is associated with NFκB-mediated retrograde signaling. Overall, our data suggest that improved stress tolerance and extension of replicative lifespan may contribute to the improved healthspan observed in methionine-restricted rodents, and also support the possibility that manipulation of the pathways engaged by methionine restriction may improve healthspan in humans.
Electrospun nanofiber composite membranes containing water-stable metal-organic frameworks (MOFs) particles (Zr-based MOF-808) supported on polyacrylonitrile (PAN) nanofiber synthesized via ...co-electrospinning have been prepared. MOF particles were dispersed in the organic polymer, and their subsequent presence was inferred by scanning electron microscopy. Membrane performance in heavy metal ion adsorption in batch filtration was evaluated on the basis of Cd2+ and Zn2+ ions sequestration. The adsorption capacities of the pristine MOF and the MOF composite membrane revealed that MOF particles in the membrane could be accessed for adsorption in the hydrophilic PAN membranes. The maximum adsorption capacities were 225.05 and 287.06 mg g–1 for Cd2+ and Zn2+, respectively. Conventional thermal activation of pristine MOF and composite membrane revealed a crystal downsizing, while “hydractivation” produced an expanded MOF with enhanced adsorption potentials. The PAN/MOF-808 “hydractivated” composite membrane could treat 580 mL of Cd, whereas the conventional vacuum-activated composite treated 464 mL. The high separation performance and reusability of the membranes and the outstanding water stability of the MOFs suggested the developed membrane as a potential candidate for water treatment.
The purification process of wastewater containing heavy metal ions (HMIs) using nano-fibrous metal-organic frameworks, MOF-808, embedded polyacrylonitrile membrane has been studied. The process ...parameters that were evaluated included feed concentration, transmembrane pressure (TMP), and membrane thickness. The effect of coexisting cations in the solution upon the removal efficiencies of Zn2+, Cd2+, Pb2+ and Hg2+ ions was also investigated. Results from the filtration experiments indicate a substantial variation in the feed volume that the membrane can treat before the permeate lead concentration reaches the allowable limit of 10 ppb, depending on the process parameter. An increase in the membrane thickness showed a significant improvement (26%) with 440 L of the treated feed volume after doubling the membrane layer. An increase in TMP could reduce the treated feed volume by 38% while a decrease in feed concentration led to a 21% increase in the treated feed volume. In the presence of other common background cations in the solution, the removal efficiency of HMIs by adsorption onto MOF-808 dropped by 18 to 37%. This result was dependent upon the HMIs, in the presence of up to three other cations but was minimal in the presence of a single cation indicative of good selectivity.
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•Metal-organic frameworks particles were enmeshed into polyacrylonitrile nanofiber membranes.•The membranes were used for the removal of Pb2+ ions from aqueous solution by adsorption.•The effects of transmembrane pressure, feed conc., and membrane thickness were investigated.•The presence of background ions on adsorption Zn2+, Cd2+, Pb2+ and Hg2+ ions was studied.•The filtration system could produce >500 L of pure water per m2 of membrane.
Although T lymphocytes have long been appreciated for their role in the immunosurveillance of cancer, it has been the realization that cancer cells may ultimately escape a response from ...tumor-reactive T cells that has ignited efforts to enhance the efficacy of anti-tumor immune responses. Recent advances in our understanding of T cell immunobiology have been particularly instrumental in informing therapeutic strategies to overcome mechanisms of tumor immune escape, and immune checkpoint blockade has emerged as one of the most promising therapeutic options for patients in the history of cancer treatment. Designed to interfere with inhibitory pathways that naturally constrain T cell reactivity, immune checkpoint blockade releases inherent limits on the activation and maintenance of T cell effector function. In the context of cancer, where negative T cell regulatory pathways are often overactive, immune checkpoint blockade has proven to be an effective strategy for enhancing the effector activity and clinical impact of anti-tumor T cells. Checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have yielded unprecedented and durable responses in a significant percentage of cancer patients in recent years, leading to U.S. FDA approval of six checkpoint inhibitors for numerous cancer indications since 2011. In this review, we highlight the clinical success of these FDA-approved immune checkpoint inhibitors and discuss current challenges and future strategies that must be considered going forward to maximize the efficacy of immune checkpoint blockade therapy for cancer.
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•CTLA-4, PD-1, and PD-L1 are key negative regulators of anti-tumor T cell reactivity.•Inhibitors of CTLA-4, PD-1, and PD-L1 can enhance anti-tumor T cell reactivity.•Immune checkpoint blockade yields significant clinical benefit in cancer patients.
The environmental impacts of the nuclear accidents of Chernobyl and Fukushima are compared. In almost every respect, the consequences of the Chernobyl accident clearly exceeded those of the Fukushima ...accident. In both accidents, most of the radioactivity released was due to volatile radionuclides (noble gases, iodine, cesium, tellurium). However, the amount of refractory elements (including actinides) emitted in the course of the Chernobyl accident was approximately four orders of magnitude higher than during the Fukushima accident. For Chernobyl, a total release of 5300PBq (excluding noble gases) has been established as the most cited source term. For Fukushima, we estimated a total source term of 520 (340–800) PBq. In the course of the Fukushima accident, the majority of the radionuclides (more than 80%) was transported offshore and deposited in the Pacific Ocean. Monitoring campaigns after both accidents reveal that the environmental impact of the Chernobyl accident was much greater than of the Fukushima accident. Both the highly contaminated areas and the evacuated areas are smaller around Fukushima and the projected health effects in Japan are significantly lower than after the Chernobyl accident. This is mainly due to the fact that food safety campaigns and evacuations worked quickly and efficiently after the Fukushima accident. In contrast to Chernobyl, no fatalities due to acute radiation effects occurred in Fukushima.
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•The environmental effects of Chernobyl and Fukushima are compared.•Releases of radionuclides from Chernobyl exceeded Fukushima by an order of magnitude.•Chernobyl caused more severe radiation-related health effects.•Overall, Chernobyl was a much more severe nuclear accident than Fukushima.•Psychological effects are neglected but important consequences of nuclear accidents.
Abstract
Demographic processes play a key role in shaping the patterns of social relations among individuals in a population. Social network analysis is a powerful quantitative tool for assessing the ...social structure formed by associations between individuals. However, demographic processes are rarely accounted for in such analyses. Here, we summarize how the structure of animal social networks is shaped by the joint effects of social behavior and turnover of individuals and suggest how a deeper understanding of these processes can open new, exciting avenues for research. Death or dispersal can have the direct effect of removing an individual and all its social connections, and can also have indirect effects, spurring changes in the distribution of social connections between remaining individuals. Recruitment and integration of juveniles and immigrant into existing social networks are critical to the emergence and persistence of social network structure. Together, these behavioral responses to loss and gain of social partners may impact how societies respond to seasonal or catastrophic turnover events. The fitness consequences of social position (e.g., survival and reproductive rates) may also create feedback between the social network structure and demography. Understanding how social structure changes in response to turnover of individuals requires further integration between long-term field studies and network modeling methods. These efforts will likely yield new insights into the connections between social networks and life history, ecological change, and evolutionary dynamics.
Lay Summary
Births, deaths, and dispersal fundamentally shape societies. We consider how demography and behavior together generate complexity in social networks. For example, how do loss of partners affect behavior? How do new individuals integrate into a society? Considering such questions can lead to new links between social network theory, life history, ecological resilience, and evolutionary dynamics.
Soil pH regulates the capacity of soils to store and supply nutrients, and thus contributes substantially to controlling productivity in terrestrial ecosystems. However, soil pH is not an independent ...regulator of soil fertility-rather, it is ultimately controlled by environmental forcing. In particular, small changes in water balance cause a steep transition from alkaline to acid soils across natural climate gradients. Although the processes governing this threshold in soil pH are well understood, the threshold has not been quantified at the global scale, where the influence of climate may be confounded by the effects of topography and mineralogy. Here we evaluate the global relationship between water balance and soil pH by extracting a spatially random sample (n = 20,000) from an extensive compilation of 60,291 soil pH measurements. We show that there is an abrupt transition from alkaline to acid soil pH that occurs at the point where mean annual precipitation begins to exceed mean annual potential evapotranspiration. We evaluate deviations from this global pattern, showing that they may result from seasonality, climate history, erosion and mineralogy. These results demonstrate that climate creates a nonlinear pattern in soil solution chemistry at the global scale; they also reveal conditions under which soils maintain pH out of equilibrium with modern climate.
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