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Abstract TP53 nonsense mutations in cancer produce truncated inactive p53 protein. We show that 5-FU metabolite 5-Fluorouridine (FUr) induces full-length p53 in human tumor cells carrying R213X nonsense mutant TP53. Ribosome profiling visualized translational readthrough at the R213X premature stop codon and demonstrated that FUr-induced readthrough is less permissive for canonical stop codon readthrough compared to aminoglycoside G418. FUr is incorporated into mRNA and can potentially base-pair with guanine, allowing insertion of Arg tRNA at the TP53 R213X UGA premature stop codon and translation of full-length wild-type p53. We confirmed that full-length p53 rescued by FUr triggers tumor cell death by apoptosis. FUr also restored full-length p53 in TP53 R213X mutant human tumor xenografts in vivo. Thus, we demonstrate a novel strategy for therapeutic rescue of nonsense mutant TP53 and suggest that FUr should be explored for treatment of patients with TP53 nonsense mutant tumors.

The urban heat island effect is a worldwide phenomenon that has been linked to species distributions and abundances in cities. However, effects of urban heat on biotic communities are nearly impossible to disentangle from effects of land cover in most cases because hotter urban sites also have less vegetation and more impervious surfaces than cooler sites within cities. We sampled phorid flies, one of the largest, most biologically diverse families of true flies (Insecta: Diptera: Phoridae), at 30 sites distributed within the central Los Angeles Basin, where we found that temperature and the density of urban land cover are decoupled. Abundance, richness, and community composition of phorids inside urban Los Angeles were most parsimoniously accounted for by mean air temperature in the week preceding sampling. Sites with intermediate mean temperatures had more phorid fly individuals and higher richness. Communities were more even at urban sites with lower minimum temperatures and sites located further away from natural areas, suggesting that communities separated from natural source populations may be more homogenized. Species composition was best explained by minimum temperature. Inasmuch as warmer areas within cities can predict future effects of climate change, phorid fly communities are likely to shift nonlinearly under future climates in more natural areas. Exhaustive surveys of biotic communities within cities, such as the one we describe here, can provide baselines for determining the effects of urban and global climate warming as they intensify.

The microbiome of built structures has considerable influence over an inhabitant's well-being, yet the vast majority of research has focused on human-built structures. Ants are well-known architects, capable of constructing elaborate dwellings, the microbiome of which is underexplored. Here, we explore the bacterial and fungal microbiomes in functionally distinct chambers within and outside the nests of Azteca alfari ants in Cecropia peltata trees. We predicted that A. alfari colonies (1) maintain distinct microbiomes within their nests compared to the surrounding environment, (2) maintain distinct microbiomes among nest chambers used for different functions, and (3) limit both ant and plant pathogens inside their nests. In support of these predictions, we found that internal and external nest sampling locations had distinct microbial communities, and A. alfari maintained lower bacterial richness in their 'nurseries'. While putative animal pathogens were suppressed in chambers that ants actively inhabited, putative plant pathogens were not, which does not support our hypothesis that A. alfari defends its host trees against microbial antagonists. Our results show that ants influence microbial communities inside their nests similar to studies of human homes. Unlike humans, ants limit the bacteria in their nurseries and potentially prevent the build-up of insect-infecting pathogens. These results highlight the importance of documenting how indoor microbiomes differ among species, which might improve our understanding of how to promote indoor health in human dwellings.

Premise of the Study:Herbarium specimens are increasingly used as records of plant flowering phenology. However, most herbarium-based studies on plant phenology focus on taxa from temperate regions. Here, we explore flowering phenologic responses to climate in the subtropical plant genus Protea (Proteaceae), an iconic group of plants that flower year-round and are endemic to subtropical Africa. Methods:We present a novel, circular sliding window approach to investigate phenological patterns developed for species with year-round flowering. We employ our method to evaluate the extent to which site-to-site and year-to-year variation in temperature and precipitation affect flowering dates using a database of 1727 herbarium records of 25 Protea species. We also explore phylogenetic conservatism in flowering phenology. Results:We show that herbarium data combined with our sliding window approach successfully captured independently reported flowering phenology patterns (r = 0.93). Both warmer sites and warmer years were associated with earlier flowering of 3-5 days/°C, whereas precipitation variation had no significant effect on flowering phenology. Although species vary widely in phenological responsiveness, responses are phylogenetically conserved, with closely related species tending to shift flowering similarly with increasing temperature. Discussion:Our results point to climate-responsive phenology for this important plant genus and indicate that the subtropical, aseasonally flowering genus Protea has temperature-driven flowering responses that are remarkably similar to those of better-studied northern temperate plant species, suggesting a generality across biomes that has not been described elsewhere.

Global change has become a central focus of modern biology. Yet, our knowledge of how anthropogenic drivers affect biodiversity and natural resources is limited by a lack of biological data spanning the Anthropocene. We propose that the hundreds of millions of plant, fungal and animal specimens deposited in natural history museums have the potential to transform the field of global change biology. We suggest that museum specimens are underused, particularly in ecological studies, given their capacity to reveal patterns that are not observable from other data sources. Increasingly, museum specimens are becoming mobilized online, providing unparalleled access to physiological, ecological and evolutionary data spanning decades and sometimes centuries. Here, we describe the diversity of collections data archived in museums and provide an overview of the diverse uses and applications of these data as discussed in the accompanying collection of papers within this theme issue. As these unparalleled resources are under threat owing to budget cuts and other institutional pressures, we aim to shed light on the unique discoveries that are possible in museums and, thus, the singular value of natural history collections in a period of rapid change.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.

Mounting evidence shows that species interactions may mediate how individual species respond to climate change. However, long-term anthropogenic effects on species interactions are poorly characterized owing to a lack of data. Insect herbivory is a major ecological process that represents the interaction between insect herbivores and their host plants, but historical data on insect damage to plants is particularly sparse. Here, we suggest that museum collections of insects and plants can fill key gaps in our knowledge on changing trophic interactions, including proximate mechanisms and the net outcomes of multiple global change drivers across diverse insect herbivore-plant associations. We outline theory on how global change may affect herbivores and their host plants and highlight the unique data that could be extracted from museum specimens to explore their shifting interactions. We aim to provide a framework for using museum specimens to explore how some of the most diverse co-evolved relationships are responding to climate and land use change.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.

Predicting how ecological interactions will respond to global change is a major challenge. Plants and their associated insect herbivores compose much of macroscopic diversity, yet how their interactions have been altered by recent environmental change remains underexplored. To address this gap, we quantified herbivory on herbarium specimens of four plant species with records extending back 112 years. Our study focused on the northeastern US, where temperatures have increased rapidly over the last few decades. This region also represents a range of urban development, a form of global change that has shown variable effects on herbivores in the past studies. Herbarium specimens collected in the early 2000s were 23% more likely to be damaged by herbivores than those collected in the early 1900s. Herbivory was greater following warmer winters and at low latitudes, suggesting that climate warming may drive increasing insect damage over time. In contrast, human population densities were negatively associated with herbivore damage. To explore whether changes in insect occurrence or abundance might explain shifts in herbivory, we used insect observational records to build climate occupancy models for lepidopteran herbivores (butterflies and moths) of our focal plant species. These models show that higher winter temperatures were associated with higher probability of insect herbivore presence, while urbanization was associated with reduced probability of herbivore presence, supporting a link between insect herbivore occurrence and herbivory mediated through environment. Synthesis. Using a temporal record of plant herbivory that spans over a century, we show that both temperature and urbanization influence insect damage to plants, but in very different ways. Our results indicate that damage to plants by insect herbivores will likely continue to increase through time in the northeastern US as global temperatures rise, but that urbanization may disrupt local effects of winter warming on herbivory by excluding certain herbivores. These changes may scale to shape ecosystem processes that are driven by herbivory, including plant productivity.

Summary: Influenza viruses (IVs) cause substantial global morbidity and mortality. Given the limited range of licensed antiviral drugs and their reduced efficacy due to resistance mutations, repurposing FDA-approved kinase inhibitors as fast-tracked host-targeted antivirals is an attractive strategy. We identified six FDA-approved non-receptor tyrosine kinase-inhibitors (NRTKIs) as potent inhibitors of viral replication of pandemic and seasonal IVs in vitro. We validated their efficacy in a biologically and clinically relevant ex vivo model of human precision-cut lung slices. We identified steps of the virus infection cycle affected by these inhibitors and assessed their effect(s) on host responses. Their overlapping targets suggest crosstalk between Abl, EGFR, and PDGFR pathways during IAV infection. Our data and established safety profiles of these NRTKIs provide compelling evidence for further clinical investigations and repurposing as host-targeted influenza antivirals. Moreover, these NRTKIs have broad-spectrum antiviral potential given that their kinase/pathway targets are critical for the replication of many viruses.

We generate extremely asymmetric sub-half-cycle terahertz waveforms with scalable field strengths at megahertz pulse-repetition rates via ultrafast excitation of spatially indirect interband transitions in tailored quantum well heterostructures.

The influence of climate on deep-time plant-insect interactions is becoming increasingly well known, with temperature, CO2 increases (and associated stoichiometric changes in plants), and aridity likely playing a critical role. In our modern climate, all three factors are shifting at an unprecedented rate, with uncertain consequences for biodiversity. To investigate effects of temperature, stoichiometry (specifically that of nitrogen), and aridity on insect herbivory, we explored insect herbivory in three modern floral assemblages and in 39 fossil floras, especially focusing on eight floras around a past hyperthermal event (the Paleocene-Eocene Thermal Maximum) from Bighorn Basin (BB). We find that higher temperatures were associated with increased herbivory in the past, especially among BB sites. In these BB sites, non-N2-fixing plants experienced a lower richness but higher frequency of herbivory damage than N2-fixing plants. Herbivory frequency but not richness was greater in BB sites compared with contemporaneous, nearby, but less arid sites from Hanna Basin. Compared with deep-time environments, herbivory frequency and richness are higher in modern sites, suggesting that current accelerated warming uniquely impacts plant-insect interactions. Overall, our work addresses multiple aspects of climate change using fossil data while also contextualizing the impact of modern anthropogenic change on Earth's most diverse interactions. [ABSTRACT FROM AUTHOR]

Introduction: The national guidelines and the Standing Committee on Vaccination (STIKO) of the Robert Koch Institute (RKI) in Germany support preventive vaccinations for patients under immunomodulatory treatments. Material and methods: Retrospective analysis of data from patients with chronic inflammatory skin diseases from December 2021 to December 2022 with a focus on preventive vaccinations against influenza virus, varicella zoster virus, or SARS-CoV-2. Results: Patients with chronic inflammatory skin diseases were referred to our university outpatient's clinic for recommendations of systemic therapy. Vaccinations against influenza virus, varicella zoster virus, or SARS-CoV-2 were documented in 7365 analyzed patient files. A total of 79.7% were completely vaccinated against SARS-CoV-2, 49.7% patients were vaccinated against the influenza virus, and only 9.2% were completely vaccinated against varicella zoster virus. Discussion: In our patients who came for counselling before or during systemic treatment, vaccination rates against SARS-CoV-2, varicella zoster virus, or influenza virus were low. Patients age 60 and above had higher rates than the average German population of the same age, but still no satisfying protection. Conclusions: We suggest informing patients about preventive vaccination before and during systemic immunomodulatory treatments and emphasize the need for active communication in this vulnerable patient group. [ABSTRACT FROM AUTHOR]

This article discusses teacher educators' response to how teacher education programs should prepare prospective teachers to be teachers of English language learners. In the case study presented, the authors note that discussions have ensued about whether teaching English language learners (ELLs) should be addressed through separate coursework or whether content areas (e.g., English language arts) should infuse this content into already existing disciplines. Though content fields, such as English language arts, have been encouraged to address the teaching of English language learners, Lucas and Villegas (2011) assert that teacher education programs have yet to adequately address the needs of ELLs throughout the curriculum. Findings illuminate the connection--and sometimes conflation--of the aims of teaching diverse learners and teaching ELLs, the importance of teacher education coherence, and the value of a partnership approach to the teaching of ELLs.

Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.

Urban forests provide important ecosystem services to city residents, including pollution removal and carbon storage. Climate change and urbanization pose multiple threats to these services. However, how these threats combine to affect urban trees, and thus how to mitigate their effects, remains largely untested because multi-factorial experiments on mature trees are impractical. We used a unique urban warming experiment paired with a laboratory chamber experiment to determine how three of the most potentially damaging factors associated with global change for urban and rural trees—warming, drought, and insect herbivory—affect growth of Quercus phellos (willow oak), the most commonly planted large shade tree in the southeastern US, which is known for its resilience to these potential stressors. In a previous study, we found that the urban heat island effect was associated with reduced growth of Q. phellos and higher abundance of Parthenolecanium scale insects, key pests of oaks in cities. Here, we tested the hypothesis that tree water stress is the mechanism for these effects of warming. We found evidence that water stress is a major, interactive factor reducing urban tree growth, but found no evidence that water stress is associated with Parthenolecanium survival or abundance. Warming and Parthenolecanium only reduced growth in Q. phellos saplings that were simultaneously water stressed. Synthesis and applications. Across many temperate cities worldwide, urban trees grow less than rural trees. Our results point to water stress as the most likely driver for this pattern. Importantly, we found that water stress both reduces tree growth on its own and exacerbates effects of warming and insect pests on tree growth. Therefore, management strategies targeted at increasing tree hydration in cities may reduce effects of these three key stressors that are expected to intensify with further urbanization and climate change.

Linked Article: https://doi.org/10.1002/ece3.3965.

Human-driven movements and extinctions of species have made plant communities across biomes more homogenous. Here the authors quantify plant vascular species and phylogenetic homogenization across the globe, finding that non-native species naturalisations have been a major driver.

This article presents three modern female writers who (re-)create forms of self-awareness and identity in their literary texts. Sibilla Aleramo, Colette, and Mela Hartwig share the experience of patriarchal hegemony, the lack of a female writing tradition and an avant-gardist search for new identity constructions. All three became successful writers, but only for a short time before they went to exile, were silenced or marginalized. Their approaches include a plurality of voices that range from the re-enactment of the past—through mythologies, childhood, foundation narratives or matrilinear genealogies—to decompositions or destructive fantasies. As contemporaries from different European countries together they paved the way for experimental approaches to the (re-)creation of female writing in the early twentieth century. However, their understanding of the female role also undermines the traditional binarism inducing new forms of expression. By comparing their literature this article highlights their decisive roles in the articulation of subjectivity and suggests to reintegrate their work into the literary canon of European modernism.

In light of global climate change, ecological studies increasingly address effects of temperature on organisms and ecosystems. To measure air temperature at biologically relevant scales in the field, ecologists often use small, portable temperature sensors. Sensors must be shielded from solar radiation to provide accurate temperature measurements, but our review of 18 years of ecological literature indicates that shielding practices vary across studies (when reported at all), and that ecologists often invent and construct ad hoc radiation shields without testing their efficacy. We performed two field experiments to examine the accuracy of temperature observations from three commonly used portable data loggers (HOBO Pro, HOBO Pendant, and iButton hygrochron) housed in manufactured Gill shields or ad hoc, custom-fabricated shields constructed from everyday materials such as plastic cups. We installed this sensor array (five replicates of 11 sensor-shield combinations) at weather stations located in open and forested sites. HOBO Pro sensors with Gill shields were the most accurate devices, with a mean absolute error of 0.2°C relative to weather stations at each site. Error in ad hoc shield treatments ranged from 0.8 to 3.0°C, with the largest errors at the open site. We then deployed one replicate of each sensor-shield combination at five sites that varied in the amount of urban impervious surface cover, which presents a further shielding challenge. Bias in sensors paired with ad hoc shields increased by up to 0.7°C for every 10% increase in impervious surface. Our results indicate that, due to variable shielding practices, the ecological literature likely includes highly biased temperature data that cannot be compared directly across studies. If left unaddressed, these errors will hinder efforts to predict biological responses to climate change. We call for greater standardization in how temperature data are recorded in the field, handled in analyses, and reported in publications.

Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple sclerosis (MS), particularly in the deep gray matter (DGM). Previous studies were able to only partially separate iron-modifying effects because of incomplete knowledge of iron-modifying processes and influencing factors. It is therefore unclear to what extent and at which stages of the disease different processes contribute to brain iron changes. We postulate that spatially covarying magnetic susceptibility networks determined with Independent Component Analysis (ICA) reflect, and allow for the study of, independent processes regulating iron levels.We applied ICA to quantitative susceptibility maps for 170 individuals aged 9–81 years without neurological disease (“Healthy Aging” (HA) cohort), and for a cohort of 120 patients with MS and 120 age- and sex-matched healthy controls (HC; together the “MS/HC” cohort).Two DGM-associated “susceptibility networks” identified in the HA cohort (the Dorsal Striatum and Globus Pallidus Interna Networks) were highly internally reproducible (i.e. “robust”) across multiple ICA repetitions on cohort subsets. DGM areas overlapping both robust networks had higher susceptibility levels than DGM areas overlapping only a single robust network, suggesting that these networks were caused by independent processes of increasing iron concentration. Because MS is thought to accelerate brain aging, we hypothesized that associations between age and the two robust DGM-associated networks would be enhanced in patients with MS. However, only one of these networks was altered in patients with MS, and it had a null age association in patients with MS rather than a stronger association. Further analysis of the MS/HC cohort revealed three additional disease-related networks (the Pulvinar, Mesencephalon, and Caudate Networks) that were differentially altered between patients with MS and HCs and between MS subtypes. Exploratory regression analyses of the disease-related networks revealed differential associations with disease duration and T2 lesion volume. Finally, analysis of ROI-based disease effects in the MS/HC cohort revealed an effect of disease status only in the putamen ROI and exploratory regression analysis did not show associations between the caudate and pulvinar ROIs and disease duration or T2 lesion volume, showing the ICA-based approach was more sensitive to disease effects.These results suggest that the ICA network framework increases sensitivity for studying patterns of brain iron change, opening a new avenue for understanding brain iron physiology under normal and disease conditions.

Globally, many grasslands have been lost or degraded via settlement, conversion to agriculture, or use as pasture. These losses have damaged the ability of migratory and nomadic birds of prey to find suitable breeding territories. Habitat restoration of degraded grasslands via the application of biosolids, the treated and sterilized remains from sewage treatment plants, improves soil water retention and nutrient profile, leading to substantial gains in plant growth and nutritive quality. Gains to wild and domestic herbivores have been documented, but impacts to predators are poorly known. Here, we test the hypothesis that biosolids-applied pastures are attractive to and support migratory and nomadic avian predators in central British Columbia, Canada. We obtained habitat records from sightings and prey remains from pellets for three vole-specialists, Long-eared Owls (Asio otus), Short-eared Owls (A. flammeus), and Northern Harriers (Circus hudsonius), as well as the generalist American Kestrels (Falco sparverius). During 5 years, the three diurnal species preferentially used biosolids-applied pastures, and kestrels and owls nested in biosolids-applied pastures or in forest patches adjacent to these pastures. Grasshoppers were more abundant on pastures with biosolids and were common prey for American Kestrels. The owls and harriers preferentially consumed voles, although Short-eared Owls consumed deermice (Peromyscus maniculatus) as a major additional food source during years when voles were scarce. Long-eared Owls were documented only in the 2 years when voles were common. Collectively, these results suggest that biosolids-amended landscapes may attract raptors, even when vole densities are low.

Here, Roxhed et al. develop a multiplexed approach to screen IgG and IgM levels against several SARS-CoV-2 proteins in home-sampled dried blood spots and estimate seroprevalence of 12.5% in Stockholm in spring of 2020.

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Public lands are often managed for multiple uses ranging from energy development to rare plant conservation. Habitat models can help land managers assess and mitigate potential effects of projects on rare plants, but it is unclear how models are currently being used. Our goal was to better understand how staff in the Bureau of Land Management currently use habitat models to inform their decisions, and perceived challenges and benefits associated with that use. We first examined litigation documents to determine whether the agency has been challenged on its use of data for rare plants and found no relevant legal challenges. Second, we analyzed model use in National Environmental Policy Act (NEPA) documents and found no clear citations of habitat models. Finally, we conducted interviews with agency staff who analyze potential effects of proposed actions on rare plants in NEPA documents. The primary challenges interviewees faced in using models related to data organization and access, model quality and accuracy, and institutional capacity. Interviewees believed models could be used more to inform decisions and actions to conserve rare plants and rare plant habitat on public lands and recommended improving staff access to models, creating models for additional species, and addressing staffing limitations. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: To support research projects that require medical data from multiple sites is one of the goals of the German Medical Informatics Initiative (MII). The data integration centers (DIC) at university medical centers in Germany provide patient data via FHIR® in compliance with the MII core data set (CDS). Requirements for data protection and other legal bases for processing prefer decentralized processing of the relevant data in the DICs and the subsequent exchange of aggregated results for cross-site evaluation. Methods: Requirements from clinical experts were obtained in the context of the MII use case INTERPOLAR. A software architecture was then developed, modeled using 3LGM², finally implemented and published in a github repository. Results: With the CDS tool chain, we have created software components for decentralized processing on the basis of the MII CDS. The CDS tool chain requires access to a local FHIR endpoint and then transfers the data to an SQL database. This is accessed by the DataProcessor component, which performs calculations with the help of rules (input repo) and writes the results back to the database. The CDS tool chain also has a frontend module (REDCap), which is used to display the output data and calculated results, and allows verification, evaluation, comments and other responses. This feedback is also persisted in the database and is available for further use, analysis or data sharing in the future. Discussion: Other solutions are conceivable. Our solution utilizes the advantages of an SQL database. This enables flexible and direct processing of the stored data using established analysis methods. Due to the modularization, adjustments can be made so that it can be used in other projects. We are planning further developments to support pseudonymization and data sharing. Initial experience is being gathered. An evaluation is pending and planned. [ABSTRACT FROM AUTHOR]

Introduction The Local Data Hub (LDH) is a platform for FAIR sharing of medical research (meta-)data. In order to promote the usage of LDH in different research communities, it is important to understand the domain-specific needs, solutions currently used for data organization and provide support for seamless uploads to a LDH. In this work, we analyze the use case of microneurography, which is an electrophysiological technique for analyzing neural activity. Methods After performing a requirements analysis in dialogue with microneurography researchers, we propose a concept-mapping and a workflow, for the researchers to transform and upload their metadata. Further, we implemented a semi-automatic upload extension to odMLtables, a template-based tool for handling metadata in the electrophysiological community. Results The open-source implementation enables the odML-to-LDH concept mapping, allows data anonymization from within the tool and the creation of custom-made summaries on the underlying data sets. Discussion This concludes a first step towards integrating improved FAIR processes into the research laboratory's daily workflow. In future work, we will extend this approach to other use cases to disseminate the usage of LDHs in a larger research community. [ABSTRACT FROM AUTHOR]