bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations to the Gut Microbiota of a Wild Juvenile Passerine in an Urban Mosaic
Authors: Maraci Öncü , Corsini Michela , Antonatou-Papaioannou Anna , Jünemann Sebastian , Sudyka Joanna , Lecce Irene Di , Caspers Barbara A. , Szulkin Marta 
Published: April 2021

AbstractUrbanisation is a major anthropogenic perturbation that progressively alters multiple environmental parameters, thereby presenting novel evolutionary challenges to wild populations. Symbiotic microorganisms residing in the gastrointestinal tracts (gut) of vertebrates have well-established mutual connections with the physiology of their hosts and respond quickly to environmental alterations. However, the impacts of anthropogenic changes and urbanisation on gut microbiota remain poorly understood, especially in early development. To address this knowledge gap, we investigated the gut microbiota in juvenile great tits (Parus major) in an urban mosaic. First, we compared the microbiota of nestlings reared in artificial nest boxes or natural cavities. Next, we analysed microbiota variations employing two distinct urbanisation frameworks, (i) the classical urban/rural dichotomy and (ii) gradual changes in the amount of impervious surface area (ISA) in the urban space and identified the environmental variables that predicted the changes in the microbial communities. Alpha diversity was influenced by cavity type and by the amount of impervious surface surrounding the breeding location. Alpha diversity was also positively correlated with the tree cover density. Beta diversity differed between urban and rural sites, and these alterations covaried with sound pollution, the distance to the city centre and the distance to the closest road. Overall, the microbial communities reflect and are possibly influenced by the heterogeneous environmental modifications that are typical of the urban space. Strikingly, the choice of framework used to define the urban space can influence the outcomes of studies investigating animal-microbe symbiosis. Our results open new perspectives from which the potential function of microbial symbionts in the adaptation of their hosts to anthropogenic stress can be investigated.
Two levels of selection of rhythmicity in gene expression: energy saving for rhythmic proteins and noise optimization for rhythmic transcripts
Authors: Laloum David , Robinson-Rechavi Marc 
Published: April 2021

AbstractMany genes have nycthemeral rhythms of expression,i.e.a 24-hours periodic variation, at either mRNA or protein level or both, and, most rhythmic genes are tissue-specific. Here, we investigate and discuss the evolutionary origins of rhythms in gene expression. Our results suggest that thythmicity of protein expression has been favored by selection for low cost. Trends are consistent in bacteria, plants and animals, and are also supported in tissue-specific patterns in mouse. Cost cannot explain rhythm at the RNA level, and we suggest instead it allows to periodically and drastically reduce expression noise. Noise control had strongest support in mouse, with limited power in other species. Genes under stronger purifying selection are rhythmically expressed at the mRNA level, probably because they are noise sensitive genes. We also suggest that mRNA rhythmicity allows to switch between optimal precision and higher stochasticity. Higher precision allows to maximize the robustness of gene expression when the function is most needed, while higher stochasticity allows to maintain oscillations and to exhibit diverse molecular phenotypes, i.e. “blind anticipation” of cells. The ability to alternate between these two states, enabled by rhythmicity at the mRNA level, might be adaptive in fluctuating environments. Finally, the adaptive role of rhythmic expression is also supported by rhythmic genes being highly expressed yet tissue-specific genes. This provides a good evolutionary explanation for the observation that nycthemeral rhythms are often tissue-specific.
A shift from competition to facilitation amplifies the temperature-dependence of microbial community respiration
Authors: García Francisca C. , Clegg Tom , Barrios O’Neill Daniel , Warfield Ruth , Pawar Samraat , Yvon-Durocher Gabriel 
Published: April 2021

ABSTRACTThe respiratory release of CO2by microbes is a dominant component of the global carbon cycle. However, large uncertainties exist about the effects of climatic warming on the respiration of microbial communities due to lack of mechanistic, empirically-tested theory that accounts for dynamic species interactions. We developed a general mathematical model which predicts that thermal sensitivity of microbial community respiration increases as species interactions become more positive, i.e., change from competition to facilitation. This is because facilitation disproportionately increases positive feedbacks between the thermal sensitivities of species-level metabolic and biomass accumulation rates at warmer temperatures. We experimentally validated this prediction in bacterial communities of 8 taxa, finding that a shift from competition to facilitation after a month of co-adaptation caused a 60% increase in the thermal sensitivity of their respiration relative tode novocommunities that had not co-adapted. Thus, rapid changes in species interactions can profoundly change the temperature-dependence of microbial community respiration and should be considered in climate change models.
Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN
Authors: Li Yihang , Pazyra-Murphy Maria F. , Avizonis Daina , Russo Mariana de Sa Tavares , Tang Sophia , Bergholz Johann S. , Jiang Tao , Zhao Jean J. , Zhu Jian , Ko Kwang Woo , Milbrandt Jeffrey , DiAntonio Aaron , Segal Rosalind A. 
Published: April 2021

SUMMARYCancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a “dying-back” axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or pharmacologic antagonists of cADPR signaling prevent paclitaxel-induced axon degeneration and allodynia symptoms, without mitigating the anti-neoplastic efficacy of paclitaxel. Our data demonstrate that cADPR is a calcium modulating factor that promotes paclitaxel-induced axon degeneration and suggest that targeting cADPR signaling provides a potential therapeutic approach for treating CIPN.HIGHLIGHTSPaclitaxel induces intra-axonal calcium fluxSarm1-dependent cADPR production promotes axonal calcium elevation and degenerationAntagonizing cADPR signaling pathway protects against paclitaxel-induced peripheral neuropathyin vitroandin vivo
Ambulacrarian insulin-related peptides and their putative receptors suggest how insulin and similar peptides may have evolved from Insulin-like Growth Factor
Authors: Veenstra Jan A. 
Published: April 2021

AbstractBackgroundSome Insulin/IGF-related peptides (irps) stimulate a receptor tyrosine kinase (RTK) that transfers the extracellular hormonal signal into an intracellular response. Other irps, such as relaxin, do not use an RTK, but a G-protein coupled receptor (GPCR). This is unusual since evolutionarily related hormones typically either use the same or paralogous receptors. In arthropods three different irps,i.e. arthropod IGF, gonadulin andDrosophilainsulin-like peptide 7 (dilp7), likely evolved from a gene triplication, as in several species genes encoding these three peptides are located next to one another on the same chromosomal fragment. These arthropod irps have homologs in vertebrates, which suggests that the initial gene triplication was perhaps already present in the last common ancestor of deuterostomes and protostomes. It would be interesting to know whether this is indeed so and how insulin might be related to this trio of irps.MethodologyGenes encoding irps as well as their putative receptors were identified in genomes and transcriptomes from echinoderms and hemichordates.ResultsA similar triplet of genes coding for irps is also found in some ambulacrarians. Two of these are orthologs of arthropod IGF and dilp7 and the third is likely a gonadulin ortholog. In echinoderms two novel irps emerged, gonad stimulating substance (GSS) and multinsulin, likely from gene duplications of the IGF and dilp7-like genes respectively. The structures of GSS diverged considerably from IGF, which would suggest they use different receptors than IGF, but no novel irp receptors evolved. If IGF and GSS use different receptors and the evolution of GSS from a gene duplication of IGF is not associated with the appearance of a novel receptor while irps are known to use two different types of receptors, it seems to suggest that the ancestor of GSS and IGF might have acted on both types of receptors while one or both of its descendants act on only one. There are three ambulacrarian GPCRs that have amino acid sequences suggestive of being irp GPCRs, two of these are orthologs of the gonadulin and dilp7 receptors. This suggests that the third might be an IGF receptor, and that by deduction GSS only acts on the RTK. The evolution of GSS from IGF may represent a pattern, where IGF gene duplications lead to novel genes coding for shorter peptides that activate an RTK. It is likely this is how insulin and the insect neuroendocrine irps evolved independently from IGF.ConclusionThe local gene triplication described from arthropods that yielded three genes encoding irps was already present in the last common ancestor of protostomes and deuterostomes. It seems plausible that irps, such as those produced by neuroendocrine cells in the brain of insects and echinoderm GSS evolved independently from IGF and thus are not true orthologs, but the result of convergent evolution.
Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2
Authors: Shi Guoli , Chiramel Abhilash I. , Li Tiansheng , Lai Kin Kui , Kenney Adam D. , Zani Ashley , Eddy Adrian , Majdoul Saliha , Zhang Lizhi , Dempsey Tirhas , Beare Paul A. , Kar Swagata , Yewdell Jonathan W. , Best Sonja M. , Yount Jacob S. , Compton Alex A. 
Published: April 2021

AbstractSARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that exposure to rapalogs increases susceptibility to SARS-CoV-2 infection in tissue culture and in immunologically naive rodents by antagonizing the cell-intrinsic immune response. By identifying one rapalog (ridaforolimus) that is less potent in this regard, we demonstrate that rapalogs promote Spike-mediated entry into cells by triggering the degradation of antiviral proteins IFITM2 and IFITM3 via an endolysosomal remodeling program called microautophagy. Rapalogs that increase virus entry inhibit the mTOR-mediated phosphorylation of the transcription factor TFEB, which facilitates its nuclear translocation and triggers microautophagy. In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.SignificanceRapamycin is an immunosuppressant used in humans to treat cancer, autoimmunity, and other disease states. Here, we show that rapamycin and related compounds promote the first step of the SARS-CoV-2 infection cycle—entry into cells—by disarming cell-intrinsic immune defenses. We outline the molecular basis for this effect by identifying a rapamycin derivative that is inactive, laying the foundation for improved mTOR inhibitors that do not suppress intrinsic immunity. We find that rapamycin analogs that promote SARS-CoV-2 entry are those that activate TFEB, a transcription factor that triggers the degradation of antiviral membrane proteins inside of cells. Finally, rapamycin administration to rodents prior to SARS-CoV-2 challenge results in enhanced viral disease, revealing that its use in humans may increase susceptibility to infection.
Software development for autologous skin substitute production
Authors: Mestrallet Guillaume 
Published: April 2021

ABSTRACTObjectiveThe gold-standard for the management of patients affected by large-surface third-degree burns is autologous skin graft. There is no way to accurately assess burned area size and predict the number of cells and the time necessary to produce a skin graft.Materials and MethodsWhen burns affect <40% total body surface area (TBSA), meshed skin samples harvested from non-affected donor sites can be used as grafts. In cases corresponding to burns affecting >40% TBSA), the donor site surfaces are insufficient. The alternative grafting strategy uses bioengineered skin substitutes that are generated using the own keratinocytes of the patient after ex vivo expansion. We developed a software for severe burn diagnosis and autologous skin substitute production.ResultsWe developed a software-assisted calculation of the required graft surface and keratinocyte numbers and the time to produce the graft needed, according to patient clinical characteristics. The software also offers assistance to estimate the Baux score, a method that links the severity of burn injuries and the prognosis for the patient.DiscussionOptimal setup of the bioengineering process involved determination of the required graft surface, adjustment of cell quantities, and control of the timing necessary for production. This could be determined and automated by this software. Accordingly, tools to assist the design of personalized protocols will contribute to care quality and cost limitation.ConclusionThis software provides a principle of assisted burned patient diagnose and skin substitute bioengineering process which development may facilitate the design of personalized protocols for skin regenerative cell therapies.
Persistent expression of interleukin‐17 and downstream effector cytokines in recalcitrant psoriatic lesions after ustekinumab treatment
Authors: Kim Bo Ri , Kim Minsu , Yang Seungkeol , Choi Chong Won , Lee Kyu Sang , Youn Sang Woong 
Published: April 2021

AbstractThe interleukin (IL)‐23/T‐helper (Th)17 axis is considered central to the pathogenesis of psoriasis, with IL‐36γ considered a marker for histological differential diagnosis. However, expression data regarding key cytokines in the pathogenesis of psoriasis, as well as data on the effects of IL‐23 inhibition on downstream cytokines in human psoriatic skin, are limited. We investigated the expression profile of key cytokines and the effect of ustekinumab (UST) on cytokine expression in human psoriatic tissue. Tumor necrosis factor (TNF)‐α, IL‐23, IL‐17A, and IL‐22 were highly expressed in the epidermis, dermal papillae, and upper dermis in patients with psoriasis compared with controls; IL‐36γ was strongly expressed in the upper epidermis. Compared with the untreated group, expression intensity and area of IL‐23 were significantly decreased in the UST group; expression areas of TNF‐α, IL‐17A, IL‐22, and IL‐36γ did not differ. This study identified the distribution and quantitative expression levels of key cytokines in psoriatic lesions and demonstrated that only IL‐23 was downregulated without blocking downstream effector cytokines in recalcitrant psoriatic lesions during UST treatment. Our results suggest that, although IL‐23 is inhibited, the persistent expression of IL‐17 through an alternative pathway maintains the vicious cycle of the TNF‐α/IL‐23/IL‐17 axis with IL‐36γ, inducing refractory psoriatic lesions in patients with well‐controlled psoriasis.
Effect of brousse tigrée on the dynamics of nurse–protégé interactions of a cactus in the Chihuahuan Desert
Authors: Aranda‐Pineda José A. , Valverde Pedro L. , Búrquez Alberto , Golubov Jordan , Mandujano María C. 
Published: April 2021

AbstractA nurse–protégé relationship is a frequent facilitation interaction in deserts that allows the recruitment of new individuals of many species. Our aim was to evaluate the relationship of Echinocereus enneacanthus during its life cycle and its nurse plants in the brousse tigrée (tiger bush) vegetation of the Chihuahuan Desert. The population structure of the cactus is skewed toward adult stages, which are commonly found in the bare areas of the brousse tigrée, whereas juveniles are located in the vegetated bands. The vegetation structure and the nurse–protégé relationship were determined using censuses of 19 permanent plots monitored between 2008 and 2019. The differential association of E. enneacanthus with potential nurse plants was evaluated using an interaction network, under the hypothesis of strict association of the seedlings and juveniles with nurse species. In addition, χ2 tests and standardized residuals were fitted among likely nurse species, weighted by the cover of the nurse and of the areas without vegetation. The study species, as well as the nurse plants, had an aggregated distribution pattern. The interaction network showed that the frequency of the association with nurse plants decreased as the size of the protégé individuals increased. At the same time, there were differences in the establishment of E. enneacanthus under particular nurse plants; Prosopis glandulosa and Hilaria mutica were the most important. The nurse–protégé relationship for seeds and seedlings is integral to the vegetation bands of the brousse tigrée.
Intraspecific competition favors ant–plant protective mutualism
Authors: Yamawo Akira 
Published: April 2021

AbstractThe dependency of the anti‐herbivore defense on ant–plant protective mutualism often varies depending on abiotic and biotic conditions. Although intraspecific competition is a primary interaction between neighboring plants, its effects on ant–plant mutualisms have yet to be sufficiently elucidated. In order to determine the effects of intraspecific competition and competitor genotype on ant–plant mutualisms, I conducted competition and ant‐removal experiments and examined their effects on damage to the leaves of Urena lobata var. tomentosa plants. I found that larger numbers of worker ants visited the plants growing with non‐siblings than plants growing alone and that plants growing with non‐siblings had a higher shoot to root ratio and secreted greater volumes of extrafloral nectar than plants growing alone and/or with siblings. Under the presence of both sibling and non‐sibling competitors, I observed that when ants were removed from plants, those grown with conspecific neighbors were characterized by a higher percentage of damaged leaf area than plants harboring ants. The effect of ant exclusion on leaf damage was more pronounced in plants grown with non‐siblings than those grown near siblings. However, when the plants were grown alone, I detected no significant difference in percentage leaf damage between the ant‐excluded and ant‐harboring plants. The results indicate that neighboring plants can exert strong effects on ant–plant protective mutualisms, thereby highlighting the need to take into consideration plant–plant interactions in studies on these mutualistic associations.
Tie Strength Dispersion and Alliance Portfolio Performance: The Moderating Effects of CEOs’ Political and International Experience
Authors: Bi Jingyu , Xie En , Sheng Shibin 
Published: April 2021

AbstractMany firms simultaneously develop multiple alliances with different partners and face the challenges of managing a complex alliance portfolio that contains both strong and weak ties. How does this dispersion of tie strength affect alliance portfolio performance? This study examines the effect of tie strength dispersion on alliance portfolio performance, as well as the contingent effects of CEOs’ experience. The empirical analyses, using a dataset consisting of 748 funds initiated by 62 fund management firms over a 10‐year period (2002–2011), reveal an inverted U‐shaped relationship between tie strength dispersion and alliance portfolio performance. The analyses also reveal that CEOs’ political experience weakens, while their international experience strengthens, this inverted U‐shaped relationship.
Characteristics, presentation and outcomes of music festival patrons with stimulant drug‐induced serotonin toxicity
Authors: Miles Lachlan F , Austin Kristy , Eade Alan , Anderson David , Graudins Andis , McGain Forbes , Maplesden Jacqueline , Greene Shaun , Rotella Joe‐Anthony , Dutch Martin 
Published: April 2021

AbstractObjectiveA large number of stimulant drug‐associated deaths at music festivals in Australia were reported during the southern hemisphere summer of 2018–2019. This led to the prehospital deployment of healthcare professional‐led critical care response teams. We aimed to describe the characteristics, clinical presentation, management and outcomes of music festival patrons with stimulant drug‐induced serotonin toxicity managed using this model during the study period.MethodsWe performed a retrospective observational study of patients presenting with stimulant drug‐induced serotonin toxicity and/or drug‐induced hyperthermia who presented between December 2017 and December 2019. Comprehensive follow‐up data were collected for those patients who required hospital admission. Data included demographics, clinical features, management and disposition, hospital outcomes and laboratory data, stratified by severity of presentation.ResultsForty‐seven patients were included. Median age was 21.9 years (interquartile range 19.6–22.2). 3,4‐Methylenedioxymetamphetamine was the most frequently reported agent ingested (32/47). After stratification, 13 of 47 patients were classified as mild, 20 of 47 as moderate and 14 of 47 as severe. Median presenting temperature in this latter cohort was 41.1°C (40.5–42.0°C). All severely ill patients required intensive care unit admission, with a median hospital stay of 4.63 days (interquartile range 2.08–8.36). End‐organ complications were reported in 11 of 14 patients. No mortalities were reported. All patients (13/13) from the mild cohort and 15 of 20 patients from the moderate cohort were treated and discharged on‐site.ConclusionsSevere illness was associated with a high incidence of end‐organ impairment. A high proportion of patients without severe disease were able to be successfully managed at the event without transport to hospital. No deaths are reported in this series.