bluuebunny/crossref_metadata_2025_split huggingface dataset:
Root-associated Fungi in Orchidaceae: Diversity, Phylogeny, Ecology, and Outstanding Questions
Authors: Wang Deyi , Lerou Jun , Nuytinck Jorinde , Gomes Sofia I.F. , Jacquemyn Hans , Merckx Vincent S.F.T. 
Published: December 2022

AbstractMycorrhizal fungi form ubiquitous symbiotic associations with almost all land plants and are of key interest to evolutionary biologists and ecologists because this ancient symbiosis was essential for the colonization of land by plants – a major turning point in the evolutionary history of the earth – and the subsequent development and functioning of the terrestrial ecosystems. Within the orchid family (Orchidaceae), plants establish unique interactions with specific orchid mycorrhizal fungi. These fungal symbionts are essential for the development of orchids as they provide carbon and soil nutrients to germinating orchid seeds and the nutritional supply continues for adult orchids to different degrees. Fueled by the development of DNA sequencing techniques, the diversity of mycorrhizal and other root-associated fungi in orchid roots has been extensively reported in evolutionary and ecophysiological studies. However, the full taxonomic range of orchid-associated fungi remains to be investigated in a broad phylogenetic framework, hampering a further understanding of the evolution and ecological adaptation of orchid mycorrhizal interactions. In this study, we used the most complete DNA dataset to date to map the phylogenetic distribution and ecological lifestyles of root-associated fungi in Orchidaceae by phylogenetic reconstructions at the fungal order level. We found that a broad taxonomic range of fungi (clustered into 1898 operational taxonomic units) resided in orchid roots, belonging to at least 150 families in 28 orders inBasidiomycotaandAscomycota. These fungi were assigned to diverse ecological lifestyles including typical orchid mycorrhizal fungi (‘rhizoctonia’), ectomycorrhizal fungi, wood- or litter-decaying saprotrophic fungi, and other endophytes/pathogens/saprotrophs. This overview reveals that among the four different mycorrhizal types, the orchid mycorrhizal symbiosis probably involves the highest diversity of fungal taxa. We hope that our newly reconstructed phylogenetic framework of orchid-associated fungi and the assessment of their potential mycorrhizal status will benefit future ecological and evolutionary studies on orchid-fungal interactions.
Morphine-induced mechanical hypersensitivity in mice requires δ receptors, β-arrestin2 and c-Src activity
Authors: Singleton Samuel , Hales Tim G. 
Published: December 2022

AbstractBackgroundMorphine diminishes acute pain, but long-term use is compromised by tolerance and hyperalgesia. Studies implicate δ receptors, β-arrestin2 and Src kinase in tolerance. We examined whether these proteins are also involved in morphine-induced hypersensitivity (MIH). A common pathway for tolerance and hypersensitivity may provide a single target to guide improved analgesic approaches.MethodsWe examined mechanical sensitivity using automated von Frey in wild type (WT) and transgenic male and female C57Bl/6 mice before and after hind paw inflammation by complete Freund’s adjuvant (CFA). We explored the expression of opioid genes in the spinal cord using quantitative RT-PCR.ResultsCFA-evoked hypersensitivity ceased on day 7 in WT mice but persisted in μ-/-mice. Recovery was delayed until day 13 in δ-/-mice. Restoration to basal sensitivity in WT mice occurred with increased δ expression. By contrast, κ expression was reduced, while μ remained unchanged. Daily morphine reduced hypersensitivity in WT mice on day 3 compared to controls, however hypersensitivity recurred on day 9 and beyond. By contrast, WT mice had no recurrence of hypersensitivity in the absence of daily morphine. We used β-arrestin2-/-, δ-/-and Src inhibition by dasatinib in WT mice to establish whether these approaches, which diminish tolerance, also attenuate MIH. While none of these approaches affected CFA-evoked inflammation or acute hypersensitivity, all caused sustained morphine anti-hypersensitivity, abolishing MIH.ConclusionsLike morphine tolerance, MIH in this model requires δ receptors, β-arrestin2 and Src activity. Our findings suggest that MIH is caused by a tolerance-induced reduction in endogenous opioid signalling.
Interleukin-17 signaling influences CD8+T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells
Authors: Rodriguez Constanza , Araujo Furlan Cintia L. , Boari Jimena Tosello , Bossio Sabrina N. , Boccardo Santiago , Fozzatti Laura , Canale Fernando P. , Beccaria Cristian G. , Nuñez Nicolás G. , Ceschin Danilo G. , Piaggio Eliane , Gruppi Adriana , Montes Carolina L. , Acosta Rodríguez Eva V. 
Published: December 2022

ABSTRACTThe role of IL-17 mediated immune responses in cancer is conflicting as pre-clinical and clinical results show tumor-promoting as wel as tumor-repressing functions. Herein, we used syngeneic tumor models from different tissue origins as a tool to evaluate the role of IL-17 signaling in cancer progression, dissecting the effects in cancer cell growth and tumor immunity. We show that absence of IL-17RA or IL-17A/F expression in the host has contrasting effects in thein vivogrowth of different tumor types. We observed that lack of IL-17A/F-IL-17RA signaling in host cells changed the expression pattern of several mediators within the tumor microenvironment in a cancer-type specific manner. Deficiencies in host IL-17RA or IL-17A/F expression resulted in reduced antitumor CD8+ T cell immunity in all cancer models and in tumor-specific changes in several lymphoid cell populations. These findings were associated to particular patterns of expression of cytokines (IL-17A and IL-17F) and receptor subunits (IL-17RA, IL-17RC and IL-17RD) of the IL-17 family in the injected tumor cell lines that, in turn, dictated tumor cell responsiveness to IL-17. We identified IL-17RC as an important determinant of the IL-17-mediated transcriptional response in tumor cells and; consequently, as a predictive biomarker of the overall effect of IL-17 signaling in tumor progression. Our findings contribute to unraveling the molecular mechanisms underlying the divergent activities of IL-17 in cancer and provide rational targets for immunotherapies based on personalized approaches.
Fatecode: Cell fate regulator prediction using classification autoencoder perturbation
Authors: Sadria Mehrshad , Layton Anita , Goyal Sidharta , Bader Gary D. 
Published: December 2022

AbstractCell reprogramming, which guides the conversion between cell states, is a promising technology for tissue repair and regeneration. Typically, a group of key genes, or master regulators, are manipulated to control cell fate, with the ultimate goal of accelerating recovery from diseases or injuries. Of importance is the ability to correctly identify the master regulators from single-cell transcriptomics datasets. To accomplish that goal, we propose Fatecode, a computational method that combines in silico perturbation experiments with cell trajectory modeling using deep learning to predict master regulators and key pathways controlling cell fate. Fatecode uses only scRNA-seq data from wild-type samples to learn and predict how cell type distribution changes following a perturbation. We assessed Fatecode’s performance using simulations from a mechanistic gene regulatory network model and diverse gene expression profiles covering blood and brain development. Our results suggest that Fatecode can detect known master regulators of cell fate from single-cell transcriptomics datasets. That capability points to Fatecode’s potential in accelerating the discovery of cell fate regulators that can be used to engineer and grow cells for therapeutic use in regenerative medicine applications.
A phylogenetic approach to studying the roles of within-host evolution and between-host transmission of resistance for clinicalEscherichia coliinfections
Authors: van Nouhuijs Florentine , Antony MaryGracy Arakkal , Orcales Faye , Gozashti Landen , Roy Scott W. , Ogbunugafor C. Brandon , Pennings Pleuni S. 
Published: December 2022

AbstractBacterial antibiotic resistance represents a public health concern that will remain relevant for the foreseeable future. Antibiotic resistant bacterial infections can occur in two ways: (1) a host is infected by a resistant bacterial strain (due to between-host transmission of resistance), or (2) a host is infected infection by a susceptible strain, followed by the de novo evolution or acquisition of resistance (due to within-host evolution of resistance). While both are critical to understanding how the evolution of resistance happens in natural settings, the relative rate at which they occur is unclear. Here, we employ phylogenetic comparative methods to examine the evolutionary dynamics of resistance inEscherichia colifor multiple common antibiotics. We report evolutionary patterns consistent with commonde novoevolution of resistance for some antibiotics and sustained transmission of resistant strains for others. For example, we observe 79 putativede novoresistance evolution events for resistance to Cefuroxime but only 31 for resistance to Ciprofloxacin, despite similar numbers of observed infections (239 and 267 respectively). We find that clusters of resistance are generally larger for Ciprofloxacin, Ceftazidima and AmoxiClav, which suggests that for these drugs, resistance is often transmitted from patient to patient. In contrast, we find that cluster sizes for resistance are generally smaller for PipTaz, Cefuroxime and Gentamicin, suggesting that resistance to these drugs is less often transmitted from patient to patient and instead evolvesde novo. In addition to differences between drugs, we also find that cluster sizes were generally larger in phylogroup B2 compared to the other phylogroups, suggesting that transmission of resistant strains is more common in this phylogroup compared to the others. Our study proposes new approaches for determining the importance ofde novoevolution or acquisition (within-host evolution) from resistance from infection with an already resistant strain (between-host transmission). Significantly, this work also bridges an important gap between evolutionary genomics and epidemiology, opening up a range of opportunities for studying the evolutionary dynamics of bacterial antibiotic resistance.
Effect of image registration on the estimation of pharmacokinetic parameters from DCE-MRI of patients with esophageal cancer
Authors: Lee Joonsang , Ma Jingfei , Carter Brett , Court Laurence E. , Lin Steven H. 
Published: December 2022

ABSTRACTWe investigated the effectiveness of the most commonly used registration methods (deformable and rigid-body registrations) with different reference images on pharmacokinetic parameters estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of esophageal cancer patients. We obtained DCE-MRI images from 10 patients with esophageal cancer. Both rigid-body and deformable registrations of the images were performed on DCE-MRI images at different time points as reference images before the pharmacokinetic parameters were estimated. The deformable registration used non-rigid B-spline transforms in a multi-resolution scheme, and Euler transform were used for the rigid body registration. A nonparametric statistical test and the intra-class correlation coefficient assessed the consistency and reproducibility of the pharmacokinetic parameters estimated with both registration methods and using images acquired at different time points. Kruskal-Wallis testing demonstrated significant differences (p < 0.05) in all the estimated parameters for deformable registration but no significant differences (p > 0.78) for rigid-body registration. The intra-class correlation coefficient for rigid-body registration was higher than that for deformable registration for each pharmacokinetic parameter, indicating that, for rigid-body registration, the parameter values from different reference images of one patient tended to be similar to each other. In contrast, the values for deformable registration were more variable. In conclusion, the choice of the reference image of deformable registration significantly affected the estimates of pharmacokinetic parameters, and rigid-body registration showed small variations in pharmacokinetic parameters over the choice of the reference images for small motion artifacts of small distal esophageal cancer on DCE-MRI.
CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection
Authors: Redford Samuel E. , Varanasi Siva Karthik , Sanchez Karina K. , Ayres Janelle S. 
Published: December 2022

AbstractCatabolic responses of lean and fat energy stores are a component of the host response to infection. Cachexia is an extreme catabolic state characterized by unintentional weight loss and muscle loss, that can include fat loss. Whether cachexia plays any role in host defense or is a maladaptive consequence of host-pathogen interactions remains unknown. Traditionally studies have focused on understanding how inflammatory mediators and cells of the innate immune system contribute to the pathogenesis of cachexia and the depletion of energy stores. The cells of the adaptive immune system that regulate infection-induced cachexia remain elusive. In the present study, we examined the role of the adaptive immune response in cachexia pathogenesis using a murine model of the chronic parasitic infectionTrypanosoma brucei, the causative agent of sleeping sickness. We found that the cachectic response occurs in two phases with the first stage occurring early in the infection and involved a loss of body fat mass associated with anorexia, and the second stage occurring later in the infection and involved a sustained loss of fat mass that was accompanied by lean mass wasting. CD4+ T cells were necessary for the development of the sickness-induced anorexic response during stage 1 of the infection, which led to adipose triglyceride lipase dependent lipolysis in adipocytes and the resulting fat wasting. Adipose tissue wasting had no impact on host resistance defenses or survival of infection, both of which were antibody-mediated and independent ofCD4+ T cell responses. Our work reveals a new mechanism for infection induced cachexia involving CD4+ T cell regulation of host feeding behavior and an unexpected decoupling of adaptive immune mediated resistance from the cachectic response during infection.
Transposon-derived transcription factors across metazoans
Authors: Mukherjee Krishanu , Moroz Leonid L. 
Published: December 2022

ABSTRACTTransposable elements (TE) could serve as sources of new transcription factors (TFs) in plants and some other model species, but such evidence is lacking for most animal lineages. Here, we discovered multiple independent co-options of TEs to generate 788 TFs across Metazoa, including all early-branching animal lineages. Six out of ten super-families of known TEs (ZBED, CENPB, FHY3, HTH-Psq, THAP, and FLYWCH) were recruited as representatives of nine phyla. The most extensive convergent domestication of TE-derived TFs occurred in the hydroid polyps, polychaete worms, cephalopods, oysters, and sea slugs. Phylogenetic reconstructions showed species-specific clustering and lineage-specific expansion; none of the identified TE-derived TFs revealed homologs in their closest neighbors. Together, our study established a framework for categorizing TE-derived TFs and informing the origins of novel genes across phyla.
No stimulant? No Problem: Analyzing Black Market Sales of Atomoxetine on StreetRx
Authors: Roe Sophie A. , DeSalve Dayna S. , Piper Brian J. 
Published: December 2022

AbstractObjectiveThe purpose of this report was to analyze black market diversions of atomoxetine, a non-stimulant medication for ADHD, submitted to StreetRx.MethodData related to black market atomoxetine purchases entered on StreetRx between 2015 and 2019 were analyzed. Data included generic drug name, dosage, purchase price, and date and location in the United States. The mean price per milligram was determined and a heatmap generated.ResultsThe average price per milligram cost of 113 diverted atomoxetine submissions was $1.35 (± $2.76 SD) (Median = $0.05, Min = $0.01, Max = $20.00). The states with the most submissions included Michigan (11), Pennsylvania (9), Indiana (8), and Ohio (8).ConclusionFurture qualitative studies should investigate reasons why individuals are motivated to purchase atomoxetine, a non-stimulant medication, on the black market (recreational vs. nootropic vs. other clinical uses).
Online social networks of individuals with adverse childhood experiences
Authors: Cao Yiding , Rajendran Suraj , Sundararajan Prathic , Law Royal , Bacon Sarah , Sumner Steven A. , Masuda Naoki 
Published: December 2022

AbstractAdverse childhood experiences (ACEs), which include abuse and neglect and various household challenges like exposure to intimate partner violence and substance use in the home can have negative impacts on lifelong health of affected individuals. Among various strategies for mitigating the adverse effects of ACEs is to enhance connectedness and social support for those who have experienced ACEs. However, how social networks of those who experienced ACEs differ from those who did not is poorly understood. In the present study, we use Reddit and Twitter data to investigate and compare social networks among individuals with and without ACEs exposure. We first use a neural network classifier to identify the presence or absence of public ACEs disclosures in social media posts. We then analyze egocentric social networks comparing individuals with self-reported ACEs to those with no reported history. We found that, although individuals reporting ACEs had fewer total followers in online social networks, they had higher reciprocity in following behavior (i.e., mutual following with other users), a higher tendency to follow and be followed by other individuals with ACEs, and a higher tendency to follow back individuals with ACEs rather than individuals without ACEs. These results imply that individuals with ACEs may try to actively connect to others having similar prior traumatic experiences as a positive connection and coping strategy. Supportive interpersonal connections online for individuals with ACEs appear to be a prevalent behavior and may be a way to enhance social connectedness and resilience in those who have experienced ACEs.
The Effect of the COVID-19 Pandemic on Life Expectancy in the US: An Application of Hybrid Life Expectancy
Authors: Sanderson Warren C. , Scherbov Sergei 
Published: December 2022

AbstractLife expectancy at birth (both sexes) in the US was 1.9 years lower in 2020 than in 2019. This reduction has been widely discussed. This 1.9 year reduction compares a group of people who would live their entire lives at the 2019 survival rates with a group that would live their entire lives experiencing the pandemic survival rates of 2020. Here we introduce hybrid life expectancy. This is the life expectancy of people who experience the 2020 survival rates for various shorter periods followed by a return to the 2019 levels. For pandemic durations of 10 years or less life expectancy at birth does not fall from its 2019 level. For a pandemic duration of 10 years, the life expectancy of 65 year-olds would fall by 0.2 years.
Subtle introgression footprints at the end of the speciation continuum in a clade ofHeliconiusbutterflies
Authors: Rougemont Quentin , Huber Bárbara , Martin Simon , Whibley Annabel , Estrada Catalina , Solano Darha , Orpet Robert , McMillan W. Owen , Frérot Brigitte , Joron Mathieu 
Published: December 2022

AbstractQuantifying gene flow between lineages at different stages of the speciation continuum is central to understanding speciation.Heliconiusbutterflies have undergone an adaptive radiation in wing colour patterns driven partly by natural selection for local mimicry. Colour patterns are also known to be used as assortative mating cues. Therefore, wing pattern divergence is considered to play a role in speciation. A corollary is that mimicry between closely-related species may be associated with hybridization and interfere with reproductive isolation. Here, we take a multifaceted approach to explore speciation history, species boundaries, and traits involved in species differentiation between the two closely-related speciesH. hecaleandH. ismenius.We focus on geographic regions where the two species mimic each other, and contrast this with geographic regions where they do not mimic each other. To examine population history and patterns of gene flow, we tested and compared a four-population model accounting for linked selection. This model suggests that the two species have remained isolated for a large part of their history, yet with a small amount of gene exchange. Accordingly, signatures of genomic introgression were small except at a major wing pattern allele and chemosensing genes, and stronger in the mimetic populations compared to non-mimetic populations. Behavioural assays confirm that visual confusion exists but that short-range cues determine strong sexual isolation. Tests for chemical differentiation between species identified major differences in putative pheromones which likely mediate mate choice and the maintenance of species differences.
Intramolecular autoinhibition of human PEX13 modulates peroxisomal import
Authors: Gaussmann Stefan , Ott Julia , Zak Krzysztof M. , Delhommel Florent , Popowicz Grzegorz M. , Schliebs Wolfgang , Erdmann Ralf , Sattler Michael 
Published: December 2022

AbstractTargeting and import of peroxisomal proteins depends on PEX5, PEX14 and PEX13. We present a biochemical and structural characterization of the PEX13 C-terminal region. By combining NMR spectroscopy, X-ray crystallography and biochemical methods, we show that the PEX13 SH3 domain mediates intramolecular interactions with a newly identified proximal FxxxF motif and also binds to WxxxF peptide motifs from the PEX5 NTD, demonstrating evolutionary conservation of this interaction from yeast to human. Strikingly, the C-terminal FxxxF motif autoinhibits the WxxxF/Y binding surface on the PEX13 SH3 domain. This is supported by high-resolution crystal structures, which show FxxxF or WxxxF/Y binding to the same, non-canonical surface on the SH3 domain. The FxxxF motif also binds the PEX14 NTD with micromolar affinity. Surprisingly, the canonical binding surface for PxxP motifs on the human PEX13 SH3 fold does not recognize PxxP motifs in PEX14, distinct from the yeast ortholog. The dynamic network of PEX13, PEX14 and PEX5 interactions mediated by diaromatic peptide motifs fine-tunes and modulates peroxisomal matrix import in cells.