bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valuing nature: the case of tropical forests and Costa Rica
Authors: Umaña Quesada Alvaro 
Published: April 2024

The paper focuses on the failure to account for the value of standing tropical forests, and of ecosystem services in general, in economic decision-making. This blindness to the values of nature has led to overexploitation, degradation and destruction of tropical forests, which, in turn, has also significantly contributed to greenhouse gas emissions. Forest conservation and restoration has a critical role to play in the fight against climate change and brings a vast array of additional benefits, from security in water, energy, food, health and livelihoods to maintaining biodiversity itself as a core component of our living planet. As first Minister of Environment and Energy under President Oscar Arias (1986–1990), I brought these views into societal decision-making in Costa Rica and here I briefly describe how.
This article is part of the theme issue ‘Bringing nature into decision-making’.
Early versus Later Anticoagulation in Post-Stroke patients with Atrial Fibrillation: A systematic review and Meta-analysis
Authors: Zavaleta-Corvera Carlos , Vasquez-Paredes Gino , Sarmiento-Falen Joaquín , Riveros-Hernandez Olmedo , Caballero-Alvarado José 
Published: April 2024

ABSTRACTBackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of ischemic stroke, one of its most serious complications. The intricate relationship between AF and stroke necessitates careful consideration in the timing of anticoagulant therapy initiation to prevent stroke recurrence, hemorrhagic transformation, and other complications.AimThis study aims to evaluate the efficacy and safety of early versus late initiation of anticoagulant treatment in patients with AF after an ischemic stroke, addressing the critical gap in optimal timing to balance the risk of recurrent stroke against bleeding risks.MethodsA systematic review and meta-analysis was conducted following the PRISMA-2020 guidelines, with searches performed across multiple databases including PubMed, Scopus, Web of Science, EMBASE, and Cochrane. Randomized controlled trials comparing early versus later initiation of anticoagulation in AF patients post-stroke were included. Data synthesis was performed using a random-effects model, considering recurrent ischemic stroke, symptomatic intracerebral hemorrhage, and mortality as primary outcomes.ResultsFrom 1444 identified records, three studies and 2989 patients were included, comprising a diverse population in terms of geography and demographics. Meta-analysis revealed that early anticoagulation initiation might be associated with a reduced risk of recurrent ischemic stroke (RR 0.72, 95% CI [0.51-1.00])(p=0.05), although statistical significance was borderline. No significant differences were found in symptomatic intracerebral hemorrhage or mortality rates between early and late initiation. Early intervention was, however, associated with a reduction in other adverse outcomes (RR 0.72, 95% CI [0.54-0.96])(p=0.03).ConclusionsEarly initiation of anticoagulation therapy in AF patients post-ischemic stroke may offer a protective effect against recurrent ischemic events with no significant increase in bleeding or mortality risks. This suggests that early anticoagulation can be safely considered, particularly in light of reducing other adverse outcomes.
Seeing halos: Spatial and consumer-resource constraints to landscape of fear patterns
Authors: Ong Theresa W. , McManus Lisa C. , Vasconcelos Vítor V. , Yang Luojun , Su Chenyang 
Published: April 2024

AbstractCoral halos are algae-free space surrounding coral patches linked to the landscape of fear hypothesis, where risk-averse herbivores avoid grazing too far from coral shelter. Halo patterns thus provide insight into the state of overfished predator populations on reefs. However, halos are absent in some protected reefs and their sizes are uncorrelated with predator abundance. Here, we show that these observations are consistent with the landscape of fear hypothesis. When coral are dispersed, herbivores have more even shelter from predators across the seascape, allowing herbivores to overgraze and halos to oscillate. When coral are clustered, shelter is limited and halos can stabilize, but reducing herbivore limitation drives critical transitions to cycles that are difficult to recover from. Discordance between theory and observations may, therefore, arise from differences in underlying coral spatial distributions, with broad implications for how the landscape of fear influences pattern formation and ecological resilience in patchy ecosystems.
Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer
Authors: Kim Nayoung , Park Sehhoon , Jo Areum , Eum Hye Hyeon , Kim Hong Kwan , Lee Kyungjong , Cho Jong Ho , Ku Bo Mi , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Lee Jung-Il , Choi Jung Won , Jeong Dasom , Na Minsu , Kang Huiram , Kim Jeong Yeon , Choi Jung Kyoon , Lee Hae-Ock , Ahn Myung-Ju 
Published: April 2024

AbstractThis study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICI). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (AUC) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.
Transgenerational epigenetic inheritance increases trait variation but is not adaptive
Authors: Shahmohamadloo René S. , Fryxell John M. , Rudman Seth M. 
Published: April 2024

AbstractUnderstanding processes that can produce adaptive phenotypic shifts in response to rapid environmental change is critical to reducing biodiversity loss. The ubiquity of environmentally induced epigenetic marks has led to speculation that epigenetic inheritance could potentially enhance population persistence in response to environmental change. Yet, the magnitude and fitness consequences of epigenetic marks carried beyond maternal inheritance are largely unknown. Here, we tested how transgenerational epigenetic inheritance (TEI) shapes the phenotypic response ofDaphniaclones to the environmental stressorMicrocystis. We split individuals from each of eight genotypes into exposure and control treatments (F0 generation) and tracked the fitness of their descendants to the F3 generation. We found transgenerational epigenetic exposure toMicrocystisled to reduced rates of survival and individual growth and no consistent effect on offspring production. Increase in trait variance in the F3 relative to F0 generations suggests potential for heritable bet hedging driven by TEI, which could impact population dynamics. Our findings are counter to the working hypothesis that TEI is a generally adaptive mechanism likely to prevent extinction for populations inhabiting rapidly changing environments.One sentence summaryTransgenerational epigenetic inheritance inDaphniaexposed toMicrocystisrevealed negative fitness effects on survival and growth rates, challenging hypotheses of a general selective advantage.
The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast
Authors: Dutcher H. Auguste , Hose James , Howe Hollis , Rojas Julie , Gasch Audrey P. 
Published: April 2024

ABSTRACTAneuploidy produces myriad consequences in health and disease, yet models of the deleterious effects of chromosome amplification are still widely debated. To distinguish the molecular determinants of aneuploidy stress, we measured the effects of duplicating individual genes in cells with varying chromosome duplications, in wild-type cells and cells sensitized to aneuploidy by deletion of RNA-binding protein Ssd1. We identified gene duplications that are nearly neutral in wild-type euploid cells but significantly deleterious in euploids lackingSSD1orSSD1+aneuploid cells with different chromosome duplications. Several of the most deleterious genes are linked to translation; in contrast, duplication of other translational regulators, including eI5Fa Hyp2, benefitssd1Δaneuploids over controls. Using modeling of aneuploid growth defects, we propose that the deleterious effects of aneuploidy emerge from an interaction between the cumulative burden of many amplified genes on a chromosome and a subset of duplicated genes that become toxic in that context. Our results suggest that the mechanism behind their toxicity is linked to a key vulnerability in translation in aneuploid cells. These findings provide a perspective on the dual impact of individual genes and overall genomic burden, offering new avenues for understanding aneuploidy and its cellular consequences.
Horizontally transferred glycoside hydrolase 26 may aid hemipteran insects in plant tissue digestion
Authors: Walt Hunter K. , Ahn Seung-Joon , Hoffmann Federico 
Published: April 2024

AbstractGlycoside hydrolases are enzymes that break down complex carbohydrates into simple sugars by catalyzing the hydrolysis of glycosidic bonds. There have been multiple instances of adaptive horizontal gene transfer of genes belonging to various glycoside hydrolase families from microbes to insects, as glycoside hydrolases can metabolize constituents of the carbohydrate-rich plant cell wall. In this study, we characterize the horizontal transfer of a gene from the glycoside hydrolase family 26 (GH26) from bacteria to insects of the order Hemiptera. Our phylogenies trace the horizontal gene transfer to the common ancestor of the superfamilies Pentatomoidea and Lygaeoidea, which include stink bugs and seed bugs. After horizontal transfer, the gene was assimilated into the insect genome as indicated by the gain of an intron, and a eukaryotic signal peptide. Subsequently, the gene has undergone independent losses and expansions in copy number in multiple lineages, suggesting an adaptive role of GH26s in some insects. Finally, we measured tissue-level gene expression of multiple stink bugs and the large milkweed bug using publicly available RNA-seq datasets. We found that the GH26 genes are highly expressed in tissues associated with plant digestion, especially in the principal salivary glands of the stink bugs. Our results are consistent with the hypothesis that this horizontally transferred GH26 was co-opted by the insect to aid in plant tissue digestion and that this HGT event was likely adaptive.
Gra-CRC-miRTar: The pre-trained nucleotide-to-graph neural networks to identify potential miRNA targets in colorectal cancer
Authors: Yin Rui , Zhao Hongru , Li Lu , Yang Qiang , Zeng Min , Yang Carl , Bian Jiang , Xie Mingyi 
Published: April 2024

AbstractColorectal cancer (CRC) is the third most diagnosed cancer and the second deadliest cancer worldwide representing a major public health problem. In recent years, increasing evidence has shown that microRNA (miRNA) can control the expression of targeted human messenger RNA (mRNA) by reducing their abundance or translation, acting as oncogenes or tumor suppressors in various cancers, including CRC. Due to the significant up-regulation of oncogenic miRNAs in CRC, elucidating the underlying mechanism and identifying dysregulated miRNA targets may provide a basis for improving current therapeutic interventions. In this paper, we proposed Gra-CRC-miRTar, a pre-trained nucleotide-to-graph neural network framework, for identifying potential miRNA targets in CRC. Different from previous studies, we constructed two pre-trained models to encode RNA sequences and transformed them into de Bruijn graphs. We employed different graph neural networks to learn the latent representations. The embeddings generated from de Bruijn graphs were then fed into a Multilayer Perceptron (MLP) to perform the prediction tasks. Our extensive experiments show that Gra-CRC-miRTar achieves better performance than other deep learning algorithms and existing predictors. In addition, our analyses also successfully revealed 172 out of 201 functional interactions through experimentally validated miRNA-mRNA pairs in CRC. Collectively, our effort provides an accurate and efficient framework to identify potential miRNA targets in CRC, which can also be used to reveal miRNA target interactions in other malignancies, facilitating the development of novel therapeutics.
Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer
Authors: Yedier-Bayram Ozlem , Cingöz Ahmet , Yilmaz Ebru , Aksu Ali Cenk , Esin Beril , Pınarbaşı-Değirmenci Nareg , Cavga Ayse Derya , Dedeoğlu Beyza , Cevatemre Buse , Syed Hamzah , Philpott Martin , Cribbs Adam P. , Oppermann Udo , Lack Nathan A. , Acilan Ceyda , Onder Tamer T. , Bagci-Onder Tugba 
Published: April 2024

ABSTRACTTriple-negative breast cancer (TNBC) stands out as a particularly aggressive and frequently recurring form of breast cancer. Due to the absence of hormone receptors, the available treatment avenues are constrained, making chemotherapy the primary approach. Unfortunately, the development of resistance to chemotherapy poses a significant challenge, further restricting the already limited therapeutic alternatives for recurrent cases. Understanding the molecular basis of chemotherapy resistance in TNBC is pivotal for improving treatment outcomes. Here, we generated two different Taxol-resistant TNBC cell lines with a dose-escalation method to mimic chemotherapy resistancein vitro. These cells exhibited hallmark features of resistance, including reduced cell growth, altered morphology, and evasion of apoptosis. Transcriptome analysis uncovered elevatedABCB1expression and multidrug-resistant phenotype in the resistant cells. To comprehensively investigate the key epigenetic regulators of Taxol resistance, we conducted chromatin-focused genetic and chemical screens and pinpointed Bromodomain and PHD Finger Containing 1 (BRPF1) as a novel regulator of Taxol resistance in TNBC cells. Knockout of BRPF1, the reader protein in the MOZ/MORF histone acetyl-transferase complex, but not the other complex members, sensitized resistant cells to Taxol. Additionally, BRPF1 inhibitors, PFI-4 and OF-1, in combination with Taxol significantly reduced cell viability. Transcriptome analysis upon BRPF1 loss or inhibition revealed a negative impact on ribosome biogenesis-related gene sets, resulting in a global decrease in protein translation in Taxol-resistant cells. Our ChIP-qPCR analysis demonstrated that active BRPF1 directly interacts with theABCB1promoter, enhancing its expression towards inducing a multidrug-resistant phenotype. Conversely, knockout or inhibition of BRPF1 leads to decreased ABCB1 expression. This dual mechanism critically sensitizes Taxol-resistant TNBC cells to chemotherapy. Our findings uncover a comprehensive molecular framework, highlighting the pivotal role of epigenetic reader protein BRPF1 in Taxol resistance and providing potential avenues for therapeutic intervention in TNBC.
FOXA1 is required for ErbB2 expression and luminal differentiation in HER2-positive breast cancer
Authors: Jeong Jaekwang , Lee Jongwon , Lim Jaechul , Shin Jaehun , Yoo Kwangmin , Kim Jonghun , Tanaka Yoshiaki , Tae Hyun Seop , Kim Lark Kyun , Park In-Hyun , Wysolmerski John , Choi Jungmin 
Published: April 2024

AbstractForkhead box protein A1 (FOXA1), a pioneering transcriptional factor known for its critical roles in prostate and ERα−positive breast cancer, is also expressed in human epidermal growth factor receptor-2 (HER2/ErbB2)-positive breast cancers. However, its role in HER2-pos tumors is less well understood. Here we investigate the function of FOXA1 in HER2/ErbB2- positive breast cancers. The loss of FOXA1 was associated with a marked decrease in the viability of HER2-positive and HER2 amplified cell lines, suggesting a pivotal involvement of FOXA1 in these breast cancers. Employing patient-derived single-cell RNA sequencing and spatial transcriptomics, we demonstrate thatFOXA1is co-expressed withErbB2in HER2- positive breast cancers. Suppression of FOXA1 expression led to the reduction of HER2 expression and signaling. Chromatin Immunoprecipitation Sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) identified FOXA1 binding motifs in theErbB2promoter and regulatory element regions, which controlledErbB2 geneexpression. Notably, FOXA1 knockdown was observed to enhance Epithelial-Mesenchymal Transition (EMT) signaling and impede luminal tumor differentiation. Furthermore, we find that FOXA1 and TRPS1 combine to regulate TEAD/YAP-TAZ activity. Taken together, these findings highlight the essential role of FOXA1 in maintaining HER2 expression and a luminal cell phenotype in HER2-positive breast cancers.
Genetic context modulates aging and degeneration in the murine retina
Authors: Marola Olivia J. , MacLean Michael , Cossette Travis L. , Diemler Cory A. , Hewes Amanda A. , Reagan Alaina M. , Skelly Daniel A. , Howell Gareth R. 
Published: April 2024

AbstractBackgroundAge is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease. However, studies investigating retinal aging have not sufficiently accounted for genetic diversity. Therefore, examining molecular aging in the retina across different genetic backgrounds will enhance our understanding of human-relevant aging and degeneration in both the retina and brain—potentially improving therapeutic approaches to these debilitating conditions.MethodsTranscriptomics and proteomics were employed to elucidate retinal aging signatures in nine genetically diverse mouse strains (C57BL/6J, 129S1/SvlmJ, NZO/HlLtJ, WSB/EiJ, CAST/EiJ, PWK/PhK, NOD/ShiLtJ, A/J, and BALB/cJ) across lifespan. These data predicted human disease-relevant changes in WSB and NZO strains. Accordingly, B6, WSB and NZO mice were subjected to human-relevantin vivoexaminations at 4, 8, 12, and/or 18M, including: slit lamp, fundus imaging, optical coherence tomography, fluorescein angiography, and pattern/full-field electroretinography. Retinal morphology, vascular structure, and cell counts were assessedex vivo.ResultsWe identified common molecular aging signatures across the nine mouse strains, which included genes associated with photoreceptor function and immune activation. Genetic background strongly modulated these aging signatures. Analysis of cell type-specific marker genes predicted age-related loss of photoreceptors and retinal ganglion cells (RGCs) in WSB and NZO, respectively. Fundus exams revealed retinitis pigmentosa-relevant pigmentary abnormalities in WSB retinas and diabetic retinopathy (DR)-relevant cotton wool spots and exudates in NZO retinas. Profound photoreceptor dysfunction and loss were confirmed in WSB. Molecular analyses indicated changes in photoreceptor-specific proteins prior to loss, suggesting photoreceptor-intrinsic dysfunction in WSB. In addition, age-associated RGC dysfunction, loss, and concomitant microvascular dysfunction was observed in NZO mice. Proteomic analyses revealed an early reduction in protective antioxidant processes, which may underlie increased susceptibility to DR-relevant pathology in NZO.ConclusionsGenetic context is a strong determinant of retinal aging, and our multi-omics resource can aid in understanding age-related diseases of the eye and brain. Our investigations identified and validated WSB and NZO mice as improved preclinical models relevant to common retinal neurodegenerative diseases.
Balancing selection and the functional effects of shared polymorphism in crypticDaphniaspecies
Authors: Murray Connor S. , Karram Madison , Bass David J. , Doceti Madison , Becker Dörthe , Nunez Joaquin C. B. , Ratan Aakrosh , Bergland Alan O. 
Published: April 2024

AbstractThe patterns of genetic variation within and between related taxa represent the genetic history of a species. Shared polymorphisms, loci with identical alleles across species, are of unique interest as they may represent cases of ancient selection maintaining functional variation post-speciation. In this study, we investigate the abundance of shared polymorphism in theDaphnia pulexspecies complex. We test whether shared mutations are consistent with the action of balancing selection or alternative hypotheses such as hybridization, incomplete lineage sorting, or convergent evolution. We analyzed over 2,000 genomes from North American and EuropeanD. pulexand several outgroup species to examine the prevalence and distribution of shared alleles between the focal species pair, North American and EuropeanD. pulex. We show that while North American and EuropeanD. pulexdiverged over ten million years ago, they retained tens of thousands of shared alleles. We found that the number of shared polymorphisms between North American and EuropeanD. pulexcannot be explained by hybridization or incomplete lineage sorting alone. Instead, we show that most shared polymorphisms could be the product of convergent evolution, that a limited number appear to be old trans-specific polymorphisms, and that balancing selection is affecting young and ancient mutations alike. Finally, we provide evidence that a blue wavelength opsin gene with trans-specific polymorphisms has functional effects on behavior and fitness in the wild. Ultimately, our findings provide insights into the genetic basis of adaptation and the maintenance of genetic diversity between species.