bluuebunny/crossref_metadata_2025_split huggingface dataset:
TLS2trees: a scalable tree segmentation pipeline for TLS data
Authors: Wilkes Phil , Disney Mathias , Armston John , Bartholomeus Harm , Bentley Lisa , Brede Benjamin , Burt Andrew , Calders Kim , Chavana-Bryant Cecilia , Clewley Daniel , Duncanson Laura , Forbes Brieanne , Krisanski Sean , Malhi Yadvinder , Moffat David , Origo Niall , Shenkin Alexander , Yang Wanxin 
Published: December 2022

AbstractAbove Ground Biomass (AGB) is an important metric used to quantify the mass of carbon stored in terrestrial ecosystems. For forests, this is routinely estimated at the plot scale (typically ≥1 ha) using inventory measurements and allometry. In recent years, Terrestrial Laser Scanning (TLS) has appeared as a disruptive technology that can generate a more accurate assessment of tree and plot scale AGB; however, operationalising TLS methods has had to overcome a number of challenges. One such challenge is the segmentation of individual trees from plot level point clouds that are required to estimate woody volume, this is often done manually (e.g. with interactive point cloud editing software) and can be very time consuming. Here we presentTLS2trees, an automated processing pipeline and set of Python command line tools that aims to redress this processing bottleneck.TLS2treesconsists of existing and new methods and is specifically designed to be horizontally scalable. The processing pipeline is demonstrated across 10 plots of 7 forest types; from open savanna to dense tropical rainforest, where a total of 10,557 trees are segmented.TLS2treessegmented trees are compared to 1,281 manually segmented trees. Results indicate thatTLS2treesperforms well, particularly for larger trees (i.e. the cohort of largest trees that comprise 50% of total plot volume), where plot-wise tree volume bias is ±0.4 m3and %RMSE is~60%. To facilitate improvements to the presented methods as well as modification for other laser scanning modes (e.g. mobile and UAV laser scanning),TLS2treesis a free and open-source software (FOSS).
Improving the detection ofA. cantonensisin brain tissues of mammalian hosts
Authors: Arango Micaela , Delgado-Serra Sofía , Haines Lee , Paredes-Esquivel Claudia 
Published: December 2022

AbstractAngiostrongylus cantonensisis an invasive nematode parasite that can cause eosinophilic meningitis in many vertebrate hosts, including humans. This parasite is spreading rapidly through the six continents, with Europe being the final frontier. Sentinel surveillance may be a cost-effective surveillance strategy to monitor the arrival of this pathogen to new geographical regions as this can be easily expanded to incorporate symptomatic wildlife. Necropsy and tissue digestion techniques are often used to recover helminth parasites from vertebrate host tissues, however their application to detect brain parasites is poorly utilized. Here we show that employing these techniques in combination can 1) help resolve false positive and negative animals, 2) provide accurate parasitic load values and 3) establish an accurate prevalence ofA. cantonensis. Our adapted tissue digestion technique can be easily performed, especially in wildlife hospitals where animal infections often precede human cases. Early detection of the parasite increases the efficacy of prevention, treatment, and disease control strategies not only in humans, but also in susceptible animal populations.Key FindingsOptimized brain digestion techniques can detect parasitic helminths (A. cantonensis) in mammalian hosts.Accuracy identifying neurotropic parasitic infections can be increased if a standard digestion protocol is applied.The technique presented here can be easily implemented to detect brain nematodes in wildlife hospitals.
Points2Regions: Fast, interactive clustering of imaging-based spatial transcriptomics data
Authors: Andersson Axel , Behanova Andrea , Avenel Christophe , Windhager Jonas , Malmberg Filip , Wählby Carolina 
Published: December 2022

AbstractImaging-based spatial transcriptomics techniques generate image data that, once processed, results in a set of spatial points with categorical labels for different mRNA species. A crucial part of analyzing downstream data involves the analysis of these point patterns. Here, biologically interesting patterns can be explored at different spatial scales. Molecular patterns on a cellular level would correspond to cell types, whereas patterns on a millimeter scale would correspond to tissue-level structures. Often, clustering methods are employed to identify and segment regions with distinct point-patterns. Traditional clustering techniques for such data are constrained by reliance on complementary data or extensive machine learning, limiting their applicability to tasks on a particular scale. This paper introduces ‘Points2Regions’, a practical tool for clustering spatial points with categorical labels. Its flexible and computationally efficient clustering approach enables pattern discovery across multiple scales, making it a powerful tool for exploratory analysis. Points2Regions has demonstrated efficient performance in various datasets, adeptly defining biologically relevant regions similar to those found by scale-specific methods. As a Python package integrated into TissUUmaps and a Napari plugin, it offers interactive clustering and visualization, significantly enhancing user experience in data exploration. In essence, Points2Regions presents a user-friendly and simple tool for exploratory analysis of spatial points with categorical labels.
Symbiotic nutrient cycling enables the long-term survival of Aiptasia in the absence of heterotrophic food sources
Authors: Rädecker Nils , Meibom Anders 
Published: December 2022

AbstractPhototrophic Cnidaria are mixotrophic organisms that can complement their heterotrophic diet with nutrients assimilated by their algal endosymbionts. Metabolic models suggest that the translocation of photosynthates and their derivatives from the algae may be sufficient to cover the metabolic energy demands of the host. However, the importance of heterotrophy to the nutritional budget of these holobionts remains unclear. Here, we report on the long-term survival of the photosymbiotic anemone Aiptasia in the absence of heterotrophic food sources. Following one year of heterotrophic starvation, these anemones remained fully viable but showed an 85 % reduction in biomass compared to their regularly fed counterparts. This shrinking was accompanied by a reduction in host protein content and algal density, indicative of severe nitrogen limitation. Nonetheless, isotopic labeling experiments combined with NanoSIMS imaging revealed that the contribution of algal-derived nutrients to the host metabolism remained unaffected due to an increase in algal photosynthesis and more efficient carbon translocation. Taken together, our results suggest that, on a one- year timescale, heterotrophic feeding is not essential to fulfilling the energy requirements of the holobiont. But, while symbiotic nutrient cycling effectively retains carbon in the holobiont over long time scales, our data suggest that heterotrophic feeding is a critical source of nitrogen required for holobiont growth under oligotrophic conditions.
On the origin and evolution of the mosquito male-determining factorNix
Authors: Biedler James K. , Aryan Azadeh , Qi Yumin , Wang Aihua , Martinson Ellen O. , Hartman Daniel A. , Yang Fan , Sharma Atashi , Morton Katherine S. , Potters Mark , Chen Chujia , Dobson Stephen L. , Ebel Gregory D. , Kading Rebekah C. , Paulson Sally , Xue Rui-De , Strand Michael R. , Tu Zhijian 
Published: December 2022

AbstractThe mosquito family Culicidae is divided into two subfamilies named the Culicinae and Anophelinae.Nix, the dominant male-determining factor, has only been found in the culicinesAedes aegyptiandAe. albopictus, two important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution ofNix. Except for the Culex genus,Nixhomologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from three highly divergent tribes comprising 4 genera, suggestingNixoriginated at least 133-165 MYA. Heterologous expression of one of three divergentNixORFs inAe. aegyptiresulted in partial masculinization of genetic females as evidenced by morphology anddoublesexsplicing. It is not clear whether insufficient transgene expression or sequence divergence or both are responsible for the lack of phenotype for the other two. Phylogenetic analysis suggestsNixis related tofemaleless(fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes.Nixfrom all species has a conserved structure, including three RNA-recognition motifs (RRMs), as doesfle. However,Nixhas evolved at a much faster rate thanfle. The RRM3 of bothNixandfleare related to the single RRM of a widely distributed and conserved splicing factortransformer-2(tra2). RRM3-based phylogenetic analysis suggests this domain inNixandflemay have evolved fromtra2in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex-determination and homomorphic sex chromosomes in mosquitoes, and will inform broad applications of mosquito-control strategies based on manipulating sex ratios towards the non-biting males.
Aldo-Keto Reductase Family 1 Member A1 (AKR1A1) Deficiency Exacerbates Alcohol-Induced Hepatic Oxidative Stress, Inflammation, Steatosis, and Fibrosis
Authors: Lan Ying-Wei , Chen Wan-Ru , Yen Chih-Ching , Chong Kowit-Yu , Chen Ying-Cheng , Fan Hueng-Chuen , Chen Ming-Shan , Chen Chuan-Mu 
Published: December 2022

AbstractBackgroundAlcohol-associated liver disease (ALD) covers a wide range of hepatic lesions that depend on the amount and duration of alcohol consumption, from early and reversible conditions to hepatic steatosis and severe lesions, including steatohepatitis and alcoholic fibrosis, to irreversible cirrhosis. AKR1A1, an aldo-keto reductase family member, participates in the detoxification of alcohol-derived acetaldehyde, but its role in ALD remains unclear. In this study, we studied the role of AKR1A1 in the development of ALD usingAkr1a1-/-knockout mice and palmitic acid/oleic acid (P/O) plus ethanol-treated AML12 hepatocyte cells.MethodsLevels of AKR1A1 were measured in mice fed with the Lieber-DeCarli diet containing 5% alcohol (alcohol-fed, AF) or control liquid diet (pair-fed, PF). The effects of AKR1A1 on the liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed in AF-inducedAkr1a1-/-and ICR control mice.ResultsData showed thatAF-Akr1a1-/-mice exhibited an exacerbation of liver injury and increased gene and protein levels of inflammatory mediators, oxidative stress, lipid accumulation, and fibrosis, whilst decreased expression of antioxidant enzymes in their livers than the AF-ICR mice. Therefore, loss of AKR1A1 can activate 4-HNE/p53 signaling to modulate ROS and antioxidant balance, increase lipid peroxidation, fatty acid synthesis and lipid droplet formation, reduced fatty acid β-oxidation, and elevated proinflammatory and fibrotic mediator, eventually exacerbate the ALD. Inin vitrostudy, we further demonstrated that knockdown ofAkrlalaggravated the effects of alcohol plus P/O-induced oxidative stress and steatosis, LPS-stimulated inflammation, and TGF-β1-induced fibrosis in AML12 hepatocyte cells.Conclusionour results revealed that AKR1A1 exerts protective effects on alcohol-induced liver injury, steatosis, and fibrosis, possibly by regulating the 4-HNE-p53 signaling pathway.
Modelling metastasis in zebrafish unveils regulatory interactions of cancer-associated fibroblasts with circulating tumour cells
Authors: Hurtado Pablo , Martínez-Pena Inés , Yepes-Rodríguez Sabrina , Bascoy-Otero Miguel , Abuín Carmen , Fernández-Santiago Cristóbal , Sánchez Laura , López-López Rafael , Piñeiro Roberto 
Published: December 2022

AbstractThe dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a higher efficiency at establishing metastases, are found in the blood of BC patients, often accompanied by CAFs in heterotypic CTC-clusters. Previously we have shown the utility of CTC-clusters models and the zebrafish embryo as a model of metastasis to understand the biology of breast cancer CTC-clusters. In this work, we use the zebrafish embryo to study the interactions between CTCs in homotypic clusters and CTC-CAFs in heterotypic CTC-clusters to identify potential pro-metastatic traits derived from CTC-CAF communication. We found that upon dissemination CAFs seem to exert a pro-survival and pro-proliferative effect on the CTCs, but only when CTCs and CAFs remain joined as cell clusters. Our data indicate that the clustering of CTC and CAF allows the establishment of physical interactions that when maintained over time favour the selection of CTCs with a higher capacity to survive and proliferate upon dissemination. Importantly, this effect seems to be dependent on the survival of disseminated CAFs and was not observed in the presence of normal fibroblasts. Moreover, we show that CAFs can exert regulatory effects on the CTCs without being involved in promoting tumour cell invasion, and these effects are differential based on the BC cell molecular phenotype, and the crosstalk between tumour cells and CAFs, i.e. paracrine or physical interaction. Lastly, we show that the physical communication between BC cells and CAFs leads to the production of soluble factors involved in BC cell survival and proliferation. These findings suggest the existence of a CAF-regulatory effect on CTC survival and proliferation sustained by cell-to-cell contacts and highlight the need to understand the molecular mechanisms that mediate the interaction between the CTCs and CAFs in clusters enhancing the metastatic capacity of CTCs.
Dalpiciclib Partially Abrogates ER Signaling Activation Induced by Pyrotinib In HER2+HR+Breast Cancer
Authors: Bu Jiawen , Zhang Yixiao , Niu Nan , Bi Kewei , Sun Lisha , Qiao Xinbo , Wang Yimin , Zhang Yinan , Jiang Xiaofan , Wang Dan , Ma Qingtian , Li Huajun , Liu Caigang 
Published: December 2022

AbstractBackgroundRecent evidences from clinical trials (NCT04486911) revealed that the combination of pyrotinib, letrozole and dalpiciclib exerted optimistic therapeutic effect to treat HER2+HR+breast cancer, however, the underlying molecular mechanism remained further investigation.MethodsThrough the drug sensitivity test, the drug combination efficacy of pyrotinib, tamoxifen and dalpiciclib to BT474 cells were tested. The underlying molecular mechanisms were investigated using immunofluorescence, western blot analysis, immunohistochemical staining and cell cycle analysis. Potential risk factor which may indicate the responsiveness to drug treatment in HER2+/HR+breast cancer was selected out using RNA-sequence and tested using immunohistochemical staining and in vivo drug susceptibility test.ResultsWe found that pyrotinib combined with dalpiciclib exerted better cytotoxic efficacy than pyrotinib combined with tamoxifen in BT474 cells. Degradation of HER2 could enhance ER nuclear transportation, activating ER signaling pathway in BT474 cells whereas dalpiciclib could partially abrogate this process. This may be the underlying mechanism by which combination of pyrotinib, tamoxifen and dalpiciclib exerted best cytotoxic effect. Furthermore, CALML5 was revealed to be a risk factor in the treatment of HER2+/HR+breast cancer and the usage of dalpiciclib might overcome this.ConclusionOur study provided evidence that the usage of dalpiciclib in the treatment of HER2+/HR+breast cancer could partially abrogate the estrogen signaling pathway activation caused by anti-HER2 therapy and revealed that CALML5 could serve as a risk factor in the treatment of HER2+/HR+breast cancer.FundingThis study was supported by the National Natural Science Foundation of China (#U20A20381, #81872159)
Latitude influences stability via stabilizing mechanisms in naturally-assembled forest ecosystems at different spatial grains
Authors: Zhou Tianyang , Craven Dylan , Kreft Holger , Zhang Jiaxin , Wang Xugao , Lian Juyu , Ye Wanhui , Jin Guangze , Mi Xiangcheng , Yao Yujun , Ren Haibao , Yang Jie , Cao Min , Wang Congrong , Qin Yuanzhi , Zhou Gang , Fei Yanan , Xu Yaozhan , Qiao Xiujuan , Jiang Mingxi , Guerrero-Ramírez Nathaly R. 
Published: December 2022

AbstractEcosystem stability reveals how ecosystems respond to global change over time. Yet, the focus of past research on small spatial grains and extents overlooks scale dependence and how broad-scale environmental gradients shape stability. Here, we use forest inventory data covering a broad latitudinal gradient from the temperate to the tropical zone to examine cross-scale variation in stability of aboveground biomass and underlying stabilizing mechanisms. While stability did not shift systematically with latitude at either spatial grain, we found evidence that species asynchrony increased towards the tropics at the small spatial grain while species stability decreased at both spatial grains. Moreover, latitude stabilized forest communitiesviaits effects on both stabilizing mechanisms, which compensated for the weak and destabilizing effects of species richness. Yet, the trade-off in the relative importance of species stability and species asynchrony for stability was not mediated by latitude, suggesting that context-dependent factors - to a greater extent than macroecological ones - underlie large-scale patterns of stability. Our results highlight the crucial role of species asynchrony and species stability in determining ecosystem stability across broad-scale environmental gradients, suggesting that conserving biodiversity alone may not be sufficient for stabilizing naturally-assembled forest ecosystems.
Targeting the TR4-induced RCC cells-derived exosomally initiated signaling increases Sunitinib efficacy
Authors: Wang Zhenwei , Sun Yin , Xu Huiyang , Huang Chi-Ping , Cheng Bo , Chou Fuju , You Bosen , Qiu Xiaofu , Yang Guosheng , Chang Chawnshang 
Published: December 2022

AbstractSunitinib is the first-line therapy for metastatic clear cell renal cell carcinoma (RCC) via suppressing neoangiogenesis and tumor growth. The detailed mechanisms, especially whether and how RCC cells can impact endothelial cells sensitivity to Sunitinib, remain unclear. Here, we found that TR4 was commonly upregulated in RCC tissue and relative to tumor angiogenesis. Tube formation and Mouse aortic ring assay showed that the overexpression or knockdown of TR4 in RCC cells enhanced or reduced the angiogenesis of endothelial cells and their resistance to Sunitinib in vitro. Mechanistically, We found that TR4 transcriptionally increase ADAM15 expression, as a consequence, exosomes carrying relatively large amounts of ADAM15 secreted from RCC cell resulted in activating the EGFR phosphorylation and reducing the efficacy of Sunitinib in endothelial cells. Targeting the TR4-induced renal cancers-derived exosomelly initiated signaling with a small molecular, CRM197, increases sunitinib efficacy in vitro and xenograft tumor models. Taken together, our findings indicate a novel function of TR4 in RCC blunted the efficacy of sunitinib via exosomal ADAM15-induced activation of EGFR signaling pathway in endothelial cells.
Interplay of p53 and XIAP protein dynamics orchestrates cell fate in response to chemotherapy
Authors: Abukwaik Roba , Vera-Siguenza Elias , Tennant Daniel A. , Spill Fabian 
Published: December 2022

AbstractChemotherapeutic drugs are used to treat almost all types of cancer, but the intended response, i.e., elimination, is often incomplete, with a subset of cancer cells resisting treatment. Two critical factors play a role in chemoresistance: the p53 tumour suppressor gene and the X-linked inhibitor of apoptosis (XIAP). These proteins have been shown to act synergistically to elicit cellular responses upon DNA damage induced by chemotherapy, yet, the mechanism is poorly understood. This study introduces a mathematical model characterising the apoptosis pathway activation by p53 before and after mitochondrial outer membrane permeabilisation upon treatment with the chemotherapy Doxorubicin (Dox).“In-silico”simulations show that the p53 dynamics change dose-dependently. Under medium to high doses of Dox, p53 concentration ultimately stabilises to a high level regardless of XIAP concentrations. However, caspase-3 activation may be triggered or not depending on the XIAP induction rate, ultimately determining whether the cell will perish or resist. Consequently, the model predicts that failure to activate apoptosis in some cancer cells expressing wild-type p53 might be due to heterogeneity between cells in upregulating the XIAP protein, rather than due to the p53 protein concentration. Our model suggests that the interplay of the p53 dynamics and the XIAP induction rate is critical to determine the cancer cells’ therapeutic response.
Limits to evolutionary rescue by conjugative plasmids
Authors: Geoffroy Félix , Uecker Hildegard 
Published: December 2022

AbstractPlasmids may carry genes coding for beneficial traits and thus contribute to adaptation of bacterial populations to environmental stress. Conjugative plasmids can horizontally transfer between cells, which a priori facilitates the spread of adaptive alleles. However, if the potential recipient cell is already colonized by another incompatible plasmid, successful transfer may be prevented. Competition between plasmids can thus limit horizontal transfer. Previous modeling has indeed shown that evolutionary rescue by a conjugative plasmid is hampered by incompatible resident plasmids in the population. If the rescue plasmid is a mutant variant of the resident plasmid, both plasmids transfer at the same rates. A high conjugation rate then has two, potentially opposing, effects – a direct positive effect on spread of the rescue plasmid and an increase in the fraction of resident plasmid cells. This raises the question whether a high conjugation rate always benefits evolutionary rescue. In this article, we systematically analyse three models of increasing complexity to disentangle the benefits and limits of increasing horizontal gene transfer in the presence of plasmid competition and plasmid costs. We find that the net effect can be positive or negative and that the optimal transfer rate is thus not always the highest one. These results can contribute to our understanding of the many facets of plasmid-driven adaptation and the wide range of transfer rates observed in nature.