bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell Mayo Map (scMayoMap): an easy-to-use tool for cell type annotation in single-cell RNA-sequencing data analysis
Authors: Yang Lu , Ng Yan Er , Sun Haipeng , Li Ying , Chini Lucas C.S. , LeBrasseur Nathan K. , Chen Jun , Zhang Xu 
Published: May 2023

AbstractSingle-cell RNA-sequencing (scRNA-seq) has become a widely used tool for both basic and translational biomedical research. In scRNA-seq data analysis, cell type annotation is an essential but challenging step. In the past few years, several annotation tools have been developed. These methods require either labeled training/reference datasets, which are not always available, or a list of predefined cell subset markers, which are subject to biases. Thus, a user-friendly and precise annotation tool is still critically needed. We curated a comprehensive cell marker database namedscMayoMapDatabaseand developed a companion R packagescMayoMap, an easy-to-use single cell annotation tool, to provide fast and accurate cell type annotation. The effectiveness ofscMayoMapwas demonstrated in 48 independent scRNA-seq datasets across different platforms and tissues.scMayoMapperforms better than the currently available annotation tools on all the datasets tested. Additionally, thescMayoMapDatabasecan be integrated with other tools and further improve their performance.scMayoMapandscMayoMapDatabasewill help investigators to define the cell types in their scRNA-seq data in a streamlined and user-friendly way.
Scalable Mesenchymal Stem Cells Enrichment from Bone Marrow Aspirate using Deterministic Lateral Displacement (DLD) Microfluidics Sorting
Authors: Kwan Zen Nicholas Tan , Kwek Kerwin Zeming , Leng Teo Kim , Loberas Mavis , Lee Jialing , Goh Chin Ren , Yang Da Hou , Oh Steve , Hoi Po James Hui , Cool Simon M. , Hou Han Wei , Han Jongyoon 
Published: May 2023

AbstractThe growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone Marrow Aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼ 2 – 3 hours). To address these issues, we have developed a scalable microfluidic technology based on Deterministic Lateral Displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (leukocytes and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel portable multiplexed DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings.
Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model
Authors: Bjørnstad Ole Vidhammer , Carrasco Manuel , Finne Kenneth , Winge Ingeborg , Askeland Cecilie , Arnes Jarle B. , Knutsvik Gøril , Kleftogiannis Dimitrios , Paulo Joao A. , Akslen Lars A. , Vethe Heidrun 
Published: May 2023

AbstractTumor neurogenesis, a process by which new nerves invade tumors, is a growing area of interest in cancer research. Nerve presence has been linked to aggressive features of various solid tumors, including breast and prostate cancer. A recent study suggested that the tumor microenvironment may influence cancer progression through recruitment of neural progenitor cells from the central nervous system. However, the presence of neural progenitors in human breast tumors has not been reported. Here, we investigate the presence of Doublecortin (DCX) and Neurofilament-Light (NFL) co-expressing (DCX+/NFL+) cells in patient breast cancer tissue using Imaging Mass Cytometry. To map the interaction between breast cancer cells and neural progenitor cells further, we created anin vitromodel mimicking breast cancer innervation, and characterized using mass spectrometry-based proteomics on the two cell types as they co- evolved in co-culture. Our results indicate stromal presence of DCX+/NFL+ cells in breast tumor tissue from a cohort of 107 patient cases, and that neural interaction contribute to drive a more aggressive breast cancer phenotype in our co-culture models. Our results support that neural involvement plays an active role in breast cancer and warrants further studies on the interaction between nervous system and breast cancer progression.
A multiscale theory for spreading and migration of adhesion-reinforced mesenchymal cells
Authors: Shu Wenya , Kaplan C. Nadir 
Published: May 2023

AbstractWe present a chemomechanical whole-cell theory for the spreading and migration dynamics of mesenchymal cells that can actively reinforce their adhesion to an underlying viscoelastic substrate as a function of its stiffness. Our multiscale model couples the adhesion reinforcement effect at the subcellular scale with the nonlinear mechanics of the nucleus-cytoskeletal network complex at the cellular scale to explain the concurrent monotonic area-stiffness and non-monotonic speed-stiffness relationships observed in experiments: We consider that large cell spreading on stiff substrates flattens the nucleus, increasing the viscous drag force on it. The resulting force balance dictates a reduction in the migration speed on stiff substrates. We also reproduce the experimental influence of the substrate viscosity on the cell spreading area and migration speed by elucidating how the viscosity may either maintain adhesion reinforcement or prevent it depending on the substrate stiffness. Additionally, our model captures the experimental directed migration behavior of the adhesion-reinforced cells along a stiffness gradient, known as durotaxis, as well as up or down a viscosity gradient (viscotaxis or anti-viscotaxis), the cell moving towards an optimal viscosity in either case. Overall, our theory explains the intertwined mechanics of the cell spreading, migration speed and direction in the presence of the molecular adhesion reinforcement mechanism.
Multi temporal multispectral UAV remote sensing allows for yield assessment across European wheat varieties already in tillering stage
Authors: Camenzind Moritz , Yu Kang 
Published: May 2023

AbstractHigh throughput field phenotyping techniques employing multispectral cameras allow to extract a variety of variables and features to predict yield and yield related traits, but little is known about which types of multispectral features may allow to forecast yield potential in the early growth phase. In this study, we hypothesized that the best features for predicting yield in an early stage might be different from the best predictors for the late growth stages. Based on a variety testing trial of 19 European wheat varieties in 2021, multispectral images were taken on 19 dates ranging from tillering to harvest by an unmanned aerial vehicle measuring reflectance in five bands, including visible bands, Red-edge and the near-infrared (NIR). Orthomosaic images were created, and then the single band reflectances, vegetation indices (VI) and texture features (TF) based on a gray level correlation matrix (GLCM) were extracted. We evaluated the performance of these three types of features for yield prediction and classification at different growth stages by, i) using features on each of the measurement dates, ii) smoothing features across the 19 dates, and iii) combining features across the directly adjacent dates, in combination with the random forest models. Our results showed that, for most features, measurements at the flowering stage showed the best performance and the Red reflectance was able to predict yield with a RMSE of 47.4 g m-2(R2= 0.63), the best VI was NDRE predicting yield with a RMSE of 47.9 g m-2(R2= 0.63), the best TF was contrast predicting yield with a RMSE of 57.2 g m-2(R2= 0.46) at the booting stage. Combining dates improved yield prediction in all dates and made the prediction errors more stable across dates. Rather than the Red-edge band, visible bands especially the Red band enabled to distinguish between the high- and low-yielding varieties already in the tillering stage, with a total accuracy of 76.7%. The study confirms our hypothesis and further implies that, in the early stages, the visible bands may be more effective than Red-edge bands in assessing the yield potential in a range of testing varieties.
Impacts of global food supply on biodiversity via land use and climate change
Authors: Boakes Elizabeth H , Dalin Carole , Etard Adrienne , Newbold Tim 
Published: May 2023

AbstractLand-use change is currently the greatest driver of biodiversity change, with climate change predicted to match or surpass its impacts by mid-century. The global food system is a key driver of both these anthropogenic pressures, thus the development of sustainable food systems will be critical to halting and reversing biodiversity loss. Previous studies of the biodiversity footprint of food tend to focus on land use alone. We use the multi-regional input-output model EXIOBASE to estimate the impacts of biodiversity embedded within the global food system. We build on prior analyses, calculating the impacts of both agricultural land-use and greenhouse gas (GHG) emission footprints for the same two metrics of biodiversity: local species richness and rarity-weighted species richness. Our biodiversity models capture regional variation in the sensitivity of biodiversity both to land-use differences and to climate change. We find that the footprint of land area does not capture the biodiversity impact embedded within trade that is provided by our metric of land-driven species richness change, and that our metric of rarity-weighted richness places a greater emphasis on the biodiversity costs in Central and South America. We find that methane emissions are responsible for 70% of the overall GHG-driven biodiversity footprint and that, in several regions, emissions from a single year’s food production cause biodiversity loss equivalent to 2% or more of that region’s total historic land use. The measures we present are simple to calculate and could be incorporated into decision making and environmental impact assessments by governments and businesses.
Rediversification Following Ecotype Isolation Reveals Hidden Adaptive Potential
Authors: Ascensao Joao A , Denk Jonas , Lok Kristen , Yu QinQin , Wetmore Kelly M , Hallatschek Oskar 
Published: May 2023

ABSTRACTMicrobial communities play a critical role in ecological processes, and their diversity is key to their functioning. However, little is known about if communities can regenerate ecological diversity following species removal or extinction, and how the rediversified communities would compare to the original ones. Here we show that simple two-ecotype communities from theE. coliLong Term Evolution Experiment (LTEE) consistently rediversified into two ecotypes following the isolation of one of the ecotypes, coexisting via negative frequency-dependent selection. Communities separated by more than 30,000 generations of evolutionary time rediversify in similar ways. The rediversified ecotype appears to share a number of growth traits with the ecotype it replaces. However, the rediversified community is also different compared to the original community in ways relevant to the mechanism of ecotype coexistence, for example in stationary phase response and survival. We found substantial variation in the transcriptional states between the two original ecotypes, whereas the differences within the rediversified community were comparatively smaller, but with unique patterns of differential expression. Our results suggest that evolution may leave room for alternative diversification processes even in a maximally reduced community of only two strains. We hypothesize that the presence of alternative evolutionary pathways may be even more pronounced in communities of many species, highlighting an important role for perturbations, such as species removal, in evolving ecological communities.
The glucocorticoid dexamethasone impairs the expression of anti-viral mediators in activated macrophages by inhibiting both expression and function of interferon β
Authors: O’Neil John D , Bolimowska Oliwia O , Clayton Sally A , Tang Tina , Daley Kalbinder K , Lara-Reyna Samuel , Warner Jordan , Martin Claire S , Mahida Rahul Y , Hardy Rowan S , Arthur J Simon C , Clark Andrew R 
Published: May 2023

AbstractGlucocorticoids potently inhibit expression of many inflammatory mediators, and have been very widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we investigated effects of the synthetic glucocorticoid dexamethasone on the responses of primary mouse bone marrow-derived macrophages to the pro-inflammatory agonist lipopolysaccharide (LPS). At the mRNA level, dexamethasone inhibited the LPS-induced expression of more than 100 genes that are involved in cell-intrinsic defence against viral pathogens. Expression of most of the corresponding proteins was also reduced by dexamethasone. This antiviral disarmament occurred at two distinct levels. First, dexamethasone strongly and dose-dependently inhibited the expression of the type I interferon IFNβ by LPS-activated macrophages. IFNβ mediates an autocrine positive feedback loop in LPS-treated macrophages, promoting the expression of antiviral genes and other interferon-stimulated genes. Hence reduction of IFNβ expression contributes to impaired expression of antiviral genes. Dexamethasone also acted downstream of IFNβ to inhibit expression of a subset of interferon-regulated genes. We tested a number of hypotheses based on previous publications, but found that no single mechanism could account for more than a small fraction of the broad suppressive impact of dexamethasone on macrophage type I interferon signaling, underlining the complexity of this pathway. Preliminary experiments indicated that dexamethasone exerted similar inhibitory effects on primary human monocyte-derived or alveolar macrophages.
Cancer associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy
Authors: Forsthuber Agnes , Aschenbrenner Bertram , Korosec Ana , Jacob Tina , Annusver Karl , Krajic Natalia , Kholodniuk Daria , Frech Sophie , Zhu Shaohua , Purkhauser Kim , Lipp Katharina , Werner Franziska , Nguyen Vy , Griss Johannes , Bauer Wolfgang , Soler Cardona Ana , Weber Benedikt , Weninger Wolfgang , Gesslbauer Bernhard , Staud Clement , Nedomansky Jakob , Radtke Christine , Wagner Stephan N. , Petzelbauer Peter , Kasper Maria , Lichtenberger Beate M. 
Published: May 2023

SummaryCancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. This study dissects the yet unresolved intra-tumoral variety of CAFs in three skin cancer types — Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma — at molecular and spatial single-cell resolution. By integral analysis of the fibroblasts with the tumor microenvironment, including epithelial, mesenchymal, and immune cells, we characterize three distinct CAF subtypes: myofibroblast-like RGS5+ CAFs, matrix CAFs (mCAFs), and immunomodulatory CAFs (iCAFs). Notably, large cohort tissue analysis reveals marked shifts in CAF subtype patterns with increasing malignancy. Two CAF types exhibit immunomodulatory capabilities via distinct mechanisms. mCAFs synthesize extracellular matrix and have the ability to ensheath tumor nests, potentially limiting T cell invasion in low-grade tumors. In contrast, iCAFs are enriched in late-stage tumors, especially infiltrative BCC and high-grade melanoma, and express unexpectedly high mRNA and protein levels of cytokines and chemokines, pointing to their integral role in immune cell recruitment and activation. This finding is further supported by our observation that in vitro exposure of primary healthy fibroblasts to skin cancer cell secretomes induces an iCAF-like phenotype with immunomodulatory functions. Thus, targeting CAF variants, particularly the immunomodulatory iCAF subtype, holds promise for improved efficacy of immunotherapy in skin cancers.
Connexin 43 mediated collective cell migration is independent of Golgi orientation
Authors: Sharma Madhav , Mukherjee Suvam , Shaw Archana Kumari , Mondal Anushka , Behera Amrutamaya , Das Jibitesh , Bose Abhishek , Sinha Bidisha , Das Sarma Jayasri 
Published: May 2023

AbstractCell migration is vital for multiple physiological functions and is involved in the metastatic dissemination of tumour cells in various cancers. For effective directional migration, cells often reorient their secretory traffic towards the leading edge by reorienting the Golgi apparatus. However, conflicting results on the positioning of the Golgi relative to the migrating cell raise questions about its regulation. Herein, we address the role of gap junction protein Connexin 43, which connects cells allowing the direct exchange of molecules and also controls the distribution of microtubules. We utilized HeLa WT (wild-type cells lacking Connexin 43) and HeLa 43 cells (stably expressing Connexin 43). We found that functional Connexin 43 channels affected Golgi morphology and reduced the ability of reorientation of Golgi (towards the leading edge) during cell migration. Although Connexin 43 also reduced migration velocity, the front displayed enhanced coherence in movement, implying an augmented collective nature of migration compared to HeLa WT cells lacking the cell-cell connectivity evidenced in HeLa 43. The increase in vimentin and basal actin in HeLa 43 shows that Connexin 43 expression alters the cytoskeleton. Non-invasive measurement of basal membrane height fluctuations revealed that HeLa 43 had a lower membrane tension and a more uniform intra- and inter-cellular distribution than HeLa WT, similar to their coherence in migration. We, therefore, propose that the reduced Golgi reorientation in HeLa 43 might be linked to lesser dependence on directed secretory trafficking, which is believed to be required to buffer the increasing tension caused by migration.
Long term trend and short-term dynamics of a willow grouse population
Authors: Willebrand Tomas , Kleiven Eivind Flittie , Willebrand Maria Hörnell , Brittas Rolf 
Published: May 2023

AbstractWillow ptarmiganLagopus lagopusand rock ptarmiganLagopus mutus,are abundant in Arctic and tundra regions, but negative trends in their distribution have recently been reported. Rapid climate change has been identified as the cause of this decline. Willow ptarmigan is adapted to harsh winter conditions, and winters with less snow could increase vulnerability when the ground is snow-free. In this study, we used a hierarchical state-space model to analyze 139 km line transects in mid-Sweden over 46 years. We assessed long-term trends in the adult population and estimated the effects of breeding success and climate on short-term changes. Contrary to our expectations, the adult population did not exhibit a negative trend. Breeding success was significantly positive for adult population change, but late spring had a significant negative effect on population change. The number of snow-free days in spring and autumn increased during the study; however, neither variable had a negative effect on adult population change. The adult willow ptarmigan followed a pattern of a stationary population under the influence of both stochastic and density-dependent factors, and changes in adults showed a negative density dependence. Our study area is in the southern range of the tundra, and we suggest that the stable dynamics of the adult population can be explained by a diverse predator assemblage that makes it impossible for the population to escape a top-down regulation.
Supporting diamond open access journals. Interest and feasibility of direct funding mechanisms
Authors: Dufour Quentin , Pontille David , Torny Didier 
Published: May 2023

AbstractMore and more academics and governements consider that the open access model based on Article Processing Charges (APC) is problematic, not only due to the inequalities it generates and reinforces, but also because it has become unsustainable and even opposed to open access values. They consider that scientific publishing based on a model where both authors and readers do not pay – the so-called Diamond, or non-APC model – should be developed and supported. However, beyond the display of such a support on an international scale, the landscape of Diamond journals is rather in the form of loosely connected archipelagos, and not systematically funded. This article explores the practical conditions to implement a direct funding mechanism to such journals, that is reccurent money provided by a funder to support the publication process. Following several recommendations from institutional actors in the open access world, we consider the hypothesis that such a funding would be fostered by research funding organizations (RFOs), which have been essential to the expansion of the APC model, and now show interest in supporting other models. Based on a questionnaire survey sent to more thant 1000 Diamond Open Access journals, this article analyzes their financial needs, as well as their capacity to interact with funders. It is structured around four issues regarding the implementation of a direct funding model : Do Diamond journals really make use of money, and to what end ? Do they need additional money? Are they able to engage monetary transactions? Are they able to meet RFOs’ visibility requirements? We show that a majority of OA Diamond journals could make use of a direct funding mechanism with certain adjustments. We conclude on the challenges that such a financial stream would spur.
HiPhase: Jointly phasing small and structural variants from HiFi sequencing
Authors: Holt James M. , Saunders Christopher T. , Rowell William J. , Kronenberg Zev , Wenger Aaron M. , Eberle Michael 
Published: May 2023

AbstractBackgroundIn diploid organisms, phasing is the problem of assigning the heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation such as structural variants. However, current phasing tools typically only phase small variants, leaving larger structural variants unphased.MethodsWe developed HiPhase, a tool that jointly phases SNVs, indels, and structural variants. The main benefits of HiPhase are 1) dual mode allele assignment for detecting structural variants, 2) a novel application of the A*-algorithm to phasing, and 3) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions.ResultsIn our assessment, HiPhase produced an average phase block NG50 of 493 kb with 933 switchflip errors and fully phased 95.2% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, and structural variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.Availabilityhttps://github.com/PacificBiosciences/HiPhase