bluuebunny/crossref_metadata_2025_split huggingface dataset:
GeneExt: a gene model extension tool for enhanced single-cell RNA-seq analysis
Authors: Zolotarov Grygoriy , Grau-Bové Xavier , Sebé-Pedrós Arnau 
Published: December 2023

AbstractIncomplete gene models negatively impact single-cell gene expression quantification. This is particularly true in non-model species where often gene 3′ ends are inaccurately annotated, while most scRNA-seq methods only capture the 3′ transcript region. This results in many genes being incorrectly quantified or not detected. GeneExt leverages scRNA-seq data to refine gene annotations, enhancing biological interpretation and cross-species comparisons of cell type expression atlases.
Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma
Authors: Manoharan Varsha Thoppey , Abdelkareem Aly , Brown Samuel , Gillmor Aaron , Hall Courtney , Seo Heewon , Narta Kiran , Grewal Sean , Dang Ngoc Ha , Ahn Bo Young , Otz Kata , Lun Xueqing , Mah Laura , Zemp Franz , Mahoney Douglas , Senger Donna L. , Chan Jennifer A. , Morrissy A. Sorana 
Published: December 2023

AbstractDiffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies. Towards this goal, we applied a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion were aligned with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs were highly prognostic in GBM patients. The compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of immediate and long-term consequences of such perturbations, including identification of compensatory programs that will inform improved combinatorial therapies.
Historical contingency influences the diversity of feather nanostructures in cuckoos
Authors: Nordén Klara K. , Cooney Christopher R. , Babarović Frane , Stoddard Mary Caswell 
Published: December 2023

AbstractStructural coloration is widespread in animals, yet we know relatively little about its evolution and development. While previous studies have explored adaptive functions of structural color, a key gap is our lack of understanding of how historical contingency (path-dependency of biological processes) influences the loss and gain of this complex trait. We shed light on this question by describing feather nanostructures responsible for plumage colors in the cuckoos (family Cuculidae), a group with widespread occurrence of shiny, metallic plumage (metallic luster). The melanosomes found in feathers with metallic luster have specialized shapes: hollow rods, thin solid rods, hollow platelets, or solid platelets. In contrast, it is generally assumed that drably colored feathers possess thick, rod-shaped melanosomes. However, we uncover that this assumption is unfounded in cuckoos. We describe metallic luster in the plumages of 126 cuckoo species and map its phylogenetic distribution. This reveals that metallic luster is widespread in cuckoos but has likely been lost several times. We then use transmission electron microscopy to describe the feather nanostructures of 21 cuckoo species. Surprisingly, the drab feathers of many cuckoo species contain melanosomes with specialized shapes. We propose that historical contingency greatly influences nanostructure diversity in cuckoos. Specialized melanosome shapes can be retained in the plumages of drab species, potentially making it easier for metallic luster to evolve again in the future. This discovery supports the idea that historical contingency plays a key role in shaping the evolution of plumage color diversity.
Intra-horn insemination in the alpacaVicugna pacos: Copulatory wounding and deep sperm deposition
Authors: Brennan Patricia LR , Purdy Stephen , Bacon Sarah J 
Published: December 2023

AbstractAlpacas (Vicugna pacos) are reported to be the rare mammal in which the penis enters the uterus in mating. To date, however, only circumstantial evidence supports this assertion. Using female alpacas culled for meat, we determined that the alpaca penis penetrates to the very tips of the uterine horns, abrading the tract and breaking fine blood vessels. All female alpacas sacrificed one hour or 24 hours after mating showed conspicuous bleeding in the epithelium of some region of their reproductive tract, including the hymen, cervix and the tips of each uterine horn, but typically not in the vagina. Unmated females showed no evidence of conspicuous bleeding. Histological examination of mated females revealed widespread abrasion of the cervical and endometrial epithelium, injuries absent in unmated females. Within one hour of mating, sperm were already present in the oviduct. The male alpaca’s cartilaginous penis tip with a hardened urethral process is likely responsible for the copulatory abrasion. The entire female reproductive tract interacts with the penis, functioning like a vagina. Alpacas are induced ovulators, and wounding may hasten delivery of the seminal ovulation-inducing factor beta-NGF into the female’s blood stream. There is no evidence of sexual conflict in copulation in alpaca, and thus wounding may also be one of a variety of mechanisms devised by mammals to induce a beneficial, short-term inflammatory response that stimulates blastocyst implantation, the uterine remodeling associated with placental development, and thus the success of early pregnancy.
Insect Detect: An open-source DIY camera trap for automated insect monitoring
Authors: Sittinger Maximilian , Uhler Johannes , Pink Maximilian , Herz Annette 
Published: December 2023

AbstractInsect monitoring is essential to design effective conservation strategies, which are indispensable to mitigate worldwide declines and biodiversity loss. For this purpose, traditional monitoring methods are widely established and can provide data with a high taxonomic resolution. However, processing of captured insect samples is often time-consuming and expensive, which limits the number of potential replicates. Automated monitoring methods can facilitate data collection at a higher spatiotemporal resolution with a comparatively lower effort and cost. Here, we present the Insect Detect DIY (do-it-yourself) camera trap for non-invasive automated monitoring of flower-visiting insects, which is based on low-cost off-the-shelf hardware components combined with open-source software. Custom trained deep learning models detect and track insects landing on an artificial flower platform in real time on-device and subsequently classify the cropped detections on a local computer. Field deployment of the solar-powered camera trap confirmed its resistance to high temperatures and humidity, which enables autonomous deployment during a whole season. On-device detection and tracking reliably estimated insect activity/abundance after metadata post-processing. Our insect classification model achieved a high top-1 accuracy on the test dataset and generalized well on a real-world dataset with captured insect images. The camera trap design and open-source software are highly customizable and can be adapted to different use cases. With custom trained detection and classification models, as well as accessible software programming, many possible applications surpassing our proposed deployment method can be realized.
Biomechanical effects of adding an articulating toe joint to a passive foot prosthesis for incline and decline walking
Authors: Teater Rachel H. , Zelik Karl E. , McDonald Kirsty A. 
Published: December 2023

AbstractWalking on sloped surfaces is challenging for many lower limb prosthesis users, in part due to the limited ankle range of motion provided by typical prosthetic ankle-foot devices. Adding a toe joint could potentially benefit users by providing an additional degree of flexibility to adapt to sloped surfaces, but this remains untested. The objective of this study was to characterize the effect of a prosthesis with an articulating toe joint on the preferences and gait biomechanics of individuals with unilateral below-knee limb loss walking on slopes. Nine active prosthesis users walked on an instrumented treadmill at a +5° incline and −5° decline while wearing an experimental foot prosthesis with two configurations: a Flexible toe joint and a Locked-out toe joint. Three participants preferred the Flexible toe joint over the Locked-out toe joint for incline and decline walking. Eight of nine participants went on to participate in a biomechanical data collection. The Flexible toe joint decreased prosthesis Push-off work by 2 J during both incline and decline walking (p=0.008). During incline walking, prosthetic limb knee flexion at toe-off was 3° greater in the Flexible configuration compared to the Locked (p=0.008). Overall, these results indicate that adding a toe joint to a passive foot prosthesis has relatively small effects on joint kinematics and kinetics during sloped walking. This study is part of a larger body of work that also assessed the impact of a prosthetic toe joint for level and uneven terrain walking and stair ascent/descent. Collectively, toe joints do not appear to substantially or consistently alter lower limb mechanics for active unilateral below-knee prosthesis users. Our findings also demonstrate that user preference for passive prosthetic technology may be both subject-specific and task-specific. Future work could investigate the inter-individual preferences and potential benefits of a prosthetic toe joint for lower-mobility individuals.
Can upwelling regions be potential thermal refugia for marine species during climate warming? The case of Mexico
Authors: Angeles-Gonzalez Luis Enrique , Torrejón-Magallanes Josymar , Osorio-Olvera Luis , Avendaño Otilio , Díaz Fernando , Rosas Carlos 
Published: December 2023

AbstractAnthropogenic climate warming will change the thermal habitats of marine species worldwide. Species are expected to migrate to higher latitudes as warming intensifies since behavioral and physiological mechanisms have been adapted to maximize fitness under a specific range of temperatures. However, given the possible intensification of upwelling ecosystems, they may act as potential thermal refugia under climate warming, which could protect the diversity of the marine ecosystems, making them important regions for marine resource management. This research aimed to predict the effects of climate warming on commercial and non-commercial marine species (vertebrate and invertebrates) reported in official Mexican documents (> 300 species) based on a thermal niche characterization with the objective to observe if the upwelling regions can act as potential thermal refugia. For this, we considered Representative Concentration Pathway (6.0 and 8.5) scenarios for the present and the future (2040-2050 and 2090-2100). Current and future patterns of suitability, species distribution, richness, and turnover were calculated via ecological niche models using the minimum volume ellipsoids as an algorithm. The results in this study highlight that beyond migration to higher latitudes, some upwelling regions (not all) could be potentially used as some type of “oasis” by marine species refuging from environmental pressure or zones of higher stability of species. Specifically, the upwelling systems in western Baja California and north of Yucatan may be essential regions for future management in Mexico. Nevertheless, it is important to note that climate change acts on numerous ecosystem features, such as trophic relationships, phenology, and other environmental variables not considered here. Future research could test our hypothesis under more realistic simulations. However, migration toward upwelling regions seems to be the most logical selection from all the available ecosystems as climate refugia for marine species beyond movement to higher latitudes or depths.
In Silico Therapeutic Intervention on Cytokine Storm in COVID-19
Authors: Bakshi Abhisek , Gangopadhyay Kaustav , Basak Sujit , Chakrabarti Amlan , Dasgupta Abhijit , De Rajat K. 
Published: December 2023

AbstractThe recent global COVID-19 outbreak, attributed by the World Health Organization to the rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), underscores the need for an extensive exploration of virological intricacies, fundamental pathophysiology, and immune responses. This investigation is vital to unearth potential therapeutic avenues and preventive strategies. Our study delves into the intricate interaction between SARS-CoV-2 and the immune system, coupled with exploring therapeutic interventions to counteract dysfunctional immune responses like the ‘cytokine storm’ (CS), a driver of disease progression. Understanding these immunological dimensions informs the design of precise multiepitopetargeted peptide vaccines using advanced immunoinformatics and equips us with tools to confront the cytokine storm. Employing a control theory-based approach, we scrutinize the perturbed behavior of key proteins associated with cytokine storm during COVID-19 infection. Our findings support ACE2 activation as a potential drug target for CS control and confirm AT1R inhibition as an alternative strategy. Leveraging deep learning, we identify potential drugs to individually target ACE2 and AT1R, with Lomefloxacin and Fostamatinib emerging as standout options due to their close interaction with ACE2. Their stability within the protein-drug complex suggests superior efficacy among many drugs from our deep-learning analysis. Moreover, there is a significant scope for optimization in fine-tuning protein-drug interactions. Strong binding alone may not be the sole determining factor for potential drugs; precise adjustments are essential. The application of advanced computational power offers novel solutions, circumventing time-consuming lab work. In scenarios necessitating both ACE2 and AT1R targeting, optimal drug combinations can be derived from our analysis of drug-drug interactions, as detailed in the manuscript.
An explainable machine learning data analytics method using TIGIT-linked genes for identifying biomarker signatures to clinical outcomes
Authors: Soorya G , Agrawal Divya , Bhat Shilpa , Mandal Tirtha , Kashipathi Shalini , Madhusudhan M. S. , Rodrigues Golding , Ghosh Maloy , Chirmule Narendra 
Published: December 2023

ABSTRACTIn the last decade, immunotherapies targeting immune checkpoint inhibitors have been extremely effective in eliminating subsets of some cancers in some patients. Multi-modal immune and non-immune factors that contribute to clinical outcomes have been utilized for predicting response to therapies and developing diagnostics. However, these data analytic methods involve a combination of complex mathematical data analytics, and even-more complex biological mechanistic pathways. In order to develop a method for data analytics of transcriptomics data sets, we have utilized an explainable machine learning (ML) model to investigate the genes involved in the signaling pathway of T-cell-immunoreceptor with immunoglobulin and ITIM domain (TIGIT). TIGIT is a receptor on T, NK, and T-regulatory cells, that has been classified as a checkpoint inhibitor due to its ability to inhibit innate and adaptive immune responses. We extracted gene whole genome sequencing data of 1029 early breast cancer patient tumors, and adjacent normal tissues from the TCGA and UCSC Xena Data Hub public databases. We followed a workflow which involved the following steps: i) data acquisition, processing, and visualization followed by ii) developed of a predictive prognostic model using input (gene expression data) and output (survival time) parameters iii) model interpretation was performed by calculating SHAP (Shapely-Additive-exPlanations); iv) the application of the model involved a Cox-regression model, trained with L-2 regularization and optimization using 5 fold cross validation. The model identified gene signatures associated with TIGIT that predicted survival outcome with a test set with a score of 0.601. In summary, we have utilized this case study of TIGIT-mediated signaling pathways to develop a roadmap for biologists to harness ML methods effectively.
Deciphering the actin structure-dependent preferential cooperative binding of cofilin
Authors: Ngo Kien Xuan , Vu Huong T , Umeda Kenichi , Trinh Minh-Nhat , Kodera Noriyuki , Uyeda Taro Q.P. 
Published: December 2023

AbstractThe mechanism underlying the preferential and cooperative binding of cofilin and the expansion of clusters toward the pointed-end side of actin filaments remains poorly understood. To address this, we conducted a principal component analysis based on available filamentous actin (F-actin) and C-actin (cofilins were excluded from cofilactin) structures and compared to monomeric G-actin. The results strongly suggest that C-actin, rather than F-ADP-actin, represented the favourable structure for binding preference of cofilin. High-speed atomic force microscopy explored that the shortened bare half helix adjacent to the cofilin clusters on the pointed end side included fewer actin protomers than normal helices. The mean axial distance (MAD) between two adjacent actin protomers along the same long-pitch strand within shortened bare half helices was longer (5.0–6.3 nm) than the MAD within typical helices (4.3–5.6 nm). The inhibition of torsional motion during helical twisting, achieved through stronger attachment to the lipid membrane, led to more pronounced inhibition of cofilin binding and cluster formation than the presence of inorganic phosphate (Pi) in solution. F-ADP-actin exhibited more naturally supertwisted half helices than F-ADP.Pi-actin, explaining how Pi inhibits cofilin binding to F-actin with variable helical twists. We propose that protomers within the shorter bare helical twists, either influenced by thermal fluctuation or induced allosterically by cofilin clusters, exhibit characteristics of C-actin-like structures with an elongated MAD, leading to preferential and cooperative binding of cofilin.
Spatial organization and stochastic fluctuations of immune cells impact clinical responsiveness to immune checkpoint inhibitors in patients with melanoma
Authors: Giuliani Giuseppe , Stewart William , Li Zihai , Jayaprakash Ciriyam , Das Jayajit 
Published: December 2023

AbstractHigh-dimensional, spatial single-cell technologies such as CyTOF imaging mass cytometry (IMC) provide detailed information regarding locations of a large variety of cancer and immune cells in microscopic scales in tumor microarray (TMA) slides obtained from patients prior to immune checkpoint inhibitor (ICI) therapy. An important question is how the initial spatial organization of these cells in the tumor microenvironment (TME) change with time, regulate tumor growth and eventually outcomes as patients undergo ICI therapy. Utilizing IMC data of melanomas of patients who later underwent ICI therapy, we develop a spatially resolved interacting cell systems model that is calibrated against patient response data to address the above question. We find that the tumor fate in these patients is determined by the spatial organization of activated CD8+ T cells, macrophages, and melanoma cells and the interplay between these cells that regulate exhaustion of CD8+ T cells. We find that fencing of tumor cell boundaries by exhausted CD8+T cells is dynamically generated from the initial conditions that can play a pro-tumor role. Furthermore, we find that specific spatial features such as co-clustering of activated CD8+ T cells and macrophages in the pre-treatment samples determine the fate of the tumor progression, despite stochastic fluctuations and changes over the treatment course. Our framework enables determination of mechanisms of interplay between a key subset of tumor and immune cells in the TME that regulate clinical response to ICIs.SignificanceRecent advances in single cell technologies allows for spatial imaging a wide variety of cancer and immune cells in tissue samples obtained from solid tumors. This detailed snapshot data of microscale organization of tumor and immune cells could provide valuable insights into underlying biology and clinical responsiveness to cancer immunotherapy. By combining published data from imaging mass-cytometry and patient response against ICI drugs with data analysis rooted in statistical physics and statistical inference theory, we developed and studied the dynamics of mechanistic spatially resolved models: we show that tumor growth during ICI treatment is regulated by non-intuitive interplay between CD8+ T cells and tumor associated macrophages, formation of a pro-tumor fencing of exhausted CD8+ T cells around melanoma cells, specific features of spatial organization of these cells prior to treatment, and stochastic fluctuations in the dynamics. The mechanisms unveiled in our studies are general and can pertain to the response of other solid tumors to ICI therapy.