bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral delivery of an RNA-guided genome editor for transgene-free germline editing inArabidopsis
Authors: Weiss Trevor , Kamalu Maris , Shi Honglue , Li Zheng , Amerasekera Jasmine , Zhong Zhenhui , Adler Benjamin A. , Song Michelle , Vohra Kamakshi , Wirnowski Gabriel , Chitkara Sidharth , Ambrose Charlie , Steinmetz Noah , Sridharan Ananya , Sahagun Diego , Banfield Jillian F. , Doudna Jennifer A. , Jacobsen Steven. E. 
Published: July 2024

AbstractGenome editing is transforming plant biology by enabling precise DNA modifications. However, delivery of editing systems into plants remains challenging, often requiring slow, genotype-specific methods such as tissue culture or transformation. Plant viruses, which naturally infect and spread to most tissues, present a promising delivery system for editing reagents. But most viruses have limited cargo capacities, restricting their ability to carry large CRISPR-Cas systems. Here, we engineered tobacco rattle virus (TRV) to carry the compact RNA-guided TnpB enzyme ISYmu1 and its guide RNA. This innovation allowed transgene-free editing ofArabidopsis thalianain a single step, with edits inherited in the subsequent generation. By overcoming traditional reagent delivery barriers, this approach offers a novel platform for genome editing, which can greatly accelerate plant biotechnology and basic research.
RWRtoolkit: multi-omic network analysis using random walks on multiplex networks in any species
Authors: Kainer David , Lane Matthew , Sullivan Kyle A. , Miller J. Izaak , Cashman Mikaela , Morgan Mallory , Cliff Ashley , Romero Jonathon , Walker Angelica , Blair D. Dakota , Chhetri Hari , Wang Yongqin , Pavicic Mirko , Furches Anna , Noshay Jaclyn , Drake Meghan , Landry Natalie , Ireland AJ , Missaoui Ali , Kang Yun , Sedbrook John , Dehal Paramvir , Canon Shane , Jacobson Daniel 
Published: July 2024

AbstractLeveraging the use of multiplex multi-omic networks, key insights into genetic and epigenetic mechanisms supporting biofuel production have been uncovered. Here, we introduce RWRtoolkit, a multiplex generation, exploration, and statistical package built for R and command line users. RWRtoolkit enables the efficient exploration of large and highly complex biological networks generated from custom experimental data and/or from publicly available datasets, and is species agnostic. A range of functions can be used to find topological distances between biological entities, determine relationships within sets of interest, search for topological context around sets of interest, and statistically evaluate the strength of relationships within and between sets. The command-line interface is designed for parallelisation on high performance cluster systems, which enables high throughput analysis such as permutation testing. Several tools in the package have also been made available for use in reproducible workflows via the KBase web application.
Integrating Phylogenies with Chronology to Assemble the Tree of Life
Authors: Barba-Montoya Jose , Craig Jack M , Kumar Sudhir 
Published: July 2024

AbstractReconstructing the global Tree of Life necessitates computational approaches to integrate numerous molecular phylogenies with limited species overlap into a comprehensive supertree. Our survey of published literature shows that individual phylogenies are frequently restricted to specific taxonomic groups due to the expertise of investigators and molecular evolutionary considerations, resulting in any given species present in a minuscule fraction of phylogenies. We present a novel approach, called the chronological supertree algorithm (Chrono-STA), that can build a supertree of species from such data by using node ages in published molecular phylogenies scaled to time. Chrono-STA builds a supertree of organisms by integrating chronological data from molecular timetrees. It fundamentally differs from existing approaches that generate consensus phylogenies from gene trees with missing taxa, as Chrono-STA does not impute nodal distances, use a guide tree as a backbone, or reduce phylogenies to quartets. Analyses of simulated and empirical datasets show that Chrono-STA can combine taxonomically restricted timetrees with extremely limited species overlap. For such data, approaches that impute missing distances or assemble phylogenetic quartets did not perform well. We conclude that integrating phylogenies via temporal dimension enhances the accuracy of reconstructed supertrees that are also scaled to time.
Multiomics-based assessment of the impact of airflow on diverse plant callus cultures
Authors: Kim June-Sik , Sato Muneo , Kojima Mikiko , Asrori Muchamad Imam , Uehara-Yamaguchi Yukiko , Takebayashi Yumiko , Do Thi Nhung , Do Thi Yen , Thi Kieu Oanh Nguyen , Sakakibara Hitoshi , Mochida Keiichi , Ogita Shijiro , Hirai Masami Yokota 
Published: July 2024

AbstractPlant cell culture has multiple applications in biotechnology and horticulture, from plant propagation to the production of high-value biomolecules. However, the interplay between cellular diversity and ambient conditions influences the metabolism of cultured tissues; understanding these factors in detail will inform efforts to optimize culture conditions. This study presents multiomics datasets from callus cultures of tobacco (Nicotiana tabacum), rice (Oryza sativa), and two bamboo species (Phyllostachys nigraandP. bambusoides). Over four weeks, calli were cultured under continuous moisture without airflow or gradually reduced ambient moisture with airflow. For each sample, gene expression was profiled with high-throughput RNA sequencing, 442 metabolites were measured using liquid chromatography (LC) with triple-quadrupole mass spectrometry (LC–QqQMS), and 31 phytohormones were quantified using ultra-performance LC coupled with a tandem quadrupole mass spectrometer equipped with an electrospray interface (UPLC-ESI-qMS/MS) and ultra-high-performance LC– orbitrap MS (UHPLC-Orbitrap MS). These datasets highlight the impact of airflow on callus cultures, revealing differences between and within species, and provide a comprehensive resource to explore the physiology of callus growth.
OPUS-BFactor: Predicting protein B-factor with sequence and structure information
Authors: Xu Gang , Yang Yulu , Lv Ying , Luo Zhenwei , Wang Qinghua , Ma Jianpeng 
Published: July 2024

AbstractProtein B-factor, also known as the Debye-Waller factor, measures the fluctuation of an atom around its average position. It serves as a crucial indicator of protein flexibility and dynamics. However, accurately predicting the B-factor of Cαatoms remains challenging. In this work, we introduce OPUS-BFactor, a tool for predicting the normalized protein B-factor. OPUS-BFactor operates in two modes: the first mode, OPUS-BFactor-seq, uses sequence information as input, allowing predictions based solely on protein sequence; the second mode, OPUS-BFactor-struct, uses structural information, requiring the 3D structure of the target protein. Evaluation on three test sets, including recently released targets from CAMEO and CASP15, demonstrates that OPUS-BFactor significantly outperforms other B-factor prediction methods. Therefore, OPUS-BFactor is a valuable tool for predicting protein properties related to the B-factor, such as flexibility, thermal stability, and region activity.
Is testing the bee-all and end-all ofvarroaeradication?
Authors: Abell Isobel R. , Flegg Jennifer A. , Le Thao P. , Baker Christopher M. 
Published: July 2024

AbstractVarroa destructoris a significant European honeybee pest, impacting agricultural industries globally. Since arriving in 2022, Australia faces the possibility thatvarroawill become established in European honeybee colonies nationally. Australia initially pursued a strategy of testing and subsequently eliminating hives infested withvarroa. These management efforts raise interesting questions about the interplay between hive testing and elimination, and the spread ofvarroabetween hives. This study uses mathematical modelling to investigate how combined hive testing and elimination strategies impact the spread ofvarroathrough a network of European honeybee hives. We develop a model of both within-hive reproduction ofvarroaand hive testing, and between-hive movement ofvarroaon a network of hives. This model is used to assess the impact of various testing and hive elimination strategies on the total number of hives eliminated on the network of hives. Each model simulation starts with a single infested hive, and from this we observed one of two dynamics: either the infestation is caught before spreading, orvarroaspreads extensively through the network before being caught by testing. Within our model we implement two common hive testing methods – sugar shake and alcohol testing. A shared limitation of these testing methods is that they can only detect mites in a specific stage of their lifecycle. As such, testing is not only dependent on how manyvarroamites are in a hive, but what lifecycle stage the mites are in at the time of testing. By varying testing and movement parameters, we see that this testing limitation greatly impacts the number of hives eliminated in various scenarios. We find that there are largely two invasion possibilities: either there is only a small incursion, or thatvarroaachieves complete spread on the network. Furthermore, testing earlier, or testing more frequently, does not guarantee a smaller invasion. Our model results suggest irregular testing schedules, e.g. testing multiple times in close succession rather than just once in a given timeframe, may help overcome the limitations of common hive testing strategies.
Transcriptional, developmental, and functional parallels of lymphatic and venous smooth muscle
Authors: Arroyo-Ataz Guillermo , Yagüe Alejandra Carrasco , Breda Julia C. , Mazzilli Sarah A. , Jones Dennis 
Published: July 2024

AbstractLymphatic muscle cells (LMCs) are indispensable for lymphatic vessel contraction and their aberrant recruitment or absence is associated with both primary and secondary lymphedema. Despite their critical role in lymphatic vessel function, the transcriptomic and developmental basis that confer the unique contractile properties to LMCs are largely undefined. In this study, we employed single-cell RNA sequencing (scRNAseq), lineage tracing andin vivoimaging to investigate the basis for the hybrid cardiomyocyte and blood vascular smooth muscle cell (SMC) characteristics that have been described for LMCs. Using scRNAseq, the transcriptomes of LMC and venous SMCs from the murine hindlimb exhibited more similarities than differences, although both were markedly distinct from that of arteriole SMCs in the same tissue. Functionally, both lymphatic vessels and blood vessels in the murine hindlimb displayed pulsatile contractility. However, despite expressing genes that overlap with the venous SMC transcriptome, through lineage tracing we show that LMCs do not originate from Myh11+ SMC progenitors. Previous studies have shown that LMCs express cardiac-related genes, whereas in our study we found that arteriole SMCs, but not LMCs, expressed cardiac-related genes. Through lineage tracing, we demonstrate that a subpopulation of LMCs and SMCs originate from WT1+ mesodermal progenitors, which are known to give rise to SMCs. LMCs, however, do not derive from Nkx2.5+ cardiomyocyte progenitors. Overall, our findings suggest that venous SMCs and LMCs and may derive from a related mesodermal progenitor and adopt a similar gene expression program that enable their contractile properties.
Linking Molecular Mechanisms to their Evolutionary Consequences: a primer
Authors: Grah Rok , Guet Calin C. , Tkačik Gasper , Lagator Mato 
Published: July 2024

ABSTRACTA major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by two proteins, allowing us to connect any promoter genotype to six phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties – the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation – can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes.
Navigating the Cold: Integrative Transcriptome Sequencing Approach Reveals Ionoregulatory and Whole-Body Responses to Cold Acclimation inDrosophila ananassae
Authors: Yılmaz Vera Miyase , Bao Zhihui , Grath Sonja 
Published: July 2024

AbstractUnderstanding how species adapt to changing environments is a major goal in evolutionary biology and can elucidate the impact of climate change. Climate imposes inevitable effects on the geographical distribution of insects as their body temperature primarily depends on the environment. The vinegar flyDrosophila ananassaeexpanded from its tropical ancestral range to more temperate regions, which requires adaptation to colder temperatures. Transcriptome and genome-wide association studies focusing on the ancestral-range population identified the targets of selection related to ionoregulatory tissues. However, how cosmopolitanD. ananassaeadapted to colder environments, where low temperatures last longer, is still unknown. Here, we present a study on the effect of long-term cold exposure onD. ananassae, examining the gene expression variation in the whole body and the ionoregulatory tissues, namely the hindgut and the Malpighian tubule. To elucidate molecular mechanisms of cold adaptation during species expansion, we included cold-tolerant and cold-sensitive strains from the ancestral species range and cold-tolerant strains from the derived species range. We show that cold acclimation improves cold tolerance and results in differential expression of more than half of the transcriptome in the ionoregulatory tissues and the whole body. Notably, we provide complementary insight into molecular processes at four levels: strains, populations, phenotypes, and tissues. By determining the biochemical pathways of phenotypic plasticity underlying cold tolerance, our results enhance our understanding of how environmental changes affect thermal adaptation in natural populations.
A Hierarchical Method to Analyze Protein-DNA Interfaces
Authors: Tagad Amol , Patwari G. Naresh 
Published: July 2024

ABSTRACTThe accessibility of genetic information and packaging of long chromosomal DNA into micron-sized nuclei is a great example of protein-DNA interaction. A large number of protein-DNA structures are available in the database and is continuously increasing. The analysis of such huge data to extract meaningful insights, several computational tools such as hydrogen bonding, SASA, all intermolecular heavy atom-to-atom contacts, as well as web-server and databases such as DNAproDB, PDIdb, PDB2PQR, Bio-python are available. Generally, the interaction between the protein and DNA is analyzed based on all heavy atom-to-atom contact matrices which are computationally expensive. Herein, a new and robust hierarchical approach is developed to analyze the protein-DNA interface. The present hierarchical method comprises two steps; the first step is to recognize the protein residue-nucleotide pairs at the interface by employing pairwise distance cut-off between the Cα of the protein residues and 05′ of the nucleotide and the second step is to calculate heavy atom-to-atom contact matrix using the first step as a qualifier. This method reduces the computational cost by three orders of magnitude making it tractable even on personal computers. On the whole, the protein-DNA interface is dominated by the arginine residues with a notable presence of lysine, serine, and tyrosine, highlighting the pivotal role of electrostatic interactions and hydrogen bonding in aggregation.Abstract Figure
Three-dimensional culture in a bioengineered matrix and somatic cell complementation to improve growth and survival of bovine preantral follicles
Authors: Candelaria Juliana I. , Botigelli Ramon C. , Guiltinan Carly , Shikanov Ariella , Denicol Anna C. 
Published: July 2024

STRUCTURED ABSTRACTPurposeHere we explored poly(ethylene glycol) (PEG) bioengineered hydrogels for bovine preantral follicle culture with or without ovarian cell co-culture and examined the potential for differentiation of bovine embryonic stem cells (bESCs) towards gonadal somatic cells to develop a system more similar to the ovarian microenvironment.MethodsBovine preantral follicles were first cultured in two-dimensional (2D) control or within PEG hydrogels (3D) and then co-cultured within PEG hydrogels with bovine ovarian cells (BOCs) to determine growth and viability. Finally, we tested conditions to drive differentiation of bESCs towards the intermediate mesoderm and bipotential gonad fate.ResultsPrimary follicles grew over the 10-day culture period in PEG hydrogels compared to 2D control. Early secondary follicles maintained a similar diameter within the PEG while control follicles decreased in size. Follicles lost viability after co-encapsulation with BOCs; BOCs lost stromal cell signature over the culture period within hydrogels. Induction of bESCs towards gonadal somatic fate under WNT signaling was sufficient to upregulate intermediate mesoderm (LHX1) and early coelomic epithelium/bipotential gonad markers (OSR1,GATA4,WT1). Higher BMP4 concentrations upregulated the lateral plate mesoderm markerFOXF1.PAX3expression was not induced, indicating absence of the paraxial mesoderm lineage.ConclusionsCulture of primary stage preantral follicles in PEG hydrogels promoted growth compared to controls; BOCs did not maintain identity in the PEG hydrogels. Collectively, we demonstrate that PEG hydrogels can be a potential culture system for early preantral follicles pending refinements, which could include addition of ESC-derived ovarian somatic cells using the protocol described here.CAPSULE SUMMARYWe demonstrate that three-dimensional bioengineered hydrogels could aid in the survival and growth of small bovine preantral follicles. Moreover, bovine embryonic stem cells have the potential to differentiate towards precursors of somatic gonadal cell types, presenting an alternative cell source for preantral follicle co-culture.
A selective S-acyltransferase inhibitor suppresses tumor growth
Authors: Lee Jia-Ying , Dilones Sebastian , Maujean Timothe , Asad Mohammad , Mohd Altaf , Auslander Noam , Brady Donita C. , Burslem George M. , Witze Eric S. 
Published: July 2024

AbstractS-acyltransferases play integral roles in essential physiological processes including regulation of oncogenic signaling pathways. While discovered over 40 years ago the field still lacks specific S-acylation inhibitors thus the potential benefit of pharmacologically targeting S-acyltransferases for human disease is still unknown. Here we report the identification of an orally bioavailable acyltransferase inhibitor SD-066-4 that inhibits the acyltransferase ZDHHC20. We identified a specific alanine residue that accommodates the methyl group of SD-066-4, thus providing isoform selectivity. SD-066-4 stably reduces EGFR S-acylation in Kras mutant cells and blocks the growth of Kras mutant lung tumors extending overall survival. We find that lung cancer patients harboring deletions in ZDHHC20 or ZDHHC14 concurrent with Kras alterations have a significant survival benefit, underscoring the translational importance of these enzymes.
SARS-CoV-2 dynamics in New York City during March 2020–August 2023
Authors: Yang Wan , Parton Hilary , Li Wenhui , Watts Elizabeth A. , Lee Ellen , Yuan Haokun 
Published: July 2024

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widespread since 2020 and will likely continue to cause substantial recurring epidemics. However, understanding the underlying infection burden (i.e., including undetected asymptomatic/mild infections) and dynamics, particularly since late 2021 when the Omicron variant emerged, is challenging due to the potential for asymptomatic and repeat SARS-CoV-2 infection, changes in testing practices, and changes in disease reporting. Here, we leverage extensive surveillance data available in New York City (NYC) and a comprehensive model-inference system to reconstruct SARS-CoV-2 dynamics therein from the pandemic onset in March 2020 to August 2023, and further validate the estimates using independent wastewater surveillance data. The validated model-inference estimates indicate a very high infection burden totaling twice the population size (>5 times documented case count) but decreasing infection-fatality risk (a >10-fold reduction) during the first 3.5 years. The detailed estimates also reveal highly complex variant dynamics and immune landscape, changing virus transmissibility, and higher infection risk during winter in NYC over this time period. These transmission dynamics and drivers, albeit based on data in NYC, may be relevant to other populations and inform future planning to help mitigate the public health burden of SARS-CoV-2.
Ecological risk-taking across age in Barbary macaques
Authors: Bosshard Tiffany Claire , Mundry Roger , Fischer Julia 
Published: July 2024

ABSTRACTWhen foraging, animals face decisions regarding unpredictable resources and varying predation risk, in which the cost-benefit trade-off must be assessed. Life-history theory focuses on resource allocation with regard to development and suggests there should be a variation in risk-taking propensity across age, manifested by a shift in goals from gain acquisition to loss aversion over time. Consequently, we aimed to assess age-related variation in decision-making strategies under risk in Barbary macaques (Macaca sylvanus) living at “La Forêt des Singes” in Rocamadour, France. We experimentally varied the perceived risk and potential gains in a 2×2 design. The high-risk stimulus was a rubber snake; the low-risk stimulus a cube with a snakeskin pattern. The high-value food reward was a peanut; the low-value food reward a popcorn. In 2022, we presented 83 subjects with one of the four possible factor combinations, and in 2023, we presented 70 individuals with the inverted combination (e.g. snake-popcorn in 2022, cube-peanut in 2023). We took each monkey’s propensity to retrieve the reward as a measure of risk-taking, and the latency to retrieve the reward as motivation to engage in the risky choice. Regardless of age, subjects generally retrieved the reward when placed next to the cube, whether peanut or popcorn, but were less likely to retrieve the reward placed next to the snake when this was popcorn rather than peanut. However, older individuals were faster than younger conspecifics to retrieve the reward when it was popcorn, whether paired with the cube or snake. Our results do not comply with the notion that risk-taking propensity declines with age, but rather suggest that in this paradigm, the animals assess the costs and benefits of a risky situation across age, and that the subjective value of a resource may change with age.