bluuebunny/crossref_metadata_2025_split huggingface dataset:
A benchmark of optimization solvers for genome-scale metabolic modeling
Authors: Machado Daniel 
Published: April 2023

AbstractGenome-scale metabolic modeling is a powerful framework for predicting metabolic phenotypes of any organism with an annotated genome. For two decades, this framework has been used for rational design of microbial cell factories. In the last decade, the range of applications has exploded, and new frontiers have emerged, including the study of the gut microbiome and its health implications, and the role of microbial communities in global ecosystems. However, all the critical steps in this framework, from model construction to simulation, require the use of powerful linear optimization solvers, with the choice often relying on commercial solvers for their well-known computational efficiency. In this work, I benchmark a total of six solvers (two commercial and four open-source) and measure their performance to solve linear and mixed-integer linear problems of increasing complexity. Although commercial solvers are still the fastest, at least two open-source solvers show comparable performance. These results show that genome-scale metabolic modeling does not need to be hindered by commercial licensing schemes and can become a truly open science framework for solving urgent societal challenges.
Bill color is dynamic across the breeding season but not condition-dependent in Atlantic puffins
Authors: Kochvar Katja Helgeson , Wilson Amy Catherine , Bitton Pierre-Paul 
Published: April 2023

AbstractSexually monomorphic species have been historically overlooked in the sexual/social selection literature, but there is growing evidence that mutual ornamentation can be driven by selective forces such as mutual sexual selection or selection for individual recognition. Examining the properties of a trait may elucidate which forces most likely play a role, especially when comparing the characteristics of quality and identity traits. Atlantic puffins(Fratercula arctica)are an example of a mutually ornamented monomorphic species, where both males and females display a bright orange-red bill and orange gape rosette during the breeding season and are ornamented to similar degrees. In this study, we investigate whether the properties of the colorful bill and rosette, specifically lability across the breeding season and condition-dependence, more closely align with signals of quality or identity. Our findings support prior work that the bill is sexually monochromatic from an avian visual perspective. We also determined that the bill changes in a discriminable way within individuals and is especially dynamic in the fleshy cere and rosette. However, no metric of color on any region of the bill or rosette were significantly related to current body condition. Ultimately, we argue that bill color likely functions as a quality signal, although further study is needed to determine which aspect of quality coloration signals, if not condition. These results provide a basis for experimentally testing the signal value of the colorful bill in Atlantic puffins, and more broadly, a framework for investigating the properties of mutual ornamentation in avian species.Lay summaryThe properties of a colorful trait inform its potential function as a signal. We investigated whether the Atlantic puffin’s colorful bill could reflect an individual’s identity or quality. Because bill color changes within the breeding season, this feature is not stable enough to reliably signal identity. Bill color is also not related to a common proxy of quality (body condition) but may communicate another aspect of quality such as foraging or parenting ability.
Contribution of cortical layers to human dynamic functional connectivity
Authors: Pais-Roldán Patricia , Yun Seong Dae , Ramkiran Shukti , Veselinović Tanja , Neuner Irene , Zimmermann Markus , Felder Jörg , Shah N. Jon 
Published: April 2023

AbstractTransitory states of the brain, sometimes linked to particular mental disorders, can be identified by conducting a dynamic analysis of connectivity in functional magnetic resonance imaging (fMRI) data. Here, we investigated whether the connectivity between corticallaminae(in contrast to between corticalareas), can vary during the course of a resting-state scan and whether this could impact the identification of brain states in the healthy brain.We performed a sliding-window connectivity analysis of high-resolution fMRI data and found that the differential participation of the cortical layers in the overall cortical connectivity constitutes a more dynamic feature of the brain compared to region-to-region connectivity, with two main states (superficial vs. deep-laminae connectivity) fluctuating over time. Laminar connectivity restricted to the default mode network appeared relatively stable (superficial connectivity preferred), while the central executive and salience networks showed a fluctuating laminar preference. We anticipate that the dynamic analysis of connectivity focused on the different depths of the cerebral cortex could play an important role in characterizing healthy brain states as well as in identifying novel targets of psychiatric diseases.
A proximity proteomics pipeline with improved reproducibility and throughput
Authors: Zhong Xiaofang , Li Qiongyu , Polacco Benjamin J. , Patil Trupti , Marley Aaron , Foussard Helene , Khare Prachi , Vartak Rasika , Xu Jiewei , DiBerto Jeffrey F. , Roth Bryan L. , Eckhardt Manon , Zastrow Mark Von , Krogan Nevan J. , Hüttenhain Ruth 
Published: April 2023

AbstractProximity labeling (PL) through biotinylation coupled with mass spectrometry (MS) has emerged as a powerful technique for capturing spatial proteomes within living cells. Large-scale sample processing for proximity proteomics requires a workflow that minimizes hands-on time while enhancing quantitative reproducibility. Here, we present a scalable PL pipeline integrating automated enrichment of biotinylated proteins in a 96-well plate format. By combining this pipeline with an optimized quantitative MS acquisition method based on data-independent acquisition (DIA), we not only significantly increased sample throughput but also improved the reproducibility of protein identification and quantification. We applied this pipeline to delineate subcellular proteomes across various cellular compartments, including endosomes, late endosomes/lysosomes, the Golgi apparatus, and the plasma membrane. Moreover, employing 5HT2Aserotonin receptor as a model, we investigated temporal changes of proximal interaction networks induced by the receptor’s activation with serotonin. Finally, to demonstrate the applicability of our PL pipeline across multiple experimental conditions, we further modified the PL pipeline for reduced sample input amounts to accommodate CRISPR-based gene knockout, and assessed the dynamics of the 5HT2Anetwork in response to the perturbation of selected proximal interactors. Importantly, the presented PL approach is universally applicable to PL proteomics using biotinylation-based PL enzymes, increasing both throughput and reproducibility of standard protocols.
DiscoGen: Learning to Discover Gene Regulatory Networks
Authors: Ke Nan Rosemary , Dunn Sara-Jane , Bornschein Jorg , Chiappa Silvia , Rey Melanie , Lespiau Jean-Baptiste , Cassirer Albin , Wang Jane , Weber Theophane , Barrett David , Botvinick Matthew , Goyal Anirudh , Mozer Mike , Rezende Danilo 
Published: April 2023

AbstractAccurately inferring Gene Regulatory Networks (GRNs) is a critical and challenging task in biology. GRNs model the activatory and inhibitory interactions between genes and are inherently causal in nature. To accurately identify GRNs, perturbational data is required. However, most GRN discovery methods only operate on observational data. Recent advances in neural network-based causal discovery methods have significantly improved causal discovery, including handling interventional data, improvements in performance and scalability. However, applying state-of-the-art (SOTA) causal discovery methods in biology poses challenges, such as noisy data and a large number of samples. Thus, adapting the causal discovery methods is necessary to handle these challenges. In this paper, we introduce DiscoGen, a neural network-based GRN discovery method that can denoise gene expression measurements and handle interventional data. We demonstrate that our model outperforms SOTA neural network-based causal discovery methods.
The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis
Authors: Coleman Jennifer C. , Tattersall Luke , Yianni Val , Knight Laura , Yu Hongqiang , Hallett Sadie , Johnson Philip , Caetano Ana , Cosstick Charlie , Ridley Anne , Gartland Alison , Conte Maria R , Grigoriadis Agamemnon E. 
Published: April 2023

SUMMARYRNA-binding proteins (RBPs) are emerging as important regulators of pathogenesis, including cancer. Here we reveal that the recently characterised RBPs LARP4A and LARP4B are differentially overexpressed in primary osteosarcoma and osteosarcoma lung metastases, as well as in prostate cancer. Depletion of LARP4A and LARP4B inhibited primary tumour growth and metastatic spread in xenograft studies, as well as inhibiting cell proliferation, motility and migration. Transcriptomic profiling combined with high content multiparametric cell cycle analysis unveiled a central role for LARP4B, but not LARP4A, in regulating cell cycle progression in osteosarcoma and prostate cancer cell lines, potentially through modulating the post-transcriptional regulation of RNA targets that include key cell cycle proteins such as Cyclins B1 and E2, Aurora B and E2F1. Our work assigns new functions to LARP4A and LARP4B as pro-tumorigenic proteins in bone and prostate cancer, highlights their similarities while indicating distinct functional aspects, and adds significantly to the rapidly increasing roles of RBPs in different cancer models. Uncovering clear biological roles for these paralogous proteins provides new avenues for identifying novel tissue-specific targets and potential druggable intervention.
Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development
Authors: Nameki Robbin A. , Chang Heidi , Yu Pak , Abbasi Forough , Lin Xianzhi , Reddy Jessica , Haro Marcela , Fonseca Marcos AS , Freedman Matthew L. , Drapkin Ronny , Corona Rosario I. , Lawrenson Kate 
Published: April 2023

ABSTRACTThe transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue of origin, the fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq and HiC) data sets and 24 profiles of RNA-seq transcription factor knock-down followed by RNA sequencing in FTSEC and HGSC models to define binding sites and gene sets regulated by these factors incisandtrans. This revealed that MECOM, PAX8, SOX17 and WT1 are lineage-enriched, super-enhancer associated master regulators whose cooperative DNA-binding patterns and target genes are re-wired during tumor development. All four TFs were indispensable for HGSC clonogenicity and survival but only depletion of PAX8 and WT1 impaired FTSEC cell survival. These four TFs were pharmacologically inhibited by transcriptional inhibitors only in HGSCs but not in FTSECs. Collectively, our data highlights that tumor-specific epigenetic remodeling is tightly related to MECOM, PAX8, SOX17 and WT1 activity and these transcription factors are targetable in a tumor-specific manner through transcriptional inhibitors.
Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage
Authors: Bonadio Alessandro , Oguche Solomon , Lavy Tali , Kleifeld Oded , Shifman Julia 
Published: April 2023

AbstractMatrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix and has been implicated as a major driver in cancer metastasis. Hence, there is a high demand for MMP-9 inhibitors for therapeutic purposes. For such drug design efforts, large amounts of MMP-9 are required. Yet, the catalytic domain of MMP-9 (MMP-9Cat) is an intrinsically unstable enzyme that tends to auto-cleave within minutes, making it difficult to use in drug design experiments and other biophysical studies. We set our goal to design MMP-9Catvariant that is active but stable to autocleavage. For this purpose, we first identified potential autocleavage sites on MMP-9Catusing mass spectroscopy and then eliminated the autocleavage site by predicting mutations that minimize autocleavage potential without reducing enzyme stability. Four computationally designed MMP-9Catvariants were experimentally constructed and evaluated for auto-cleavage and enzyme activity. Our best variant, Des2, with 2 mutations, was as active as the wild-type enzyme but did not exhibit auto-cleavage after seven days of incubation at 37°C. This MMP-9Catvariant, with an identical to MMP- 9CatWT active site, is an ideal candidate for drug design experiments targeting MMP-9 and enzyme crystallization experiments. The developed strategy for MMP-9CATstabilization could be applied to redesign of other proteases to improve their stability for various biotechnological applications.
Physcomitrium patensSMXL homologs are PpMAX2-dependent negative regulators of growth
Authors: Guillory Ambre , Lopez-Obando Mauricio , Bouchenine Khalissa , Lambret Louis , Bris Philippe Le , Lécureuil Alain , Pillot Jean-Paul , Steinmetz Vincent , Boyer François-Didier , Rameau Catherine , de Saint Germain Alexandre , Bonhomme Sandrine 
Published: April 2023

AbstractSMXL proteins are a plant-specific clade of type I HSP100/Clp-ATPases.SMXLgenes are found in virtually all land plant genomes. However, they have mainly been studied in angiosperms. InArabidopsis thaliana, three SMXL functional subclades have been identified: SMAX1/SMXL2, SMXL345 and SMXL678. Out of these, two subclades ensure transduction of endogenous hormone signals: SMAX1/SMXL2 are involved in KAI2-ligand (KL) signaling, while SMXL678 are involved in strigolactone (SL) signaling. Many questions remain regarding the mode of action of these proteins, as well as their ancestral role. We addressed these questions by investigating the function of the fourSMXLgenes of the mossPhyscomitrium patens.We demonstrate that PpSMXL proteins are involved in the conserved ancestral MAX2-dependent KL signaling pathway and act as negative regulators of growth. However, PpSMXL proteins expressed inA. thalianaunexpectedly cannot replace SMAX1/SMXL2 function in KL signaling, whereas they can functionally replace SMXL4/5 and restore root growth. Therefore, the molecular function of SMXL could be conserved, but not their interaction network. Moreover, one PpSMXL clade positively regulates transduction of the SL signal inP. patens.So far, this function has only been reported herein in moss, where it represents a novel crosstalk between SL and KL signaling pathways.
Frizzled2 receives the WntA morphogen during butterfly wing pattern formation
Authors: Hanly Joseph J , Loh Ling S , Mazo-Vargas Anyi , Rivera-Miranda Teomie S , Livraghi Luca , Tendolkar Amruta , Day Christopher R , Liutikaite Neringa , Earls Emily A , Corning Olaf BWH , D’Souza Natalie , Hermina-Perez José J , Mehta Caroline , Ainsworth Julia , Rossi Matteo , McMillan W. Owen , Perry Michael W , Martin Arnaud 
Published: April 2023

AbstractButterfly color patterns provide visible and biodiverse phenotypic readouts of the patterning processes that occur in a developing epithelium. While the secreted ligand WntA was shown to instruct the color pattern formation in butterflies, its modes of reception and signal transduction remain elusive. Butterfly genomes encode four homologues of the Frizzled-family of Wnt receptors. Here we show that CRISPR mosaic knock-outs offrizzled2(fz2) phenocopy the color pattern effects ofWntAloss-of-function in multiple nymphalids. WhileWntAmosaic clones result in intermediate patterns of reduced size, consistently with a morphogen function,fz2clones are cell-autonomous. Shifts in pupal expression inWntAcrispants show thatWntAandfz2are under positive and negative feedback, respectively. Fz1 is required for Wnt-independent planar cell polarity (PCP) in the wing epithelium. Fz3 and Fz4 show phenotypes consistent with Wnt competitive-antagonist functions in vein formation (Fz3 and Fz4), wing margin specification (Fz3), and color patterning in the Discalis and Marginal Band Systems (Fz4). Overall, these data show that the WntA/Frizzled2 morphogen-receptor pair forms a signaling axis that instructs butterfly color patterning, and shed light on the functional diversity of insect Frizzled receptors.
Color traits of soybean conventional and trangenic cultivars are affected by glyphosate concentrations using digital imaging
Authors: Costa Francisco Cleilson Lopes , Piza Mateus Ribeiro , Rodrigues Lais Nóbrega , Bruzi Adriano Teodoro , Pereira Welison Andrade 
Published: April 2023

AbstractSoybean is the most cultivated oilseed crop in the world, with much of the merit obtained in recent years due to genetic improvement in which greater genetic progress can be obtained by improving physiological characteristics, which result in a greater impact on yield. Color spectra can be good indicators of the physiological quality of plants by quantifying the intensity of colors in the RGB spectra, being a non-destructive method that allows optimizing the collection and the number of data. We aimed to identify differences in spectral reflection between conventional, transgenic RR1 and RR2 soybean cultivars under the effect of glyphosate herbicide. The plants were cultivated in five-liter pots in a greenhouse in a randomized block design, following cultural treatments recommended for the soybean crop. Leaves of plants in vegetative stages V1 or V2 were collected and duly identified to compose a second experiment, being then submitted to incubation in plastic trays in which the treatments were organized in a completely randomized design in a 6×6 factorial scheme, with three replications. Glyphosate herbicide doses (0.0, 0.03%, 0.06%, 0.12% and 0.24% AE/ha) were added to the leaf petiole on a cotton pad in order to maintain constant contact with the respective dose. The trays were kept under ambient conditions for 14 days after incubation under 16h-light and 8h-dark of artificial light. Images were collected with a smartphone camera on the 13th day after leaves collection (DAC) in an appropriate studio to maintain adequate lighting, and on the 14th DAC SPAD index data were collected in three locations on the leaf, avoiding the midrib. The images were cropped and then segmented using manual thresholding in which the average values for the red, green and blue channels were extracted. The Excess Red Index (ExR) was calculated using the red and green channels data. The data obtained were analyzed and the significant effects of the model were analyzed by the Skott-Knott test for the cultivar factor and regression models were adjusted for the dose factor. Spearman’s correlation was used to verify the relationship between the studied variables. In view of our results, glyphosate affects the chlorophyll of resistant plants when subjected to continuous exposure and at high doses, leading to senescence and that the red channel information can be used to infer the level of interference in the photosynthetic activity of plants subjected to the herbicide.
Different strategies and bio-removal mechanisms of petroleum hydrocarbons from contaminated sites
Authors: Ahmed Salim , Kumari Khushboo , Singh Durgeshwer 
Published: April 2023

PurposePetroleum hydrocarbons are naturally occurring flammable fossil fuels used as conventional energy sources. It has carcinogenic, mutagenic properties and is considered a hazardous pollutant. Soil contaminated with petroleum hydrocarbons adversely affects the properties of soil. This paper aim to remove pollutants from the environment is an urgent need of the hour to maintain the proper functioning of soil ecosystems.Design/methodology/approachThe ability of micro-organisms to degrade petroleum hydrocarbons makes it possible to use these microorganisms to clean the environment from petroleum pollution. For preparing this review, research papers and review articles related to petroleum hydrocarbons degradation by micro-organisms were collected from journals and various search engines.FindingsVarious physical and chemical methods are used for remediation of petroleum hydrocarbons contaminants. However, these methods have several disadvantages. This paper will discuss a novel understanding of petroleum hydrocarbons degradation and how micro-organisms help in petroleum-contaminated soil restoration. Bioremediation is recognized as the most environment-friendly technique for remediation. The research studies demonstrated that bacterial consortium have high biodegradation rate of petroleum hydrocarbons ranging from 83% to 89%.Social implicationsProper management of petroleum hydrocarbons pollutants from the environment is necessary because of their toxicity effects on human and environmental health.Originality/valueThis paper discussed novel mechanisms adopted by bacteria for biodegradation of petroleum hydrocarbons, aerobic and anaerobic biodegradation pathways, genes and enzymes involved in petroleum hydrocarbons biodegradation.
What determines the development of a rural collective economy? A fuzzy set qualitative comparative analysis (fsQCA) approach
Authors: Hong Ruling , Zhan Minlu , Wang Fuxi 
Published: April 2023

PurposeThis study explores configurations that promote the development of collective economies in China's rural villages and reveals the multiple development pathways that otherwise remain relatively unexamined in the literature.Design/methodology/approachThe authors obtained first-hand representative case data from 20 villages in 12 counties in 5 provinces in East, West and Central China via fieldwork and applied fuzzy set qualitative comparative analysis (fsQCA) to conduct a configurational comparative study of the development of village collective economies.FindingsThis paper identifies five factors in the current literature that affect the development of village collectives, based on an “entrepreneur–situation” analytical framework. Using the fsQCA method, this study further obtains two main configurations of conditions that culminate in the growth of rural collective economies in China. The first solution is the “top-down path”: When entrepreneurial leadership (EL), resource endowment (RE) and government assistance (GA) are present, a village collective economy will experience a high level of development, irrespective of policy support (PS) and villagers' participation (VP). The second solution is the “bottom-up path”: When EL, VP and PS are present and GA is not present, a village collective economy will experience a high level of development, irrespective of RE. In both situations, EL stands out as the core condition for the development of village collective economies, implying the need for the government to vigorously cultivate the entrepreneurial skills and aspirations of village cadres.Originality/valueTaking a configurational perspective and using an fsQCA approach, this research constructs an “entrepreneur–situation” analytical framework to investigate the key combinations of factors and pathways involved in the high level of development of Chinese village collective economies.