bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptomics of Hirschfeldia incana and relatives highlights differences in photosynthetic pathways
Authors: Garassino Francesco , Luoni Sofia Bengoa , Cumerlato Tommaso , Marquez Francisca Reyes , Harbinson Jeremy , Aarts Mark G. M. , Nijveen Harm , Smit Sandra 
Published: October 2023

AbstractPhotosynthesis is the only yield-related trait that has not yet been substantially improved by plant breeding. The limited results of previous attempts to increase yield via improvement of photosynthetic pathways suggest that more knowledge is still needed to achieve this goal. To learn more about the genetic and physiological basis of high photosynthetic light-use efficiency (LUE) at high irradiance, we studyHirschfeldia incana. Here, we compare the transcriptomic response to high light ofH. incanawith that of three other members of the Brassicaceae,Arabidopsis thaliana, Brassica rapa, andBrassica nigra, which have a lower photosynthetic LUE.First, we built a high-light, high-uniformity growing environment in a climate-controlled room. Plants grown in this system developed normally and showed no signs of stress during the whole growth period. Then we compared gene expression in low and high-light conditions across the four species, utilizing a panproteome to group homologous proteins efficiently. As expected, all species actively regulate genes related to the photosynthetic process. An in-depth analysis on the expression of genes involved in three key photosynthetic pathways revealed a general trend of lower gene expression in high-light conditions. However,H. incanadistinguishes itself from the other species through higher expression of certain genes in these pathways, either through constitutive higher expression, as forLHCB8, ordinary differential expression, as forPSBE, or cumulative higher expression obtained by simultaneous expression of multiple gene copies, as seen forLHCA6.These differentially expressed genes in photosynthetic path-ways are interesting leads to further investigate the exact relationship between gene expression, protein abundance and turnover, and ultimately the LUE phenotype. In addition, we can also exclude thousands of genes from “explaining” the phenotype, because they do not show differential expression between both light conditions. Finally, we deliver a transcriptomic resource of plant species fully grown under, rather than briefly exposed to, a very high irradiance, supporting efforts to develop highly efficient photosynthesis in crop plants.
The genetic evolution of acral melanoma
Authors: Wang Meng , Fukushima Satoshi , Sheen Yi-Shuan , Ramelyte Egle , Pacheco Noel Cruz , Shi Chenxu , Liu Shanshan , Banik Ishani , Aquino Jamie D. , Acosta Martin Sangueza , Levesque Mitchell , Dummer Reinhard , Liau Jau-Yu , Chu Chia-Yu , Shain A. Hunter , Yeh Iwei , Bastian Boris C. 
Published: October 2023

AbstractAcral melanoma is an aggressive type of melanoma with unknown origins, arising on the sole, palm, or nail apparatus. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. Our study examined exome sequencing data from 139 tissue samples, spanning different progression stages, collected from 37 patients. We found that 78.4% of the melanomas displayed one or more clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These genomic “hailstorms” were typically shared across all progression stages within individual patients. Genetic alterations known to activateTERTalso arose early. By contrast, mutations in the MAP- kinase pathway appeared later during progression, often leading to different tumor areas harboring non-overlapping driver mutations. We conclude that the evolutionary trajectories of acral melanomas substantially diverge from those of melanomas on sun-exposed skin, where MAP-kinase pathway activation initiates the neoplastic cascade followed by immortalization later. The punctuated formation of hailstorms, paired with earlyTERTactivation, suggests a unique mutational mechanism underlying the origins of acral melanoma. Our findings highlight an essential role for telomerase, likely in re-stabilizing tumor genomes after hailstorms have initiated the tumors. The marked genetic heterogeneity, in particular of MAP-kinase pathway drivers, may partly explain the limited success of targeted and other therapies in treating this melanoma subtype.
Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan
Authors: Bomba-Warczak Ewa K. , Velez Karen M. , Zhou Luhan T , Guillermier Christelle , Edassery Seby , Steinhauser Matthew L. , Savas Jeffrey N. , Duncan Francesca E. 
Published: October 2023

AbstractThe mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries and gametes across the reproductive lifespan. Ovaries exhibit localized structural and cell-type specific enrichment of stable macromolecules in both the follicular and extrafollicular environments. Moreover, ovaries and oocytes both harbor a panel of exceptionally long-lived proteins, including cytoskeletal, mitochondrial, and oocyte-derived proteins. The exceptional persistence of these long-lived molecules suggest a critical role in lifelong maintenance and age-dependent deterioration of reproductive tissues.One sentence summaryExceptionally long-lived macromolecules in mammalian ovaries and oocytes as pillars for lifelong reproductive health span.
Perturbation-response analysis ofin silicometabolic dynamics in nonlinear regime: Hard-coded responsiveness in the cofactors and network sparsity
Authors: Himeoka Yusuke , Furusawa Chikara 
Published: October 2023

AbstractHomeostasis is a fundamental characteristic of living systems. Unlike rigidity, homeostasis necessitates that systems respond flexibly to diverse environments. Understanding the dynamics of biochemical systems when subjected to perturbations is essential for the development of a quantitative theory of homeostasis. In this study, we analyze the response of bacterial metabolism to externally imposed perturbations using kinetic models ofEscherichia coli’s central carbon metabolism in nonlinear regimes. We found that three distinct kinetic models consistently display strong responses to perturbations; In the strong responses, minor initial discrepancies in metabolite concentrations from steady-state values amplify over time, resulting in significant deviations. This pronounced responsiveness is a characteristic feature of metabolic dynamics, especially since such strong responses are seldom seen in toy models of the metabolic network. Subsequent numerical studies show that adenyl cofactors consistently influence the responsiveness of the metabolic systems across models. Additionally, we examine the impact of network structure on metabolic dynamics, demonstrating that as the metabolic network becomes denser, the perturbation response diminishes—a trend observed commonly in the models. To confirm the significance of cofactors and network structure, we constructed a simplified metabolic network model, underscoring their importance. By identifying the structural determinants of responsiveness, our findings offer implications for bacterial physiology, the evolution of metabolic networks, and the design principles for robust artificial metabolism in synthetic biology and bioengineering.
cMYC-mediated immune repression is reversed by inhibition of H3K9/H3K27 methylation maintenance
Authors: Dye Isabel , Laing Sarah , Garner Ian , Mirza Hasan B. , Iyer Nayana , Brady Nicola , Spiliopoulou Pavlina , Spear Sarah , Robinson James , Fiorentino Francesca , Fuchter Matthew J. , Murphy Daniel J. , McNeish Iain A. , Brown Robert 
Published: October 2023

AbstractAberrant cMYC activity is a key driver of cancer, involved in several hallmark processes. Alongside the canonical hallmark of proliferation, cMYC represses immune signalling in a cell-intrinsic manner. The histone methyltransferases EZH2 and G9a interact with cMYC to modulate gene expression, including repression of immune genes via H3K27 and H3K9 histone methylation. Analyses of 565 cell lines derived from solid cancers demonstrated that greater cMYC-G9a/EZH2-mediated repression correlates with lower immune gene scores in a cell-intrinsic manner (innate, Type I and Type II IFN response), an effect most evident inMYC-amplified cell lines. In ovarian high-grade serous carcinoma (HGSC) cell lines and anin vivomurine model of HGSC, HKMTi-1-005, an inhibitor of H3K27/H3K9 methylation maintenance, relieved cMYC-G9a/EZH2 repression whilst inducing an immune response. A 7-gene immune signature (7ISG), related to viral mimicry signalling, is at the core of the HGSC immune response to HKMTi-1-005. InMYC-amplified HGSC patients, a low 7ISG score was associated with poor survival. Additionally,MYC-amplified cell lines were significantly more sensitive to HKMTi-1-005, whilst a low 7ISG score was associated with greater HKMTi-1-005 sensitivity, effects that were independent of canonical cMYC transcriptional activation. Examining the effects of HKMTi-1-005 treatment in aMYC-deregulated lung adenocarcinoma (LuAd) revealed induction of an immune responsein vitroand prolonged survivalin vivo.This suggests that inhibition of H3K27/H3K9 methylation maintenance will have efficacy in cMYC-deregulated tumours with low 7ISG scores, via disruption of cMYC-mediated repression of cell autonomous immune signalling and induction of an anti-tumour immune response.Statement of significanceOver 70% of cancers are cMYC-deregulated. We show that inhibition of H3K27/H3K9 methylation maintenance relieves cMYC-dependent immune repression and prolongs survival of animal tumour models, suggesting a novel approach to treating cMYC-deregulated tumours.
Nearly half of all bacterial gene families are biased toward specific chromosomal positions
Authors: Hu Xiao-Pan , Lercher Martin J. 
Published: October 2023

AbstractMany bacterial genes encoding components of the translation and transcription machinery occupy genomic positions close to the origin of genome replication. These positional biases are thought to result from selection for high expression levels, as genes close to the origin are the first to be duplicated after the initiation of DNA replication. However, recent work indicates that positional biases of RNA genes involved in translation have evolved to support optimal growth rate dependence of expression levels rather than high expression per se. We hypothesized that, more generally, natural selection may have favored the location of different genes at specific chromosomal positions to optimize the growth rate dependence of their relative gene copy numbers. Here we show that 49% of bacterial gene families are preferentially localized to specific chromosomal regions, with most families biased toward either the origin or the terminus of replication. From our hypothesis, we derive six specific predictions regarding the genes’ chromosomal positioning and functional categories, as well as the minimum cellular doubling times. All six predictions are robustly supported by comparative genomic analyses of 773 bacterial species and by proteomics data fromEscherichia coliandBacillus subtilis. Our findings reveal a complex relationship between bacterial growth, resource allocation and genome organization, and they provide new insights into the physiological significance and potential functions of a large number of gene families.
The structural OFF and ON states of myosin can be decoupled from the biochemical super-relaxed and disordered-relaxed states
Authors: Ma Weikang , Jani Vivek P. , Song Taejeong , Gao Chengqian , Gong Henry , Sadayappan Sakthivel , Kass David A. , Irving Thomas C. 
Published: October 2023

AbstractThere is a growing awareness that both thick filament and classical thin filament regulation play central roles in modulating muscle contraction. Myosin ATPase assays have demonstrated that under relaxed conditions, myosin may reside in either a high energy-consuming disordered-relaxed (DRX) state available for binding actin to generate force, or in an energy-sparing super-relaxed (SRX) state unavailable for actin binding. X-ray diffraction studies have shown the majority of myosin heads are in a quasi-helically ordered OFF state in a resting muscle and that this helical ordering is lost when myosin heads are turned ON for contraction. It has been assumed that myosin heads in SRX and DRX states are equivalent to the OFF and ON state respectively and the terms have been used interchangeably. Here, we use X-ray diffraction and ATP turnover assays to track the structural and biochemical transitions of myosin heads respectively induced with either omecamtiv mecarbil (OM) or piperine in relaxed porcine myocardium. We find that while OM and piperine induce dramatic shifts of myosin heads from the OFF to ON states, there are no appreciable changes in the population of myosin heads in the SRX and DRX states in both unloaded and loaded preparations. Our results show that biochemically defined SRX and DRX can be decoupled from structurally-defined OFF and ON states. In summary, while SRX/DRX and OFF/ON transitions can be correlated in some cases, these two phenomena are measured using different approaches, do not necessarily reflect the same properties of the thick filament and should be investigated and interpreted separately.SignificanceMyosin based thick filament regulation is now known to be critical for muscle contraction with myosin dysregulation found in hypertrophic and dilated cardiomyopathies. While previously thought to be synonymous, this study finds that biochemical and structural thick filament disengagement are distinct properties and should be investigated as independent phenomena. Understanding the details of thick filament regulation will be of great relevance to defining sarcomere-level dysfunction in myopathies and understanding and better designing and testing sarcomere therapies aimed at reversing them for treatment of cardiomyopathy.
The type of carbon source not the growth rate it supports can determine diauxie
Authors: Huo Yu , Danecka Weronika , Farquhar Iseabail , Mailliet Kim , Moses Tessa , Wallace Edward W. J. , Swain Peter S. 
Published: October 2023

AbstractHow cells choose between potential carbon sources is a classic example of cellular decision-making, and we know that many organisms prioritise glucose. Yet there has been little investigation of whether other sugars are also preferred, blinkering our view of carbon sensing. Here we study eukaryotic budding yeast and its growth on mixtures of palatinose, an isomer of sucrose, with other sugars. We find that yeast prioritise galactose over palatinose, but not sucrose or fructose, despite all three of these sugars being able to support faster growth than palatinose. Our results therefore disfavour carbon flux-sensing as the sole mechanism. By using genetic perturbations and transcriptomics, we show that repression is active and through Gal4, the master regulator of the GAL regulon. Cells enforce their preference for galactose over palatinose by preventing runaway positive feedback in the MAL regulon, whose genes enable palatinose catabolism. They do so both by repressing MAL11, the gene encoding the palatinose transporter, and by first expressing the isomaltases, IMA1 and IMA5, which cleave palatinose and so prevent its intracellular concentration becoming enough to induce further MAL expression. Our results demonstrate that budding yeast actively maintain a preference for carbon sources other than glucose and that such preferences have been selected by more than differences in growth rates. They imply that carbon-sensing strategies even in unicellular organisms are more complex than previously thought.
Machine learning predicts system-wide metabolic flux control in cyanobacteria
Authors: Kugler Amit , Stensjö Karin 
Published: October 2023

AbstractMetabolic fluxes and their control mechanisms are fundamental in cellular metabolism, offering insights for the study of biological systems and biotechnological applications. However, quantitative and predictive understanding of controlling biochemical reactions in microbial cell factories, especially at the system level, is limited. In this work, we present ARCTICA, a computational framework that integrates constraint-based modelling with machine learning tools to address this challenge. Using the model cyanobacteriumSynechocystissp. PCC 6803 as chassis, we demonstrate that ARCTICA effectively simulates global-scale metabolic flux control. Key findings are that (i) the photosynthetic bioproduction is mainly governed by enzymes from the Calvin–Benson–Bassham (CBB) cycle, rather than by those involve in the biosynthesis of the end-product, (ii) the catalytic capacity of the CBB cycle limits the photosynthetic activity and downstream pathways and (iii) ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is a major, but not the most, limiting step in the CBB cycle. Predicted metabolic reactions qualitatively align with prior experimental observations, validating our modelling approach. ARCTICA serves as a valuable pipeline for understanding cellular physiology and predicting rate-limiting steps in genome-scale metabolic networks, providing guidance for bioengineering of cyanobacteria.HighlightsA workflow for flux control analysis inSynechocystissp. PCC 6803.Machine learning with features derived from genome-scale metabolic modelling.Identification of potential key reactions for metabolic adaptations and cell bioengineering.
TBL38 is an atypical homogalacturonan acetylesterase with a peculiar cell wall microdomain localization in Arabidopsis seed mucilage secretory cells
Authors: Dauphin Bastien G. , Ropartz David , Ranocha Philippe , Rouffle Maxime , Carton Camille , Ru Aurélie Le , Martinez Yves , Fourquaux Isabelle , Ollivier Simon , Mac-Bear Jessica , Trezel Pauline , Geairon Audrey , Jamet Elisabeth , Dunand Christophe , Pelloux Jérôme , Ralet Marie-Christine , Burlat Vincent 
Published: October 2023

AbstractPlant cell walls are made of complex polysaccharidic/proteinaceous network whose biosynthesis and dynamics implicate several cell compartments and impact plant development. The synthesis and remodeling of homogalacturonan pectins is associated with multiple developmental processes ranging from growth to response to biotic/abiotic stress. It encompasses Golgi-localized methylation and acetylation and subsequent demethylation and deacetylation in the cell wall. In the last decade, our comprehension of plant polysaccharides acetylation has increased significantly thanks to the study of the TRICHOME BIREFRINGENCE-LIKE (TBL) protein family. TBLs are mostly described as Golgi-localized acetyltransferases specifically targeting diverse hemicelluloses or pectins. Varioustblmutants showed altered wall mechanical properties and dynamics. Here, we studyTBL38that is co-expressed withPECTIN METHYLESTERASE INHIBITOR6(PMEI6) andPEROXIDASE 36(PRX36) during the development of Arabidopsis seed mucilage secretory cells (MSCs). We demonstrate the atypical TBL38 cell wall localization restricted to the PMEI6/PRX36 MSC cell wall microdomain. Atbl38mutant displays an intriguing homogalacturonan immunological phenotype in this cell wall microdomain and in a MSC surface-enriched abrasion powder. This fraction was further characterized by mass spectrometry oligosaccharide profiling revealing an increased homogalacturonan acetylation phenotype. Finally, a recombinant TBL38 is shown to display pectin acetylesterase activityin vitro. These results indicate that TBL38 is an atypical cell wall-localized TBL that displays a homogalacturonan acetylesterase activity rather than a Golgi-localized acetyltransferase activity as observed in previously studied TBLs. TBL38 function during seed development is discussed.
Evaluating the use of GPT-3.5-turbo to provide clinical recommendations in the Emergency Department
Authors: Williams Christopher Y.K. , Miao Brenda Y. , Butte Atul J. 
Published: October 2023

AbstractThe release of GPT-3.5-turbo (ChatGPT) and other large language models (LLMs) has the potential to transform healthcare. However, existing research evaluating LLM performance on real-world clinical notes is limited. Here, we conduct a highly-powered study to determine whether GPT-3.5-turbo can provide clinical recommendations for three tasks (admission status, radiological investigation(s) request status, and antibiotic prescription status) using clinical notes from the Emergency Department. We randomly select 10,000 Emergency Department visits to evaluate the accuracy of zero-shot, GPT-3.5-turbo-generated clinical recommendations across four different prompting strategies. We find that GPT-3.5-turbo performs poorly compared to a resident physician, with accuracy scores 24% lower on average. GPT-3.5-turbo tended to be overly cautious in its recommendations, with high sensitivity at the cost of specificity. Our findings demonstrate that, while early evaluations of the clinical use of LLMs are promising, LLM performance must be significantly improved before their deployment as decision support systems for clinical recommendations and other complex tasks.
Parenting Self-Efficacy within the First Year Postpartum in Non-Birthing Parents: A Scoping Review Protocol
Authors: Dol Justine , Parker Jennifer A. , Chambers Christine T , Joy Phillip , Leahy-Warren Patricia , Dennis Cindy-Lee , Macdonald Marilyn , Hancock Kristy 
Published: October 2023

AbstractObjectiveThe objective of this scoping review is to identify and analyze the literature on parenting self-efficacy in the non-birthing parent within the first year postpartum.IntroductionParenting self-efficacy is a parent’s confidence in their ability to organize and execute a set of tasks related raising children and providing them with protection and care in order to ensure their healthy development. To date, much of the work on parenting selfefficacy has focused on the birthing parent (e.g., mothers) excluding the non-birthing parent (e.g., fathers and LGBTQ+ parents).Inclusion criteriaStudies that include participants that identify as the non-birthing parent (regardless of sex or gender) who have had an infant less than 12 months of age. Various self-efficacy outcomes related to parenting will be included, as well as sub-types of selfefficacy (e.g., chest/breastfeeding). No limitations based on context, geography, or parity will be applied. All qualitative and quantitative study designs will be included.MethodsDatabases to be searched will include MEDLINE, Embase, Web of Science, CINAHL, and PsycINFO with no time limitations applied. Title and abstracts and full text will be screened by two reviewers with disagreements solved with a third reviewer. The data extracted will include specific details about the population, study, methods, and outcomes. Data will be reported narratively and in tables, as appropriate.