bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interaction between abiotic and biotic soil factors drive heterosis expression in maize
Authors: Clouse Kayla M. , Ellis Martel L. , Ford Natalie E. , Hostetler Rachel , Balint-Kurti Peter J. , Kleiner Manuel , Wagner Maggie R. 
Published: September 2024

AbstractHeterosis or hybrid vigor refers to the superior phenotypes of hybrids relative to their parental inbred lines. Recently, soil microbes were identified as an environmental driver of maize heterosis. While manipulation of the soil microbial community consistently altered heterosis, the direction of the effect appeared to be dependent on the microbiome composition, environment, or both. Abiotic factors are well-known modifiers of heterosis expression, however, how the interactive effects between the soil microbial community and abiotic factors contribute to heterosis are poorly understood. To disentangle the proposed mechanisms by which microbes influence heterosis, we characterize the variation in heterosis expression when maize was grown in soil inocula derived from active maize farms or prairies. While we did not observe consistent differences in heterosis among plants grown in these inocula, our observations reaffirm that microbial effects on heterosis are likely specific to the local microbial community. The introduction of a nutrient amendment resulted in greater heterosis expression in the presence of an agricultural inoculum but not a prairie inoculum. We also observed an effect of soil inocula and nutrient treatment on the composition of bacterial and fungal communities in the root endosphere. In addition, the interaction between soil and nutrient treatment significantly affected bacterial community composition, whereas fungal community composition was only marginally affected by this interaction. These results further suggest that the soil microbial community plays a role in maize heterosis expression but that the abiotic environment is likely a larger driver.
Model uncertainty estimates for deep learning mammographic density prediction using ordinal and classification approaches
Authors: Squires Steven , Kuling Grey , Evans D. Gareth , Martel Anne L. , Astley Susan M. 
Published: September 2024

AbstractPurposeMammographic density is associated with the risk of developing breast cancer and can be predicted using deep learning methods. Model uncertainty estimates are not produced by standard regression approaches but would be valuable for clinical and research purposes. Our objective is to produce deep learning models with in-built uncertainty estimates without degrading predictive performance.ApproachWe analyse data from over 150,000 mammogram images with associated continuous density scores from expert readers in the Predicting Risk Of Cancer At Screening (PROCAS) study. We re-designate the continuous density scores to 100 density classes then train classification and ordinal deep learning models. Distributions and distribution-free methods are applied to extract predictions and uncertainties. A deep learning regression model is trained on the continuous density scores to act as a direct comparison.ResultsThe root mean squared error (RMSE) between expert assigned density labels and predictions of the standard regression model are 8.42 (8.34-8.51) while the RMSE for the classification and ordinal classification are 8.37 (8.28-8.46) and 8.44 (8.35-8.53) respectively. The average uncertainties produced by the models are higher when the density scores from pairs of expert readers density scores differ more, are higher when different mammogram views of the same views are more variable and when two separately trained models show higher variation.ConclusionsUsing either a classification or ordinal approach we can produce model uncertainty estimates without loss of predictive performance.
Efficacy and safety of neoadjuvant stereotactic body radiation therapy plus dalpiciclib and exemestane for hormone receptor-positive, HER2-negative breast cancer: A prospective pilot study
Authors: Zhang Yu , Cao Shuo , Niu Nan , Shan Huilian , Xue Jinqi , Chen Guanglei , Xu Yongqing , Yin Jianqiao , Liu Chao , Sun Lisha , Jiang Xiaofan , Tang Meiyue , Xu Qianshi , Jia Mingxuan , Zhang Xu , Zhang Zhenyong , Zhang Qingfu , Wang Jianfei , Li Ailin , Yang Yongliang , Liu Caigang 
Published: September 2024

AbstractBackgroundBoth neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rates (ORR) in hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer, more promising alternatives are urgently needed. With proven synergistic effect of cyclin dependent kinase 4/6 (CDK4/6) inhibitor and radiotherapy in preclinical studies, this pilot study aimed to explore the efficacy and safety of neoadjuvant stereotactic body radiation therapy (SBRT) followed by dalpiciclib and exemestane in HR-positive, HER2-negative breast cancer.MethodsThis was a single-arm, non-controlled prospective pilot study. Treatment-naïve patients with unilateral HR-positive, HER2-negative breast cancer received neoadjuvant radiotherapy (24Gy/3F) followed by dalpiciclib and exemestane for 6 cycles. The primary endpoint was the proportion of patients with residual cancer burden (RCB) score of 0-I. Key secondary endpoints included ORR, breast-conservation rate, biomarker analysis, and safety.ResultsAll 12 enrolled patients completed the study treatment and surgery. Two (16.7%) of them achieved the RCB 0-I with the ORR of 91.7% (11/12). Analyses of tumor specimens showed significant increase of infiltrating T cells rather than alteration of PD-L1 positive immune cells. The most common grade 3 adverse events (AEs) were neutropenia (66.7%) and leukopenia (25.0%), but no grade 4-5 AE or death occurred.ConclusionsOur results suggested neoadjuvant SBRT followed by dalpiciclib and exemestane are effective and tolerable, and provides novel insights for the neoadjuvant treatment of HR+/HER2-breast cancer, which may be considered as a feasible option for patients with HR-positive, HER2-negative breast cancer.
Effect of fumarate and live yeast on methane emissions, rumen fermentation, blood metabolites, and lactation performance in dairy goats
Authors: Dong Huixin , Tan Jinlei , Li Shuaishuai , Ma Jingbo , Tang Guangfu , Dai Jiake , Yao Junhu , Li Zongjun 
Published: September 2024

AbstractThe objective of this study was to evaluate the effects and combined effects of fumarate (32 g/d) and active dry yeast (ADY) (1.5 g/d) on methane emissions, rumen fermentation, microbial community and function, apparent total tract digestibility, blood metabolites, and lactation performance in 28 lactating goats using a randomized complete block design with a 2 × 2 factorial arrangement. Fumarate supplementation inhibited methane emission rates for 3 h post-feeding, while ADY increased the methane emission rates for 2 h pre-feeding, without combined effects between them. Fumarate increased the rumen pH and reduced total VFA concentration without changing the VFA profiles before feeding. Based on two custom dataset of 4,674 metagenome-assembled genomes and 7,758,615 nonredundant genes, neither fumarate nor live yeast influenced the rumen microbial community and function. The addition of fumarate reduced the concentrations of glucose, serum malondialdehyde (MDA), and ammonia in the serum, as well as the activity of insulin, while increasing the activity of serum malate dehydrogenase (MDH) and the levels of urea in both serum and milk. The addition of live yeast reduced serum glucose levels and increased serum MDA concentrations and MUN levels. There was a negative interaction between fumaric acid and live yeast on the levels of urea nitrogen in serum and milk.ConclusionsThe methane inhibition effect of fumaric acid persists for 3 h post-feeding, reflecting its retention or metabolism time in the rumen. Fumaric acid enhances the TCA cycle and the urea cycle in dairy goats, thereby improving energy utilization efficiency and reducing the risk of ammonia toxicity.
Developing simple DNA extraction and PCR-RFLP forMALE STERILITY 4(MS4) gene inCryptomeria japonicaD. Don: Toward an environmentally friendly protocol
Authors: Ueno Saneyoshi , Ito Yukiko , Hasegawa Yoichi , Moriguchi Yoshinari 
Published: September 2024

AbstractThis study presents the development of a simple DNA extraction method and a novel PCR-RFLP protocol for genotyping theMALE STERILITY 4(MS4) gene inCryptomeria japonicaas a proof of concept. Traditional CTAB-based DNA extraction methods, while effective, involve hazardous chemicals and require high-speed centrifugation, which are impractical in many field settings. Our approach utilizes a household dish detergent-based buffer, sodium chloride, and polyvinylpyrrolidone K-30 to extract DNA fromC. japonicaneedle leaf tissues—without the need for liquid nitrogen. The simplicity of this method makes it more accessible and environmentally friendly. The extracted DNA was successfully used in PCR-RFLP analysis, targeting a single nucleotide polymorphism in theMS4gene, demonstrating its efficacy for genotyping. The PCR-RFLP markers reliably discriminated between individual genotypes, confirming the practical application of our simple extraction method, even for conifers containing inhibitory substances. This technique is particularly advantageous for use in arboretums and field stations, where the use of hazardous chemicals, specialized equipment, and a draft chamber is limited. Our study contributes to genetic resource management by providing an easy, reliable, and safer method for DNA extraction and genetic analysis.
Evolution of lateralized gustation in nematodes
Authors: Mackie Marisa , Le Vivian Vy , Carstensen Heather R. , Kushnir Nicole R. , Castro Dylan L. , Dimov Ivan M. , Quach Kathleen T. , Cook Steven J. , Hobert Oliver , Chalasani Sreekanth H. , Hong Ray L. 
Published: September 2024

AbstractAnimals with small nervous systems have a limited number of sensory neurons that must encode information from a changing environment. This problem is particularly exacerbated in nematodes that populate a wide variety of distinct ecological niches but only have a few sensory neurons available to encode multiple modalities. How does sensory diversity prevail within this neuronal constraint? To identify the genetic basis for patterning different nervous systems, we demonstrate that sensory neurons in thePristionchus pacificusrespond to various salt sensory cues in a manner that is partially distinct from that of the distantly related nematodeC. elegans. By visualizing neuronal activity patterns, we show that contrary to previous expectations based on its genome sequence, the salt responses ofP. pacificusare encoded in a left/right asymmetric manner in the bilateral ASE neuron pair. Our study illustrates patterns of evolutionary stability and change in the gustatory system of nematodes.
Translation components in adultDrosophila melanogasteradipocytes regulate the ovarian germline stem cell lineage
Authors: Sahu Subhshri , Armstrong Alissa Richmond 
Published: September 2024

AbstractAdult stem cells, which support tissue homeostasis and damage repair, are influenced by whole organism physiology. Dietary input has a major impact on the stem cell supported ovary inDrosophila melanogasterfemales, appropriately matching reproductive output to nutrient availability. Previous work has shown that inter-organ communication plays a role in modulating the ovarian response to diet. Specifically, amino acid sensing by the adipose tissue remotely controls germline stem cells and their progeny. While we have shown that activation of the amino acid response pathway, a part of the integrated stress response, and mTOR signaling in adipocytes impacts germline stem cell maintenance and ovulation, it is unclear how downstream signaling mediates these responses. Here, using a combination of genetic and cell biological tools, we show that regulation of translation in adult adipocytes impacts the ovarian germline stem cell lineage, from stem cell maintenance to ovulation of mature oocytes. This work strongly suggests that the adipose tissue produces specific factors to control stem cell activity in the ovary and highlights how inter-organ communication underlies organismal physiological responses to diet.
Inter- and intra-specific variation in the pelagic larval duration of four Tropical Eastern Pacific damselfishes (Pomacentridae:Stegastes) with contrasting distribution patterns
Authors: Lozano-Cortés D. F. , Rodríguez-Moreno M. , Zapata F. A. 
Published: September 2024

AbstractDispersal is a key ecological function in marine populations that are naturally fragmented and sometimes isolated. Pelagic larval duration (PLD) is thought to approximate the dispersal potential of coral reef fishes and may reflect the extent of connectivity in reef fish populations. Inter- and intra-specific variation in PLD of four damselfish species was investigated in the Colombian Pacific at four locations (two on the mainland coast, one at a continental island and one at an oceanic island) at multiple spatial scales (between localities and between sites within a single locality). Two of the species (Stegastes acapulcoensisandS. flavilatus) are broadly distributed on the continental coast while the other two (S. beebeiandS. arcifrons) are largely restricted to oceanic islands. Nonetheless, individuals of continental species sporadically colonize oceanic habitats, and vice- versa. The PLD was estimated using counts of otolith growth increments from juveniles collected at all localities. Species with an oceanic distribution had longer PLDs than their congeners with continental distributions. Differences in PLD between the two continental species varied between localities and significant intra- specific spatial variability was observed between localities but not within a single locality. Although the species studied have the necessary PLD to reach all available habitat, there are no apparent colonization events between mainland and oceanic islands suggesting that their distribution is not limited by dispersal but by other processes. We discuss the possible underlying causes of the observed variability, and suggest the need to consider spatial variability in the development of dispersal models and connectivity patterns for better management of coral reef fish populations.
Reciprocal regulation of m6A modification and miRNA production machineries via phase separation-dependent and -independent mechanisms
Authors: Zhong Songxiao , Li Xindi , Li Changhao , Bai Haiyan , Chen Jingjing , Gan Lu , Zhu Jiyun , Oh Taerin , Yan Xingxing , Zhu Jiaying , Li Niankui , Koiwa Hisashi , Meek Thomas , Peng Xu , Yu Bin , Zhang Zhonghui , Zhang Xiuren 
Published: September 2024

AbstractMethyltransferase complex (MTC) depositsN6-adenosine (m6A) onto RNA, whereas microprocessor produces miRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B (MTB) tends to form insoluble condensates with poor activity, with its level monitored by 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promotes solubility and stability of MTB, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behavior, exhibit reduced m6A level. Reciprocally, MTC can recruit microprocessor toMIRNAloci, prompting co-transcriptional cleavage of primary miRNA (pri-miRNAs) substrates. Additionally, pri-miRNAs carrying m6A modifications at their single-stranded basal regions are enriched by m6A readers, which retain microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.
Analytic validation of anFGFR-focused cell-free DNA liquid biopsy assay (FGFR-Dx)
Authors: Reeser Julie W. , Wing Michele R. , Samorodnitsky Eric , Dao Thuy , Smith Amy , Stein Leah , Paruchuri Anoosha , Miya Jharna , Bonneville Russell , Chang Yi-Seok , Avenarius Matthew , Freud Aharon G. , Yu Lianbo , Roychowdhury Sameek 
Published: September 2024

ABSTRACTCommercial liquid biopsy assays are routinely used by oncologists to monitor disease response and resistance to therapy. Additionally, in cases where tumor tissue is not available, clinicians may rely on cell-free DNA (cfDNA) testing as a surrogate for comprehensive tumor testing. While some gene rearrangements are well detected, current commercial liquid biopsy assays exhibit low sensitivity for fibroblast growth factor receptor (FGFR) rearrangements.FGFRsare altered in ∼2.5% of all cancers, includingFGFR2rearrangements in 10% of intrahepatic cholangiocarcinoma andFGFR3point mutations and rearrangements in 10-15% of urothelial carcinoma. Therefore, we developed and analytically validated FGFR-Dx, anFGFR-focused cfDNA assay with improved sensitivity forFGFRrearrangements. FGFR-Dx comprehensively targets the introns inFGFR1-3previously shown to be involved in gene fusions as well as all coding exons. CustomFGFRsynthetic reference standards representing both single nucleotide variants (SNVs) and gene rearrangements were utilized at a range of variant frequencies and revealed a detection limit of 0.5% with sensitivities of 97.2% and 92.9% for SNVs and rearrangements, respectively. Furthermore, FGFR-Dx detected rearrangements and identified the intronic breakpoints from cfDNA collected from 13 of 15 patients with known FGFR fusions.
Cross-Cultural Validation of Acculturation Measures: Expanding the East Asian Acculturation Framework for Global Applicability
Authors: Idemudia Erhabor Sunday , Karing Constance , Ugwu Lawrence Ejike 
Published: September 2024

AbstractIn a globalised world, understanding acculturation—the process by which individuals adapt to new cultural environments—is crucial, especially in multicultural societies. The East Asian Acculturation Measure (EAAM), rooted in Berry’s acculturation model, has been extensively used to assess acculturation strategies among East Asian populations in the United States. However, its application to other cultural groups remains limited due to its specificity. This study aims to adapt and validate the EAAM for broader applicability across diverse cultural contexts, particularly among populations outside the East Asian demographic.The study involved 819 international students in Germany and South Africa from 112 countries. It was conducted in two phases: the first included 490 and 329 in the second. The psychometric properties of the EAAM were evaluated through Confirmatory Factor Analysis (CFA) and Exploratory Factor Analysis (EFA). Initial CFA results showed that the original four-factor model did not adequately fit the diverse sample, prompting further EFA, which revealed a more suitable five-factor structure. This new structure termed the Shortened Adapted Acculturation Scale (SAAS), comprises five dimensions: Social Disconnection, Cultural Adaptation, Social Perception, Interpersonal Comfort, and Language Integration. The SAAS demonstrated high internal consistency and reliability across all factors, with significant evidence of measurement invariance across genders.The findings emphasise the importance of culturally adapting psychological measures to ensure validity and reliability across diverse populations. The SAAS offers a robust tool for assessing acculturation beyond East Asian contexts, providing valuable insights into the complexities of cultural adaptation. The study’s outcomes contribute significantly to the field of cross-cultural psychology and highlight the need for continued research on acculturation processes in an increasingly diverse world.
Evolverator: An engineeredin celluloyeast system to drive rapid continuous evolution of proteins
Authors: Azizoglu Asli , Bijman Eline Y. , Stelling Jörg , Brent Roger 
Published: September 2024

AbstractIn vivocontinuous directed evolution generates genetic diversity and selects a target phenotype to generate proteins with desired functionality. However, in current systems, the two processes do not operate simultaneously in the same cell, restricting applications such as evolution of eukaryotic protein-ligand binding. Here, we describe EvolveratorSaccharomyces cerevisiaecells that combine inducible targeted mutagenesis with engineered gene circuits that link the emergence of a desired function to graded increases in cell proliferation. Poor ligand binding induces targeted mutagenesis and cells with mutations that improve ligand binding overtake the cell population. By combining strain development with mathematical modeling for systems and process design, we evolved ligand specificities of the human estrogen receptor and more effective variants of the bacterial lacI repressor. Previously undescribed mutations affected residues plausibly involved in ligand binding and residues that exert allosteric effects. Evolverator should aid generation of proteins that bind new targets for many applications.
Genome-wide CRISPRi-seq identified ferredoxin-NADP reductase FprB as a synergistic target for gallium therapy inPseudomonas aeruginosa
Authors: Zhang Yu , Zhang Tingting , Xiao Xue , Kawalek Adam , Ou Jinzhao , Ren Anmin , Sun Wenhao , de Bakker Vincent , Liu Yujie , Li Yuelong , Yang Liang , Ye Liang , Jia Ning , Veening Jan-Willem , Wang Yejun , Liu Xue 
Published: September 2024

AbstractWith the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium are increasingly gaining attention. Gallium ions exhibit potent activity against multidrug-resistant bacteria and intravenous gallium nitrite is under phase 2 clinical trials to treat chronicPseudomonas aeruginosainfections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we applied a genome-wide CRISPR interference approach (CRISPRi-seq), to identify potential synergistic targets with gallium. Through the systemic screening, we classified the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identified a highly conserved genefprB, encoding a ferredoxin-NADP+reductase, the downregulation of which dramatically sensitized the cells to gallium. Using a null mutant, we confirmed the loss offprBlowers the minimum inhibitory concentration of gallium from 320 µM to 10 µM and shifted gallium’s mode of action from bacteriostatic to bactericidal. Further investigation revealed that FprB plays a critical role in modulating oxidative stress induced by gallium, via control of the iron homeostasis and reactive oxygen species accumulation. DeletingfprBalso enhanced gallium’s efficacy against biofilms formation and improved outcomes in murine lung infection model ofP. aeruginosa,suggesting FprB as a promising drug target in combination with gallium. Overall, our data showed CRISPRi-seq as a powerful tool for systematic genetic analysis ofP. aeruginosa, advancing identification of novel therapeutic targets.