bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of annatto pigment synthesis and accumulation revealed by integrated chemical, anatomical, and RNA-Seq analyses
Authors: Moreira Viviane Santos , de Souza Vinicius Carius , Soares Virgínia Lúcia Fontes , Sousa Aurizangela Oliveira , de Nascimento Katiucia Ticila de Souza , de Santana Monique Reis , Rebouças Tiyoko Nair Hojo , Leitão Carlos André Espolador , Goliatt Priscila Vanessa Zabala Capriles , Faria Daniele Vidal , Otoni Wagner Campos , Costa Marcio Gilberto Cardoso 
Published: September 2022

AbstractBixin is a commercially valuable apocarotenoid pigment found in the seed aril of Bixa orellana. The dynamics and regulation of its biosynthesis and accumulation during seed development remain largely unknown. Here, we combined chemical, anatomical, and transcriptomic data to provide stage-specific resolution of the cellular and molecular events occurring during B. orellana seed development. Seeds at five developmental stages (S1–S5) were used for analysis of bixin content and seed anatomy, and three of them (S1, S3 and S4) selected for Illumina HiSeq sequencing. Bixin accumulated sharply during seed development, particularly during the S2 stage, peaking at the S4 stage, and then decreasing slightly in the S5 stage. Anatomical analysis revealed that bixin accumulated in the large central vacuole of specialized cells, which were scattered throughout the developing mesotesta at the S2 stage, but enlarged progressively at later stages, until they occupied most of the parenchyma in the aril. A total of 13 million reads were generated and assembled into 73,381 protein-encoding contigs, from which 312 were identified as containing 1-deoxy-D-xylulose-5-phosphate/2-C-methyl-D-erythritol-4-phosphate (DOXP/MEP), carotenoid, and bixin pathways genes. Differential expression analysis of these genes revealed that 50 of them were differentially expressed between all the seed developmental stages, including seven carotenoid cleavage dioxygenases, eight aldehyde dehydrogenases and 22 methyltransferases. Taken together, these results provide a comprehensive description of the cellular and molecular events related to the dynamics of bixin synthesis and accumulation during seed development in B. orellana.
Hospital-wide Natural Language Processing summarising the health data of 1 million patients
Authors: Bean Daniel , Kraljevic Zeljko , Shek Anthony , Teo James , Dobson Richard 
Published: September 2022

AbstractElectronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR’s try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King’s College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.
Cellular Heterogeneity of Pluripotent Stem Cell Derived Cardiomyocyte Grafts is Mechanistically Linked to Treatable Arrhythmias
Authors: Selvakumar Dinesh , Clayton Zoe E. , Prowse Andrew , Dingwall Steve , George Jacob , Shah Haisam , Chen Siqi , Hume Robert D. , Tjahjadi Laurentius , Igoor Sindhu , Skelton Rhys J.P. , Hing Alfred , Paterson Hugh , Foster Sheryl L. , Pearson Lachlan , Wilkie Emma , Jeyaprakash Prajith , Wu Zhixuan , McArthur Jeffrey R. , Barry Tony , Lu Juntang , Tran Vu , Bennett Richard , Kotake Yasuhito , Campbell Timothy , Turnbull Samual , Nguyen Quan , Ni Guiyan , Grieve Stuart M. , Palpant Nathan J. , Pathan Faraz , Kizana Eddy , Kumar Saurabh , Gray Peter P. , Chong James J.H. 
Published: September 2022

AbstractBackgroundExciting pre-clinical data have confirmed that human pluripotent stem cell derived cardiomyocytes (PSC-CMs) can remuscularise the injured or diseased heart, with several clinical trials now in planning or recruitment stages worldwide. However, ventricular arrhythmias are a predictable complication following engraftment of intramyocardially injected PSC-CMs. Therefore, there is an urgent unmet need to gain mechanistic insights and treatment strategies to control or prevent these engraftment arrhythmias (EAs).MethodsWe used a porcine model of myocardial infarction and PSC-CM transplantation to investigate efficacy of pharmacologic and catheter based anti-arrhythmic strategies in mitigating EAs. Furthermore, cell doses were robustly phenotyped using single cell ribonucleic acid sequencing and high parameter flow cytometry to identify cellular characteristics predictive of arrhythmogenesis.ResultsCombination therapy with amiodarone and ivabradine significantly reduced EA rate and burden following PSC-CM transplantation. Catheter ablation was also a feasible and effective treatment strategy which could be considered in the case of pharmacologically refractory arrhythmias. In addition, we show that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. We further describe two unique surface marker signatures, SIRPA+/CD90-/CD200+ and SIRPA+/CD90-/CD200-, which identify arrhythmogenic and non-arrhythmogenic cardiomyocytes respectively.ConclusionOur data deepens mechanistic understanding of EAs and suggests that modifications to current PSC-CM production and/or selection protocols could ameliorate this problem. We further show that current clinical pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias, an important safety consideration given several impending clinical trials.
Colistin resistance mutations in phoQ sensitize Klebsiella pneumoniae to IgM-mediated complement killing
Authors: van der Lans Sjors P.A. , Janet-Maitre Manon , Masson Frerich M. , Walker Kimberly A. , Doorduijn Dennis J. , Janssen Axel B. , van Schaik Willem , Attrée Ina , Rooijakkers Suzan H. M. , Bardoel Bart W. 
Published: September 2022

AbstractThe Gram-negative bacterium Klebsiella pneumoniae is notorious for a strong increase of infections with antibiotic resistant strains. To treat infections with antibiotic resistant K. pneumoniae, clinicians increasingly need to use the last resort antibiotic colistin. K. pneumoniae can develop colistin resistance by modifying its membranes. During infection the membranes of Gram-negative bacteria are also targeted by the human immune system via the complement system. Gram-negative bacteria have an outer and inner membrane separated by a thin cell wall. Activation of the complement system leads to the formation of the membrane attack complex (MAC), a pore that inserts into the outer membrane, and ultimately leads to lysis of the bacterium. As both colistin and the MAC interact with the outer membrane of Gram-negative bacteria, we wondered if developing colistin resistance influences MAC-mediated killing of K. pneumoniae.Using clinical isolates that developed colistin resistance, we found that the strain Kp209_CSTR became more sensitive to MAC-mediated killing compared to the wild-type strain. MAC-mediated membrane permeabilization of Kp209_CSTR required antibody dependent activation of the classical complement pathway. Strikingly, Kp209_CSTR was bound by IgM in human serum that did not recognise the wild-type strain. Depletion of Kp209_CSTR-specific antibodies from serum prevented MAC-mediated membrane permeabilization, which was restored by adding back IgM. Genomic sequence comparison revealed that Kp209_CSTR has a deletion in the phoQ gene. RNAseq analysis suggested that this mutation locks PhoQ in a constitutively active state. These results indicate that PhoQ activation in Kp209_CSTR leads to both colistin resistance and sensitivity to MAC-mediated killing. Together, our results show that developing colistin resistance can sensitize K. pneumoniae to killing by the immune system.
A toxin-antitoxin system ensures plasmid stability in Coxiella burnetii
Authors: Wachter Shaun , Cockrell Diane C , Miller Heather E , Virtaneva Kimmo , Kanakabandi Kishore , Darwitz Benjamin , Heinzen Robert A , Beare Paul A 
Published: September 2022

SummaryCoxiella burnetii is the causative agent of Q fever. All C. burnetii isolates encode either an autonomous replicating plasmid (QpH1, QpDG, QpRS, or QpDV) or QpRS-like chromosomally integrated plasmid sequences. The role of the ORFs present on these sequences is unknown. Here, the role of the ORFs encoded on QpH1 was investigated. Using a new C. burnetii shuttle vector (pB-TyrB-QpH1ori) we cured Nine Mile Phase II of QpH1. The ΔQpH1 strain grew normally in axenic media but had a significant growth defect in Vero cells, indicating QpH1 was important for C. burnetii virulence. We developed an inducible CRISPR interference system to examine the role of individual QpH1 plasmid genes. CRISPRi of cbuA0027 resulted in significant growth defects in axenic media and THP-1 cells. The cbuA0028/cbuA0027 operon encodes CBUA0028 and CBUA0027, which are homologous to the HigB2 toxin and HigA2 anti-toxin, respectively, from Vibrio cholerae. Consistent with toxin-antitoxin systems, overexpression of cbuA0028 resulted in a severe intracellular growth defect that was rescued by co-expression of cbuA0027. CBUA0028 inhibited protein translation. CBUA0027 bound the cbuA0028 promoter (PcbuA0028) and CBUA0028, with the resulting complex binding also PcbuA0028. In summary, our data indicates C. burnetii maintains an autonomously replicating plasmid because of a plasmid-based toxin-antitoxin system.
City spatial structure and smart city innovation: the case of China
Authors: Chen Yongtai , Li Rui , Zeng En-yu , Li Pengfei 
Published: September 2022

PurposeThis study aims to analyze the relevance of the city spatial structure for smart city innovation from the perspective of agglomeration externalities, and discusses whether there is heterogeneity in innovation across different geographical areas and population scales of cities.Design/methodology/approachThe authors construct the centralization and concentration indexes to conceptualize the city spatial structure of 286 cities (prefecture-level) in China based on the LandScan Global Population Dataset from 2001 to 2016. A fixed-effects panel data model is employed to analyze the relationship between the spatial structure and the innovation ability of smart cities; the results were validated through robustness tests and heterogeneity analyses.FindingsThe study found that the more concentrated and more evenly the distribution of urban population, namely the more city spatial structure tends to be weak-monocentricity, the higher the level of innovation in smart cities. The relevance of the weak-monocentricity structure and smart city innovation varies significantly depending on their geographical location and the size of the city. This result is more applicable to cities in the eastern and central regions, as well as to cities with smaller populations.Originality/valueThe adjustment and optimization of the city spatial structure is important for enhancing smart city construction. Unlike previous studies, which mostly use a single dimension of “the proportion of population in sub-centres to the population of all central areas” to measure city spatial structure, the authors employed the spatial centralization and spatial concentration. It is hoped that this study can guide smart city construction from the perspective of the development model of city spatial structure.
A study of Silicon Valley firms' accounting losses
Authors: Ivanov Stoyu I. , Faulkner Matthew 
Published: September 2022

PurposeSmall firms, which represent much of the Silicon Valley region, tend to experience losses due to their small scale, small customer base and lack of diversification. The authors study the impact of accounting conservatism and losses on firm value and as such this study is an appropriate addition to this growing field of financial management.Design/methodology/approachThe authors use methodology developed in prior literature to examine Silicon Valley and non-Silicon Valley firms' and their behavior when facing losses and the factors, which might play a role in their valuation. The authors focus particularly on earnings and accounting conservatism. Accounting conservatism captures how fast firms record losses relative to gains. The faster losses are recognized than gains the more accounting conservatism is exhibited. The authors examine the seemingly unrelated estimation of differences in means for our independent variables of interest across the two samples of Silicon Valley and non-Silicon Valley firms, both earnings and accounting conservatism. The authors use matched sample analysis of these firms based on four digit SIC code, size and date. In robustness, the authors run a more in-depth propensity score matched sample analysis.FindingsThe authors document that market values of Silicon Valley firms with accounting losses are affected less by negative earnings than other firms with accounting losses in the United States outside of the Silicon Valley region, noting the “lose big, win bigger” sentiment of Silicon Valley. Additionally, the authors document that accounting conservatism does play a role in influencing valuations of companies with accounting losses both in Silicon Valley and the rest of the United States, marginally more for Silicon Valley firms.Originality/valueThis study would be of interest to fund managers who need to consider smaller firms for inclusion in their portfolios. A lot of small firms have experienced losses ever since going public, especially Silicon Valley start-up firms.
Phospholipase D and phosphatidic acid mediate regulation in the biosynthesis of spermidine and ganoderic acids by activating GlMyb in Ganoderma lucidum under heat stress
Authors: Han Xiaofei , Wang Zi , Shi Lingyan , Zhu Jing , Shi Liang , Ren Ang , Zhao Mingwen 
Published: September 2022

AbstractPolyamines are essential for all kinds of organisms and take part in the regulation of multiple biological processes. Our previous study revealed that heat stress promoted the conversion of putrescine to spermidine and subsequently promoted the accumulation of ganoderic acids (GAs). However, how heat stress affects polyamine homeostasis remains unclear. To explore the underlying mechanism by which heat stress promoted spermidine biosynthesis, we assessed the effects of signalling molecules that respond to heat stress on spermidine biosynthesis. Our data suggested that heat stress‐induced spermidine biosynthesis and GAs accumulation via a phospholipase D (PLD)‐mediated phosphatidic acid (PA) signal. Further research revealed that the transcription factor GlMyb promoted spermidine biosynthesis via regulating spermidine synthase genes (spds1 and spds2) expression by directly bonding to their promoters and it responded to heat stress and PA signal. In summary, heat stress activated GlMyb by PLD‐mediated PA signalling and subsequently induced the expression of spds1 and spds2 to promote the biosynthesis of spermidine and the accumulation of GAs. Our findings firstly reveal a detailed mechanism by which heat signalling regulates polyamine homeostasis by PLD‐mediated PA signal in fungi and provide a greater understanding of how organisms alter polyamine levels in response to environmental changes.
Evangelization and Language Change: A Transition from the Progressive Aspect to the Future Tense in Two Mayan Languages
Authors: Vinogradov Igor 
Published: September 2022

AbstractThis paper revisits the role that evangelization may have played in the diachronic development of Amerindian languages, with a focus on grammatical changes. Based on an analysis of written materials dating back to the colonial period and first‐hand fieldwork data, it discusses the semantic transition from the progressive aspect to the future tense that occurred similarly in the verbal systems of Q’eqchi’ and Poqomchi’, two Mayan languages spoken in Guatemala. Although the diachronic path is shared, the morphemes and constructions involved are clearly different in the two languages. The spread of this particular change from one language to the other is attributed to contact between their speakers that could be reinforced by the considerable number of translations of authoritative religious texts made by Dominican missionaries during the colonial period.
Knowledge Politics, Historic Memory and The Virginia House‐wife
Authors: Pellissier Marie 
Published: September 2022

ABSTRACTOver the two centuries since its publication, Mary Randolph's 1824 cookbook has become embedded in discourses of historic memory. These discourses have obscured the racial and gendered politics, resistance and conflict present in the book. Randolph's text, when read closely, illuminates the kitchen spaces in which enslaved Black cooks both cooperated and came into conflict with the white women who enslaved them. White supremacy is embedded in the text, and has also shaped its legacy, as museums and historic sites in Virginia and across the nation have used The Virginia House‐wife to bolster simplified and nostalgic views of the antebellum and colonial past.
Age alters the oncogenic trajectory toward luminal mammary tumors that activate unfolded proteins responses
Authors: Jenkins Edmund Charles , Chattopadhyay Mrittika , Gomez Maria , Torre Denis , Ma'ayan Avi , Torres‐Martin Miguel , Sia Daniela , Germain Doris 
Published: September 2022

AbstractA major limitation in the use of mouse models in breast cancer research is that most mice develop estrogen receptor‐alpha (ERα)‐negative mammary tumors, while in humans, the majority of breast cancers are ERα‐positive. Therefore, developing mouse models that best mimic the disease in humans is of fundamental need. Here, using an inducible MMTV‐rtTA/TetO‐NeuNT mouse model, we show that despite being driven by the same oncogene, mammary tumors in young mice are ERα‐negative, while they are ERα‐positive in aged mice. To further elucidate the mechanisms for this observation, we performed RNAseq analysis and identified genes that are uniquely expressed in aged female‐derived mammary tumors. We found these genes to be involved in the activation of the ERα axis of the mitochondrial UPR and the ERα‐mediated regulation of XBP‐1s, a gene involved in the endoplasmic reticulum UPR. Collectively, our results indicate that aging alters the oncogenic trajectory towards the ERα‐positive subtype of breast cancers, and that mammary tumors in aged mice are characterized by the upregulation of multiple UPR stress responses regulated by the ERα.
Effects of exposure to mother's and father's alcohol use on young children's normative perceptions of alcohol
Authors: Cook Megan , Smit Koen , Voogt Carmen , Kuntsche Sandra , Kuntsche Emmanuel 
Published: September 2022

AbstractBackgroundWhile consumption of alcohol does not often begin until early adolescence, young children are highly capable of internalizing normative information through observational learning. We used a longitudinal multiple‐informant family study to examine the impact of exposure to mothers' and fathers' drinking on young children's normative perceptions of who drinks alcohol.MethodsThree hundred twenty‐nine children (4 to 6 years old at baseline [Mage 4.78 (SD = 0.725)], 51% girls) completed the Dutch electronic appropriate beverage task [eABT] where they attributed alcoholic beverages to a variety of persons depicted in an illustrated scenario. Their parents completed an online survey that included information on alcohol use and exposure.ResultsChildren more frequently exposed to their mothers' drinking provided females shown in the eABT illustrations with alcohol significantly more often than children less frequently exposed to mothers' drinking. There was no effect of mother's exposure on providing males in the eABT with alcoholic beverages. Similarly, children more frequently exposed to their fathers' drinking provided fathers with alcoholic beverages significantly more often than children less frequently exposed to their fathers' drinking. There was no effect of father's exposure on providing the females with alcoholic beverages, nor was there an effect of father's exposure on providing “other males” with alcohol. These patterns held after adjusting for age and sex.ConclusionsThis study demonstrates that there are gender‐specific effects of exposure to parents' (particularly mothers') drinking on young children's perceptions of person‐specific drinking norms. The findings provide unique evidence in a young population group of effects on an understudied dimension of alcohol‐related perceptions with implications for future drinking behavior.
The effects of agricultural policy on supply and productivity: Evidence from differential changes in distortions
Authors: Hendricks Nathan P. , Smith Aaron , Villoria Nelson B. , Stigler Matthieu 
Published: September 2022

AbstractIncentives in agriculture are highly distorted. It has long been argued that these distortions were a key explanation for differences in supply and productivity across countries, but the empirical evidence is limited. We revisit this issue using data on policy distortions across 63 countries for the period 1961–2011. We estimate the effects of differential changes in agricultural distortions across countries on supply and productivity. We highlight concerns in our analysis and previous work about endogeneity that biases the estimated effect downward—countries that lose comparative advantage are likely to increase support for agriculture. We address these concerns by including country and region‐time fixed effects, along with a rich set of controls. Overall, we find evidence that enhanced incentives through policy changes can increase the rate of production growth, with about half of the increase due to productivity increases. This result is strongest in Sub‐Saharan Africa where anti‐agricultural policies on exports were reduced and in Europe where pro‐agricultural policies on imports were reduced, driven largely by external pressure. Endogeneity appears to be strongest in Asia where countries have followed the typical pattern of raising support for agriculture during industrialization due to a rising farm‐urban income gap.
Background context affects word‐object mapping
Authors: Tippenhauer Nicholas , Saylor Megan M. 
Published: September 2022

AbstractChildren encounter new words across variable and noisy contexts. This variability may affect word learning, but the literature includes discrepant findings. The current experiment investigated one source of these discrepant findings: whether contexts with familiar, nameable objects are associated with less robust label learning. Two year olds were exposed to word‐object pairings on variable contexts that either included nameable objects or did not. Target selection was more robust when exposure occurred without other nameable objects. The difference was present immediately, but not after a delay. This study provides the evidence that context effects are context‐bound.