bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Model for Severe Coronary Artery Calcification in ESKD Patients
Authors: Tang Xinfang , Qian Hanyang , Zeng Ming , Huang Hui , Lu Shijiu , Wang Jing , Li Fan , Bian Anning , Ye Xiaoxue , Yang Guang , Ma Kefan , Xing Changying , Xu Yi , Wang Ningning
Published: December 2023

Introduction

The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients.

Methods

CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres.

Results

369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 < CACS ≤ 400, n = 141) and severe calcification (CACS > 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, β-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity.

Conclusion

CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.
Six-month mortality has decreased for patients with curative treatment for head and neck cancer in Sweden
Authors: Talani Charbél , Högmo Anders , Laurell Göran , Mäkitie Antti , Farnebo Lovisa
Published: December 2023

Background

In general, survival outcome for head and neck cancer (HNC) patients has improved. However, mortality within six months after diagnosis with curative intent remains high. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over the recent years.

Material and Method

This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included 16,786 patients with curative treatment decision at the multidisciplinary tumor board from 2008 to 2020.

Results

During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months from diagnosis. Patients diagnosed between 2008–2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed 2017–2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy in the 2008–2012 cohort was 38 days, compared to 22 days for the 2017– 2020 cohort, (p<0.001). The mean time to surgery from diagnosis was 22 days in 2008–2012, compared to 15 days for the 2017–2020 cohort, (p <0.001).

Females had a 20% lower risk of dying within six months compared to males (p =0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001)

Conclusions

We found that the risk of early death decreased significantly from 2008 to 2020. During this period the mean time to the start of treatment, was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

Brief description

*The risk of early death decreased significantly from 2008 to 2020.

*Time from diagnosis to treatment decreased between 2008 to 2020.

*Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

Ethical Considerations

The Regional Ethical Review Board in Gothenburg and Lund reviewed and approved the study, (Gothenburg, number 299–14, T230-17 and Lund 2020-01972). This study was carried out in accordance with the current Helsinki Declaration of the World Medical Association from 2013. Data are available upon request.
The effect of variable inertial resistance on force, velocity, power and muscle activation during a chest press exercise
Authors: Zoffoli Luca , Biscarini Andrea , Zanuso Silvano
Published: December 2023

This study investigated the effect of the inertial component of the resistance (INERTIA) at different intensity levels (LOAD) on force (FORCE), velocity (VELOCITY), power (POWER), and the muscle activity of the pectoralis major (EMGPM), anterior deltoid (EMGDA) and triceps brachii (EMGTB) muscles during a chest press exercise.

A motor-driven exercise apparatus was programmed to offer resistance with different inertial profiles over the range of movement (ROM): gravitational-type constant inertia (IFULL); no-inertia (IZERO); linearly descending inertia along theROM(IVAR). Nine healthy adults performed five, maximal-effort, explosive movements with each inertial profile at 30, 50 and 70% of their 1 repetition maximum. Meanwhile, theEMGPM,EMGDAandEMGTBsignals were obtained jointly with theFORCE, VELOCITYandPOWERreadings returned by the exercise apparatus.

One-dimensional statistical non-parametric maps based on 2-way repeated measures ANOVA (SnPM) were employed to evaluate the effect ofLOADandINERTIAon the collected timeseries. Paired t-tests were then used as post-hoc tests on the portions of theROMdenoting significant differences in theSnPM.

HigherLOADresulted in elevated outcomes over large portions of theROMin all the investigated timeseries. Compared toIFULL,IZEROallowed greaterVELOCITYat the cost of lowerFORCEthroughout theROM, whileIVAR, despite the lowerVELOCITYthanIZERO, resulted in higherFORCEandPOWERoutput. In addition,IZEROandIVARelevatedEMGTBat the end of theROMwith respect toIFULL.IVARovercame bothIFULLandIZEROin terms ofFORCEandPOWER, which indicates that variable inertial profiles might be effectively integrated into resistance exercise programs. Ultimately, this study suggested thatINERTIAacts independently to the imposedLOADon theFORCE, VELOCITYandPOWERproduction. Coaches and therapists are encouraged to account for the type ofINERTIAas one of the parameters considered during the exercise selection for their athletes or patients.
Open Soil Spectral Library (OSSL): Building reproducible soil calibration models through open development and community engagement
Authors: Safanelli José L. , Hengl Tomislav , Parente Leandro , Minarik Robert , Bloom Dellena E. , Todd-Brown Katherine , Gholizadeh Asa , Mendes Wanderson de Sousa , Sanderman Jonathan
Published: December 2023

Soil spectroscopy is a widely used method for estimating soil properties that are important to environmental and agricultural monitoring. However, a bottleneck to its more widespread adoption is the need for establishing large reference datasets for training machine learning (ML) models, which are called soil spectral libraries (SSLs). Similarly, the prediction capacity of new samples is also subject to the number and diversity of soil types and conditions represented in the SSLs. To help bridge this gap and enable hundreds of stakeholders to collect more affordable soil data by leveraging a centralized open resource, the Soil Spectroscopy for Global Good has created the Open Soil Spectral Library (OSSL). In this paper, we describe the procedures for collecting and harmonizing several SSLs that are incorporated into the OSSL, followed by exploratory analysis and predictive modeling. The results of 10-fold cross-validation with refitting show that, in general, mid-infrared (MIR)-based models are significantly more accurate than visible and near-infrared (VisNIR) or near-infrared (NIR) models. From independent model evaluation, we found that Cubist comes out as the best-performing ML algorithm for the calibration and delivery of reliable outputs (prediction uncertainty and representation flag). Although many soil properties are well predicted, total sulfur, extractable sodium, and electrical conductivity performed poorly in all spectral regions, with some other extractable nutrients and physical soil properties also performing poorly in one or two spectral regions (VisNIR or Neospectra NIR). Hence, the use of predictive models based solely on spectral variations has limitations. This study also presents and discusses several other open resources that were developed from the OSSL, aspects of opening data, current limitations, and future development. With this genuinely open science project, we hope that OSSL becomes the driver of the soil spectroscopy community to accelerate the pace of scientific discovery and innovation.
Macrophages control pathological interferon responses during viral respiratory infection
Authors: Hoagland Daisy A. , Rodríguez-Morales Patricia , Mann Alexander O. , Yu Shuang , Lai Alicia , Vazquez Alan Baez , Pope Scott D. , Lim Jaechul , Li Shun , Zhang Xian , Li Ming O. , Medzhitov Ruslan , Franklin Ruth A.
Published: December 2023

Antiviral immune mediators, including interferons and their downstream effectors, are critical for host defense yet can become detrimental when uncontrolled. Here, we identify a macrophage-mediated anti-inflammatory mechanism that limits type I interferon (IFN-I) responses. Specifically, we found that cellular stress and pathogen recognition induce Oncostatin M (OSM) production by macrophages. OSM-deficient mice succumbed to challenge with influenza or a viral mimic due to heightened IFN-I activation. Macrophage-derived OSM restricted excessive IFN-I production by lung epithelial cells following viral stimulation. Furthermore, reconstitution of OSM in the respiratory tract was sufficient to protect mice lacking macrophage-derived OSM against morbidity, indicating the importance of local OSM production. This work reveals a host strategy to dampen inflammation in the lung through the negative regulation of IFN-I by macrophages.

One-Sentence Summary

Type I interferons induced by viral stimuli are negatively regulated by macrophage-derived Oncostatin M.
Microbial communities living inside plant leaves or on the leaf surface are differently shaped by environmental cues
Authors: Mahmoudi Maryam , Almario Juliana , Lutap Katrina , Nieselt Kay , Kemen Eric
Published: December 2023

Leaf-associated microbial communities can promote plant health and resistance to biotic and abiotic stresses. However, the importance of environmental cues in the assembly of the leaf endo- and epi-microbiota remains elusive. Here we aimed to investigate the impact of seasonal environmental variations, on the establishment of the leaf microbiome, focusing on long-term changes (five years) in bacterial, fungal, and non-fungal eukaryotic communities colonizing the surface and endosphere of six wildArabidopsis thalianapopulations. While leaf-microbial communities were found to be highly stochastic, the leaf niche had a predominant importance with endophytic microbial communities consistently exhibiting a lower diversity and variability. Furthermore, our analyses revealed that among environmental factors, radiation and humidity-related factors are the most important drivers of diversity paderns in the leaf, albeit with stronger effects on epiphytic communities. Using linear models, we further identified 30 important genera whose relative abundance in leaf compartments could be modeled from environmental variables, suggesting specific niche preferences for these taxa. With the hypothesis that these environmental factors could impact interactions within microbial communities, we analyzed the seasonal paderns of microbial interaction networks across leaf compartments. We showed that epiphytic networks are more complex than endophytic, and that the complexity and connectivity of these networks are partially correlated with the mentioned environmental cues. Our results indicate that humidity and solar radiation function as major environmental cues shaping the phyllosphere microbiome at the micro-scale (leaf compartment) and macro-scale (site). These findings could have practical implications for selecting and developing field-adapted microbes in the face of, and for predicting microbial invasions in response to global change.
Unbiased Complete Estimation of Chloroplast Number in Plant Cells Using Deep Learning Methods
Authors: Su Qun , Liu Le , Hu Zhengsheng , Wang Tao , Wang Huaying , Guo Qiuqi , Liao Xinyi , Dong Zhao , Yang Shaokai , Liu Ningjing , Zhao Qiong
Published: December 2023

Chloroplasts are essential organelles in plants that are involved in plant development and photosynthesis. Accurate quantification of chloroplast numbers is important for understanding the status and type of plant cells, as well as assessing photosynthetic potential and efficiency. Traditional methods of counting chloroplasts using microscopy are time-consuming and face challenges such as the possibility of missing out-of-focus samples or double counting when adjusting the focal position. Here, we developed an innovative approach called Detecting- and-Counting-chloroplasts (D&Cchl) for automated detection and counting of chloroplasts. This approach utilizes a deep-learning-based object detection algorithm called You-Only-Look-Once (YOLO), along with the Intersection Over Union (IOU) strategy. The application of D&Cchl has shown excellent performance in accurately identifying and quantifying chloroplasts. This holds true when applied to both a single image and a three-dimensional (3D) structure composed of a series of images. Furthermore, by integrating Cellpose, a cell-segmentation tool, we were able to successfully perform single-cell 3D chloroplast counting. Compared to manual counting methods, this approach improved the accuracy of detection and counting to over 95%. Together, our work not only provides an efficient and reliable tool for accurately analyzing the status of chloroplasts, enhancing our understanding of plant photosynthetic cells and growth characteristics, but also makes a significant contribution to the convergence of botany and deep learning.

One-sentence summary

This deep learning-based approach enables the accurate complete detection and counting of chloroplasts in 3D single cells using microscopic image stacks, and showcases a successful example of utilizing deep learning methods to analyze subcellular spatial information in plant cells.

The authors responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plcell/) is: Zhao Dong (dongzhao@hebeu.edu.cn), Shaokai Yang, (shaokai1@ualberta.ca), Ningjing Liu (liuningjing1@yeah.net), and Qiong Zhao (qzhao@bio.ecnu.edu.cn).
Iron promotes copper entry inStreptococcus pneumoniae
Authors: Sanchez-Rosario Yamil , Johnson Michael D.L.
Published: December 2023

Metals serve an important function at the host-pathogen interface, being used to leverage bacterial survival. To reduce bacterial viability in the host, some metals such as iron, are sequestered by the host, while others, such as copper are used to intoxicate bacteria. During infection, this serves the dual purpose of starving the bacteria of valuable resources while providing it with a toxic substance. By growingStreptococcus pneumoniae,a causative agent of multiple diseases including pneumonia, middle ear infections and sepsis, in the medium RPMI 1640 with a nanomolar concentration of iron, followed by exposure to a higher concentration of iron and copper, we observed an iron-dependent increase in copper association. This process was specific for iron and conserved in otherS. pneumoniaeserotypes. We performed single and double knockouts in selected iron transport systems and observed that under the same experimental conditions as wild-type strain, there was significantly less copper associated with the iron transport knockout bacteria. Taken together, we conclude that copper is inadvertently imported into the bacterial cell during iron acquisition.
COMPUTATIONAL IDENTIFICATION OF ANTIBODY-BINDING EPITOPES FROM MIMOTOPE DATASETS
Authors: Li Rang , Wilderotter Sabrina , Stoddard Madison , Van Egeren Debra , Chakravarty Arijit , Joseph-McCarthy Diane
Published: December 2023

A fundamental challenge in computational vaccinology is that most B-cell epitopes are conformational and therefore hard to predict from sequence alone. Another significant challenge is that a great deal of the amino acid sequence of a viral surface protein might not in fact be antigenic. Thus, identifying the regions of a protein that are most promising for vaccine design based on the degree of surface exposure may not lead to a clinically relevant immune response. Linear peptides selected by phage display experiments that have high affinity to the monoclonal antibody of interest (“mimotopes”) usually have similar physicochemical properties to the antigen epitope corresponding to that antibody. The sequences of these linear peptides can be used to find possible epitopes on the surface of the antigen structure or a homology model of the antigen in the absence of an antigen-antibody complex structure. Herein we describe two novel methods for mapping mimotopes to epitopes. The first is an ensemble approach, which combines the prediction results from two existing methods. The second is a novel algorithm named MimoTree, that allows for gaps in the mimotopes and epitopes on the antigen. More specifically, a mimotope may have a gap that does not match to the epitope to allow it to adopt a conformation relevant for binding to an antibody and residues may similarly be discontinuous in conformational epitopes. MimoTree is a fully automated epitope detection algorithm suitable for the identification of conformational as well as linear epitopes.
Effects of aging on glucose and lipid metabolism in mice
Authors: Lien Evan C. , Vu Ngoc , Westermark Anna M. , Danai Laura V. , Lau Allison N. , Gültekin Yetiş , Kukurugya Matthew A. , Bennett Bryson D. , Vander Heiden Matthew G.
Published: December 2023

Aging is accompanied by multiple molecular changes that contribute to aging-associated pathologies, such as accumulation of cellular damage and mitochondrial dysfunction. Tissue metabolism can also change with age, in part because mitochondria are central to cellular metabolism. Moreover, the co-factor NAD+, which is reported to decline across multiple tissue types during aging, plays a central role in metabolic pathways such as glycolysis, the tricarboxylic acid cycle, and the oxidative synthesis of nucleotides, amino acids, and lipids. To further characterize how tissue metabolism changes with age, we intravenously infused [U-13C]-glucose into young and old C57BL/6J, WSB/EiJ, and Diversity Outbred mice to trace glucose fate into downstream metabolites within plasma, liver, gastrocnemius muscle, and brain tissues. We found that glucose incorporation into central carbon and amino acid metabolism was robust during healthy aging across these different strains of mice. We also observed that levels of NAD+, NADH, and the NAD+/NADH ratio were unchanged in these tissues with healthy aging. However, aging tissues, particularly brain, exhibited evidence of up-regulated fatty acid and sphingolipid metabolism reactions that regenerate NAD+from NADH. Because mitochondrial respiration, a major source of NAD+regeneration, is reported to decline with age, our data supports a model where NAD+-generating lipid metabolism reactions may buffer against changes in NAD+/NADH during healthy aging.
A genome and tissue-specific transcriptomes of the large-polyp coral,Fimbriaphyllia(Euphyllia)ancora: Recipe for a coral polyp
Authors: Shikina Shinya , Yoshioka Yuki , Chiu Yi-Ling , Uchida Taiga , Chen Emma , Cheng Yin-Chu , Lin Tzu-Chieh , Chu Yu-Ling , Kanda Miyuki , Kawamitsu Mayumi , Fujie Manabu , Takeuchi Takeshi , Zayasu Yuna , Satoh Noriyuki , Shinzato Chuya
Published: December 2023

Coral “polyps” are composed of several tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of the four tissues that comprise polyps: tentacle (Te), mesenterial filament (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral,Fimbriaphyllia ancora. A draftF. ancoragenome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) ofTeare related to biological defense, predation, and coral-algal symbiosis.Meexpresses multiple digestive enzymes, whereasBoexpresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed inMP. The established dataset and new insights into tissue functions will facilitate a deeper understanding of coral biology.
Orbitofrontal Cortex Modulates Auditory Cortical Sensitivity and Sound Perception
Authors: Macedo-Lima Matheus , Hamlette Lashaka Sierra , Caras Melissa L.
Published: December 2023

Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Though decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remains uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving animals under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervate the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing, and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds.

Significance Statement

Sensory perception depends on the context in which stimuli are presented. For example, perception is enhanced when stimuli are informative, such as when they are important to solve a task. Perceptual enhancements result from an increase in the sensitivity of sensory cortical neurons; however, we do not fully understand how such changes are initiated in the brain. Here, we tested the role of the orbitofrontal cortex (OFC) in controlling auditory cortical sensitivity and sound perception. We found that OFC neurons change their activity when animals perform a sound detection task. Inactivating OFC impairs sound detection and prevents task-dependent increases in auditory cortical sensitivity. Our findings suggest that the OFC controls contextual modulations of the auditory cortex and sound perception.
The killifish germline regulates longevity and somatic repair in a sex-specific manner
Authors: Moses Eitan , Atlan Tehila , Sun Xue , Franek Roman , Siddiqui Atif , Marinov Georgi K. , Shifman Sagiv , Zucker David M. , Oron-Gottesman Adi , Greenleaf William J. , Cohen Ehud , Ram Oren , Harel Itamar
Published: December 2023

Classical evolutionary theories propose tradeoffs between reproduction, damage repair, and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. Here, we use the turquoise killifish (N. furzeri) to genetically arrest germline development at discrete stages, and examine how different modes of infertility impact life-history. We first construct a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. Next, we show that germline depletion - but not arresting germline differentiation - enhances damage repair in female killifish. Conversely, germline-depleted males instead showed an extension in lifespan and rejuvenated metabolic functions. Through further transcriptomic analysis, we highlight enrichment of pro-longevity pathways and genes in germline-depleted male killifish and demonstrate functional conservation of how these factors may regulate longevity in germline-depletedC. elegans. Our results therefore demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs.
EFEMP1 contributes to light-dependent ocular growth in zebrafish
Authors: Xie Jiaheng , Bui Bang V. , Goodbourn Patrick T. , Jusuf Patricia R.
Published: December 2023

Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicatesefemp1in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modifyefemp1expression specifically in the retina of zebrafish. We found that under normal lighting,efemp1mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function.Efemp1modification changed the expression ofefemp1,egr1,tgfb1a,vegfabandrbp3genes in the eye, and changes the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins.Efemp1modification also impacted dark-rearing-induced responses ofvegfabandwnt2bgenes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated byefemp1.

This study shows that retina-specific modification ofefemp1expression in zebrafish results in myopic eye, and impacts responses to myopia-inducing dark-rearing in eye growth, retinal function, and myopia-associated molecular expression and distribution, implicating light-dependent regulation ofefemp1in ocular development.
Long-read sequencing of extrachromosomal circular DNA and genome assembly of aSolanum lycopersicumbreeding line revealed active LTR retrotransposons originating fromS. peruvianumL. introgressions
Authors: Merkulov Pavel , Serganova Melania , Petrov Georgy , Mityukov Vladislav , Kirov Ilya
Published: December 2023

Transposable elements (TEs) are a major force in the evolution of plant genomes. Differences in the transposition activities and landscapes of TEs can vary substantially, even in closely related species. Interspecific hybridization, a widely employed technique in tomato breeding, results in the creation of novel combinations of TEs from distinct species. The implications of this process for TE transposition activity have not been studied in modern cultivars. In this study, we used nanopore sequencing of extrachromosomal circular DNA (eccDNA) and identified two highly active Ty1/CopiaLTR retrotransposon families of tomato (Solanum lycopersicum), calledSalsaandKetchup. Elements of these families produce thousands of eccDNAs under controlled conditions and epigenetic stress. EccDNA sequence analysis revealed that the major parts of eccDNA produced byKetchupandSalsaexhibited low similarity to theS. lycopersicumgenomic sequence. To trace the origin of these TEs, whole-genome nanopore sequencing and de novo genome assembly were performed. We found that these TEs occurred in a tomato breeding line via interspecific introgression fromS. peruvianum. Our findings collectively show that interspecific introgressions can contribute to both genetic and phenotypic diversity not only by introducing novel genetic variants, but also by importing active transposable elements from other species.
Ferritinophagy is a Druggable Vulnerability of Quiescent Leukemic Stem Cells
Authors: Larrue Clement , Mouche Sarah , Angelino Paolo , Sajot Maxime , Birsen Rudy , Vergez François , Recher Christian , Mas Véronique Mansat-De , Gu Qiong , Xu Jun , Tsantoulis Petros , Sarry Jean-Emmanuel , Tamburini Jerome
Published: December 2023

Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Leukemic stem cells (LSCs) contributes to therapeutic failure, post-therapy relapse and adverse outcome. Here, we investigated the role of quiescence and its associated molecular mechanisms in AML pathogenesis and LSCs functions, and identified potential vulnerabilities for therapeutic intervention. We found that LSC-enriched quiescent cell population exhibited a distinct gene set of prognostic significance in AML patients. Furthermore, this quiescent cells subset displayed heightened autophagic activity with a reliance on ferritinophagy, a selective form of autophagy mediated by Nuclear Receptor Coactivator 4 (NCOA4) regulating iron bioavailability. Inhibition of NCOA4 genetically or chemically showed potent anti-leukemic effects, particularly targeting the LSC compartment. These findings uncover that ferritinophagy inhibition may represent a promising therapeutic strategy for patients with AML.

One Sentence Summary

Targeting quiescent leukemic stem cells via NCOA4-dependent ferritinophagy inhibition may improve therapeutic outcomes in acute myeloid leukemia.
Disproportion among reticulon-like 16 (RTNLB16) splice variants disrupts growth and decreases sensitivity to ABA and senescence in Arabidopsis
Authors: Khazma Tami , Levi Dikla , Ben-Asher Hiba Waldman , Miller Gad
Published: December 2023

The Reticulon family proteins (RTNs) are membrane-spanning proteins found in the endoplasmic reticulum (ER) with diverse functions, such as ER membrane morphogenesis, vesicle formation, and trafficking. The plant-specific reticulon-like protein family (RTNLBs) comprises multiple members, yet their functions remain poorly understood. The Arabidopsis RTNLB16 gene has seven splice variants, each encoding seven distinct protein isoforms.

We identified an Arabidopsis mutant (Salk_122275/rtnlb16-1) as a knockout for the upper coding frame, isoform 7, of RTNLB16 while overexpressing the other six isoforms through the CaMV 35S promoter at the left border of the T-DNA insertion.rtnlb16-1exhibits distinctive growth retardation and reduced chlorophyll levels. Under photoperiodic long day (16:8 h) conditions, activation of the 35S promoter intensifiesRTNLB16expression in the mutant, resulting in profound growth inhibition. Conversely, growth under continuous low-light (CLL) conditions restrains the overexpression and significantly mitigatesrtnlb16-1phenotype. Confocal microscopy experiments revealed the localization of RTNLB16:GFP in the tubular ER network, plasmodesmata, and potentially in Golgi bodies.

Peculiarly, RTLB16/rtnlb16heterozygote plants exhibit non-Mendelian reduced fertility, suggesting potential involvement of RTNLB16 in reproductive development. Transcriptomics comparisons betweenrtnlb16-1and the wild type under CLL and 16:8h conditions revealed differential gene expression involved in salicylic acid, jasmonic acid, and abscisic acid responses, indicating activation of defense and osmotic stress responses contributing to the growth inhibition in the mutant. We further demonstrate thatrtnlb16has decreased sensitivity to abscisic acid and enhanced tolerance to darkness-induced senescence.

Our findings highlight the importance of balanced expression among RTNLB16 isoforms for normal cellular and physiological activities in Arabidopsis. Additionally, our study underscores the significance of employing T-DNA mutants to investigate genes with multiple splice variants.
Inhibition of MMP 2&9 protects the endothelial glycocalyx and improves diastolic function in diabetic cardiomyopathy
Authors: Buffonge Stanley , Qiu Yan , Fawaz Sarah , Gamez Monica , Crompton Michael , Butler Matthew J , Welsh Gavin I , Madeddu Paolo , Foster Rebecca R , Satchell Simon C
Published: December 2023

The coronary microvascular endothelial glycocalyx (EGlx) is a vital regulator of vascular permeability and EGlx damage contributes to the development of diabetic cardiomyopathy. Matrix metalloproteinases 2 and 9 (MMP2/9) have been identified as key enzymes in the degradation of EGlx components, notably syndecan 4 (SDC4), and are upregulated in diabetes. We tested the hypothesis that inhibition of MMP2/9 can protect the EGlx and improve diastolic function in diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by streptozotocin (STZ) injections. Mice were treated with daily injections of the MMP2/9 inhibitor, SB-3CT, for 2 weeks from 7 weeks post STZ. Echocardiography was utilised to assess heart function and lectin staining for the measurement of EGlx depth. Immunolabelling of heart sections for albumin provided an indication of albumin extravasation. A mechanism of EGlx shedding was investigated in vitro in human coronary microvascular endothelial cells treated with TNF-α and SB-3CT. Diabetic mice developed diastolic dysfunction from 6 weeks post STZ. MMP2/9 inhibition reversed diastolic dysfunction, EGlx thinning and albumin extravasation in diabetic animals. In vitro, TNF-α caused an increase in MMP9 activity and SDC4 shedding from human coronary microvascular endothelial cells. Treatment with SB-3CT reduced MMP9 activity and prevented SDC4 shedding. Knockdown of MMP9 expression prevented TNF-α induced SDC4 shedding. This study demonstrates MMP2/9 inhibition as a strategy to protect the EGlx and improve diastolic function in diabetic cardiomyopathy. Our findings suggest new avenues for therapeutic interventions in cardiovascular complications associated with diabetes.

Statements and Declarations

Competing interests

The authors have no competing interests to declare that are relevant to the content of this article.
Secondary metabolite profiling of Pseudomonas aeruginosa isolates reveals rare genomic traits
Authors: Neve Rachel L , Giedraitis Emily , Akbari Madeline S , Cohen Shirli , Phelan Vanessa V.
Published: December 2023

Pseudomonas aeruginosa is a ubiquitous gram-negative opportunistic pathogen with remarkable phylogenetic and phenotypic variability. In this work, we applied classical molecular networking analysis to secondary metabolite profiling data from seven Pseudomonas aeruginosa strains, including five clinical isolates from the lung secretions of people with cystic fibrosis. Combined with whole-genome sequencing, we show that some P. aeruginosa isolates, including nmFLRO1, produce a previously unreported class of acyl putrescines, isolate SH3A does not produce di-rhamnolipids because its genome belongs to phylogenetic clade 5, and the secondary metabolite profile of isolate SH1B reflects a frame-shift mutation in the quorum sensing regulator rhlR. This study highlights for the first time that secondary metabolite profiling provides unique insight into genetic variation of P. aeruginosa.
A nonneural miRNA cluster mediates hearing via repression of two neural targets
Authors: Zhang Binglong , Duan Hong , Kavaler Joshua , Wei Lu , Eberl Daniel F. , Lai Eric C.
Published: December 2023

We show here thatmir-279/996are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ inDrosophila. Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these seed-related miRNAs function autonomously to suppress neural fate in nonneuronal cells. Finally, genetic interactions pinpoint two neural targets (elavandinsensible) that underlie miRNA mutant JO phenotypes. This work uncovers how critical post-transcriptional regulation of specific miRNA targets governs cell specification and function of the auditory system.
Modeling barriers to adoption of digitization in supply chains using FTOPSIS and its impact on sustainability TBL
Authors: Rane Santosh B. , Abhyankar Gayatri J. , Kirkire Milind Shrikant , Agrawal Rajeev
Published: December 2023

Purpose

This article aims at - exploring and prioritizing the barriers to adoption of digitization in supply chains (SCs), categorizing them into sustainability triple bottom line (STBL) based upon their direct impact and suggesting digital technologies to address each barrier.

Design/methodology/approach

A five-phase methodology is used which consists of an exploration of 44 barriers to the adoption of digitization in SCs, analysis of 44 barriers for mean, standard deviation and Cronbach alpha based on questionnaire-based feedback of 25 experts, extraction of 10 most significant barriers through 05 experts, followed by categorization of the barriers into STBL referring to their direct impact on STBL, prioritization of ten barriers using Fuzzy Technique for Order Performance by Similarity to Ideal Solution and recommendation of digital technologies to address each barrier.

Findings

While all the barriers considered in this study significantly impede the adoption of digitization in SCs, lack of top management commitment (B1) is found to be most crucial while lack of culture toward use of information and communication technology required for digitization (B3) has minimum impact. Large investment in digital infrastructure (B6), difficulty in integration of cyber physical systems (CPSs) on varied platforms (B8) and lack of experts having knowledge of digital technologies (B2) are equally important barriers requiring more attention while adopting digitization in SCs.

Research limitations/implications

This study is mainly based on feedback from 25 seasoned experts; a wider cross section of experts will give more insight.

Practical implications

The outcomes are very significant for organizations looking to adopt digitization in their SCs. Simultaneous consideration to all the barriers becomes impractical hence prioritization of same will be useful for the SC managers to benchmark their preparedness and decide strategies for the adoption of digitization with due consideration toward the impact of barriers on STBL. The digital technologies recommended will further aid in planning the digital strategies to address each barrier.

Originality/value

A unique approach to explore, analyze, prioritize and categorize the barriers to adoption of digitization in SCs is used to provide a deeper understanding of factors deterring the same. It implies that a supportive top management along with systematic allocation of finances plays a crucial role. The importance of availability of digital experts for integrating CPSs on a single platform is also highlighted. The digital technologies recommended will further assist the organizations toward adoption of digitization in SCs with due consideration to STBL.
Exploring the impact of institutional forces on the social sustainability of logistics service providers: insights from a high terrorism-affected region
Authors: Khan Muhammad Naveed , Rafi-ul-Shan Piyya Muhammad , Akhtar Pervaiz , Khan Zaheer , Shamim Saqib
Published: December 2023

Purpose

Achieving social sustainability has become a critical challenge in global supply chain networks, particularly during complex crises such as terrorism. The purpose of this study is to explore how institutional forces influence the social sustainability approaches of logistics service providers (LSPs) in high terrorism-affected regions (HTAR). This then leads to investigating how the key factors interact with Institutional Theory.

Design/methodology/approach

An exploratory multiple-case study research method was used to investigate six cases of different-sized logistics LSPs, each in an HTAR. The data was collected using semistructured interviews and triangulated using on-site observations and document analysis. Thematic analysis was used in iterative cycles for cross-case comparisons and pattern matching.

Findings

The findings interact with Institutional Theory and the three final-order themes. First, management processes are driven by coopetition and innovation. Second, organizational resources, structure and culture lead to an ineffective organizational design. Finally, a lack of institutionalization creates institutional uncertainty. These factors are rooted in many other first-order factors such as information sharing, communication, relationship management, capacity development, new process developments, workforce characteristics, technology, microlevel culture and control aspects.

Originality/value

This study answers the call for social sustainability research and enriches the literature on social sustainability, Institutional Theory and LSPs in HTARs by providing illustrations showing that institutional forces act as driving forces for social sustainability initiatives by shaping the current management processes. Conversely, the same forces impede social sustainability initiatives by shaping the current organizational designs and increasing institutional uncertainty.
Talking with venture capitalists: gender perceptions in investment decisions
Authors: Karlstrøm Birgitte , Jansen Tiril Marie , Solheim Marte C.W.
Published: December 2023

Purpose

The venture capital industry is an important provider of capital to start-ups and has grown considerably in recent decades. This study explores how investors' gender perceptions influence venture capital investment decisions in an industry that remains highly gender imbalanced, both amongst the venture capital decision-makers and with respect to the allocation of capital to entrepreneurs.

Design/methodology/approach

The authors' approach was informed by a thorough literature review and in-depth qualitative interviews with ten decision-makers at some of the foremost venture capital funds in Norway. Interviews were recorded, transcribed and coded using NVivo.

Findings

The authors' findings demonstrate that the Norwegian venture capital industry is influenced by homophily and role congruity. The authors highlight the challenges entrepreneurs face in gaining access to venture capital if they are not already members of the investors' network, a situation that results in a recycling effect that helps maintain the industry’s gender imbalance. Moreover, it appears that venture capitalists (VCs) favour masculine characteristics when assessing entrepreneurs, revealing a potential incongruence between female characteristics and perceived entrepreneurial attributes.

Originality/value

The authors' study contributes to and extends the extant literature on homophily and role congruity. Indeed, through investigating the gender-based perceptions of VCs, the authors shed new light on the mechanisms involved in their assessment of entrepreneurs, as well as on the drivers and barriers affecting female entrepreneurs.
Child labor and youth crime: evidence for Brazil
Authors: Santos Fabrício Rios Nascimento , Lírio Viviani Silva , dos Santos Anderson Moreira Aristides
Published: December 2023

Purpose

In addition to being a violation of human rights, the practice of child labor can be related to criminality against young people. In view of this, the hypothesis tested in this article was that child labor aggravates youth homicide through educational level.

Design/methodology/approach

This study used annual data for the 26 states plus the Federal District for the period 2001 to 2014. To do so, the authors used the iterated feasible generalized least squares (IFGLS) estimator under the seemingly unrelated regressions (SUR) model.

Findings

The results showed that child labor positively affects the homicide of young people, showing education as a transmission channel through which the effect is materialized. The general conclusion, given this, that work is an alternative for children not to enter the world of crime due to its socializing character, cannot be sustained.

Practical implications

This evidence provides input to the formulation of policies and programs to eradicate or slow child labor. In addition to the social and economic rise of individuals, it is important to emphasize the role of education (human capital) in explaining economic growth.

Originality/value

So far, there is no record of national research that sought to empirically assess the effect of child labor on crime, in particular, on the homicide of young people, considering education as a transmission channel, and this assessment is the contribution of the present study to the economic literature on crime.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-03-2023-0163
Exploring collaborative innovation evolution of China’s energy conservation and environmental protection industry: a social network analysis based on patents
Authors: Liu Weiwei , Guo Yuqi , Bi Kexin
Published: December 2023

Purpose

Energy conservation and environmental protection industry (ECEPI) is a strategic choice to promote energy conservation and emission reduction, develop green economy and circular economy. However, China’s ECEPI is still in the stage of rapid development and the overall scale is relatively small, what development periods have the ECEPI experienced? This study aims to contribute to a better understanding of collaborative innovation evolution based on social network analysis from the perspective of multi-dimensional proximity.

Design/methodology/approach

Methodologically, this study uses social network analysis method to explore the co-evolution of multidimensional collaboration networks. It divides China’s ECEPI into four periods based on national policies from 2001 to 2020. This contribution constructs collaborative innovation networks from geographical, technological and organizational proximity.

Findings

The results show that the collaborative innovation network was initially formed in the central region of China, gradually expanded to neighboring cities and the core positions of Beijing, Jiangsu and Guangdong have been continuously consolidated. C02F has been the core of the collaboration networks, and the research focus has gradually shifted from the treatment of wastewater, sewage or sludge to the separation field. Enterprises always occupy a dominant position in the collaboration networks.

Originality/value

This research investigates the dynamic evolution process of collaborative innovation network in China’s ECEPI from the perspective of multidimensional proximity, explores the community structure, important nodes and multidimensional proximity features in the network, expands the research perspective on evolution characteristics of innovative network and the research field of social network analysis. Theoretically, this study enriches collaborative innovation theory, social network theory and multi-dimensional proximity theory.