bluuebunny/crossref_metadata_2025_split huggingface dataset:
SnRK1 acts upstream ofPRODUCTION OF ANTHOCYANIN PIGMENT1, contributing to fine-tuning flavonoid biosynthesis during acclimation
Authors: Dieckmann Josephine , Stracke Ralf , Richter Andreas S. 
Published: June 2024

AbstractIn land plants, one of the processes vital to cope with environmental changes is the accumulation of photoprotective flavonoids such as flavonols and anthocyanins. The inactivation of SUCROSE NON-FERMENTING1 RELATED PROTEIN KINASE1 (SnRK1), which acts in a chloroplast-derived sugar signalling pathway, permits the activation of flavonoid biosynthesis in high-light. The present study provides genetic evidence that SnRK1 acts upstream ofPRODUCTION OF ANTHOCYANIN PIGMENT1 (PAP1), encoding a crucial transcription factor that activates the anthocyanin branch of flavonoid biosynthesis during high-light acclimation. A time-resolved expression analysis indicates a two-step suppression of MYB LIKE2 (MYBL2), a repressor of anthocyanin production, involving SnRK1 inactivation for stable anthocyanin accumulation during prolonged high-light exposure. Furthermore, overexpression ofPAP1resulted in the marked suppression ofMYB11, MYB12andMYB111andFLAVONOL SYNTHASE1, initiating the flavonol branch of the pathway. Analysis of a flavonoid-deficientCHALCONE SYNTHASEmutant overexpressingPAP1suggests that regulation of flavonoid biosynthesis is independent of flavonoid intermediates and end products but PAP1-dependent. It is proposed that PAP1 suppresses the flavonol branch by an as yet unknown mechanism, thereby promoting the consumption of carbon building blocks for anthocyanin production to permit the fine-tuning of the pathway.
Ethylene signaling is essential for mycorrhiza-induced resistance against chewing herbivores in tomato
Authors: Lidoy Javier , Rivero Javier , Ramšak Živa , Petek Marko , Križnik Maja , Flors Victor , Lopez-Raez Juan A. , Martinez-Medina Ainhoa , Gruden Kristina , Pozo Maria J. 
Published: June 2024

SummaryRoot colonization by certain beneficial microbes can prime plant defenses aboveground, modifying plant responses to potential attackers. Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with most plant species, usually enhancing plant resistance to biotic stresses, leading to Mycorrhiza-Induced Resistance (MIR). Still, our knowledge of the complex molecular regulation leading to MIR is very limited. Here we show that the AM fungusFunneliformis mosseaeprotects tomato plants against two different chewing herbivores,Spodoptera exiguaandManduca sexta, and we explore the underlying molecular mechanism.We explore the impact of AM symbiosis on the plant response to the herbivores through genome-wide transcriptional profiling, followed by bioinformatics network analyses and functional bioassays. Herbivore-triggered JA-regulated defenses were primed in leaves of mycorrhizal plants, while ET biosynthesis and signaling was also higher both before and after herbivory. We hypothesized that fine-tuned ET signaling is required for the primed defensive response leading to MIR in mycorrhizal plants. We followed analytical, functional, and genetic approaches to test this hypothesis and get mechanistic insights into the ET signaling in MIR.ET is a complex regulator of plant responses to stress, and although ET is generally considered a negative regulator of plant defenses against herbivory, tomato lines deficient in ET synthesis or perception could not develop MIR against either herbivore. Thus, we demonstrate that hormone crosstalk is central to the priming of plant immunity by beneficial microbes, with ET fine-tuning being essential for the primed JA biosynthesis and boosted defenses leading to MIR in tomato.
Cas12a/3 crRNAs RNP transformation enables transgene-free multiplex genome editing, long deletions, and inversions in citrus chromosome in the T0 generation
Authors: Su Hang , Wang Yuanchun , Xu Jin , Omar Ahmad A. , Grosser Jude W. , Wang Nian 
Published: June 2024

AbstractCitrus canker, caused byXanthomonas citrisubsp. citri (Xcc), is a devastating disease worldwide. Previously, we successfully generated canker-resistantCitrus sinensiscv. Hamlin lines in the T0 generation, achieving a mutation efficiency of 97.4%. This was achieved through the transformation of embryogenic protoplasts using the Cas12a/1 crRNA ribonucleoprotein (RNP) system to edit the canker susceptibility gene,CsLOB1, which led to small indels. Here, we transformed embryogenic protoplasts of Hamlin with Cas12a/3 crRNAs RNP, resulting in 100% efficiency in editing theCsLOB1gene in the T0 generation. Among the 10 transgene-free genome-edited lines, long deletions were obtained in five lines. Additionally, inversions were observed in three of the five edited lines with long deletions, but not in any edited lines with short indel mutations, suggesting long deletions are required for inversions. Biallelic mutations were observed for each of the three target sites in 4 of the 10 edited lines when 3 crRNAs were used, demonstrating that transformation of embryogenic citrus protoplasts with Cas12a/3 crRNAs RNP can be very efficient for multiplex editing. Our analysis revealed the absence of off-target mutations in the edited lines. Thesecslob1mutant lines were canker-resistant and no canker symptoms were observed after inoculation withXccandXccgrowth was significantly reduced in thecslob1mutant lines compared to the wild type plants. Taken together, Cas12a/3 crRNAs RNP transformation of embryogenic protoplasts of citrus provides a promising solution for transgene-free multiplex genome editing with high efficiency and for deletion of long fragments.
The up-regulation of TGF-β1 by miRNA-132-3p/WT1 is involved in inducing leukemia cells to differentiate into macrophages
Authors: Wang Zhimin , Wang Chaozhe , Zhang Danfeng , Wang Xidi , Wu Yunhua , Sun Ruijing , Sun Xiaolin , Li Qing , Bi Kehong , Jiang Guosheng 
Published: June 2024

AbstractAlthough it has been shown that abnormal expression of Wilm’s tumor gene 1 (WT1) is associated with the occurrence of leukemia, the specific mechanism via which it induces leukemia cells to differentiate into macrophages remains poorly understood. Based on the prediction that the microRNA miRNA-132-3p is the miRNA that possibly lies upstream of the WT1 gene, we hypothesized that miRNA-132-3p may participate in the polarization process of macrophages through regulating expression of the WT1 gene. The focus of the present study was therefore to investigate the role of the miRNA-132-3p/WT1 signaling axis in the differentiation of THP-1 leukemia cells into macrophages induced by PMA. The results obtained indicated that, compared with the control group, the proliferation of THP-1 cells was clearly inhibited by PMA, and the cell cycle was arrested at G0/G1 phase, associated with an upregulation of CD11b and CD14 expression. Induced by PMA, the expression level of miRNA-132-3p was increased, WT1 expression was decreased, and the expression level of TGF-β1 was increased. Following transfection with miRNA-132-3p mimics, however, the expression of WT1 in the THP-1 cells was downregulated, with upregulation of the CD11b and CD14 antigens, whereas this downregulation of WT1 mediated by miRNA-132-3p mimics could be reversed by co-transfection with WT1 vector, which was accompanied by downregulation of the CD11b and CD14 antigens. The luciferase activity of the co-transfected miRNA-132-3p mimic + WT1-wild-type (WT) group was found to be statistically significantly lower compared with that of the co-transfected miRNA-132-3p mimic + WT1-mutated (MUT) group. Furthermore, chromatin immunoprecipitation experiments showed that WT1 was able to directly target the promoter of the downstream target gene TGF-β1, which led to the negative modulation of TGF-β1 expression, whereas downregulation of WT1 led to an upregulation of the expression of TGF-β1, which thereby promoted the differentiation of THP-1 cells into macrophages. Taken together, the present study has provided evidence, to the best of the authors’ knowledge for the first time, that the miRNA-132-3p/WT1/TGF-β1 axis is able to regulate the committed differentiation of leukemia cells into macrophages.
Yeast adapts to diverse ecological niches driven by genomics and metabolic reprogramming
Authors: Wang Haoyu , Nielsen Jens , Zhou Yongjin , Lu Hongzhong 
Published: June 2024

AbstractThe famous model organism -Saccharomyces cerevisiaeis widely present in a variety of natural and human-associated habitats. Despite extensive studies of this organism, the metabolic mechanisms driving its adaptation to varying niches remain elusive. We here gathered genomic resources from 1,807S. cerevisiaestrains and assembled them into a high-quality pan-genome, facilitating the comprehensive characterization of genetic diversity across isolates. Utilizing the pan-genome, 1,807 strain-specific genome-scale metabolic models (ssGEMs) were generated, which performed well in quantitative predictions of cellular phenotypes, thus helping to examine the metabolic disparities among allS. cerevisiaestrains. Integrative analyses of fluxomic and transcriptomics with ssGEMs showcased the ubiquitous transcriptional regulation in certain metabolic sub-pathways (i.e., amino acid synthesis) at a population level. Additionally, the gene/reaction loss analysis through the ssGEMs refined by transcriptomics showed thatS. cerevisiaestrains from various ecological niches had undergone reductive evolution at both the genomic and metabolic network levels when compared to wild isolates. Finally, the compiled analyses of the pan-genome, transcriptome, and metabolic fluxome revealed remarkable metabolic differences amongS. cerevisiaestrains originating from distinct oxygen-limited niches, including human gut and cheese environments, and identified convergent metabolic evolution, such as downregulation of oxidative phosphorylation pathways. Together, these results illustrate how yeast adapts to distinct niches modulated by genomic and metabolic reprogramming, and provide computational resources for translating yeast genotype to fitness in future studies.
Assessing the use of RIVPACS-derived invertebrate taxonomic predictions for river management
Authors: Johnson A. , Murray-Bligh J. , Brown L.E. , Milner A.M. , Klaar M.J. 
Published: June 2024

AbstractThe River Invertebrate Prediction and Classification System (RIVPACS) is used widely in freshwater management to set targets for macroinvertebrate ecological health based on the expected scores of metrics such as WHPT or LIFE in the absence of anthropogenic stressors. An underutilised capability of RIVPACS-type models is the capability to predict expected macroinvertebrate community composition, which could function as a novel management metric for river health. We present a novel Monte-Carlo simulation approach that generates simulated expected communities for England’s rivers based on RIVPACS predictions. This allows for assessments of macroinvertebrate health using similarity calculations between observed and expected communities. We assess 10-year trends in similarity between 2010 and 2019 at 4172 sites in England, and contrast these trends with WHPT ASPT O/E trends in the same period. Similarity scores include both Chi-Squared and Hellinger methods, to prioritise rare and common species, respectively. We find that whilst most sites (63.3%) showed improvement in WHPT ASPT O/E in this period, most sites showed declines in similarity for Chi-Squared and Hellinger O/E (51.1% and 58.8%, respectively). We identified three case study regions showing contrasting trends and illustrate how the new RIVPACS-derived similarity calculations can track meaningful shifts in composition associated with water quality and multiple stressors including invasive species. RIVPACS-derived similarity calculations potentially provide a sensitive and practical management metric to assess ecosystem health, although further work is required to understand the composition of communities in changing environments with clear changes in stressor regimes.
Mitochondrial Signatures Shape Phenotype Switching and Apoptosis in Response to PLK1 and RSK Inhibitors in Melanoma
Authors: Lavallée Émilie , Roulet-Matton Maëline , Giang Viviane , Hurtado Roxana Cardona , Chaput Dominic , Gravel Simon-Pierre 
Published: June 2024

SummaryPLK1 inhibitors are emerging anti-cancer agents being tested in monotherapy and combination therapies for various cancers. Although PLK1 inhibition in experimental models shows potent antitumor effects, translation to the clinic has been hampered by low antitumor activity and tumor relapse. Here, we report the identification of mitochondrial protein signatures that determine sensitivity to approaches targeting PLK1 in human melanoma cell lines. In response to PLK1 inhibition or gene silencing, resistant cells adopt a pro-inflammatory and dedifferentiated phenotype, while sensitive cells engage apoptosis. Mitochondrial DNA depletion and silencing of the ABCD1 transporter sensitize cells to PLK1 inhibition and attenuate the associated pro-inflammatory response. We also found that non-selective inhibitors of the p90 ribosomal S6 kinase (RSK) exert their anti-proliferative and pro-inflammatory effects via PLK1 inhibition. This work reveals overlooked impacts of PLK1 on phenotype switching and suggests that mitochondrial precision medicine can help improve response to targeted therapies.
Residual force enhancement is not altered while force depression is amplified at the cellular level in old age
Authors: Njai Binta S. , Hinks Avery , Patterson Makenna A. , Power Geoffrey A. 
Published: June 2024

AbstractResidual force enhancement (rFE) and residual force depression (rFD) are history-dependent properties of muscle which refer to increased and decreased isometric force following a lengthening or shortening contraction, respectively. The history-dependence of force is greater in older than younger adults when assessed at the joint level. However, it is unclear whether this amplification of the history-dependence of force in old age is owing to cellular mechanisms or a consequence of age-related remodeling of muscle architecture. Single muscle fibres from the psoas major of old and young F344BN rats were dissected and chemically permeabilized. Single muscle fibres were mounted between a force transducer and length controller, then maximally activated (pCa 4.5). To assess rFD, fibers were actively shortened from 3.1 to 2.5µm at both a slow (0.15Lo/s) and fast (0.6Lo/s) speed, with a fixed-end isometric reference contraction at 2.5µm. To assess rFE, fibers were activated and stretched at 0.3Lo/s from a sarcomere length of 2.2 to 2.5µm, and 2.7 to 3.0µm, and compared to fixed-end isometric reference contractions at 2.5 and 3.0µm, respectively. Isometric force was ≈19% lower in old as compared with young (p<0.001). Upon normalizing to fibre cross-sectional area, there was no age-related difference in specific force (p>0.05). rFD was ≈33% greater in old as compared with young (p<0.05), while rFE did not differ between groups (p>0.05). rFD is amplified in old age at the cellular level, while rFE appears to be unchanged, thus previously reported age-related modification of rFE occurs upstream from the cellular level.
Predicting and Monitoring Symptoms in Diagnosed Depression Using Mobile Phone Data: An Observational Study
Authors: Ikäheimonen Arsi , Luong Nguyen , Baryshnikov Ilya , Darst Richard , Heikkilä Roope , Holmen Joel , Martikkala Annasofia , Riihimäki Kirsi , Saleva Outi , Isometsä Erkki , Aledavood Talayeh 
Published: June 2024

AbstractBackgroundClinical diagnostic assessments and outcome monitoring of patients with depression rely predominantly on interviews by professionals and the use of self-report questionnaires. The ubiquity of smartphones and other personal consumer devices has prompted research into the potential of data collected via these devices to serve as digital behavioral markers for indicating presence and monitoring of outcome of depression.ObjectiveThis paper explores the potential of using behavioral data collected with mobile phones to detect and monitor depression symptoms in patients diagnosed with depression.MethodsIn a prospective cohort study, we collected smartphone behavioral data for up to one year. The study consists of observations from 99 subjects, including healthy controls (n=25) and patients diagnosed with various depressive disorders: major depressive disorder (MDD) (n=46), major depressive disorder with comorbid borderline personality disorder (MDD|BPD) (n=16), and bipolar disorder with major depressive episodes (MDE|BD) (n=12). Data were labeled based on depression severity, using the 9-item Patient Health Questionnaire (PHQ-9) scores. We performed statistical analysis and employed supervised machine learning on the data to classify the severity of depression and observe changes in the depression state over time.ResultsWe identified 32 behavioral markers associated with the changes in depressive state. Our analysis classified depressed subjects with an accuracy of 82% and depression state transitions with an accuracy of 75%.ConclusionsThe use of mobile phone digital behavioral markers to supplement clinical evaluations may aid in detecting the presence and relapse of clinical depression and monitoring its outcome, particularly if combined with intermittent use of self-report of symptoms.
Protocol for the development of Pituitary Surgery Core Outcomes and Priorities (PitCOP)
Authors: Newall Nicola , Valetopoulou Alexandra , Khan Danyal Z , Borg Anouk , Bremner Fion , Dorward Neil , Fleseriu Maria , Ginn Joy , Gurnell Mark , Korbonits Marta , Serrano Inma , Baldeweg Stephanie E , Kolias Angelos G , Marcus Hani J 
Published: June 2024

AbstractObjectivesWe aim to (i) identify the most important research priorities in pituitary surgery through a priority setting partnership (PSP) and (ii) develop a core outcome set (COS) for pituitary surgery research.DesignInternational modified Delphi consensus processes.SubjectsParticipants are key stakeholders in pituitary surgery, including: healthcare professionals (HCPs) (nurse specialists, neurosurgeons, endocrinologists, ophthalmologists, otolaryngologists, radiologists, pathologists, and oncologists); service users (patients, family members and carers); and charity representatives.MethodsIn PSP round one, participants are asked what questions relating to diagnosis, treatment, long-term care and follow-up they would like answered by future research. Responses will be grouped thematically, and a systematic literature review will identify which research priorities remain unanswered. In round two, participants will rank their top 10 unanswered research priorities.In COS round one, participants are presented with an initial list of outcomes identified from relevant literature,1,2and asked to (i) rate outcomes based on perceived importance for inclusion in a core outcome set, and (ii) suggest additional outcomes. In round two, participants will re-score each outcome, while considering the summarised group scores from round one.The final round of PSP and COS will be held as a live consensus workshop (with equal representation of stakeholder groups) to determine the top 10 research priorities and the final core outcome set.ResultsThe study is currently underway, and aims to be complete by August 2024.ConclusionsThe PitCOP study will establish patient-centred research priorities and a core outcome set for pituitary surgery research. This will help to improve the relevance, efficiency, and quality of future pituitary surgery research.
A multi-trait approach identified seven novel genes for back pain-related phenotypes
Authors: Belonogova Nadezhda M. , Elgaeva Elizaveta E. , Zorkoltseva Irina V. , Kirichenko Anatoliy V. , Svishcheva Gulnara R. , Freidin Maxim B. , Williams Frances M. K. , Suri Pradeep , Axenovich Tatiana I. , Tsepilov Yakov A. 
Published: June 2024

AbstractBack pain (BP) is a major contributor to disability worldwide. We conducted a cross-sectional study analyzing three BP-related phenotypes: chronic BP (CBP), dorsalgia and intervertebral disc disorders (IDD), with heritability estimated at 40-60%. Less than half of the heritability is explained by common genetic variants identified by GWAS. More powerful methods of statistical analysis may offer additional insight. Using imputed genotypes from the UK Biobank we performed a multi-trait gene-based association analysis of three BP-related phenotypes: CBP, dorsalgia, and IDD. We identified and replicated 16 genes associated with BP-related traits. Seven of the detected genes, namely,MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, andRERG, were previously unreported. Several new genes have been previously detected as associated with traits genetically correlated with BP or as included in pathways associated with BP. Our results verify the role of these genes in BP-related traits and provide new insights into the genetics of back pain.
Traveling wave chemotaxis of neutrophil-like HL-60 cells
Authors: Ishida Motohiko , Uwamichi Masahito , Nakajima Akihiko , Sawai Satoshi 
Published: June 2024

AbstractThe question of how changes in chemoattractant concentration translate into the chemotactic response of immune cells serves as a paradigm for the quantitative understanding of how cells perceive and process temporal and spatial information. Here, using a microfluidic approach, we analyzed the migration of neutrophil-like HL-60 cells to a traveling wave of the chemoattractants fMLP and leukotriene B4 (LTB4). We found that under a pulsatile wave that travels at a speed of 95 and 170 µm/min, cells move forward in the front of the wave but slow down and randomly orient at the back due to temporal decrease in the attractant concentration. Under a slower wave, cells re-orient and migrate at the back of the wave; thus, cell displacement is canceled out or even becomes negative as cells chase the receding wave. FRET-based analysis indicated that these patterns of movement correlated well with spatiotemporal changes in Cdc42 activity. Furthermore, pharmacological perturbations suggested that migration in front of the wave depends on Cdc42, whereas that in the back of the wave depends more on PI3K/Rac and ROCK. These results suggest that pulsatile attractant waves may recruit or disperse neutrophils, depending on their speed and degree of cell polarization.Significance statementThe way neutrophil chemotaxis is directed by attractants is thought to depend on temporal and spatial concentration changes, however the response to a transient pulsatile stimulus has not been well explored.A moderately fast traveling wave of fMLP and leukotrieneB4 (LTB4) directs unidirectional cell migration. Under slow waves, cells respond to the back of the wave; thus, cell displacement is canceled out. Cdc42, PI3K, Rac, and ROCK contributed differently to responses at the front and back of the wave.These findings suggest that traveling waves of attractant can guide immune cell recruitment and dispersal.
Crystal structure ofAnophelesgambiae actin depolymerizing factor explains high affinity to monomeric actin
Authors: Lasiwa Devaki , Kursula Inari 
Published: June 2024

AbstractActin is an intrinsically dynamic protein, the function and state of which are modulated by actin-binding proteins. Actin depolymerizing factors (ADF)/cofilins are ubiquitous actin-binding proteins that accelerate actin turnover. Malaria is an infectious disease caused by parasites of the genusPlasmodium, which belong to the phylum Apicomplexa. The parasites require two hosts to complete their life cycle: the definitive host, or the vector, which is anAnophelesspp. mosquito, and a vertebrate intermediate host, such as humans. Here, the crystal structure of the malaria vectorAnopheles gambiaeADF (AgADF) is reported.AgADF has a conserved ADF/cofilin fold with six central β-strands surrounded by five α-helices with a long β-hairpin loop protruding out of the structure. The G and F-actin binding sites ofAgADF are conserved, and the structure shows features of potential importance for regulation by membrane binding and redox state.AgADF binds monomeric ATP- and ADP-actin with a high affinity, having a nanomolar Kd, and binds to and effectively destabilizes actin filaments.