bluuebunny/crossref_metadata_2025 huggingface dataset:
Patho-transcriptomic analysis of invasive mucinous adenocarcinoma of the lung (IMA): comparison with lung adenocarcinoma with signet ring cell features (SRCC)
Authors: Stuart William D. , Ito Masaoki , Baldauf Iris-Fink , Fukazawa Takuya , Yamatsuji Tomoki , Tsuchiya Tomoshi , Watanabe Hideo , Okada Morihito , Snyder Eric L. , Mino-Kenudson Mari , Guo Minzhe , Maeda Yutaka
Published: June 2024

Background

Invasive mucinous adenocarcinoma (IMA) comprises ∼5% of lung adenocarcinoma. There is no effective therapy for IMA when surgical resection is not possible. IMA is sometimes confused with adenocarcinoma with signet ring cell features (SRCC) pathologically since both adenocarcinomas feature tumor cells with abundant intracellular mucin. The molecular mechanisms by which such mucin-producing lung adenocarcinomas develop remain unknown.

Methods

Using a Visium spatial transcriptomics approach, we analyzed IMA and compared it with SRCC patho-transcriptomically. Combining spatial transcriptomics data within vitrostudies using RNA-seq and ChIP-seq, we assessed downstream targets of transcription factors HNF4A and SPDEF that are highly expressed in IMA and/or SRCC.

Results

Spatial transcriptomics analysis indicated that there are 6 distinct cell clusters in IMA and SRCC. Notably, two clusters (C1 and C3) of mucinous tumor cells exist in both adenocarcinomas albeit at a different ratio. Importantly, a portion of genes (e.g.,NKX2-1,GKN1,HNF4AandFOXA3) are distinctly expressed while some mucous-related genes (e.g.,SPDEFandFOXA2) are expressed in both adenocarcinomas. We determined that HNF4A inducesMUC3A/BandTM4SF4and that BI 6015, an HNF4A antagonist, suppressed the growth of IMA cells. Using mutant SPDEF that is associated with COVID-19, we also determined that an intact DNA-binding domain of SPDEF is required for SPDEF-mediated induction of mucin genes (MUC5AC,MUC5BandAGR2). Additionally, we found that XMU-MP-1, a SPDEF inhibitor, suppressed the growth of IMA cells.

Conclusion

These results revealed that IMA and SRCC contain heterogenous tumor cell types, some of which are targetable.
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

In 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

Root 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

Citrus 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

Although 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

The 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.
Cryptic Variation in Adaptive Phenotypes Revealed by PanspecificflcMutants
Authors: Lutz Ulrich , Bezrukov Ilja , Schwab Rebecca , Yuan Wei , Kollmar Marius , Weigel Detlef
Published: June 2024

The study of mutants is one of the best tools for understanding the genetic basis of phenotypes that contribute to adaptation. Oddly, mutant analyses are almost always restricted to single genetic backgrounds and findings therefore can not be easily generalized. A case in point is the key regulator of flowering,FLOWERING LOCUS C(FLC), which has been inferred to explain much of the flowering time variation inArabidopsis thaliana, yet mutants have been examined in very few backgrounds. We have previously established a set of panspecificflcmutants in 62 accessions ofA. thaliana(Ruffley et al. 2024). Here, we investigate how genetic background modulates mutant effects on flowering and vegetative traits, as well as on physiology and transcriptomes. Time to onset of flowering in the genome-editedflclines was reduced by up to 83%, but considerable variation remained. Genetic mapping showed that extremely early flowering in the absence ofFLCwas mostly explained by natural variation at the known FLC targetFT, with additional contribution from loci colocalizing withFLC. Prognostic sequence analyses of accessions did not suggest that extremely-early combinations of engineeredflcand naturalFTalleles would be deleterious, yet extremely early flowering accessions are not represented in the commonly used collections ofA. thalianaaccessions. To test whether this discrepancy could be due to sampling bias, we undertook a focused collection effort of wild populations in Southern Italy, which confirmed that extremely early flowering accessions exist in natural populations. Apart from its specific role in flowering time regulation,FLChas pleiotropic effects on other ecophysiological traits such as growth, and these were also dependent on the genetic background, which was further supported by transcriptomic comparisons. Together we conclude that the various roles ofFLChave greatly diversified in different genetic backgrounds. Our study provides a proof-of-concept on how analysis of panspecific mutants can reveal the true extent of genetic networks in which a focal gene participates in.
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

The 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

PLK1 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

Residual 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

Background

Clinical 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.

Objective

This paper explores the potential of using behavioral data collected with mobile phones to detect and monitor depression symptoms in patients diagnosed with depression.

Methods

In 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.

Results

We 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%.

Conclusions

The 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

Objectives

We 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.

Design

International modified Delphi consensus processes.

Subjects

Participants 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.

Methods

In 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.

Results

The study is currently underway, and aims to be complete by August 2024.

Conclusions

The 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

Back 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

The 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 statement

The 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

Actin 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.
Forecasting the adoption and spread of a community-based marine management initiative using agent-based models
Authors: Jørgensen Andreas Christ Sølvsten , Pienkowski Thomas , Clark Matthew , Dunn Mathilda , Jagadish Arundhati , Bellot Alvaro Roel , Mangubhai Sangeeta , Tawake Alifereti , Vakalalabure Margaret Tabunakawai , Waqa Elisabeta , O’Garra Tanya , Govan Hugh , Shahrezaei Vahid , Mills Morena
Published: June 2024

While many successful initiatives for conserving nature exist, efforts to take them to scale have been inadequate. Moreover, conservation science currently lacks a systematic methodology for determining if or when interventions will reach effective scales and how programmatic decisions will affect the scaling process. This paper presents a modelling framework that aims to address both issues by operationalizing Diffusion of Innovations theory and local knowledge using agent-based modelling and Bayesian inference. By applying our framework to existing data on the spatiotemporal adoption of a community-based marine management initiative in Fiji, we demonstrate that our approach can identify the mechanisms that govern the observed adoption patterns. In this case, the relative advantage of the intervention, village social networks, and perceived knowledge stand out as important drivers of adoption. Using the identified causal processes, our approach can forecast business-as-usual and counterfactual future scenarios and hence inform conservation policy. Finally, we highlight the importance of spatiotemporal data for making detailed scaling predictions. We structure the paper as a step-by-step guide, highlighting our modelling decisions and possible limitations. Thus, besides presenting a case study, this paper serves as a template for practitioners and researchers to better model the scaling process of other conservation interventions.
Low-dimensional olfactory signatures of fruit ripening and fermentation
Authors: Zhou Yuansheng , O’Connell Thomas F. , Ghaninia Majid , Smith Brian H. , Hong Elizabeth J. , Sharpee Tatyana O.
Published: June 2024

Odors provide an important communication channel between plants and animals. Fruits, vital nutrient sources for animals, emit a complex array of monomolecular volatiles. Animals can use the structure of these mixtures to assess properties of fruit predictive of their nutritive and reproductive value. We analyzed the statistics of fruit odor mixtures sampled across stages of ripening and fermentation to find that they fall on a low-dimensional hyperbolic map. Hyperbolic maps, with their negative curvature and an exponentially expanding state options, are adept at describing hierarchical relationships in the data such as those arising from metabolic processes within fruits. In the hyperbolic map, samples followed a striking spiral trajectory. The spiral initiated near the map’s core, representing the under-ripe phase with specific profiles of monomolecular volatiles. Progressively mapping along the unfolding spiral trajectory were scent mixtures corresponding to ripening, and then rotting or fermentation. The unfolding process depended on the specific fermentation processes that dominated in the samples, determined largely by the microbes (e.g. bacteria or yeast) present in the sample. These results generalized across fruit types and describe trajectories in the natural odorant space with significant behavioral relevance for insects.
Data processing of product ion spectra: Methods to control false discovery rate in compound search results for non-targeted metabolomics
Authors: Matsuda Fumio
Published: June 2024

In non-targeted metabolomics utilizing high-resolution mass spectrometry, several database search methods have been used to comprehensively annotate the acquired product ion spectra. Recent advancements in variousin silicoprediction techniques have facilitated compound searches by scoring the degree of coincidence between a query product ion spectrum and a compound in a compound database. Certain search results may be false positives, thus necessitating a method for controlling the false discovery rate (FDR). This study proposed two simple methods for controlling the FDR in compound search results. In the pseudo-target decoy method, the FDR can be estimated without creating a separate decoy database by treating such as the positive ion mode spectra as targets and converting the negative ion mode spectra as decoys. Further, the second-rank method uses the score distribution of the second-ranked hits from the compound search as an approximation of the false-positive distribution of the top-ranked hits. The performance of these methods was evaluated by annotating the product ion spectra from

MassBank using the SIRIUS 5 CSI:Finger ID scoring method. The results indicated that the second-rank method was closer to the true FDR of 0.05. When applied to the four human metabolomics datasets, the second-rank method provided more conservative FDR estimations than the pseudo-target-decoy method. These methods enabled the identification of metabolites not present in human metabolome databases. Overall, this study demonstrates the utility of these simple methods for FDR control in non-targeted metabolomics, facilitating more reliable compound identification and the potential discovery of novel metabolites.
Structural connectivity matures along a sensorimotor-association connectional axis in youth
Authors: Xu Xiaoyu , Yang Hang , Cong Jing , Sydnor Valerie , Cui Zaixu
Published: June 2024

Childhood and adolescence are associated with protracted developmental remodeling of cortico-cortical structural connectivity. However, how heterochronous development in white matter structural connectivity spatially and temporally unfolds across the macroscale human connectome remains unknown. Leveraging non-invasive diffusion MRI data from both cross-sectional (N = 590) and longitudinal (baseline: N = 3,949; two-year follow-up: N = 3,155) developmental datasets, we found that structural connectivity development diverges along a pre-defined sensorimotor-association (S-A) connectional axis from ages 8.1 to 21.9 years. Specifically, we observed a continuum of developmental profiles that spans from an early childhood increase in connectivity strength in sensorimotor-sensorimotor connections to a late adolescent increase in association-association connectional strength. The S-A connectional axis also captured spatial variations in associations between structural connectivity and both higher-order cognition and general psychopathology. Together, our findings reveal a hierarchical axis in the development of structural connectivity across the human connectome.
Atomic-scale mechanisms of GDP extraction by SOS1 in KRAS-G12 and KRAS-D12 oncogenes
Authors: Hu Zheyao , Martí Jordi
Published: June 2024

The guanine exchange factor SOS1 is a crucial node into the positive feedback regulation of the KRAS signaling pathway. Currently, the regulation of KRAS-SOS1 interactions and KRAS downstream effector proteins has become a new hotspot in the development of KRAS-driven cancer therapies. However, the detailed dynamic mechanisms of SOS1-catalyzed GDP extraction and the impact of KRAS mutations remain unknown. Herein, the main mechanisms of GDP extraction from KRAS oncogenes by means of the guanine exchange factor SOS1 are disclosed and described with full details at the atomic-level. For GDP-bound wild-type KRAS, four amino acids (Lys811, Glu812, Lys939 and Glu942) responsible for the catalytic function of SOS1 were identified. With the occurrence of KRAS-G12D mutation, the GDP extraction rate is significantly increased. The molecular interactions behind this phenomenon have been subsequently identified being mainly hydrogen bonding interactions between the mutated residue Asp12 and a positively charged pocket located at the intrinsically disordered region807−818and composed by Ser807, Trp809, Thr810 and Lys811. Our findings provide new insights into the SOS1-KRAS interactions and facilitate the development of related anti-cancer strategies based on the blockage of the above described mechanisms.
Chiral photoelectron spectroscopy using unpolarized light
Authors: Suzuki Yoshi-Ichi
Published: June 2024

This Letter studies the symmetry properties of general vector correlations resulting from one-photon excitation of chiral molecules. We show that the parity-odd second rank tensor is nonzero for molecules in all chiral point groups Cn, Dn, T, O, and I. This chirality-sensitive tensor is nonzero even for chiral isotopomers excited by linearly polarized or even unpolarized light. We develop an irreducible tensor theory based on Curie's limiting groups. As an example of vector correlations, recoil-frame photoelectron angular distributions (RFPADs) are calculated for methyloxirane and CHFCl35Cl37. The difference in the RFPAD between a chiral molecule and its mirror image reaches ±35% of the maximum value for the RFPAD for unpolarized light and ±55% of the value for linearly polarized light. Chiral sensitivity in vector correlation is a quite general phenomenon arising from one-photon excitation by unpolarized and linearly polarized light, and we expect it to be of great importance in time-resolved spectroscopy of ultrafast chemical reactions.

Published by the American Physical Society
2024
Spin Hall effect: Symmetry breaking, twisting, and giant disorder renormalization
Authors: Perkins David T. S. , Veneri Alessandro , Ferreira Aires
Published: June 2024

Atomically thin materials based on transition-metal dichalcogenides and graphene offer a promising avenue for unlocking the mechanisms underlying the spin Hall effect (SHE) in heterointerfaces. Here we develop a microscopic theory of the SHE for twisted van der Waals heterostructures that fully incorporates twisting and disorder effects and illustrate the critical role of symmetry breaking in the generation of spin Hall currents. We find that an accurate treatment of vertex corrections leads to a qualitatively and quantitatively different SHE than that obtained from the popular iη and ladder approximations. A pronounced oscillatory behavior of skew-scattering processes with twist angle θ is predicted, reflecting a nontrivial interplay of Rashba and valley-Zeeman effects and yields a vanishing SHE for θ=30∘ and, for graphene-WSe2 heterostructures, an optimal SHE for θ≈17∘. Our findings reveal disorder and broken symmetries as important knobs to optimize interfacial SHEs.

Published by the American Physical Society
2024
Mixed-species charge and baryon balance functions studies with PYTHIA
Authors: Pruneau Claude , Basu Sumit , Gonzalez Victor , Hanley Brian , Marin Ana , Dobrin Alexandru F. , Manea Alexandru
Published: June 2024

Mixed species charge and baryon balance functions are computed based on proton-proton (pp) collisions simulated with the PYTHIA8 model. Simulations are performed with selected values of the collision energy s and the Monash tune and the ropes and shoving modes of PYTHIA8 to explore whether such measurements provide useful new information and constraints on mechanisms of particle production in pp collisions. Charge balance functions are studied based on mixed pairs of pions, kaons, and protons, whereas baryon balance functions are computed for mixed low mass strange and nonstrange baryons. Both charge and baryon balance functions of mixed particle pairs feature shapes and amplitudes that sensitively depend on the particle considered owing largely to the particle production mechanisms implemented in PYTHIA. The evolution of balance functions integrals with the longitudinal width of the acceptance are presented and one finds that sums of such integrals for a given reference particle obey expected sum rules for both charge and baryon balance functions. Additionally, both types of balance functions are found to evolve in shape and amplitude with increasing collision energy s and the PYTHIA tunes considered.

Published by the American Physical Society
2024
Transient internal wave excitation of resonant modes in a density staircase
Authors: Bracamontes-Ramirez Joel , Sutherland Bruce R.
Published: June 2024

The density of the ocean generally increases continuously with depth as a consequence of variations in salinity and temperature. In some regions, however, the density profile of the ocean adopts a (double diffusive) staircase structure in which successive layers of uniform density fluid are separated by rapid density jumps. Previous work has theoretically examined the transmission and reflection of periodic internal (gravity) waves incident upon a density staircase. This predicted the existence of transmission spikes (global modes) for certain combinations of frequency and horizontal wave number in which the incident waves transmit perfectly across a density staircase. It was hypothesized that the transmission spikes occur when the incident waves resonate with natural modes of disturbances in the staircase. Here we derive theory to investigate the interactions between incident internal waves and modes. We demonstrate a close correspondence between the frequency for incident waves at a transmission spike and the real part of the frequency of modes at the same horizontal wave number. However, the frequency of the corresponding modes has a negative imaginary part corresponding to exponential decay of the modes in time. We perform numerical simulations to examine the impact of this near-resonant coupling when a vertically localized, quasimonochromatic internal wave packet interacts with a density staircase. In a range of simulations with fixed incident wave frequency and varying horizontal wave number, the measured transmission coefficient does not exhibit transmission spikes, but decreases monotonically with increasing horizontal wave number about the critical wave number separating strong and weak transmission. We show this occurs because the incident wave excites modes that then slowly transmit energy above and below the staircase at a rate consistent with the predicted decay rate of the modes. This rate is slower for staircases with more steps with the decay time increasing as the cube of the number of steps.

Published by the American Physical Society
2024
Consumer attitudes in the ecological sociotechnical transition: a comparative study between Argentina, Brazil, China, France and Italy
Authors: Cunha Christiano França da , Xavier Laura dos Santos , Nunes Rubens , Silva Vivian Lara
Published: June 2024

Purpose

This article investigated how consumer choices guided by their underlying microfoundations can either facilitate or hinder socio-technical transitions in the agri-food system. To this end, consumers from five countries (Argentina, Brazil, China, France and Italy) were asked to choose products common to the food basket of these five countries (coffee, yogurt and chicken) with different sensorial and ecological attributes.

Design/methodology/approach

To this end, 1,417 interviews were carried out in these countries. Data were collected on four choices (from the most sustainable to the least sustainable) as well as sociodemographic elements and whether or not the price was mentioned. These choices were observed using two logit models (A and B).

Findings

The article provides evidence that the propensity to choose ecologically beneficial foods is affected by country, gender, income and level of formal education as well as by the microfoundations of choice, such as individual values and attitudes.

Practical implications

To offer truly sustainable products, it is essential to take into account the role of countries and the microfoundations of their inhabitants’ food choices. By recognizing this crucial element, we can raise the probability of successful eco-friendly products, reducing their impact on the environment and enhancing welfare.

Social implications

According to the results observed in this paper, to truly offer sustainable products, we must take into account the microfoundation and the sociotechnological transition elements. By doing so, we hope that efforts toward sustainability not only benefit the environment but also the surrounding communities. So, paying attention to consumers' food choice process helps to create products that are truly sustainable in every sense of the word and will benefit very much the society, in other words, will have a greater social implication.

Originality/value

This article makes a significant contribution to the theory by revealing how micro-foundations driving consumers' choices toward sustainable food products can accelerate the ecological sociotechnical transition in agri-food systems. By shedding light on this crucial aspect, we can pave the way for a more sustainable future.
Multi-central bank digital currencies arrangements: a multivocal literature review
Authors: Sood Kirti , Singh Simarjeet
Published: June 2024

Purpose

The present study aims to systematically synthesize the academic and industrial literature on multi-central bank digital currencies (m-CBDCs) arrangements.

Design/methodology/approach

The study adopted a unique multivocal literature review methodology that considers both white and grey literature. For white literature searches, the study relied on Scopus, Web of Science (WOS), and Google Scholar bibliometric databases; for grey literature searches, the study used the Google search engine.

Findings

The findings of the study illustrated that M-CBDC arrangements, through various design options, have the potential to revolutionize the contemporary international payment system. M-CBDC arrangements will lead to more integrated financial systems and promote economic growth. However, m-CBDC arrangements will also have serious macroeconomic implications, such as contagion and currency substitution risks.

Research limitations/implications

The present review is one of the earliest reviews of m-CBDC arrangements. In addition, the findings of the study offer valuable insights for both academicians and policymakers.

Originality/value

The study is also one of the pioneer studies in management studies that apply a multivocal literature review methodology.