bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of significant genome-wide associations and QTL underlying variation in seed protein composition in pea (Pisum sativumL.)
Authors: Warsame Ahmed O. , Balk Janneke , Domoney Claire 
Published: July 2024

AbstractPea seeds are a valuable source of plant proteins for human and animal nutrition and have various industrial applications. The relative abundance of different seed storage proteins affects protein quality, including digestibility and functional properties of protein extracts. Thus, understanding the genetic basis of seed protein composition is crucial to enhance protein quality and nutritional value through breeding. In this study, we employed two complementary approaches, Genome-Wide Association Study (GWAS) and Quantitative Trait Locus (QTL) mapping, to identify genetic loci underlying seed protein composition in pea. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to separate the seed proteins, and their relative abundance was quantified using densitometric analysis. For GWAS, we analysed a diverse panel of 209 accessions genotyped with an 84,691 SNP array and identified genetic loci significantly associated with globulins, such as convicilin, vicilin, legumins; and non-globulins, including lipoxygenase, late embryogenesis abundant protein (LEA), and annexin-like protein. Additionally, using QTL mapping with 96 recombinant inbred lines (RILs), we mapped 11 QTL, including five that overlapped with regions identified by GWAS for the same proteins. Within these regions, we identified structural genes for seed proteins and other genes with predicted functions in protein biosynthesis, trafficking, and modification. This comprehensive genetic mapping study serves as a foundation for future breeding efforts to improve protein quality in pea and other legumes.
The Impact of a Polyphenol-Rich Supplement on Epigenetic and Cellular Markers of Immune Age: A Pilot Clinical Study
Authors: Perlmutter Austin , Bland Jeffrey S. , Chandra Arti , Malani Sonia S. , Smith Ryan , Mendez Tavis L. , Dwaraka Varun B. 
Published: July 2024

AbstractAge-related alterations in immune function are believed to increase risk for a host of age-related diseases leading to premature death and disability. Programming of the immune system by diet, lifestyle, and environmental factors occurs across the lifespan and influences both makeup and function of the immune system. This programming is believed to act in large part through epigenetic modification.One group of dietary molecules linked to generally healthier aging and relative immune resilience and homeostasis are polyphenols, which are consumed by humans primarily in the form of plant foods. While polyphenols are widely distributed throughout the plant and fungal kingdoms, certain foods are known to possess distinctive and relatively higher levels of these compounds. One such food is Tartary buckwheat (fagopyrum tataricum), an ancient seed historically prized for its health benefits. It is suggested that the specific composition of polyphenols found in foods like Tartary buckwheat may lead to a unique impact on longevity-related physiological pathways that could be interrogated through immune and epigenetic analyses.The objective of this study was to investigate the epigenetic effects on peripheral immune cells in healthy individuals of a standardized polyphenol concentrate based on naturally occurring nutrients in Tartary buckwheat. A pilot clinical trial was designed to test the effects of consuming 90 days of this concentrate on immune cell epigenetic methylation patterns and immune cell phenotypes in 50 healthy male (40%) and female (60%) participants aged 18-85 years using epigenetic age clocks and deconvolution methods. Analysis revealed significant intervention-related changes in multiple epigenetic age clocks and immune markers as well as population-wide alterations in gene ontology (GO) pathways related to longevity and immunity. This study provides previously unidentified insights into the immune, longevity and epigenetic effects of consumption of polyphenol-rich plants and generates additional support for health interventions built around historically consumed plants like Tartary buckwheat while offering compelling opportunities for additional research.
Insights into the RNA virome of the corn leafhopperDalbulus maidis, a major emergent threat of Maize in Latin America
Authors: Debat Humberto , Farrher Esteban Simon , Bejerman Nicolas 
Published: July 2024

AbstractThe maize leafhopper (Dalbulus maidis) is a significant threat to maize crops in tropical and subtropical regions, causing extensive economic losses. While its ecological interactions and control strategies are well-studied, its associated viral diversity remains largely unexplored. Here, we employ high-throughput sequencing data mining to comprehensively characterize theD. maidisRNA virome, revealing novel and diverse RNA viruses. We characterized six new viral members belonging to distinct families, with evolutionary cues of beny-like viruses (Benyviridae), bunya-like viruses (Bunyaviridae) iflaviruses (Iflaviridae), orthomyxo-like viruses (Orthomyxoviridae), and rhabdoviruses (Rhabdoviridae). Phylogenetic analysis of the iflaviruses places them within the genusIflavirusin affinity with other leafhoppers-associated iflaviruses. The five-segmented and highly divergent orthomyxo-like virus showed a relationship with other insect associated orthomyxo-like viruses. The rhabdo virus is related with a leafhopper associated rhabdo-like virus. Furthermore, the beny-like virus belonged to a cluster of insect-associated beny-like viruses, while the bi-segmented bunya-like virus was related with other bi-segmented insect-associated bunya-like viruses. These results highlight the existence of a complex virome linked toD. maidisand paves the way for future studies investigating the ecological roles, evolutionary dynamics, and potential biocontrol applications of these viruses on theD. maidis—maize pathosystem.
Identification of P-type ATPase as a bacterial transporter for host-derived small RNA
Authors: Dong Pu-Ting , Yang Mengdi , Cen Lujia , Zhou Peng , Xu Difei , Xiong Peng , Wu Chenggang , Li Jiahe , He Xuesong 
Published: July 2024

ABSTRACTHost-derived small RNAs represent a finely tuned host response to maintain the host-microbial homeostasis. Among these, an emerging class known as transfer RNA-derived small RNA (tsRNA) has been implicated in modulating microbial-host interaction. Our previous study showed that when challenged with an oral pathobiont,Fusobacterium nucleatum (Fn), an immortalized human oral keratinocyte cell line releases certainFn-targeting tsRNAs that selectively inhibit the growth ofFnvia their ribosome-targeting function. We also revealed the sequence- and energy-dependent uptake of tsRNAs byFn. However, the mechanism underlying the tsRNA uptake at the molecular level remains elusive. In this study, using RNA affinity pull-down assay in combination with Mass Spectrometry, we identified a putative P-type ATPase transporter (PtaT) inFn, which bindsFn-targeting tsRNAs in a sequence-specific manner. AlphaFold 3 simulation provides further evidence supporting the specific binding between PtaT and tsRNA compared to the scrambled control and the DNA counterpart. Through targeted mutagenesis and phenotypic characterization, we demonstrated the important role of PtaT in the uptake and antimicrobial capacity of tsRNAs againstFnin both ATCC 23726 type strain and a clinical tumor isolate (FnCTI). Furthermore, global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences betweenFnwild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Collectively, our work identifies a bacterial transporter for tsRNAs and provides critical information for a fundamental understanding of how the host-generated tsRNAs specifically interact with its targeted bacteria at the molecular level.
Valence and Salience Encoding in the Central Amygdala
Authors: Kong Mi-Seon , Ancell Ethan , Witten Daniela M. , Zweifel Larry S. 
Published: July 2024

AbstractThe central amygdala (CeA) has emerged as an important brain region for regulating both negative (fear and anxiety) and positive (reward) affective behaviors. The CeA has been proposed to encode affective information in the form of valence (whether the stimulus is good or bad) or salience (how significant is the stimulus), but the extent to which these two types of stimulus representation occur in the CeA is not known. Here, we used single cell calcium imaging in mice during appetitive and aversive conditioning and found that majority of CeA neurons (∼65%) encode the valence of the unconditioned stimulus (US) with a smaller subset of cells (∼15%) encoding the salience of the US. Valence and salience encoding of the conditioned stimulus (CS) was also observed, albeit to a lesser extent. These findings show that the CeA is a site of convergence for encoding oppositely valenced US information.
Non canonical activation of the ESCRT machinery is required for division ofLeishmania donovaniparasitophorous vacuoles and parasite persistence
Authors: Rosero Javier , Kima Peter E. 
Published: July 2024

AbstractIn the mammalian host,L. donovaniare intracellular pathogens that reside in vacuolar compartments (often calledLeishmaniaparasitophorous vacuoles (LdLPVs)). LdLPVs harbor individual parasites that enigmatically divide upon replication of the parasite. In this study, we evaluated the role of the ESCRT machinery in the division of LdLPVs and parasite persistence in infected cells. We found that the ESCRT I member, TSG101 and the ESCRT III members, CHMP2B and CHMP4B are recruited to LdLPVs. In addition, Vps4a, an accessory molecule required for recycling of ESCRT III molecules is also recruited to LdLPVs. Interestingly, infection of cells expressing a dominant negative version of Vps4a that prevents the recycling of ESCRT III revealed that most LdLPVs recruit ESCRT components constitutively. Based on that finding, we proposed that the recruitment of ESCRT molecules to LdLPVs is enabled by the display of the phosphoinositide, PI(3,4)P2 on LdLPVs. To assess the functional importance of recruiting ESCRT molecules to LdLPVs, we monitoredL. donovaniinfections in cells in which ALIX or TSG101 were knocked down. ALIX knock down resulted in LdLPVs that were distended and harbored 4 or more parasites, which is significantly different from LdLPVs in ‘wild type’ macrophages that harbor at most, 2 parasites. Moreover, reduced levels of ALIX resulted in a significant reduction in parasite numbers. These findings revealed the critical role for activation of the ALIX-ESCRTIII axis inL. donovanipathogenesis. This is the first demonstration that the ESCRT machinery plays a role in the division of pseudo-organelles that harbor an intracellular pathogen.SignificanceThe endosomal sorting complex required for transport (ESCRT) machinery plays critical mechanistic roles in physiological processes including cell division (cytokinesis). It can be hijacked to promote the spread and persistence of infectious agents including in the budding of viruses and nutrient acquisition by intracellular pathogens. In this study, we uncover a new role for the ESCRT machinery in the infection of macrophages byLeishmania donovani(Ld). Within infected cells, each Ld parasite resides in aLeishmaniaparasitophorous vacuole (LPV) that enigmatically divides to accommodate daughter parasites. We show that a non-canonical activation of the ESCRT machinery is required for division of LPVs and for parasite persistence. Future studies on the mechanisms for selective activation of the ESCRT machinery would reveal targets for the control of this deadly pathogen.
Elraglusib induces cytotoxicity via direct microtubule destabilisation independently of GSK3 inhibition
Authors: Coats Josh T. , Li Shuyu , Tanaka Tomoyuki U. , Tauro Sudhir , Sutherland Calum , Saurin Adrian T. 
Published: July 2024

AbstractElraglusib (9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3) with pre-clinical studies demonstrating broad activity against many tumour types. Promising early-phase clinical trial data led to FDA orphan drug status, and a randomized phase 2 study in combination with cytotoxic chemotherapy in pancreatic cancer has recently completed its recruitment. Similarly, single-agent responses in adult T-cell leukaemia/lymphoma and melanoma, and combination treatment data in several other tumour types have been encouraging. The elraglusib mechanism of action is unknown, but it is unlikely to act through GSK3 inhibition because cytotoxicity is observed below the IC50for GSK3 and other small molecule GSK3 inhibitors do not produce cytotoxic effects, at least in lymphoma cells. We show here that elraglusib perturbs chromosomal alignment to cause a mitotic arrest in multiple tumour lines. This arrest is caused by direct microtubule depolymerisation, which prevents the attachment of kinetochores to microtubules. At clinically relevant doses, these mitotically arrested cells eventually undergo mitotic slippage, leading to gross chromosome missegregation, DNA damage and apoptosis. These effects explain the cytotoxicity of elraglusib because temporarily pausing cell cycle progression with the CDK4/6 inhibitor palbociclib abolishes any drug-induced genotoxicity and apoptosis. In summary, elraglusib acts as a potent direct microtubule destabilizer bothin vitroand across multiple cancer types, resulting in mitotic arrest, DNA damage and apoptosis. These effects likely account for its broad pan-cancer activity, which does not rely upon GSK3 inhibition as they are not replicated by other GSK3 inhibitors.
MINFLUX fluorescence nanoscopy in biological tissue
Authors: Moosmayer Thea , Kiszka Kamila A. , Westphal Volker , Pape Jasmin K. , Leutenegger Marcel , Steffens Heinz , Grant Seth G. N. , Sahl Steffen J. , Hell Stefan W. 
Published: July 2024

AbstractOptical imaging access to nanometer-level protein distributions in intact tissue is a highly sought-after goal, as it would provide visualization in physiologically relevant contexts. Under the unfavorable signal-to-background conditions of increased absorption and scattering of the excitation and fluorescence light in the complex tissue medium, super-resolution fluorescence microscopy methods are severely challenged in attaining precise localization of molecules. We reasoned that the typical use of a confocal detection pinhole in MINFLUX nanoscopy, suppressing background and providing optical sectioning, should facilitate the detection and resolution of single fluorophores even amid scattering and optically challenging tissue environments. Here, we investigated the performance of MINFLUX imaging for different synaptic targets and fluorescent labels in tissue sections of the mouse brain. Single fluorophores were localized with a precision of<5 nm at up to 80 µm sample depth. MINFLUX imaging in two color channels allowed to probe PSD95 localization relative to the spine head morphology, while also visualizing presynaptic VGlut clustering and AMPA receptor clustering at the post-synapse. Our two-dimensional (2D) and three-dimensional (3D) two-color MINFLUX results in tissue, with<10 nm 3D fluorophore localization, open up new avenues to investigate protein distributions on the single-synapse level in fixed and living brain slices.
INF2-mediated actin polymerization at ER-organelle contacts regulates organelle size and movement
Authors: Schiavon Cara R. , Wang Yuning , Feng Jasmine W. , Garrett Stephanie , Sung Tsung-Chang , Dayn Yelena , Wang Chunxin , Youle Richard J. , Quintero-Carmona Omar A. , Shadel Gerald S. , Manor Uri 
Published: July 2024

AbstractProper regulation of organelle dynamics is critical for cellular function, but the mechanisms coordinating multiple organelles remain poorly understood. Here we show that actin polymerization mediated by the endoplasmic reticulum (ER)-anchored formin INF2 acts as a master regulator of organelle morphology and movement. Using high-resolution imaging, we demonstrate that INF2-polymerized actin filaments assemble at ER contact sites on mitochondria, endosomes, and lysosomes just prior to their fission. Genetic manipulation of INF2 activity alters the size, shape and motility of all three organelles. Our findings reveal a conserved mechanism by which the ER uses actin polymerization to control diverse organelles, with implications for understanding organelle dysfunction in neurodegenerative and other diseases. This work establishes INF2-mediated actin assembly as a central coordinator of organelle dynamics and inter-organelle communication.
Einstein from Noise: Statistical Analysis
Authors: Balanov Amnon , Huleihel Wasim , Bendory Tamir 
Published: July 2024

Abstract“Einstein from noise” (EfN) is a prominent example of the model bias phenomenon: systematic errors in the statistical model that lead to erroneous but consistent estimates. In the EfN experiment, one falsely believes that a set of observations contains noisy, shifted copies of a template signal (e.g., an Einstein image), whereas in reality, it contains only pure noise observations. To estimate the signal, the observations are first aligned with the template using cross-correlation, and then averaged. Although the observations contain nothing but noise, it was recognized early on that this process produces a signal that resembles the template signal! This pitfall was at the heart of a central scientific controversy about validation techniques in structural biology.This paper provides a comprehensive statistical analysis of the EfN phenomenon above. We show that the Fourier phases of the EfN estimator (namely, the average of the aligned noise observations) converge to the Fourier phases of the template signal, explaining the observed structural similarity. Additionally, we prove that the convergence rate is inversely proportional to the number of noise observations and, in the high-dimensional regime, to the Fourier magnitudes of the template signal. Moreover, in the high-dimensional regime, the Fourier magnitudes converge to a scaled version of the template signal’s Fourier magnitudes. This work not only deepens the theoretical understanding of the EfN phenomenon but also highlights potential pitfalls in template matching techniques and emphasizes the need for careful interpretation of noisy observations across disciplines in engineering, statistics, physics, and biology.
Feasibility of Incorporating More Walking into Commuting with Public Transportation
Authors: Hadas Yuval , Katz Dan Emanuel , Rabinowitz Jonathan 
Published: July 2024

AbstractRegular physical activity is vital for improving and maintaining overall health. Despite this, many people struggle to incorporate physical activity into their daily lives. Previous studies, based primarily on simulations and synthetic data, have reported the potential for increased walking resulting from mode shifts in public transport (PT). This suggests that it may be possible for PT commuters to meet some of their physical activity goals while commuting. PT users rely on trip planning apps, but these apps do not currently prioritize walking as part of the journey. This research is aimed at investigating the potential of more walking on PT accessibility and level of service. It is the first stage of the More Walking population-based wellness initiative aimed at facilitating more walking by modifying trip planning apps to increase walking. For this phase of the project, we examined the impact of various walking thresholds using a trip planning algorithm and conducted a study of the feasibility of increasing walking thresholds among all 2,149 commuters to the same work destination in a suburb of Tel-Aviv. We found that when more walking is introduced, more potential trips are available, more origins are covered--meaning better accessibility, waiting time is decreased, less transfers are required and that it can reduce total travel time. The results are encouraging that introducing more walking into a commute will be a feasible way to increase physical activity and promote wellness.
Diel changes in the expression of a marker gene and candidate genes for intracellular amorphous CaCO3biomineralization inMicrocystis
Authors: Bruley Apolline , Gaëtan Juliette , Gugger Muriel , Pancrace Claire , Millet Maxime , Gaschignard Geoffroy , Dezi Manuela , Humbert Jean-François , Leloup Julie , Skouri-Panet Fériel , Callebaut Isabelle , Benzerara Karim , Duprat Elodie 
Published: July 2024

ABSTRACTPhylogenetically diverse cyanobacteria biomineralize intracellular amorphous calcium carbonate (iACC) inclusions. This includes several genotypes of theMicrocystisgenus, a potentially toxic, bloom-forming cyanobacterium found worldwide in freshwater ecosystems. While we ignore the biological function of iACC and the molecular mechanisms driving their formation, this process may impact local geochemical cycles and/or be used for bioremediation strategies. Recently, a marker gene of this biomineralization pathway, namedccyA, was discovered. However, the function of the calcyanin protein encoded byccyAremains unknown. Here, based on an RNA- Seq approach, we assess the expression of theccyAgene inMicrocystis aeruginosaPCC 7806 during a 24 h day/night cycle. TheccyAgene shows a clear day/night expression pattern with maximum transcript abundances during the second half of the night. This is consistent with the assumption that iACC biomineralization is related with photosynthesis and may therefore follow a day/night cycle as well. Moreover, several genes directly co-localized upstream and downstream ofccyA, on the same DNA strand show a similar expression pattern, including acaxgene encoding a calcium/proton exchanger and a gene encoding a protein with a domain also present in the N-terminal region of calcyanins in many iACC-forming cyanobacteria. This suggests that they all could be part of an operon, and may play a concerted role in iACC formation. Last, several other genes involved in carbon concentrating mechanisms and calcium transport show an expression pattern similar to that ofccyA. Overall, this study provides a list of candidate genes that may be involved in the biomineralization of iACC by cyanobacteria and whose role could be, in the future, analyzed by biochemistry and genetics approaches.
Unveiling reversibility and plasticity in cardiac hypertrophy: insights from a transverse aortic constriction-release model
Authors: Shiraishi Manabu 
Published: July 2024

AbstractTransverse aortic constriction (TAC) is a well-established animal model used to study the pathomechanisms of pressure overload-induced heart failure. A number of studies have shown that treatment of the heart failure in this model may reverse the associated hypertrophy and fibrosis. However, because no TAC-release model in which hemodynamics improve upon alleviation of the physical stenosis has yet been established, the histologic changes and regulatory molecular biological mechanisms underlying the reversibility of cardiac hypertrophy and fibrosis are unknown. This study was conducted to establish an animal TAC-release model and thereby investigate the mechanisms that govern reversibility and plasticity of myocardial hypertrophy, fibrosis, and angiogenesis. TAC surgery was performed on rats, and 4 weeks later TAC release was achieved by cutting the constricting threads. TAC-subjected heart exhibited severe myocardial hypertrophy, fibrosis, and increased angiogenesis, along with diastolic dysfunction. Heart released from TAC showed reduced hypertrophy and fibrosis and improved diastolic function. Gene expression analysis uncovered regulator of calcineurin 1 (Rcan1) as a key player in cardiac function and histologic changes after TAC release.Rcan1knockdown exacerbated myocardial hypertrophy and fibrosis in heart released from TAC. The left ventricular afterload relief model revealed that increased oxidative stress andRcan1upregulation, which suppresses the calcineurin-NFAT pathway, are key to structural and functional recovery from pressure overload-induced cardiac hypertrophy.