bluuebunny/crossref_metadata_2025 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

Pea 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

Age-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

The 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

Host-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.
A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates
Authors: Hossain Md. Faruk , Popsuj Sydney , Vitrinel Burcu , Kaplan Nicole A. , Stolfi Alberto , Christiaen Lionel , Ruggiu Matteo
Published: July 2024

In mammals, neuromuscular synapses rely on clustering of acetylcholine receptors (AChRs) in the muscle plasma membrane, ensuring optimal stimulation by motor neuron-released acetylcholine neurotransmitter. This clustering depends on a complex pathway based on alternative splicing of Agrin mRNAs by the RNA-binding proteins Nova1/2. Neuron-specific expression of Nova1/2 ensures the inclusion of small "Z" exons in Agrin, resulting in a neural-specific form of this extracellular proteoglycan carrying a short peptide motif that is required for binding to Lrp4 receptors on the muscle side, which in turn stimulate AChR clustering. Here we show that this intricate pathway is remarkably conserved in Ciona robusta, a non-vertebrate chordate in the tunicate subphylum. We use in vivo tissue-specific CRISPR/Cas9-mediated mutagenesis and heterologous "mini-gene" alternative splicing assays in cultured mammalian cells to show that Ciona Nova is also necessary and sufficient for Agrin Z exon inclusion and downstream AChR clustering. We present evidence that, although the overall pathway is well conserved, there are some surprising differences in Nova structure-function between Ciona and mammals. We further show that, in Ciona motor neurons, the transcription factor Ebf is a key activator of Nova expression, thus ultimately linking this RNA switch to a conserved, motor neuron-specific transcriptional regulatory network.
Valence and Salience Encoding in the Central Amygdala
Authors: Kong Mi-Seon , Ancell Ethan , Witten Daniela M. , Zweifel Larry S.
Published: July 2024

The 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.
Acidotolerant soil nitrite oxidiser 'CandidatusNitrobacter laanbroekii' NHB1 alleviates constraints on growth of acidophilic soil ammonia oxidisers
Authors: Hink Linda , Bachtsevani Ella , Meng Yiyu , Sedlacek Christopher J , Lee Sungeun , Daims Holger , Wagner Michael , Gubry-Rangin Cecile , de Boer Wietse , Hazard Christina , Prosser James I , Nicol Graeme W
Published: July 2024

Nitrobacterstrain NHB1 is a nitrite-oxidising bacterium previously co-enriched with the neutrophilic ammonia-oxidising bacteriumNitrosospiraAHB1, a consortium that nitrifies in acidic conditions in co-culture. Here we characterise the growth of the isolateNitrobacterstrain NHB1 as a function of pH and nitrite (NO2-) concentration, and its influence on the activity of acidophilic soil ammonia-oxidising archaea (AOA). NHB1 is acidotolerant and grows optimally at pH 6.0 (range 5.0 - 7.5) at initial NO2-concentrations of 500 μM. However, the optimum decreases to pH 5.0 at lower initial NO2-concentrations typically found in soil, with detectable growth down to pH 3.5. NHB1 has a comparatively high affinity for NO2-with an apparent-half-saturation constant (54 μM) one order of magnitude lower than its closest relative, the neutrophilic strainNitrobacter hamburgensisX14. In co-culture, NHB1 enhances the growth of acidophilic AOA. Specifically,Nitrosotalea devaniterraeNd1 andNitrosotalea sinensisNd2 are sensitive to NO2--derived compounds and only oxidise ~200-300 μM ammonia (NH3) in batch cultures. However, in co-culture with NHB1, pH ranges were lowered by ~0.5 pH units and both strains could oxidise up to 3 mM NH3, only limited by buffering capacity. NHB1 possesses a cyanase facilitating reciprocal cross-feeding via generating cyanate-derived NH3and utilising AOA-derived NO2-. Removal of NO2-is likely crucial for the growth of nitrifiers in acidic soils and this study highlights the importance of considering substrate and metabolic product concentrations when characterising physiology. Genome analysis reveals NHB1 is distinct from validated species and the name "Nitrobacter laanbroekii" is proposed.
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

In 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.

Significance

The 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

Abstract

Elraglusib (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

Optical 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

Proper 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

“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

Regular 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

Phylogenetically 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

Transverse 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.
Jellyfish blooms - an overlooked hotspot and potential vector for the transmission of antimicrobial resistance in marine environments
Authors: Elena Alan X. , Orel Neža , Fang Peiju , Herndl Gerhard J. , Berendonk Thomas U. , Tinta Tinkara , Klümper Uli
Published: July 2024

Jellyfish, and gelatinous zooplankton (GZ) in general, represent an important component of marine food webs. Certain GZ species are capable of generating massive blooms of severe environmental impact. These blooms are often followed by a sudden collapse of the entire population, introducing considerable amounts of organic matter (GZ-OM) in the ocean’s interior. GZ-OM represents an abundant substrate to promote bacterial growth and copious colonizable surface for microbial interactions. Hence we hypothesized that this GZ-OM serves as a yet overlooked hotspot for transmitting antimicrobial resistance genes (ARGs) in marine environments. For this we experimentally evolved and analyzed marine microbial communities in microcosms in presence and absence of OM from scyphozoanAurelia auritas.l. and ctenophoreMnemiopsis leidyi. Communities evolved under GZ-OM exposure displayed an up to 4-fold increase in relative ARG and an up to 10-fold increase in abundance of horizontally transferable mobile genetic elements (MGEs) per 16S rRNA gene copy compared to the controls. This trait was consistent across ARG and MGE classes and independent of the GZ species, suggesting that the underlying mechanism is indeed based on the general influx of nutrients and colonizable surfaces. Potential ARG carriers included known key GZ-OM degraders, but also genera containing potential pathogens hinting towards an increased risk of ARG transfer to pathogenic strains. Here,Vibriowere pinpointed as potential key species directly associated with several significantly elevated ARGs and MGEs. Subsequent whole-genome sequencing of aVibrioisolate from the microcosm experiment revealed the genetic potential for the mobilization and transfer of ARGs in GZ-OM degrading microbial consortia. With this study, we established the first link between two emerging issues of marine coastal zones, jellyfish blooms and AMR spread, both likely increasing in projected future ocean scenarios.
Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct expression patterns and potential markers of progression
Authors: Wang Yuefan , Lih T. Mamie , Lee Jae W. , Ohtsuka Takao , Hozaka Yuto , Mino-Kenudson Mari , Adsay N. Volkan , Luchini Claudio , Scarpa Aldo , Maker Ajay V. , Kim Grace E. , Paulino Jorge , Chen Lijun , Jiao Liyuan , Sun Zhenyu , Goodman Davina , Pflüger Michael J. , Roberts Nicholas J. , Matthaei Hanno , Wood Laura D. , Furukawa Toru , Zhang Hui , Hruban Ralph H.
Published: July 2024

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies.

Significance

This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.
Exploring potential of AI usage in the knowledge and evidence services of a public health body: a working group approach
Authors: Simmons Zalaya , Bruce Charlotte , Thomas Samuel , Lacey Patricia , Marsh Wendy , Rosenberg Scott , Duval Daphne
Published: July 2024

The UK Health Security Agency (UKHSA)’s Knowledge and Library Services (KLS) established an Artificial Intelligence (AI) working group in 2022 to explore potential applications of AI of relevance to its function. This paper describes the working group’s approach to testing and evaluating AI and machine learning-assisted tools for information retrieval and evidence review processes, including duplicate reference removal, citation searching, title and abstract screening, full text screening, data extraction and critical appraisal. Initial tests have demonstrated varying degrees of potential for implementation, while also contributing to broader discussions on ethical considerations, copyright and licensing issues, transparency of AI methodology and evidence integrity. This overview outlines the methodology used and insights gained from navigating the rapidly evolving AI landscape and its potential implications for knowledge and library services within a public health organisation.
Knowledge, uptake and intention to use antibiotic post-exposure prophylaxis and meningococcal B vaccine (4CMenB) for gonorrhoea among a large, online community sample of gay, bisexual and other men who have sex with men in the UK
Authors: Ogaz Dana , Edney Jessica , Phillips Dawn , Mullen Dolores , Reid David , Wilkie Ruth , Buitendam Erna , Bell James , Lowndes Catherine M , Hughes Gwenda , Fifer Helen , Mercer Catherine H , Saunders John , Mohammed Hamish
Published: July 2024

Introduction

Novel STI prevention interventions, including doxycycline post-exposure prophylaxis (doxyPEP) and meningococcal B vaccination (4CMenB) against gonorrhoea, have been increasingly examined as tools to aid STI control. There is emerging evidence of the efficacy of doxyPEP in preventing bacterial STIs; however limited data exist on the extent of use in the UK. We examined self-reported knowledge and use of antibiotic post-exposure prophylaxis (PEP), and intention to use (ITU) doxyPEP and 4CMenB among a large, community sample of gay, bisexual and other men who have sex with men (GBMSM) in the UK.

Methods

Using data collected by the RiiSH survey (November/December 2023), part of a series of online surveys of GBMSM in the UK, we describe (%, [95% CI]) self-reported knowledge and use of antibiotic PEP (including doxyPEP) and doxyPEP and 4CMenB ITU. Using bivariate and multivariable logistic regression, we examined correlates of ever using antibiotic PEP, doxyPEP ITU, and 4CMenB ITU, respectively, adjusting for sociodemographic characteristics and a composite marker of sexual risk defined as reporting (in the last three months): ≥5 condomless anal sex partners, bacterial STI diagnosis, chemsex, and/or meeting partners at sex-on-premises venues, sex parties, or cruising locations.

Results

Of 1,106 participants (median age: 44 years [IQR: 34-54]), 34% (30%-37%) knew of antibiotic PEP; 8% (6%-10%) ever reported antibiotic PEP use. Among those who did, most reported use in the last year (84%, 73/87) and exclusively used doxycycline (69%, 60/87). Over half of participants reported doxyPEP ITU (51% [47%-56%]) while over two-thirds (64% [60%-69%]) reported 4CMenB ITU. GBMSM with markers of sexual risk and with uptake of other preventative interventions were more likely to report ever using antibiotic PEP as well as doxyPEP and 4CMenB ITU, respectively. HIV-PrEP users and people living with HIV (PLWHIV) were more likely to report STI prophylaxis use and ITU than HIV-negative GBMSM not reporting recent HIV-PrEP use.

Discussion

There were high levels of intended use of novel STI prevention interventions. Fewer than one in ten GBMSM had reported ever using antibiotic PEP, with usage more common among those at greater risk of STIs. Future guidelines and health promotion for 4CMenB and antibiotic PEP must be carefully crafted alongside clinical experts and community partners, given intervention complexity and the risk of presenting conflicting public health messages regarding antimicrobial stewardship.
The protease ADAMTS5 controls ovarian cancer cell invasion, downstream of Rab25
Authors: Yuan Shengnan , Bacchetti Rachele , Adams Jamie , Rainero Elena
Published: July 2024

Ovarian cancer is the 3rdmost common gynaecological malignancy worldwide, with a 5-year survival rate of less than 30% in the presence of metastasis. Metastatic progression is characterised by extensive remodelling of the extracellular matrix, primarily mediated by secreted matrix metalloproteinases, including members of the ‘a disintegrin and metalloprotease with thrombospondin motif’ (ADAMTS) family. In particular, ADAMTS5 has been reported to be upregulated in ovarian malignant tumours compared to borderline and benign lesions, suggesting it might play a role in metastatic progression. Furthermore, it has been suggested that Rab25, a small GTPase of the Ras family, might upregulate ADAMTS5 expression in ovarian cancer cells. Here we demonstrated that Rab25 promotes ADAMTS5 expression, through the activation of the NF-κB signalling pathway. Furthermore, ADAMTS5 was necessary and sufficient to stimulate ovarian cancer cell migration through complex fibroblast-secreted matrices, while ADAMTS5 inhibition prevented ovarian cancer spheroid invasion in 3D systems. Finally, in ovarian cancer patients high ADAMTS5 expression correlated with poor prognosis. Altogether, these data identify ADAMTS5 as a novel regulator of ovarian cancer cell migration and invasion, suggesting it might represent a novel therapeutic target to prevent ovarian metastasis.
Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue
Authors: Venkat Aarthi , Carlino Maximillian J. , Lawton Betty R. , Prasad Manju L. , Amodio Matthew , Gibson Courtney E. , Zeiss Caroline J. , Youlten Scott E. , Krishnaswamy Smita , Krause Diane S.
Published: July 2024

Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adultM. mulattareveals a continuous trajectory of epithelial cell states. Pseudotime analysis based on transcriptomic signatures suggests a progression fromGCM2hiprogenitors to mature parathyroid hormone (PTH)–expressing epithelial cells with increasing core mitochondrial transcript abundance along pseudotime. We sequenced, as a comparator, four histologically characterized hyperfunctioning human parathyroids with varying oxyphil and chief cell abundance and leveraged advanced computational techniques to highlight similarities and differences from non-human primate parathyroid expression dynamics. Predicted cell–cell communication analysis reveals abundant endothelial cell interactions in the parathyroid cell microenvironment in both human and NHP parathyroid glands. We show abundantRARRES2transcripts in both human adenoma and normal primate parathyroid cells and use coimmunostaining to reveal high levels of RARRES2 protein (also known as chemerin) in PTH-expressing cells, which could indicate that RARRES2 plays an unrecognized role in parathyroid endocrine function. The data obtained are the first single-cell RNA transcriptome to characterize nondiseased parathyroid cell signatures and to show a transcriptomic progression of cell states within normal parathyroid glands, which can be used to better understand parathyroid cell biology.
Comparative genomics ofCryptosporidium parvumreveals the emergence of an outbreak-associated population in Europe and its spread to the United States
Authors: Bellinzona Greta , Nardi Tiago , Castelli Michele , Batisti Biffignandi Gherard , Adjou Karim , Betson Martha , Blanchard Yannick , Bujila Ioana , Chalmers Rachel , Davidson Rebecca , D'Avino Nicoletta , Enbom Tuulia , Gomes Jacinto , Karadjian Gregory , Klotz Christian , Östlund Emma , Plutzer Judith , Rimhanen-Finne Ruska , Robinson Guy , Sannella Anna Rosa , Sroka Jacek , Stensvold Christen Rune , Troell Karin , Vatta Paolo , Zalewska Barbora , Bandi Claudio , Sassera Davide , Cacciò Simone M.
Published: July 2024

The zoonotic parasiteCryptosporidium parvumis a global cause of gastrointestinal disease in humans and ruminants. Sequence analysis of the highly polymorphicgp60gene enabled the classification ofC. parvumisolates into multiple groups (e.g., IIa, IIc, Id) and a large number of subtypes. In Europe, subtype IIaA15G2R1 is largely predominant and has been associated with many water- and food-borne outbreaks. In this study, we generated new whole-genome sequence (WGS) data from 123 human- and ruminant-derived isolates collected in 13 European countries and included other available WGS data from Europe, Egypt, China, and the United States (n = 72) in the largest comparative genomics study to date. We applied rigorous filters to exclude mixed infections and analyzed a data set from 141 isolates from the zoonotic groups IIa (n = 119) and IId (n = 22). Based on 28,047 high-quality, biallelic genomic SNPs, we identified three distinct and strongly supported populations: Isolates from China (IId) and Egypt (IIa and IId) formed population 1; a minority of European isolates (IIa and IId) formed population 2; and the majority of European (IIa, including all IIaA15G2R1 isolates) and all isolates from the United States (IIa) clustered in population 3. Based on analyses of the population structure, population genetics, and recombination, we show that population 3 has recently emerged and expanded throughout Europe to then, possibly from the United Kingdom, reach the United States, where it also expanded. The reason(s) for the successful spread of population 3 remain elusive, although genes under selective pressure uniquely in this population were identified.
Tight quantum depth lower bound for solving systems of linear equations
Authors: Wang Qisheng , Zhang Zhicheng
Published: July 2024

Since Harrow [A. W. Harrow, A. Hassidim, and S. Lloyd, ] showed that a system of linear equations with N variables and condition number κ can be solved on a quantum computer in poly[log(N),κ] time, exponentially faster than any classical algorithms, its improvements and applications have been extensively investigated. The state-of-the-art quantum algorithm for this problem is due to Costa [P. C. S. Costa, D. An, Y. R. Sanders, Y. Su, R. Babbush, and D. W. Berry, ], with optimal query complexity Θ(κ). An important question that is left is whether parallelism can bring further optimization. In this paper, we study the limitation of parallel quantum computing on this problem. We show that any quantum algorithm for solving systems of linear equations with time complexity poly[log(N),κ] has a lower bound of Ω(κ) on the depth of queries, which is tight up to a constant factor.

Published by the American Physical Society
2024
Deterministic preparation of a dual-species two-ion crystal
Authors: Zawierucha Maximilian J. , Rehmert Till , Keller Jonas , Mehlstäubler Tanja E. , Schmidt Piet O. , Wolf Fabian
Published: July 2024

The demand for efficient preparation methods for dual-species ion crystals is rapidly expanding across quantum technology and fundamental physics applications with trapped ions. We present a deterministic and efficient technique to produce such crystals, utilizing the segmented structure of a linear Paul trap. By precisely tailoring the trapping potentials, we can split, move, and discard parts of an ion chain. This process is automated in a sequence that converts a larger ion sample into the desired configuration. A critical component of our approach is the accurate identification of crystal constituents. This is achieved by matching the measured positions of fluorescing ions against theoretical expectations for larger crystals, thus facilitating the detection of nonfluorescing ions and enabling accurate ion counting. We demonstrate that our method reliably produces two-ion crystals within minutes. These results represent a significant advance in the production of two-species ion crystals with applications ranging from quantum logic spectroscopy and optical clocks to quantum computing and simulations with trapped ions.

Published by the American Physical Society
2024
Generalized threshold of longitudinal multibunch instability in synchrotrons
Authors: Karpov Ivan , Shaposhnikova Elena
Published: July 2024

Beam stability is a crucial requirement for all particle accelerators. Coupled-bunch instability (CBI) is driven by beam interaction with narrowband impedance of the resonant accelerator components. Loss of Landau damping (LLD) for a single bunch is mainly determined by broadband impedance and can lead to undamped bunch oscillations. For the first time, we solve numerically the longitudinal stability problem in a self-consistent way for a general case of two impedance types and propose a simple analytical criterion describing how the obtained LLD and CBI thresholds are combined. We demonstrate that LLD can modify the CBI mechanism and reduce the instability threshold even below the LLD threshold. These findings allow the existing beam observations in CERN Super Proton Synchrotron and Large Hadron Collider to be explained and should be considered in design of the future accelerators.

Published by the American Physical Society
2024
Confined magnon dispersion in ferromagnetic and antiferromagnetic thin films in a second quantization approach: The case of Fe and NiO
Authors: do Nascimento Julio A. , Kerrigan Adam , Cavill S. A. , Kepaptsoglou Demie , Ramasse Quentin M. , Hasnip Phil J. , Lazarov Vlado K.
Published: July 2024

We present a methodology based on the calculation of the inelastic scattering from magnons via the spin-scattering function in confined geometries such as thin films using a second quantization formalism, for both ferromagnetic and antiferromagnetic materials. The case studies are chosen with an aim to demonstrate the effects of film thickness and crystal orientation on magnon modes, using bcc Fe(100) and NiO with (100) and (111) crystallographic orientations as prototypical systems. Due to the quantization of the quasimomentum, we observe a granularity in the inelastic spectra in the reciprocal space path reflecting the orientation of the thin film. This approach also allows for the capture of softer modes that appear due to the partial interaction of magnetic moments close to the surface in a thin film geometry, in addition to bulk modes. The softer modes are also affected by crystallographic orientation, as illustrated by the different surface-related peaks of the NiO magnon density of states at approximately ∼65meV for (100) and ∼42meV for a (111)-oriented film. Additionally, we explore the role of anisotropy, revealing that anisotropy increases the overall hardness of the magnon modes. The introduction of a surface anisotropy produces a shift of the surface-related magnon DOS peak to higher energies with increased surface anisotropy, and in some cases leads to a surface-confined mode.

Published by the American Physical Society
2024
QCD critical point, Lee-Yang edge singularities, and Padé resummations
Authors: Başar Gökçe
Published: July 2024

I analyze the trajectory of the Lee-Yang edge singularities of the QCD equation of state in the complex baryon chemical potential (μB) plane for different values of the temperature by using the recent lattice results for the Taylor expansion coefficients up to eighth order in μB and various resummation techniques that blend in Padé expansions and conformal maps. By extrapolating from this information, I estimate for the location of the QCD critical point: Tc≈100 MeV, μc≈580 MeV. I also estimate the crossover slope at the critical point to be α1≈9∘ and further constrain the nonuniversal mapping parameters between the three-dimensional Ising model and QCD equations of state.

Published by the American Physical Society
2024