bluuebunny/crossref_metadata_2025_split huggingface dataset:
Availability of an inflammatory macrophage niche drives phenotypic and functional alterations in Kupffer cells
Authors: Huang Han-Ying , Chen Yan-Zhou , Zheng Xin-Nan , Yue Jia-Xing , Ju Huai-Qiang , Shi Yan-Xia , Tian Lin 
Published: April 2024

AbstractInflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into disease-associated macrophages1–3. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated4. Here, we employed multiple lineage tracing models and confirmed that monocyte-derived macrophages (mo-macs) are the major population of liver metastasis-associated macrophages (LMAMs), while the population of Kupffer cells (KCs), liver-resident macrophages, is diminished in liver metastatic nodules. Paradoxically, genetic ablation of mo-macs resulted in only a marginal decrease in LMAMs. Using a proliferation recording system and a KC tracing model in a monocyte-deficient background, we found that LMAMs can be replenished either via increased local macrophage proliferation or by promoting KC infiltration. After occupying macrophage niches left vacant by monocyte depletion, KCs exhibit substantial phenotypic and functional alterations through epigenetic reprogramming. These data suggest that dual blockade of monocytes and macrophages could be used to effectively target immunosuppressive myelopoiesis and to reprogram the microenvironment towards an immunostimulatory state.
Linking phenology, harvest index and genetics to improve chickpea grain yield
Authors: Gimenez R. , Lake L. , Cossani M. C. , Ortega Martinez R. , Hayes J. E. , Dreccer M. F. , French R. , Weller J. L. , Sadras V. O. 
Published: April 2024

AbstractPhenology is critical to crop adaptation. We grew 24 chickpea genotypes in 12 environments to analyse: the environmental and genotypic drivers of phenology; associations between phenology and yield; and phenotypes associated with allelic variants of three flowering related candidate loci:CaELF3a; a cluster of threeFTgenes on chromosome 3; and a region on chromosome 4 with an orthologue of the floral promoterGIGANTEA. A simple model with 3 genotype-specific parameters explained the differences in flowering response to daylength. Environmental factors causing flower abortion, such as low temperature and radiation and high humidity, led to a longer flowering-to-podding interval. Late podding associated with poor partition to grain, limiting yield in favourable environments. Sonali, carrying the early allele ofCaelf3a(elf3a), was generally the earliest to set pod, had low biomass but the highest harvest index. Genotypes combining the early variants ofGIGANTEAandFTorthologuesFTdel, where a deletion in the intergenic region ofFTa1-FTa2was associated with slow development, usually featured early reproduction and high harvest index, returning high yield in favourable environments. We emphasise the importance of pod set, rather than flowering, as a target for breeding, agronomic, and modelling applications.HighlightThis paper analyses the environmental and genetic controls of chickpea phenology and its effects on grain yield, in a multi-environment trial including 24 genotypes with varying combinations of flowering related genes.
Co-infection with two iflaviruses (deformed wing virus and sacbrood virus) affects viral and immune dynamics and synergistically increases honey bee mortality
Authors: Durand Tristan , Dubois Eric , Bonjour-Dalmon Anne 
Published: April 2024

AbstractThe honey bee microbiome includes a wide variety of viruses. While most of them usually remain commensal, some can become pathogenic in specific contexts. Of these, one is that of deformed wing virus (DWV) and another, sacbrood virus (SBV). Although co-infection is the norm rather than the exception, most of the time these viruses have been studied independently. When investigated as co-infections, past studies have focused on their effects on the honey bee brood. In this study, we co-inoculated adult honey bees at emergence with DWV by injection and SBV orally (acting as the viral transmission byVarroa destructorand by trophallaxis or food, respectively), either simultaneously or sequentially. Using optical counters, we were able to track the survival and behaviour of these honey bees within colonies. Through regular in-hive sampling, we monitored the evolution of their viral loads as well as the expression of eight immune genes involved in honey bee anti-viral immunity. Here, we show that co-inoculations of DWV and SBV synergistically increase the virulence of DWV and conditionally promote the replication of both viruses. Finally, our results show that immune responses in adult honey bees depend on DWV genotypes and whether replication originates from a superinfecting virus or a virus already present in bees.Author SummaryHoney bees are highly social pollinators that live in crowded colonies. Their population density and the high frequency of interactions between individuals favours disease transmission and makes colonies susceptible to pathogen outbreaks. Many viruses commonly infect honey bees, however, they are often studied as single infections. As an effort to better understand interactions between honey bees and multiple viral populations, we co-inoculated young bees with two common honey bee viruses (deformed wing virus and sacbrood virus), released them in colonies and monitored their health and behaviour. Our findings show evidence of synergies between both viruses, as we show that a virus seemingly harmless for adult bees (sacbrood virus) may actually increase the virulence of another virus (deformed wing virus). These results highlight the importance of monitoring and studying multiple pathogens at once for a better understanding of the threat they represent to colony health and survival.
Surface lipids influence developmental and species- specific chemical signalling in nematodes
Authors: Kotowska Anna M. , Hiramatsu Fumie , Alexander Morgan R. , Scurr David J. , Lightfoot James W. , Chauhan Veeren M. 
Published: April 2024

ABSTRACT/SUMMARYChemical signalling facilitates organismal communication and coordinates physiological and behavioural processes. In nematodes, signalling has predominantly focused on secreted molecules leaving the surface’s communicative potential unexplored. By utilising 3D-OrbiSIMS, an advanced surface-sensitive mass spectrometry method, we directly characterised the molecular composition of the outermost regions (50 nm in depth) ofCaenorhabditis elegansandPristionchus pacificusto improve the understanding of surface-mediated chemical communication. We found that nematode surfaces consist of a lipid-dominated landscape (> 81 %C. elegansand > 69 %P. pacificusof all surveyed chemistries) with distinct compositions, which enrich in granularity and complexity through development. The surface-anchored lipids are also species-specific, reflecting evolutionary and ecological adaptations to their environmental niches. By exploring the effect of mutations on lipid production we found the peroxisomal fatty acid β-oxidation componentdaf-22is essential for defining the surface molecular fingerprint. This pathway is conserved across species in producing distinct chemical profiles, indicating its fundamental role in lipid metabolism and for maintaining surface integrity and function. Furthermore, we discovered that variations in surface-anchored lipids ofC. elegans daf-22larvae contribute to significantly increased susceptibility to predation byP. pacificus. Therefore, our findings reveal that the nematode surface is not just a passive boundary but a dynamic signalling platform with evolved, species-specific signatures. These molecular mechanisms are pivotal in shaping identity and communication strategies, providing new insights into the evolutionary and ecological dynamics of chemical signalling across organisms.HIGHLIGHTSNematode surfaces are lipid-rich, changing with development.Surface lipids are species-specific, reflecting adaptations.Thedaf-22gene is key in shaping the surface lipid profile.Surface lipids mediate predator-prey interactions in nematodes.
The reindeer circadian clock is rhythmic and temperature-compensated but shows evidence of weak coupling between the secondary and core molecular clock loops
Authors: Appenroth Daniel , Ravuri Chandra S , Torppa Sara K , Wood Shona H , Hazlerigg David G , West Alexander C 
Published: April 2024

ABSTRACTCircadian rhythms synchronize the internal physiology of animals allowing them to anticipate daily changes in their environment. Arctic habitats may diminish the selective advantages of circadian rhythmicity by relaxing daily rhythmic environmental constraints, presenting a valuable opportunity to study the evolution of circadian rhythms. In reindeer, circadian control of locomotor activity and melatonin release is weak or absent, and the molecular clockwork is reportedly non-functional. Here we present new evidence that the circadian clock in cultured reindeer fibroblasts is rhythmic and temperature-compensated. Compared to mouse fibroblasts, however, reindeer fibroblasts have a short free-running period, and temperature cycles have an atypical impact on clock gene regulation. In reindeer cells,Per2andBmal1reporters show rapid responses to temperature cycles, with a disintegration of their normal antiphasic relationship. The antiphasicPer2-Bmal1relationship re-emerges immediately after release from temperature cycles, but without complete temperature entrainment and with a marked decline in circadian amplitude. Experiments usingBmal1promoter reporters with mutated RORE sites showed that a reindeer-like response to temperature cycles can be mimicked in mouse or human cell lines by decouplingBmal1reporter activity from ROR / REV-ERB dependent transcriptional regulation. We suggest that weak coupling between core and secondary circadian feedback loops accounts for the observed behaviour of reindeer fibroblastsin vitro. Our findings highlight diversity in how the thermal environment affects the temporal organisation of mammals living under different thermoenergetic constraints.
Virological characteristics of the SARS-CoV-2 KP.2 variant
Authors: Kaku Yu , Uriu Keiya , Kosugi Yusuke , Okumura Kaho , Yamasoba Daichi , Uwamino Yoshifumi , Kuramochi Jin , Sadamasu Kenji , Yoshimura Kazuhisa , Asakura Hiroyuki , Nagashima Mami ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ito Jumpei , Sato Kei 
Published: April 2024

AbstractThe JN.1 variant (BA.2.86.1.1), arising from BA.2.86(.1) with the S:L455S substitution, exhibited increased fitness and outcompeted the previous dominant XBB lineage by the biggening of 2024. JN.1 subsequently diversified, leading to the emergence of descendants with spike (S) protein substitutions such as S:R346T and S:F456L. Particularly, the KP.2 (JN.1.11.1.2) variant, a descendant of JN.1 bearing both S:R346T and S:F456L, is rapidly spreading in multiple regions as of April 2024. Here, we investigated the virological properties of KP.2. KP.2 has three substitutions in the S protein including the two above and additional one substitution in non-S protein compared with JN.1. We estimated the relative effective reproduction number (Re) of KP.2 based on the genome surveillance data from the USA, United Kingdom, and Canada where >30 sequences of KP.2 has been reported, using a Bayesian multinomial logistic model. The Reof KP.2 is 1.22-, 1.32-, and 1.26-times higher than that of JN.1 in USA, United Kingdom, and Canada, respectively. These results suggest that KP.2 has higher viral fitness and potentially becomes the predominant lineage worldwide. Indeed, as of the beginning of April 2024, the estimated variant frequency of KP.2 has already reached 20% in United Kingdom.The pseudovirus assay showed that the infectivity of KP.2 is significantly (10.5-fold) lower than that of JN.1. We then performed a neutralization assay using monovalent XBB.1.5 vaccine sera and breakthrough infection (BTI) sera with XBB.1.5, EG.5, HK.3 and JN.1 infections. In all cases, the 50% neutralization titer (NT50) against KP.2 was significantly lower than that against JN.1. Particularly, KP.2 shows the most significant resistance to the sera of monovalent XBB.1.5 vaccinee without infection (3.1-fold) as well as those who with infection (1.8-fold). Altogether, these results suggest that the increased immune resistance ability of KP.2 partially contributes to the higher Remore than previous variants including JN.1.
Post-mortem evidence for a reciprocal relationship between genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies
Authors: Koss David J. , Todd Olivia , Menon Hariharan , Anderson Zoe , Yang Tamsin , Attems Johannes , LeBeau Fiona E. , Erskine Daniel , Outeiro Tiago F. 
Published: April 2024

AbstractDNA damage and DNA damage repair (DDR) dysfunction are insults with broad implications on cellular physiology, including in proteostasis, and have been recently implicated in many neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-synaptic and nuclear protein associated with neurodegenerative disorders known as synucleinopathies, has been implicated in DNA double strand break (DSB) repair function. Consistently, DSB induction has been demonstrated in cell and animal models of synucleinopathy. Nevertheless, the types of DNA damage and the contribution of DNA damage towards Lewy body (LB) formation in synucleinopathies are unknown. Here, we demonstrate the increase of DSB in neuronal and non-neuronal cellular populations of post-mortem temporal cortex tissue from dementia with Lewy body (DLB) patients and demonstrate increases in DSBs early at a presymptomatic age of aSyn transgenic mice. Strikingly, in postmortem DLB tissue, DNA damage-derived ectopic cytoplasmic genomic material (eCGM) was evident within the majority of LBs examined. The observed cellular pathology was consistent with nucleoproteasomal upregulation of associated DNA damage repair proteins, particularly in base excision repair and DSB repair pathways. Collectively our study demonstrates the early occurrence of DNA damage and associated nucleoproteasomal changes in response to nuclear aSyn pathology. Furthermore, the data suggests a potential involvement for DNA damage derived eCGM for the facilitation of cytoplasmic aSyn aggregates. Ultimately, uncovering pathological mechanisms underlying DNA damage in DLB sheds light into novel disease mechanisms and opens novel possibilities for diagnosing and treating synucleinopathies.
Angiotensin Converting Enzyme (ACE) expression in microglia reduces amyloid β deposition and neurodegeneration by increasing SYK signaling and endolysosomal trafficking
Authors: Gomez Andrew R. , Byun Hyae Ran , Wu Shaogen , Muhammad AKM Ghulam , Ikbariyeh Jasmine , Chen Jaelin , Muro Alek , Li Lin , Bernstein Kenneth E. , Ainsworth Richard , Tourtellotte Warren G. 
Published: April 2024

ABSTRACTGenome-wide association studies (GWAS) have identified many gene polymorphisms associated with an increased risk of developing Late Onset Alzheimer’s Disease (LOAD). Many of these LOAD risk-associated alleles alter disease pathogenesis by influencing microglia innate immune responses and lipid metabolism. Angiotensin Converting Enzyme (ACE), a GWAS LOAD risk-associated gene best known for its role in regulating systemic blood pressure, also enhances innate immunity and lipid processing in peripheral myeloid cells, but a role for ACE in modulating the function of myeloid-derived microglia remains unexplored. Using novel mice engineered to express ACE in microglia and CNS associated macrophages (CAMs), we find that ACE expression in microglia reduces Aβ plaque load, preserves vulnerable neurons and excitatory synapses, and greatly reduces learning and memory abnormalities in the 5xFAD amyloid mouse model of Alzheimer’s Disease (AD). ACE-expressing microglia show enhanced Aβ phagocytosis and endolysosomal trafficking, increased clustering around amyloid plaques, and increased SYK tyrosine kinase activation downstream of the major Aβ receptors, TREM2 and CLEC7A. Single microglia sequencing and digital spatial profiling identifies downstream SYK signaling modules that are expressed by ACE expression in microglia that mediate endolysosomal biogenesis and trafficking, mTOR and PI3K/AKT signaling, and increased oxidative phosphorylation, while gene silencing or pharmacologic inhibition of SYK activity in ACE-expressing microglia abrogates the potentiated Aβ engulfment and endolysosomal trafficking. These findings establish a role for ACE in enhancing microglial immune function and they identify a potential use for ACE-expressing microglia as a cell-based therapy to augment endogenous microglial responses to Aβ in AD.
Pseudomonas aeruginosa-infected Myeloid-derived suppressor cells (MDSC) down-regulate lymphocyte activity and improves mice survival, followingin vivolung transfer
Authors: Born-Bony Maëlys , Cornu Clémentine , Villeret Bérengère , Voulhoux Romé , Sallenave Jean-Michel 
Published: April 2024

ABSTRACTPseudomonas aeruginosa(P.a.) is a pathogenic opportunistic bacterium, classified as a priority by the WHO for the research of new treatments. As this bacterium is harmful trough the inflammation and tissue damage it causes, we investigated the role of Myeloid Derived Suppressor Cells (MDSC) inP.a.infections and their potential as a therapeutic target. We found that uponP.a.exposure, MDSC activity is increased and gain contact-independent properties. Interestingly, this activation is dependent onP.a.mobility but not its flagellin nor TLR5-MyD88 pathway. We also show that MDSC adoptive transfer increases mice survival inP.a.acute lung infection both in therapeutic and prophylactic set ups. Finally, usingan in vitroscratch assay model, we suggest that MDSC acts directly on lung epithelium to stimulate its repair. Together, we highlight a potential beneficial role of MDSC inP.a.infection response. We believe that the unique properties of MDSC make them attractive potential new therapeutic tools for patients with acute or chronic inflammatory diseases, where inflammation has to be kept in check.
Heterogenous transcriptomes ofNicotiana tabacumBY-2 suspension cell lines adapted to various osmoticum
Authors: Skrzypczak Tomasz , Wojtaszek Przemysław , Kasprowicz-Maluśki Anna 
Published: April 2024

AbstractPlants abiotic stress response and adaptation belong to the most important subjects in plants biology. Here, we presentNicotiana tabacumsuspension cell lines adapted during long term cultures to high concentrations of NaCl, KCl, mannitol and sorbitol. Obtained lines differ in osmotic stress agents and final media osmolarities. RNA-seq analysis revealed similarities, as well as differences in adapted lines transcriptomes. Presented here BY-2 cells lines form a good model to reveal molecular mechanisms of plants adaptations to salt and osmotic stress on cellular level.
DeepGene: An Efficient Foundation Model for Genomics based on Pan-genome Graph Transformer
Authors: Zhang Xiang , Yang Mingjie , Yin Xunhang , Qian Yining , Sun Fei 
Published: April 2024

ABSTRACTDecoding the language of DNA sequences is a fundamental problem in genome research. Mainstream pre-trained models like DNABERT-2 and Nucleotide Transformer have demonstrated remarkable achievements across a spectrum of DNA analysis tasks. Yet, these models still face the pivotal challenge of (1) genetic language diversity, or the capability to capture genetic variations across individuals or populations in the foundation models; (2) model efficiency, specifically how to enhance performance at scalable costs for large-scale genetic foundational models; (3) length extrapolation, or the ability to accurately interpret sequences ranging from short to long within a unified model framework. In response, we introduce DeepGene, a model leveraging Pan-genome and Minigraph representations to encompass the broad diversity of genetic language. DeepGene employs the rotary position embedding to improve the length extrapolation in various genetic analysis tasks. On the 28 tasks in Genome Understanding Evaluation, DeepGene reaches the top position in 9 tasks, second in 5, and achieves the overall best score. DeepGene outperforms other cutting-edge models for its compact model size and superior efficiency in processing sequences of varying lengths. The datasets and source code of DeepGene are available at GitHub (https://github.com/wds-seu/DeepGene).
Combining EEG and Eye-Tracking in Virtual Reality - Obtaining Fixation-Onset ERPs and ERSPs
Authors: Nolte Debora , Vidal De Palol Marc , Keshava Ashima , Madrid-Carvajal John , Gert Anna L. , von Butler Eva-Marie , Kömürlüoğlu Pelin , König Peter 
Published: April 2024

AbstractExtensive research conducted in controlled laboratory settings has prompted an inquiry into how results can be generalized to real-world situations influenced by the subjects’ actions. Virtual reality lends itself ideally to investigating complex situations but requires accurate classification of eye movements, especially when combining it with time-sensitive data such as EEG. We recorded eye-tracking data in virtual reality and classified it into gazes and saccades using a velocity-based classification algorithm, and we cut the continuous data into smaller segments to deal with varying noise levels, as introduced in the REMoDNav algorithm. Furthermore, we corrected for participants’ translational movement in virtual reality. Various measures, including visual inspection, event durations, and the velocity and dispersion distributions before and after gaze onset, indicate that we can accurately classify the continuous, free-exploration data. Combining the classified eye-tracking with the EEG data, we generated fixation-onset ERPs and ERSPs, providing further evidence for the quality of the eye movement classification and timing of the onset of events. Finally, investigating the correlation between single trials and the average ERP and ERSP identified that fixation-onset ERSPs are less time-sensitive, require fewer repetitions of the same behavior, and are potentially better suited to study EEG signatures in naturalistic settings. We modified, designed, and tested an algorithm that allows the combination of EEG and eye-tracking data recorded in virtual reality.