bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dnajc3(HSP40) Enhances Axon Regeneration in the Mouse Optic Nerve
Authors: Wang Jiaxing , Li Ying , Struebing Felix L. , Jardines Sandra , Lin Su-Ting , Lin Fangyu , Geisert Eldon E. 
Published: October 2024

ABSTRACTA forward genetics approach was used to identify genomic elements enhancing axon regeneration in the BXD recombinant mouse strains. Axon regeneration was induced by knocking downPtenin retinal ganglion cells (RGCs) using adeno-associated virus (AAV) to deliver an shRNA followed by an intravitreal injection of Zymosan with CPT-cAMP that produced a mild inflammatory response. RGC axons were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by intravitreal injection of Cholera Toxin B (CTB) conjugated with Alexa Fluor 647. Two days later, labeled axons within the optic nerve were examined to determine the number of regenerating axons and the distance they traveled down the optic nerve. The analysis revealed a surprising difference in the amount of axonal regeneration across all 33 BXD strains. There was a 7.5-fold difference in the number of regenerating axons and a 4-fold difference in distance traveled by regenerating axons. These data were used to generate an integral map defining genomic loci modulating the enhanced axonal regeneration. A quantitative trait locus modulating axon regeneration was identified on Chromosome 14 (115 to 119 Mb). Within this locus were 16 annotated genes. Subsequent testing revealed that one candidate gene,Dnajc3, modulates axonal regeneration.Dnajc3encodes Heat Shock Protein 40 (HSP40), which is a molecular chaperone. Knocking downDnajc3in the high regenerative strain (BXD90) led to a decreased regeneration response, while overexpression ofDnajc3in a low regenerative strain (BXD34) resulted in an increased regeneration response. These findings suggest thatDnajc3not only increases the number of regenerating axons, it also increases the distance those axons travel. This may prove to be critical for functional recovery in large mammals, where the distance axons travel to their target is considerably longer than that of the mouse. Thus,Dnajc3may play a critical role for functional recovery in humans by increasing the number of regenerating axons and the distance the regenerating axons travel.
Ethanol drinking sex-dependently alters cortical IL-1β synaptic signaling and cognitive behavior in mice
Authors: Liss A , Siddiqi MT , Podder D , Scroger MV , Vessey G , Martin K , Paperny NM , Vo KT , Astefanous A , Belachew N , Idahor E , Varodayan FP 
Published: October 2024

AbstractIndividuals with alcohol use disorder (AUD) struggle with inhibitory control, decision making, and emotional processing. These cognitive symptoms reduce treatment adherence, worsen clinical outcomes, and promote relapse. Neuroimmune activation is a key factor in the pathophysiology of AUD, and targeting this modulatory system is less likely to produce unwanted side effects compared to directly targeting neurotransmitter dysfunction. Notably, the cytokine interleukin-1β (IL-1β) has been broadly associated with the cognitive symptoms of AUD, though the underlying mechanisms are not well understood. Here we investigated how chronic intermittent 24-hour access two bottle choice ethanol drinking affects medial prefrontal cortex (mPFC)-related cognitive function and IL-1 synaptic signaling in male and female C57BL/6J mice. In both sexes, ethanol drinking decreased reference memory and increased mPFC IL-1 receptor 1 (IL-1R1) mRNA levels. In neurons, IL-1β can activate either pro-inflammatory or neuroprotective intracellular pathways depending on the isoform of the accessory protein (IL-1RAcP) recruited to the IL-1R1 complex. Moreover, ethanol drinking sex-dependently shifted mPFC IL-1RAcP isoform gene expression and IL-1β regulation of mPFC GABA synapses, both of which may contribute to female mPFC resiliency and male mPFC susceptibility. This type of signaling bias has become a recent focus of rational drug development. Therefore, in addition to increasing our understanding of how IL-1β sex-dependently contributes to mPFC dysfunction in AUD, our current findings also support the development of a new class of pharmacotherapeutics based on biased IL-1 signaling.Highlights- Female mice consumed more ethanol, but were less cognitively impaired than males- Ethanol altered IL-1β effects at mPFC GABA synapses, with females less sensitive than males- Ethanol altered mPFCIl1rapmRNA to promote female neuroprotection and male neuroinflammation
Modelling Microbiome Association with Host Phenotypes Using a Bayesian Dirichlet Process Model
Authors: Awany Denis , Chimusa Emile R. 
Published: October 2024

AbstractDysbiosis in the human gut microbiome has been shown to be intimately involved in the pathogenesis of a wide range of communicable and non-communicable diseases. As microbiome wide association study becomes the workhorse for identifying association between microbial taxa and human diseases/traits, proper modelling of microbial taxa abundances is critical. In particular, statistical frameworks need to effectively model correlation among microbial taxa as well as latent heterogeneity across samples. Here, a Bayesian method using the Dirichlet process random effects model is devised for microbiome association study. The proposed method uses a weighted combination of phylogenetic and radial basis function kernels to model taxa effects, and a non-parametrically modelled latent variable to model latent heterogeneity among samples. Using simulated and real microbiome datasets, it is shown that the method has high statistical power for association inference.SoftwareThe R codes to implement the method has been incorporated into a script phy-loDPM.R, and is available online athttps://github.com/AwanyDenis/phyloDPM.
Analysis of the dynamics of a complex, multipathway reaction: Insulin dimer dissociation
Authors: Jeong Kwanghoon , Guo Spencer C. , Allaw Sammy , Dinner Aaron R. 
Published: October 2024

AbstractThe protein hormone insulin forms a homodimer that must dissociate to bind to its receptor. Understanding the kinetics and mechanism of dissociation is essential for rational design of therapeutic analogs. In addition to its physiological importance, this dissociation process serves as a paradigm for coupled (un)folding and (un)binding. Based on previous free energy simulations, insulin dissociation is thought to involve multiple pathways with comparable free energy barriers. Here, we analyze the mechanism of insulin dimer dissociation using a recently developed computational framework for estimating kinetic statistics from short-trajectory data. These statistics indicate that the likelihood of dissociation (the committor) closely tracks the decrease in the number of (native and nonnative) intermonomer contacts and the increase in the number of water contacts at the dimer interface; the transition state with equal likelihood of association and dissociation corresponds to an encounter complex with relatively few native contacts and many nonnative contacts. We identify four pathways out of the dimer state and quantify their contributions to the rate, as well as their exchange, by computing reactive fluxes. We show that both the pathways and their extents of exchange can be understood in terms of rotations around three axes of the dimer structure. Our results provide insights into the kinetics of insulin analogues and, more generally, how to characterize complex, multipathway processes.
Genetic reduction of the translational repressors FMRP and 4E-BP2 preserves memory in mouse models of Alzheimer’s disease
Authors: Ribeiro Felipe C. , Cozachenco Danielle , Lacaille Jean-Claude , Nader Karim , De Felice Fernanda G. , Lourenco Mychael V. , Aguilar-Valles Argel , Sonenberg Nahum , Ferreira Sergio T. 
Published: October 2024

AbstractAlzheimer’s disease (AD) is characterized by progressive memory decline. Converging evidence indicates that hippocampal mRNA translation (protein synthesis) is defective in AD. Here, we show that genetic reduction of the translational repressors, Fragile X messenger ribonucleoprotein (FMRP) or eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), prevented the attenuation of hippocampal protein synthesis and memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Moreover, genetic reduction of 4E-BP2 rescued memory deficits in aged APPswe/PS1dE9 (APP/PS1) transgenic mouse model of AD. Our findings demonstrate that strategies targeting repressors of mRNA translation correct hippocampal protein synthesis and memory deficits in AD models. Results suggest that modulating pathways controlling brain mRNA translation may confer memory benefits in AD.
A scientific note on “Rapid brood decapping” – a method for assessment of honey bee (Apis mellifera) brood infestation withTropilaelaps mercedesae
Authors: Uzunov Aleksandar , Janashia Irakli , Chen Chao , Costa Cecilia , Kovačić Marin 
Published: October 2024

ABSTRACTTropilaelaps mercedesaeis a parasitic mite species that negatively affects the health of theApis melliferacolonies. Recent reports show that it is spreading westwards, through Central Asia into Europe. Several field and laboratory methods have been proposed to detectTropilaelapsspp. inA. melliferacolonies; however, most of them are either laborious, costly or ineffective. Here we introduce a novel method for detectingT. mercedesaebased on the mite’s characteristic biology (reduced feeding as bee pupae mature, brief dispersal phase on adult bees and agility) and the use of wax strips. Sealed worker brood cells at the development stage of white to purple-eyed pupae are swiftly decapped with wax strips to observe and count surfacing adult mites. Our study shows over 90 % detection efficacy and brood survival, and ease of application. Therefore, we recommend the novel “Rapid brood decapping” method as a reliable tool for detecting and monitoringT. mercedesaeinfestation.
Metabolism fine tuning and cardiokines secretion represent adaptative responses of the heart to High Fat and High Sugar Diets in flies
Authors: Khamvongsa-Charbonnier Lucie , Kremmer Laurent , Torres Magali , Krifa Sallouha , Aubert Charis , Corbet Alice , Crespo Loïc , Röder Laurence , Perrin Laurent , Arquier Nathalie 
Published: October 2024

SUMMARYCardiopathies are one of the leading causes of death in obese diabetics. Resulting in part from junk food, diabetic cardiomyopathies are notably characterized by contractile dysfunctions. Using theDrosophilamodel for cardiac function in pathophysiological context, we identified a set of candidate genes, expressed by the heart, whose expression is modulated by acute challenge on High Sugar and High Fat regimes. Genes encoding core components of key homeostatic pathways and proteins such as 1C-metabolism homeostasis, the Galactose metabolism pathway and metabolites transporters, were identified and characterized as adaptative factors of cardiac function under nutritional stresses. In addition, putative secreted proteins were found dysregulated, highlighting the heart as a secretory organ in hyperglycemia and hyperlipidemia. In particular, we characterized the Fit satiety hormone as a new fly cardiokine, which autonomously modulates the cardiac function and remotely affects feeding behavior. Overall, our study uncovered new roles for metabolic pathways and cardiokines, and highlights autonomous and systemic adjustable responses of the heart to nutritional stresses.
Whole genome resequencing of a global collection of Napier grass (Cenchrus purpureus) to explore global population structure and QTL governing yield and feed quality traits
Authors: Teshome A. , Lire H. , Higgins J. , Olango T. , Habte E. , Negawo A.T. , Muktar M.S. , Assefa Y. , Pereira J.F. , Azevedo A.S. , Machado J.C. , Nyamongo D.S. , Zhang J. , Qi Y. , Anderson W. , De Vega J. , Jones C.S. 
Published: October 2024

AbstractNapier grass (Cenchrus purpureus) is a C4perennial grass species native to Sub-Saharan Africa (SSA), primarily used to feed cattle in SSA. In this study, we sequenced the genomes of 450 Napier grass individuals, sourced from 20 different countries. More than 170 million DNA variants (SNPs and Indels) were detected, of which ∼1% informative SNPs were used to assess genetic diversity in the collection. Our resequencing study provided valuable insights into the genetic diversity across a global Napier grass collection. Furthermore, a genome-wide association study on two independent populations, identified multiple quantitative trait loci (QTL) that were significantly associated with desirable agronomic traits, such as biomass yield, nitrogen and cellulose content. Therefore, our results will serve as a valuable resource in safeguarding and unravelling the patterns of Napier grass genetic diversity, in the face of climate change, and spearhead genomics-based breeding programs to develop high-yielding and drought-tolerant varieties suitable for forage and biofuel production.
Human BNST volume is not simply sexually dimorphic
Authors: Berry Samuel C. , Suri Harsimran K. , Lisi Matteo , Aggleton John P. , Hodgetts Carl J. 
Published: October 2024

Abstract‘The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region’, is a claim prevalent across rodent and human neuroscience research, with particular emphasis on its substantially larger size in males. Despite the pervasiveness of this claim, with potential implications for understanding sex differences in anxiety and substance use disorders, inspection of prior literature reveals a complex and nuanced picture. Direct evidence for larger male BNST size in humans comes solely from a handful of mostly small-scale post-mortem studies, which show either no, moderate, or very large differences, therefore indicating the need for a larger systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol of the BNST, which was applied to ultra-high resolution T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing post-mortem data, and controlling for total brain volume, age, and sibship, we find little evidence for total BNST volume differences between males and females. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.
Modeling of transcriptomic variation among subgenomes in 25 accessions of common wheat reveals cis- and trans- regulation architectures
Authors: Nomura Yasuyuki , Okada Moeko , Tameshige Toshiaki , Takenaka Shotaro , Shimizu Kentaro K. , Nasuda Shuhei , Nagano Atsushi J. 
Published: October 2024

ABSTRACTCommon wheat is an allohexaploid plant, thus making it difficult to obtain homoeolog-distinguished transcriptome data. Lasy-Seq, a type of 3’ RNA-seq, is efficient for obtaining homoeolog-distinguished transcriptomes and can thus overcome this measurement difficulty. This study obtained transcriptome data from the seedlings, second leaves, and root tips of 25 lines from mainly eastern transmitted area using Lasy-Seq. Roots and seedlings exhibited similar transcriptome profiles; however, they were different from those of the leaves. We determined the effects of subgenomes, lines and their interactions with leaves, roots, and seedlings on the expression levels of each homoeolog triad. Of the 19,805 homoeolog triads, 50.9–55.4%, 24.2–29.5%, and 7.7–9.0% showed significant effects on their expression levels from subgenome, line, and interaction, respectively. 51–55% and 24–30% have genetic variation in thecis- andtrans-regulation. Hierarchical clustering and co-transregulation network analysis of homoeolog triads revealed that the patterns of expression polymorphisms among the lines were shared in different genes. The triads in which the statistical model detected as line effects imply that expression variation between lines is caused by changes in a smaller number of commontrans-factors. We assigned gene ontology (GO) terms of theArabidopsisorthologs to wheat homoeolog triads via reciprocal BLAST between common wheat andArabidopsis, thus improving the percentage of gene-assigned GO terms to all analyzed GO terms from 19.1% to 90.6%. GO term enrichment analysis revealed that GO terms related to each tissue type function were enriched in genes expressed in the leaves and roots. Our information provides fundamental knowledge for the future breeding of plants possessing complex gene regulatory networks such as common wheat.
Osmoregulation affects elimination of microplastics in fish in freshwater and marine environments
Authors: Pratiwi Hilda Mardiana , Takagi Toshiyuki , Rusni Suhaila , Inoue Koji 
Published: October 2024

AbstractIn recent decades, microplastics (MPs) have emerged as one of the biggest environmental challenges in aquatic environments. Ingestion and toxicity of MPs in seawater (SW) and freshwater (FW) fish have been studied extensively both in field and laboratory settings. However, the basic mechanism of how fish deal with MPs in SW and FW remains unclear, although physiological conditions of fish differ significantly in the two environments. In this study, using Javanese medaka (Oryzias javanicus), a euryhaline fish which adapts readily to both SW and FW, we investigated elimination of MPs in fish in SW and FW environments. We exposedO. javanicuslarvae (21 days post-hatching) to 0.25 mg/L of fluorescent polystyrene microspheres (1 µm) for 24 h and then conducted an elimination test for up to 5 days. The results showed that the gut retention time (GRT) of MPs is longer in FW than in SW, indicating that MP elimination occurs more quickly in SW than in FW. However, despite shorter GRTs, higher numbers of MPs tended to be retained for a longer period in SW larvae than FW larvae. Subsequently, using a fluorescent marker, gastrointestinal fluid was found to move more rapidly in the SW group. This finding indicates that water drinking accelerates gastrointestinal fluid movement, which moves MPs through the gut in SW larvae. Beside the difference in physiological conditions, MP elimination was faster when food was available, suggesting that feeding also affects MP elimination in fish. Internal factors such as body size and intestine length were also examined, but indicated no significant difference between SW and FW. Therefore, osmoregulation and feeding both influence MP elimination in fish.
Anatomical and functional organization of the interpeduncular nucleus in larval zebrafish
Authors: Wu You Kure , Petrucco Luigi , Portugues Ruben 
Published: October 2024

AbstractThe habenulo-interpeduncular pathway is a highly conserved neural circuit across vertebrates, but the anatomical and functional architecture of the interpeduncular nucleus (IPN) remains poorly understood. Here, we use a combination of immunohistochemistry, volumetric electron microscopy (EM), and two-photon imaging to provide the first detailed characterization of the internal organization of the IPN in larval zebrafish. We show that the IPN receives extensive projections from the tegmentum, and reveal a strict segregation between the dorsal (dIPN) and ventral (vIPN) subcircuits, with minimal cross-communication. In the dIPN, we characterise in detail the inputs and outputs of r1π neurons, which have been recently identified as representing the animal’s heading direction. In the vIPN, we identify six distinct glomerular structures, each exhibiting specific patterns of reciprocal connections and projection pathways. Finally, we demonstrate that the connectivity and spontaneous activity patterns of habenular axons are shaped by the local anatomical features of the IPN, suggesting a role for the local interneurons in modulating presynaptic dynamics. Together, these results enhance our understanding of the internal organization of the IPN, and provide a framework for future investigations into both its physiology and its involvement in behavior.
Male Dimorphism and Emergence Strategies: A Mathematical Model of Protandry inFabriciana nerippeFelder, 1862
Authors: Kubo Hidaka , Nakaoka Shinji , Yamaguchi Ryo 
Published: October 2024

AbstractIn many butterfly species, males emerge earlier than females as part of a strategy to maximize male reproductive success. Although behavioral ecological studies using mathematical models have been conducted to explain this phenomenon, certain emergence patterns remain unexplained. In the butterfly speciesFabriciana nerippe, some males emerge at the same time as females, in addition to males that emerge earlier than the females. However, it is unclear what emergence patterns occur in populations with male dimorphism, as observed in this species. In this study, we showed the existence of male body size dimorphism inFabriciana nerippeby conducting a comparative analysis of forewing lengths between males and females. In addition, we developed a comprehensive mathematical model to investigate emergence patterns in the presence of dimorphic males. By introducing a trade-off between large size and early emergence, the model considered a scenario where small early-emerging and large late-emerging males could coexist. Numerical analysis demonstrated the emergence patterns of these two male types with a switch in emergence time. Furthermore, the higher the death rate before emergence, the earlier the emergence switch. These findings suggested that the timing of the switch depends on the death rate and is influenced by environmental factors. This work contributes to ecological and theoretical studies on timing dimorphism in life-history strategies across a broader range of species.HighlightsWe confirmed the existence of male body-size dimorphism corresponding to emergence timing inFabriciana nerippe.We developed a comprehensive model of male emergence patterns incorporateing male dimorphism.We assumed a trade-off between early emergence and large body size.The timing of male emergence switching is influenced by death rate and reproductive advantage of large males.
NK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice
Authors: Guerrero Claudia , Moreo Eduardo , Araujo-Voces Miguel , Uranga Santiago , Gómez Ana Belén , Martín Carlos , Aguiló Nacho 
Published: October 2024

ABSTRACTLung metastases frequently arise from primary tumors, including bladder cancer, and represent a critical negative prognostic factor. Natural Killer (NK) cells have shown to play a vital role in controlling metastasis. Consequently, tumor cells have evolved specific mechanisms to evade NK cell-mediated immune surveillance, promoting metastasis and resistance to immunotherapy. In this study, we investigated the prophylactic and therapeutic potential of intravenous Bacillus Calmette–Guérin (BCG) in preventing lung metastases from bladder cancer cells using a murine model. We demonstrated that prophylactic BCG administration significantly reduced tumor burden and prolonged survival, largely through NK cell activation. However, BCG treatment was ineffective when administered over established tumors, likely due to tumor-driven immune evasion mechanisms. Our results revealed the contribution of interferon-gamma (IFN-γ) to tumor resistance. Tumor cells exposed to IFN-γ upregulated were more resistant to BCGin vivo, which correlated with the overexpression of immune checkpoint molecules, whereas disruption of the IFN-γ signaling pathway in tumor cells partially restored the therapeutic efficacy of BCG. Our findings highlight the importance of understanding tumor immune escape mechanisms and suggest that BCG could be a promising treatment for preventing lung metastases in bladder cancer.