bluuebunny/crossref_metadata_2025_split huggingface dataset:
AustralianCulex annulirostrismosquitoes are competent vectors for Japanese encephalitis virus genotype IV
Authors: Klein Melissa J. , Jackson Sarah A. , Suen Willy W. , Payne Jean , Beveridge Darcy , Hargreaves Mel , Gillies Donna , Wang Jianning , Blasdell Kim R. , Dunn Mike , López-Denman Adam J. , Williams David T. , Paradkar Prasad N. 
Published: June 2024

AbstractJapanese encephalitis virus (JEV) is transmitted byCulexspecies of mosquitoes. In 2022, JEV belonging to a previously unrecognised lineage of genotype IV (GIV) caused a major outbreak of JE in South-eastern Australia, resulting in human cases and affecting piggeries.Cx. annulirostrishas previously been implicated as the major vector of JEV in northern Australia where the virus has circulated since its first detection in 1995. Here, we showed that experimental infection of a laboratory colony of AustralianCx. annulirostriswith the isolate JEV NSW/22 resulted in a 100% mosquito infection rate, with 87% of mosquito saliva samples testing positive by RT-qPCR at 14 days post-infection. Immunohistochemistry confirmed the presence of a replicating virus in the mosquito midgut and dissemination throughout the body, including the salivary glands. Our results also showed evidence of transovarial transmission of this virus; however, transstadial transmission from the eggs to the adult stage was not found. Comparison with an Indonesian isolate of GIV JEV and previous Australian isolates belonging to genotypes I and II showed that infection with JEV NSW/22 resulted in higher viral titres in the early stage of infection and higher proportions of mosquitoes with JEV-positive saliva, indicating a greater transmission potential compared to other isolates. This study provides compelling experimental evidence that AustralianCx. annulirostrisis a highly efficient vector for the 2022 Australian JEV GIV outbreak strain.
Parasitoid wasp venoms degradeDrosophilaimaginal discs for successful parasitism
Authors: Kamiyama Takumi , Shimada-Niwa Yuko , Mori Hitoha , Tani Naoki , Takemata-Kawabata Hitomi , Fujii Mitsuki , Takasu Akira , Katayama Minami , Kuwabara Takayoshi , Seike Kazuki , Matsuda-Imai Noriko , Senda Toshiya , Katsuma Susumu , Nakamura Akira , Niwa Ryusuke 
Published: June 2024

AbstractParasitoid wasps, one of the most diverse and species-rich animal taxa on Earth, produce venoms that manipulate host development and physiology to exploit host resources. However, mechanisms of venom action remain poorly understood. Here, we show that infection of hostDrosophilaby the endoparasitoid wasp,Asobara japonica, triggers imaginal disc degradation (IDD) by inducing apoptosis, autophagy, and mitotic arrest, leading to impaired host metamorphosis. A multi-omics approach identified two venom proteins ofA. japonicanecessary for IDD. Knockdown experiments targeting the venom genes revealed that in concert with host immune suppression, IDD is essential for successful parasitism. Our study highlights a venom-mediated hijacking strategy of the parasitoid wasp that allows host larvae to grow, but ultimately kills the hosts.
Poxvirus A52 is a host range factor for modified vaccinia virus Ankara (MVA) and promotes viral replication by disturbing the formation of autolysosomes
Authors: Niu Kang , Fang Yongxiang , Deng Yining , Wang Ziyue , Xie Shijie , Zhu Junda , Song Baifen , Wu Wenxue , Jing Zhizhong , Peng Chen 
Published: June 2024

SUMMARYMany members of the poxvirus family are important zoonotic pathogens that pose a significant threat to human and animal health worldwide. Autophagy is a multi-step degradation pathway within cells, and one of its primary biological functions includes the clearance of invading viruses. Nevertheless, the interplay between poxviruses and host cell autophagy has not been fully elucidated. Here, we demonstrate that vaccinia virus (VACV) and lumpy skin disease virus (LSDV) induce incomplete autophagy and inhibit the fusion of autophagosomes and lysosomes, while modified vaccinia virus Ankara (MVA), an attenuated strain of VACV unable to replicate in almost all human cells, does not. Additionally, we screened and identified the VACV protein A52 as a key factor that obstruct the formation of autolysosomes. Mechanistically, A52 interacts with SNAP29 and inhibits its interaction with STX17 and VAMP8, both of which are binding partners of SNAP29 and are essential for complete autophagy. Moreover, A52 promotes the proteasomal degradation of SNAP29, which facilitates viral replication. We further revealed that SNAP29 functions as a restriction factor for MVA, as the suppression of SNAP29 allowed the replication of MVA in human cells. In summary, our data present a molecular mechanism by which poxviruses manipulate the cellular autophagic machinery and provide additional explanation for the restriction of MVA in human cells.
Is subjective perceptual similarity metacognitive?
Authors: Moharramipour Ali , Zhou William , Rahnev Dobromir , Lau Hakwan 
Published: June 2024

ABSTRACTPerceptual similarity is a cornerstone for human learning and generalization. However, in assessing the similarity between two stimuli differing in multiple dimensions, it is not well-defined which feature(s) one should focus on. The problem has accordingly been considered ill-posed. We hypothesize that similarity judgments may be, in a sense, metacognitive: The stimuli rated as subjectively similar are those that are in fact more challenging for oneself to discern in practice, in near-threshold settings (e.g., psychophysics experiments). This self-knowledge about one’s own perceptual capacities provides a quasi-objective ground truth as to whether two stimuli ‘should’ be judged as similar. To test this idea, we measure perceptual discrimination capacity between face pairs, and ask subjects to rank the similarity between them. Based on pilot data, we hypothesize a positive association between perceptual discrimination capacity and subjective dissimilarity, with this association being importantly specific to each individual.
Ultra-High Dose Rate Helium Ion Beams: Minimizing Brain Tissue Damage while Preserving Tumor Control
Authors: Dokic Ivana , Moustafa Mahmoud , Tessonnier Thomas , Meister Sarah , Ciamarone Federica , Akbarpour Mahdi , Krunic Damir , Haberer Thomas , Debus Jürgen , Mairani Andrea , Abdollahi Amir 
Published: June 2024

AbstractUltra-high dose rate radiotherapy with electrons and protons has shown potential for cancer treatment by effectively targeting tumors while sparing healthy tissues (FLASH effect). This study aimed to investigate the potential FLASH sparing effect of ultra-high-dose rate helium ion irradiation, focusing on acute brain injury and subcutaneous tumor response in a preclinical in vivo setting. Raster-scanned helium ion beams were used to compare the effects of standard dose rate (SDR at 0.2 Gy/s) and FLASH (at 141 Gy/s) radiotherapy on healthy brain tissue. Irradiation-induced brain injury was studied in C57BL/6 mice via DNA damage response, using nuclear γH2AX as a marker for double-strand breaks (DSB). The integrity of neurovascular and immune compartments was assessed through CD31+microvascular density and activation of microglia/macrophages. Iba1+ ramified and CD68+phagocytic microglia/macrophages were quantified, along with the expression of inducible nitric oxide synthetase (iNOS). Tumor response to SDR (0.2 Gy/s) and FLASH (250 Gy/s) radiotherapy was evaluated in A549 carcinoma model, using tumor volume and Kaplan-Meier survival as endpoints. The results showed that helium FLASH radiotherapy significantly reduced acute brain tissue injury compared to SDR, evidenced by lower levels of DSB and preserved neurovascular endothelium. Additionally, FLASH radiotherapy reduced neuroinflammatory signals compared to SDR, as indicated by fewer CD68+ iNOS+ microglia/macrophages. FLASH radiotherapy achieved tumor control comparable to that of SDR radiotherapy. This study is the first to report the FLASH sparing effect of raster scanning helium ion radiotherapy in vivo, highlighting its potential for neuroprotection and effective tumor control.
Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition
Authors: Yang Shengtao , Datta Dibyadeep , Krienen Fenna M. , Ling Emi , Woo Elizabeth , May Athena , Anderson George M. , Galvin Veronica C. , Gonzalez-Burgos Guillermo , Lewis David A. , McCarroll Steven A. , Arnsten Amy FT , Wang Min 
Published: June 2024

SummaryCognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer’s disease, and have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may cause higher cognitive deficits in these disorders. The current study found that KYNA and its synthetic enzyme, KAT II, have greatly expanded expression in primate dlPFC in both glia and neurons. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys, suggesting a therapeutic avenue for the treatment of cognitive deficits in neuroinflammatory disorders.
A common neural signature between genetic and environmental risk
Authors: Vedechkina Maria , Holmes Joni , Warrier Varun , Astle Duncan 
Published: June 2024

ABSTRACTNot everyone is equally likely to experience mental illness. What is the contribution of an individual’s genetic background, or experiences of childhood adversity, to that likelihood? And how do these dimensions of risk interact at the level of the brain? We investigated the relationship between genetic liability for mental illness, childhood adversity, and cortico-limbic connectivity in a large developmental sample drawn from the ABCD cohort. First, we used Canonical Correlation Analysis to uncover two genetic dimensions of mental health using polygenic risk scores for ADHD, Anxiety, Depression, and Psychosis. The first dimension represented liability for broad psychopathology which positively correlated with adversity, while the second represented neurodevelopmental-specific risk which negatively interacted with adversity. Next, we investigated the cortico-limbic signature of adversity and genetic liability using Partial Least Squares. We found that the neural correlates of adversity broadly mirrored those of genetic liability, with adversity capturing most of the shared variance. These novel findings suggest that genetic and environmental riskoverlapin the neural connections that underlie behavioural symptomatology.
A novel monomeric amyloid β-activated signaling pathway regulates brain development via inhibition of microglia
Authors: Kwon Hyo Jun , Santhosh Devi , Huang Zhen 
Published: June 2024

ABSTRACTAmyloid β (Aβ) forms aggregates in the Alzheimer’s disease brain and is well known for its pathological roles. Recent studies show that it also regulates neuronal physiology in the healthy brain. Whether Aβ also regulates glial physiology in the normal brain, however, has remained unclear. In this article, we describe the discovery of a novel signaling pathway activated by the monomeric form of Aβ in vitro that plays essential roles in the regulation of microglial activity and the assembly of neocortex during development in vivo. We find that activation of this pathway depends on the function of amyloid precursor (APP) and the heterotrimeric G protein regulator Ric8a in microglia and inhibits microglial immune activation at transcriptional and post-transcriptional levels. Genetic disruption of this pathway during neocortical development results in microglial dysregulation and excessive matrix proteinase activation, leading to basement membrane degradation, neuronal ectopia, and laminar disruption. These results uncover a previously unknown function of Aβ as a negative regulator of brain microglia and substantially elucidate the underlying molecular mechanisms. Considering the prominence of Aβ and neuroinflammation in the pathology of Alzheimer’s disease, they also highlight a potentially overlooked role of Aβ monomer depletion in the development of the disease.
Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos
Authors: Finnerty Ryan M. , Carulli Daniel J. , Hegde Akshata , Wang Yanli , Baodu Frimpong , Winuthayanon Sarayut , Cheng Jianlin , Winuthayanon Wipawee 
Published: June 2024

ABSTRACTThe oviduct is the site of fertilization and preimplantation embryo development in mammals. Evidence suggests that gametes alter oviductal gene expression. To delineate the adaptive interactions between the oviduct and gamete/embryo, we performed a multi-omics characterization of oviductal tissues utilizing bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and proteomics collected from distal and proximal at various stages after mating in mice. We observed robust region-specific transcriptional signatures. Specifically, the presence of sperm induces genes involved in pro-inflammatory responses in the proximal region at 0.5 days post-coitus (dpc). Genes involved in inflammatory responses were produced specifically by secretory epithelial cells in the oviduct. At 1.5 and 2.5 dpc, genes involved in pyruvate and glycolysis were enriched in the proximal region, potentially providing metabolic support for developing embryos. Abundant proteins in the oviductal fluid were differentially observed between naturally fertilized and superovulated samples. RNA-seq data were used to identify transcription factors predicted to influence protein abundance in the proteomic data via a novel machine learning model based on transformers of integrating transcriptomics and proteomics data. The transformers identified influential transcription factors and correlated predictive protein expressions in alignment with thein vivo-derived data. Lastly, we found some differences between inflammatory responses in sperm-exposed mouse oviducts compared to hydrosalpinx fallopian tubes from patients. In conclusion, our multi-omics characterization and subsequentin vivoconfirmation of proteins/RNAs indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner.Significance StatementWe conducted a detailed molecular study of how the oviduct changes its gene expression and protein production in response to sperm and embryos after mating in mice. We found that the oviduct has distinct molecular signatures in different regions – upper versus lower regions. Shortly after mating, inflammatory responses are turned on in the lower regions due to the presence of sperm. A day later, metabolic genes ramp up in the lower regions, likely to provide nutrients for the developing embryos. Overall, this multi-omics study revealed that the oviduct dynamically adapts its molecular makeup over time and space to accommodate and support sperm, eggs and embryos.
Children Who Develop Celiac Disease Exhibit Distinct Metabolic Pathways Among Their Gut Microbiota Years Before Diagnosis
Authors: Kelley Kristina , Dogru Dogus , Huang Qian , Yang Yi , Palm Noah W. , Ludvigsson Johnny , Altindis Emrah 
Published: June 2024

ABSTRACTCeliac disease (CD) is an autoimmune condition caused by a loss of tolerance to gluten in genetically predisposed individuals. While 30-40% of people possess the predisposing alleles, only 1-2% of the population is diagnosed with CD. This indicates environmental factors play a role in the pathogenesis of the disease, however the trigger of gluten tolerance loss is unknown. The gut microbiome composition of CD patients differs in comparison to their healthy counterparts; however, a causal link has not been established. In this study, we examined the alterations in the composition of the gut microbiota in a retrospective, longitudinal cohort of 10 children at age 1, matched for sex, human leukocyte antigen (HLA) genotype and breastfeeding duration. All samples were obtained from the pediatric donors prior to diagnosis (CD progressors). We used Ig-A sequencing combined with 16S sequencing for samples obtained at age 1. We also identified the functional metabolic pathways enriched in CD progressors compared to the healthy controls at ages 1, 2.5 (n=15-16) and 5 (n=9-13) using data from a similar study that we previously completed. Our findings demonstrate that CD progressors have ASV-level alterations in their gut microbiome as early as the first year of life, including the increased presence of some taxa that have been previously been reported to be enriched in CD. Using PICRUSt analysis, we also showed that inflammatory- and pathogenicity-related functions are enriched in CD progressors’ gut microbiome years before diagnosis. These pathways include glycine, serine and threonine metabolism, N-glycan biosynthesis and fatty acid biosynthesis and beta-lactam resistance, which are potentially contributing to chronic inflammation in CD. Overall, our results indicate distinct metabolic pathways enriched in the gut microbiome of CD progressors years before diagnosis. Understanding these pathways could advance our understanding of CD pathogenesis and its link to the gut microbiome.
Viral Insulin/IGF-like Peptides Selectively Activate Host Insulin/IGF Signaling pathways during Grouper Iridovirus Infection
Authors: Chuard Aurelien , Nesarajah Kalaimagal , Danazumi Khadija , Reiners Kaitlin , Zhang Fa , Levintov Lev , Vashisth Harish , Dimarchi Richard , Altindis Emrah 
Published: June 2024

ABSTRACTUntil our recent discovery of viral insulin/IGF-1-like peptides (VILPs), examples of viral mimicry were mostly limited to immunomodulatory proteins and growth factors. We previously showed that six viruses in the Iridoviridae family encode genes mimicking insulin and IGF-1. While VILP-carrying viruses are isolated from fish, the role of VILPs in host-pathogen interactions remain elusive. In this study, we used the Grouper Iridovirus (GIV), one of the VILP-carrying viruses, to examine the impact of the GIV-VILPs on the host IGF-1R/IR system during infection. Our structural analysis revealed that GIV-VILP is 35% identical to both zebrafish insulin and 35 IGF-1. We also showed that GIV-VILPs are early viral transcripts and resulting peptides are secreted during viral infection. Both single-chain (sc, resembling IGF-1) and double chain (dc, resembling insulin) forms of chemically synthesized GIV-VILPs can stimulate insulin receptor (IR) and IGF-1 receptor (IGF1R) phosphorylation. They could also stimulatepost-receptor signaling in both grouper kidney (GK) and zebrafish AB.9 cells as potently as insulin. Notably, supernatants obtained from GIV-infected cells could stimulate insulin/IGF system in a dose dependent manner. Interestingly, GIV-VILP was able to selectively activate the Akt/PI3K pathway while had no or minimal effect on Erk/MAPK pathway. Using either IR, IGF1R or dual inhibitors, we illustrated that inhibition of IR signaling suppressed GIV viral replication while inhibition of IGF1R enhanced viral replication. Consistent with selective signaling action of PI3K/Akt pathway, inhibition of the Akt reduced GIV viral replication however Erk pathway inhibition did not affect it. In summary, GIV-VILP is produced during GIV infection and manipulates host insulin/IGF signaling in a selective manner. Our findings reveal a previously unknown viral strategy in which viruses mimic a host hormone to exploit the host’s endocrine system. This discovery unveils a novel viral pathogenesis mechanism, broadens our understanding of viral mimicry, and opens a new avenue to better understand viral strategies to manipulate the host.
Deriving connectivity from spiking activity in biophysical cortical microcircuits
Authors: Moghbel Faraz , Hassan Muhammad Taaha , Guet-McCreight Alexandre , Hay Etay 
Published: June 2024

AbstractInferring detailed cortical microcircuit connectivity is essential for uncovering how information is processed in the brain. A common methodin vivouses short-lag spike cross-correlations to derive putative monosynaptic connections between pairs of neurons, but previous studies did not address confounds of physiological large-scale networks such as correlated firing and inactive neurons. We tested connectivity derivation methods on ground-truth spiking data from detailed models of human cortical microcircuits in different layers and between key neuron types. We showed that physiological oscillations in the large-scale microcircuits hindered derivation accuracy, which was improved using a shorter cross-correlogram analysis window. We then showed that connection derivation was poor in cortical layer 2/3 microcircuits compared to layer 5, due to low firing rates and inactive neurons. General stimulation strategies for layer 2/3 microcircuits led to only a moderate improvement in derivation performance, due to a trade-off between the proportions of inactive neurons and overactive neurons, indicating the need for more refined strategies. Lastly, we showed that derivation of inhibitory connections from somatostatin interneurons targeting distal dendrites required a longer timescale of cross-correlation lags. Our results identify key physiological challenges and methods to improve accuracy in deriving connections from spiking activity in large-scale neuronal microcircuits.
Closely matched comparisons suggest that separable processes mediate contextual size illusions
Authors: Yu Xinran A. , Fischer Livia F. , Schwarzkopf Dietrich S. 
Published: June 2024

AbstractPrevious research suggests the magnitudes of the Ebbinghaus, Delboeuf, Ponzo, and tilt illusions all depend on the cortical distance between the neural representations of target stimuli and the surrounding context. However, several psychophysical studies found no compelling association between these illusions, calling this hypothesis into question. Here we ask if these discrepant reports could arise from methodological differences between these studies. We ran a battery of visual size illusion and basic discrimination tasks with carefully matched geometric properties, using a classic forced-choice design. In our small, homogenous sample, the Ebbinghaus and Delboeuf illusion magnitudes were strongly correlated, consistent with the idea that they reflect the same underlying mechanism when other sources of individual differences are minimised. Ponzo illusion magnitude also correlated with these two illusions, although less strongly in the case of the Ebbinghaus. Interestingly, the classic arrowhead version of the Mueller-Lyer illusion did not correlate with any of the other illusions or even with the objective ability to discriminate line length. This suggests that an altogether separate process underlies this perceptual effect. We further demonstrate that presenting stimuli briefly with central fixation critically affects measurements of the Ebbinghaus illusion. Additionally, we found that measuring illusion magnitude via adjustment is less reliable compared to two-alternative forced-choice procedures. Taken together, our findings suggest that different tasks probe separable processes determining illusion measurements. They further highlight the importance of the experimental design when testing relationships between perceptual effects and their links to neural processing.