bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the impact of artifact correction and artifact rejection on the performance of SVM-based decoding of EEG signals
Authors: Zhang Guanghui , Luck Steven J. 
Published: February 2025

AbstractNumerous studies have demonstrated that eyeblinks and other large artifacts can decrease the signal-to-noise ratio of EEG data, resulting in decreased statistical power for conventional univariate analyses. However, it is not clear whether eliminating these artifacts during preprocessing enhances the performance of multivariate pattern analysis (MVPA;decoding), especially given that artifact rejection reduces the number of trials available for training the decoder. This study aimed to evaluate the impact of artifact-minimization approaches on the decoding performance of support vector machines.Independent component analysis (ICA) was used to correct ocular artifacts, and artifact rejection was used to discard trials with large voltage deflections from other sources (e.g., muscle artifacts). We assessed decoding performance in relatively simple binary classification tasks using data from seven commonly-used event-related potential paradigms (N170, mismatch negativity, N2pc, P3b, N400, lateralized readiness potential, and error-related negativity), as well as more challenging multi-way decoding tasks, including stimulus location and stimulus orientation. The results indicated that the combination of artifact correction and rejection did not improve decoding performance in the vast majority of cases. However, artifact correction may still be essential to minimize artifact-related confounds that might artificially inflate decoding accuracy. Researchers who are decoding EEG data from paradigms, populations, and recording setups that are similar to those examined here may benefit from our recommendations to optimize decoding performance and avoid incorrect conclusions.
Endoplasmic reticulum stress protein GRP78 for ketamine’s antidepressant effects
Authors: Cui Wanpeng , Shen Chen , Xiong Wen-Cheng , Mei Lin 
Published: February 2025

SummaryKetamine is a fast-acting, long-lasting novel antidepressant. However, underpinning intracellular mechanisms remain unclear. We conducted an unbiased screening for genes that were less expressed in the prefrontal cortex (PFC) of mice that did not display antidepression-like effects to ketamine. GO analysis implicated endoplasmic reticulum and protein folding; in particular, GRP78, a stress-induced chaperone protein critical for protein folding, was reduced. We showed that GRP78 deficiency in PFC neurons induced depressive-like behaviors, whereas its overexpression produced anti-depression-like effects, revealing a novel function of GRP78. Prefrontal GRP78 was necessary for ketamine’s antidepressant-like effects. GRP78 was also required for ketamine to increase calcium activity and glutamatergic transmission. Enhancing GRP78 by viral infection and azoramide enabled non-responsive mice to respond to ketamine. Together, our results demonstrate that GRP78 is critical for ketamine to execute antidepressant effects by potentiating glutamatergic transmission in the PFC.HighlightsGRP78 was identified in non-biased screens for proteins that were lower in the PFC of mice that failed to exhibit antidepression-like effects after ketamine.Reducing GRP78 in the PFC induced depressive-like behaviors while increasing GRP78 had opposite effects in wildtype mice.GRP78 is required for ketamine to increase calcium activity in excitatory neurons and glutamatergic transmission.Enhancing GRP78 by viral infection and by azoramide enabled non-responsive mice to respond to ketamine.
Layered stomatal immunity contributes to resistance ofVitis ripariaagainst downy mildewPlasmopara viticola
Authors: Ji Wei , Zheng Wei , Mei JunJie , Liu Xiaoyu , Abe-Kanoh Naomi , Rhaman Mohammad Saidur , Qin Guochen , Ye Wenxiu 
Published: February 2025

ABSTRACTDowny mildew (DM), caused byPlasmopara viticola, is one of the most serious grapevine diseases. Resistant grapevines are a well-known tool for mitigating pathogen-caused damage. We evaluated 29 global grapevine cultivars from 7 species for the sensitivity toP. viticola. Chardonnay belonging to the sensitive speciesV. viniferaand Qingdahean belonging to the well-known resistant speciesV. ripariawere chosen for further investigation on the resistance mechanism against DM. Unlike Chardonnay, Qingdahean exerted an inhibitory effect on stomatal targeting, suppression of stomatal closure, stomatal penetration ofP. viticola, and the development of primary hyphae and haustoria during the early phase of infection, and contained higher levels of malondialdehyde (MDA), which was significantly increased byP. viticolainfection, toxic to the pathogen and had an interfering effect on the stomatal targeting. Furthermore, Qingdahean resisted pathogen invasion through the rapid induction of guard cell death and the hypersensitive responses (HR) of other cell types. These findings suggest that resistance toP. viticolaconsists of layered stomatal immunity in addition to the well-known HR inV. riparia, which is overcome by the pathogen inV. vinifera.
Essential role of CFAP77-CCDC105-TEX43 subcomplex in connecting axonemal A and B tubules for mammalian sperm motility
Authors: Xia Lan , Yin Guo-Liang , Long Yu , Sun Fei , Wang Bin-Bin , Zhu Yun , Chen Su-Ren 
Published: February 2025

AbstractThe assembly and physiological function of cilia and flagella depend on the stable association of A and B tubules, which form axonemal microtubule doublets (DMTs).CFAP77encodes a core outer junction (OJ) protein within DMTs that is conserved across species and cell types. However, whether and how CFAP77 mediates the connection of B tubules to A tubules of DMTs in mammalian cilia/flagella are unknown. In this study,Cfap77-KO mice were generated to reveal that CFAP77 is essential for sperm progressive motility and male fertility. Loss of CFAP77 led to opened B tubules specifically at the OJ regions of axonemal DMTs as revealed by conventional transmission electron microscopy. Cryo-electron tomography further resolved thein situstructure of sperm axonemal DMTs fromCfap77-KO mice, which exhibited a loss of large filamentous density corresponding to the CFAP77-CCDC105-TEX43 ternary subcomplex at the OJ regions. Additionally, sperm proteomic analysis confirmed that CFAP77 knockout led to the complete loss of this ternary complex. Our work not only explores the physiological role of OJ protein CFAP77 on axonemal A-B tubule connection in mammals but also combinesin situstructural biology and knockout mice to reveal the underlying structural/molecular mechanism.
The CRAC channel inhibitor BTP2 restricts Tulane virus and human norovirus replication independent of store-operated calcium entry
Authors: Scribano Francesca J. , Gebert J. Thomas , Engevik Kristen A. , Hayes Nicole M. , Pham Son , Kaundal Soni , Dave Janam J. , Prasad B V Venkataram , Estes Mary K. , Ramani Sasirekha , Hyser Joseph M. 
Published: February 2025

AbstractHuman norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that Tulane virus encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and genetically engineered cell lines, we establish that the SOCE inhibitor, BTP2, reduces TV replication in an SOCE-independent manner. We observed a significant reduction in TV replication, protein expression, and RNA synthesis in cells with both pre- and post-infection BTP2 treatment. By serial passage and plaque isolation, we demonstrate that TV quasi-species have mixed susceptibility and resistance to BTP2. Sequence comparison of the quasi-species revealed that amino acid changes in the structural proteins were associated with drug resistance. We utilized reverse genetics to generate TV with the resistance-associated VP1 and VP2 amino acid changes and found that a single amino acid change in VP1 (I380M) conferred BTP2 resistance. Further, expression of resistant VP2 alone was sufficient to partially rescue the replication of susceptible virus. Together, this supports that TV structural proteins are the targets of BTP2. Finally, using human intestinal organoids, we demonstrate that BTP2 significantly reduces human norovirus replication.ImportanceOur work identifies BTP2 as a potential human norovirus antiviral pharmacophore and highlights the utility of targeting calicivirus structural proteins to restrict viral replication. Further, we establish a system whereby Tulane virus can be used to screen novel antiviral candidates and establish their mechanism of action. Together, this will facilitate rapid preclinical validation of other novel human norovirus therapeutics.
Knowledge, Attitude, and Practice among school students and teachers about the Human Papillomavirus vaccine in Central Kerala- a cross-sectional study
Authors: Pious Thomas , John Anjum , Reshma V.R , Idicula Mercy John 
Published: February 2025

AbstractBackgroundHuman Papillomavirus (HPV) is the fourth most common cancer among women globally and a major public health concern. Uptake of HPV vaccine remains low despite its availability, in several countries, including India. India planned to introduce the HPV vaccine into the Universal Immunization Program (UIP), aiming to improve vaccine coverage. Knowledge, attitude, and practice (KAP) regarding the HPV vaccine among school-going adolescents, their parents, and teachers remain largely unexplored in Kerala, despite its high literacy. Understanding the awareness and perceptions of these stakeholders is critical for the successful implementation of vaccination programs.MethodsThis cross-sectional study will assess the KAP regarding HPV vaccination among school students (aged 11–15 years), their parents, and teachers in Thiruvalla Municipality, Kerala. A structured, validated questionnaire will be used to collect data from randomly selected government, private, and aided schools. Stratified random sampling will be used for student selection, while all teachers in the selected schools will be included through census sampling. Parents will be recruited using a convenience sampling approach. Descriptive and inferential statistical analyses will examine KAP levels, compare demographic groups, and identify predictors of vaccine acceptance.The study has received ethical approval and currently is in the process of obtaining necessary permissions from school authorities and fulfilling administrative requirements for implementation.Expected ResultsWe anticipate finding gaps in knowledge and varying levels of acceptance of the HPV vaccine among students, parents, and teachers. While some stakeholders may be aware of HPV and its link to cervical cancer, misconceptions and cultural barriers may hinder vaccine uptake. We expect that health education with access to reliable information will be associated with higher knowledge and a positive attitude toward vaccination.Expected ConclusionsThe study will provide insights into existing knowledge gaps and barriers to HPV vaccination in Kerala. Findings will inform the design of targeted educational interventions and policy recommendations to improve vaccine acceptance and coverage. Strengthening school-based awareness programs and involving teachers and parents as key advocates may significantly enhance HPV vaccine uptake and contribute to cervical cancer prevention efforts in India.
Method of loci training yields unique neural representations that support effective memory encoding
Authors: Ren Jingyuan , Konrad Boris N. , Zhu Yannan , Li Fan , Czisch Michael , Dresler Martin , Wagner Isabella C. 
Published: February 2025

AbstractThe method of loci is a technique to effectively boost memory, but its impact on the underlying neural representations is poorly understood. Here, we used functional magnetic resonance imaging and representational similarity analysis to compare the neural representations of memory athletes ranked among the world’s top 50 in memory sports to those of mnemonics-naïve controls. In a second study, mnemonics-naïve individuals underwent a 6-week-long memory training, working memory training, or no intervention. Results showed distinct neural representations in the prefrontal cortex, inferior temporal, and posterior parietal regions as memory athletes and the memory training group studied novel content. Neural representations were also distinct between these experienced individuals, which was related to better memory performance after 4 months. Our findings highlight how extensive memory training affects neocortical memory engrams. We suggest that the method of loci may bolster memory uniqueness within one’s “memory palace”, setting the stage for exceptional memory performance.
Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease
Authors: Farrell Clíona , Buhidma Yazead , Mumford Paige , Heywood Wendy E. , Hällqvist Jenny , Flores-Aguilar Lisi , Andrews Elizabeth , Rahimzadah Negin , Taso Orjona Stella , Doran Eric , Swarup Vivek , Head Elizabeth , Lashley Tammaryn , Mills Kevin , Toomey Christina E. , Wiseman Frances K. 
Published: February 2025

AbstractTrisomy of chromosome 21, the cause of Down syndrome (DS), is the most commonly occurring genetic cause of Alzheimer’s disease (AD). Here, we compare the frontal cortex proteome of people with Down syndrome-Alzheimer’s disease (DSAD) to demographically matched cases of early-onset AD and healthy ageing controls. We find wide dysregulation of the proteome, beyond proteins encoded by chromosome 21, including an increase in the abundance of the key AD-associated protein, APOE, in people with DSAD compared to matched cases of AD. To understand the cell types that may contribute to changes in protein abundance, we undertook a matched single-nuclei RNA-sequencing study, which demonstrated thatAPOEexpression was elevated in subtypes of astrocytes, endothelial cells and pericytes in DSAD. We further investigate how trisomy 21 may cause increased APOE. Increased abundance of APOE may impact the development of, or response to, AD pathology in the brain of people with DSAD, altering disease mechanisms with clinical implications. Overall, these data highlight that trisomy 21 alters both the transcriptome and proteome of people with DS in the context of AD, and that these differences should be considered when selecting therapeutic strategies for this vulnerable group of individuals who have high-risk of early-onset dementia.
Caloric restriction worsens decision-making impairments and gut dysbiosis after brain injury in male rats
Authors: Speas Reagan L. , McCloskey Jenna E. , Bressler Noah M. , Frankot Michelle A. , Gratzol Carissa , Pechacek Kristen M. , Martens Kris M. , Vonder Haar Cole 
Published: February 2025

AbstractTraumatic brain injury (TBI) causes long-term deficits in decision-making and disrupts the gut microbiome. Dysbiosis of the gut microbiome is a potential contributor to the development of multiple psychiatric and neurological disorders and may be a contributor to chronic symptoms from TBI. Caloric restriction is often used to assess psychiatric-related behaviors in animals, but also affects the gut microbiome. In the current study, we evaluated the effects of caloric restriction versus free feeding on a frontal controlled cortical impact TBI. Rats were trained on the rodent gambling task, an analog of the Iowa gambling task, to assess risk-based decision-making. The microbiome was sampled through the acute to subacute period post-injury and lesion size and microglia counts evaluated at 10 weeks post-injury. Caloric restriction did not affect decision-making at baseline, but did affect motivational variables. TBI impaired decision-making and this effect was exacerbated by caloric restriction. Other motivation-related variables followed a similar pattern of impairment with TBI driving impairments that were worsened by caloric restriction. The gut microbiome was initially dysbiotic, but largely recovered within 14 days post-injury. Despite this, acute gut measurements were predictive of chronic decision-making impairment. These data indicate a role for the gut microbiome in the evolution of TBI deficits and suggest that interventions targeting the gut may have a limited window of opportunity to treat long-term deficits.
Remembering the opponent: neuronal activation associated with social memory in Zebrafish
Authors: Cavallino Luciano , Pedreira María E , Pozzi Andrea G , Scaia María F 
Published: February 2025

AbstractLearning and remembering an opponent and the characteristics of a previous encounter may allow individuals to modify their behavior based on that acquired information. In the present study, using a long-term memory paradigm associated with social interactions, we aimed to evaluate the neuronal activation underlying individual recognition and memory of a previous agonistic encounter in male zebrafish. By quantifying a marker of neuronal activation, the immediate early gene c-fos, we compared the activation in different telencephalic nuclei belonging to the social decision-making network. Two dorsal nuclei, the medial (Dm) and the lateral (Dl), and two ventral nuclei, the ventral (Vv) and the dorsal (Vd), were evaluated by quantifying c-fos protein by immunohistochemical techniques. Two agonistic encounters between the same pair of opponents were performed, and the number of c-fos-immunopositive cells was quantified immediately after the second encounter in fish that had been treated with an amnesic agent after the first encounter (MK-801) and untreated individuals (Water), as well as a Control group with no physical interaction. We found that the Vv nucleus showed lower activation in individuals not exposed to physical interaction than those exposed (MK-801 and Water treatment). The Dl nucleus showed a higher activation only in individuals previously treated with MK-801, who would face an unremembered opponent, but not in those treated with water, which recognized the opponent. Our study provides evidence as a first step to understanding the neuronal processes underlying individual recognition and retrieval of an opponent.Summary statementOur study provides new information about the neuronal activation related to individual recognition and social interaction in zebrafish
Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations
Authors: Hawkes Gareth , Wright Harrison I. W. , Beaumont Robin N. , Chundru Kartik , Hanson Aimee , Jackson Leigh , Murray Anna , Patel Kashyap , Frayling Timothy M. , Wright Caroline F. , Wood Andrew R. , Weedon Michael N. 
Published: February 2025

AbstractGenetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,976 individuals of diverse ancestry to evaluate the contribution and architecture of rare non-coding variants to three commonly studied anthropometric traits: height, body mass index (BMI) and waist-hip ratio adjusted for BMI (WHRadjBMI). Analysing 447,461 individuals in UK Biobank for discovery and 225,515 individuals in All of Us for replication, we identified 90 novel rare and low-frequency single variant associations. This includes two independent rare variants upstream ofIGF2BP2that both substantially reduce WHRadjBMI, but have distinct effects on other adiposity traits. We identified 135 coding variant aggregates, several of which were missed by exome sequencing studies. For example,UBR3protein-truncating variants were associated with a 2.7kg/m2 increase in BMI. We additionally identified 51 non-coding variant aggregate associations, including in the 5’UTR ofFGF18(a highly constrained gene with no previously reported coding associations) associated with up to 6cm effects on height. We show that 97% of rare variant associations occur near GWAS loci demonstrating convergence of rare and common variant associations. Finally, we show that ultra rare variants (MAF<0.01%) explain a small fraction of heritability (<10%) compared to common variants for these traits, that heritability is largely shared across ancestries, and that this heritability is concentrated at or near common variant loci. Our work demonstrates the importance of large-scale WGS for fully understanding the genetic architecture of complex traits.
Expression of the Close homolog of L-1 and embigin identifies activated myofibroblasts
Authors: Stock Angus T , Day Jess , Huckstep Hannah , Garnham Alexandra L , Wicks Ian P 
Published: February 2025

AbstractFibrosis is driven by the emergence of myofibroblasts, which are the primary producers of the extracellular matrix proteins that form fibrotic lesions. Despite this critical role, detecting myofibroblasts remains challenging due to the paucity of selective markers. We therefore screened for novel myofibroblast-specific markers, discovering that the expression of the close homolog of L1 (ChL-1) and embigin (Emb) distinguish activated myofibroblasts from their quiescent precursors. We report that ChL-1+/Emb+ fibroblasts: (1) emerge during cardiac inflammation, (2) have elevated expression of collagens and inflammatory factors and (3) localise to fibrotic zones - consistent with activated myofibroblasts. Mechanistically, Chl1+/Emb+ myofibroblasts differentiate from resident fibroblasts which upregulate these markers in response to proinflammatory cytokines, such as IL-1 and IL-17. Moreover, we show that embigin could be exploited to target antibody-based therapies to myofibroblasts and confirm this protein as a conserved marker of activated fibroblasts in multiple tissues and settings. Collectively, these findings identify ChL-1 and embigin as novel myofibroblast surface-markers that could be used to identify, enumerate and target this pathogenic population.