bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune History Modifies Disease Severity to HPAI H5N1 Clade 2.3.4.4b Viral Challenge
Authors: Brigleb Pamela H. , Sharp Bridgett , Roubidoux Ericka Kirkpatrick , Meliopoulos Victoria , Tan Shaoyuan , Livingston Brandi , Morris Dorothea , Ripperger Tyler , Lazure Lauren , Balaraman Velmurugan , Thompson Alexis C. , Kleinhenz Katie , Dimitrov Kiril , Thomas Paul G. , Schultz-Cherry Stacey 
Published: October 2024

AbstractThe most recent outbreak of highly pathogenic avian H5 influenza (HPAI) virus in cattle is now widespread across the U.S. with spillover events happening to other mammals, including humans. Several human cases have been reported with clinical signs ranging from conjunctivitis to respiratory illness. However, most of those infected report mild to moderate symptoms, while previously reported HPAI H5Nx infections in humans have had mortality rates upwards of 50%. We recently reported that mice with pre-existing immunity to A/Puerto Rico/08/1934 H1N1 virus were protected from lethal challenge from highly pathogenic clade 2.3.4.4b H5N1 influenza virus. Here, we demonstrate that mice infected with the 2009 pandemic H1N1 virus strain A/California/04/2009 (Cal09) or vaccinated with a live-attenuated influenza vaccine (LAIV) were moderately-to-highly protected against a lethal A/bovine/Ohio/B24OSU-439/2024 H5N1 virus challenge. We also observed that ferrets with mixed pre-existing immunity—either from LAIV vaccination and/or from Cal09 infection—showed protection against a HPAI H5N1 clade 2.3.4.4b virus isolated from a cat. Notably, this protection occurred independently of any detectable hemagglutination inhibition titers (HAIs) against the H5N1 virus. To explore factors that may contribute to protection, we conducted detailed T cell epitope mapping using previously published sequences from H1N1 strains. This analysis revealed a high conservation of amino acid sequences within the internal proteins of our bovine HPAI H5N1 virus strain. These data highlight the necessity to explore additional factors that contribute to protection against HPAI H5N1 viruses, such as memory T cell responses, in addition to HA-inhibition or neutralizing antibodies.
Enhanced immune evasion of SARS-CoV-2 KP.3.1.1 and XEC through NTD glycosylation
Authors: Liu Jingyi , Yu Yuanling , Jian Fanchong , Yang Sijie , Song Weiliang , Wang Peng , Yu Lingling , Shao Fei , Cao Yunlong 
Published: October 2024

AbstractKP.3.1.1 has surpassed KP.3 to become the new globally dominant strain, while XEC, a recombinant variant of KS.1.1/KP.3.3, is rapidly expanding across Europe and North America. Notably, both variants carry mutations, S31del of KP.3.1.1 and T22N of XEC, that could introduce new N-linked glycans on the Spike N-terminal domain (NTD), emphasizing the urgent need to assess their potential changes in viral characteristics. Here, we found that both KP.3.1.1 and XEC maintained the high ACE2-Spike binding affinity and pseudovirus infectivity of KP.3. Importantly, compared to KP.3, KP.3.1.1, and especially XEC, could further evade the neutralizing antibodies in convalescent plasma, even those elicited by KP.2-like breakthrough infections. Interestingly, both variants demonstrated increased resistance against monoclonal neutralizing antibodies targeting various epitopes on the receptor-binding domain (RBD). These suggest that the additional NTD glycosylation of KP.3.1.1 and XEC could enhance immune evasion via allosteric effects, and supports the future prevalence of XEC.
Size Selection of Giant Unilamellar Vesicles (GUVs) via Modified cDICE Method
Authors: Chen Ariel , Gat Shachar , Ohana Lior , Yekimov Evgeni , Tsori Yoav , Bernheim-Groswasser Anne 
Published: October 2024

ABSTRACTThe production of giant unilamellar vesicles (GUVs) plays a pivotal role in various scientific disciplines, particularly in the development of synthetic cells. While numerous methods exist for GUV preparation, the modified continuous droplet interface crossing encapsulation (cDICE) method offers the advantages of simplicity and high encapsulation efficiency. However, a significant limitation of this technique is the generation of vesicles with a broad size distribution and the inability to control the desired size range. This raises a key question: Can the modified cDICE method be optimized to produce GUVs with controlled size distribution? In this study, we examined the effects of two experimental parameters—rotation time (tROT) and the angular frequency (ω) of the cDICE chamber—on the size distribution of GUVs. Our results show that reducing either the angular frequency or rotation time shifts the size distribution toward larger vesicles, enabling effective size selection. These findings are further supported by a physical model, which provides insights into the mechanisms underlying size selection. This work demonstrates that control over GUV size distribution can be achieved through straightforward adjustments of system parameters. The ability to fine-tune vesicle size offers researchers a powerful tool for developing customizable experimental systems for synthetic biology and related fields.
The role of dopaminergic, cholinergic and noradrenergic networks in hyposmia in Parkinson’s disease
Authors: Pérot Jean-Baptiste , Kozlowski Esther , Fraysse Audrey , Ouarab Salim , Valabregue Romain , Rebbah Sana , Lejeune François-Xavier , Massy Emma , Gaurav Rahul , Arnulf Isabelle , Corvol Jean-Christophe , Vidailhet Marie , Pyatigorskaya Nadya , Galléa Cécile , Lehéricy Stéphane 
Published: October 2024

AbstractBackgroundOlfactory impairment is frequently observed in Parkinson’s disease (PD) before motor symptom onset. Patients with isolated rapid eye movement sleep behaviour disorder (iRBD) are at risk to develop PD and present olfactory dysfunction. Subcortical neuromodulatory nuclei including the substantia nigra, the nucleus basalis of Meynert, and the locus coeruleus, may all contribute to olfactory dysfunction.ObjectiveThe objective of this study was to understand the network alterations underlying olfactory dysfunction in PD and in the early prodromal iRBD patients using multimodal MRI.MethodsPD (n = 107), iRBD patients (n = 35) and healthy controls (HC, n = 39) were recruited from the ICEBERG cohort for a cross-sectional study. We separated subjects in Healthy Controls, iRBD patients, and PD patients with or without RBD and with or without anosmia. Olfactory, motor, and cognitive scores were assessed and combined with multimodal imaging.ResultsWe found that olfaction positively correlated with (i) striatal DaT signal in PD patients; (ii) neuromelanin contrast in the locus coeruleus and (iii) Nucleus Basalis of Meynert grey matter (GM) volume in all patients. These signals were uncorrelated with motor and cognitive scores. Functional connectivity was reduced in regions of the cholinergic olfactory network in anosmic patients. Functional connectivity was also reduced in the noradrenergic network of patients with RBD.DiscussionOur results indicate the implication of the cholinergic network in PD patients with anosmia and a contribution of the noradrenergic network to olfactory dysfunction, only in patients with RBD.
Distractor anticipation during working memory is associated with theta and beta oscillations across spatial scales
Authors: Jung Dennis Y. , Sahoo Bikash C. , Snyder Adam C. 
Published: October 2024

AbstractAnticipating distractors during working memory maintenance is critical to reduce their disruptive effects. In this study, we aimed to identify the oscillatory correlates of this process across different spatial scales of neural activity. We simultaneously recorded local field potentials (LFP) from the LPFC and electroencephalograms (EEG) from the scalp of monkeys performing a modified memory-guided saccade (MGS) task. The monkeys were required to remember the location of a target visual stimulus while anticipating distracting visual stimulus, flashed at 50% probability during the delay period. We found significant theta-band activity across spatial scales during anticipation of a distractor, closely linked with underlying working memory dynamics, through decoding and cross-temporal generalization analyses. EEG particularly reflected reactivation of memory around the anticipated time of a distractor, even in the absence of stimuli. During this anticipated time, beta-band activity exhibited transiently enhanced intrahemispheric communication between the LPFC and occipitoparietal brain areas. These oscillatory phenomena were observed only when the monkeys successfully performed the task, implicating their possible functional role in mitigating anticipated distractors. Our results demonstrate that distractor anticipation recruits multiple oscillatory processes across the brain during working memory maintenance, with a key activity observed predominantly in the theta and beta bands.
Soil properties in agricultural systems affect microbial genomic traits
Authors: Goodall Tim , Busi Susheel Bhanu , Griffiths Robert I. , Jones Briony , Pywell Richard F. , Richards Andrew , Nowakowski Marek , Read Daniel S. 
Published: October 2024

AbstractUnderstanding the relationships between bacterial taxa, their ecological and genomic traits, and their environment, is important for elucidating the mechanisms that drive microbial community dynamics and their roles in ecosystem functioning. This is especially true for soils, where dramatic shifts in resource input or physicochemical properties occur through land use and agricultural practices. Here, we examined the relationships between soil properties and bacterial traits within highly managed agricultural soil systems subjected to arable crop rotations or management as permanent pasture. We assessed the bacterial communities within these soils using amplicon sequencing and assigned each amplicon trait scores for rRNA copy number, genome size, and GC content, which are classically associated with potential growth rates and specialisation. We also calculated the niche breadth trait of each amplicon as a measure of social ubiquity within the examined samples. Within this soil system, we demonstrated that pH was the primary driver of bacterial traits. The weighted mean trait scores of the samples revealed that bacterial communities associated with soils at lower pH (<7) tended to have larger genomes (possess more potential plasticity), have more rRNA (higher growth rate potential), and are more ubiquitous (have less niche specialisation) than the bacterial communities from higher pH soils. Our findings highlight not only the association between pH and bacterial community composition but also the importance of pH in driving community functionality by directly influencing genomic and niche traits.
Equivalence between representational similarity analysis, centered kernel alignment, and canonical correlations analysis
Authors: Williams Alex H. 
Published: October 2024

AbstractCentered kernel alignment (CKA) and representational similarity analysis (RSA) of dissimilarity matrices are two popular methods for comparing neural systems in terms of representational geometry. Although they follow a conceptually similar approach, typical implementations of CKA and RSA tend to result in numerically different outcomes. Here, I show that these two approaches are largely equivalent once one incorporates a mean-centering step into RSA. This equivalence holds for both linear and nonlinear variants of these methods. These connections are simple to derive, but appear to have been thus far overlooked in the context of comparing neural representations. By unifying these measures, this paper hopes to simplify a complex and fragmented literature on this subject.
Cortex-wide characterization of decision-making neural dynamics during spatial navigation
Authors: Haley Samuel P. , Surinach Daniel A. , Nietz Angela K. , Carter Russell E. , Zecker Lucas S. , Popa Laurentiu S. , Kodandaramaiah Suhasa B. , Ebner Timothy J. 
Published: October 2024

SummaryDecision-making during freely moving behaviors involves complex interactions among many cortical and subcortical regions. However, the spatiotemporal coordination across regions to generate a decision is less understood. Using a head-mounted widefield microscope, cortex-wide calcium dynamics were recorded in mice expressing GCaMP7f as they navigated an 8-maze using two paradigms. The first was an alternating pattern that required short term memory of the previous trial to make the correct decision and the second after a rule change to a fixed path in which rewards were delivered only on the left side. Identification of cortex-wide activation states revealed differences between the two paradigms. There was a higher probability for a visual/retrosplenial cortical state during the alternating paradigm and higher probability of a secondary motor and posterior parietal state during left-only. Three state sequences (motifs) illustrated both anterior and posterior activity propagations across the cortex. The anterior propagating motifs had the highest probability around the decision and posterior propagating motifs peaked following the decision. The latter, likely reflecting internal feedback to influence future actions, were more common in the left-only paradigm. Therefore, the probabilities and sequences of cortical states differ when working memory is required versus a fixed trajectory reward paradigm.
Pseudomonas aeruginosaAlkyl Quinolone Response is dampened by Enterococcus faecalis
Authors: Fink Maggie M. , Weaver Abigail A. , Parmar Dharmeshkumar , Paczkowski Jon E. , Li Lingyun , Klaers Maggie K. , Junker Ella A. , Jarocki Elizabeth A. , Sweedler Jonathan V. , Shrout Joshua D. 
Published: October 2024

AbstractThe bacteriumPseudomonas aeruginosais an opportunistic pathogen that can cause lung, skin, wound, joint, urinary tract, and eye infections. WhileP. aeruginosais known to exhibit a robust competitive response towards other bacterial species, this bacterium is frequently identified in polymicrobial infections where multiple species survive. For example, in prosthetic joint infections (PJIs),P. aeruginosacan be identified along with other pathogenic bacteria includingStaphylococcus aureus, Enterococcus faecalis,andCorynebacterium striatum.Here we have explored the survival and behavior of such microbes and find thatE. faecalisreadily survives culturing withP. aeruginosawhile other tested species do not. In each of the tested conditions,E. faecalisgrowth remained unchanged by the presence ofP. aeruginosa,indicating a unique mutualistic interaction between the two species. We find thatE. faecalisproximity leadsP. aeruginosato attenuate competitive behaviors as exemplified by reduced production ofPseudomonasquinolone signal (PQS) and pyocyanin. Reduced alkyl quinolones is important toE. faecalisas it will grow in supernatant from a quinolone mutant but not P. aeruginosa wildtype in planktonic culture. The reduced pyocyanin production ofP. aeruginosais attributable to production of ornithine byE. faecalis, which we recapitulate by adding exogenous ornithine toP. aeruginosamono-cultures. Similarly, co-culture with an ornithine-deficient strain ofE. faecalisleadsP. aeruginosato yield near mono-culture amounts of pyocyanin. Here, we directly demonstrate how notorious pathogens such asP. aeruginosamight persist in polymicrobial infections under the influence of metabolites produced by other bacterial species.ImportanceWhile we now appreciate that many infections are polymicrobial, we understand little of the specific actions between a given set of microbes to enable combinatorial survival and pathogenesis. The bacteriaPseudomonas aeruginosaandEnterococcus faecalisare both prevalent pathogens in wound, urinary tract, and bacteremic infections. WhileP. aeruginosaoften kills other species in standard laboratory culture conditions, we present here thatE. faecaliscan be reliably co-cultured withP. aeruginosa.We specifically detail that ornithine produced byE. faecalisreduces the Pseudomonas Quinolone Signal response ofP. aeruginosa. This reduction of the Pseudomonas Quinolone Signal response aidsE. faecalisgrowth.
RTL4,a retrovirus-derived gene implicated in autism spectrum disorder, is a microglial gene that responds to noradrenaline in the postnatal brain
Authors: Ishino Fumitoshi , Itoh Johbu , Matsuzawa Ayumi , Irie Masahito , Suzuki Toru , Hiraoka Yuichi , Yoshikawa Masanobu , Kaneko-Ishino Tomoko 
Published: October 2024

AbstractRTL4, a gene acquired from a retrovirus, is a causative gene in autism spectrum disorder. Its KO mice exhibit increased impulsivity, impaired short-term spatial memory, failure to adapt to novel environments, and delayed noradrenaline (NA) recovery in the frontal cortex. However, due to its very low expression in the brain, it remains unknown which brain cells express RTL4 and its dynamics in relation to NA. Here, using knock-in mice carrying endogenousRtl4fused toVenus, we demonstrated thatRTL4is a microglial gene with several important properties. The RTL4-Venus fusion protein was detected as a secreted protein in the midbrain, hypothalamus, hippocampus and amygdala in the postnatal brain. Its signal intensity was high during critical periods of neonatal adaptation to novel environments and was upregulated by various stimuli, such as handling the mice, mild environmental changes and administration of isoproterenol, an agonist of adrenergic beta receptors. It was decreased by anesthesia but was maintained by the administration of milnacipran, an NA reuptake inhibitor. These results suggest that RTL4 intensity depends on the arousal state via NA and is somehow related to the NA reuptake process.In vitromixed glial culture experiments demonstrated thatRtl4is a microglial gene and suggested that RTL4 secretion responds rapidly to isoproterenol. Taken together with previous results fromRtl4KO mice, microglial RTL4 plays an important role in the NA response and it is likely involved in the development of the NAergic neuronal network in the brain.
Depletion of BBSome Subunits Alters Receptor Endocytosis and Promotes EMT via TGF-β Signaling
Authors: Solarat C. , Barra-Carneiro J. , Vila-Almuíña S. , Barbeito P. , Schrøder Holm M. , Gammoh N. , Christensen S.T. , Valverde D. 
Published: October 2024

SummaryCiliopathies are genetic disorders caused by defects in the structure or function of the cilia and their related structures. Bardet-Biedl syndrome (BBS) is a complex ciliopathy with varied symptoms, probably due to altered membrane receptor signalling pathways. This study explores the role ofBBS1andBBS4gene deficiencies in receptor trafficking and epithelial-mesenchymal transition (EMT) in retinal epithelial cells. Deficiencies in these genes, key components of the BBSome complex, led to shorter cilia and disrupted receptor endocytosis.BBS1knockout (KO) cells showed delayed transferrin internalisation and increased recycling of TGFBR1, promoting EMT. On the contrary,BBS4KO cells had higher receptor degradation but no affected recycling. These disruptions suggest that BBSome regulates both ciliary and nonciliary pathways. Increased EMT markers inBBS1KO cells were associated with higher cell migration and reduced proliferation, highlighting the role in receptor trafficking and potential therapeutic targets for retinal degeneration in BBS.HighlightsDepletion of BBS1 and BBS4 alters endocytic trafficking as well as length and/or frequency of primary cilia, affecting the internalisation of receptors at the ciliary pocket.BBS1knockout cells show increased EMT, up-regulation of mesenchymal markers, enhanced migration, and reduced proliferation after TGF-β stimulation.BBS1knockout cells exhibit increased TGFBR1 recycling, whileBBS4KO cells exhibit balanced receptor degradation and recycling, indicating distinct roles of these two BBSome components in receptor trafficking.Targeting the TGF-β pathway and EMT may provide therapeutic options for retinal degeneration in Bardet-Biedl syndrome.
Comparative genomic analysis reveals reduced pathogenicity ofRalstoniaspp. in water
Authors: Liu Gaopeng , Mao Chengzhi , Li Qi , Huo Da , Li Tao 
Published: October 2024

AbstractRalstoniaspp., known for their adaptability across various habitats, are known to cause infections. The adaptive metabolic diversity of those inhabiting aquatic ecosystems remains poorly understood. We report four newRalstonia pickettiigenomes enriched in the cyanobacterial culture derived from bloom-forming cyanobacteria,Dolichospermum. A total of 228 complete genomes from theRalstoniagenus were utilized for phylogenetic inference, categorizing them based on isolation environment and host: water, soil, plant, and human groups. Meanwhile, the abundance of carbohydrate-active enzymes and secondary metabolites in water and human groups differed from the plant-host associate habitat.CeoBand two β-lactamases types ofOXAwere identified in the water habitat, showing similarities to certain strains in the human-host but differences from other habitats. The infectivity within water habitats seems to diminish, as evidenced by the decreased abundance of T3SS virulence proteins. Moreover, a distinctive pyrimidine degradation pathway in water degrades exogenous pyrimidines to supply nitrogen and other compounds for energy metabolism to provide a potential for broader habitat adaptability. Fluorescence in situ hybridization results confirmed thatR. pickettiirarely attached to cyanobacterial cells, indicating that they are not parasitic relationships. We postulate that the absence of T3SS and the unique metabolic profile represent adaptations ofRalstoniato an aquatic free-living lifestyle.
Human gut commensalAlistipes timonensismodulates the host lipidome and delivers anti-inflammatory outer membrane vesicles to suppress colitis in anIl10-deficient mouse model
Authors: Older Ethan A. , Mitchell Mary K. , Campbell Andrew , Lian Xiaoying , Madden Michael , Wang Yuzhen , van de Wal Lauren E. , Zaw Thelma , VanderVeen Brandon N. , Tatum Rodney , Murphy E. Angela , Chen Yan-Hua , Fan Daping , Ellermann Melissa , Li Jie 
Published: October 2024

AbstractCorrelative studies have linked human gut microbes to specific health conditions.Alistipesis one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role ofAlistipesin IBD has not been studied and the underlying molecular mechanisms also remain unknown. In this study, colonization ofIl10-deficient mice withAlistipes timonensisDSM 27924 delays the development of colitis. Colonization withAlistipesdoes not significantly alter the gut microbiome composition during colitis development, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived fromAlistipesare also detected in the plasma of colonized mice, which carry metabolites with immunomodulatory potential into the host circulatory system. We further demonstrate that fractions ofA. timonensisOMVs suppress LPS-inducedIl6,Il1b, andTnfaexpressionin vitroin murine macrophages. We detect immunomodulatory sulfonolipids (SoLs) in the active fraction, which are also increased in the blood ofA. timonensis-colonized mice; and we identify other putative bioactive lipids in theA. timonensisOMVs. Thus,A. timonensisOMVs represent a potential mechanism forAlistipes-mediated delay of colitis progression inIl10-deficient mice through the delivery of immunomodulatory lipids, including SoLs, and modulation of the host plasma lipidome.