bluuebunny/crossref_metadata_2025_split huggingface dataset:
BTSP, not STDP, Drives Shifts in Hippocampal Representations During Familiarization
Authors: Madar A.D. , Dong C. , Sheffield M.E.J. 
Published: October 2023

ABSTRACTSynaptic plasticity is widely thought to support memory storage in the brain, but the rules determining impactful synaptic changes in-vivo are not known. We considered the trial-by-trial shifting dynamics of hippocampal place fields (PFs) as an indicator of ongoing plasticity during memory formation. By implementing different plasticity rules in computational models of spiking place cells and comparing to experimentally measured PFs from mice navigating familiar and novel environments, we found that Behavioral-Timescale-Synaptic-Plasticity (BTSP), rather than Hebbian Spike-Timing-Dependent-Plasticity, is the principal mechanism governing PF shifting dynamics. BTSP-triggering events are rare, but more frequent during novel experiences. During exploration, their probability is dynamic: it decays after PF onset, but continually drives a population-level representational drift. Finally, our results show that BTSP occurs in CA3 but is less frequent and phenomenologically different than in CA1. Overall, our study provides a new framework to understand how synaptic plasticity shapes neuronal representations during learning.
Modulating the Unfolded Protein Response with ISRIB Mitigates Cisplatin Ototoxicity
Authors: Li Jiang , Rouse Stephanie L. , Matthews Ian R. , Sherr Elliott H. , Chan Dylan K. 
Published: October 2023

AbstractCisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancies, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathyin vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin and UPR-modulating drugs, and UPR marker gene expression and cell death measured. Treatment with ISRIB, a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested in anin vivomouse model of cisplatin ototoxicity and well as a head and neck squamous cell carcinoma (HNSCC) cell-based assay of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose-response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin’s cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.
Chronically disrupted sleep induces senescence in the visceral adipose tissue of C57BL/6 mice
Authors: Timonina Daria , Hormazabal Genesis V , Heckenbach Indra , Anderton Edward , Haky Lauren , Floro Ariel , Riley Rebeccah , Kwok Ryan , Breslin Stella , Ingle Harris , Tiwari Ritesh , Bielska Olga , Scheibye-Knudsen Morten , Kasler Herbert , Campisi Judith , Walter Marius , Verdin Eric 
Published: October 2023

AbstractThe role of sleep in systemic aging remains poorly understood, despite sleep’s essential function in preserving overall health and the prevalence of reduced sleep quality in modern society. Although reduced sleep correlates with an elevated risk of age-related diseases in humans, the mechanisms underlying this are unclear. In this study, we established a link between sleep and aging by demonstrating that disrupting sleep in C57BL/6 mice drives cellular senescence in the visceral adipose tissue. Sleep disruption also led to increased oxidative stress and DNA damage, both recognized triggers for senescence induction. Cellular senescence is implicated in numerous age-related conditions which are associated with insufficient sleep, such as cardiovascular disease, type 2 diabetes, and chronic inflammation. Our findings identify an accumulation of senescent cells in the adipose tissue, which serves as a potential target through which disturbed sleep accelerates the aging process and elevates the risk of age-related diseases.
The sensor of the bacterial histidine kinase CpxA is a novel dimer of extracytoplasmic Per-ARNT-Sim (PAS) domains
Authors: Cho Timothy H. S. , Murray Cameron , Malpica Roxana , Margain-Quevedo Rodrigo , Thede Gina L. , Lu Jun , Edwards Ross A. , Glover J. N. Mark , Raivio Tracy L. 
Published: October 2023

AbstractHistidine kinases are key bacterial sensors that recognize diverse environmental stimuli. While mechanisms of phosphorylation and phosphotransfer by cytoplasmic kinase domains are relatively well-characterized, the ways in which extracytoplasmic sensor domains regulate activation remain mysterious. The Cpx envelope stress response is a conserved Gram-negative two-component system which is controlled by the sensor kinase CpxA. We report the structure of theEscherichia coliCpxA sensor domain (CpxA-SD) as a globular Per-ARNT-Sim (PAS)-like fold highly similar to that ofVibrio parahaemolyticusCpxA as determined by X-ray crystallography. Because sensor kinase dimerization is important for signaling, we used AlphaFold2 to model CpxA-SD in the context of its connected transmembrane domains, which yielded a novel dimer of PAS domains possessing a distinct dimer organization compared to previously characterized sensor domains. Gain of functioncpxA* alleles map to the dimer interface, and mutation of other residues in this region also leads to constitutive activation. CpxA activation can be suppressed by mutations that restore inter-monomer interactions, suggesting that inhibitory interactions between CpxA-SD monomers are the major point of control for CpxA activation and signaling. Searching through hundreds of structural homologues revealed the sensor domain ofPseudomonas aeruginosasensor kinase PfeS as the only PAS structure in the same novel dimer orientation as CpxA, suggesting that our dimer orientation may be utilized by other extracytoplasmic PAS domains. Overall, our findings provide insight into the diversity of the organization of PAS sensory domains and how they regulate sensor kinase activation.SignificanceBacterial two-component systems play an essential role in sensing environmental cues, mitigating stress, and regulating virulence. We approach the study of a key Gram-negative sensor kinase CpxA with both classical methods in structural biology and genetic analysis and emerging protein-folding prediction software. This approach provides a wholistic perspective on the structure and function of histidine kinases as proteins with modular and cellular compartment-spanning domain architectures. We report a novel organization of PAS domains in CpxA, highlighting the versatility and diversity of this sensory fold. Ultimately, these studies will facilitate the continued development of novel antimicrobials against sensor kinases, including CpxA, which is a previously studied target for antimicrobials.
Scene-selective regions encode the vertical position of navigationally relevant information in young and older adulthood
Authors: Durteste Marion , Liebi Luca R. , Sapoval Emma , Delaux Alexandre , Arleo Angelo , Ramanoël Stephen 
Published: October 2023

AbstractPosition within the environment influences the navigational relevance of objects. However, the possibility that vertical position represents a central object property has yet to be explored. Considering that the upper and lower visual fields afford distinct types of visual cues and that scene-selective regions exhibit retinotopic biases, it is of interest to elucidate whether the vertical location of visual information modulates neural activity in these high-level visual areas. The occipital place area (OPA), parahippocampal place area (PPA) and medial place area (MPA) demonstrate biases for the contralateral lower visual field, contralateral upper visual field, and contralateral hemifield, respectively. Interesting insights could also be gained from studying older adulthood as recent work points towards an age-related preference for the lower visual field. In the present study, young and older participants learned the position of a goal in a virtual environment that manipulated two variables: the vertical position of navigationally-relevant objects and the presence of non-relevant objects. Results revealed that all three scene-selective regions parsed the vertical position of useful objects independently of their subtending retinotopic biases. It therefore appears that representations in the higher-level visual system combined information about vertical position and navigational value for wayfinding purposes. This property was maintained in healthy aging emphasizing the enduring significance of visual processing along the vertical dimension for spatial navigation abilities across the lifespan.
Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons
Authors: Bastille Isle , Lee Lucy , Moncada-Reid Cynthia , Yu Wei-Ming , Sitko Austen , Yung Andrea , Goodrich Lisa 
Published: October 2023

SummaryNeurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity have been identified, it remains unclear how other synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three subtypes of spiral ganglion neurons (SGNs) that collectively encode sound information. Here, we show that a combinatorial Maf transcription factor code establishes SGN subtype identity and shapes both shared and subtype-appropriate synaptic properties. We find thatc-MafandMafbhave independent and opposing effects on synaptic morphology and auditory function, while also acting redundantly to impart subtype identities and drive synaptic differentiation needed for normal auditory responses. Additionally,c-MafandMafbare expressed at different levels across subtypes and regulate subtype-appropriate gene expression in a dose-dependent manner. Thus, functional diversity of Maf family members enables flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.
Control of poly(A)-tail length and translation in vertebrate oocytes and early embryos
Authors: Xiang Kehui , Ly Jimmy , Bartel David P. 
Published: October 2023

SUMMARYDuring oocyte maturation and early embryogenesis, changes in mRNA poly(A)-tail lengths strongly influence translation, but how these tail-length changes are orchestrated has been unclear. Here, we performed tail-length and translational profiling of mRNA reporter libraries (each with millions of 3ʹ-UTR sequence variants) in frog oocytes and embryos, and fish embryos. We found that the UUUUA element, together with the polyadenylation signal (AAUAAA or AUUAAA), specifies cytoplasmic polyadenylation, and identified contextual features that modulate the activity of both elements. In maturing oocytes, this tail lengthening occurs against a backdrop of global deadenylation and the action of C-rich elements that specify tail-length-independent translational repression. In embryos, cytoplasmic polyadenylation becomes more permissive, and additional elements specify waves of stage-specific deadenylation. Together, these findings largely explain the complex tapestry of tail-length changes observed in early frog and fish development, with strong evidence of conservation in both mice and humans.HighlightsUUUUA, modulated by contextual features, specifies most cytoplasmic polyadenylationStage-specific sequence motifs drive waves of tail-length shortening in embryosUUUUA and C-rich motifs can direct tail-length-independent translational repressionTail-length control is conserved in oocytes of frogs, mice, and humans
THE DUAL ROLE OF THEMICROCYSTIS AERUGINOSAMICROBIOME ON CYANOTOXIN PRODUCTION: COMPETITION FOR AND REMINERALIZATION OF ORGANIC NITROGEN
Authors: Li Wei , Baliu-Rodriguez David , Premathilaka Sanduni H. , Thenuwara Sharmila I. , Kimbrel Jeffrey , Samo Ty , Ramon Christina , Kiledal E. Anders , Rivera Sara R. , Kharbush Jenan , Isailovic Dragan , Weber Peter K. , Dick Gregory J. , Mayali Xavier 
Published: October 2023

AbstractNutrient-induced blooms of the globally abundant freshwater toxic cyanobacteriumMicrocystisare the cause of worldwide public and ecosystem health concerns. The response ofMicrocystisgrowth and toxin production to new and recycled nitrogen (N) inputs, and the impact of heterotrophic bacteria in theMicrocystisphycosphere on these processes are not well understood. Here, using microbiome transplant experiments, cyanotoxin analysis, and stable isotope tracing to measure N incorporation and exchange at single cell resolution, we monitored the growth, cyanotoxin production, and microbiome community structure of severalMicrocystisstrains grown on amino acids and proteins as the sole N source. We demonstrate that 1) organic N availability shapes the microbiome community structure in theMicrocystisphycosphere; 2) external organic N input leads to lower bacterial colonization of the phycosphere; 3) certainMicrocystisstrains can directly uptake amino acids, but with lower rates than heterotrophic bacteria; 4) biomass-specific microcystin production is not impacted by N source (i.e., nitrate, amino acids and protein) but rather by total N availability; and 5) some bacterial communities compete withMicrocystisfor organic N, but others remineralize organic N, in the process producing bio-available N forMicrocystis. We conclude that organic N input can supportMicrocystisblooms and toxin production, andMicrocystis-associated microbial communities play critical roles by influencing cyanobacterial succession through either decreasing (via competition) or increasing (via remineralization) N availability, especially under inorganic N scarcity.
Per- and polyfluoroalkyl substances concentrations are associated with an unfavorable cardio-metabolic risk profile: findings from two population-based cohort studies
Authors: Faquih Tariq O. , Landstra Elvire N. , van Hylckama Vlieg Astrid , Aziz N.Ahmad , Li-Gao Ruifang , de Mutsert Renée , Rosendaal Frits R. , Noordam Raymond , van Heemst Diana , Mook-Kanamori Dennis O. , Willems van Dijk Ko , Breteler Monique M.B. 
Published: October 2023

AbstractPer- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular risk profile, the distribution of levels and relations with cardio-metabolic risk markers in the general population have not been fully characterized. We assessed the association between blood levels of perfluorooctaneic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) and a range of lipoproteins and metabolites as well as clinical lipid measurements. We used data from participants of the Netherlands Epidemiology of Obesity study (NEO) (n= 584) and the Rhineland Study (n= 1,962), jointly spanning an age range of 30 to 89 years. PFAS were measured with the Metabolon HD4 platform, and lipoprotein and metabolite profiles were measured using Nightingale’s nuclear magnetic resonance-spectroscopy platform, and mainly comprised lipoprotein markers. Using linear regression analyses, we quantified age-, sex- and education-adjusted associations of PFOA, PFOS, and PFHxS with clinical lipid measurements and 224 lipoproteins and metabolites.Higher levels of PFAS, particularly PFOS and PFHxS, were associated with higher concentrations of total lipid, cholesterol and phospholipid content in most HDL, IDL, LDL and VLDL subclasses. The effect sizes were age-dependent for the majority of the associations, with the deleterious effects of PFAS being generally stronger in people below compared to those above median age. Our observation that in the general population even low PFAS concentrations are associated with an unfavorable lipid profile, calls for further critical regulation of PFAS substances.
Association between common adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations in a population-based prospective cohort study in the Netherlands
Authors: Holwerda M.R. , Hoeve C.E. , Huiberts A.J. , den Hartog G. , de Melker H.E. , Van den Hof S. , Knol M.J. 
Published: October 2023

AbstractINTRODUCTIONAdverse events (AE) such as pain at injection site or fever are common after COVID-19 vaccination. We aimed to describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.METHODSParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within two months after COVID-19 vaccination and provided 6-monthly serum samples. Data from May 2021 to November 2022 were included. Logistic regression analyses were performed to investigate determinants of AE after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2 naïve participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.RESULTS47,947 AE questionnaires were completed by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention due to AE. AE were reported significantly more frequently by women, younger participants (<60 years), participants with medical risk conditions and Spikevax recipients (versus Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38, 95%CI 1.23-1.54).CONCLUSIONOur study suggests that high pre-vaccination antibody levels are associated with AE, and that experiencing AE may be a marker for a good antibody response to vaccination.
XIST dampens X chromosome activity in a SPEN-dependent manner during early human development
Authors: Alfeghaly Charbel , Castel Gaël , Cazottes Emmanuel , Moscatelli Madeleine , Moinard Eva , Casanova Miguel , Boni Juliette , Mahadik Kasturi , Lammers Jenna , Freour Thomas , Chauviere Louis , Piqueras Carla , Boers Ruben , Boers Joachim , Gribnau Joost , David Laurent , Ouimette Jean-François , Rougeulle Claire 
Published: October 2023

AbstractXIST long non-coding RNA is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female pre-implantation embryos without triggering X chromosome silencing. The long non-coding RNA XACT co-accumulates with XIST on active Xs and may antagonize XIST function. Here we used human ES cells in a naïve state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during pre-implantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and attenuates transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional prior to XCI, confirms the existence of a transient process of X chromosome dosage compensation, and reveals that X chromosome inactivation and dampening rely on the same set of factors.
Identifying characterizations of BPM methodology in hotel industry: evidence from listed hotel companies in Egypt
Authors: Moussa Mohamed Hany B. , Sayed M.S. , Allam Batta R. 
Published: October 2023

PurposeThe purpose of this study is to identify the characterizations of business process management (BPM) methodology in hotel industry through an aggregate processing of the core cyclesteps (CCCs) of the highly-cited BPM life-cycle models in the literature aiming to highlight the major issues of the current methodological approach of BPM in hotels when to put the notion of service process into practice.Design/methodology/approachThe paper identifies and examines the most popular BPM life-cycles models in the literature and locates 15 life-cycles that are highly cited. The paper then focuses on applying the theory on nine listed hotel companies in Egypt using a questionnaire in the form of a semi-structured interview technique.FindingsThe CCSs of BPM life-cycle model applied in hotels revealed a gap between BPM theory and practice in this sector. Utilizing this model of BPM life-cycle, the paper focuses on describing several of the main problems or pitfalls found in the methodological approach of BPM in hotels, which brings the essence of the whole operation management problems.Practical implicationsIn light of these findings, the paper discusses the practical implications and focuses on recommendations on how to properly improve the methodological approach of BPM in hotels in order to get better business results.Originality/valueThe paper bridges the gap between BPM theory and practice and suggests recommendations that will assist hotel companies to eliminate the problems of poor process management (PM). There are also future research recommendations to enhance the knowledge of BPM theory in the service sector.
The airfoil design and parameter optimization of the deformable micro air vehicle
Authors: Huang Shengxian , Qiu Huihe , Wang Ying 
Published: October 2023

PurposeSince most of the existing literature do not disclose the node coordinate data of its fixed-wing aircraft airfoil, in order to develop and obtain a practical and suitable deformation airfoil for fixed-wing micro air vehicle (MAV), this paper proposes an improved airfoil design method of fixed-wing MAV based on the profile data of S5010 airfoil.Design/methodology/approachCombined with the body shape variation of the stingray in the propulsion process, the parametric study of the aerodynamic shape of the original design airfoil is carried out to explore the influence of a single parameter change on the aerodynamic performance of the airfoil. Then, according to the influence law of single parameter variation on the aerodynamic performance of the airfoil, the original airfoil is synthetically deformed by changing multiple parameters.FindingsBy comparing the aerodynamic performance of the multi-parameter deformed airfoil with the original airfoil, it is found that the lift coefficient of the multi-parameter deformed airfoil changes from negative to positive value when AOA = 0°. When AOA = 2°, the lift coefficient growth rate is the largest, which is 47.27%, and the lift-to-drag ratio is increased by 50.00%. At other angles of attack, the lift, drag, and torque coefficients of the multi-parameter deformed airfoil are optimized to some extent.Originality/valueCombined the body shape variation of the stingray in the propulsion process, the parametric study of the aerodynamic shape of the original design airfoil is carried out to explore the influence of a single parameter change on the aerodynamic performance of the airfoil.