bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step
Authors: Wu Wesley , Gupta Sasha , Sagan Sharon A. , Moseley Carson E. , Zamvil Scott S. , Pak John E. 
Published: July 2024

1.1ABSTRACTExperimental autoimmune encephalomyelitis (EAE) is a model for central nervous system (CNS) autoimmune demyelinating diseases such as multiple sclerosis (MS) and MOG antibody-associated disease (MOGAD). Immunization with the extracellular domain of recombinant human MOG (rhMOG), which contains pathogenic antibody and T cell epitopes, induces B cell-dependent EAE for studies in mice. However, these studies have been hampered by rhMOG availability due to its insolubility when overexpressed in bacterial cells, and the requirement for inefficient denaturation and refolding. Here, we describe a new protocol for the high-yield production of soluble rhMOG in SHuffle cells, a commercially availableE. colistrain engineered to facilitate disulfide bond formation in the cytoplasm. SHuffle cells can produce a soluble fraction of rhMOG yielding >100 mg/L. Analytical size exclusion chromatography multi-angle light scattering (SEC-MALS) and differential scanning fluorimetry of purified rhMOG reveals a homogeneous monomer with a high melting temperature, indicative of a well-folded protein. Anin vitroproliferation assay establishes that purified rhMOG can be processed and recognized by T cells expressing a T cell receptor (TCR) specific for the immunodominant MOG35-55peptide epitope. Lastly, immunization of wild-type, but not B cell deficient, mice with rhMOG resulted in robust induction of EAE, indicating a B cell-dependent induction. Our SHuffle cell method greatly simplifies rhMOG production by combining the high yield and speed of bacterial cell expression with enhanced disulfide bond formation and folding, which will enable further investigation of B cell-dependent EAE and expand human research of MOG in CNS demyelinating diseases.
Parallel patterns of cognitive aging in marmosets and macaques
Authors: Vanderlip Casey R. , Jutras Megan L. , Asch Payton A. , Zhu Stephanie Y. , Lerma Monica N. , Buffalo Elizabeth A. , Glavis-Bloom Courtney 
Published: July 2024

ABSTRACTAs humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain’s susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.
Smooth Muscle Cells-Expressed Bmal1 Regulates Vascular Calcification Independent of the Canonical Circadian Pathway
Authors: He Ming , Sun Yong , Huang Fengyuan , Zhu Zhehao , Velazquez-Miranda Erandi , Chong Zechen , Chen Yabing 
Published: July 2024

AbstractVascular calcification is a major cardiovascular issue that increases morbidity and mortality in diabetes patients. While dysregulation of the circadian master regulator Basic Helix-Loop-Helix ARNT-Like Protein 1 (Bmal1) in vascular smooth muscle cells (VSMC) under diabetic conditions has been suggested, its role in vascular calcification is unclear. In VSMC, Bmal1 was upregulated under high glucose treatment and in aortic tissues from a diabetic mouse model. RNA sequencing from isolated VSMC between Bmal1 deletion and wildtype mice indicated Bmal1’s pro-calcification role. Indeed, reduced levels of the osteogenic master regulator, Runt-Related Transcription Factor 2 (Runx2), were found in Bmal1 deletion VSMC under diabetic conditions. Alizarin red staining showed reduced calcification in Bmal1 deletion VSMCin vitroand vascular ringsex vivo. Furthermore, in a diabetic mouse model, SMC-Bmal1 deletion showed reduced calcium deposition in aortas. Collectively, diabetes-upregulated circadian regulator Bmal1 in VSMC contributes to vascular calcification. Maintaining normal circadian regulation may improve vascular health in diabetes.
Iron limitation differentially affects viral replication in key marine microbes
Authors: Yung Charmaine C. M. , Kelly Rachel L. , Kauffman Kathryn M. , Cunningham Brady , Zimmerman Amy , Worden Alexandra Z. , John Seth G. 
Published: July 2024

AbstractViral lysis accounts for much of microbial mortality in the ocean, and iron (Fe) is a critical micronutrient that can limit phytoplankton growth, yet interactions between Fe-nutrition and viral lysis are not well known. Here, we present viral infection dynamics under Fe-limited and Fe-replete conditions for three distinct marine microbes, the photosynthetic picoeukaryoteOstreococcus lucimarinus, the cyanobacteriumSynechococcus, and two strains of the heterotrophic bacteriumVibrio. Iron limitation ofOstreococcusresulted in slowed growth, and a corresponding decrease in viral burst sizes was observed; this is similar to results from studies of larger eukaryotic phytoplankton (Slagter et al. 2016; Kranzler et al. 2021), where reduced viral replication under Fe-limitation is attributed to the viral reliance on host metabolism and replication machinery. For one strain ofVibrio, Fe-limitation similarly impacted viral dynamics, increasing the latent period before infected cells burst to release new virus, and reducing the number of infective viral particles released upon viral lysis. Unexpectedly, for another strain ofVibrio, Fe-limitation had no discernible effect on viral replication. Furthermore, dynamics of threeSynechococcuscyanophages was not affected by Fe-limitation of the host, either in terms of latent period or burst size. The results illuminate the extraordinary ability of some marine viruses, particularly cyanophages, to highjack host metabolism to produce new viral particles, even when host growth is compromised. This has implications for marine ecology and carbon cycling in Fe-limited regions of the global ocean.
Characterizing the heterogeneity of neurodegenerative diseases through EEG normative modeling
Authors: Tabbal Judie , Ebadi Aida , Mheich Ahmad , Kabbara Aya , Güntekin Bahar , Yener Görsev , Paban Veronique , Gschwandtner Ute , Fuhr Peter , Verin Marc , Babiloni Claudio , Allouch Sahar , Hassan Mahmoud 
Published: July 2024

AbstractNeurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s (AD) exhibit considerable heterogeneity of functional brain features within patient populations, complicating diagnosis, treatment, prognosis, and drug discovery. Here, we use electroencephalography (EEG) and normative modeling to investigate neurophysiological oscillatory mechanisms underpinning this heterogeneity. To this aim, we use resting-state EEG activity collected by 14 clinical units, in healthy older persons (n=499) and patients with PD (n=237) and AD (n=197), aged over 40 years old. Spectral and source connectivity analyses of EEG activity provided EEG features for normative modeling and deviation measures in the PD and AD patients. Normative models confirmed significant deviations of the EEG features in PD and AD patients over population norms, characterized by high heterogeneity and frequency-dependence. The percentage of patients with at least one deviating EEG feature was ∼30% for spectral measures and ∼80% for functional source connectivity. Notably, the spatial overlap of the deviant EEG features did not exceed 60% for spectral analysis and 25% for functional source connectivity analysis. Furthermore, the patient-specific deviations were correlated with relevant clinical measures, such as the UPDRS for PD (⍴=0.24,p=0.025) and the MMSE for AD (⍴=-0.26,p=0.01), indicating that greater deviations from normative EEG features are associated with worsening score values. These results suggest that the deviation percentage from EEG norms may enrich clinical assessment in PD and AD patients at individual levels in the framework of Precision Neurology.
The role of methylation and structural variants in shaping the recombination landscape of barley
Authors: Casale Federico , Arlt Christopher , Kühl Marius , Li Jinquan , Engelhorn Julia , Hartwig Thomas , Stich Benjamin 
Published: July 2024

ABSTRACTMeiotic recombination is not only a key mechanism for sexual adaptation in eukaryotes but crucial for the accumulation of beneficial alleles in breeding populations. The effective manipulation of recombination requires, however, a better understanding of the mechanisms regulating the rate and distribution of recombination events in genomes. Here, we identified the genomic features that best explain the recombination variation among a diverse set of segregating populations of barley at a resolution of 1 Mbp and investigated how methylation and structural variants determine recombination hotspots and coldspots at a high-resolution of 10 kb. Hotspots were found to be in proximity to genes and the genetic effects not assigned to methylation were found to be the most important factor explaining differences in recombination rates among populations along with the methylation and the parental sequence divergence. Interestingly, the inheritance of a highly-methylated genomic fragment from one parent only was enough to generate a coldspot, but both parents must be equally low methylated at a genomic segment to allow a hotspot. The parental sequence divergence was shown to have a sigmoidal correlation with recombination indicating an upper limit of mismatch among homologous chromosomes for CO formation. Structural variants (SVs) were shown to suppress COs, and their type and size were not found to influence that effect. Methylation and SVs act jointly determining the location of coldspots in barley and the weight of their relative effect depends on the genomic region. Our findings suggest that recombination in barley is highly predictable, occurring mostly in multiple short sections located in the proximity to genes and being modulated by local levels of methylation and SV load.
STK19 drives Transcription-Coupled Repair by stimulating repair complex stability, Pol II ubiquitylation and TFIIH recruitment
Authors: Ramadhin Anisha R. , Lee Shun-Hsiao , Zhou Di , Salmazo Anita , Gonzalo-Hansen Camila , van Sluis Marjolein , Blom Cindy M.A. , Janssens Roel C. , Raams Anja , Dekkers Dick , Bezstarosti K , Slade Dea , Vermeulen Wim , Pines Alex , Demmers Jeroen A.A. , Bernecky Carrie , Sixma Titia K. , Marteijn Jurgen A. 
Published: July 2024

AbstractDNA damage forms a major obstacle for gene transcription by RNA polymerase II (Pol II). Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates transcription-blocking lesions (TBLs), thereby safeguarding accurate transcription, preserving correct cellular function and counteracting aging. TC-NER initiation involves the recognition of lesion-stalled Pol II by CSB, which recruits the CRL4CSAE3 ubiquitin ligase complex and UVSSA. TBL-induced ubiquitylation of Pol II at lysine 1268 of the RPB1 subunit by CRL4CSAserves as a critical TC-NER checkpoint, governing Pol II stability and initiating TBL excision by TFIIH recruitment. However, the precise regulatory mechanisms of the CRL4CSAE3 ligase activity and TFIIH recruitment remain elusive. Here, we reveal Inactive Serine/Threonine Kinase 19 (STK19) as a novel TC-NER factor, that is essential for correct TBL removal repair and subsequent transcription restart. Cryo-EM studies demonstrate that STK19 is an integral part of the Pol II-TC-NER complex, bridging CSA with UVSSA, RPB1 and downstream DNA. Live-cell imaging and interaction studies show that STK19 stimulates TC-NER complex stability and CRL4CSAactivity, resulting in efficient Pol II ubiquitylation and correct UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as a core component of the TC-NER machinery and its key involvement in the cellular responses to DNA damage that interfere with transcription.
Super-resolution imaging of proteins inside live mammalian cells with mLIVE-PAINT
Authors: Bhaskar Haresh , Gidden Zoe , Virdi Gurvir , Kleinjan Dirk-Jan , Rosser Susan J. , Gandhi Sonia , Regan Lynne , Horrocks Mathew H. 
Published: July 2024

AbstractSuper-resolution microscopy has revolutionized biological imaging, enabling the visualization of structures at the nanometer length scale. Its application in live cells, however, has remained challenging. To address this, we adapted LIVE-PAINT, an approach we established in yeast, for application in live mammalian cells. Using the 101A/101B coiled-coil peptide pair as a peptide-based targeting system, we successfully demonstrate the super-resolution imaging of two distinct proteins in mammalian cells, one localized in the nucleus, and the second in the cytoplasm. This study highlights the versatility of LIVE-PAINT, suggesting its potential for live-cell super-resolution imaging across a range of protein targets in mammalian cells. We name the mammalian cell version of our original method mLIVE-PAINT.
Binocular processing facilitates escape behavior through multiple pathways to the superior colliculus
Authors: Broersen Robin , Thompson Genevieve , Thomas Felix , Stuart Greg J. 
Published: July 2024

SummaryThe superior colliculus (SC) is the main brain region regulating innate defensive behaviors to visual threat. Yet, how the SC integrates binocular visual information and to what extent binocular vision drives defensive behaviors is unknown. Here, we show that binocular vision facilitates visually-evoked escape behavior. Furthermore, we find that SC neurons respond to binocular visual input with diverse synaptic and spiking responses, and summate visual inputs largely sublinearly. Using pathway-specific optogenetic silencing we find that contralateral and ipsilateral visual information is carried to binocular SC neurons through retinal, interhemispheric and corticotectal pathways. These pathways carry binocular visual input to the SC in a layer-specific manner, with superficial layers receiving visual information through retinal input, whereas intermediate and deep layers rely on interhemispheric and corticotectal pathways. Together, our data shed light on the cellular and circuit mechanisms underlying binocular visual processing in the SC and its role in escape behavior.
Variation in the fitness impact of translationally optimal codons among animals
Authors: Bénitìere Florian , Lefébure Tristan , Duret Laurent 
Published: July 2024

AbstractEarly studies in invertebrate model organisms (fruit flies, nematodes) showed that their synonymous codon usage is under selective pressure to optimize translation efficiency in highly expressed genes (a process called translational selection). In contrast, mammals show little evidence of selection for translationally optimal codons. To understand this difference, we examined the use of synonymous codons in 223 metazoan species, covering a wide range of animal clades. For each species, we predicted the set of optimal codons based on the pool of tRNA genes present in its genome, and we analyzed how the frequency of optimal codons correlates with gene expression to quantify the intensity of translational selection (S). Surprisingly, few metazoans show clear signs of translational selection. As predicted by the nearly neutral theory, the highest values ofSare observed in species with large effective population sizes (Ne). Overall, however,Neappears to be a poor predictor of the intensity of translational selection, suggesting important differences in the fitness effect of synonymous codon usage across taxa. We propose that the few animal taxa that are clearly affected by translational selection correspond to organisms with strong constraints for a very rapid growth rate.
Gut and oral microbial community characterization from women with breast cancer, women with ductal carcinoma in situ, and healthy women reveals differences in gut but not oral microbiota
Authors: McCune Emma , Sharma Anukriti , Johnson Breanna , O’Meara Tess , Theiner Sarah , Campos Maribel , Heditsian Diane , Brain Susie , Gilbert Jack A. , Esserman Laura , Campbell Michael J. 
Published: July 2024

ABSTRACTThis study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC versus healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified 5 bacterial guilds dominated by eitherPrevotella, Enterobacteriaceae,Akkermansia, Clostridiales, orBacteroides. TheBacteroidesand Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes and very few differentially abundant taxa were observed. NMF analysis of the oral microbiota samples identified 7 guilds dominated byVeillonella,Prevotella, Gemellaceae,Haemophilus,Neisseria,Propionibacterium, andStreptococcus,however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota, but not oral microbiota, may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis.IMPORTANCEEmerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC) and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. These findings suggest that the oral microbiome is unlikely to be an effective risk marker for DCIS or breast cancer compared to the gut microbiome. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.
Experimentally induced pain and paresthesia respond differently to parameter changes of cuff-based compression in pain-free young individuals
Authors: Skalski Jacek , Swoboda Sylwia , Szikszay Tibor M. , Wodarski Piotr , Bieniek Andrzej , Luedtke Kerstin , Adamczyk Wacław M. 
Published: July 2024

AbstractNeuropathic pain is a significant therapeutic challenge due to the co-occurrence with other neurological symptoms such as paresthesia. Human-based models such as cuff algometry can enhance our understanding of pain-paresthesia relationships. This experiment aimed to characterize (psychophysically) pain and paresthesia evoked by stimuli of different temporal and intensity parameters and to demonstrate the reliability of experimental induction of these two symptoms using cuff algometry. Forty participants, aged 18-35, were exposed to mechanical pressure stimuli at three intensities (100, 150, 200 mmHg) and three durations (90, 120, 150s). Skin Conductance (SC) was continuously monitored, and participants rated pain and paresthesia in real-time using a computerized visual analog scale. The General Linear Model analysis revealed significant differences in paresthesia across all durations (p<0.01), but not all intensities, as paresthesia did not increase from 150 to 200 mmHg (p>0.05). Conversely, pain responses showed significant differences across all pressure intensities (p<0.05) but not durations, as pain did not increase from 90 to 120 and from 120 to 150s (p>0.05). No interaction effects were found for either symptom. SC analysis showed no significant main or interaction effects. Intraclass correlation coefficients (ICCs) indicated moderate to good reliability for pain and paresthesia induction across different durations and intensities (ICC: 0.52-0.90), while SC showed poor to moderate reliability (ICC: 0.21-0.73). In conclusion, computerized cuff algometry seems to be an effective and reliable method for simultaneously inducing and assessing pain and paresthesia, revealing that these symptoms follow different patterns based on pressure duration and intensity.
A new trait in a well-studied ant: low aggression between workers fromLasius niger(Hymenoptera, Formicidae) nest complexes
Authors: Stukalyuk Stanislav 
Published: July 2024

AbstractThe formicine antLasius nigeris one of the most abundant and most intensively studied Palaearctic ant species and was believed so far to form exclusively monogynous colonies, to spread via single-queen dispersal and to found claustrally. Two closely neighboring nest complexes ofLasius nigerwere observed in an abandoned field near Kyiv / Ukraine in 2017-2020. Nest complex A includes 14650 mounds on an area of 11.8 ha and nest complex B 15600 mounds on 13.3 ha. The nests within the nest complexes are connected via a developed trail network. Aggression tests revealed a low level of aggression between workers from different zones of the same nest complex but increased aggression in confrontations of nest complex workers with workers from a remote monodomous population. Reduced aggression between workers facilitate the integrity of the nest complex and its rapid growth.
Unveiling the
a0(1710)
nature in the process
J/ψ→K¯0K+ρ−
Authors: Ding Yan , Wang En , Li De-Min , Geng Li-Sheng , Xie Ju-Jun 
Published: July 2024

We have investigated the process J/ψ→K¯0K+ρ− by taking into account the S-wave K*K¯*, ρω, and ρϕ final-state interactions, where the scalar meson a0(1710) is generated. In addition, we also take into account the contributions from the scalar a0(980)(→K¯0K+) and the intermediate resonances K1(1270)−(→K¯0ρ−) and K1(1270)0(→K+ρ−). Our results show that, in the K¯0K+ invariant mass distribution, a clear peak structure around 1.8 GeV appears, which could be associated with the scalar a0(1710), however, no significant structure of the a0(980) is observed. On the other hand, one can find clear peaks of the K1(1270) in the K¯0ρ− and K+ρ− invariant mass distributions. The future precise measurement of this process by the BESIII and Belle II Collaborations and the planned Super Tau-Charm Facility in the future could shed light on the nature of a0(1710).

Published by the American Physical Society
2024