bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting CD74-positive macrophages improves neoadjuvant therapy in cervical cancer as revealed by single-cell transcriptomics analysis
Authors: Wang Zixiang , Wang Bingyu , Feng Yuan , Ye Jinwen , Mao Zhonghao , Zhang Teng , Xu Meining , Zhang Wenjing , Jiao Xinlin , Zhang Youzhong , Cui Baoxia 
Published: November 2023

AbstractUterine cervical cancer (UCC) has the second-highest mortality rate among malignant tumors of the female reproductive system. Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy for cervical cancer. However, the efficacy of PD-1 (programmed cell death protein 1) blockade combined with neoadjuvant chemotherapy (NACT) and the ensuing alterations within the tumor microenvironment need further investigation. We conducted single-cell RNA sequencing using 46,950 cells from nine sequential human cervical cancer tissues representing different stages of NACT and PD-1 blockade combination therapy. We delineated the trajectory of cervical epithelial cells and unveiled crucial factors involved in the combination therapy. Cell communication analysis revealed the inferred interaction strength decreased between T cell-cancer cells, while the communication between macrophage-cancer cells intensified after NACT therapy. We verified that macrophages are necessary for PD-1 blockade combination to exert antitumor effects in vitro. Detailed analysis unraveled the CD74-positive macrophages frequently interacted with the immunoreactive Epi 3 subgroup during neoadjuvant combination therapy. CD74 upregulation limited phagocytosis and stimulated M2 polarization. The CD74 blockade enhanced macrophage phagocytosis, resulting in decreased viability of cervical cancer cells in vitro and in vivo. This study unveils the dynamic microenvironment of UCC influenced by NACT and PD-1 blockade combination therapy, and targeting CD74 was a potential strategy to augment the therapy efficacy.
Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity
Authors: Tierney Jack A. S. , Świrski Michał , Tjeldnes Håkon , Mudge Jonathan M. , Kufel Joanna , Whiffin Nicola , Valen Eivind , Baranov Pavel V. 
Published: November 2023

AbstractThe application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, both within annotated protein-coding and non-coding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term Ribosome Decision Graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the later ‘translons’. Non-deterministic events, such as initiation, re-initiation, selenocysteine insertion or ribosomal frameshifting are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions, analysis of genetic variation and quantitative genome-wide data on translation for characterisation of regulatory modulators of translation.
The SARS-CoV-2 Omicron sub-variant BA.2.86 is attenuated in hamsters
Authors: Herder Vanessa , Mendonca Diogo Correa , Upfold Nicole , Furnon Wilhelm , Kerr Karen , Ilia Georgios , Allan Jay , Sigal Alex , Patel Arvind H. , Palmarini Massimo 
Published: November 2023

AbstractSARS-CoV-2 variants have emerged throughout the COVID-19 pandemic. There is a need to risk-assess newly emerged variants in near “real-time” to estimate their potential threat to public health. The recently emerged Omicron sub-variant BA.2.86 raised concerns as it carries a high number of mutations compared to its predecessors. Here, we assessed the virulence of BA.2.86 in hamsters. We compared the pathogenesis of BA.2.86 and BA.2.75, as the latter is one of the most virulent Omicron sub-variants in this animal model. Using digital pathology pipelines, we quantified the extent of pulmonary lesions measuring T cell and macrophage infiltrates, in addition to alveolar epithelial hyperplasia. We also assessed body weight loss, clinical symptoms, virus load in oropharyngeal swabs, and virus replication in the respiratory tract. Our data show that BA.2.86 displays an attenuated phenotype in hamsters, suggesting that it poses no greater risk to public health than its parental Omicron sub-variants.Article summary lineThe newly emerged Omicron sub-variant BA.2.86 is attenuated in hamsters.
Non-muscle myosin II regulates presynaptic actin assemblies and neuronal mechanobiology inDrosophila
Authors: Ermanoska Biljana , Baets Jonathan , Rodal Avital A. 
Published: November 2023

AbstractNeuromuscular junctions (NMJs) are evolutionarily ancient, specialized contacts between neurons and muscles. They endure mechanical strain from muscle contractions throughout life, but cellular mechanisms for managing this stress remain unclear. Here we identify a novel actomyosin structure atDrosophilalarval NMJs, consisting of a long-lived, low-turnover presynaptic actin core that co-localizes with non-muscle myosin II (NMII). This core is likely to have contractile properties, as manipulating neuronal NMII levels or activity disrupts its organization. Intriguingly, depleting neuronal NMII triggered changes in postsynaptic muscle NMII levels and organization near synapses, suggesting transsynaptic propagation of actomyosin rearrangements. We also found reduced levels of Integrin adhesion receptors both pre- and postsynaptically upon NMII knockdown, indicating disrupted neuron-muscle connections. Mechanical severing of axons caused similar actin core fragmentation and Integrin loss to NMII depletion, suggesting this structure responds to tension. Our findings reveal a presynaptic actomyosin assembly that maintains mechanical continuity between neurons and muscle, possibly facilitating mechanotransduction at the NMJ via Integrin-mediated adhesion.
Sleep disturbance as a precursor to anxiety, depression, and PTSD among rural Kenyans: a cross-lagged panel analysis from a rural Kenyan interventional cohort
Authors: Goodman Michael L. , Lee Miryoung , Springer Andrew , Schick Vanessa , Vaughan Elizabeth , Markham Christine , Gitari Stanley , Mukiri Fridah 
Published: November 2023

ABSTRACTSleep quality is essential to biopsychosocial functioning, yet there remains limited longitudinal research on sleep and mental or social well-being within low- or middle-income countries. This study utilizes longitudinal cohort data from a community-based empowerment program in Meru County, Kenya to assess cross-lagged correlations between sleep disturbance, social support, symptoms of depression, anxiety, and posttraumatic stress,Participants (n=373; 92% women; age range 18-86 years) who reported more sleep disturbance at T1 reported significantly more symptoms of depression, anxiety and PTSD, and significantly less social support at T2 (average 11 weeks later), controlling for all within-time correlations across measures, within-measure correlations across time, and sociodemographic background characteristics.Findings are consistent with research across high-income countries, underscoring the need for more contextualized research into sleep behaviors across low- and middle-income countries. Findings may inform interventions to increase mental and social well-being within Kenya.
Pathophysiological Mechanisms of the Onset, Development, and Disappearance Phases of Skin Eruptions in Chronic Spontaneous Urticaria
Authors: Seirin-Lee Sungrim , Takahagi Shunsuke , Hide Michihiro 
Published: November 2023

AbstractChronic spontaneous urticaria (CSU) is a typical example of an intractable skin disease with no clear cause and significantly affects daily life of patients. Because CSU is a human-specific disease and lacks proper animal model, there are many questions regarding its pathophysiological dynamics. On the other hand, most clinical symptoms of urticaria are notable as dynamic appearance of skin eruptions (wheals). In this study, we explored dynamics of wheal by dividing it into three phases using a mathematical model: onset, development, and disappearance. Our results suggest that CSU onset is critically associated with endovascular dynamics triggered by basophils positive feedback. In contrast, the development phase is regulated by mast cell dynamics via vascular gap formation. We also suggest a disappearance mechanism of skin eruptions in CSU through an extension of the mathematical model using qualitative and quantitative comparisons of wheal expansion data of real patients with urticaria. Our results suggest that the wheal dynamics of the three phases and CSU development are hierarchically related to endovascular and extravascular pathophysiological networks.
Recreating the Biological Steps of Viral Infection on a Bioelectronic Platform to Profile Viral Variants of Concern
Authors: Chao Zhongmou , Selivanovitch Ekaterina , Kallitsis Konstantinos , Lu Zixuan , Pachaury Ambika , Owens Róisín , Daniel Susan 
Published: November 2023

AbstractViral mutation rates frequently outpace the development of technologies used to detect and identify harmful variants; for SARS Coronavirus-2 (SARS-CoV-2), these are called variants of concern (VOC). Given the continual emergence of VOC, there is a critical need to develop platforms that can identify the presence of a virus and readily identify its propensity for infection. We present an electronic biomembrane sensing platform that recreates the multifaceted and sequential biological cues that give rise to distinct SARS-CoV-2 virus host cell entry pathways and reports the progression of entry steps of these pathways as electrical signals. Within these electrical signals, two necessary entry processes mediated by the viral Spike protein, virus binding and membrane fusion, can be distinguished. Remarkably, we find that closely related VOC exhibit distinct fusion signatures that correlate with trends reported in cell-based infectivity assays, allowing us to report quantitative differences in fusion characteristics among them that inform their infectivity potentials. This cell-free biomimetic infection platform also has a virus-free option that equally reports infectivity potential of the Spike proteins. We used SARS-CoV-2 as our prototype, but we anticipate that this platform will extend to other enveloped viruses and cell lines to quantifiably explore virus/host interactions. This advance should aid in faster determination of entry characteristics and fusogenicities of future VOC, necessary for rapid response.
Pre-processing of paleogenomes: Mitigating reference bias and postmortem damage in ancient genome data
Authors: Koptekin Dilek , Yapar Etka , Vural Kıvılcım Başak , Sağlıcan Ekin , Altınışık N. Ezgi , Malaspinas Anna-Sapfo , Alkan Can , Somel Mehmet 
Published: November 2023

ABSTRACTAncient DNA analysis is subject to various technical challenges, including bias towards the reference allele (“reference bias”), postmortem damage (PMD) that confounds real variants, and limited coverage. Here, we conduct a systematic comparison of alternative approaches against reference bias and against PMD. To reduce reference bias, we either (a) mask variable sites before alignment or (b) align the data to a graph genome representing all variable sites. Compared to alignment to the linear reference genome, both masking and graph alignment effectively remove allelic bias when using simulated or real ancient human genome data, but only if sequencing data is available in FASTQ or unfiltered BAM format. Reference bias remains indelible in quality-filtered BAM files and in 1240K-capture data. We next study three approaches to overcome postmortem damage: (a) trimming, (b) rescaling base qualities, and (c) a new algorithm we present here,bamRefine, which masks only PMD-vulnerable polymorphic sites. We find that bamRefine is optimal in increasing the number of genotyped loci up to 20% compared to trimming and in improving accuracy compared to rescaling. We propose graph alignment coupled with bamRefine to minimise data loss and bias. We also urge the paleogenomics community to publish FASTQ files.
Molecular and Cellular Context Influences SCN8A Variant Function
Authors: Vanoye Carlos G. , Abramova Tatiana V. , DeKeyser Jean-Marc , Ghabra Nora F. , Oudin Madeleine J. , Burge Christopher B. , Helbig Ingo , Thompson Christopher H. , George Alfred L. 
Published: November 2023

ABSTRACTPathogenic variants inSCN8A, which encodes the voltage-gated sodium (NaV) channel NaV1.6, are associated with neurodevelopmental disorders including epileptic encephalopathy. Previous approaches to determineSCN8Avariant function may be confounded by the use of a neonatal-expressed alternatively spliced isoform of NaV1.6 (NaV1.6N), and engineered mutations to render the channel tetrodotoxin (TTX) resistant. In this study, we investigated the impact ofSCN8Aalternative splicing on variant function by comparing the functional attributes of 15 variants expressed in two developmentally regulated splice isoforms (NaV1.6N, NaV1.6A). We employed automated patch clamp recording to enhance throughput, and developed a novel neuronal cell line (ND7/LoNav) with low levels of endogenous NaVcurrent to obviate the need for TTX-resistance mutations. Expression of NaV1.6N or NaV1.6A in ND7/LoNav cells generated NaVcurrents that differed significantly in voltage-dependence of activation and inactivation. TTX-resistant versions of both isoforms exhibited significant functional differences compared to the corresponding wild-type (WT) channels. We demonstrated that many of the 15 disease-associated variants studied exhibited isoform-dependent functional effects, and that many of the studiedSCN8Avariants exhibited functional properties that were not easily classified as either gain- or loss-of-function. Our work illustrates the value of considering molecular and cellular context when investigatingSCN8Avariants.
Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood
Authors: Sisk Lucinda M. , Keding Taylor J. , Cohodes Emily M. , McCauley Sarah , Pierre Jasmyne C. , Odriozola Paola , Kribakaran Sahana , Haberman Jason T. , Zacharek Sadie J. , Hodges H. R. , Caballero Camila , Gold Gillian , Huang Audrey Y. , Talton Ashley , Gee Dylan G. 
Published: November 2023

AbstractEarly-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.
Conserved 5-methyluridine tRNA modification modulates ribosome translocation
Authors: Jones Joshua D. , Franco Monika K. , Tardu Mehmet , Smith Tyler J. , Snyder Laura R. , Eyler Daniel E. , Polikanov Yury , Kennedy Robert T. , Niederer Rachel O. , Koutmou Kristin S. 
Published: November 2023

ABSTRACTWhile the centrality of post-transcriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one the most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (m5U54). Here, we uncover contributions of m5U54 to both tRNA maturation and protein synthesis. Our mass spectrometry analyses demonstrate that cells lacking the enzyme that installs m5U in the T-loop (TrmA inE. coli, Trm2 inS. cerevisiae) exhibit altered tRNA modifications patterns. Furthermore, m5U54 deficient tRNAs are desensitized to small molecules that prevent translocationin vitro.This finding is consistent with our observations that, relative to wild-type cells,trm2Δ cell growth and transcriptome-wide gene expression are less perturbed by translocation inhibitors. Together our data suggest a model in which m5U54 acts as an important modulator of tRNA maturation and translocation of the ribosome during protein synthesis.
Genetically stable kill-switch using “demon and angel” expression construct of essential genes
Authors: Kato Yusuke , Mori Hirotada 
Published: November 2023

ABSTRACTGenetic instability of synthetic genetic devices is a key obstacle for practical use. This problem is particularly critical in kill-switches for conditional host killing. Here, we propose a genetically stable kill-switch based on a “demon and angel” expression construct of a toxic essential gene. The kill-switch conditionally overexpresses the toxic essential gene. Additionally, the identical essential gene is deleted in the genome. The essential gene is expressed at a low level to maintain host survival in the OFF state and kills the host by the overexpression in the ON state. The single expression construct is responsible for both killing the hosts and maintaining viability, reducing the emergence of loss-of-function mutants. We constructed the kill-switch using the toxic essential gene encoding tyrosyl-tRNA synthetase,tyrS, inEscherichia coli. The bacteria harboring the kill-switch were conditionally suicidal over 300 generations. Toxic overexpression of essential genes has also been found in other organisms, suggesting that the “demon and angel” kill switch is scalable to various organisms.GRAPHICAL ABSTRACT
What affects consumers' choice behaviour towards organic food restaurants? By applying organic food consumption value model
Authors: Ray Arghya , Das Biswadip , She Long 
Published: November 2023

PurposeAlthough there is a rising demand for organic food restaurants (OFRs), limited studies have attempted at understanding the drivers of customers' intention to visit OFRs. There is also a need to examine customers' choice behaviour in the context of OFRs.Design/methodology/approachThis study has assessed the effect of consumption values (functional, emotional, epistemic, conditional, quality and social) on the intention to visit OFRs by utilizing 1863 online customer reviews about different Indian OFRs (Study 1) and 205 survey-based responses of Indian customers (Study 2).FindingsFindings show an overall positive sentiment towards OFRs. Results of Study 1 and Study 2 reveal that functional, quality, social and emotional values have a significant impact on customers' OFR visit intention. Interestingly, Study 2 found that epistemic values have an insignificant impact on customers' visit intention.Practical implicationsStudy findings suggest that the OFR management need to provide a better ambience, and good quality organic food in OFRs. Additionally, managers of OFRs can train their staff to be well mannered, cooperative and sincere.Originality/valueThe study on OFRs is still in its nascent stage. The findings of this study will thus provide academicians and policy makers an idea of the consumption values that affect customers' intention to visit OFRs.
Mass development of aquatic plants: Effects of contrasting management scenarios on a suite of ecosystem services
Authors: Vermaat Jan E. , Thiemer Kirstine , Immerzeel Bart , Schneider Susanne C. , Sebola Keneilwe , Coetzee Julie , Petruzzella Antonella , Motitsoe Samuel N. , Baldo Mathieu , Misteli Benjamin , Thiébaut Gabrielle , Hilt Sabine , Köhler Jan , Harpenslager Sarah F. 
Published: November 2023

Abstract

Dense beds of aquatic plants are often perceived as nuisance and therefore mechanically removed, often at substantial cost. Such removal, however, may affect a range of ecosystem functions and consequently also the ecosystem services that benefit society.

We studied five cases: River Otra (Norway), River Spree (Germany), Lake Kemnade (Germany), Lake Grand‐Lieu (France) and Hartbeespoort Dam (South Africa). In all, nuisance aquatic plant growth is managed, but dominant species, geographic setting and major societal uses are different. We quantified 12 final ecosystem services as flows per area and year in biophysical and monetary terms. Quantified services were food and fodder production, commercial fisheries, hunting and gathering wild products, hydropower production, drinking and irrigation water production, flood prevention, carbon sequestration, active and passive recreation and biodiversity conservation (nonuse).

These services were related to aquatic plant cover via a range of ecosystem functions, and the effects were estimated of three plant removal regimes on the relative importance of the quantified ecosystem services and on the total sum of the monetary estimates (total economic value, TEV). The three removal regimes were ‘maximum removal’, ‘current practice’ and ‘do nothing’.

In all five cases, TEV was dominated by different forms of recreation. TEV was highest for Lake Kemnade, where visitor densities were highest. TEV was most sensitive to the different management regimes in Lake Kemnade, because a threshold in aesthetic appreciation was passed in the ‘do‐nothing’ regime, and in Hartbeespoort Dam, because of the effect on boating and angling. In the other cases, the different removal regimes had little effect on the estimated TEV.

Synthesis and applications. Since recreation dominated the estimated societal benefits in the studied ecosystems, also where provision of hydropower, drinking water or irrigation water were relevant, effects on recreation should be a core consideration in the management of nuisance aquatic plants. Furthermore, aquatic plant management strategies will benefit from taking into account the differences in perceived nuisance among different categories of recreative users before engaging in costly removal.