bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 Omicron sub-lineages
Authors: Touret Franck , Giraud Emilie , Bourret Jérôme , Donati Flora , Tran-Rajau Jaouen , Chiaravalli Jeanne , Lemoine Frédéric , Agou Fabrice , Simon-Lorière Etienne , van der Werf Sylvie , de Lamballerie Xavier 
Published: December 2022

SummaryThe landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1 and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1 and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1 and XBB variants.
An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells
Authors: Salerno Fiamma , Howden Andrew J. M. , Matheson Louise S. , Gizlenci Özge , Screen Michael , Lingel Holger , Brunner-Weinzierl Monika C. , Turner Martin 
Published: December 2022

AbstractDuring B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. We used label-free mass spectrometry to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription- and translation initiation-factors that define cellular identity and function. By comparing the full-length transcriptome and proteome within the same sample, we identified mRNAs linked to B cell activation and antibody secretion that are expressed without detectable protein. These “poised” mRNAs might enable rapid protein production through increased translation or protein stability. In addition, through interrogation of our proteomic dataset, we found that the translational repressor PDCD4 restrains the response of marginal zone B cells to a T-independent antigen. Our molecular characterization of B cell maturation is a valuable resource to further explore the mechanisms underpinning the specialised functions of B cell subsets.
Past human expansions shaped the spatial pattern of Neanderthal ancestry
Authors: Quilodrán Claudio S. , Rio Jérémy , Tsoupas Alexandros , Currat Mathias 
Published: December 2022

SummaryThe worldwide expansion of modern humans (Homo sapiens) from Africa started before the extinction of Neanderthals (Homo neanderthalensis). Both species coexisted and interbred, as revealed by the sequencing of Neanderthal genomes, leading to ~2% Neanderthal DNA in modern Eurasians1,2, with slightly higher introgression in East Asians than in Europeans3–6. These distinct levels of ancestry have been argued to result from selection processes7,8. However, recent theoretical simulations have shown that range expansions could be another explanation9,10. This hypothesis would lead to the generation of spatial gradients of introgression, increasing with the distance from the source of the expansion, i.e., Africa for modern humans. Here, we investigate the presence of Neanderthal introgression gradients after past human expansions by analysing an extended palaeogenomic dataset of Eurasian populations. Our results show that the Out-of-Africa expansion of modern humans into Eurasia resulted in spatial gradients of Neanderthal ancestry that persisted through time. Moreover, while keeping the same gradient orientation, the expansion of early Neolithic farmers into western Eurasia contributed decisively to reducing the average level of Neandertal genomic introgression in European compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Palaeolithic hunter-gatherers. This study shows that inferences about past population dynamics within our species can be made from the spatiotemporal variation in archaic introgression.
Spatial modeling of telomere intra-nuclear distribution reveals non-random organization that varies during cell cycle and depends on LAP2 and BAF
Authors: Keller Debora , Stinus Sonia , Umlauf David , Gourbeyre Edith , Biot Eric , Olivier Nicolas , Mahou Pierre , Beaurepaire Emmanuel , Andrey Philippe , Crabbe Laure 
Published: December 2022

AbstractGenome organization within the 3D nuclear volume influences major biological processes but is completely lost during mitosis, which represents a major challenge to maintain cellular identity and cell fate. To restore a functional G1 nucleus for the next cell cycle, it is imperative to reestablish genome organization during post-mitotic nuclear assembly. Importantly, the configuration of linear chromosomes has been shown to directly impact spatial genome architecture. Both centromeres and telomeres are known to associate with nuclear structures, such as the nuclear envelope, and support chromatin distribution. Here, using high-resolution 3D imaging combined with 3D spatial statistics and modeling, we showed that telomeres generally followed a regular distribution compared to what is expected under a random organization. While the preferential localization of telomeres at nuclear periphery was restricted to early G1, we found a strong clustering of centromeres in addition to their predominant peripheral localization at all cell cycle stages. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope. Among these factors, we could show that LAP2α transiently localizes to telomeres in anaphase, at a stage where LAP2α initiates the reformation of the nuclear envelope. Moreover, co-depletion of LAP proteins and their partner BAF impacted telomere redistribution in the next interphase. There results suggest that in addition to their crucial role in genome protection, telomeres also participate in reshaping functional G1 nuclei after mitosis.
Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis
Authors: Maynard Adam G. , Pohl Nancy K. , Petrova Boryana , Wong Alan Y.L. , Wang Peng , Culhane Andrew J. , Hirsch Leah , Hoang Ngoc , Kirkland Orville , Braun Tatum , Ducamp Sarah , Fleming Mark D. , Li Hojun , Kanarek Naama 
Published: December 2022

AbstractAll dividing cells require the essential vitamin folate. Hematopoietic cells harbor a unique sensitivity to folate deprivation, as implied by the development of folate-deficient anemia and the utility of anti-folate chemotherapy in blood cancer. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines, as well as primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis that is followed by enhanced heme metabolism, hemoglobin synthesis and erythroid differentiation. This finding is phenocopied by inhibition of folate metabolism using SHIN1, an inhibitor of the folate enzymes SHMT1/2. The metabolically-driven differentiation is rescued by supplementation of purine precursors, yet occurs independent of nucleotide sensing through mTORC1 and AMPK. Our work profiles the metabolic response to folate depletion in erythroid cells and suggest that premature differentiation of folate-deprived erythroid progenitor cells is a mechanistic etiology to folate-deficiency induced anemia.
Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma
Authors: Zou Dan-Dan , Sun Ya-Zhou , Li Xin-Jie , Wu Wen-Juan , Xu Dan , He Yu-Tong , Qi Jue , Tu Ying , Tang Yang , Tu Yun-Hua , Wang Xiao-Li , Li Xing , Lu Feng-Yan , Huang Ling , Long Heng , He Li , Li Xin 
Published: December 2022

AbstractCutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors (TFs) along AK to cSCC progression. Immunohistochemistry (IHC) / immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.
Motor adaptation does not differ when a perturbation is introduced abruptly or gradually
Authors: Bansal Ambika , ’t Hart Bernard Marius , Chauhan Udai , Eggert Thomas , Straube Andreas , Henriques Denise YP 
Published: December 2022

ABSTRACTPeople continuously adapt their movements to ever-changing circumstances, and particularly in skills training and rehabilitation, it is crucial that we understand how to optimize implicit adaptation in order for these processes to require as little conscious effort as possible. Although it is generally assumed that the way to do this is by introducing perturbations gradually, the literature is ambivalent on the effectiveness of this approach. Here we test whether there are differences in motor performance when adapting to an abrupt compared to a ramped visuomotor rotation. Using a within-subjects design, we test this question under 3 different rotation sizes: 30°, 45°, and 60°, as well as in 3 different populations: younger adults, older adults, and patients with mild cerebellar ataxia. We find no significant differences in either the behavioural outcomes, or model fits, between abrupt and gradual learning across any of the different conditions. Neither age, nor cerebellar ataxia had any significant effect on motor adaptation either. These findings together indicate that motor adaptation is not modulated by introducing a perturbation abruptly compared to gradually, and is also unaffected by age or mild cerebellar ataxia.
Cdc14 spatiotemporally regulates Rim4-mRNA complex assembly and stability during meiosis
Authors: Zhang Rudian , Feng Wenzhi , Qian Suhong , Li Shunjin , Wang Fei 
Published: December 2022

AbstractIn budding yeast, Rim4 sequesters a subset of meiotic transcripts and essentially suppresses their translation until being degraded at the end of meiosis I. We found that Rim4 loads mRNAs in the nucleus as a prerequisite for relocating Rim4 into the cytoplasm, where mRNAs protect Rim4 from autophagy. Nonetheless, the underlying mechanism remains unknown. Using genetic, biochemical, and cell imaging approaches, here, we revealed that phosphorylation states regulate Rim4’s intracellular interactions with mRNAs and the yeast 14-3-3 proteins Bmh1 and Bmh2. Our data showed that Rim4 forms a heterotrimeric complex with Bmh1 and Bmh2 via multiple phosphorylated sites with the consensus of a PKA kinase target. Remarkably, the Bmh1/2-Rim4 complex excludes mRNAs and is resistant to autophagy. We further found that Cdc14, a conserved cell cycle phosphatase, binds to a canonical Cdc14 docking site (PxL) in Rim4’s C-terminal low complexity domain (LCD) to de-phosphorylate Rim4 at multiple sites, resulting in Bmh1/2-Rim4 disassembly. Notably, before meiotic cell divisions, Cdc14 primarily resides in the nucleus, where mRNAs are transcribed. Therefore, Cdc14-triggered Bmh1/2 dissociation facilitates the nuclear Rim4 to target and sequester the nascent mRNAs. In contrast, during the meiotic divisions, Rim4-sequestered mRNAs are released for translation, while Cdc14 mediates Rim4-Bmh1/2 disassembly in the cytoplasm due to its temporary cytoplasmic relocation at the anaphases; subsequently, loss of protection from mRNAs and Bmh1/2 leads to autophagy-mediated Rim4 degradation at this stage. We conclude that phosphorylation states spatiotemporally regulate Rim4’s meiotic interactions, subcellular localization, and stability, regulated by Cdc14.
Systematic multi-trait AAV capsid engineering for efficient gene delivery
Authors: Eid Fatma-Elzahraa , Chen Albert T. , Chan Ken Y. , Huang Qin , Zheng Qingxia , Tobey Isabelle G. , Pacouret Simon , Brauer Pamela P. , Keyes Casey , Powell Megan , Johnston Jencilin , Zhao Binhui , Lage Kasper , Tarantal Alice F. , Chan Yujia A. , Deverman Benjamin E. 
Published: December 2022

AbstractBroadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that evenly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models. Combining six models, we designed a multi-trait (liver-targeted, manufacturable) capsid library and validated 89% of library variants on all six predetermined criteria. Furthermore, the models, trained only on mousein vivoand humanin vitroFit4Function data, accurately predicted AAV capsid variant biodistribution in macaque. Top candidates exhibited high production yields, efficient murine liver transduction, up to 1000-fold greater human hepatocyte transduction, and increased enrichment, relative to AAV9, in a screen for liver transduction in macaques. The Fit4Function strategy ultimately makes it possible to predict cross-species traits of peptide-modified AAV capsids and is a critical step toward assembling an ML atlas that predicts AAV capsid performance across dozens of traits.
Physico-chemical and microbiological characteristics of honey produced by stingless bees(Meliponula beccarii)from the Oromia Region, Ethiopia
Authors: Damto Teferi , Kebeba Deresa , Gemeda Meseret 
Published: December 2022

AbstractThe study was designed to characterize the Physico-chemical and microbiological properties of stingless bee honey (Meliponula beccarii L.) in the Oromia Region, Ethiopia. About thirty-nine (39) honey samples were collected from underground soils through an excavation of natural nests. The study revealed that the mean values of physicochemical parameters for honey samples were: moisture content (30.69±0.29), ash content (0.16±0.01), electrical conductivity (0.44±0.2), pH (3.30±0.03), free acidity (92.39±4.45), HMF (6.58±0.36), fructose (36.48±0.54), glucose (27.67±0.43),sucrose(1.24±0.18), maltose (1.2±0.18) and reducing sugar (64.15±0.75). Stingless bee honey in this study is characterized as possessing higher moisture content and free acidity, but a lower level of sugar as compared to Apis mellifera honey standard. The occurrence of microorganisms in the stingless honey sample ranged from 2.55 × 104to 1.9 × 103CFU/ml for Aerobic Mesophilic, 1.68 x104to 9 x102CFU/ml for yeast, and 1.8 x103to 2 x102CFU/ml for mold. The number of aerobic spore-forming bacteria was at non-detectable levels in all samples while Staphylococci species was detectable only in a sample obtained from Guduru. This indicated that there might be contamination during the harvesting, processing, and storage of stingless bee honey samples. The microbiological and physicochemical properties of stingless bee honey are different from those of A. mellifera honey and need to establish for specific quality standards to promote its commercialization.
ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice
Authors: Xie Zhifang , Ma Xian-Hua , Bai Qiu-Fang , Tang Jie , Sun Jian-He , Jiang Fei , Guo Wei , Wang Chen-Ma , Yang Rui , Wen Yin-Chuan , Wang Fang-Yuan , Chen Yu-Xia , Zhang Hai , He David Z. , Kelley Matthew W. , Yang Shiming , Zhang Weiping J. 
Published: December 2022

AbstractThe mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral non-sensory region. Here we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear non-sensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane, a flattened spiral prominence, and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the non-sensory epithelium covering the outer border Claudius cells, outer sulcus root cells and spiral prominence epithelial cells. Transcriptome analysis shows ZBTB20 regulates genes coding for tectorial membrane proteins in the greater epithelial ridge, and those preferentially expressed in root cells and spiral prominence epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral non-sensory domain.
Solvency and performance persistence of defined benefit private and public pension plans
Authors: Mazonga Mfoutou Bruvine Orchidée , Xie Yuan Tao 
Published: December 2022

PurposeThis study aims to examine the solvency and performance persistence of defined benefit private and public pension plans (DBPPs) in the Republic of Congo.Design/methodology/approachThe authors use the 2 × 2 contingency table approach and the time product ratio (TPR)-based cross-product ratio (CPR) on data covering ten years from 2011 to 2020, with variable funded ratios and excess returns, to determine the solvency and performance persistence of defined benefit pension plans.FindingsThe authors document a lack of solvency and performance persistence in DBPP funds. They conclude that the solvency and performance of DBPP funds are not repetitive. The previous year's private and public defined benefit pension funds’ results do not repeat in the current year. Hence, the current solvency and performance of defined benefit pension funds are not good predictors of future funds' solvency and performance.Originality/valueTo the best of the authors’ knowledge, this study is the first to combine solvency and performance to examine the persistence of defined benefit pension plans in sub-Saharan Africa.
Supplements purchase intention: young consumer's perspective
Authors: Yeo Sook Fern , Tan Cheng Ling , Leong Irene Yoke Chu , Palmucci Dario Natale , Then Yu Jian 
Published: December 2022

PurposeThis study aims to investigate the factors that influence young consumers' purchase intention towards dietary supplements (DS) in Malaysia.Design/methodology/approachThe supplement industry in Malaysia has been growing rapidly recently due to a paradigm shift in healthcare management, from curative to prevention. Thus, it has sparked interest to conduct a study on the factors that influence young consumers' purchase intentions towards DS. With a response rate of 74.5%, a survey questionnaire was used to elicit data from 149 Gen-Y respondents who consume supplements on a regular basis.FindingsThe results revealed that the influencing factors towards purchase decisions among these Gen-Y respondents aged between 17 and 25 are based on product knowledge and product quality. The implications of these findings and directions for future research are outlined at the end of this paper.Originality/valueThis study offers empirical insights from the perspective of an emerging digital economy on the factors that influence young consumers' purchase intentions towards DS in Malaysia.
Elevating the boutique appeal: generating a sense of place in luxury hospitality through virtual tours
Authors: Pohlmann Attila , Velasco Franklin , Guerra-Leal Eva M. , Sepulveda Cesar J. 
Published: December 2022

PurposePlace identity refers to the combination of physical setting, social interactions, emotions and associated meanings. This research paper aims to broaden knowledge about boutique concepts and to examine the role of advertisement types suited to generate a heightened sense of place for customers. The design and delivery of tangible and intangible components of the boutique service experience are investigated to better understand business-relevant customer outcomes.Design/methodology/approachAn introductory qualitative study explores the key features and managerial relevance of the boutique appeal as a means to communicate personalization and a sense of place. Interviews with managers of a boutique catering service are conducted and thematically analyzed. A quantitative follow-up study examines the effect of the boutique appeal on hotel image, purchase intention and willingness to pay.FindingsA boutique hotel appeal is more attractive to customers (compared to traditional luxury appeals) when it is advertised using visually engaging virtual tours because it augments customers’ sensation of place identity. The mediating psychological mechanism, place identity, represents the essential emotional component evoked by boutique concepts and its positive effect on managerially relevant customer outcomes.Originality/valueThis paper provides insight for the design and management of boutique concepts to better shape and predict consumer responses in various luxury hospitality industries. The process by which customers identify with the location where the service is provided, socialize with staff and attach meaning to these settings evokes a sense of place identity, a critical resource in the process of value co-creation.
Post-disaster research: inspirational early career scholars transcript for the disasters: deconstructed livestream on 15 September 2021
Authors: Alburo-Cañete Kaira Zoe , Campbell Nnenia , Lakhina Shefali Juneja , Le Dé Loïc , Rodríguez Alarcón María N. 
Published: December 2022

PurposeThis conversation presents the reflections from four inspirational early career disaster scholars on the opportunities and challenges associated with post-disaster research and disaster studies in general.Design/methodology/approachThis paper is based on the conversations that took place on Disasters: Deconstructed Podcast livestream on the 15th September 2021.FindingsThe prominent themes in this conversation include representation, power imbalances and research extractivism and reciprocity.Originality/valueThe conversation contributes to the ongoing discussions around how research is conducted immediately following disasters.