bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates
Authors: Cardon Sébastien , Hervis Yadira P. , Bolbach Gérard , Lopin-Bon Chrystel , Jacquinet Jean-Claude , Illien Françoise , Walrant Astrid , Ravault Delphine , He Bingwei , Molina Laura , Burlina Fabienne , Lequin Olivier , Joliot Alain , Carlier Ludovic , Sagan Sandrine 
Published: April 2023

AbstractEngrailed2 (En2) is a transcription factor that transfers from cell to cell through unconventional pathways. The poorly understood internalization mechanism of this cationic protein is proposed to require an initial interaction with cell-surface glycosaminoglycans (GAGs). To decipher the role of GAGs in En2 internalization, we have quantified the entry of its homeodomain region in model cells that differ in their content in cell-surface GAGs. The binding specificity to GAGs and the influence of this interaction on the structure and dynamics of En2 was also investigated at the amino acid level. Our results show that a high-affinity GAG-binding sequence (RKPKKKNPNKEDKRPR), upstream of the homeodomain, controls En2 internalization through selective interactions with highly-sulfated heparan sulfate GAGs. Our data underline the functional importance of the intrinsically disordered basic region upstream of En2 internalization domain, and demonstrate the critical role of GAGs as an entry gate, finely tuning homeoprotein capacity to internalize into cells.
Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis
Authors: Cai Xiaojie , Han Maoying , Lou Fangzhou , Sun Yang , Yin Qianqian , Sun Libo , Wang Zhikai , Li Xiangxiao , Zhou Hong , Xu Zhenyao , Wang Hong , Deng Siyu , Zheng Xichen , Zhang Taiyu , Li Qun , Zhou Bin , Wang Honglin 
Published: April 2023

AbstractDermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals aTnc+papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.
Encoding reprogrammable properties into magneto-mechanical materials via topology optimization
Authors: Zhao Zhi , Zhang Xiaojia Shelly 
Published: April 2023

AbstractThe properties of materials and structures typically remain fixed after being designed and manufactured. There is a growing interest in systems with the capability of altering their behaviors without changing geometries or material constitutions, because such reprogrammable behaviors could unlock multiple functionalities within a single design. We introduce an optimization-driven approach, based on multi-objective magneto-mechanical topology optimization, to design magneto-active metamaterials and structures whose properties can be seamlessly reprogrammed by switching on and off the external stimuli fields. This optimized material system exhibits one response under pure mechanical loading, and switches to a distinct response under joint mechanical and magnetic stimuli. We discover and experimentally demonstrate magneto-mechanical metamaterials and metastructures that realize a wide range of reprogrammable responses, including multi-functional actuation responses, adaptable snap-buckling behaviors, switchable deformation modes, and tunable bistability. The proposed approach paves the way for promising applications such as magnetic actuators, soft robots, and energy harvesters.
Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome
Authors: Russell Seongmi K. , Harrison Jessica K. , Olson Benjamin S. , Lee Hyung Joo , O’Brien Valerie P. , Xing Xiaoyun , Livny Jonathan , Yu Lu , Roberson Elisha D. O. , Bomjan Rajdeep , Fan Changxu , Sha Marina , Estfanous Shady , Amer Amal O. , Colonna Marco , Stappenbeck Thaddeus S. , Wang Ting , Hannan Thomas J. , Hultgren Scott J. 
Published: April 2023

AbstractPrevious urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding—responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection.
Maximum likelihood pandemic-scale phylogenetics
Authors: De Maio Nicola , Kalaghatgi Prabhav , Turakhia Yatish , Corbett-Detig Russell , Minh Bui Quang , Goldman Nick 
Published: April 2023

AbstractPhylogenetics has a crucial role in genomic epidemiology. Enabled by unparalleled volumes of genome sequence data generated to study and help contain the COVID-19 pandemic, phylogenetic analyses of SARS-CoV-2 genomes have shed light on the virus’s origins, spread, and the emergence and reproductive success of new variants. However, most phylogenetic approaches, including maximum likelihood and Bayesian methods, cannot scale to the size of the datasets from the current pandemic. We present ‘MAximum Parsimonious Likelihood Estimation’ (MAPLE), an approach for likelihood-based phylogenetic analysis of epidemiological genomic datasets at unprecedented scales. MAPLE infers SARS-CoV-2 phylogenies more accurately than existing maximum likelihood approaches while running up to thousands of times faster, and requiring at least 100 times less memory on large datasets. This extends the reach of genomic epidemiology, allowing the continued use of accurate phylogenetic, phylogeographic and phylodynamic analyses on datasets of millions of genomes.
Comparison of transformations for single-cell RNA-seq data
Authors: Ahlmann-Eltze Constantin , Huber Wolfgang 
Published: April 2023

AbstractThe count table, a numeric matrix of genes × cells, is the basic input data structure in the analysis of single-cell RNA-sequencing data. A common preprocessing step is to adjust the counts for variable sampling efficiency and to transform them so that the variance is similar across the dynamic range. These steps are intended to make subsequent application of generic statistical methods more palatable. Here, we describe four transformation approaches based on the delta method, model residuals, inferred latent expression state and factor analysis. We compare their strengths and weaknesses and find that the latter three have appealing theoretical properties; however, in benchmarks using simulated and real-world data, it turns out that a rather simple approach, namely, the logarithm with a pseudo-count followed by principal-component analysis, performs as well or better than the more sophisticated alternatives. This result highlights limitations of current theoretical analysis as assessed by bottom-line performance benchmarks.
Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape
Authors: Ren Jingyi , Zhou Haowen , Zeng Hu , Wang Connie Kangni , Huang Jiahao , Qiu Xiaojie , Sui Xin , Li Qiang , Wu Xunwei , Lin Zuwan , Lo Jennifer A. , Maher Kamal , He Yichun , Tang Xin , Lam Judson , Chen Hongyu , Li Brian , Fisher David E. , Liu Jia , Wang Xiao 
Published: April 2023

AbstractSpatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap—a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed ‘kinetic gene clusters’ whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.
A co-transcriptional ribosome assembly checkpoint controls nascent large ribosomal subunit maturation
Authors: Sanghai Zahra A. , Piwowarczyk Rafal , Broeck Arnaud Vanden , Klinge Sebastian 
Published: April 2023

AbstractDuring transcription of eukaryotic ribosomal DNA in the nucleolus, assembly checkpoints exist that guarantee the formation of stable precursors of small and large ribosomal subunits. While the formation of an early large subunit assembly checkpoint precedes the separation of small and large subunit maturation, its mechanism of action and function remain unknown. Here, we report the cryo-electron microscopy structure of the yeast co-transcriptional large ribosomal subunit assembly intermediate that serves as a checkpoint. The structure provides the mechanistic basis for how quality-control pathways are established through co-transcriptional ribosome assembly factors, that structurally interrogate, remodel and, together with ribosomal proteins, cooperatively stabilize correctly folded pre-ribosomal RNA. Our findings thus provide a molecular explanation for quality control during eukaryotic ribosome assembly in the nucleolus.
AmelHap: Leveraging drone whole-genome sequence data to create a honey bee HapMap
Authors: Parejo M. , Talenti A. , Richardson M. , Vignal A. , Barnett M. , Wragg D. 
Published: April 2023

AbstractHoney bee, Apis mellifera, drones are typically haploid, developing from an unfertilized egg, inheriting only their queen’s alleles and none from the many drones she mated with. Thus the ordered combination or ‘phase’ of alleles is known, making drones a valuable haplotype resource. We collated whole-genome sequence data for 1,407 drones, including 45 newly sequenced Scottish drones, collectively representing 19 countries, 8 subspecies and various hybrids. Following alignment to Amel_HAv3.1, variant calling and quality filtering, we retained 17.4 M high quality variants across 1,328 samples with a genotyping rate of 98.7%. We demonstrate the utility of this haplotype resource, AmelHap, for genotype imputation, returning >95% concordance when up to 61% of data is missing in haploids and up to 12% of data is missing in diploids. AmelHap will serve as a useful resource for the community for imputation from low-depth sequencing or SNP chip data, accurate phasing of diploids for association studies, and as a comprehensive reference panel for population genetic and evolutionary analyses.
New insights into how popular electronic cigarette aerosols and aerosol constituents affect SARS-CoV-2 infection of human bronchial epithelial cells
Authors: Phandthong Rattapol , Wong Man , Song Ann , Martinez Teresa , Talbot Prue 
Published: April 2023

AbstractThe relationship between the use of tobacco products and SARS-CoV-2 infection is poorly understood and controversial. Few studies have examined the effect of electronic cigarettes (ECs) on SARS-CoV-2 infection. We tested the hypothesis that EC fluids and aerosols with nicotine promote SARS-COV-2 infection by increasing viral entry into human respiratory epithelial cells. Responses of BEAS-2B cells to JUUL aerosols or their individual constituents were compared using three exposure platforms: submerged culture, air–liquid-interface (ALI) exposure in a cloud chamber, and ALI exposure in a Cultex system, which produces authentic heated EC aerosols. In general, nicotine and nicotine + propylene glycol/vegetable glycerin aerosols increased ACE2 (angiotensin converting enzyme 2) levels, the SARS-CoV-2 receptor; and increased the activity of TMPRSS2 (transmembrane serine protease 2), an enzyme essential for viral entry. Lentivirus pseudoparticles with spike protein were used to test viral penetration. Exposure to nicotine, EC fluids, or aerosols altered the infection machinery and increased viral entry into cells. While most data were in good agreement across the three exposure platforms, cells were more responsive to treatments when exposed at the ALI in the Cultex system, even though the exposures were brief and intermittent. While both nicotine and JUUL aerosols increased SARS-CoV-2 infection, JUUL significantly decreased the effect of nicotine alone. These data support the idea that vaping can increase the likelihood of contracting COVID-19 and that e-liquid composition may modulate this effect.
Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI
Authors: Ajčević Miloš , Iscra Katerina , Furlanis Giovanni , Michelutti Marco , Miladinović Aleksandar , Buoite Stella Alex , Ukmar Maja , Cova Maria Assunta , Accardo Agostino , Manganotti Paolo 
Published: April 2023

AbstractCognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects. We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis. Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M). The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE). The hypoperfusion areas identified in the right hemisphere regions were more extensive. These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.
The efficacy of a range of hygiene measures for boot cleaning to protect natural vegetation from Phytophthora cinnamomi
Authors: Liew Edward C. Y. , Phelan Maureen , McDougall Keith L. 
Published: April 2023

AbstractPhytophthora cinnamomiis an oomycete found in the soil and capable of invading the roots of a wide range of host plants globally, potentially killing them and affecting the ecosystems they inhabit. This pathogen is often inadvertently dispersed in natural vegetation on the footwear of humans. A range of equipment is often provided or recommended to be carried for cleaning footwear in places whereP. cinnamomiposes a threat to biodiversity. These are typically a brush for mechanically removing soil and/or a disinfectant for killing the pathogen. Despite their widespread use, to our knowledge, the majority of hygiene measures have not been experimentally tested for their efficacy. In the current study, we tested whether two types of brush and the two most widely used disinfectants (70% methylated spirits and benzalkonium chloride) were effective in removing the pathogen from boots. We tested the brushes and disinfectants in two soil types and two moisture levels. All hygiene measures were found to be better than doing nothing, although some were only effective with sandy or dry soils. Benzalkonium chloride was largely ineffective as a spray but highly effective when used in a footbath. Brushing did not improve cleaning when used with 70% methylated spirits. None of the hygiene measures was completely effective for cleaning boots that had been in wet loamy soil. Our findings have important implications for management of this threat because some recommended hygiene practices are not doing what they claim.
Application of a novel deep eutectic solvent as a capable and new catalyst for the synthesis of tetrahydropyridines and 1,3-thiazolidin-4-ones
Authors: Goudarzi Hadis , Habibi Davood , Monem Arezo 
Published: April 2023

AbstractA novel deep eutectic solvent (ETPP-Br/THF-TCA-DES) was prepared by a mixture of ethyl triphenylphosphonium bromide (ETPP-Br) and tetrahydrofuran-2,3,4,5-tetra-carboxylic acid (THF-TCA, mole ratio 7:3), characterized by FT-IR, TGA/DTA, densitometer, eutectic point, and 1H NMR techniques and used as a capable and new catalyst for the synthesis of two sets of compounds: (1) the four new [a(1–4)] and the eleven [a(5–15)] known alkyl 1,2,6-trisubstituted-4-[(hetero)arylamino]-1,2,5,6-tetrahydropyridine-3-carboxylates and (2) the two new [b(1–2)] and the eight [b(3–10)] known 1,3-thiazolidin-4-ones in DES with short reaction time, high yields, and easy recycling and separation of the DES catalyst. There is a nice consistency between the proposed structure of the DES compound, the integration values of the 1H NMR peaks and the ratio of ETPP-Br to THF-TCA obtained from the eutectic point phase diagram. Also, the decrease in splitting patterns of the peaks in DES, compared to the two starting materials can be the good evidence of the hydrogen bond formation between the two components.
Exogenous lactate augments exercise-induced improvement in memory but not in hippocampal neurogenesis
Authors: Hwang Deunsol , Kim Jisu , Kyun Sunghwan , Jang Inkwon , Kim Taeho , Park Hun-Young , Lim Kiwon 
Published: April 2023

AbstractAdult hippocampal neurogenesis (AHN), the lifelong process of formation of new neurons in the mammalian brain, plays an important role in learning and memory. Exercise is an effective enhancer of AHN; however, the molecular mediators of exercise-induced AHN are unknown. Recently, lactate was considered as an important mediator of exercise-induced AHN. Therefore, we hypothesized that exercise with lactate intake could augment exercise-induced AHN. This study was conducted for 5 weeks with 7-week-old ICR male mice that performed mild-intensity exercise (just below lactate threshold, 55–60%VO2max) with or without oral administration of lactate 5 days/week. Cell proliferation, neuronal differentiation, neurogenesis-relevant factors, reference and retention memory, and spatial working memory were evaluated at the end of the experiment. The results showed that AHN was enhanced by lactate intake, but exercise-induced AHN was not augmented by exercise with lactate intake. Nevertheless, exercise-induced improvement in reference and retention memory was augmented by exercise with lactate intake. And spatial working memory was promoted by the co-treatment, also protein expression of hippocampal FNDC5, BDNF, PGC1α, and MCT2 were elevated by the co-treatment. Therefore, our findings suggest that lactate has a potential to be developed as a novel supplement that improves the positive effects of exercise on the hippocampus and its cognitive function.
Using inertial measurement units for quantifying the most intense jumping movements occurring in professional male volleyball players
Authors: Lima Ricardo Franco , Silva Ana Filipa , Matos Sérgio , de Oliveira Castro Henrique , Rebelo André , Clemente Filipe Manuel , Nobari Hadi 
Published: April 2023

AbstractThe purpose of this study was to use an inertial measurement unit (IMU) to analyze variations in the jump outcomes concerning weekly training days, and the dependencies between the number of jumps per minute and the jump height. An experimental research design was adopted across three weeks of the final play-off of a volleyball championship. Through an IMU, the external load of seven male elite volleyball athletes of a top rating team from Portuguese 1st Division (age: 30.5 ± 3.5 years; height: 200.2 ± 6.3 cm; body mass: 93.0 ± 8.1 kg; BMI: 23.1 ± 2.3 kg/m2) was monitored. Repeated measures ANOVA was executed to compare the outcomes between training days. It was observed a similar density of jumps during the week. However, when comparing MD-1 to MD-2, a more significant average number of jumps per minute was observed in MD-1 (1.3 ± 0.2 vs. 1.0 ± 0.2). Additionally, a positive, large and significant correlation was registered between the number of jumps and the height of the jump. Those results highlight the benefits of the specific training, leading to greater stimulation and improvement, in a game-like context, of the stretching-shortening cycle, observed in every jump action in volleyball.
PDLIM1 inhibits cell migration and invasion in diabetic retinopathy via negatively regulating Wnt3a
Authors: Xie Pinxue , You Qisheng , Zhu Jiang , Xie Wuxiang , Wei Ping , Zhu Siquan , Du Yunhui , Gao Xinxiao 
Published: April 2023

AbstractThe injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell’s ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.