bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute protein quantification using fluorescence measurements with FPCountR
Authors: Csibra Eszter , Stan Guy-Bart 
Published: November 2022

AbstractThis paper presents a generalisable method for the calibration of fluorescence readings on microplate readers, in order to convert arbitrary fluorescence units into absolute units. FPCountR relies on the generation of bespoke fluorescent protein (FP) calibrants, assays to determine protein concentration and activity, and a corresponding analytical workflow. We systematically characterise the assay protocols for accuracy, sensitivity and simplicity, and describe an ‘ECmax’ assay that outperforms the others and even enables accurate calibration without requiring the purification of FPs. To obtain cellular protein concentrations, we consider methods for the conversion of optical density to either cell counts or alternatively to cell volumes, as well as examining how cells can interfere with protein counting via fluorescence quenching, which we quantify and correct for the first time. Calibration across different instruments, disparate filter sets and mismatched gains is demonstrated to yield equivalent results. It also reveals that mCherry absorption at 600 nm does not confound cell density measurements unless expressed to over 100,000 proteins per cell. FPCountR is presented as pair of open access tools (protocol and R package) to enable the community to use this method, and ultimately to facilitate the quantitative characterisation of synthetic microbial circuits.
Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure
Authors: Stutz Matthew R. , Dylla Nicholas P. , Pearson Steven D. , Lecompte-Osorio Paola , Nayak Ravi , Khalid Maryam , Adler Emerald , Boissiere Jaye , Lin Huaiying , Leiter William , Little Jessica , Rose Amber , Moran David , Mullowney Michael W. , Wolfe Krysta S. , Lehmann Christopher , Odenwald Matthew , De La Cruz Mark , Giurcanu Mihai , Pohlman Anne S. , Hall Jesse B. , Chaubard Jean-Luc , Sundararajan Anitha , Sidebottom Ashley , Kress John P. , Pamer Eric G. , Patel Bhakti K. 
Published: November 2022

AbstractRespiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.
Ultra-low-noise microwave to optics conversion in gallium phosphide
Authors: Stockill Robert , Forsch Moritz , Hijazi Frederick , Beaudoin Grégoire , Pantzas Konstantinos , Sagnes Isabelle , Braive Rémy , Gröblacher Simon 
Published: November 2022

AbstractMechanical resonators can act as excellent intermediaries to interface single photons in the microwave and optical domains due to their high quality factors. Nevertheless, the optical pump required to overcome the large energy difference between the frequencies can add significant noise to the transduced signal. Here we exploit the remarkable properties of thin-film gallium phosphide to demonstrate bi-directional on-chip conversion between microwave and optical frequencies, realized by piezoelectric actuation of a Gigahertz-frequency optomechanical resonator. The large optomechanical coupling and the suppression of two-photon absorption in the material allows us to operate the device at optomechanical cooperativities greatly exceeding one. Alternatively, when using a pulsed upconversion pump, we demonstrate that we induce less than one thermal noise phonon. We include a high-impedance on-chip matching resonator to mediate the mechanical load with the 50-Ω source. Our results establish gallium phosphide as a versatile platform for ultra-low-noise conversion of photons between microwave and optical frequencies.
A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases
Authors: Yasuhara Atsuhiro , Yamayoshi Seiya , Kiso Maki , Sakai-Tagawa Yuko , Okuda Moe , Kawaoka Yoshihiro 
Published: November 2022

AbstractImproved vaccines and antiviral agents that provide better, broader protection against seasonal and emerging influenza viruses are needed. The viral surface glycoprotein hemagglutinin (HA) is a primary target for the development of universal influenza vaccines and therapeutic antibodies. The other major surface antigen, neuraminidase (NA), has been less well studied as a potential target and fewer broadly reactive anti-NA antibodies have been identified. In this study, we isolate three human monoclonal antibodies that recognize NA from A/H1N1 subtypes, and find that one of them, clone DA03E17, binds to the NA of A/H3N2, A/H5N1, A/H7N9, B/Ancestral-lineage, B/Yamagata-lineage, and B/Victoria-lineage viruses. DA03E17 inhibits the neuraminidase activity by direct binding to the enzyme active site, and provides in vitro and in vivo protection against infection with several types of influenza virus. This clone could, therefore, be useful as a broadly protective therapeutic agent. Moreover, the neutralizing epitope of DA03E17 could be useful in the development of an NA-based universal influenza vaccine.
Degradation mechanism analysis of LiNi0.5Co0.2Mn0.3O2 single crystal cathode materials through machine learning
Authors: Sha Wuxin , Guo Yaqing , Cheng Danpeng , Han Qigao , Lou Ping , Guan Minyuan , Tang Shun , Zhang Xinfang , Lu Songfeng , Cheng Shijie , Cao Yuan-Cheng 
Published: November 2022

AbstractLiNi0.5Co0.2Mn0.3O2(NCM523) has become one of the most popular cathode materials for current lithium-ion batteries due to its high-energy density and cost performance. However, the rapid capacity fading of NCM severely hinders its development and applications. Here, the single crystal NCM523 materials under different degradation states are characterized using scanning transmission electron microscopy (STEM). Then we developed a neural network model with a two-sequential attention block to recognize the crystal structure and locate defects in STEM images. The number of point defects in NCM523 is observed to experience a trend of increasing first and then decreasing in the degradation process. The space between the transition metal columns shrinks obviously, inducing dramatic capacity decay. This analysis sheds light on the defect evolution and chemical transformation correlated with layered material degradation. It also provides interesting hints for researchers to regenerate the electrochemical capacity and design better battery materials with longer life.
Single-cell measurements and modelling reveal substantial organic carbon acquisition by Prochlorococcus
Authors: Wu Zhen , Aharonovich Dikla , Roth-Rosenberg Dalit , Weissberg Osnat , Luzzatto-Knaan Tal , Vogts Angela , Zoccarato Luca , Eigemann Falk , Grossart Hans-Peter , Voss Maren , Follows Michael J. , Sher Daniel 
Published: November 2022

AbstractMarine phytoplankton are responsible for about half of the photosynthesis on Earth. Many are mixotrophs, combining photosynthesis with heterotrophic assimilation of organic carbon, but the relative contribution of these two lifestyles is unclear. Here single-cell measurements reveal that Prochlorococcus at the base of the photic zone in the Eastern Mediterranean Sea obtain only ~20% of carbon required for growth by photosynthesis. This is supported by laboratory-calibrated calculations based on photo-physiology parameters and compared with in situ growth rates. Agent-based simulations show that mixotrophic cells could grow tens of metres deeper than obligate photo-autotrophs, deepening the nutricline by ~20 m. Time series from the North Atlantic and North Pacific indicate that, during thermal stratification, on average 8–10% of the Prochlorococcus cells live without enough light to sustain obligate photo-autotrophic populations. Together, these results suggest that mixotrophy underpins the ecological success of a large fraction of the global Prochlorococcus population and its collective genetic diversity.
Hierarchically self-assembled homochiral helical microtoroids
Authors: Du Cong , Li Zujian , Zhu Xuefeng , Ouyang Guanghui , Liu Minghua 
Published: November 2022

AbstractFabricating microscale helical structures from small molecules remains challenging due to the disfavoured torsion energy of twisted architectures and elusory chirality control at different hierarchical levels of assemblies. Here we report a combined solution–interface-directed assembly strategy for the formation of hierarchically self-assembled helical microtoroids with micrometre-scale lengths. A drop-evaporation assembly protocol on a solid substrate from pre-assembled intermediate colloids of enantiomeric binaphthalene bisurea compounds leads to microtoroids with preferred helicity, which depends on the molecular chirality of the starting enantiomers. Collective variable-temperature spectroscopic analyses, electron microscopy characterizations and theoretical simulations reveal a mechanism that simultaneously induces aggregation and cyclization to impart a favourable handedness to the final microtoroidal structures. We then use monodispersed luminescent helical toroids as chiral light-harvesting antenna and show excellent Förster resonance energy transfer ability to a co-hosted chiral acceptor dye, leading to unique circularly polarized luminescence. Our results shed light on the potential of the combined solution–interface-directed self-assembly approach in directing hierarchical chirality control and may advance the prospect of chiral superstructures at a higher length scale.
Effects of vessel traffic and ocean noise on gray whale stress hormones
Authors: Lemos Leila S. , Haxel Joseph H. , Olsen Amy , Burnett Jonathan D. , Smith Angela , Chandler Todd E. , Nieukirk Sharon L. , Larson Shawn E. , Hunt Kathleen E. , Torres Leigh G. 
Published: November 2022

AbstractHuman use of marinescapes is rapidly increasing, especially in populated nearshore regions where recreational vessel traffic can be dense. Marine animals can have a physiological response to such elevated human activity that can impact individual health and population dynamics. To understand the physiological impacts of vessel traffic on baleen whales, we investigated the adrenal stress response of gray whales (Eschrichtius robustus) to variable vessel traffic levels through an assessment of fecal glucocorticoid metabolite (fGC) concentrations. This analysis was conducted at the individual level, at multiple temporal scales (1–7 days), and accounted for factors that may confound fGC: sex, age, nutritional status, and reproductive state. Data were collected in Oregon, USA, from June to October of 2016–2018. Results indicate significant correlations between fGC, month, and vessel counts from the day prior to fecal sample collection. Furthermore, we show a significant positive correlation between vessel traffic and underwater ambient noise levels, which indicates that noise produced by vessel traffic may be a causal factor for the increased fGC. This study increases knowledge of gray whale physiological response to vessel traffic and may inform management decisions regarding regulations of vessel traffic activities and thresholds near critical whale habitats.
Platelet factor 4 (CXCL4/PF4) upregulates matrix metalloproteinase-2 (MMP-2) in gingival fibroblasts
Authors: Le Hoa T. , Golla Kalyan , Karimi Ryan , Hughes Michael R. , Lakschevitz Flavia , Cines Douglas B. , Kowalska M. Anna , Poncz Mortimer , McNagny Kelly M. , Häkkinen Lari , Kim Hugh 
Published: November 2022

AbstractPeriodontitis is a chronic inflammatory disease characterized by the release of matrix metalloproteinases (MMPs) from resident connective tissue cells in tooth-supporting tissues (periodontium). Platelet activation, and the attendant release of pro-inflammatory chemokines such as platelet factor 4 (CXCL4/PF4), are associated with periodontitis although the associated biochemical pathways remain undefined. Here we report that recombinant PF4 is internalized by cultured human gingival fibroblasts (hGFs), resulting in significant (p < 0.05) upregulation in both the production and release of MMP-2 (gelatinase A). This finding was corroborated by elevated circulating levels of MMP-2 (p < 0.05) in PF4-overexpressing transgenic mice, relative to controls. We also determined that PF4 induces the phosphorylation of NF-κB; notably, the suppression of NF-κB signaling by the inhibitor BAY 11-7082 abrogated PF4-induced MMP-2 upregulation. Moreover, the inhibition of surface glycosaminoglycans (GAGs) blocked both PF4 binding and NF-κB phosphorylation. Partial blockade of PF4 binding to the cells was achieved by treatment with either chondroitinase ABC or heparinase III, suggesting that both chondroitin sulfate and heparan sulfate mediate PF4 signaling. These results identify a novel pathway in which PF4 upregulates MMP-2 release from fibroblasts in an NF-κB- and GAG-dependent manner, and further our comprehension of the role of platelet signaling in periodontal tissue homeostasis.
An improved multi-view spectral clustering based on tissue-like P systems
Authors: Chen Huijian , Liu Xiyu 
Published: November 2022

AbstractMulti-view spectral clustering is one of the multi-view clustering methods widely studied by numerous scholars. The first step of multi-view spectral clustering is to construct the similarity matrix of each view. Consequently, the clustering performance will be greatly affected by the quality of the similarity matrix of each view. To solve this problem well, an improved multi-view spectral clustering based on tissue-like P systems is proposed in this paper. The optimal per-view similarity matrix is generated in an iterative manner. In addition, spectral clustering is combined with the symmetric nonnegative matrix factorization method to directly output the clustering results to avoid the secondary operation, such as k-means or spectral rotation. Furthermore, improved multi-view spectral clustering is integrated with the tissue-like P system to enhance the computational efficiency of the multi-view clustering algorithm. Extensive experiments verify the effectiveness of this algorithm over other state-of-the-art algorithms.
Comparison of deep learning segmentation and multigrader-annotated mandibular canals of multicenter CBCT scans
Authors: Järnstedt Jorma , Sahlsten Jaakko , Jaskari Joel , Kaski Kimmo , Mehtonen Helena , Lin Ziyuan , Hietanen Ari , Sundqvist Osku , Varjonen Vesa , Mattila Vesa , Prapayasotok Sangsom , Nalampang Sakarat 
Published: November 2022

AbstractDeep learning approach has been demonstrated to automatically segment the bilateral mandibular canals from CBCT scans, yet systematic studies of its clinical and technical validation are scarce. To validate the mandibular canal localization accuracy of a deep learning system (DLS) we trained it with 982 CBCT scans and evaluated using 150 scans of five scanners from clinical workflow patients of European and Southeast Asian Institutes, annotated by four radiologists. The interobserver variability was compared to the variability between the DLS and the radiologists. In addition, the generalisation of DLS to CBCT scans from scanners not used in the training data was examined to evaluate its out-of-distribution performance. The DLS had a statistically significant difference (p < 0.001) with lower variability to the radiologists with 0.74 mm than the interobserver variability of 0.77 mm and generalised to new devices with 0.63 mm, 0.67 mm and 0.87 mm (p < 0.001). For the radiologists’ consensus segmentation, used as a gold standard, the DLS showed a symmetric mean curve distance of 0.39 mm, which was statistically significantly different (p < 0.001) compared to those of the individual radiologists with values of 0.62 mm, 0.55 mm, 0.47 mm, and 0.42 mm. These results show promise towards integration of DLS into clinical workflow to reduce time-consuming and labour-intensive manual tasks in implantology.
Increased autophagy leads to decreased apoptosis during β-thalassaemic mouse and patient erythropoiesis
Authors: Chaichompoo Pornthip , Nithipongvanitch Ramaneeya , Kheansaard Wasinee , Tubsuwan Alisa , Srinoun Kanitta , Vadolas Jim , Fucharoen Suthat , Smith Duncan R. , Winichagoon Pranee , Svasti Saovaros 
Published: November 2022

Abstractβ-Thalassaemia results from defects in β-globin chain production, leading to ineffective erythropoiesis and subsequently to severe anaemia and other complications. Apoptosis and autophagy are the main pathways that regulate the balance between cell survival and cell death in response to diverse cellular stresses. Herein, the death of erythroid lineage cells in the bone marrow from both βIVS2-654-thalassaemic mice and β-thalassaemia/HbE patients was investigated. Phosphatidylserine (PS)-bearing basophilic erythroblasts and polychromatophilic erythroblasts were significantly increased in β-thalassaemia as compared to controls. However, the activation of caspase 8, caspase 9 and caspase 3 was minimal and not different from control in both murine and human thalassaemic erythroblasts. Interestingly, bone marrow erythroblasts from both β-thalassaemic mice and β-thalassaemia/HbE patients had significantly increased autophagy as shown by increased autophagosomes and increased co-localization between LC3 and LAMP-1. Inhibition of autophagy by chloroquine caused significantly increased erythroblast apoptosis. We have demonstrated increased autophagy which led to minimal apoptosis in β-thalassaemic erythroblasts. However, increased PS exposure occurring through other mechanisms in thalassaemic erythroblasts might cause rapid phagocytic removal by macrophages and consequently ineffective erythropoiesis in β-thalassaemia.
A survey of simian Plasmodium infections in humans in West Kalimantan, Indonesia
Authors: Sugiarto Sri Riyati , Natalia Diana , Mohamad Dayang Shuaisah Awang , Rosli Nawal , Davis Wendy A. , Baird J. Kevin , Singh Balbir , Elyazar Iqbal , Divis Paul C. S. , Davis Timothy M. E. 
Published: November 2022

AbstractThe simian parasite Plasmodium knowlesi is the predominant species causing human malaria infection, including hospitalisations for severe disease and death, in Malaysian Borneo. By contrast, there have been only a few case reports of knowlesi malaria from Indonesian Borneo. This situation seems paradoxical since both regions share the same natural macaque hosts and Anopheles mosquito vectors, and therefore have a similar epidemiologically estimated risk of infection. To determine whether there is a true cross-border disparity in P. knowlesi prevalence, we conducted a community-based malaria screening study using PCR in Kapuas Hulu District, West Kalimantan. Blood samples were taken between April and September 2019 from 1000 people aged 6 months to 85 years attending health care facilities at 27 study sites within or close to jungle areas. There were 16 Plasmodium positive samples by PCR, five human malarias (two Plasmodium vivax, two Plasmodium ovale and one Plasmodium malariae) and 11 in which no species could be definitively identified. These data suggest that, if present, simian malarias including P. knowlesi are rare in the Kapuas Hulu District of West Kalimantan, Indonesian Borneo compared to geographically adjacent areas of Malaysian Borneo. The reason for this discrepancy, if confirmed in other epidemiologically similar regions of Indonesian Borneo, warrants further studies targeting possible cross-border differences in human activities in forested areas, together with more detailed surveys to complement the limited data relating to monkey hosts and Anopheles mosquito vectors in Indonesian Borneo.
P2X4 receptor stimulation enhances MrgprB2-mediated mast cell activation and pseudoallergic reactions in mice
Authors: Yoshida Kazuki , Tanihara Shota , Miyashita Yuki , Obayashi Kosuke , Ito Masa-aki , Yamamoto Kimiko , Imai Toshiyashu , Matsuoka Isao 
Published: November 2022

AbstractPseudoallergies caused by drugs make disease treatment difficult. Mas-relate G protein-coupled receptor X2 (MRGPRX2), which is specifically expressed in mast cells (MCs), has been implicated in pseudoallergies. High concentrations of therapeutic agents are typically required to stimulate MRGPRX2. Although regulatory mechanisms may enhance this response, the factors involved in this regulation are not well-understood. In this study, the effects of extracellular ATP on MC activation induced by MrgprB2, the mouse ortholog of human MRGPRX2, were examined in mouse peritoneal MCs (PMCs). ATP alone induced minimal PMC degranulation but markedly enhanced degranulation induced by the MrgprB2 agonist compound 48/80 (CP48/80), substance P, PAMP-12, and vancomycin. ATP promoted CP48/80-induced increase in intracellular Ca2+ in PMCs. This enhancement effect of ATP was absent in PMCs prepared from P2X4 receptor (P2X4R)-deficient mice and inhibited by the PI3K inhibitor wortmannin. In addition, P2X4R deficiency reduced the skin-specific and systemic anaphylactic responses to CP48/80 in vivo. In MC-deficient KitW-sh/W-sh mice, reconstitution with MCs obtained from wild-type mice led to a more severe anaphylactic response to CP48/80 compared to that from P2X4R-deficient mice. P2X4R-mediated effect may be involved in MrgprB2-mediated MC activation in vivo and is a potential target for alleviating pseudoallergic reactions.
A simple stochastic model describing the evolution of genomic GC content in asexually reproducing organisms
Authors: Bohlin Jon 
Published: November 2022

AbstractA genome’s nucleotide composition can usually be summarized with (G)uanine + (C)ytosine (GC) or (A)denine + (T)hymine (AT) frequencies as GC% = 100% − AT%. Genomic AT/GC content has been linked to environment and selective processes in asexually reproducing organisms. A model is presented relating the evolution of genomic GC content over time to AT $$\rightarrow$$
→
GC and GC $$\rightarrow$$
→
AT mutation rates. By employing Itô calculus it is shown that if mutation rates are subject to random perturbations, that can vary over time, several implications follow. In particular, an extra Brownian motion term appears influencing genomic nucleotide variability; the greater the random perturbations the more genomic nucleotide variability. This can have several interpretations depending on the context. For instance, reducing the influence of the random perturbations on the AT/GC mutation rates and thus genomic nucleotide variability, to limit fitness decreasing and deleterious mutations, will likely suggest channeling of resources. On the other hand, increased genomic nucleotide diversity may be beneficial in variable environments. In asexually reproducing organisms, the Brownian motion term can be considered to be inversely reflective of the selective pressures an organism is subjected to at the molecular level. The presented model is a generalization of a previous model, limited to microbial symbionts, to all asexually reproducing, non-recombining organisms. Last, a connection between the presented model and the classical Luria–Delbrück mutation model is presented in an Itô calculus setting.