bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
Authors: Gracias Jessica , Orhan Funda , Hörbeck Elin , Holmén-Larsson Jessica , Khanlarkani Neda , Malwade Susmita , Goparaju Sravan K. , Schwieler Lilly , Demirel İlknur Ş. , Fu Ting , Fatourus-Bergman Helena , Pelanis Aurimantas , Goold Carleton P. , Goulding Anneli , Annerbrink Kristina , Isgren Anniella , Sparding Timea , Schalling Martin , Yañez Viviana A. Carcamo , Göpfert Jens C. , Nilsson Johanna , Brinkmalm Ann , Blennow Kaj , Zetterberg Henrik , Engberg Göran , Piehl Fredrik , Sheridan Steven D. , Perlis Roy H. , Cervenka Simon , Erhardt Sophie , Landen Mikael , Sellgren Carl M.
Published: November 2022

Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34–0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22–0.35], healthy controls: median 0.28 [CI = 0.24–0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)−1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01–0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
Photonic quadrupole topological insulator using orbital-induced synthetic flux
Authors: Schulz Julian , Noh Jiho , Benalcazar Wladimir A. , Bahl Gaurav , von Freymann Georg
Published: November 2022

The rich physical properties of multiatomic crystals are determined, to a significant extent, by the underlying geometry and connectivity of atomic orbitals. The mixing of orbitals with distinct parity representations, such as s and p orbitals, has been shown to be useful for generating systems that require alternating phase patterns, as with the sign of couplings within a lattice. Here we show that by breaking the symmetries of such mixed-orbital lattices, it is possible to generate synthetic magnetic flux threading the lattice. We use this insight to experimentally demonstrate quadrupole topological insulators in two-dimensional photonic lattices, leveraging both s and p orbital-type modes. We confirm the nontrivial quadrupole topology by observing the presence of protected zero-dimensional states, which are spatially confined to the corners, and by confirming that these states sit at mid-gap. Our approach is also applicable to a broader range of time-reversal-invariant synthetic materials that do not allow for tailored connectivity, and in which synthetic fluxes are essential.
Constraining extreme precipitation projections using past precipitation variability
Authors: Zhang Wenxia , Furtado Kalli , Zhou Tianjun , Wu Peili , Chen Xiaolong
Published: November 2022

Projected changes of future precipitation extremes exhibit substantial uncertainties among climate models, posing grand challenges to climate actions and adaptation planning. Practical methods for narrowing the projection uncertainty remain elusive. Here, using large model ensembles, we show that the uncertainty in projections of future extratropical extreme precipitation is significantly correlated with the model representations of present-day precipitation variability. Models with weaker present-day precipitation variability tend to project larger increases in extreme precipitation occurrences under a given global warming increment. This relationship can be explained statistically using idealized distributions for precipitation. This emergent relationship provides a powerful constraint on future projections of extreme precipitation from observed present-day precipitation variability, which reduces projection uncertainty by 20–40% over extratropical regions. Because of the widespread impacts of extreme precipitation, this has not only provided useful insights into understanding uncertainties in current model projections, but is also expected to bring potential socio-economic benefits in climate change adaptation planning.
Subcutaneous power supply by NIR-II light
Authors: Lyu Shanzhi , He Yonglin , Tao Xinglei , Yao Yuge , Huang Xiangyi , Ma Yingchao , Peng Zhimin , Ding Yanjun , Wang Yapei
Published: November 2022

Implantable medical devices are wished to be recharged via contactless power transfer technologies without interventional operations. Superior to subcutaneous power supply by visible light or electromagnetic wave, second near-infrared (NIR-II) light is predicted to possess 60 times subcutaneous power transmission but hard to be utilized. Here we report a photo-thermal-electric converter via the combination of photothermal conversion and thermoelectric conversion. It is able to generate an output power as high as 195 mW under the coverage of excised tissues, presenting advantages of non-invasion, high output power, negligible biological damage, and deep tissue penetration. As an in vivo demonstration, the output power of a packaged converter in the abdominal cavity of a rabbit reaches 20 mW under NIR-II light irradiation through the rabbit skin with a thickness of 8.5 mm. This value is high enough to recharge an implanted high-power-consumption wireless camera and transfer video signal out of body in real-time.
Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
Authors: Satti Iman , Wittenberg Rachel E. , Li Shuailin , Harris Stephanie A. , Tanner Rachel , Cizmeci Deniz , Jacobs Ashley , Williams Nicola , Mulenga Humphrey , Fletcher Helen A. , Scriba Thomas J. , Tameris Michele , Hatherill Mark , McShane Helen
Published: November 2022

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-$$\alpha$$
α
2, TNF-$$\alpha$$
α
, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.
Generating intense electric fields in 2D materials by dual ionic gating
Authors: Weintrub Benjamin I. , Hsieh Yu-Ling , Kovalchuk Sviatoslav , Kirchhof Jan N. , Greben Kyrylo , Bolotin Kirill I.
Published: November 2022

The application of an electric field through two-dimensional materials (2DMs) modifies their properties. For example, a bandgap opens in semimetallic bilayer graphene while the bandgap shrinks in few-layer 2D semiconductors. The maximum electric field strength achievable in conventional devices is limited to ≤0.3 V/nm by the dielectric breakdown of gate dielectrics. Here, we overcome this limit by suspending a 2DM between two volumes of ionic liquid (IL) with independently controlled potentials. The potential difference between the ILs falls across an ultrathin layer consisting of the 2DM and the electrical double layers above and below it, producing an intense electric field larger than 4 V/nm. This field is strong enough to close the bandgap of few-layer WSe2, thereby driving a semiconductor-to-metal transition. The ability to apply fields an order of magnitude higher than what is possible in dielectric-gated devices grants access to previously-inaccessible phenomena occurring in intense electric fields.
Cooperative assembly of p97 complexes involved in replication termination
Authors: Kochenova Olga V. , Mukkavalli Sirisha , Raman Malavika , Walter Johannes C.
Published: November 2022

The p97 ATPase extracts polyubiquitylated proteins from diverse cellular structures in preparation for destruction by the proteasome. p97 functions with Ufd1-Npl4 and a variety of UBA-UBX co-factors, but how p97 complexes assemble on ubiquitylated substrates is unclear. To address this, we investigated how p97 disassembles the CMG helicase after it is ubiquitylated during replication termination. We show that p97Ufd1-Npl4 recruitment to CMG requires the UBA-UBX protein Ubxn7, and conversely, stable Ubxn7 binding to CMG requires p97Ufd1-Npl4. This cooperative assembly involves interactions between Ubxn7, p97, Ufd1-Npl4, and ubiquitin. Another p97 co-factor, Faf1, partially compensates for the loss of Ubxn7. Surprisingly, p97Ufd1-Npl4-Ubxn7 and p97Ufd1-Npl4-Faf1 also assemble cooperatively on unanchored ubiquitin chains. We propose that cooperative and substrate-independent recognition of ubiquitin chains allows p97 to recognize an unlimited number of polyubiquitylated proteins while avoiding the formation of partial, inactive complexes.
RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation
Authors: Spaulding Emily L. , Feidler Alexis M. , Cook Lio A. , Updike Dustin L.
Published: November 2022

The intrinsically disordered RG/RGG repeat domain is found in several nucleolar and P-granule proteins, but how it influences their phase separation into biomolecular condensates is unclear. We survey all RG/RGG repeats in C. elegans and uncover nucleolar and P-granule-specific RG/RGG motifs. An uncharacterized protein, K07H8.10, contains the longest nucleolar-like RG/RGG domain in C. elegans. Domain and sequence similarity, as well as nucleolar localization, reveals K07H8.10 (NUCL-1) to be the homolog of Nucleolin, a protein conserved across animals, plants, and fungi, but previously thought to be absent in nematodes. Deleting the RG/RGG repeats within endogenous NUCL-1 and a second nucleolar protein, GARR-1 (GAR1), demonstrates these domains are dispensable for nucleolar accumulation. Instead, their RG/RGG repeats contribute to the phase separation of proteins into nucleolar sub-compartments. Despite this common RG/RGG repeat function, only removal of the GARR-1 RG/RGG domain affects worm fertility and development, decoupling precise sub-nucleolar structure from nucleolar function.
Absolute protein quantification using fluorescence measurements with FPCountR
Authors: Csibra Eszter , Stan Guy-Bart
Published: November 2022

This 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

Respiratory 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

Mechanical 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

Improved 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

LiNi0.5Co0.2Mn0.3O2(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

Marine 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

Fabricating 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

Human 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

Periodontitis 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

Multi-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

Deep 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

β-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

The 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

Pseudoallergies 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

A 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.
Influence of the nutritional status on facial morphology in young Japanese women
Authors: Tanikawa Chihiro , Kurata Miki , Tanizaki Noriko , Takeuchi Mika , Zere Edlira , Fukuo Keisuke , Takada Kenji
Published: November 2022

Evidence regarding the possible influence of nutritional status on the facial morphology has thus far been insufficient. We examined whether or not the physical body compositions and dietary behaviors were correlated with any morphological characteristics of the face. One hundred and fifteen young Japanese women participated. Variables representing the dietary behaviors were extracted from self-reported survey data, and corresponding three-dimensional (3D) facial images and body compositions were examined. Multivariate analyses identified significant relationships between the nutritional status and facial topography (p < 0.05). The clustering method revealed the existence of three dietary condition patterns (“balanced diet”, “high-calorie-diet” with obesity tendency, and “imbalanced low-calorie-diet” with sarcopenic obesity tendency). Among these three patterns, a round face (increased facial width; analysis of variance [ANOVA], p < 0.05) was observed in the high-calorie-diet pattern, while the imbalanced low-calorie-diet pattern showed a more masculine face (increased face height, decreased eye height, increased non-allometric sexual shape differences; ANOVA, p < 0.05), thus suggesting the possibility of sex-hormonal influences. In summary, the body composition and dietary behaviors were found to influence the facial morphology, and potential biological influences were discussed.
Numerical simulation and experimental research on mechanical behaviour of hydraulic disc brakes based on multi-body dynamics
Authors: Zhang Wenyue , Zhao Cunbao , Chen Pengyu , Chen Enli , Lei Tianyu
Published: November 2022

As a vital road construction machine, the bridge erecting machine works in a very complex environment. The brake as an important link to maintain the safety and stability of the bridge erecting machine, it will have serious consequences if it is failed. Establishing the brake simulation model and specifying the fault characteristics according to the actual operation status will make it more efficient to find the cause of faults and maintain the safety of machine for a long time. A simulation model of brake of the bridge erecting machine was established by Adams. The brake arms and center axis with obvious data characteristics were flexibly processed, and finite elements were analysed using Abaqus. To verify the accuracy of simulation models, rectangular rosettes were applied to special geometric points, and the strain data were gathered by using the DH3816N collector and compared with the simulation model. The Adams kinematic simulation model was used to simulate the actual operating conditions by the experiment of the disc springs. Two typical fault phenomena were selected: reduced insufficient of disc spring and oil pressure, and two fault characteristics were extracted: variation of the brake shoe clearance and variation of the braking system pressure. When the brake generates the fault characteristics, the normal operation of the brake will not be affected if the fault characteristics are in the first stage. When the fault characteristics are beyond the critical threshold, the faults phenomena of the brake are generated. The results of the simulation experiments proved that the method of using the simulation model to extract the fault characteristics of the braking system and distinguish the causes of the fault was feasible.
Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase
Authors: Knorr Debbra Y. , Schneider Kristin , Büschgens Luca , Förster Jan , Georges Nadine S. , Geurten Bart R. H. , Heinrich Ralf
Published: November 2022

Cytokine receptor-like factor 3 (CRLF3) is a conserved but largely uncharacterized orphan cytokine receptor of eumetazoan animals. CRLF3-mediated neuroprotection in insects can be stimulated with human erythropoietin. To identify mechanisms of CRLF3-mediated neuroprotection we studied the expression and proapoptotic function of acetylcholinesterase in insect neurons. We exposed primary brain neurons from Tribolium castaneum to apoptogenic stimuli and dsRNA to interfere with acetylcholinesterase gene expression and compared survival and acetylcholinesterase expression in the presence or absence of the CRLF3 ligand erythropoietin. Hypoxia increased apoptotic cell death and expression of both acetylcholinesterase-coding genes ace-1 and ace-2. Both ace genes give rise to single transcripts in normal and apoptogenic conditions. Pharmacological inhibition of acetylcholinesterases and RNAi-mediated knockdown of either ace-1 or ace-2 expression prevented hypoxia-induced apoptosis. Activation of CRLF3 with protective concentrations of erythropoietin prevented the increased expression of acetylcholinesterase with larger impact on ace-1 than on ace-2. In contrast, high concentrations of erythropoietin that cause neuronal death induced ace-1 expression and hence promoted apoptosis. Our study confirms the general proapoptotic function of AChE, assigns a role of both ace-1 and ace-2 in the regulation of apoptotic death and identifies the erythropoietin/CRLF3-mediated prevention of enhanced acetylcholinesterase expression under apoptogenic conditions as neuroprotective mechanism.
Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU
Authors: Bychinin Mikhail V. , Klypa Tatiana V. , Mandel Irina A. , Yusubalieva Gaukhar M. , Baklaushev Vladimir P. , Kolyshkina Nadezhda A. , Troitsky Aleksandr V.
Published: November 2022

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.

Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.
Continuous spark plasma synthesis of Au/Co binary nanoparticles with tunable properties
Authors: Villy Lajos Péter , Kohut Attila , Kéri Albert , Bélteki Ádám , Radnóczi György , Fogarassy Zsolt , Radnóczi György Zoltán , Galbács Gábor , Geretovszky Zsolt
Published: November 2022

We present here a scalable and environmentally friendly gas phase technique employing atmospheric pressure electrical spark discharge plasmas for the production of Au/Co binaries, an effective catalyst system for the decomposition of hydrogen-rich compounds, such as ammonium borane. We demonstrate that Au/Co alloy nanoparticles can be produced via the spark plasma-based technique. The possibility of varying the morphology and phase structure via real time heat treatment of the generated aerosol to form Au/Co/CoO particles with continuous control over a wide particle compositional range (from 24 to 64 at.% [Co]/([Co] + [Au]) content) is also demonstrated. Since our spark-based approach is proven to be capable of providing reasonable particle yields, these results may contribute to the transition of lab-scale, nanocatalyst-based hydrogen storage systems to real world applications.
Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker
Authors: Kumar Pardeep , Thakur Riptee , Acharya Pratap Chandra , Mohan Hosahalli K. , Pallavi U. N. , Maheshwari Divya , Mohammed K M Afsal , Kumar Aishwarya , Goud Nerella Sridhar , Joshi Raman Kumar , Kumar Manoj , Nagaraj Chandana
Published: November 2022

P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.
Evaluating the quality of care for postpartum hemorrhage with a new quantitative tool: a population-based study
Authors: Didelot Hélène , Goffinet François , Seco Aurélien , Deneux-Tharaux Catherine ,   The EPIMOMS (EPIdémiologie de la MOrbidité Maternelle Sévère) Study Group, Azria Elie , Baunot Nathalie , Beucher Gaël , Bonnet Marie-Pierre , Bouvier-Colle Marie-Hélène , Carbillon Lionel , Chantry Anne , Chiesa-Dubruille Coralie , Crenn-Hebert Catherine , Deneux-Tharaux Catherine , Dupont Corinne , Fresson Jeanne , Kayem Gilles , Langer Bruno , Mignon Alexandre , Rozenberg Patrick , Rudigoz René-Charles , Seco Aurélien , Touzet Sandrine , Vendittelli Françoise
Published: November 2022

To develop a new tool to assess the global quality of care for post-partum hemorrhage (PPH)—the leading preventable cause of maternal mortality worldwide—and to identify characteristics of maternity units associated with inadequate PPH management. This is a secondary analysis of the EPIMOMS population-based study conducted in 2012–2013 in 119 french maternity units (182,309 women who gave birth). We included women with severe PPH. We first developed a score to quantify the quality of care for PPH. Then, we identified characteristics of the maternity units associated with “inadequate care” defined by a score below the 25th percentile, with multi-level logistic regression adjusted for individual characteristics. The score combined 8 key components of care and took into account delivery mode and PPH cause. For PPH after vaginal delivery, the risk of inadequate care was increased in low versus high-volume maternity units (< 1000 deliveries/year: aOR-2.20 [1.12–4.32], [1000–2000 [deliveries/year: aOR-1.90 [1.02–3.56] compared to ≥ 3500 deliveries/year), in private versus public units (aOR-1.72 [1.00–2.97]), and in low versus high-level of care units (aOR-2.04 [1.24–3.35]). For PPH after cesarean, the only characteristic associated with an increased risk of inadequate care was the absence of 24/24-onsite anesthesiologist (aOR-4.34 [1.41–13.31]). These results indicate where opportunities for improvement are the greatest.