bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies
Authors: Yan Renhong , Wang Ruoke , Ju Bin , Yu Jinfang , Zhang Yuanyuan , Liu Nan , Wang Jia , Zhang Qi , Chen Peng , Zhou Bing , Li Yaning , Shen Yaping , Zhang Shuyuan , Tian Long , Guo Yingying , Xia Lu , Zhong Xinyue , Cheng Lin , Ge Xiangyang , Zhao Juanjuan , Wang Hong-Wei , Wang Xinquan , Zhang Zheng , Zhang Linqi , Zhou Qiang 
Published: March 2021

AbstractNeutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the “up” conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio: a subanalysis of pregnant Japanese women from the PROGNOSIS Asia study
Authors: Ohkuchi Akihide , Saito Shigeru , Yamamoto Tatsuo , Minakami Hisanori , Masuyama Hisashi , Kumasawa Keiichi , Yoshimatsu Jun , Nagamatsu Takeshi , Dietl Angela , Grill Sonja , Hund Martin 
Published: March 2021

AbstractTwo prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.
Long-distance electron transfer in a filamentous Gram-positive bacterium
Authors: Yang Yonggang , Wang Zegao , Gan Cuifen , Klausen Lasse Hyldgaard , Bonné Robin , Kong Guannan , Luo Dizhou , Meert Mathijs , Zhu Chunjie , Sun Guoping , Guo Jun , Ma Yuxin , Bjerg Jesper Tataru , Manca Jean , Xu Meiying , Nielsen Lars Peter , Dong Mingdong 
Published: March 2021

AbstractLong-distance extracellular electron transfer has been observed in Gram-negative bacteria and plays roles in both natural and engineering processes. The electron transfer can be mediated by conductive protein appendages (in short unicellular bacteria such as Geobacter species) or by conductive cell envelopes (in filamentous multicellular cable bacteria). Here we show that Lysinibacillus varians GY32, a filamentous unicellular Gram-positive bacterium, is capable of bidirectional extracellular electron transfer. In microbial fuel cells, L. varians can form centimetre-range conductive cellular networks and, when grown on graphite electrodes, the cells can reach a remarkable length of 1.08 mm. Atomic force microscopy and microelectrode analyses suggest that the conductivity is linked to pili-like protein appendages. Our results show that long-distance electron transfer is not limited to Gram-negative bacteria.
dCas9 regulator to neutralize competition in CRISPRi circuits
Authors: Huang Hsin-Ho , Bellato Massimo , Qian Yili , Cárdenas Pablo , Pasotti Lorenzo , Magni Paolo , Del Vecchio Domitilla 
Published: March 2021

AbstractCRISPRi-mediated gene regulation allows simultaneous control of many genes. However, highly specific sgRNA-promoter binding is, alone, insufficient to achieve independent transcriptional regulation of multiple targets. Indeed, due to competition for dCas9, the repression ability of one sgRNA changes significantly when another sgRNA becomes expressed. To solve this problem and decouple sgRNA-mediated regulatory paths, we create a dCas9 concentration regulator that implements negative feedback on dCas9 level. This allows any sgRNA to maintain an approximately constant dose-response curve, independent of other sgRNAs. We demonstrate the regulator performance on both single-stage and layered CRISPRi-based genetic circuits, zeroing competition effects of up to 15-fold changes in circuit I/O response encountered without the dCas9 regulator. The dCas9 regulator decouples sgRNA-mediated regulatory paths, enabling concurrent and independent regulation of multiple genes. This allows predictable composition of CRISPRi-based genetic modules, which is essential in the design of larger scale synthetic genetic circuits.
Ligand assisted growth of perovskite single crystals with low defect density
Authors: Liu Ye , Zheng Xiaopeng , Fang Yanjun , Zhou Ying , Ni Zhenyi , Xiao Xun , Chen Shangshang , Huang Jinsong 
Published: March 2021

AbstractA low defect density in metal halide perovskite single crystals is critical to achieve high performance optoelectronic devices. Here we show the reduction of defect density in perovskite single crystals grown by a ligand-assisted solution process with 3‐(decyldimethylammonio)‐propane‐sulfonate inner salt (DPSI) as an additive. DPSI ligands anchoring with lead ions on perovskite crystal surfaces not only suppress nucleation in solution, but also regulate the addition of proper ions to the growing surface, which greatly enhances the crystal quality. The grown CH3NH3PbI3 crystals show better crystallinity and a 23-fold smaller trap density of 7 × 1010 cm−3 than the optimized control crystals. The enhanced material properties result in significantly suppressed ion migration and superior X-ray detection sensitivity of CH3NH3PbI3 detectors of (2.6 ± 0.4) × 106 µC Gy−1air cm−2 for 60 kVp X-ray and the lowest detectable dose rate reaches (5.0 ± 0.7) nGy s−1, which enables reduced radiation dose to patients in medical X-ray diagnostics.
Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during antifungal azole treatment
Authors: Henneberg Sophie , Hasenberg Anja , Maurer Andreas , Neumann Franziska , Bornemann Lea , Gonzalez-Menendez Irene , Kraus Andreas , Hasenberg Mike , Thornton Christopher R. , Pichler Bernd J. , Gunzer Matthias , Beziere Nicolas 
Published: March 2021

AbstractInvasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immunocompromised humans, caused by the opportunistic fungal pathogen Aspergillus fumigatus. Inadequacies in current diagnostic procedures mean that early diagnosis of the disease, critical to patient survival, remains a major clinical challenge, and is leading to the empiric use of antifungal drugs and emergence of azole resistance. A non-invasive procedure that allows both unambiguous detection of IPA and its response to azole treatment is therefore needed. Here, we show that a humanised Aspergillus-specific monoclonal antibody, dual labelled with a radionuclide and fluorophore, can be used in immunoPET/MRI in vivo in a neutropenic mouse model and 3D light sheet fluorescence microscopy ex vivo in the infected mouse lungs to quantify early A. fumigatus lung infections and to monitor the efficacy of azole therapy. Our antibody-guided approach reveals that early drug intervention is critical to prevent complete invasion of the lungs by the fungus, and demonstrates the power of molecular imaging as a non-invasive procedure for tracking IPA in vivo.
Orbital structure of the effective pairing interaction in the high-temperature superconducting cuprates
Authors: Mai Peizhi , Balduzzi Giovanni , Johnston Steven , Maier Thomas A. 
Published: March 2021

AbstractThe nature of the effective interaction responsible for pairing in the high-temperature superconducting cuprates remains unsettled. This question has been studied extensively using the simplified single-band Hubbard model, which does not explicitly consider the orbital degrees of freedom of the relevant CuO2 planes. Here, we use a dynamical cluster quantum Monte Carlo approximation to study the orbital structure of the pairing interaction in the three-band Hubbard model, which treats the orbital degrees of freedom explicitly. We find that the interaction predominately acts between neighboring copper orbitals, but with significant additional weight appearing on the surrounding bonding molecular oxygen orbitals. By explicitly comparing these results to those from the simpler single-band Hubbard model, our study provides strong support for the single-band framework for describing superconductivity in the cuprates.
Bacteria-host transcriptional response during endothelial invasion by Staphylococcus aureus
Authors: Grønnemose Rasmus Birkholm , Garde Christian , Wassmann Claes Søndergaard , Klitgaard Janne Kudsk , Nielsen Ronni , Mandrup Susanne , Mattsson Andreas Holm , Andersen Thomas Emil 
Published: March 2021

AbstractStaphylococcus aureus is the cause of serious vascular infections such as sepsis and endocarditis. These infections are notoriously difficult to treat, and it is believed that the ability of S. aureus to invade endothelial cells and persist intracellularly is a key mechanism for persistence despite ongoing antibiotic treatment. Here, we used dual RNA sequencing to study the simultaneous transcriptional response of S. aureus and human endothelial cells during in vitro infections. We revealed discrete and shared differentially expressed genes for both host and pathogen at the different stages of infection. While the endothelial cells upregulated genes involved in interferon signalling and antigen presentation during late infection, S. aureus downregulated toxin expression while upregulating genes related to iron scavenging. In conclusion, the presented data provide an important resource to facilitate functional investigations into host–pathogen interaction during S. aureus invasive infection and a basis for identifying novel drug target sites.
Course induced dexterity development and cerebellar grey matter growth of dentistry students: a randomised trial
Authors: Siman Benedek , Janszky Jozsef , Perlaki Gabor , Fazekas Adrien , Sandor Balazs , Katona Krisztian , Marada Gyula , Szanto Ildiko 
Published: March 2021

AbstractThis study primarily focuses on the assessment of dentistry students’ improvement of manual skills resulting from their participation in courses. We aimed to prove that systematic manual skills development significantly improves dexterity. We hypothesized that the dexterity training regimen improves manual dexterity demonstrated by the HAM-Man (Hamburg Assessment Test for Medicine-Manual Dexterity) test scores and CGM (cerebellar grey matter) growth. Thirty volunteers were randomly divided into two equal groups (study and control). Firstly, volunteers were examined by the HAM-Man test and baseline MRI scans. Afterwards, a manual skills development course was launched for the “study group”. Secondly, all the manual skills of the students were evaluated longitudinally, by the HAM-Man test. Simultaneously, the follow-up MRI scans were taken to observe morphologic changes in the cerebellum. The Wilcoxon signed-rank test and Student Paired t-test were used for statistical analyses. Value p < 0.05 was considered significant. After the training, significant growth of CGM as well as improvement on manual skill assessment tests, were found in the study group. Training courses are suitable for preparing students with low levels of dexterity for performing demanding tasks. The improvement is demonstrable by a wire bending test and by bilateral CGM enlargement as well.
Contrast enhanced X-ray computed tomography imaging of amyloid plaques in Alzheimer disease rat model on lab based micro CT system
Authors: Kavkova Michaela , Zikmund Tomas , Kala Annu , Salplachta Jakub , Proskauer Pena Stephanie L. , Kaiser Josef , Jezek Karel 
Published: March 2021

AbstractAmyloid plaques are small (~ 50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer’s disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer’s disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.
Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
Authors: Nunoue Tomokazu , Yamaguchi Satoshi , Teshigawara Sanae , Katayama Akihiro , Nakatsuka Atsuko , Eguchi Jun , Niki Toshiro , Wada Jun 
Published: March 2021

AbstractThe adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.
Electrostatic wave breaking limit in a cold electronegative plasma with non-Maxwellian electrons
Authors: Elkamash I. S. , Kourakis I. 
Published: March 2021

AbstractA one-dimensional multifluid hydrodynamic model has been adopted as basis for an investigation of the role of suprathermal electrons on the wave breaking amplitude limit for electrostatic excitations propagating in an electronegative plasma. A three-component plasma is considered, consisting of two inertial cold ion populations of opposite signs, evolving against a uniform background of (non-Maxwellian) electrons. A kappa-type (non-Maxwellian) distribution function is adopted for the electrons. By employing a traveling wave approximation, the first integral for the fluid-dynamical system has been derived, in the form of a pseudo-energy balance equation, and analyzed. The effect of intrinsic plasma parameters (namely the ion density ratio, the ion mass ratio, and the superthermal index of the nonthermal electrons) on the wave breaking amplitude limit is explored, by analyzing the phase space topology of the associated pseudopotential function. Our results are relevant to particle acceleration in Space environments and to recent experiments based on plasma-based accelerator schemes, where the simultaneous presence of negative ions and nonthermal electrons may be observed.
On the morphological relations of the Achilles tendon and plantar fascia via the calcaneus: a cadaveric study
Authors: Singh A. , Zwirner J. , Templer F. , Kieser D. , Klima S. , Hammer N. 
Published: March 2021

AbstractCurrent treatments of plantar fasciitis are based on the premise that the Achilles tendon (AT) and plantar fascia (PF) are mechanically directly linked, which is an area of debate. The aim of this study was to assess the morphological relationship between the AT and PF. Nineteen cadaveric feet were x-ray imaged, serially sectioned and plastinated for digital image analyses. Measurements of the AT and PF thicknesses and cross-sectional areas (CSA) were performed at their calcaneal insertion. The fiber continuity was histologically assessed in representative subsamples. Strong correlations exist between the CSA of the AT and PF at calcaneal insertion and the CSA of PF’s insertional length (r = 0.80), and between the CSAs of AT’s and PF’s insertional lengths. Further correlations were observed between AT and PF thicknesses (r = 0.62). This close morphological relationship could, however, not be confirmed through x-ray nor complete fiber continuity in histology. This study provides evidence for a morphometric relationship between the AT and PF, which suggests the presence of a functional relationship between these two structures following the biological key idea that the structure determines the function. The observed morphological correlations substantiate the existing mechanical link between the AT and PF via the posterior calcaneus and might explain why calf stretches are a successful treatment option for plantar heel pain.
PIM kinases mediate resistance to cisplatin chemotherapy in hepatoblastoma
Authors: Marayati Raoud , Stafman Laura L. , Williams Adele P. , Bownes Laura V. , Quinn Colin H. , Aye Jamie M. , Stewart Jerry E. , Yoon Karina J. , Anderson Joshua C. , Willey Christopher D. , Beierle Elizabeth A. 
Published: March 2021

AbstractDespite increasing incidence, treatment for hepatoblastoma has not changed significantly over the past 20 years. Chemotherapeutic strategies continue to rely on cisplatin, as it remains the most active single agent against hepatoblastoma. However, chemoresistance remains a significant challenge with 54–80% of patients developing resistance to chemotherapy after 4–5 cycles of treatment. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to play a role in chemoresistance and disease recurrence. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia virus (PIM) kinases, specifically PIM3, play a role in hepatoblastoma cell proliferation and tumor growth and maintain the SCLCC phenotype. Here, we describe the development of a cisplatin-resistant hepatoblastoma xenograft model of the human HuH6 cell line and a patient-derived xenograft, COA67. We provide evidence that these cisplatin-resistant cells are enriched for SCLCCs and express PIM3 at higher levels than cisplatin-naïve cells. We demonstrate that PIM inhibition with AZD1208 sensitizes cisplatin-resistant hepatoblastoma cells to cisplatin, enhances cisplatin-mediated apoptosis, and decreases the SCLCC phenotype seen with cisplatin resistance. Together, these findings indicate that PIM inhibition may be a promising adjunct in the treatment of hepatoblastoma to effectively target SCLCCs and potentially decrease chemoresistance and subsequent disease relapse.
Stage-dependent effects of intermittent hypoxia influence the outcome of hippocampal adult neurogenesis
Authors: Khuu Maggie A. , Nallamothu Thara , Castro-Rivera Carolina I. , Arias-Cavieres Alejandra , Szujewski Caroline C. , Garcia III Alfredo J. 
Published: March 2021

AbstractOver one billion adults worldwide are estimated to suffer from sleep apnea, a condition with wide-reaching effects on brain health. Sleep apnea causes cognitive decline and is a risk factor for neurodegenerative conditions such as Alzheimer’s disease. Rodents exposed to intermittent hypoxia (IH), a hallmark of sleep apnea, exhibit spatial memory deficits associated with impaired hippocampal neurophysiology and dysregulated adult neurogenesis. We demonstrate that IH creates a pro-oxidant condition that reduces the Tbr2+ neural progenitor pool early in the process, while also suppressing terminal differentiation of adult born neurons during late adult neurogenesis. We further show that IH-dependent cell-autonomous hypoxia inducible factor 1-alpha (HIF1a) signaling is activated in early neuroprogenitors and enhances the generation of adult born neurons upon termination of IH. Our findings indicate that oscillations in oxygen homeostasis, such as those found in sleep apnea, have complex stage-dependent influence over hippocampal adult neurogenesis.
Polystyrene microplastic contamination versus microplankton abundances in two lagoons of the Florida Keys
Authors: Badylak Susan , Phlips Edward , Batich Christopher , Jackson Miranda , Wachnicka Anna 
Published: March 2021

AbstractA microscopic study of microplankton in two coastal lagoons in the Florida Keys coincidently, and unexpectedly, revealed the widespread presence of high concentrations of polystyrene microplastic particles. The polystyrene particles were first observed in the second year of a 2-year study of phytoplankton communities, with peak densities in the spring/summer of 2019 at all ten sampling sites in the two lagoons. Polystyrene particle densities reached levels up to 76,000 L−1. The particles ranged in size from 33 to 190 µm, similar to the size range of microplanktonic algae (20–200 µm). Over the period of peak polystyrene densities, average particle densities were similar to average densities of microplanktonic algae cells. The latter observation highlights the potential significance of the microplastic particles for the ecology of the pristine waters of the Florida Keys, if they persist.