bluuebunny/crossref_metadata_2025_split huggingface dataset:
HO-1 nuclear accumulation and interaction with NPM1 protect against stress-induced endothelial senescence independent of its enzymatic activity
Authors: Luo Wenwei , Li Jingyan , Li Ziqing , Lin Tong , Zhang Lili , Yang Wanqi , Mai Yanqi , Liu Ruiming , Chen Meiting , Dai Chunmei , Yang Hanwei , Lu Jing , Li Hong , Guan Guimei , Huang Min , Liu Peiqing , Li Zhuoming 
Published: July 2021

AbstractHeme oxygenase-1 (HO-1) has attracted accumulating attention for its antioxidant enzymatic activity. However, the exact regulatory role of its non-enzymatic activity in the cardiovascular system remains unaddressed. Here, we show that HO-1 was accumulated in the nuclei of stress-induced senescent endothelial cells, and conferred protection against endothelial senescence independent of its enzymatic activity. Overexpression of ΔHO-1, a truncated HO-1 without transmembrane segment (TMS), inhibited H2O2-induced endothelial senescence. Overexpression of ΔHO-1H25A, the catalytically inactive form of ΔHO-1, also exhibited anti-senescent effect. In addition, infection of recombinant adenovirus encoding ΔHO-1 with three nuclear localization sequences (NLS), alleviated endothelial senescence induced by knockdown of endogenous HO-1 by CRISPR/Cas9. Moreover, repression of HO-1 nuclear translocation by silencing of signal peptide peptidase (SPP), which is responsible for enzymatic cleavage of the TMS of HO-1, exacerbated endothelial senescence. Mechanistically, nuclear HO-1 interacted with NPM1 N-terminal portion, prevented NPM1 translocation from nucleolus to nucleoplasm, thus disrupted NPM1/p53/MDM2 interactions and inhibited p53 activation by NPM1, finally resisted endothelial senescence. This study provides a novel understanding of HO-1 as a promising therapeutic strategy for vascular senescence-related cardiovascular diseases.
Generation of non-stabilized alkyl radicals from thianthrenium salts for C–B and C–C bond formation
Authors: Chen Cheng , Wang Zheng-Jun , Lu Hongjian , Zhao Yue , Shi Zhuangzhi 
Published: July 2021

AbstractSulfonium salts bearing a positively charged sulfur atom with three organic substituents have intrigued chemists for more than a century for their unusual structures and high chemical reactivity. These compounds are known to undergo facile single-electron reduction to emerge as a valuable and alternative source of aryl radicals for organic synthesis. However, the generation of non-stabilized alkyl radicals from sulfonium salts has been a challenge for several decades. Here we report the treatment of S-(alkyl) thianthrenium salts to generate non-stabilized alkyl radicals as key intermediates granting the controlled and selective outcome of the ensuing reactions under mild photoredox conditions. The value of these reagents has been demonstrated through the efficient construction of alkylboronates and other transformations, including heteroarylation, alkylation, alkenylation, and alkynylation. The developed method is practical, and provides the opportunity to convert C–OH bond to C–B and C–C bonds.
BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons
Authors: Vierock Johannes , Rodriguez-Rozada Silvia , Dieter Alexander , Pieper Florian , Sims Ruth , Tenedini Federico , Bergs Amelie C. F. , Bendifallah Imane , Zhou Fangmin , Zeitzschel Nadja , Ahlbeck Joachim , Augustin Sandra , Sauter Kathrin , Papagiakoumou Eirini , Gottschalk Alexander , Soba Peter , Emiliani Valentina , Engel Andreas K. , Hegemann Peter , Wiegert J. Simon 
Published: July 2021

AbstractOptogenetic manipulation of neuronal activity through excitatory and inhibitory opsins has become an indispensable experimental strategy in neuroscience research. For many applications bidirectional control of neuronal activity allowing both excitation and inhibition of the same neurons in a single experiment is desired. This requires low spectral overlap between the excitatory and inhibitory opsin, matched photocurrent amplitudes and a fixed expression ratio. Moreover, independent activation of two distinct neuronal populations with different optogenetic actuators is still challenging due to blue-light sensitivity of all opsins. Here we report BiPOLES, an optogenetic tool for potent neuronal excitation and inhibition with light of two different wavelengths. BiPOLES enables sensitive, reliable dual-color neuronal spiking and silencing with single- or two-photon excitation, optical tuning of the membrane voltage, and independent optogenetic control of two neuronal populations using a second, blue-light sensitive opsin. The utility of BiPOLES is demonstrated in worms, flies, mice and ferrets.
Neural attentional-filter mechanisms of listening success in middle-aged and older individuals
Authors: Tune Sarah , Alavash Mohsen , Fiedler Lorenz , Obleser Jonas 
Published: July 2021

AbstractSuccessful listening crucially depends on intact attentional filters that separate relevant from irrelevant information. Research into their neurobiological implementation has focused on two potential auditory filter strategies: the lateralization of alpha power and selective neural speech tracking. However, the functional interplay of the two neural filter strategies and their potency to index listening success in an ageing population remains unclear. Using electroencephalography and a dual-talker task in a representative sample of listeners (N = 155; age=39–80 years), we here demonstrate an often-missed link from single-trial behavioural outcomes back to trial-by-trial changes in neural attentional filtering. First, we observe preserved attentional–cue-driven modulation of both neural filters across chronological age and hearing levels. Second, neural filter states vary independently of one another, demonstrating complementary neurobiological solutions of spatial selective attention. Stronger neural speech tracking but not alpha lateralization boosts trial-to-trial behavioural performance. Our results highlight the translational potential of neural speech tracking as an individualized neural marker of adaptive listening behaviour.
Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance
Authors: Mahrt Niels , Tietze Alexandra , Künzel Sven , Franzenburg Sören , Barbosa Camilo , Jansen Gunther , Schulenburg Hinrich 
Published: July 2021

AbstractDuring antibiotic treatment, the evolution of bacterial pathogens is fundamentally affected by bottlenecks and varying selection levels imposed by the drugs. Bottlenecks—that is, reductions in bacterial population size—lead to an increased influence of random effects (genetic drift) during bacterial evolution, and varying antibiotic concentrations during treatment may favour distinct resistance variants. Both aspects influence the process of bacterial evolution during antibiotic therapy and thereby treatment outcome. Surprisingly, the joint influence of these interconnected factors on the evolution of antibiotic resistance remains largely unexplored. Here we combine evolution experiments with genomic and genetic analyses to demonstrate that bottleneck size and antibiotic-induced selection reproducibly impact the evolutionary path to resistance in pathogenic Pseudomonas aeruginosa, one of the most problematic opportunistic human pathogens. Resistance is favoured—expectedly—under high antibiotic selection and weak bottlenecks, but—unexpectedly—also under low antibiotic selection and severe bottlenecks. The latter is likely to result from a reduced probability of losing favourable variants through drift under weak selection. Moreover, the absence of high resistance under low selection and weak bottlenecks is caused by the spread of low-resistance variants with high competitive fitness under these conditions. We conclude that bottlenecks, in combination with drug-induced selection, are currently neglected key determinants of pathogen evolution and outcome of antibiotic treatment.
Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination
Authors: Schmidt Tina , Klemis Verena , Schub David , Mihm Janine , Hielscher Franziska , Marx Stefanie , Abu-Omar Amina , Ziegler Laura , Guckelmus Candida , Urschel Rebecca , Schneitler Sophie , Becker Sören L. , Gärtner Barbara C. , Sester Urban , Sester Martina 
Published: July 2021

AbstractHeterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
Effect of substitution on the superconducting phase of transition metal dichalcogenide Nb(Se$$_{x}$$S$$_{1-x}$$)$$_{2}$$ van der Waals layered structure
Authors: Tsuppayakorn-aek Prutthipong , Pluengphon Prayoonsak , Phansuke Piya , Inceesungvorn Burapat , Busayaporn Wutthikrai , Kaewtubtim Pungtip , Bovornratanaraks Thiti 
Published: July 2021

AbstractBy means of first-principles cluster expansion, anisotropic superconductivity in the transition metal dichalcogenide Nb(Se$$_{x}$$

x

S$$_{1-x}$$

1
-
x

)$$_{2}$$

2

forming a van der Waals (vdW) layered structure is observed theoretically. We show that the Nb(Se$$_{0.5}$$

0.5

S$$_{0.5}$$

0.5

)$$_{2}$$

2

vdW-layered structure exhibits minimum ground-state energy. The Pnnm structure is more thermodynamically stable when compared to the 2H–NbSe$$_{2}$$

2

and 2H–NbS$$_{2}$$

2

structures. The characteristics of its phonon dispersions confirm its dynamical stability. According to electronic properties, i.e., electronic band structure, density of states, and Fermi surface indicate metallicity of Nb(Se$$_{0.5}$$

0.5

S$$_{0.5}$$

0.5

)$$_{2}$$

2

. The corresponding superconductivity is then investigated through the Eliashberg spectral function, which gives rise to a superconducting transition temperature of 14.5 K. This proposes a remarkable improvement of superconductivity in this transition metal dichalcogenide.
Extracellular NLRP3 inflammasome particles are internalized by human coronary artery smooth muscle cells and induce pro-atherogenic effects
Authors: Gaul Susanne , Schaeffer Karen Marie , Opitz Lena , Maeder Christina , Kogel Alexander , Uhlmann Luisa , Kalwa Hermann , Wagner Ulf , Haas Jan , Behzadi Amirhossein , Pelegrin Pablo , Boeckel Jes-Niels , Laufs Ulrich 
Published: July 2021

AbstractInflammation driven by intracellular activation of the NLRP3 inflammasome is involved in the pathogenesis of a variety of diseases including vascular pathologies. Inflammasome specks are released into the extracellular compartment from disrupting pyroptotic cells. The potential uptake and function of extracellular NLRP3 inflammasomes in human coronary artery smooth muscle cells (HCASMC) are unknown. Fluorescently labeled NLRP3 inflammasome particles were isolated from a mutant NLRP3-YFP cell line and used to treat primary HCASMC for 4 and 24 h. Fluorescent and expressional analyses showed that extracellular NLRP3-YFP particles are internalized into HCASMC, where they remain active and stimulate intracellular caspase-1 (1.9-fold) and IL-1β (1.5-fold) activation without inducing pyroptotic cell death. Transcriptomic analysis revealed increased expression level of pro-inflammatory adhesion molecules (ICAM1, CADM1), NLRP3 and genes involved in cytoskleleton organization. The NLRP3-YFP particle-induced gene expression was not dependent on NLRP3 and caspase-1 activation. Instead, the effects were partly abrogated by blocking NFκB activation. Genes, upregulated by extracellular NLRP3 were validated in human carotid artery atheromatous plaques. Extracellular NLRP3-YFP inflammasome particles promoted the secretion of pro-atherogenic and inflammatory cytokines such as CCL2/MCP1, CXCL1 and IL-17E, and increased HCASMC migration (1.8-fold) and extracellular matrix production, such as fibronectin (5.8-fold) which was dependent on NFκB and NLRP3 activation. Extracellular NLRP3 inflammasome particles are internalized into human coronary artery smooth muscle cells where they induce pro-inflammatory and pro-atherogenic effects representing a novel mechanism of cell-cell communication and perpetuation of inflammation in atherosclerosis. Therefore, extracellular NLRP3 inflammasomes may be useful to improve the diagnosis of inflammatory diseases and the development of novel anti-inflammatory therapeutic strategies.
Relationship between abnormalities detected by magnetic resonance imaging and knee symptoms in early knee osteoarthritis
Authors: Ota Seiya , Sasaki Eiji , Sasaki Shizuka , Chiba Daisuke , Kimura Yuka , Yamamoto Yuji , Kumagai Mika , Ando Masataka , Tsuda Eiichi , Ishibashi Yasuyuki 
Published: July 2021

AbstractWe investigated the prevalence of magnetic resonance imaging (MRI) findings and their relationship with knee symptoms in women without radiographic evidence of knee osteoarthritis (KOA). This cross-sectional cohort study included 359 Japanese women without radiographic evidence of KOA (Kellgren‒Lawrence grade < 2). All participants underwent T2-weighted fat-suppressed MRI of their knees. Structural abnormalities (cartilage damage, bone marrow lesions [BMLs], subchondral cysts, bone attrition, osteophytes, meniscal lesions, and synovitis) were scored according to the whole-organ MRI score method. Knee symptoms were evaluated using the Knee Injury and Osteoarthritis Outcome Score. Participants were divided into early and non-KOA groups based on early KOA classification criteria. Logistic regression analysis was performed to evaluate the relationship between MRI abnormalities and knee symptoms. Cartilage damage was the most common abnormality (43.5%). The prevalences of cartilage damage, BMLs, subchondral cysts, bone attrition, meniscal lesions, and synovitis were higher in patients with early KOA than in those without. Synovitis (odds ratio [OR] 2.254, P = 0.002) and meniscal lesions (OR 1.479, P = 0.031) were positively associated with the presence of early KOA. Synovitis was most strongly associated with knee pain and might be a therapeutic target in patients with early KOA.
Unveiling the Nottingham Inversion Instability during the thermo-field emission from refractory metal micro-protrusions
Authors: Mofakhami Darius , Seznec Benjamin , Minea Tiberiu , Landfried Romaric , Testé Philippe , Dessante Philippe 
Published: July 2021

AbstractThe electron emission by micro-protrusions has been studied for over a century, but the complete explanation of the unstable behaviors and their origin remains an open issue. These systems often evolve towards vacuum breakdown, which makes experimental studies of instabilities very difficult. Modeling studies are therefore necessary. In our model, refractory metals have shown the most striking results for discontinuities or jumps recorded on the electron emitted current under high applied voltages. Herein, we provide evidence on the mechanisms responsible for the initiation of a thermal instability during the field emission from refractory metal micro-protrusions. A jump in the emission current at steady state is found beyond a threshold electric field, and it is correlated to a similar jump in temperature. These jumps are related to a transient runaway of the resistive heating that occurs after the Nottingham flux inversion. That causes the hottest region to move beneath the apex, and generates an emerging heat reflux towards the emitting surface. Two additional conditions are required to initiate the runaway. The emitter geometry must ensure a large emission area and the thermal conductivity must be high enough at high temperatures so that the heat reflux can significantly compete with the heat diffusion towards the thermostat. The whole phenomenon, that we propose to call the Nottingham Inversion Instability, can explain unexpected thermal failures and breakdowns observed with field emitters.
Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswax
Authors: McAfee Alison , Milone Joseph P , Metz Bradley , McDermott Erin , Foster Leonard J , Tarpy David R 
Published: July 2021

AbstractHoney bee queen health is crucial for colony health and productivity, and pesticides have been previously associated with queen loss and premature supersedure. Prior research has investigated the effects of indirect pesticide exposure on queens via workers, as well as direct effects on queens during development. However, as adults, queens are in constant contact with wax as they walk on comb and lay eggs; therefore, direct pesticide contact with adult queens is a relevant but seldom investigated exposure route. Here, we conducted laboratory and field experiments to investigate the impacts of topical pesticide exposure on adult queens. We tested six pesticides commonly found in wax: coumaphos, tau-fluvalinate, atrazine, 2,4-DMPF, chlorpyriphos, chlorothalonil, and a cocktail of all six, each administered at 1, 4, 8, 16, and 32 times the concentrations typically found in wax. We found no effect of any treatment on queen mass, sperm viability, or fat body protein expression. In a field trial testing queen topical exposure of a pesticide cocktail, we found no impact on egg-laying pattern, queen mass, emergence mass of daughter workers, and no proteins in the spermathecal fluid were differentially expressed. These experiments consistently show that pesticides commonly found in wax have no direct impact on queen performance, reproduction, or quality metrics at the doses tested. We suggest that previously reported associations between high levels of pesticide residues in wax and queen failure are most likely driven by indirect effects of worker exposure (either through wax or other hive products) on queen care or queen perception.
FDG-PET predicts bone invasion and prognosis in patients with oral squamous cell carcinoma
Authors: Lin Nan-Chin , Su I-Hsien , Hsu Jui-Ting , Tsai Kuo-Yang , Chen Michael Y. C. 
Published: July 2021

Abstract18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is widely used for tumor staging. This study sought to determine the relationship of preoperative primary tumor SUVmax (tSUVmax) with the clinicopathological features of patients with OSCC and to compare the prognostic ability of tSUVmax with that of other recurrence factors. Data of 340 patients with OSCC who were diagnosed, treated, and followed up at the Changhua Christian Hospital were retrospectively analyzed. Only patients with OSCC arising from gingiva, palate, floor of the mouth, and retromolar trigone and those who had received preoperative FDG-PET within 2 weeks before surgery were included. tSUVmax value > 9.2 was the strong predictor of bone invasion (area under the receiver operating characteristic curve, 0.844). tSUVmax value > 7.2 showed a strong association with advanced pathological T stage and recurrence factors and was associated with poor survival; tSUVmax > 7.2 showed stronger predictive power for poor disease-free survival (DFS) than pT stage and the other recurrence factors related to primary tumor. FDG-PET can be a useful supplement to contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging for diagnosing bone invasion by OSCC. The tSUVmax value was an independent predictor of DFS in this study.
Clinical outcomes of hospitalized COVID-19 patients with renal injury: a multi-hospital observational study from Wuhan
Authors: Chen Kehong , Lei Yu , He Yani , Xiao Fei , Yu Yan , Lai Xiaodong , Liu Yang , Wang Jiang , Dai Huanzi 
Published: July 2021

AbstractRenal injury is common in patients with coronavirus disease 2019 (COVID‐19). We aimed to determine the relationship of estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI) with the characteristics, progression, and prognosis of COVID-19 in-patients. We retrospectively reviewed 1851 COVID-19 patients admitted to 3 hospitals in Wuhan, China. Clinical, laboratory, radiological, treatment, complication, and outcome data were analyzed. Patients were stratified according to levels of eGFR (≥ 90 vs. 60–89 vs. < 60 mL/min/1.73 m2). The risk of reaching the composite endpoint—intensive care unit admission, invasive ventilation, or death—was compared. On admission, 25.5% patients had renal impairment (eGFR < 90 mL/min/1.73 m2), but only 2.6% patients had chronic kidney disease (CKD). The overall in-hospital AKI incidence was 6.7%. Severe illness and comorbidities (hypertension, diabetes, CKD, and cardiovascular/cerebrovascular diseases) were more common among patients with low eGFR (< 90 mL/min/1.73 m2). Despite the more frequent use of intensive oxygen therapy, continuous blood purification, and glucocorticoid treatment, the prognosis of these patients was unsatisfactory, with the incidence of the composite endpoint (15.4% vs. 19.6% vs. 54.5%; P = 0.000) and complications (AKI, respiratory failure, cardiac injury, coagulation disorders, sepsis, etc.) increasing with decreasing eGFR. Kaplan–Meier survival analysis revealed that patients with eGFR < 90 mL/min/1.73 m2 or AKI had significantly escalated risks of reaching the composite endpoint. Multivariate regression analysis showed that renal insufficiency (eGFR < 60 mL/min/1.73 m2) on admission and in-hospital AKI independently predicted poor prognosis among COVID-19 in-patients. And renal impairment on admission was a greater predictor of poor prognosis in non-elderly patients than that in elderly patients. Early and continuous renal-function monitoring and early AKI diagnosis are necessary to predict and prevent the progression of COVID-19.
Madrepora oculata forms large frameworks in hypoxic waters off Angola (SE Atlantic)
Authors: Orejas Covadonga , Wienberg Claudia , Titschack Jürgen , Tamborrino Leonardo , Freiwald André , Hebbeln Dierk 
Published: July 2021

AbstractThis study aims to map the occurrence and distribution of Madrepora oculata and to quantify density and colony sizes across recently discovered coral mounds off Angola. Despite the fact that the Angolan populations of M. oculata thrive under extreme hypoxic conditions within the local oxygen minimum zone, they reveal colonies with remarkable heights of up to 1250 mm—which are the tallest colonies ever recorded for this species—and average densities of 0.53 ± 0.37 (SD) colonies m−2. This is particularly noteworthy as these values are comparable to those documented in areas without any oxygen constraints. The results of this study show that the distribution pattern documented for M. oculata appear to be linked to the specific regional environmental conditions off Angola, which have been recorded in the direct vicinity of the thriving coral community. Additionally, an estimated average colony age of 95 ± 76 (SD) years (total estimated age range: 16–369 years) indicates relatively old M. oculata populations colonizing the Angolan coral mounds. Finally, the characteristics of the Angolan populations are benchmarked and discussed in the light of the existing knowledge on M. oculata gained from the North Atlantic and Mediterranean Sea.