bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction Between Aseismic Slip and Fluid Invasion in Earthquake Swarms Revealed by Dense Geodetic and Seismic Observations
Authors: Yukutake Y. , Yoshida K. , Honda R.
Published: March 2022

Recent seismic and geodetic observations suggest the involvement of pressurized fluid and aseismic slip during earthquake swarms. However, the interaction between these two factors is not fully understood. In this study, we show geodetic signals induced by aseismic opening and shear dislocation on a fault, accompanied by hypocenter migration during an earthquake swarm in the Hakone volcano, central Japan. The hypocenters were concentrated on a vertical plane, and the focal mechanisms were strike‐slip faults whose nodal planes were consistent with the hypocenter distribution. Precursory seismicity occurred 1 week before the main swarm. We observed a complex pattern of hypocenter migration during the seismic sequence; namely, the lower limit of the seismicity appears to expand downward during the precursory seismicity, followed by an upward hypocenter diffusion. We also observed tilt changes that could be explained by opening and shear dislocation on the fault plane inferred from the planar hypocenter distribution. Furthermore, we identified several groups of repeating earthquakes. The average aseismic slip history inferred from the repeating earthquakes indicated a minor aseismic slip of 0.4 mm during the precursory seismic activity, which accelerated by up to 3 mm during the main swarm. The total cumulative slip was consistent with the geodetic model results. These observations may suggest that fluid intrusion caused the aseismic slip, and the complex migration of the hypocenters reflects the aseismic slip propagation. We hypothesize that aseismic deformation acts as the driving force for the earthquake swarms together with the intrusion of pressurized fluid.
Improved Imaging of the Large‐Scale Structure of a Groundwater System With Airborne Electromagnetic Data
Authors: Kang Seogi , Knight Rosemary , Goebel Meredith
Published: March 2022

Working with airborne electromagnetic (AEM) data acquired in the Kaweah Subbasin in the Central Valley of California, USA, we developed a new approach for imaging the bedrock surface and the confining Corcoran Clay layer. Our approach, which incorporated the prior knowledge of the targets for the improved imaging, included multiple L2‐norm and Lp‐norm inversions as well as an interpolation process. The major improvement in imaging the targets was made in the Lp‐norm inversion step by incorporating prior knowledge. For the Corcoran Clay, pairs of resistivity and driller's logs at two wells guided the selection of the primary resistivity model and were used to increase the accuracy of the estimated Corcoran Clay thickness. The bedrock surface was poorly constrained by well data in the existing groundwater model, appearing as a flat surface. Acquired AEM data covered most of the area, so we had higher confidence in the obtained map of the bedrock surface at depths ranging from 15 to 160 m. There was relatively good agreement between the location of the Corcoran Clay in the AEM data (depth ranging from 50 to 130 m and thickness ranging from 3 to 25 m) and the existing groundwater model, with both depth and thickness showing ∼15% relative difference. The AEM data provided information about the continuity of the Corcoran Clay that is challenging to capture in the well data. The locations of the bedrock and Corcoran Clay were used in a structurally constrained inversion to improve the imaging of the smaller‐scale resistivity structure.
Sexual dimorphism in cardiometabolic and cardiac mitochondrial function in obese rats following sex hormone deprivation
Authors: Shinlapawittayatorn Krekwit , Pongkan Wanpitak , Sivasinprasasn Sivaporn , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: March 2022

Objective

Our study aims to test the hypothesis that poorer function of cardiac mitochondria in males, under sex hormone-deprived and obese-insulin-resistant conditions, is responsible for a worse cardiometabolic function than females.

Methods

One hundred and forty-four rats were subjected to receive either 12 weeks of normal diet (ND) or a high-fat diet (HFD) consumption following the induction of sex hormone deprivation. Temporal evaluations of metabolic parameters, cardiac autonomic modulation, left ventricular (LV) contractile, and mitochondrial functions were measured after starting each feeding protocol for 4, 8, and 12 weeks.

Results

After HFD feeding for 8 weeks, increased plasma insulin and HOMA index were initially observed in male HFD-fed sham-operated rats (M-HFS), male HFD-fed orchiectomized rats (M-HFO), female ND-fed ovariectomized rats (F-OVX), female HFD-fed sham-operated rats (F-HFS), and female HFD-fed ovariectomized rats (F-HFO) groups. In addition, as early as week 4, male ND-fed orchiectomized rats (M-ORX) and M-HFO exhibited impaired cardiac autonomic balance, LV contractile and mitochondrial functions, whereas M-HFS and F-HFO developed these impairments at week 8 and F-OVX and F-HFS exhibited them at week 12.

Conclusion

We concluded that sex hormone-deprived females are prone to develop metabolic impairments, whereas males are more likely to have cardiac autonomic impairment, LV contractile and mitochondrial dysfunction even in the absence of obese-insulin-resistant condition. However, under estrogen-deprived condition, these impairments were further accelerated and aggravated by obese-insulin resistance.
Circulating tumour DNA monitoring and early treatment for relapse: views from patients with early-stage melanoma
Authors: Woof Victoria G. , Lee Rebecca J. , Lorigan Paul , French David P.
Published: March 2022

Background

Circulating tumour DNA (ctDNA) monitoring is a new technology that detects cancer DNA fragments in blood circulation. Regular monitoring with ctDNA has the potential to detect and treat cancer relapse earlier, but there is little evidence on patient acceptability. This study examines the views of patients with early-stage melanoma on the acceptability of the test and early treatment.

Methods

A qualitative cross-sectional design using one-to-one semi-structured telephone interviews was employed. Twenty-five patients diagnosed with early-stage melanoma (Stage IA–IIC) were asked for their views on ctDNA monitoring and early treatment for relapse. Interviews were analysed using reflexive thematic analysis.

Results

Two themes were generated:ctDNA monitoring would add service valuewhere participants described regular ctDNA monitoring in follow-up care as more reassuring, more “scientific” than skin checks and preferable to scans.Test results provide opportunity and knowledgefocuses on how participants wanted to know when to expect results to manage anxiety, with a positive result seen as an opportunity to receive treatment early.

Conclusions

Participants were positive about ctDNA monitoring and early treatment and would welcome extra surveillance, as well as trust ctDNA tests. This indicates the feasibility of the wider implementation of ctDNA tests, which have applicability for many tumour types and disease stages.
A novel HIF-2α targeted inhibitor suppresses hypoxia-induced breast cancer stemness via SOD2-mtROS-PDI/GPR78-UPRER axis
Authors: Yan Yuanyuan , He Miao , Zhao Lin , Wu Huizhe , Zhao Yanyun , Han Li , Wei Binbin , Ye Dongman , Lv Xuemei , Wang Yan , Yao Weifan , Zhao Haishan , Chen Bo , Jin Zining , Wen Jian , Zhu Yan , Yu Tao , Jin Feng , Wei Minjie
Published: March 2022

Hypoxic tumor microenvironment (TME) plays critical roles in induction of cancer stem cell-like phenotype in breast cancer and contribute to chemoresistance. However, the mechanism underlying stemness reprogramming of breast cancer cells (BCs) by hypoxic TME remains largely unknown. In the present study, we illustrated that HIF-2α, but not HIF-1α, induces stemness in BCs under hypoxia through SOD2-mtROS-PDI/GRP78-UPRER pathway, linking mitochondrial metabolic state to endoplasmic reticulum (ER) response via mitochondrial reactive oxygen species (mtROS) level. HIF-2α activates endoplasmic reticulum unfolded protein response (UPRER) in drug-sensitive MCF7 and T47D cells to induce drug-resistant stem-like phenotype. Genetic depletion or pharmacological inhibition (YQ-0629) of HIF-2α abolished hypoxia-induced stem-like phenotype in vitro and in vivo. Mechanistically, HIF-2α activates transcription of superoxide dismutase 2 (SOD2) under hypoxia and thereby decreases mtROS level. With less mtROS transported to endoplasmic reticulum, the expression and activity of protein disulfide isomerase (PDI) is suppressed, allowing glucose-regulated protein 78 (GRP78) to dissociate from receptor proteins of UPRER and bind misfolded protein to activate UPRER, which eventually confer chemoresistance and stem-like properties to BCs. Moreover, the increase in mtROS and PDI levels caused by HIF-2α knockdown and the subsequent UPRER inhibition could be substantially rescued by mitoTEMPOL (a mtROS scavenger), 16F16 (a PDI inhibitor), or GRP78 overexpression. Overall, we reported the critical roles of HIF-2α-SOD2-mtROS-PDI/GRP78-UPRER axis in mediating hypoxia-induced stemness in BCs, highlighting the interaction between organelles and providing evidence for further development of targeted HIF-2α inhibitor as a promising therapeutic strategy for chemoresistant breast cancer.
Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases
Authors: Risso Vesna , Lafont Elodie , Le Gallo Matthieu
Published: March 2022

Cell death plays a pivotal role in the maintenance of tissue homeostasis. Key players in the controlled induction of cell death are the Death Receptors (DR). CD95 is a prototypic DR activated by its cognate ligand CD95L triggering programmed cell death. As a consequence, alterations in the CD95/CD95L pathway have been involved in several disease conditions ranging from autoimmune diseases to inflammation and cancer. CD95L-induced cell death has multiple roles in the immune response since it constitutes one of the mechanisms by which cytotoxic lymphocytes kill their targets, but it is also involved in the process of turning off the immune response. Furthermore, beyond the canonical pro-death signals, CD95L, which can be membrane-bound or soluble, also induces non-apoptotic signaling that contributes to its tumor-promoting and pro-inflammatory roles. The intent of this review is to describe the role of CD95/CD95L in the pathophysiology of cancers, autoimmune diseases and chronic inflammation and to discuss recently patented and emerging therapeutic strategies that exploit/block the CD95/CD95L system in these diseases.
Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity
Authors: Zhou Changping , Ma Lu , Xu Han , Huo Yingqing , Luo Jincai
Published: March 2022

As a first-line treatment, radiotherapy (RT) is known to modulate the immune microenvironment of glioma, but it is unknown whether the meningeal lymphatic vessel (MLV)-cervical lymph node (CLN) network regulates the process or influences RT efficacy. Here, we show that the MLV-CLN network contributes to RT efficacy in brain tumors and mediates the RT-modulated anti-tumor immunity that is enhanced by vascular endothelial growth factor C (VEGF-C). Meningeal lymphatic dysfunction impaired tumor-derived dendritic cell (DC) trafficking and CD8+ T cell activation after RT, whereas tumors overexpressing VEGF-C with meningeal lymphatic expansion were highly sensitive to RT. Mechanistically, VEGF-C-driven modulation of RT-triggered anti-tumor immunity was attributed to C-C Motif Chemokine Ligand 21 (CCL21)-dependent DC trafficking and CD8+ T cell activation. Notably, delivery of VEGF-C mRNA significantly enhanced RT efficacy and anti-tumor immunity in brain tumors. These findings suggest an essential role of the MLV-CLN network in RT-triggered anti-tumor immunity, and highlight the potential of VEGF-C mRNA for brain tumor therapy.
Ultrafast time-evolution of chiral Néel magnetic domain walls probed by circular dichroism in x-ray resonant magnetic scattering
Authors: Léveillé Cyril , Burgos-Parra Erick , Sassi Yanis , Ajejas Fernando , Chardonnet Valentin , Pedersoli Emanuele , Capotondi Flavio , De Ninno Giovanni , Maccherozzi Francesco , Dhesi Sarnjeet , Burn David M. , van der Laan Gerrit , Latcham Oliver S. , Shytov Andrey V. , Kruglyak Volodymyr V. , Jal Emmanuelle , Cros Vincent , Chauleau Jean-Yves , Reyren Nicolas , Viret Michel , Jaouen Nicolas
Published: March 2022

Non-collinear spin textures in ferromagnetic ultrathin films are attracting a renewed interest fueled by possible fine engineering of several magnetic interactions, notably the interfacial Dzyaloshinskii-Moriya interaction. This allows for the stabilization of complex chiral spin textures such as chiral magnetic domain walls (DWs), spin spirals, and magnetic skyrmions among others. We report here on the behavior of chiral DWs at ultrashort timescale after optical pumping in perpendicularly magnetized asymmetric multilayers. The magnetization dynamics is probed using time-resolved circular dichroism in x-ray resonant magnetic scattering (CD-XRMS). We observe a picosecond transient reduction of the CD-XRMS, which is attributed to the spin current-induced coherent and incoherent torques within the continuously varying spin texture of the DWs. We argue that a specific demagnetization of the inner structure of the DW induces a flow of spins from the interior of the neighboring magnetic domains. We identify this time-varying change of the DW texture shortly after the laser pulse as a distortion of the homochiral Néel shape toward a transient mixed Bloch-Néel-Bloch texture along a direction transverse to the DW.
Mismatching integration-enabled strains and defects engineering in LDH microstructure for high-rate and long-life charge storage
Authors: Guo Wei , Dun Chaochao , Yu Chang , Song Xuedan , Yang Feipeng , Kuang Wenzheng , Xie Yuanyang , Li Shaofeng , Wang Zhao , Yu Jinhe , Fu Guosheng , Guo Jinghua , Marcus Matthew A. , Urban Jeffrey J. , Zhang Qiuyu , Qiu Jieshan
Published: March 2022

Layered double hydroxides (LDH) have been extensively investigated for charge storage, however, their development is hampered by the sluggish reaction dynamics. Herein, triggered by mismatching integration of Mn sites, we configured wrinkled Mn/NiCo-LDH with strains and defects, where promoted mass & charge transport behaviors were realized. The well-tailored Mn/NiCo-LDH displays a capacity up to 518 C g−1 (1 A g−1), a remarkable rate performance (78%@100 A g−1) and a long cycle life (without capacity decay after 10,000 cycles). We clarified that the moderate electron transfer between the released Mn species and Co2+ serves as the pre-step, while the compressive strain induces structural deformation with promoted reaction dynamics. Theoretical and operando investigations further demonstrate that the Mn sites boost ion adsorption/transport and electron transfer, and the Mn-induced effect remains active after multiple charge/discharge processes. This contribution provides some insights for controllable structure design and modulation toward high-efficient energy storage.
Structure-guided unlocking of NaX reveals a non-selective tetrodotoxin-sensitive cation channel
Authors: Noland Cameron L. , Chua Han Chow , Kschonsak Marc , Heusser Stephanie Andrea , Braun Nina , Chang Timothy , Tam Christine , Tang Jia , Arthur Christopher P. , Ciferri Claudio , Pless Stephan Alexander , Payandeh Jian
Published: March 2022

Unlike classical voltage-gated sodium (NaV) channels, NaX has been characterized as a voltage-insensitive, tetrodotoxin-resistant, sodium (Na+)-activated channel involved in regulating Na+ homeostasis. However, NaX remains refractory to functional characterization in traditional heterologous systems. Here, to gain insight into its atypical physiology, we determine structures of the human NaX channel in complex with the auxiliary β3-subunit. NaX reveals structural alterations within the selectivity filter, voltage sensor-like domains, and pore module. We do not identify an extracellular Na+-sensor or any evidence for a Na+-based activation mechanism in NaX. Instead, the S6-gate remains closed, membrane lipids fill the central cavity, and the domain III-IV linker restricts S6-dilation. We use protein engineering to identify three pore-wetting mutations targeting the hydrophobic S6-gate that unlock a robust voltage-insensitive leak conductance. This constitutively active NaX-QTT channel construct is non-selective among monovalent cations, inhibited by extracellular calcium, and sensitive to classical NaV channel blockers, including tetrodotoxin. Our findings highlight a functional diversity across the NaV channel scaffold, reshape our understanding of NaX physiology, and provide a template to demystify recalcitrant ion channels.
Trajectory of immune evasion and cancer progression in hepatocellular carcinoma
Authors: Nguyen Phuong H. D. , Wasser Martin , Tan Chong Teik , Lim Chun Jye , Lai Hannah L. H. , Seow Justine Jia Wen , DasGupta Ramanuj , Phua Cheryl Z. J. , Ma Siming , Yang Jicheng , Suthen Sheena D/O , Tam Wai Leong , Lim Tony K. H. , Yeong Joe , Leow Wei Qiang , Pang Yin Huei , Soon Gwyneth , Loh Tracy Jiezhen , Wan Wei Keat , Chan Chung Yip , Cheow Peng Chung , Toh Han Chong , Kow Alfred , Dan Yock Young , Kam Juinn Huar , Iyer Shridhar , Madhavan Krishnakumar , Chung Alexander , Bonney Glenn K. , Goh Brian K. P. , Fu Naiyang , Yu Victor C. , Zhai Weiwei , Albani Salvatore , Chow Pierce K. H. , Chew Valerie
Published: March 2022

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.
LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy
Authors: Hwang Hyun Jung , Ha Hongseok , Lee Ban Seok , Kim Bong Heon , Song Hyun Kyu , Kim Yoon Ki
Published: March 2022

LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding protein that directly binds to mRNAs with a preference for a consensus AAUAAA motif corresponding to a polyadenylation sequence. Autophagic activation promotes an association between LC3B and target mRNAs and triggers rapid degradation of target mRNAs in a CCR4-NOT–dependent manner before autolysosome formation. Furthermore, our transcriptome-wide analysis reveals that PRMT1 mRNA, which encodes a negative regulator of autophagy, is one of the major substrates. Rapid degradation of PRMT1 mRNA by LC3B facilitates autophagy. Collectively, we demonstrate that LC3B acts as an RNA-binding protein and an mRNA decay factor necessary for efficient autophagy.
Conversion of twisted light to twisted excitons using carbon nanotubes
Authors: Zang Xiaoning , Singh Nirpendra , Lusk Mark T. , Schwingenschlögl Udo
Published: March 2022

Carbon nanotubes are explored as a means of coherently converting the orbital angular momentum of light to an excitonic form that is more amenable to quantum information processing. An analytical analysis, based on dynamical conductivity, is used to show that orbital angular momentum is conserved, modulo N, for a carbon nanotube illuminated by radially polarized, twisted light. This result is numerically demonstrated using real-time time-dependent density functional theory which captures the absorption of twisted light and the subsequent transfer of twisted excitons. The results suggest that carbon nanotubes are promising candidates for constructing optoelectronic circuits in which quantum information is more readily processed while manifested in excitonic form.
A programmable encapsulation system improves delivery of therapeutic bacteria in mice
Authors: Harimoto Tetsuhiro , Hahn Jaeseung , Chen Yu-Yu , Im Jongwon , Zhang Joanna , Hou Nicholas , Li Fangda , Coker Courtney , Gray Kelsey , Harr Nicole , Chowdhury Sreyan , Pu Kelly , Nimura Clare , Arpaia Nicholas , Leong Kam W. , Danino Tal
Published: March 2022

Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer.
The Terrific Skink bite force suggests insularity as a likely driver to exceptional resource use
Authors: Jowers Michael J. , Simone Yuri , Herrel Anthony , Cabezas M. Pilar , Xavier Raquel , Holden Magaly , Boistel Renaud , Murphy John C. , Santin Mathieu , Caut Stephane , Auguste Renoir J. , van der Meijden Arie , Andreone Franco , Ineich Ivan
Published: March 2022

Natural history museum collections hold extremely rare, extinct species often described from a single known specimen. On occasions, rediscoveries open new opportunities to understand selective forces acting on phenotypic traits. Recent rediscovery of few individuals of Bocourt´s Terrific Skink Phoboscincus bocourti, from a small and remote islet in New Caledonia allowed to genetically identify a species of land crab in its diet. To explore this further, we CT- and MRI-scanned the head of the holotype, the only preserved specimen dated to about 1870, segmented the adductor muscles of the jaw and bones, and estimated bite force through biomechanical models. These data were compared with those gathered for 332 specimens belonging to 44 other skink species. Thereafter we recorded the maximum force needed to generate mechanical failure of the exoskeleton of a crab specimen. The bite force is greater than the prey hardness, suggesting that predation on hard-shelled crabs may be an important driver of performance. The high bite force seems crucial to overcome low or seasonal variations in resource availability in these extreme insular environments. Phoboscincus bocourti appears to be an apex predator in a remote and harsh environment and the only skink known to predate on hard-shelled land crabs.
Circulating Lipocalin-2 level is positively associated with cognitive impairment in patients with metabolic syndrome
Authors: Pinyopornpanish Kanokporn , Phrommintikul Arintaya , Angkurawaranon Chaisiri , Kumfu Sirinart , Angkurawaranon Salita , Yarach Uten , Buawangpong Nida , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: March 2022

The association between Lipocalin-2 (LCN2) and cognition in patients with metabolic syndrome (MetS) has not been thoroughly investigated. We aimed to evaluate whether serum LCN2 levels are associated with the alteration of cognitive function in patients with MetS. The total of 191 non-demented participants with MetS were enrolled onto the study in 2015, and a cohort study was conducted in a subpopulation in 2020. After adjustment for sex, age, waist circumference, creatinine levels, and HbA1C, an association between the higher serum LCN2 levels and the lower Montreal cognitive assessment (MoCA) scores was observed (B = − 0.045; 95%CI − 0.087, − 0.004; p 0.030). A total of 30 participants were followed-up in 2020. Serum LCN2 levels were decreased in correlation with age (23.31 ± 12.32 ng/ml in 2015 and 15.98 ± 11.28 ng/ml in 2020, p 0.024), while other metabolic parameters were unchanged. Magnetic resonance imaging studies were conducted on a subsample of patients in 2020 (n = 15). Associations between high serum LCN2 levels from 2015 and 2020 and changes in brain volume of hippocampus and prefrontal cortex from 2020 have been observed. These findings suggest a relationship between changes of the level of circulating LCN2, cognitive impairment, and changes in brain volume in patients with MetS. However, further investigation is still needed to explore the direct effect of circulating LCN2 on the cognition of MetS patients.
SARS-CoV-2 host prediction based on virus-host genetic features
Authors: Kawashima Irina Yuri , Lopez Maria Claudia Negret , Cunha Marielton dos Passos , Hashimoto Ronaldo Fumio
Published: March 2022

The genetic diversity of the Coronaviruses gives them different biological abilities, such as infect different cells and/or organisms, a wide spectrum of clinical manifestations, their different routes of dispersion, and viral transmission in a specific host. In recent decades, different Coronaviruses have emerged that are highly adapted for humans and causing serious diseases, leaving their host of unknown origin. The viral genome information is particularly important to enable the recognition of patterns linked to their biological characteristics, such as the specificity in the host-parasite relationship. Here, based on a previously computational tool, the Seq2Hosts, we developed a novel approach which uses new variables obtained from the frequency of spike-Coronaviruses codons, the Relative Synonymous Codon Usage (RSCU) to shed new light on the molecular mechanisms involved in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host specificity. By using the RSCU obtained from nucleotide sequences before the SARS-CoV-2 pandemic, we assessed the possibility of know the hosts capable to be infected by these new emerging species, which was first identified infecting humans during 2019 in Wuhan, China. According to the model trained and validated using sequences available before the pandemic, bats are the most likely the natural host to the SARS-CoV-2 infection, as previously suggested in other studies that searched for the host viral origin.
Gauging mixed climate extreme value distributions in tropical cyclone regions
Authors: O’Grady J. G. , Stephenson A. G. , McInnes K. L.
Published: March 2022

In tropical cyclone (TC) regions, tide gauge or numerical hindcast records are usually of insufficient length to have sampled sufficient cyclones to enable robust estimates of the climate of TC-induced extreme water level events. Synthetically-generated TC populations provide a means to define a broader set of plausible TC events to better define the probabilities associated with extreme water level events. The challenge is to unify the estimates of extremes from synthetically-generated TC populations with the observed records, which include mainly non-TC extremes resulting from tides and more frequently occurring atmospheric-depression weather and climate events. We find that extreme water level measurements in multiple tide gauge records in TC regions, some which span more than 100 years, exhibit a behaviour consistent with the combining of two populations, TC and non-TC. We develop an equation to model the combination of two populations of extremes in a single continuous mixed climate (MC) extreme value distribution (EVD). We then run statistical simulations to show that long term records including both historical and synthetic events can be better explained using MC than heavy-tailed generalised EVDs. This has implications for estimating extreme water levels when combining synthetic cyclone extreme sea levels with hindcast water levels to provide actionable information for coastal protection.
Design and implementation of a highly accurate spatiotemporal monitoring and early warning platform for air pollutants based on IPv6
Authors: Yang Rongjin , Hao Xuejie , Zhao Long , Yin Lizeyan , Liu Lu , Li Xiuhong , Liu Qiang
Published: March 2022

The development of industry has brought about the pollution of the atmospheric environment. Pollution is harmful to people's health. Realizing the real-time monitoring of atmospheric environmental quality parameters can improve the above-mentioned effects. China's existing environmental monitoring systems focus on the accuracy of the system hardware itself for assessment, lack of data analysis and forecasting and early warning, and cannot provide managers and ordinary people with decision-making and activity guidance. This paper develops an IPV6-based high-spatial–temporal precision air pollutant monitoring and early warning platform. The feasibility of the system is verified through networking tests, operation tests, and early warning tests. Through actual data analysis and comparison, it is concluded that the monitoring system has field feasibility, and the atmospheric environment monitoring for the target observation area has achieved the desired observation function. This system integrates GIS technology and B/S architecture to analyze changes in the regional environment to provide support for regional environmental air quality management. The forecast and early warning module constructed by combining the weight method of the influence of different input factors on the environmental quality index and minute-level observations can provide technical support for the government to improve the level of supervision.
Uncertainty quantification of granular computing-neural network model for prediction of pollutant longitudinal dispersion coefficient in aquatic streams
Authors: Ghiasi Behzad , Noori Roohollah , Sheikhian Hossein , Zeynolabedin Amin , Sun Yuanbin , Jun Changhyun , Hamouda Mohamed , Bateni Sayed M. , Abolfathi Soroush
Published: March 2022

Discharge of pollution loads into natural water systems remains a global challenge that threatens water and food supply, as well as endangering ecosystem services. Natural rehabilitation of contaminated streams is mainly influenced by the longitudinal dispersion coefficient, or the rate of longitudinal dispersion (Dx), a key parameter with large spatiotemporal fluctuations that characterizes pollution transport. The large uncertainty in estimation of Dx in streams limits the water quality assessment in natural streams and design of water quality enhancement strategies. This study develops an artificial intelligence-based predictive model, coupling granular computing and neural network models (GrC-ANN) to provide robust estimation of Dx and its uncertainty for a range of flow-geometric conditions with high spatiotemporal variability. Uncertainty analysis of Dx estimated from the proposed GrC-ANN model was performed by alteration of the training data used to tune the model. Modified bootstrap method was employed to generate different training patterns through resampling from a global database of tracer experiments in streams with 503 datapoints. Comparison between the Dx values estimated by GrC-ANN to those determined from tracer measurements shows the appropriateness and robustness of the proposed method in determining the rate of longitudinal dispersion. The GrC-ANN model with the narrowest bandwidth of estimated uncertainty (bandwidth-factor = 0.56) that brackets the highest percentage of true Dx data (i.e., 100%) is the best model to compute Dx in streams. Considering the significant inherent uncertainty reported in the previous Dx models, the GrC-ANN model developed in this study is shown to have a robust performance for evaluating pollutant mixing (Dx) in turbulent environmental flow systems.
Argonaute 2 is lost from neuromuscular junctions affected with amyotrophic lateral sclerosis in SOD1G93A mice
Authors: Shapiro Dillon , Massopust Ryan , Taetzsch Thomas , Valdez Gregorio
Published: March 2022

miRNAs are necessary for neuromuscular junction (NMJ) health; however, little is known about the proteins required for their activity in this regard. We examined expression of Argonaute 2 (Ago2) and miRNA biogenesis genes in skeletal muscles during development, following nerve injury and in the SOD1G93A ALS mouse model. We found that these genes are enriched in neonate muscles and in adult muscles following nerve injury. Despite widespread NMJ deterioration, these genes were not increased in muscles of SOD1G93A mice. We also found that Ago2 distribution is linked to maturation, innervation, and health of NMJs. Ago2 increasingly concentrates in synaptic regions during NMJ maturation, disperses following experimental denervation and reconcentrates at the NMJ upon reinnervation. Similar to experimentally denervated muscles, a homogenous distribution of Ago2 was observed in SOD1G93A muscle fibers. To determine if Ago2 is necessary for the health of adult muscles, we excised Ago2 from Ago2fl/fl mice using adeno-associated virus mediated Cre recombinase expression. We observed modest changes in muscle histology after 3 months of Ago2 knockdown. Together, these data provide critical insights into the role of Ago2 and miRNA biogenesis genes in healthy and ALS-afflicted skeletal muscles and NMJs.
Two-dimensional biphenylene: a promising anchoring material for lithium-sulfur batteries
Authors: Al-Jayyousi Hiba Khaled , Sajjad Muhammad , Liao Kin , Singh Nirpendra
Published: March 2022

Trapping lithium polysulfides (LiPSs) on a material effectively suppresses the shuttle effect and enhances the cycling stability of Li–S batteries. For the first time, we advocate a recently synthesized two-dimensional material, biphenylene, as an anchoring material for the lithium-sulfur battery. The density functional theory calculations show that LiPSs bind with pristine biphenylene insubstantially with binding energy ranging from −0.21 eV to −1.22 eV. However, defect engineering through a single C atom vacancy significantly improves the binding strength (binding energy in the range −1.07 to −4.11 eV). The Bader analysis reveals that LiPSs and S8 clusters donate the charge (ranging from −0.05 e to −1.12 e) to the biphenylene sheet. The binding energy of LiPSs with electrolytes is smaller than those with the defective biphenylene sheet, which provides its potential as an anchoring material. Compared with other reported two-dimensional materials such as graphene, MXenes, and phosphorene, the biphenylene sheet exhibits higher binding energies with the polysulfides. Our study deepens the fundamental understanding and shows that the biphenylene sheet is an excellent anchoring material for lithium-sulfur batteries for suppressing the shuttle effect because of its superior conductivity, porosity, and strong anchoring ability.
Force-enhanced biophysical connectivity of platelet β3 integrin signaling through Talin is predicted by steered molecular dynamics simulations
Authors: Su Shuixiu , Ling Yingchen , Fang Ying , Wu Jianhua
Published: March 2022

Platelet β3-integrin signaling through Talin is crucial in platelet transmembrane signaling, activation, adhesion, spreading and aggregation, and remains unclear in mechano-microenvironments. In order to examine Talin-β3 integrin biophysical connectivity, a series of “ramp-clamp” steered molecular dynamics (SMD) simulations were performed on complex of F3 domain of Talin and cytoplasmic tail of β3 integrin to imitate different force-loads in platelet. Pull-induced allostery of the hydrophobic pocket in F3 domain might markedly enhance complex rupture-force (> 150pN) and slow down breakage of the complex; the complex should mechano-stable for its conformational conservation under loads (≤ 80pN); increasing force below 60pN would decrease the complex dissociation probability, and force-induced extension of β5 strand on Talin and binding site residues, ASP740 and ALA742 as well as Asn744, on β3-integrin were responsible for the force-enhanced linkage of the Talin-β3 integrin. Force might enhance biophysical connectivity of β3-integrin signaling through Talin by a catch bond mechanism, which be mediated by the force-induced allostery of complex at clamped stage. This work provides a novel insight into the force-regulated transmembrane β3-integrin signaling and its molecular basis for platelet activation, and exhibited a potential power of the present computer strategy in predicting mechanical regulation on ligand-receptor interaction under loads.
Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions
Authors: Kopecky Jan , Pérez Julio Enríquez , Eriksson Håkan , Visse Edward , Siesjö Peter , Darabi Anna
Published: March 2022

Glioblastoma has remained the deadliest primary brain tumor while its current therapy offers only modest survival prolongation. Immunotherapy has failed to record notable benefits in routine glioblastoma treatment. Conventionally, immunotherapy relies on T cells as tumor-killing agents; however, T cells are outnumbered by macrophages in glioblastoma microenvironment. In this study, we explore the effect of AF16, a peptide from the endogenous antisecretory factor protein, on the survival of glioma-bearing mice, the tumor size, and characteristics of the tumor microenvironment with specific focus on macrophages. We elucidate the effect of AF16 on the inflammation-related secretome of human and murine macrophages, as well as human glioblastoma cells. In our results, AF16 alone and in combination with temozolomide leads to cure in immunocompetent mice with orthotopic GL261 gliomas, as well as prolonged survival in immunocompromised mice. We recorded decreased tumor size and changes in infiltration of macrophages and T cells in the murine glioma microenvironment. Human and murine macrophages increased expression of proinflammatory markers in response to AF16 treatment and the same effect was seen in human primary glioblastoma cells. In summary, we present AF16 as an immunomodulatory factor stimulating pro-inflammatory macrophages with a potential to be implemented in glioblastoma treatment protocols.
Hyaluronic acid functionalized ZnO nanoparticles co-deliver AS and GOD for synergistic cancer starvation and oxidative damage
Authors: Ren Zhenkun , Han Xibin , Wang Lixin , Wang Yi
Published: March 2022

Artesunate was reported to have inhibition effect on tumors via amplified oxidative stress while the lack of intratumoral ferrous ions supply greatly hinders its efficacy. Herein, the AS/GOD@HAZnO NPs we proposed could be efficiently taken in by the affinity between hyaluronic acid and the CD44 receptors. DLS and TEM results manifested the nano-size (~ 160 nm) and circular shape of AS/GOD@HAZnO NPs. Due to the acid-responsive degradation, AS/GOD@HAZnO NPs realized responsive release (up to 80%) in acid environment while only 20% was released in neutral medium. The cellular and in vivo experiment showed that co-delivery of AS and GOD via HAZnO NPs could effectively induce the overproduction of ROS and cut the glucose supply of tumor cells, and thus result in efficient cell apoptosis and tumor inhibition.
Effects of a reduction of the number of electrodes in the EEG montage on the number of identified seizure patterns
Authors: Tacke Moritz , Janson Katharina , Vill Katharina , Heinen Florian , Gerstl Lucia , Reiter Karl , Borggraefe Ingo
Published: March 2022

Continuous EEG monitoring (cEEG) is frequently used in neurocritical care. The detection of seizures is one of the main objectives. The placement of the EEG electrodes is time consuming, therefore a reduced montage might lead to an increased availability in the ICU setting. It is unknown whether such a reduction of electrodes reduces the number of seizure patterns that are detected. A total of 95 seizure and 95 control EEG sequences from a pediatric epilepsy monitoring unit (EMU) were anonymized and reduced to an eight-lead montage. Two experts evaluated the recordings and the seizure detection rates using the reduced and the full montage were compared. Sensitivity and specificity for the seizure detection were calculated using the original EMU findings as gold standard. The sensitivity to detect seizures was 0.65 for the reduced montage compared to 0.76 for the full montage (p = 0.031). The specificities (0.97 and 0.96) were comparable (p = 1). A total of 4/9 (44%) of the generalized, 12/44 (27%) of the frontal, 6/14 (43%) of the central, 0/1 (0%) of the occipital, 6/20 (30%) of the temporal, and 5/7 (71%) of the parietal seizure patterns were not detected using the reduced montage. The median time difference between the onset of the seizure pattern in the full and reduced montage was 0.026s (IQR 5.651s). In this study the reduction of the EEG montage from 21 to eight electrodes reduced the sensitivity to detect seizure patterns from 0.76 to 0.65. The specificity remained virtually unchanged.
In vivo competition assays between Vip3 proteins confirm the occurrence of shared binding sites in Spodoptera littoralis
Authors: Lázaro-Berenguer María , Quan Yudong , Hernández-Martínez Patricia , Ferré Juan
Published: March 2022

Due to their different specificity, the use of Vip3 proteins from Bacillus thuringiensis in combination with the conventionally used Cry proteins in crop protection is being essential to counteract the appearance of insect resistance. Therefore, understanding the mode of action of Vip3 proteins is crucial for their better application, with special interest on the binding to membrane receptors as the main step for specificity. Derived from in vitro heterologous competition binding assays using 125I-Vip3A and other Vip3 proteins as competitors, it has been shown that Vip3 proteins share receptors in Spodoptera frugiperda and Spodoptera exigua brush border membrane vesicles (BBMV). In this study, using 125I-Vip3Aa, we have first extended the in vitro competition binding site model of Vip3 proteins to Spodoptera littoralis. With the aim to understand the relevance (in terms of toxicity) of the binding to the midgut sites observed in vitro on the insecticidal activity of these proteins, we have performed in vivo competition assays with S. littoralis larvae, using disabled mutant (non-toxic) Vip3 proteins as competitors for blocking the toxicity of Vip3Aa and Vip3Af. The results of the in vivo competition assays confirm the occurrence of shared binding sites among Vip3 proteins and help understand the functional role of the shared binding sites as revealed in vitro.
The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway
Authors: Carlile Graeme W. , Yang Qi , Matthes Elizabeth , Liao Jie , Birault Véronique , Sneddon Helen F. , Poole Darren L. , Hall Callum J. , Hanrahan John W. , Thomas David Y.
Published: March 2022

Most cases of cystic fibrosis (CF) are caused by class 2 mutations in the cystic fibrosis transmembrane regulator (CFTR). These proteins preserve some channel function but are retained in the endoplasmic reticulum (ER). Partial rescue of the most common CFTR class 2 mutant, F508del-CFTR, has been achieved through the development of pharmacological chaperones (Tezacaftor and Elexacaftor) that bind CFTR directly. However, it is not clear whether these drugs will rescue all class 2 CFTR mutants to a medically relevant level. We have previously shown that the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen can correct F508del-CFTR trafficking. Here, we utilized RNAi and pharmacological inhibitors to determine the mechanism of action of the NSAID glafenine. Using cellular thermal stability assays (CETSAs), we show that it is a proteostasis modulator. Using medicinal chemistry, we identified a derivative with a fourfold increase in CFTR corrector potency. Furthermore, we show that these novel arachidonic acid pathway inhibitors can rescue difficult-to-correct class 2 mutants, such as G85E-CFTR > 13%, that of non-CF cells in well-differentiated HBE cells. Thus, the results suggest that targeting the arachidonic acid pathway may be a profitable way of developing correctors of certain previously hard-to-correct class 2 CFTR mutations.
Agrivoltaic systems have the potential to meet energy demands of electric vehicles in rural Oregon, US
Authors: Steadman Casey L. , Higgins Chad W.
Published: March 2022

Electrification of the transportation industry is necessary; however, range anxiety has proven to be a major hindrance to individuals adopting electric vehicles (EVs). Agrivoltaic systems (AVS) can facilitate the transition to EVs by powering EV charging stations along major rural roadways, increasing their density and mitigating range anxiety. Here we conduct case study analyses of future EV power needs for Oregon, USA, and identify 174 kha of AVS viable agricultural land outside urban boundaries that is south facing and does not have prohibitive attributes (designated wetland, forested land, or otherwise protected lands). 86% highway access points have sufficient available land to supply EV charging stations with AVS. These AVS installations would occupy less than 3% (5 kha) of the identified available land area. Installing EV charging stations at these 86% highway access points would yield 231 EV charging stations with a median range of 5.9 km (3.6 mi), a distance comparable to driver expectations, suggesting that this approach would serve to mitigate range anxiety. AVS powered rural charging stations in Oregon could support the equivalent of 673,915 electric vehicles yr−1, reducing carbon emissions due to vehicle use in OR by 3.1 mil MTCO2 yr−1, or 21%.
High-performance freestanding supercapacitor electrode based on polypyrrole coated nickel cobalt sulfide nanostructures
Authors: Barazandeh Mohammad , Kazemi Sayed Habib
Published: March 2022

In the present work, we report the successful fabrication of dandelion-like Nickel–Cobalt Sulfide@Polypyrrole microspheres through the hydrothermal method and its possible application as a binder-free electrode in supercapacitors. This electrode exhibited low charge transfer resistance with a remarkable specific capacitance of 2554.9 F g−1 at 2.54 A g−1, in addition to considerable cycle life stability. Also, an asymmetric device was prepared using NiCo2S4@PPy/NF as positive and rGO/NF as negative electrodes. This asymmetric supercapacitor exhibited a specific capacitance of 98.9 F g−1 at 1.84 A g−1 and delivered an energy density of 35.17 Wh kg−1 at a power density of 1472 W kg−1. Such a remarkable performance can be originated from the synergy effect of NiCo2S4 and PPy and the direct deposition of the composite on the current collector. Our findings suggest the dandelion-like NiCo2S4@PPy as a promising material for making high-performance supercapacitors.