bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithospheric Structure of the South India Precambrian Terrains From Surface Wave Tomography
Authors: Mullick N. , Rai S. S. , Saha G. 
Published: June 2022

AbstractWe have developed a 3‐D shear velocity (Vsv) model of Precambrian terrains of South India with a lateral resolution of 55 km to a depth of 250 km by inversion of fundamental mode Rayleigh wave phase velocity dispersion data in the period of 30–140s, combined with a well‐constrained crustal velocity model from an earlier study. The dispersion data were computed from 748 earthquakes recorded at 85 homogeneously distributed seismographs. Our velocity model shows 150–200 km thick lithosphere in most of the Archean Dharwar craton where Vsv is >4.7 km/s in the depth of 50–100 km and progressively decreases to 4.6 km/s at 120–150 km followed by a constant velocity of 4.5 km/s beyond 150–200 km depth. It correlates well with the results of the petrological studies of kimberlite xenoliths. An extraordinary high shear velocity (up to 4.8 km/s) and thick lithosphere (150 km) are observed beneath the Proterozoic Carbonatite complex, located at the south‐eastern edge of the Dharwar craton. We infer compositional modification of lower lithosphere at the south‐western margin of the Dharwar craton and lithospheric erosion at the Granulite terrain both possibly due to interaction with the Marion mantle plume at ∼90 Ma. The region is underlain by a 2%–3% lower velocity channel at ∼180–220 km depth in the asthenosphere, uncorrelated with the overlying lithosphere, possibly due to relative motion between them. It may be attributed to deep Earth‐processes such as asthenospheric upwelling.
A Dual Regime of Mesoscale Convective Systems in the East Asian Monsoon Annual Cycle
Authors: Cheng Tat Fan , Dong Qizhen , Dai Lun , Lu Mengqian 
Published: June 2022

AbstractEastern China is perennially hit by mesoscale convective systems (MCSs), yet it remains an open question as to whether and how their general properties change throughout the annual cycle. By leveraging high‐resolution satellite observations and a hybrid tracking algorithm, we present a 20‐year (2001–2020) climatology of MCSs over eastern China during eight subseasonal‐to‐seasonal (S2S) monsoon stages. MCSs contribute up to 50% of the stage‐total precipitation and over 60% of the rainband‐zone precipitation during the Pre‐Meiyu and Meiyu episodes, and their contributions remain non‐trivial during the transition seasons. We discover two contrasting regimes of MCSs that alternate immediately upon the Pre‐Meiyu and the Fall onsets. The wintertime regime features fast‐propagating shallow systems initiated at night in a strongly sheared and dry environment. The summertime regime, instead, features an outbreak of MCSs in the south, where the systems often initiate in the afternoon and propagate 2–3 times slower than the cold‐season ones. Based on multivariate clustering analysis, the nighttime MCSs that dictate the winter stages often initiate over a deep nocturnal boundary layer with moist rear inflows upgliding above it. In contrast, the afternoon‐initiated MCSs under the summertime regime feature a pronounced convective available potential energy (CAPE) "tongue" and upslope flows in their southeast quadrant. The southwesterly moist ascending flows are likely to shallow the convective inhibition at the tip of the CAPE tongue and facilitate the intense updrafts of the MCSs. Findings here may offer insights into S2S weather prediction and facilitate agricultural and water management throughout the year.
Enhanced Oxidation of SO2 by H2O2 During Haze Events: Constraints From Sulfur Isotopes
Authors: Han Xiaokun , Lang Yunchao , Guo Qingjun , Li Xiaodong , Ding Hu , Li Siliang 
Published: June 2022

AbstractSulfate aerosols play a critical role in atmospheric chemistry and climate change. However, the mechanism of sulfate formation during haze events remains highly uncertain. In this study, sulfur isotopic compositions of SO2 and sulfate in PM2.5 samples collected in Tianjin, China as well as a Rayleigh distillation model are used to constrain SO2 oxidation pathways. The sulfur isotopic fractionation (ε) between SO2 and sulfate displays a seasonal change with low values in summer (−0.1 ± 1.0‰, n = 16) and high values in winter (2.1 ± 1.2‰, n = 16). Although an influence of temperature effect to this seasonal trend cannot be ignored, the relation between ε values and SO2 oxidation ratios indicates that the seasonality is mainly attributed to the changes in relative contributions of oxidation pathways. In addition, an elevated ε value has been observed during the first stage of haze event, suggesting that the relative contribution of H2O2 pathway to sulfate formation is higher in haze days than that in normal days. Our results highlight the important role of SO2 oxidation by H2O2 in the first stage of haze event.
Low quality of life in men with chronic prostatitis-like symptoms
Authors: Sugimoto Mikio , Hijikata Yasukazu , Tohi Yoichiro , Kuroda Hideya , Takei Mineo , Matsuki Takakazu , Kamitani Tsukasa , Kakehi Yoshiyuki , Yamamoto Yosuke , Fukuhara Shunichi 
Published: June 2022

Abstract
Background
Chronic prostatitis (CP) can impair health-related quality of life (QOL), but the full impact of CP, including the impact of CP-like symptoms in men who have no CP diagnosis (CPS), is unknown. We estimated the impact of diagnosed CP (DCP) and CPS on Health-related QOL.

Methods
From a representative nationwide survey of men aged 20–84 in Japan, we determined the prevalence of DCP and also of CPS. For CPS, we used Nickel’s criteria, which were used previously to estimate the prevalence of CP and are based on the NIH Chronic Prostatitis Symptom Index. To test the robustness of Nickel’s criteria, we used two other definitions of CPS (two sensitivity analyses). We measured QOL with the Short-Form 12-Item Health Survey. We compared the participants’ QOL scores with the national-norm scores, and with the scores of men who had benign prostatic hyperplasia (BPH).

Results
Among the 5 010 participants, 1.4% had DCP and 3.7% had CPS. The sensitivity analyses resulted in CPS prevalence estimates of 3.1% and 4.5%. CPS was particularly common in younger participants (5.7% of those in their 30 s had CPS). QOL was very low among men with CP: In most areas (domains) of QOL, their scores were more than 0.5 standard deviation below the national-norm mean. Their mental-health scores were lower than those of men with BPH. The lowest scores among all 8 QOL domains were in role-functioning.

Conclusions
CP is common, but it is underdiagnosed, particularly in younger men. Whether diagnosed or only suspected, CP’s impact on QOL is large. Because CP is common, and because it substantially impairs individuals’ QOL and can also reduce societal productivity, it requires more attention. Specifically, needed now is a simple tool for urologists and for primary care providers, to identify men, particularly young men, whose QOL is impaired by CP.
Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials
Authors: Shi Yuncong , Zhang Huanji , Huang Suli , Yin Li , Wang Feng , Luo Pei , Huang Hui 
Published: June 2022

AbstractEpigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses and candidate gene approaches illustrate the multigenic complexity of cardiovascular disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding RNA, which are of importance for cardiovascular disease development and regression. Targeting epigenetic key enzymes, especially the DNA methyltransferases, histone methyltransferases, histone acetylases, histone deacetylases and their regulated target genes, could represent an attractive new route for the diagnosis and treatment of cardiovascular diseases. Herein, we summarize the knowledge on epigenetic history and essential regulatory mechanisms in cardiovascular diseases. Furthermore, we discuss the preclinical studies and drugs that are targeted these epigenetic key enzymes for cardiovascular diseases therapy. Finally, we conclude the clinical trials that are going to target some of these processes.
ATF6 prevents DNA damage and cell death in colon cancer cells undergoing ER stress
Authors: Benedetti Rossella , Romeo Maria Anele , Arena Andrea , Gilardini Montani Maria Saveria , Di Renzo Livia , D’Orazi Gabriella , Cirone Mara 
Published: June 2022

AbstractColon cancer represents one of the most common and aggressive cancers in its advanced state. Among the most innovative anti-cancer approaches, the manipulation of UPR is a promising one, effective also against cancers carrying dysfunctional p53. Interestingly, it is emerging that UPR cross-talks with DDR and that targeting the interplay between these two adaptive responses may be exploited to overcome the resistance to the single DDR- and UPR-targeting treatments. Previous studies have highlighted the role of IRE1 alpha and PERK UPR sensors on DDR, while the impact of ATF6 on this process remains under-investigated. This study shows for the first time that ATF6 sustains the expression level of BRCA-1 and protects colon cancer cells from the cytotoxic effect of ER stressors DPE and Thapsigargin. At molecular level, ATF6 activates mTOR to sustain the expression of HSP90, of which BRCA-1 is a client protein. Therefore, pharmacological or genetic inhibition of ATF6 promoted BRCA-1 degradation and increased DNA damage and cell death, particularly in combination with Adriamycin. All together this study suggests that targeting ATF6 may not only potentiate the cytotoxic effect of drugs triggering ER stress but may render colon cancer cells more sensitive to Adriamycin and possibly to other DNA damaging agents used to treat colon cancer.
Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children
Authors: Dewald Felix , Suárez Isabelle , Johnen Ronja , Grossbach Jan , Moran-Tovar Roberto , Steger Gertrud , Joachim Alexander , Rubio Gibran Horemheb , Fries Mira , Behr Florian , Kley Joao , Lingnau Andreas , Kretschmer Alina , Gude Carina , Baeza-Flores Guadelupe , del Valle David Laveaga , Roblero-Hernandez Alberto , Magana-Cerino Jesus , Hernandez Adriana Torres , Ruiz-Quinones Jesus , Schega Konstantin , Linne Viktoria , Junker Lena , Wunsch Marie , Heger Eva , Knops Elena , Di Cristanziano Veronica , Meyer Meike , Hünseler Christoph , Weber Lutz T. , Lüers Jan-Christoffer , Quade Gustav , Wisplinghoff Hilmar , Tiemann Carsten , Zotz Rainer , Jomaa Hassan , Pranada Arthur , Herzum Ileana , Cullen Paul , Schmitz Franz-Josef , Philipsen Paul , Kirchner Georg , Knabbe Cornelius , Hellmich Martin , Buess Michael , Wolff Anna , Kossow Annelene , Niessen Johannes , Jeworutzki Sebastian , Schräpler Jörg-Peter , Lässig Michael , Dötsch Jörg , Fätkenheuer Gerd , Kaiser Rolf , Beyer Andreas , Rybniker Jan , Klein Florian 
Published: June 2022

AbstractSystematic SARS-CoV-2 testing is a valuable tool for infection control and surveillance. However, broad application of high sensitive RT-qPCR testing in children is often hampered due to unpleasant sample collection, limited RT-qPCR capacities and high costs. Here, we developed a high-throughput approach (‘Lolli-Method’) for SARS-CoV-2 detection in children, combining non-invasive sample collection with an RT-qPCR-pool testing strategy. SARS-CoV-2 infections were diagnosed with sensitivities of 100% and 93.9% when viral loads were >106 copies/ml and >103 copies/ml in corresponding Naso-/Oropharyngeal-swabs, respectively. For effective application of the Lolli-Method in schools and daycare facilities, SEIR-modeling indicated a preferred frequency of two tests per week. The developed test strategy was implemented in 3,700 schools and 698 daycare facilities in Germany, screening over 800,000 individuals twice per week. In a period of 3 months, 6,364 pool-RT-qPCRs tested positive (0.64%), ranging from 0.05% to 2.61% per week. Notably, infections correlated with local SARS-CoV-2 incidences and with a school social deprivation index. Moreover, in comparison with the alpha variant, statistical modeling revealed a 36.8% increase for multiple (≥2 children) infections per class following infections with the delta variant. We conclude that the Lolli-Method is a powerful tool for SARS-CoV-2 surveillance and can support infection control in schools and daycare facilities.
The force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail
Authors: Kuo Yin-Wei , Mahamdeh Mohammed , Tuna Yazgan , Howard Jonathon 
Published: June 2022

AbstractSevering enzymes and molecular motors extract tubulin from the walls of microtubules by exerting mechanical force on subunits buried in the lattice. However, how much force is needed to remove tubulin from microtubules is not known, nor is the pathway by which subunits are removed. Using a site-specific functionalization method, we applied forces to the C-terminus of α-tubulin with an optical tweezer and found that a force of ~30 pN is required to extract tubulin from the microtubule wall. Additionally, we discovered that partial unfolding is an intermediate step in tubulin removal. The unfolding and extraction forces are similar to those generated by AAA-unfoldases. Lastly, we show that three kinesin-1 motor proteins can also extract tubulin from the microtubule lattice. Our results provide the first experimental investigation of how tubulin responds to mechanical forces exerted on its α-tubulin C-terminal tail and have implications for the mechanisms of severing enzymes and microtubule stability.
Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing
Authors: Yuan Baolei , Zhou Xuan , Suzuki Keiichiro , Ramos-Mandujano Gerardo , Wang Mengge , Tehseen Muhammad , Cortés-Medina Lorena V. , Moresco James J. , Dunn Sarah , Hernandez-Benitez Reyna , Hishida Tomoaki , Kim Na Young , Andijani Manal M. , Bi Chongwei , Ku Manching , Takahashi Yuta , Xu Jinna , Qiu Jinsong , Huang Ling , Benner Christopher , Aizawa Emi , Qu Jing , Liu Guang-Hui , Li Zhongwei , Yi Fei , Ghosheh Yanal , Shao Changwei , Shokhirev Maxim , Comoli Patrizia , Frassoni Francesco , Yates John R. , Fu Xiang-Dong , Esteban Concepcion Rodriguez , Hamdan Samir , Izpisua Belmonte Juan Carlos , Li Mo 
Published: June 2022

AbstractThe diverse functions of WASP, the deficiency of which causes Wiskott-Aldrich syndrome (WAS), remain poorly defined. We generated three isogenic WAS models using patient induced pluripotent stem cells and genome editing. These models recapitulated WAS phenotypes and revealed that WASP deficiency causes an upregulation of numerous RNA splicing factors and widespread altered splicing. Loss of WASP binding to splicing factor gene promoters frequently leads to aberrant epigenetic activation. WASP interacts with dozens of nuclear speckle constituents and constrains SRSF2 mobility. Using an optogenetic system, we showed that WASP forms phase-separated condensates that encompasses SRSF2, nascent RNA and active Pol II. The role of WASP in gene body condensates is corroborated by ChIPseq and RIPseq. Together our data reveal that WASP is a nexus regulator of RNA splicing that controls the transcription of splicing factors epigenetically and the dynamics of the splicing machinery through liquid-liquid phase separation.
Self-sustained electricity generator driven by the compatible integration of ambient moisture adsorption and evaporation
Authors: Tan Jin , Fang Sunmiao , Zhang Zhuhua , Yin Jun , Li Luxian , Wang Xiang , Guo Wanlin 
Published: June 2022

AbstractGenerating sustainable electricity from ambient humidity and natural evaporation has attracted tremendous interest recently as it requires no extra mechanical energy input and is deployable across all weather and geography conditions. Here, we present a device prototype for enhanced power generation from ambient humidity. This prototype uses both heterogenous materials assembled from a LiCl-loaded cellulon paper to facilitate moisture adsorption and a carbon-black-loaded cellulon paper to promote water evaporation. Exposing such a centimeter-sized device to ambient humidity can produce voltages of around 0.78 V and a current of around 7.5 μA, both of which can be sustained for more than 10 days. The enhanced electric output and durability are due to the continuous water flow that is directed by evaporation through numerous, negatively charged channels within the cellulon papers. The voltage and current exhibit an excellent scaling behavior upon device integration to sufficiently power commercial devices including even cell phones. The results open a promising prospect of sustainable electricity generation based on a synergy between spontaneous moisture adsorption and water evaporation.
Echolocation-related reversal of information flow in a cortical vocalization network
Authors: García-Rosales Francisco , López-Jury Luciana , González-Palomares Eugenia , Wetekam Johannes , Cabral-Calderín Yuranny , Kiai Ava , Kössl Manfred , Hechavarría Julio C. 
Published: June 2022

AbstractThe mammalian frontal and auditory cortices are important for vocal behavior. Here, using local-field potential recordings, we demonstrate that the timing and spatial patterns of oscillations in the fronto-auditory network of vocalizing bats (Carollia perspicillata) predict the purpose of vocalization: echolocation or communication. Transfer entropy analyses revealed predominant top-down (frontal-to-auditory cortex) information flow during spontaneous activity and pre-vocal periods. The dynamics of information flow depend on the behavioral role of the vocalization and on the timing relative to vocal onset. We observed the emergence of predominant bottom-up (auditory-to-frontal) information transfer during the post-vocal period specific to echolocation pulse emission, leading to self-directed acoustic feedback. Electrical stimulation of frontal areas selectively enhanced responses to sounds in auditory cortex. These results reveal unique changes in information flow across sensory and frontal cortices, potentially driven by the purpose of the vocalization in a highly vocal mammalian model.
Spin relaxation in a single-electron graphene quantum dot
Authors: Banszerus L. , Hecker K. , Möller S. , Icking E. , Watanabe K. , Taniguchi T. , Volk C. , Stampfer C. 
Published: June 2022

AbstractThe relaxation time of a single-electron spin is an important parameter for solid-state spin qubits, as it directly limits the lifetime of the encoded information. Thanks to the low spin-orbit interaction and low hyperfine coupling, graphene and bilayer graphene (BLG) have long been considered promising platforms for spin qubits. Only recently, it has become possible to control single-electrons in BLG quantum dots (QDs) and to understand their spin-valley texture, while the relaxation dynamics have remained mostly unexplored. Here, we report spin relaxation times (T1) of single-electron states in BLG QDs. Using pulsed-gate spectroscopy, we extract relaxation times exceeding 200 μs at a magnetic field of 1.9 T. The T1 values show a strong dependence on the spin splitting, promising even longer T1 at lower magnetic fields, where our measurements are limited by the signal-to-noise ratio. The relaxation times are more than two orders of magnitude larger than those previously reported for carbon-based QDs, suggesting that graphene is a potentially promising host material for scalable spin qubits.
Detection of SARS-CoV-2 intra-host recombination during superinfection with Alpha and Epsilon variants in New York City
Authors: Wertheim Joel O. , Wang Jade C. , Leelawong Mindy , Martin Darren P. , Havens Jennifer L. , Chowdhury Moinuddin A. , Pekar Jonathan E. , Amin Helly , Arroyo Anthony , Awandare Gordon A. , Chow Hoi Yan , Gonzalez Edimarlyn , Luoma Elizabeth , Morang’a Collins M. , Nekrutenko Anton , Shank Stephen D. , Silver Stefan , Quashie Peter K. , Rakeman Jennifer L. , Ruiz Victoria , Torian Lucia V. , Vasylyeva Tetyana I. , Kosakovsky Pond Sergei L. , Hughes Scott 
Published: June 2022

AbstractRecombination is an evolutionary process by which many pathogens generate diversity and acquire novel functions. Although a common occurrence during coronavirus replication, detection of recombination is only feasible when genetically distinct viruses contemporaneously infect the same host. Here, we identify an instance of SARS-CoV-2 superinfection, whereby an individual was infected with two distinct viral variants: Alpha (B.1.1.7) and Epsilon (B.1.429). This superinfection was first noted when an Alpha genome sequence failed to exhibit the classic S gene target failure behavior used to track this variant. Full genome sequencing from four independent extracts reveals that Alpha variant alleles comprise around 75% of the genomes, whereas the Epsilon variant alleles comprise around 20% of the sample. Further investigation reveals the presence of numerous recombinant haplotypes spanning the genome, specifically in the spike, nucleocapsid, and ORF 8 coding regions. These findings support the potential for recombination to reshape SARS-CoV-2 genetic diversity.
Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
Authors: Villars Alexis , Matamoro-Vidal Alexis , Levillayer Florence , Levayer Romain 
Published: June 2022

AbstractThe expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is still poorly understood. Using theDrosophilapupal notum, a single layer epithelium where extrusions are caspase-dependent, we showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration and dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion, while microtubule stabilisation strongly impairs cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting step of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.
Ru(II) photocages enable precise control over enzyme activity with red light
Authors: Havrylyuk Dmytro , Hachey Austin C. , Fenton Alexander , Heidary David K. , Glazer Edith C. 
Published: June 2022

AbstractThe cytochrome P450 family of enzymes (CYPs) are important targets for medicinal chemistry. Recently, CYP1B1 has emerged as a key player in chemotherapy resistance in the treatment of cancer. This enzyme is overexpressed in a variety of tumors, and is correlated with poor treatment outcomes; thus, it is desirable to develop CYP1B1 inhibitors to restore chemotherapy efficacy. However, possible off-target effects, such as inhibition of liver CYPs responsible for first pass metabolism, make selective inhibition a high priority to avoid possible drug-drug interactions and toxicity. Here we describe the creation of light-triggered CYP1B1 inhibitors as “prodrugs”, and achieve >6000-fold improvement in potency upon activation with low energy (660 nm) light. These systems provide a selectivity index of 4,000–100,000 over other off-target CYPs. One key to the design was the development of coordinating CYP1B1 inhibitors, which suppress enzyme activity at pM concentrations in live cells. The metal binding group enforces inhibitor orientation in the active site by anchoring to the iron. The second essential component was the biologically compatible Ru(II) scaffold that cages the inhibitors before photochemical release. These Ru(II) photocages are anticipated to provide similar selectivity and control for any coordinating CYP inhibitors.