bluuebunny/crossref_metadata_2025 huggingface dataset:
Russia as a great power: from 1815 to the present day Part II
Authors: Ellman Michael
Published: October 2022

This article is Part II of a survey of Russia's position as one of the great powers and how it has evolved from 1815 to the present day. Part 1 ended on the eve of the Great Patriotic War (1941‒1945), and Part II begins where Part 1 left off, with some data on the Great Patriotic War and its influence on the USSR's position as a great power. It deals with post-war reconstruction and then considers the Cold War and post-Soviet Russia (1992‒2022). Attention is paid to Soviet economic policies, the reasons for the long-run decline in Soviet economic growth, and the state collapse of 1991. Explanatory theories used include List's economic recommendations for medium-developed countries, Wintrobe's political economy of dictatorship, and Tilly's analysis of the war–state relationship. It is concluded that a relatively poor country can become a great power and maintain that position for long periods if it has institutions that enable it to squeeze its population for military purposes.
Locating TWAIL Scholarship in China
Authors: WANG Yilin
Published: October 2022

This paper opens a scholarly discourse about Chinese scholars’ engagement with TWAIL (Third World Approach to International Law). This paper shows that Chinese international law scholars and TWAIL align in their resistance to Eurocentrism in international law, while they differ in their attitude towards whether to refrain from “national allegories” and criticize international law as a state-centric invention. A state-centric approach means that mainstream Chinese international lawyers tend to adopt a pragmatic attitude towards international law, employing it as a strategic weapon. During the course of this inquiry, this paper also observes a critical strand in Chinese academics – mostly outside of the international law discipline, and within the disciplines of history and philosophy – that is dedicated to redeeming China's subjectivity and history, which may be useful to understand Chinese critical spirit.
Resilienz, ein Modewort?
Authors: Ruhwinkel Bernadette , Buchmann Michael
Published: October 2022

Zusammenfassung. Das Bewusstsein für die Wichtigkeit von Resilienz wird heute in vielen Bereichen unserer Gesellschaft immer grösser. In der Forschung geht man weitgehend davon aus, dass Resilienz trainierbar ist und zur Prävention von Leiden oder zur besseren Überwindung von Krisen nutzbar gemacht werden kann. In diesem Artikel wird der Frage nachgegangen, was unter Resilienz verstanden wird und wie man sie trainieren kann.
Linking Critical Zone With Watershed Science: The Example of the Heihe River Basin
Authors: Li Xin , Cheng Guodong , Fu Bojie , Xia Jun , Zhang Ling , Yang Dawen , Zheng Chunmiao , Liu Shaomin , Li Xiubin , Song Changqing , Kang Shaozhong , Li Xiaoyan , Che Tao , Zheng Yi , Zhou Yanzhao , Wang Haibo , Ran Youhua
Published: October 2022

Watersheds are the basic unit of Earth's terrestrial systems and are therefore ideal units for the study of critical zones (CZs). However, grand challenges remain regarding the observation, modeling, and management of CZs and watershed systems. We synthesize the progress and breakthroughs associated with watershed science and CZ research in the Heihe River basin (HRB), a large‐scale endorheic river basin with unique mountain cryosphere‐oasis‐desert landscapes and prominent human‐nature competition for water resources. The HRB observation system consists of mountain cryosphere, agricultural oasis, and natural oasis observatories and is promoted by large‐scale comprehensive experiments to achieve multiscale observations. A watershed system model that couples ecohydrological models with socioeconomic models is developed to investigate the complex interactions among water, ecology, and socioeconomics in the HRB. The model is embedded in a decision support system to bridge science and decision‐making and to better serve river basin sustainability. Significant progress and breakthroughs have been made in CZ and watershed process research (e.g., cryospheric hydrological processes, ecological and hydrological interactions, and surface‐groundwater interactions) in the HRB. Nevertheless, observation and modeling of geochemical and geomorphological processes in the CZ have not been well addressed in integrated watershed studies of the HRB. In the future, new observation technologies, agent‐based models, machine learning, and data assimilation will benefit both watershed science and CZ science and help to address complexity and dynamics in the CZ at the river basin scale. Overall, the HRB has successfully demonstrated how an experimental river basin can link CZ science with watershed science.
Converging Toward Solutions to Grand Challenges
Authors: McGranaghan Ryan , Kellerman Adam , Olson Mark
Published: October 2022

A hypothetical, space weather–induced power grid catastrophe served as a practice case for building unity and collaborative skills among disparate communities to address a major global hazard.
Quantifying Inclination Shallowing and Representing Flattening Uncertainty in Sedimentary Paleomagnetic Poles
Authors: Pierce James , Zhang Yiming , Hodgin Eben B. , Swanson‐Hysell Nicholas L.
Published: October 2022

Inclination is the angle of a magnetization vector from horizontal. Clastic sedimentary rocks often experience inclination shallowing whereby syn‐ to post‐depositional processes result in flattened detrital remanent magnetizations relative to local geomagnetic field inclinations. The deviation of recorded inclinations from true values presents challenges for reconstructing paleolatitudes. A widespread approach for estimating flattening factors (f) compares the shape of an assemblage of magnetization vectors to that derived from a paleosecular variation model (the elongation/inclination [E/I] method). Few studies exist that compare the results of this statistical approach with empirically determined flattening factors and none in the Proterozoic Eon. In this study, we evaluate inclination shallowing within 1.1 billion‐year‐old, hematite‐bearing red beds of the Cut Face Creek Sandstone that is bounded by lava flows of known inclination. Taking this inclination from the volcanics as the expected direction, we found that detrital hematite remanence is flattened with whereas the pigmentary hematite magnetization shares a common mean with the volcanics. Using the pigmentary hematite direction as the expected inclination results in . These flattening factors are consistent with those estimated through the E/I method supporting its application in deep time. However, all methods have significant uncertainty associated with determining the flattening factor. This uncertainty can be incorporated into paleomagnetic poles with the resulting ellipse approximated with a Kent distribution. Rather than seeking to find “the flattening factor,” or assuming a single value, the inherent uncertainty in flattening factors should be recognized and incorporated into paleomagnetic syntheses.
Hurricanes and Anomalous Heat in the Caribbean
Authors: Guido Zack , Allen Teddy , Mason Simon , Méndez‐Lázaro Pablo
Published: October 2022

Co‐occurring hazards present unparalleled challenges to development and disaster recovery. In this study, we investigate the relationship between anomalous heat in the aftermath of tropical cyclones in the eastern Caribbean between 1991 and 2020. We analyze the spatial patterns of anomalous heat index (HI) values for 53 tropical storms and hurricanes using a Lagrangian analysis framework. Furthermore, we analyze temporal patterns of 205 city‐storms pairings. The spatial patterns displayed distinct and statistically significant areas of anomalously warm conditions regardless of the storm intensity classification. Moreover, all 205 city‐storm events had positive HI anomalies following the storms' passage with a maximum of 5°C. The results show that HI anomalies can be high, have a time lag of days, and be observed in locations not directly impacted by the storm. The results have implications for tropical cyclones preparedness, including suggesting that preparedness include informing the public about heat impacts.
Velocity Gradients Below the 410‐km Discontinuity Beneath Eastern Asia and Its Implication on Water Content Distribution
Authors: Wang Yi , He Yumei , Li Juan
Published: October 2022

The velocity gradient below the 410‐km discontinuity provides clues for the water content gradient in the mantle transition zone. Here we report an abnormal X phase refracted below the 410, providing a unique opportunity to constrain the velocity gradient at that depth. We observe the X phase sampling the MTZ beneath south and southwest China close to the subducted Paleo‐Pacific slab, compared to the typical triplication waveforms sampling northeast Asia, the modern Pacific subduction system. The P velocity gradient below the 410 is 0.0028 s−1 or lower beneath south and southwest China, indicating a uniform water content; while it is 0.0037 s−1 or higher beneath northeast Asia, suggesting a water content decreasing from the 410‐km downward. Our research provides seismic evidence for water infiltrating the MTZ from a hydrous layer atop the 410 and then widely diffused into the MTZ after long‐term subduction.
Quantifying Ice‐Sheet Derived Lead (Pb) Fluxes to the Ocean; A Case Study at Nioghalvfjerdsbræ
Authors: Krisch Stephan , Huhn Oliver , Al‐Hashem Ali , Hopwood Mark J. , Lodeiro Pablo , Achterberg Eric P.
Published: October 2022

Concentrations of the toxic element lead (Pb) are elevated in seawater due to historical emissions. While anthropogenic atmospheric emissions are the dominant source of dissolved Pb (dPb) to the Atlantic Ocean, evidence is emerging of a natural source associated with subglacial discharge into the ocean but this has yet to be constrained around Greenland. Here, we show subglacial discharge from the cavity underneath Nioghalvfjerdsbræ floating ice tongue, is a previously unrecognized source of dPb to the NE Greenland Shelf. Contrasting cavity‐inflowing and cavity‐outflowing waters, we constrain the associated net‐dPb flux as 2.2 ± 1.4 Mg·yr−1, of which ∼90% originates from dissolution of glacial bedrock and cavity sediments. We propose that the retreat of the floating ice tongue, the ongoing retreat of many glaciers on Greenland, associated shifts in sediment dynamics, and enhanced meltwater discharges into shelf waters may result in pronounced changes, possibly increases, in net‐dPb fluxes to coastal waters.
Faster Tropical Upper Stratospheric Upwelling Drives Changes in Ozone Chemistry
Authors: Strahan Susan E. , Coy Lawrence , Douglass Anne R. , Damon Megan R.
Published: October 2022

Tropospheric trends in long‐lived source gases N2O and the chlorofluorocarbons cause trends in O3 through changes in their reactive product gases. Transport affects the product gases because it controls the distribution of the long‐lived source gases. We find that large changes in tropical upwelling 10–5 hPa since 2012 have strengthened the northern branch of the upper stratospheric (UpS) transport circulation, dramatically altering the abundances of N2O and its odd nitrogen product gases, NOx and HNO3. Increased upwelling is connected to stronger and more frequent Quasi‐Biennial Oscillation easterly winds at 10 hPa and above. We use simulations with and without time varying MERRA2 meteorology to quantify the impact of dynamical changes on O3 loss via the NOx and ClOx cycles. We find that dynamical impacts on these cycles explain the mid‐stratospheric tropical O3 increase and Arctic UpS O3 decrease since 2005.
Quantification of the Dominant Drivers of Acidification in the Coastal Mid‐Atlantic Bight
Authors: Wright‐Fairbanks E. K. , Saba G. K.
Published: October 2022

In shallow coastal shelves like the Mid‐Atlantic Bight (MAB), ocean acidification due to increased atmospheric carbon dioxide (CO2) is compounded by highly variable coastal processes including riverine freshwater inputs, nutrient loading, biogeochemical influence, coastal currents and water mass mixing, and seasonal transitions in physical parameters. Past deconstructions of carbonate system drivers in the MAB have focused on nearshore zones or single season data, and thus lack the spatial and temporal resolution required to assess impacts to important species occupying the shelf. Deconstructing highly resolved data collected during four seasonal Slocum glider deployments in the MAB, this study uses a Taylor Series decomposition to quantify the influence of temperature, salinity, biogeochemical activity, and water mass mixing on pH and aragonite saturation state from sea surface to bottom. Results show that water mass mixing and biogeochemical activity were the most significant drivers of the carbonate system in the MAB. Nearshore water was more acidic year‐round due to riverine freshwater input, but photosynthesis reduced acidity at certain depths and times. Water mass mixing increased acidity in bottom water on the shelf, particularly in summer. Gulf Stream intrusions at the shelf break during fall acted to mitigate acidification on the shelf in habitats occupied by carbonate‐bearing organisms. The relationships quantified here can be used to improve biogeochemical forecast models and determine habitat suitability for commercially important fin and shellfish species residing in the MAB.
A systematic review of non-surgical management in Peyronieʼs disease
Authors: Hayat Sulaiman , Brunckhorst Oliver , Alnajjar Hussain M , Cakir Onur Omer , Muneer Asif , Ahmed Kamran
Published: October 2022

The efficacy of many non-surgical treatments for Peyronie’s disease is unclear. This systematic review aims to critically assess the currently available options and provide a recommendation for treatment based on this. A systematic literature search utilising the Medline (Pubmed), Embase, global health and Cochrane library databases was conducted up to May 2021. All randomised controlled trials assessing non-surgical treatment modalities for Peyronie’s Disease were included. Individual study risk of bias was evaluated using the Cochrane tool and GRADE was used to assess evidence strength. Outcome measures were the change in penile curvature (degrees), plaque size (volume or size), International Index of Erectile Function score, pain scores and change in penile length. Prospero registration number: CRD42017064618. Amongst the 5549 articles identified, 41 studies (42 reports) were included. Seven different oral treatment options including vitamin E supplementation showed evidence for improving outcomes such as penile curvature and plaque size. Of the intralesional treatments, Collagenase Clostridium Histolyticum showed evidence for improving penile curvature (Range: 16.3–17 degrees, moderate level certainty of evidence). Intralesional Interferon demonstrated some improvement in curvature (Range: 12–13.5 degrees), plaque size (Range: 1.67–2.2 cm2) and pain, whilst intralesional calcium channel blockers such as Verapamil showed variable evidence for changes in the plaque size and pain. Extracorporeal Shockwave Therapy consistently demonstrated evidence for improving penile pain in stable disease, and two mechanical traction devices improved curvature. Iontophoresis, topical medications, and combination therapies did not demonstrate any consistent improvements in outcome measures. Intralesional options demonstrate the best potential. Overall, results varied with few high-quality randomised trials present.
Multi-omics characterization of autophagy-related molecular features for therapeutic targeting of autophagy
Authors: Luo Mei , Ye Lin , Chang Ruimin , Ye Youqiong , Zhang Zhao , Liu Chunjie , Li Shengli , Jing Ying , Ruan Hang , Zhang Guanxiong , He Yi , Liu Yaoming , Xue Yu , Chen Xiang , Guo An-Yuan , Liu Hong , Han Leng
Published: October 2022

Autophagy is a major contributor to anti-cancer therapy resistance. Many efforts have been made to understand and overcome autophagy-mediated therapy resistance, but these efforts have been unsuccessful in clinical applications. In this study, we establish an autophagy signature to estimate tumor autophagy status. We then classify approximately 10,000 tumor samples across 33 cancer types from The Cancer Genome Atlas into autophagy score-high and autophagy score-low groups. We characterize the associations between multi-dimensional molecular features and tumor autophagy, and further analyse the effects of autophagy status on drug response. In contrast to the conventional view that the induction of autophagy serves as a key resistance mechanism during cancer therapy, our analysis reveals that autophagy induction may also sensitize cancer cells to anti-cancer drugs. We further experimentally validate this phenomenon for several anti-cancer drugs in vitro and in vivo, and reveal that autophagy inducers potentially sensitizes tumor cells to etoposide through downregulating the expression level of DDIT4. Our study provides a comprehensive landscape of molecular alterations associated with tumor autophagy and highlights an opportunity to leverage multi-omics analysis to utilize multiple drug sensitivity induced by autophagy.
Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly
Authors: Fischer Elyse S. , Yu Conny W. H. , Hevler Johannes F. , McLaughlin Stephen H. , Maslen Sarah L. , Heck Albert J. R. , Freund Stefan M. V. , Barford David
Published: October 2022

In response to improper kinetochore-microtubule attachments in mitosis, the spindle assembly checkpoint (SAC) assembles the mitotic checkpoint complex (MCC) to inhibit the anaphase-promoting complex/cyclosome, thereby delaying entry into anaphase. The MCC comprises Mad2:Cdc20:BubR1:Bub3. Its assembly is catalysed by unattached kinetochores on a Mad1:Mad2 platform. Mad1-bound closed-Mad2 (C-Mad2) recruits open-Mad2 (O-Mad2) through self-dimerization. This interaction, combined with Mps1 kinase-mediated phosphorylation of Bub1 and Mad1, accelerates MCC assembly, in a process that requires O-Mad2 to C-Mad2 conversion and concomitant binding of Cdc20. How Mad1 phosphorylation catalyses MCC assembly is poorly understood. Here, we characterized Mps1 phosphorylation of Mad1 and obtained structural insights into a phosphorylation-specific Mad1:Cdc20 interaction. This interaction, together with the Mps1-phosphorylation dependent association of Bub1 and Mad1, generates a tripartite assembly of Bub1 and Cdc20 onto the C-terminal domain of Mad1 (Mad1CTD). We additionally identify flexibility of Mad1:Mad2 that suggests how the Cdc20:Mad1CTD interaction brings the Mad2-interacting motif (MIM) of Cdc20 near O-Mad2. Thus, Mps1-dependent formation of the MCC-assembly scaffold functions to position and orient Cdc20 MIM near O-Mad2, thereby catalysing formation of C-Mad2:Cdc20.
Monolithically integrated, broadband, high-efficiency silicon nitride-on-silicon waveguide photodetectors in a visible-light integrated photonics platform
Authors: Lin Yiding , Yong Zheng , Luo Xianshu , Azadeh Saeed Sharif , Mikkelsen Jared C. , Sharma Ankita , Chen Hong , Mak Jason C. C. , Lo Patrick Guo-Qiang , Sacher Wesley D. , Poon Joyce K. S.
Published: October 2022

Visible and near-infrared spectrum photonic integrated circuits are quickly becoming a key technology to address the scaling challenges in quantum information and biosensing. Thus far, integrated photonic platforms in this spectral range have lacked integrated photodetectors. Here, we report silicon nitride-on-silicon waveguide photodetectors that are monolithically integrated in a visible light photonic platform on silicon. Owing to a leaky-wave silicon nitride-on-silicon design, the devices achieved a high external quantum efficiency of >60% across a record wavelength span from λ ~ 400 nm to ~640 nm, an opto-electronic bandwidth up to 9 GHz, and an avalanche gain-bandwidth product up to 173 ± 30 GHz. As an example, a photodetector was integrated with a wavelength-tunable microring in a single chip for on-chip power monitoring.
A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin
Authors: Zhang Hongjiao , Li Zixin , Zhou Shuang , Li Shu-Ming , Ran Huomiao , Song Zili , Yu Tao , Yin Wen-Bing
Published: October 2022

Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using onep-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, we report a fungal non-ribosomal peptide synthetase -polyketide synthase (NRPS-PKS) hybrid FnsA for the naringenin formation. Feeding experiments with isotope-labelled precursors demonstrate that FnsA accepts not onlyp-coumaric acid (p-CA), but alsop-hydroxybenzoic acid (p-HBA) as starter units, with three or four malonyl-CoA molecules for elongation, respectively. In vitro assays and MS/MS analysis prove that bothp-CA andp-HBA are firstly activated by the adenylation domain of FnsA. Phylogenetic analysis reveals that the PKS portion of FnsA shares high sequence homology with type I PKSs. Refactoring the biosynthetic pathway in yeast with the involvement offnsAprovides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.
Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing
Authors: Miyatake Satoko , Koshimizu Eriko , Fujita Atsushi , Doi Hiroshi , Okubo Masaki , Wada Taishi , Hamanaka Kohei , Ueda Naohisa , Kishida Hitaru , Minase Gaku , Matsuno Atsuhiro , Kodaira Minori , Ogata Katsuhisa , Kato Rumiko , Sugiyama Atsuhiko , Sasaki Ayako , Miyama Takabumi , Satoh Mai , Uchiyama Yuri , Tsuchida Naomi , Hamanoue Haruka , Misawa Kazuharu , Hayasaka Kiyoshi , Sekijima Yoshiki , Adachi Hiroaki , Yoshida Kunihiro , Tanaka Fumiaki , Mizuguchi Takeshi , Matsumoto Naomichi
Published: October 2022

We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.
On the growth dynamics of the cyanobacterium Anabaena sp. PCC 7938 in Martian regolith
Authors: Ramalho Tiago P. , Chopin Guillaume , Salman Lina , Baumgartner Vincent , Heinicke Christiane , Verseux Cyprien
Published: October 2022

The sustainability of crewed infrastructures on Mars will depend on their abilities to produce consumables on site. These abilities may be supported by diazotrophic, rock-leaching cyanobacteria: from resources naturally available on Mars, they could feed downstream biological processes and lead to the production of oxygen, food, fuels, structural materials, pharmaceuticals and more. The relevance of such a system will be dictated largely by the efficiency of regolith utilization by cyanobacteria. We therefore describe the growth dynamics of Anabaena sp. PCC 7938 as a function of MGS-1 concentration (a simulant of a widespread type of Martian regolith), of perchlorate concentration, and of their combination. To help devise improvement strategies and predict dynamics in regolith of differing composition, we identify the limiting element in MGS-1 – phosphorus – and its concentration-dependent effect on growth. Finally, we show that, while maintaining cyanobacteria and regolith in a single compartment can make the design of cultivation processes challenging, preventing direct physical contact between cells and grains may reduce growth. Overall, we hope for the knowledge gained here to support both the design of cultivation hardware and the modeling of cyanobacterium growth within.
Single-mode quantum non-Gaussian light from warm atoms
Authors: Mika Jaromír , Lachman Lukáš , Lamich Tomáš , Filip Radim , Slodička Lukáš
Published: October 2022

The distributed quantum information processing and hybridization of quantum platforms raises increasing demands on the quality of light-matter interaction and realization of efficient quantum interfaces. This becomes particularly challenging for needed states possessing fundamental quantum non-Gaussian (QNG) aspects. They correspond to paramount resources in most potent applications of quantum technologies. We demonstrate the generation of light with provably QNG features from a warm atomic ensemble in a single-mode regime. The light is generated in a spontaneous four-wave mixing process in the presence of decoherence effects caused by a large atomic thermal motion. Despite its high sensitivity to any excess noise, direct observability of heralded QNG light could be achieved due to a combination of a fast resonant excitation, large spectral bandwidth, and a low absorption loss of resonant photons guaranteed by the source geometry.
Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice
Authors: Kienesberger Sabine , Cosic Amar , Kitsera Maksym , Raffl Sandra , Hiesinger Marlene , Leitner Eva , Halwachs Bettina , Gorkiewicz Gregor , Glabonjat Ronald A. , Raber Georg , Lembacher-Fadum Christian , Breinbauer Rolf , Schild Stefan , Zechner Ellen L.
Published: October 2022

Klebsiella spp. that secrete the DNA-alkylating enterotoxin tilimycin colonize the human intestinal tract. Numbers of toxigenic bacteria increase during antibiotic use, and the resulting accumulation of tilimycin in the intestinal lumen damages the epithelium via genetic instability and apoptosis. Here we examine the impact of this genotoxin on the gut ecosystem. 16S rRNA sequencing of faecal samples from mice colonized with Klebsiella oxytoca strains and mechanistic analyses show that tilimycin is a pro-mutagenic antibiotic affecting multiple phyla. Transient synthesis of tilimycin in the murine gut antagonized niche competitors, reduced microbial richness and altered taxonomic composition of the microbiota both during and following exposure. Moreover, tilimycin secretion increased rates of mutagenesis in co-resident opportunistic pathogens such as Klebsiella pneumoniae and Escherichia coli, as shown by de novo acquisition of antibiotic resistance. We conclude that tilimycin is a bacterial mutagen, and flares of genotoxic Klebsiella have the potential to drive the emergence of resistance, destabilize the gut microbiota and shape its evolutionary trajectory.
Cryo-EM structure of the SEA complex
Authors: Tafur Lucas , Hinterndorfer Kerstin , Gabus Caroline , Lamanna Chiara , Bergmann Ariane , Sadian Yashar , Hamdi Farzad , Kyrilis Fotis L. , Kastritis Panagiotis L. , Loewith Robbie
Published: October 2022

The SEA complex (SEAC) is a growth regulator that acts as a GTPase-activating protein (GAP) towards Gtr1, a Rag GTPase that relays nutrient status to the Target of Rapamycin Complex 1 (TORC1) in yeast1. Functionally, the SEAC has been divided into two subcomplexes: SEACIT, which has GAP activity and inhibits TORC1, and SEACAT, which regulates SEACIT2. This system is conserved in mammals: the GATOR complex, consisting of GATOR1 (SEACIT) and GATOR2 (SEACAT), transmits amino acid3 and glucose4 signals to mTORC1. Despite its importance, the structure of SEAC/GATOR, and thus molecular understanding of its function, is lacking. Here, we solve the cryo-EM structure of the native eight-subunit SEAC. The SEAC has a modular structure in which a COPII-like cage corresponding to SEACAT binds two flexible wings, which correspond to SEACIT. The wings are tethered to the core via Sea3, which forms part of both modules. The GAP mechanism of GATOR1 is conserved in SEACIT, and GAP activity is unaffected by SEACAT in vitro. In vivo, the wings are essential for recruitment of the SEAC to the vacuole, primarily via the EGO complex. Our results indicate that rather than being a direct inhibitor of SEACIT, SEACAT acts as a scaffold for the binding of TORC1 regulators.
Database of SARS-CoV-2 and coronaviruses kinetics relevant for assessing persistence in food processing plants
Authors: Luong Ngoc-Du Martin , Guillier Laurent , Martin-Latil Sandra , Batejat Christophe , Leclercq India , Druesne Christine , Sanaa Moez , Chaix Estelle
Published: October 2022

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), a virus causing severe acute respiratory disease in humans, emerged in late 2019. This respiratory virus can spread via aerosols, fomites, contaminated hands or surfaces as for other coronaviruses. Studying their persistence under different environmental conditions represents a key step for better understanding the virus transmission. This work aimed to present a reproducible procedure for collecting data of stability and inactivation kinetics from the scientific literature. The aim was to identify data useful for characterizing the persistence of viruses in the food production plants. As a result, a large dataset related to persistence on matrices or in liquid media under different environmental conditions is presented. This procedure, combining bibliographic survey, data digitalization techniques and predictive microbiological modelling, identified 65 research articles providing 455 coronaviruses kinetics. A ranking step as well as a technical validation with a Gage Repeatability & Reproducibility process were performed to check the quality of the kinetics. All data were deposited in public repositories for future uses by other researchers.
Histoarchitecture of the fibrillary matrix of human fetal posterior tibial tendons
Authors: Macedo Rodrigo Sousa , Teodoro Walcy Rosolia , Capellozzi Vera Luiza , Rosemberg Dov Lagus , Sposeto Rafael Barban , de Cesar Netto Cesar , Deland Jonathan T. , Maffulli Nicola , Ellis Scott J. , Godoy-Santos Alexandre Leme
Published: October 2022

Adult tendons are highly differentiated. In mature individuals, tendon healing after an injury occurs through fibrotic tissue formation. Understanding the intrinsic reparative properties of fetal tendons would help to understand the maturation tissue process and tendon tissue repair. The present study evaluated the evolution of histoarchitecture, cellularity and the distribution of collagens I, III and V in the posterior tibial tendon in human fetuses at different gestational ages. Morphological profiles were assessed in nine fresh spontaneously aborted fetuses (Group I: five fetuses aged between 22 and 28 weeks of gestation; Group II: four fetuses aged between 32 and 38 weeks of gestation), characterized by a combination of histology, fluorescence and immunohistochemistry. In Group I, the posterior tibial tendon showed statistically significant greater cellularity and presence of collagen III and V than in Group II tendon, which showed a predominance of collagenous I and a better organization of the extracellular matrix compared with Group I tendons. In addition, a statistically significant higher rate of CD90, a marker of mesenchymal cells, was found in Group I tendons. In fetuses with gestational age between 22 and 28 weeks, the posterior tibialis tendons showed a thin and disorganized fibrillar structure, with an increase in collagen III and V fibers and mesenchymal cells. In the posterior tibialis tendons of fetuses with gestational age between 32 and 38 weeks, the fibrillar structure was thicker with a statistically significant increase in type I collagen and decreased cellularity.
ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway
Authors: Liu Wen , Zhu Xiaoying , Tang Ling , Shen Na , Cheng Fanjun , Zou Ping , You Yong , Yuan Guolin , Li Qing , Zhu Xiaojian
Published: October 2022

Although tyrosine kinase inhibitors (TKIs) improve the prognosis of chronic myeloid leukemia (CML) patients, resistance to TKIs and residual leukemia stem cells (LSCs) inevitably become the bottleneck of cure. Therefore, we need to explore novel treatment strategies based on conventional treatment strategies. Our previous study found that CML cell senescence may be one of the main factors to achieve clinical cure of CML. Studies have shown that lipid metabolism plays a key role in cellular senescence. Here, we found that long-chain acyl-CoA synthetase 1 (ACSL1) was significantly up-regulated in senescent CML cells. Furthermore, we demonstrated that overexpression of ACSL1 induces senescence and inhibits cell growth in K562 cells by altering cell cycle progression, and enhances the proliferation-inhibiting effect of imatinib. Overexpression of ACSL1 enhances imatinib-induced tumorigenic decline in K562 cells in vivo. Knockdown of ACSL1 reverses imatinib-induced senescence in K562 cells. Mechanistically, overexpression of ACSL1 induced senescence in K562 cells via the SIRT1/p53/p21 axis. Collectively, our study showed that ACSL1 promotes imatinib-induced K562 cells senescence and tumor growth by regulating SIRT1/p53/p21 pathway. The ACSL1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CML and a new potential target for eradication of CML LSCs.
Transcriptome analysis and prediction of the metabolic state of stress-induced viable but non-culturable Bacillus subtilis cells
Authors: Morawska Luiza P. , Kuipers Oscar P.
Published: October 2022

Many bacteria adapt their physiology and enter the viable but non-culturable state to survive prolonged exposure to adverse environmental conditions. The VBNC cells maintain active metabolism, membrane integrity and gene transcription. However, they lose the ability to form colonies on a conventional culture media. Thus, standard colony counting methods cannot detect these alive but dormant cells. The Gram-positive bacterium Bacillus subtilis was found to enter the VBNC state when pre-exposed to osmotic stress and treated with a lethal dose of kanamycin. These cells reduced their metabolic activity, ceased growth and division and became kanamycin-tolerant. Interestingly, despite active metabolism, the majority of the kanamycin tolerant cells could not be revived on LB agar. In this study, we use a robust RNA-Seq technique to elucidate the differences in transcriptional profiles of B. subtilis VBNC cells. A comparative analysis of differently expressed genes and operons performed in this study indicates high similarities in transcriptional responses of VBNC and kanamycin-sensitive cells to antibiotic treatment. Moreover, this work reveals that VBNC cells strongly upregulate genes involved in proline uptake and catabolism, suggesting a putative role of proline as nutrient in VBNC cells.
MicroRNA-25-5p negatively regulates TXNIP expression and relieves inflammatory responses of brain induced by lipopolysaccharide
Authors: Wang Jiabing , Ye Zhinan , Chen Yuan , Qiao Xinyu , Jin Yong
Published: October 2022

Sepsis is one of the most common causes of death in patients suffering from severe infection or injury. Currently, a specific effective therapy remains to be established. In the present study, miR-25-5p, miR-105, miR-106b-5p, miR-154-3p, miR-20b-5p, miR-295-3p, miR-291-3p, miR-301b, miR-352, and miR-93-5p were predicted to target TXNIP mRNA from the databases of miRDB, Targetscan, and microT-CDS. The luciferase reporter assay confirmed that miR-25-5p negatively regulates TXNIP expression. The ELISA analyses and western blotting demonstrated that miR-25-5p downregulated the production of IL-1β, IL-6, IL-8, and TNF-α in lipopolysaccharide (LPS)-stimulated cells or rats, as well as the protein levels of TXNIP, NLRP3, and cleaved caspase-1. In addition, miR-25-5p increased the cell viability and decreased the apoptosis in LPS-stimulated CTX TNA2 cells and reduced the abnormal morphology of the brain in LPS-stimulated rats. Besides, miR-25-5p decreased the relative mean fluorescence intensity of DCF in LPS-stimulated CTX TNA2 cell, apoptosis, and protein levels of MnSOD and catalase in LPS-stimulated brains. These findings indicate that miR-25-5p downregulated LPS-induced inflammatory responses, reactive oxygen species production, and brain damage, suggesting that miR-25-5p is a candidate treatment for septic encephalopathy.
Feasibility of transthoracic esophagectomy with a next-generation surgical robot
Authors: Puntambekar Shailesh , Bharambe Suyog , Pawar Swapnil , Chitale Mihir , Panse Mangesh
Published: October 2022

Robot-assisted minimal access surgery (MAS), compared with conventional MAS, has shown a number of benefits across several therapeutic indications but its use for transthoracic esophagectomy (TTE) requires further evaluation. Here, we report the first-in-human series of major esophageal resections performed using a next-generation tele-operated robotic surgical system in a single center. Robot-assisted TTE was performed using the Versius Surgical System by a single surgeon to assess the robotic system’s ability to achieve tumor clearance (measured by R0 resection rates) whilst reducing anastomotic leakage rates. Intra- and post-operative outcomes such as median operative time, length of hospitalization, intra-operative blood loss, and the number of complications were also assessed. Fifty-seven patients underwent robot-assisted TTE between August 2019 and June 2021. All procedures were completed successfully with no unplanned conversions to alternative surgical methods. Estimated blood loss was minimal, and no adverse events, complications or deaths were reported. Our experience with the Versius Surgical System demonstrates its safe adoption and implementation for TTE.
Plant growth acceleration using a transparent Eu3+-painted UV-to-red conversion film
Authors: Shoji Sunao , Saito Hideyuki , Jitsuyama Yutaka , Tomita Kotono , Haoyang Qiang , Sakurai Yukiho , Okazaki Yuhei , Aikawa Kota , Konishi Yuki , Sasaki Kensei , Fushimi Koji , Kitagawa Yuichi , Suzuki Takashi , Hasegawa Yasuchika
Published: October 2022

The stimulation of photosynthesis is a strategy for achieving sustainable plant production. Red light is useful for plant growth because it is absorbed by chlorophyll pigments, which initiate natural photosynthetic processes. Ultraviolet (UV)-to-red wavelength-converting materials are promising candidates for eco-friendly plant cultures that do not require electric power. In this study, transparent films equipped with a UV-to-red wavelength-converting luminophore, the Eu3+ complex, were prepared on commercially available plastic films for plant growth experiments. The present Eu3+-based films absorb UV light and exhibit strong red luminescence under sunlight. Eu3+-painted films provide significant growth acceleration with size increment and biomass production for vegetal crops and trees in a northern region. The plants cultured with Eu3+-painted films had a 1.2-fold height and 1.4-fold total body biomass than those cultures without the Eu3+ luminophores. The present film can promote the plant production in fields of agriculture and forestry.
Hetastarch induced volume changes of starving adenoma and suggested mechanism of action
Authors: Jakabčin P. , Kello M. , Záň J. , Kolář J. , Uličný Jozef
Published: October 2022

Submucosal injection is often required step during endoscopic mucosal resection (EMR). In clinical practice we have observed that the EMR injection solution containing hetastarch (HES) lead to selective increase of the neoplasms volume, facilitating their resection. The aim of this study was to explore the possible mechanisms of such behaviour, which was not reported elsewhere. The HCT116 cell line of human colon cancer was exposed to the same EMR solution in vitro. The significant volume increase of HCT116 cells was observed, but only for starving cell culture, suggesting that the starving is essential for the neoplasms-specific volume change. We suggest, that for the iso-oncotic composition of the EMR submucosa injection solution the HES component is crucial, as it can be subject of the starch hydrolysis followed by facilitated transport of resulting monosaccharides from the submucosa into the neoplastic tissue.
The language of opinion change on social media under the lens of communicative action
Authors: Monti Corrado , Aiello Luca Maria , De Francisci Morales Gianmarco , Bonchi Francesco
Published: October 2022

Which messages are more effective at inducing a change of opinion in the listener? We approach this question within the frame of Habermas’ theory of communicative action, which posits that theillocutionary intentof the message (its pragmatic meaning) is the key. Thanks to recent advances in natural language processing, we are able to operationalize this theory by extracting the latent social dimensions of a message, namely archetypes of social intent of language, that come from social exchange theory. We identify key ingredients to opinion change by looking at more than 46k posts and more than 3.5M comments on Reddit’s , a debate forum where people try to change each other’s opinion and explicitly mark opinion-changing comments with a special flag calleddelta. Comments that express no intent are about 77% less likely to change the mind of the recipient, compared to comments that convey at least one social dimension. Among the various social dimensions, the ones that are most likely to produce an opinion change are knowledge, similarity, and trust, which resonates with Habermas’ theory of communicative action. We also find other new important dimensions, such as appeals to power or empathetic expressions of support. Finally, in line with theories of constructive conflict, yet contrary to the popular characterization of conflict as the bane of modern social media, our findings show that voicing conflict in the context of a structured public debate can promote integration, especially when it is used to counter another conflictive stance. By leveraging recent advances in natural language processing, our work provides an empirical framework for Habermas’ theory, finds concrete examples of its effects in the wild, and suggests its possible extension with a more faceted understanding of intent interpreted as social dimensions of language.
Bond-specific fragmentation of oligopeptides via electronic stopping of swift heavy ions in molecular films
Authors: Schneider P. , Keller P. , Schubert I. , Bender M. , Trautmann C. , Dürr M.
Published: October 2022

Highly bond-specific fragmentation of oligopeptides induced by swift heavy ion (SHI) irradiation was investigated by means of mass spectrometry. In pronounced contrast to measurements of samples irradiated with keV ions, oligopeptides which were exposed to 946 MeV Au ions show a high abundance of specific fragments. The highly bond-specific nature of SHI-induced fragmentation is attributed to electronic stopping as the most relevant energy loss mechanism for SHI in the oligopeptide samples in combination with the subsequent coupling between the excited electronic and the atomic subsystem. Fragmentation induced by SHI is observed to be further influenced by the structure of the oligopeptides, suggesting that electronic excitation and/or the electronic-vibrational coupling depend on the details of the molecular structure.
Paleomagnetic techniques can date speleothems with high concentrations of detrital material
Authors: Sánchez-Moreno Elisa M. , Font Eric , Pavón-Carrasco F. Javier , Dimuccio Luca A. , Hillaire-Marcel Claude , Ghaleb Bassam , Cunha Lúcio
Published: October 2022

The U-series dating of young and ‘dirty’ speleothems is challenging due to difficulties in assessing the isotopic composition of detrital contaminants and the low-abundance of 230Th generated in situ. Here we propose a new dating approach based on the comparison of a speleothem’s paleomagnetic directions to reference curves from global paleomagnetic reconstructions. This approach is demonstrated on a stalagmite collected from the Soprador do Carvalho cave in the Central Region of Portugal. A radioisotopic age model, built using four U-series ages and three 14C, suggests relatively steady carbonate precipitation from ~ 5760 BCE until ~ 1920 CE. Forty-five 6 mm-thick subsamples were analyzed using alternating field and thermal demagnetization protocols, providing well-defined, primary magnetic directions. An age model of the stalagmite was obtained by fitting its paleomagnetic record with the reference paleosecular variation curves obtained by previous paleo-reconstruction models, applying statistical bootstrapping analysis to define their best fit. The resulting age models fit closely with the radioisotopic age model but provide a significantly higher time resolution. We reach the same conclusion when applying this approach to another stalagmite from the Algarve region of Portugal. Our approach thus appears a promising alternative to date young speleothems with high detrital contents.
Viscosupplementation in the upper and lower compartments of the temporomandibular joint checked by ultrasonography in an ex vivo and in vivo study
Authors: Januzzi Eduardo , Cunha Thays Crosara Abrahão , Silva Graziella , Souza Beatriz Dulcinéia Mendes , Duarte Adriana Soares Bicalho , Zanini Marcella Rezende Serpa , Andrade Adriana Maria , Pedrosa Alexsander Ribeiro , Custódio Antônio Luís Neto , Castro Maurício Augusto Aquino
Published: October 2022

Viscosupplementation (VS) of the temporomandibular joint (TMJ) aims to treat temporomandibular dysfunction (TMD) by stimulating synovial cells to improve intracapsular lubrication. The purpose of the present study was to assess a VS protocol planned with the aid of cone-beam computed tomography (CBCT) and checked by ultrasonography (US). The study was carried out in 3 stages. The first was to check the correspondence between the proposed facial reference points and the osseous components of the joint by means of CBCT. In the second stage, the upper and lower compartments of 20 TMJs of fresh frozen cadavers were injected with coloured liquids, and the accuracy of the technique was confirmed by dissecting the anatomical specimens. The third stage consisted of VS in 10 patients (20 TMJs), with real-time verification of the location of the needle tip by means of ultrasonography. CBCT confirmed the correct locations of the marked points used in the proposed VS protocol. The dissections showed that 13 of the 14 injections effectively reached the upper and lower compartments. The location of the needle tip was effectively verified by ultrasonography, confirming the correct access to both compartments. The proposed protocol was effective for accessing the upper and lower compartments of the TMJ. The evaluated protocol proved to be accurate, safe and clinically reproducible means of VS in the upper and lower compartments of the TMJ.
Seasonal nearshore ocean acidification and deoxygenation in the Southern California Bight
Authors: Kekuewa Samuel A. H. , Courtney Travis A. , Cyronak Tyler , Andersson Andreas J.
Published: October 2022

The California Current System experiences seasonal ocean acidification and hypoxia (OAH) owing to wind-driven upwelling, but little is known about the intensity, frequency, and depth distribution of OAH in the shallow nearshore environment. Here we present observations of OAH and dissolved inorganic carbon and nutrient parameters based on monthly transects from March 2017 to September 2018 extending from the surf zone to the ~ 40 m depth contour in La Jolla, California. Biologically concerning OAH conditions were observed at depths as shallow as 10 m and as close as 700 m to the shoreline. Below 20 m depth, 8% of observations were undersaturated with respect to aragonite, 28% of observations had a pHTless than 7.85, and 19% of observations were below the sublethal oxygen threshold of 157 µmol kg−1. These observations raise important questions about the impacts of OAH on coastal organisms and ecosystems and how future intensified upwelling may exacerbate these conditions.