bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiometric calibration stability assessment of Sentinel-1B using point targets at Surat Basin, Australia
Authors: Badatala Sowkhya , Sharma Shweta , Tripathi Saurabh , Patel Parul R. , Mathur Aloke K.
Published: February 2022

The launch of the Sentinel-1B satellite in April 2016 completed the two-satellite synthetic aperture radar (SAR) constellation of the European Copernicus Sentinel-1 mission. The European Space Agency executed the calibration of this sensor during the commissioning phase and an independent calibration by the German Aerospace Center (DLR) in 2016. The calibration parameters must be monitored to assess the stability of the instrument. This study reports the temporal stability assessment of radiometric calibration and image quality parameters of Sentinel-1B SAR data using the corner reflector (CR) array, Surat Basin, Australia. Impulse response functions generated from the CRs in the satellite images were used to derive the image quality parameters. The average radar cross-section difference between estimated and theoretical values (38.40 dB m2) was 0.53 dB m2 for 1.5 m CRs, which is accordant with the absolute radiometric accuracy specified for the Sentinel-1 SAR system. Derived image quality parameters viz. the mean peak-to-side lobe ratio, mean integrated side lobe ratio, and spatial resolutions in the range and azimuth directions were found to be accordant with the specified value for the Sentinel-1 SAR system. The results indicate the excellent quality of the Sentinel-1B data.
Die Borderline-Persönlichkeitsstörung im somatischen Behandlungssetting
Authors: Euler Sebastian , Pape Eva , Matthes Oliver
Published: February 2022

Zusammenfassung. Die Borderline-Persönlichkeitsstörung ist eine häufige psychische Erkrankung, die durch die Kernsymptome Emotionsregulationsstörungen, Impulsivität, Identitätsstörung, interpersonelle Probleme und selbstverletzendes Verhalten gekennzeichnet ist. Diese Probleme manifestieren sich oft auch in der Beziehungsgestaltung zu Kontaktpersonen im Gesundheitssystem. Die Wahrnehmung als «schwierig» oder manipulativ begünstigt die Stigmatisierung und medizinische Unterversorgung der Betroffenen, obwohl die Komorbidität mit weiteren psychiatrischen und somatischen Erkrankungen eine umfassende, qualitativ hochwertige medizinische Versorgung erfordert. Mit einer evidenz-basierten, störungsspezifischen Psychotherapie ist die BPS gut behandelbar, während der Psychopharmakotherapie eine untergeordnete Rolle zur Krisenbewältigung zukommt. Durch ein besseres Verständnis der Erkrankung, die aktive Kommunikation mit anderen involvierten Behandlungsstellen und eine dialektische Beziehungsgestaltung, die Halt/Fürsorge und Grenzziehung gleichermassen vermittelt, kann die Versorgungsqualität der Patientinnen und Patienten nachhaltig verbessert werden.
CME: Fieber bei Reiserückkehrern nach Tropenaufenthalt
Authors: Ginten Christina , Eberhard-Kuhn Nadia , Braun Dominique , Kälin Marisa
Published: February 2022

Zusammenfassung. Aufgrund der Zunahme an Auslandsreisen in tropische Regionen nehmen Konsultationen von Patientinnen und Patienten mit Verdacht auf tropische Infektionskrankheiten in der Grundversorgung und Notaufnahme zu. Dabei gilt es potenziell lebensbedrohliche und übertragbare Infektionskrankheiten zu erkennen. Zudem bekommt die Beratung zur Prävention von Tropen-assoziierten Erkrankungen einen zunehmenden Stellenwert in der Praxis. Dieser Artikel gibt eine Übersicht der wichtigsten in den Tropen erworbenen Infektionen und bietet eine Hilfestellung für den klinischen Alltag.
Oriented Magnetite Inclusions in Plagioclase: Implications for the Anisotropy of Magnetic Remanence
Authors: Ageeva O. , Habler G. , Gilder S. A. , Schuster R. , Pertsev A. , Pilipenko O. , Bian G. , Abart R.
Published: February 2022

Micron to sub‐micron sized ferromagnetic inclusions in rock forming silicate minerals may give rise to particularly stable remanent magnetizations. When a population of inclusions have a preferred crystallographic or shape orientation in a rock, the recorded paleomagnetic direction and intensity may be biased by magnetic anisotropy. To better understand this effect, we investigated plagioclase grains from oceanic gabbro dredged from the Mid‐Atlantic Ridge at 11°–17°N. The plagioclase grains contain abundant needle and lath shaped magnetite inclusions aligned along specific directions of the plagioclase lattice. Electron back scatter diffraction and anisotropy of magnetic remanence measurements are used to correlate the orientation distribution of the magnetite inclusions in the host plagioclase that contains multiple twin types (Manebach, Carlsbad, Albite, and Pericline) with the bulk magnetic anisotropy of the inclusion‐host assembly. In non‐modified plagioclase, the anisotropy ellipsoid of magnetic remanence has oblate shapes that parallels the plagioclase (010) plane. It is suggested that recrystallization of magnetite inclusions during hydrothermal overprint shifts the relative abundance of the inclusions pertaining to the different orientation classes. We show that the maximum axis of the anisotropy ellipsoid of magnetic remanence parallels the plagioclase [001] direction, which in turn controls the recorded remanent magnetization direction. Our results are relevant for paleointensity and paleodirection determinations and for the interpretation of magnetic fabrics.
Along‐Dip Segmentation of the Slip Behavior and Rheology of the Copiapó Ridge Subducted in North‐Central Chile
Authors: Pastén‐Araya F. , Potin B. , Azúa K. , Sáez M. , Aden‐Antoniów F. , Ruiz S. , Cabrera L. , Ampuero J. P. , Nocquet J. M. , Rivera L. , Duputel Z.
Published: February 2022

We studied the along‐dip influence of the Copiapó ridge subduction in the Atacama region, North‐Central Chile by building a new seismicity catalog, including similar events and non‐volcanic tremors (NVTs). We also obtained a 3‐D tomographic model for P and S‐waves velocity (and the implied Vp/Vs ratio). We identify along‐dip segmentation involving four distinct segments: a locked seismogenic zone hosting ordinary seismicity and clusters of similar events; a transition zone with NVTs and low seismicity; an aseismic zone with slow‐slip events; and a deep zone with abundant intraslab seismicity. The velocity models show differences among these zones, with low velocity anomalies of Vp and Vs coinciding with aseismic slip zones, indicating the possible presence of fluids. Due to the spatial distribution along‐strike and along‐dip of the aseismic zones, we propose that these differences in seismogenic behavior are generated by subduction of the heterogeneous seamounts associated with the Copiapó ridge.
Volcanic Climate Warming Through Radiative and Dynamical Feedbacks of SO2 Emissions
Authors: Guzewich Scott D. , Oman Luke D. , Richardson Jacob A. , Whelley Patrick L. , Bastelberger Sandra T. , Young Kelsey E. , Bleacher Jacob E. , Fauchez Thomas J. , Kopparapu Ravi K.
Published: February 2022

Volcanic flood basalt eruptions have been linked to or are contemporaneous with major climate disruptions, ocean anoxic events, and mass extinctions throughout at least the last 400 M years of Earth's history. Previous studies and recent history have shown that volcanically‐driven climate cooling can occur through reflection of sunlight by H2SO4 aerosols, while longer‐term climate warming can occur via CO2 emissions. We use the Goddard Earth Observing System Chemistry‐Climate Model to simulate a 4‐year duration volcanic SO2 emission of the scale of the Wapshilla Ridge member of the Columbia River Basalt eruption. Brief cooling from H2SO4 aerosols is outweighed by dynamically and radiatively driven warming of the climate through a three orders of magnitude increase in stratospheric H2O vapor.
A Revised Adiabatic Temperature Profile for the Mantle
Authors: Katsura Tomoo
Published: February 2022

This study reevaluates the adiabatic temperature profile of the Earth's mantle. The global average temperature at the 410‐km discontinuity is estimated to be 1839 (38) K by comparing the globally averaged depths of the 410‐km discontinuity with the previously determined phase diagram of the olivine‐wadsleyite transition in the system (Mg,Fe)2SiO4 at two temperatures. The temperature at the 410‐km discontinuity is extrapolated to shallower and deeper regions using the adiabatic temperature gradient, which is estimated from the pressure‐volume‐temperature relations and heat capacities of the major mantle minerals, namely, olivine, wadselyite, ringwoodite, and bridgmanite. The experimental temperatures and pressures in the original studies used in these evaluations are recalculated using the recently proposed pressure correction on EMF of the W97Re3‐W75Re25 thermocouple. The uncertainties are evaluated by the Monte Carlo simulation. The temperatures on the adiabatic temperature profile are found to be 1646 (35), 1994 (40), 1960 (40), and 2587 (60) K, respectively, at a 50‐km depth, just above the 660‐km discontinuity, just below the 660‐km discontinuity, and at 2,800‐km depth. The lower mantle temperatures in the current estimation are lower than those given by Katsura et al. (2010), https://doi.org/10.1016/j.pepi.2010.07.001. The 50‐km depth temperature is slightly higher but generally agrees to that estimated from the melting of depleted peridotite.
A Landscape Evolution Modeling Approach for Predicting Three‐Dimensional Soil Organic Carbon Redistribution in Agricultural Landscapes
Authors: Kwang Jeffrey S. , Thaler Evan A. , Quirk Brendon J. , Quarrier Caroline L. , Larsen Isaac J.
Published: February 2022

Soil erosion diminishes agricultural productivity by driving the loss of soil organic carbon (SOC). The ability to predict SOC redistribution is important for guiding sustainable agricultural practices and determining the influence of soil erosion on the carbon cycle. Here, we develop a landscape evolution model that couples soil mixing and transport to predict soil loss and SOC patterns within agricultural fields. Our reduced complexity numerical model requires the specification of only two physical parameters: a plow mixing depth, Lp, and a hillslope diffusion coefficient, D. Using topography as an input, the model predicts spatial patterns of surficial SOC concentrations and complex 3D SOC pedostratigraphy. We use soil cores from native prairies to determine initial SOC‐depth relations and the spatial pattern of remote sensing‐derived SOC in adjacent agricultural fields to evaluate the model predictions. The model reproduces spatial patterns of soil loss comparable to those observed in satellite images. Our results indicate that the distribution of soil erosion and SOC in agricultural fields can be predicted using a simple geomorphic model where hillslope diffusion plays a dominant role. Such predictions can aid estimates of carbon burial and evaluate the potential for future soil loss in agricultural landscapes.
Modeling Concurrent Hydroclimatic Extremes With Parametric Multivariate Extreme Value Models
Authors: Sharma Shailza , Mujumdar P. P.
Published: February 2022

Estimating the dependence structure of concurrent extremes is a fundamental issue for accurate assessment of their occurrence probabilities. Identifying the extremal dependence behavior is also crucial for scientific understanding of interactions between the variables of a multidimensional environmental process. This study investigates the suitability of parametric multivariate extreme value models to correctly represent and estimate the dependence structure of concurrent extremes. Probabilistic aspects of multivariate extreme value theory with point process representation are discussed and illustrated with application to the concurrence of rainfall deficits, soil moisture deficits, and high temperatures. Application is concerned with the investigation of extremal behavior and risk assessment in Marathwada, a drought‐prone region of Maharashtra state, India. To characterize the multivariate extremes, marginal distributions are specified first and transformed into unit Fréchet margins. Standardized distributions are represented by a Poisson point process and coordinates of data points are transformed to pseudo‐polar coordinates to make the dependence form more explicit. The extremal dependence structure is described through angular densities on the unit simplex. Strong dependence is observed between soil moisture deficits and high temperatures, whereas rainfall deficits are mildly dependent on these two variables. Overall, a weak dependence is observed between the variables considered. Estimated extremal dependence is further used to compute probabilities of a few critical extreme combinations. Results demonstrate the ability of parametric multivariate models to characterize the complex dependence structure of concurrent extremes. These models can provide a powerful new perspective for appropriate statistical analysis of dependent hydroclimatic extremes in higher dimensions.
More Fires, More Problems
Authors: Beurteaux Danielle
Published: February 2022

Increasing incidents of wildfires in the Arctic are not only thawing permafrost but changing the entire underlying structure of the region.
Identification of cytotoxic T cells and their T cell receptor sequences targeting COVID-19 using MHC class I-binding peptides
Authors: Hikichi Tetsuro , Sakamoto Michiko , Harada Makiko , Saito Maki , Yamane Yuka , Tokumura Kimihisa , Nakamura Yusuke
Published: February 2022

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) was first reported in China in December 2019, various variants have been identified in different areas of the world such as United Kingdom (alpha), South Africa (beta and omicron), Brazil (gamma), and India (delta). Some of SARS-CoV-2 variants, each of which is characterized by a unique mutation(s) in spike protein, are concerned due to their high infectivity and the capability to escape from neutralizing antibodies elicited by vaccinations. To identify peptide epitopes that are derived from SARS-CoV-2 viral proteins and possibly induce CD8+ T cell immunity, we investigated SARS-CoV-2-derived peptides that are likely to bind to major histocompatibility complex (MHC) class I molecules. We identified a total of 15 peptides that bind to human leukocyte antigen (HLA)-A*24:02, HLA-A*02:01, or HLA-A*02:06, and possibly induce cytotoxic T lymphocytes (CTLs); thirteen of them corresponded to ORF1ab polyprotein, one peptide to spike protein and the remaining one to membrane glycoprotein. CD8+ T cells that recognize these peptides were detected in peripheral blood samples in three individuals recovered from COVID-19 as well as non-infected individuals. Since most of these peptides are commonly conserved among other coronaviruses including SARS-CoV and/or MERS-CoV, these might be useful to maintain T cell responses to coronaviruses that are pandemic at present and will become the future threat. We could define pairs of TRA and TRB sequences of nine CTL clones that recognize SARS-CoV-2-derived peptides. We might use these SARS-CoV-2-derived peptide-reactive TCR sequences for investigating the history of SARS-CoV-2 infection.
The projected impact of the COVID-19 lockdown on breast cancer deaths in England due to the cessation of population screening: a national estimation
Authors: Duffy Stephen W. , Seedat Farah , Kearins Olive , Press Mike , Walton Jackie , Myles Jonathan , Vulkan Daniel , Sharma Nisha , Mackie Anne
Published: February 2022

Background

Population breast screening services in England were suspended in March 2020 due to the COVID-19 pandemic. Here, we estimate the number of breast cancers whose detection may be delayed because of the suspension, and the potential impact on cancer deaths over 10 years.

Methods

We estimated the number and length of screening delays from observed NHS Breast Screening System data. We then estimated additional breast cancer deaths from three routes: asymptomatic tumours progressing to symptomatically diagnosed disease, invasive tumours which remain screen-detected but at a later date, and ductal carcinoma in situ (DCIS) progressing to invasive disease by detection. We took progression rates, prognostic characteristics, and survival rates from published sources.

Results

We estimated that 1,489,237 women had screening delayed by around 2–7 months between July 2020 and June 2021, leaving 745,277 outstanding screens. Depending on how quickly this backlog is cleared, around 2500–4100 cancers would shift from screen-detected to symptomatic cancers, resulting in 148–452 additional breast cancer deaths. There would be an additional 164–222 screen-detected tumour deaths, and 71–97 deaths from DCIS that progresses to invasive cancer.

Conclusions

An estimated 148–687 additional breast cancer deaths may occur as a result of the pandemic-related disruptions. The impact depends on how quickly screening services catch up with delays.
LncRNA FIRRE functions as a tumor promoter by interaction with PTBP1 to stabilize BECN1 mRNA and facilitate autophagy
Authors: Wang Yajie , Li Zhengyang , Xu Shizan , Li Wenjun , Chen Mengyun , Jiang Miao , Fan Xiaoming
Published: February 2022

Long non-coding RNAs (lncRNAs) play critical functions in various cancers. Firre intergenic repeating RNA element (FIRRE), a lncRNA located in the nucleus, was overexpressed in colorectal cancer (CRC). However, the detailed mechanism of FIRRE in CRC remains elusive. Results of RNA sequence and qPCR illustrated overexpression of FIRRE in CRC cell lines and tissues. The aberrant expression of FIRRE was correlated with the migration, invasion, and proliferation in cell lines. In accordance, it was also associated with lymphatic metastasis and distant metastasis in patients with CRC. FIRRE was identified to physically interact with Polypyrimidine tract-binding protein (PTBP1) by RNA pull-down and RNA immunoprecipitation (RIP). Overexpression of FIRRE induced the translocation of PTBP1 from nucleus to cytoplasm, which was displayed by immunofluorescence and western blot. In turn, delocalization of FIRRE from nucleus to cytoplasm is observed after the loss of PTBP1. The RNA-protein complex in the cytoplasm directly bound to BECN1 mRNA, and the binding site was at the 3' end of the mRNA. Cells with FIRRE and PTBP1 depletion alone or in combination were treated by Actinomycin D (ACD). Results of qPCR showed FIRRE stabilized BECN1 mRNA in a PTBP1-medieated manner. In addition, FIRRE contributed to autophagy activity. These findings indicate FIRRE acts as an oncogenic factor in CRC, which induces tumor development through stabilizing BECN1 mRNA and facilitating autophagy in a PTBP1-mediated manner.
Adenine overload induces ferroptosis in human primary proximal tubular epithelial cells
Authors: Khan Muhammad Ali , Nag Purba , Grivei Anca , Giuliani Kurt T. K. , Wang Xiangju , Diwan Vishal , Hoy Wendy , Healy Helen , Gobe Glenda , Kassianos Andrew J.
Published: February 2022

The pathogenesis of crystal nephropathy involves deposition of intratubular crystals, tubular obstruction and cell death. The deposition of 8-dihydroxyadenine (DHA) crystals within kidney tubules, for instance, is caused by a hereditary deficiency of adenine phosphoribosyl transferase in humans or adenine overload in preclinical models. However, the downstream pathobiological patterns of tubular cell attrition in adenine/DHA-induced nephropathy remain poorly understood. In this study, we investigated: (i) the modes of adenine-induced tubular cell death in an experimental rat model and in human primary proximal tubular epithelial cells (PTEC); and (ii) the therapeutic effect of the flavonoid baicalein as a novel cell death inhibitor. In a rat model of adenine diet-induced crystal nephropathy, significantly elevated levels of tubular iron deposition and lipid peroxidation (4-hydroxynonenal; 4-HNE) were detected. This phenotype is indicative of ferroptosis, a novel form of regulated necrosis. In cultures of human primary PTEC, adenine overload-induced significantly increased mitochondrial superoxide levels, mitochondrial depolarisation, DNA damage and necrotic cell death compared with untreated PTEC. Molecular interrogation of adenine-stimulated PTEC revealed a significant reduction in the lipid repair enzyme glutathione peroxidase 4 (GPX4) and the significant increase in 4-HNE compared with untreated PTEC, supporting the concept of ferroptotic cell death. Moreover, baicalein treatment inhibited ferroptosis in adenine-stimulated PTEC by selectively modulating the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) and thus, suppressing mitochondrial superoxide production and DNA damage. These data identify ferroptosis as the primary pattern of PTEC necrosis in adenine-induced nephropathy and establish baicalein as a potential therapeutic tool for the clinical management of ferroptosis-associated crystal nephropathies (e.g., DHA nephropathy, oxalate nephropathy).
Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation
Authors: Li Minle , Zhao Xue , Yong Hongmei , Xu Jian , Qu Pengfei , Qiao Shuxi , Hou Pingfu , Li Zhongwei , Chu Sufang , Zheng Junnian , Bai Jin
Published: February 2022

Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.
A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experiments
Authors: Zhao Boyang , Rao Yiyun , Leighow Scott , O’Brien Edward P. , Gilbert Luke , Pritchard Justin R.
Published: February 2022

A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, not synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.
Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells
Authors: Borriello Lucia , Coste Anouchka , Traub Brian , Sharma Ved P. , Karagiannis George S. , Lin Yu , Wang Yarong , Ye Xianjun , Duran Camille L. , Chen Xiaoming , Friedman Madeline , Sosa Maria Soledad , Sun Dan , Dalla Erica , Singh Deepak K. , Oktay Maja H. , Aguirre-Ghiso Julio A. , Condeelis John S. , Entenberg David
Published: February 2022

Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.
A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase
Authors: Shannon Ashleigh , Fattorini Véronique , Sama Bhawna , Selisko Barbara , Feracci Mikael , Falcou Camille , Gauffre Pierre , El Kazzi Priscila , Delpal Adrien , Decroly Etienne , Alvarez Karine , Eydoux Cécilia , Guillemot Jean-Claude , Moussa Adel , Good Steven S. , La Colla Paolo , Lin Kai , Sommadossi Jean-Pierre , Zhu Yingxiao , Yan Xiaodong , Shi Hui , Ferron François , Canard Bruno
Published: February 2022

The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). AT-527 recently entered phase III clinical trials for the treatment of COVID-19. Once in cells, AT-527 is converted into its triphosphate form, AT-9010, that presumably targets the viral RNA-dependent RNA polymerase (RdRp, nsp12), for incorporation into viral RNA. Here we report a 2.98 Å cryo-EM structure of the SARS-CoV-2 nsp12-nsp7-nsp82-RNA complex, showing AT-9010 bound at three sites of nsp12. In the RdRp active-site, one AT-9010 is incorporated at the 3′ end of the RNA product strand. Its modified ribose group (2′-fluoro, 2′-methyl) prevents correct alignment of the incoming NTP, in this case a second AT-9010, causing immediate termination of RNA synthesis. The third AT-9010 is bound to the N-terminal domain of nsp12 - known as the NiRAN. In contrast to native NTPs, AT-9010 is in a flipped orientation in the active-site, with its guanine base unexpectedly occupying a previously unnoticed cavity. AT-9010 outcompetes all native nucleotides for NiRAN binding, inhibiting its nucleotidyltransferase activity. The dual mechanism of action of AT-527 at both RdRp and NiRAN active sites represents a promising research avenue against COVID-19.
Delayed Antarctic sea-ice decline in high-resolution climate change simulations
Authors: Rackow Thomas , Danilov Sergey , Goessling Helge F. , Hellmer Hartmut H. , Sein Dmitry V. , Semmler Tido , Sidorenko Dmitry , Jung Thomas
Published: February 2022

Despite global warming and Arctic sea-ice loss, on average the Antarctic sea-ice extent has not declined since 1979 when satellite data became available. In contrast, climate model simulations tend to exhibit strong negative sea-ice trends for the same period. This Antarctic sea-ice paradox leads to low confidence in 21st-century sea-ice projections. Here we present multi-resolution climate change projections that account for Southern Ocean mesoscale eddies. The high-resolution configuration simulates stable September Antarctic sea-ice extent that is not projected to decline until the mid-21st century. We argue that one reason for this finding is a more realistic ocean circulation that increases the equatorward heat transport response to global warming. As a result, the ocean becomes more efficient at moderating the anthropogenic warming around Antarctica and hence at delaying sea-ice decline. Our study suggests that explicitly simulating Southern Ocean eddies is necessary for providing Antarctic sea-ice projections with higher confidence.
Gut microbiome of the largest living rodent harbors unprecedented enzymatic systems to degrade plant polysaccharides
Authors: Cabral Lucelia , Persinoti Gabriela F. , Paixão Douglas A. A. , Martins Marcele P. , Morais Mariana A. B. , Chinaglia Mariana , Domingues Mariane N. , Sforca Mauricio L. , Pirolla Renan A. S. , Generoso Wesley C. , Santos Clelton A. , Maciel Lucas F. , Terrapon Nicolas , Lombard Vincent , Henrissat Bernard , Murakami Mario T.
Published: February 2022

The largest living rodent, capybara, can efficiently depolymerize and utilize lignocellulosic biomass through microbial symbiotic mechanisms yet elusive. Herein, we elucidate the microbial community composition, enzymatic systems and metabolic pathways involved in the conversion of dietary fibers into short-chain fatty acids, a main energy source for the host. In this microbiota, the unconventional enzymatic machinery from Fibrobacteres seems to drive cellulose degradation, whereas a diverse set of carbohydrate-active enzymes from Bacteroidetes, organized in polysaccharide utilization loci, are accounted to tackle complex hemicelluloses typically found in gramineous and aquatic plants. Exploring the genetic potential of this community, we discover a glycoside hydrolase family of β-galactosidases (named as GH173), and a carbohydrate-binding module family (named as CBM89) involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to carbohydrate-active enzymes. Together, these results demonstrate how the capybara gut microbiota orchestrates the depolymerization and utilization of plant fibers, representing an untapped reservoir of enzymatic mechanisms to overcome the lignocellulose recalcitrance, a central challenge toward a sustainable and bio-based economy.
Microwave background temperature at a redshift of 6.34 from H2O absorption
Authors: Riechers Dominik A. , Weiss Axel , Walter Fabian , Carilli Christopher L. , Cox Pierre , Decarli Roberto , Neri Roberto
Published: February 2022

Distortions of the observed cosmic microwave background provide a direct measurement of the microwave background temperature at redshifts from 0 to 1 (refs. 1,2). Some additional background temperature estimates exist at redshifts from 1.8 to 3.3 based on molecular and atomic line-excitation temperatures in quasar absorption-line systems, but are model dependent3. No deviations from the expected (1 + z) scaling behaviour of the microwave background temperature have been seen4, but the measurements have not extended deeply into the matter-dominated era of the Universe at redshifts z > 3.3. Here we report observations of submillimetre line absorption from the water molecule against the cosmic microwave background at z = 6.34 in a massive starburst galaxy, corresponding to a lookback time of 12.8 billion years (ref. 5). Radiative pumping of the upper level of the ground-state ortho-H2O(110–101) line due to starburst activity in the dusty galaxy HFLS3 results in a cooling to below the redshifted microwave background temperature, after the transition is initially excited by the microwave background. This implies a microwave background temperature of 16.4–30.2 K (1σ range) at z = 6.34, which is consistent with a background temperature increase with redshift as expected from the standard ΛCDM cosmology4.
Crystallographic snapshots of a B12-dependent radical SAM methyltransferase
Authors: Fyfe Cameron D. , Bernardo-García Noelia , Fradale Laura , Grimaldi Stéphane , Guillot Alain , Brewee Clémence , Chavas Leonard M. G. , Legrand Pierre , Benjdia Alhosna , Berteau Olivier
Published: February 2022

By catalysing the microbial formation of methane, methyl-coenzyme M reductase has a central role in the global levels of this greenhouse gas1,2. The activity of methyl-coenzyme M reductase is profoundly affected by several unique post-translational modifications3–6, such as  a unique C-methylation reaction catalysed by methanogenesis marker protein 10 (Mmp10), a radical S-adenosyl-l-methionine (SAM) enzyme7,8. Here we report the spectroscopic investigation and atomic resolution structure of Mmp10 from Methanosarcina acetivorans, a unique B12 (cobalamin)-dependent radical SAM enzyme9. The structure of Mmp10 reveals a unique enzyme architecture with four metallic centres and critical structural features involved in the control of catalysis. In addition, the structure of the enzyme–substrate complex offers a glimpse into a B12-dependent radical SAM enzyme in a precatalytic state. By combining electron paramagnetic resonance spectroscopy, structural biology and biochemistry, our study illuminates the mechanism by which the emerging superfamily of B12-dependent radical SAM enzymes catalyse chemically challenging alkylation reactions and identifies distinctive active site rearrangements to provide a structural rationale for the dual use of the SAM cofactor for radical and nucleophilic chemistry.
Differentiation of intestinal tuberculosis and Crohn’s disease through an explainable machine learning method
Authors: Weng Futian , Meng Yu , Lu Fanggen , Wang Yuying , Wang Weiwei , Xu Long , Cheng Dongsheng , Zhu Jianping
Published: February 2022

Differentiation between Crohn’s disease and intestinal tuberculosis is difficult but crucial for medical decisions. This study aims to develop an effective framework to distinguish these two diseases through an explainable machine learning (ML) model. After feature selection, a total of nine variables are extracted, including intestinal surgery, abdominal, bloody stool, PPD, knot, ESAT-6, CFP-10, intestinal dilatation and comb sign. Besides, we compared the predictive performance of the ML methods with traditional statistical methods. This work also provides insights into the ML model’s outcome through the SHAP method for the first time. A cohort consisting of 200 patients’ data (CD = 160, ITB = 40) is used in training and validating models. Results illustrate that the XGBoost algorithm outperforms other classifiers in terms of area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision and Matthews correlation coefficient (MCC), yielding values of 0.891, 0.813, 0.969, 0.867 and 0.801 respectively. More importantly, the prediction outcomes of XGBoost can be effectively explained through the SHAP method. The proposed framework proves that the effectiveness of distinguishing CD from ITB through interpretable machine learning, which can obtain a global explanation but also an explanation for individual patients.
Bacterial distribution on the ocular surface of patients with primary Sjögren’s syndrome
Authors: Kim Yong Chan , Ham Baknoon , Kang Kui Dong , Yun Jun Myeong , Kwon Man Jae , Kim Hyun Seung , Hwang Hyung Bin
Published: February 2022

Many studies have shown that gut microbial dysbiosis is a major factor in the etiology of autoimmune diseases but none have suggested that the ocular surface (OS) microbiome is associated with Sjögren’s syndrome (SS). In this prospective study, we analyzed bacterial distribution on the OS in patients with primary SS. Among the 120 subjects included in this study, 48 patients (group A) had primary SS, whereas 72 subjects (group B) had dry eye symptoms that were unrelated to SS. We evaluated clinical dry eye parameters such as the OS disease index, ocular staining score (OSS), Schirmer’s I test, and tear break-up time (TBUT). Conjunctival swabs were used to analyze the microbial communities from the two groups. Bacterial 16S rRNA genes were sequenced using the Illumina MiSeq platform, and the data were analyzed using the QIIME 1.9.1 program. The Shannon index was significantly lower in group A than in group B microbiota (p < 0.05). An analysis of similarity using the Bray–Curtis distance method found no difference in beta-diversity between the two groups (p > 0.05). In group A, Actinobacteria at the phylum level and Corynebacteria at the genus level exhibited low abundance than group B, but the differences were not statistically significant (p > 0.05). SS apparently decreases the diversity of the OS microbial community. These observations may be related to the pathophysiology of SS and should be investigated in future studies.
Features of the cytoprotective effect of selenium nanoparticles on primary cortical neurons and astrocytes during oxygen–glucose deprivation and reoxygenation
Authors: Turovsky E. A. , Mal’tseva V. N. , Sarimov R. M. , Simakin A. V. , Gudkov S. V. , Plotnikov E. Y.
Published: February 2022

The study is aimed at elucidating the effect of selenium nanoparticles (SeNPs) on the death of cells in the primary culture of mouse cerebral cortex during oxygen and glucose deprivation (OGD). A primary cell culture of the cerebral cortex containing neurons and astrocytes was subjected to OGD and reoxygenation to simulate cerebral ischemia-like conditions in vitro. To evaluate the neuroprotective effect of SeNPs, cortical astrocytes and neurons were incubated for 24 h with SeNPs, and then subjected to 2-h OGD, followed by 24-h reoxygenation. Vitality tests, fluorescence microscopy, and real-time PCR have shown that incubation of primary cultured neurons and astrocytes with SeNPs at concentrations of 2.5–10 µg/ml under physiological conditions has its own characteristics depending on the type of cells (astrocytes or neurons) and leads to a dose-dependent increase in apoptosis. At low concentration SeNPs (0.5 µg/ml), on the contrary, almost completely suppressed the processes of basic necrosis and apoptosis. Both high (5 µg/ml) and low (0.5 µg/ml) concentrations of SeNPs, added for 24 h to the cells of cerebral cortex, led to an increase in the expression level of genes Bcl-2, Bcl-xL, Socs3, while the expression of Bax was suppressed. Incubation of the cells with 0.5 µg/ml SeNPs led to a decrease in the expression of SelK and SelT. On the contrary, 5 µg/ml SeNPs caused an increase in the expression of SelK, SelN, SelT, SelP. In the ischemic model, after OGD/R, there was a significant death of brain cells by the type of necrosis and apoptosis. OGD/R also led to an increase in mRNA expression of the Bax, SelK, SelN, and SelT genes and suppression of the Bcl-2, Bcl-xL, Socs3, SelP genes. Pre-incubation of cell cultures with 0.5 and 2.5 µg/ml SeNPs led to almost complete inhibition of OGD/R-induced necrosis and greatly reduced apoptosis. Simultaneously with these processes we observed suppression of caspase-3 activation. We hypothesize that the mechanisms of the protective action of SeNPs involve the activation of signaling cascades recruiting nuclear factors Nrf2 and SOCS3/STAT3, as well as the activation of adaptive pathways of ESR signaling of stress arising during OGD and involving selenoproteins SelK and SelT, proteins of the Bcl-2 family ultimately leading to inactivation of caspase-3 and inhibition of apoptosis. Thus, our results demonstrate that SeNPs can act as neuroprotective agents in the treatment of ischemic brain injuries.
Comparing Geant4 physics models for proton-induced dose deposition and radiolysis enhancement from a gold nanoparticle
Authors: Rajabpour Saeed , Saberi Hassan , Rasouli Javad , Jabbari Nasrollah
Published: February 2022

Gold nanoparticles (GNPs) are materials that make the tumor cells more radiosensitive when irradiated with ionizing radiation. The present study aimed to evaluate the impact of different physical interaction models on the dose calculations and radiochemical results around the GNP. By applying the Geant4 Monte Carlo (MC) toolkit, a single 50-nm GNP was simulated, which was immersed in a water phantom and irradiated with 5, 50, and 150 MeV proton beams. The present work assessed various parameters including the secondary electron spectra, secondary photon spectra, radial dose distribution (RDD), dose enhancement factor (DEF), and radiochemical yields around the GNP. The results with an acceptable statistical uncertainty of less than 1% indicated that low-energy electrons deriving from the ionization process formed a significant part of the total number of secondary particles generated in the presence of GNP; the Penelope model produced a larger number of these electrons by a factor of about 30%. Discrepancies of the secondary electron spectrum between Livermore and Penelope were more obvious at energies of less than 1 keV and reached the factor of about 30% at energies between 250 eV and 1 keV. The RDDs for Livermore and Penelope models were very similar with small variations within the first 6 nm from NP surface by a factor of 10%. In addition, neither the G-value nor the REF was affected by the choice of physical interaction models with the same energy cut-off. This work illustrated the similarity of the Livermore and Penelope models (within 15%) available in Geant4 for future simulation studies of GNP enhanced proton therapy with physical, physicochemical, and chemical mechanisms.
Impacts of rice-husk biochar on soil microbial biomass and agronomic performances of tomato (Solanum lycopersicum L.)
Authors: Adebajo Seun Owolabi , Oluwatobi Folasade , Akintokun Pius Olugbenga , Ojo Abidemi Esther , Akintokun Aderonke Kofoworola , Gbodope Ige Samuel
Published: February 2022

Tomato is beneficial to human health because it contains valuable vitamins such as vitamins A, C and several minerals. However, to meet up with the demands of the ever increasing population, there is need to improve tomato production. This research, thus, investigated the impact of rice-husk biochar on the agronomic performances of tomato plant and microbial biomass of carbon, nitrogen and phosphorus in different tomato growth stages. The rice husk biochar pyrolyzed at 350 °C was amended with soil at four different application rates: 0, 2.5, 5.0 and 7.5 t/ha. Physicochemical property of soil was conducted using Mid Infrared Reflectance Spectroscopy method. Impact of biochar on Microbial Biomass Carbon, Microbial Biomass Nitrogen and Microbial Biomass Phosphorous was conducted using fumigation extraction method and monitored at three functional stages. Biochar application appreciably increase the soil physicochemical properties such as pH, Ca, Na, H+, S, P, B, C, Zn and cation exchangeable capacity in comparison with the control. Biochar amended soil significantly enhanced tomato height, stem girth, leaf area, flowers, fruit yields and weight. Although, B3 recorded the lowest leaf area, it possessed the highest number of fruits and fruit weight of 3 and 40%, respectively. The ratio of Microbial biomass C:N:P for biochar amended soil at 7.5 t/ha (B3) was 302.30:18.81:11.75 µg/g, compared to control, which was 242.12:18.30:11.49 µg/g. This study revealed that biochar amendments significantly (p < 0.05) increased the yields and microbial biomass of tomato plants. Conclusively, the application of rice-husk biochar (7.5 t/ha) to soil is considered as a suitable approach to improve tomato growth and yield.
Influence of misorientation angle and local dislocation density on β-phase distribution in Al 5xxx alloys
Authors: Desai Choundraj Jahnavi , Kacher Josh
Published: February 2022

Al–Mg alloys undergo sensitization when exposed to elevated temperatures, making them susceptible to intergranular corrosion and stress corrosion cracking. Most of the existing research on microstructure effects on sensitization is centered on the effect of intrinsic grain boundary characteristics such as misorientation angle and coincident site lattice (CSL) values. Very few studies have systematically investigated the influence of extrinsic characteristics such as dislocation density. In this paper, the influence of local microstructure characteristics on the sensitization susceptibility of AA5456 was investigated using in situ optical microscopy corrosion experiments and electron back scattering diffraction analysis. The results show a clear trend between the local geometrically necessary dislocation (GND) density and β phase precipitation, with higher GND densities correlating with higher rates sensitized boundaries. This trend held true even for low angle grain boundaries. These results demonstrate the importance of considering factors beyond grain boundary characteristics in determining susceptibility to sensitization.
Four-wave-cooling to the single phonon level in Kerr optomechanics
Authors: Bothner Daniel , Rodrigues Ines C. , Steele Gary A.
Published: February 2022

Cavity optomechanics has achieved groundbreaking control and detection of mechanical oscillators, based on their coupling to linear electromagnetic modes. Recently, however, there is increasing interest in cavity nonlinearities as resource in radiation-pressure interacting systems. Here, we present a flux-mediated optomechanical device combining a nonlinear superconducting quantum interference cavity with a mechanical nanobeam. We demonstrate how the Kerr nonlinearity of the circuit can be used to enhance the device performance by suppressing cavity frequency noise, and for a counter-intuitive sideband-cooling scheme based on intracavity four-wave-mixing. With a large single-photon coupling rate of up to g0 = 2π ⋅ 3.6 kHz and a high mechanical quality factor Qm ≈ 4 ⋅ 105, we achieve an effective four-wave cooperativity of $${{{{{{{{\mathcal{C}}}}}}}}}_{{{{{{{{\rm{fw}}}}}}}}}\, > \, 100$$

C

fw

>

100
and demonstrate four-wave cooling of the mechanical oscillator close to its quantum groundstate. Our results advance the recently developed platform of flux-mediated optomechanics and demonstrate how cavity Kerr nonlinearities can be utilized in cavity optomechanics.
Feed microbiome: confounding factor affecting fish gut microbiome studies
Authors: Karlsen Christian , Tzimorotas Dimitrios , Robertsen Espen Mikal , Kirste Katrine Hånes , Bogevik André Sture , Rud Ida
Published: February 2022

There is an increasing interest in the impact of feed on the fish gut microbiome. Most of the studies are based on sequencing the bacterial housekeeping gene 16S rRNA from extracted total DNA, including resident and non-resident live bacteria as well as dead bacteria. It has not been a common practice to include the feed as control, although it contains various nutritious ingredients that microorganisms can use before or after feed preparation. Thus, study designs using digesta as a proxy for the intestinal microbiome raise the concern that composition of the gut microbiome might be biased by carry-over of microbial DNA from the feed itself. Here we report analysis of 15 feeds and representative intestinal digesta of Atlantic salmon (Salmo salar) from five independent case studies. This allowed us to identify “feed microbiomes” that were microbially diverse and shared taxa with digesta microbiomes. Digesta-specific microbiomes were identified, though they were mainly enriched by a few taxa, such as Mycoplasma and Ruminococcaceae. Overall, findings are consistent with a model wherein gut microbial profiles are to a different degree influenced by bacterial DNA present in the feed itself through a “feed microbiome” carry-over effect.
Investigation of metformin hydrochloride–bovine serum albumin interaction by narrow-bore capillary zone electrophoresis
Authors: Wang Lijuan , Zhao Lei , Zhang Wenmei , Wu Yuanyuan , Liang Yingqi , Guo Guangsheng , Wang Xiayan
Published: February 2022

A narrow-bore capillary zone electrophoresis (ID = 2 μm) method was developed to study the metformin hydrochloride–bovine serum albumin interaction.
An array-based nanosensor for detecting cellular responses in macrophages induced by femtomolar levels of pesticides
Authors: Jiang Mingdi , Chattopadhyay Aritra Nath , Geng Yingying , Rotello Vincent M.
Published: February 2022

Subtle phenotypic changes of macrophages under exposure to pesticides at the femtomolar concentration.
Hierarchy of relaxation times in supramolecular polymer model networks
Authors: Koziol Martha Franziska , Nguyen Phuong Loan , Gallo Shannon , Olsen Bradley D. , Seiffert Sebastian
Published: February 2022

A multitude of synergistic experimental techniques are used to investigate the hierarchy of relaxation modes coming along with the formation of a supramolecular polymer network.
Understanding excited state properties of host materials in OLEDs: simulation of absorption spectrum of amorphous 4,4-bis(carbazol-9-yl)-2,2-biphenyl (CBP)
Authors: Inanlou Samaneh , Cortés-Mejía Rodrigo , Özdemir Ali Deniz , Höfener Sebastian , Klopper Wim , Wenzel Wolfgang , Xie Weiwei , Elstner Marcus
Published: February 2022

4,4-Bis(carbazol-9-yl)-2,2-biphenyl (CBP) is widely used as a host material in phosphorescent organic light-emitting diodes (PhOLEDs).