bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic nutritional index as indicator of immune nutritional	status of patients with COVID-19
Authors: Ekinci Iskender , Uzun Hafize , Utku Irem Kirac , Ozkan Hanise , Buyukkaba Mitat , Cinar Ahmet , Akarsu Murat , Kumbasar Abdulbaki , Tabak Omur
Published: September 2021

Abstract. Purpose: This study aimed to investigate the effect of the nutritional status, as assessed by the prognostic nutritional index (PNI) on the disease prognosis of patients with COVID-19. Methods: This retrospective study included 282 patients with COVID-19. The PNI score of all patients, 147 of whom were male, with a mean age of 56.4±15.3 years, was calculated. According to the PNI score, the patients with normal and mild malnutrition constituted group-1 (n=159) and the patients with moderate-to-severe and serious malnutrition constituted group-2 (n=123). Results: The PNI score was correlated with age (r=−0.146, p=0.014); oxygen saturation (r=0.190, p=0.001); heart rate (r=−0.117, p=0.05); hospitalization duration (r=−0.266, p<0.001); white blood cells (r=0.156, p=0.009); hemoglobin (r=0.307, p<0.001); C-reactive protein (CRP) (r=−0.346, p<0.001); creatinine (r=−0.184, p=0.002); D-dimer (r=−0.304, p<0.001); ferritin (r=−0.283, p<0.001); procalcitonin (r=−0.287, p<0.001); the confusion, urea, respiratory rate, blood pressure, and age ≥65 years score (r=−0.217, p<0.001); and the quick sequential organ failure assessment score (r=−0.261, p<0.001) in patients with COVID-19. Mortality was significantly higher in Group 2 (p<0.001). Survival was significantly higher if PNI score was >41.2 (p<0.001, sensitivity: 78.7% and specificity: 84.2%). In multivariate regression analysis, among various other parameters, only PNI score and oxygen saturation had a significant effect on the disease course (p=0.02 and p=0.045, respectively). Conclusion: PNI, calculated from the serum albumin concentration and total lymphocyte count, is a simple and objective indicator that assesses the immune nutritional status of patients with COVID-19. The presence of malnutrition has a high predictive value in predicting the severity of COVID-19. Our data suggest that the PNI might be useful for risk stratification of patients with COVID-19 in clinical practice.
Numerical Weather Prediction Ocean Calibration for the Chinese‐French Oceanography Satellite Wind Scatterometer and Wind Retrieval Evaluation
Authors: Li Zhen , Stoffelen Ad , Verhoef Anton , Verspeek Jeroen
Published: September 2021

The rotating fan‐beam architecture wind scatterometer Chinese‐French Oceanography Satellite (CSCAT) onboard the Chinese‐French Oceanography Satellite leads to varying geometries and varying wind retrieval performance across the swath. To assess this, the wind vector cells (WVCs) are classified into three groups: outer, sweet, and nadir. The sweet swath WVCs contain the most diverse geometries, which give the best wind retrieval performance, whereas on the opposite the outer swath WVCs have the least diverse geometries, which makes the wind retrieval and ambiguity removal more challenging. NWP Ocean Calibration (NOC) is used to calibrate the radar backscatter prior to the wind inversion. It computes the difference between measured backscatter and simulated backscatter from collocated NWP winds through the geophysical model function. The difference is applied as a correction. An improved NOC method, NOC as a function of incidence angle and azimuth angle (NOCant) is introduced, which takes the orientation of the antenna into account. This method is compared with the widely used NOC as a function of incidence angle only (NOCinc). It shows a better fit with the geophysical model function, except for the outer swath WVCs which have limited geometry diversity. It also corrects the asymmetric wind direction bias distribution across the swath and reduced the nadir swath relative wind direction bias which is caused by the poor azimuth diversity. In conclusion, the rotating fan‐beam architecture of CSCAT leads to unique and varying data characteristics across the swath. Overall, the performance of the proposed NOCant correction is better than NOCinc and improves the wind statistics.
Source Imaging With a Multi‐Array Local Back‐Projection and Its Application to the 2019Mw6.4 andMw7.1 Ridgecrest Earthquakes
Authors: Xie Y. , Bao H. , Meng L.
Published: September 2021

This study aims to improve the multi‐array local back‐projection (MLBP) approach and to apply it to the 2019Mw6.4 andMw7.1 Ridgecrest, California earthquakes to resolve more details about their kinematic process, with the dense seismic network in California. Compared with teleseismic BPs, seismic array processing with stations located at local to regional distances images earthquake rupture process more quickly with higher resolution. To increase the objectivity of stations selection criteria and to be prepared for future real‐time BP implementations, we improve MLBP with an automatic procedure to group stations based on waveform coherence. We also apply empirical aftershock calibrations to account for the 3D path effect. Our MLBP highlights the rupture complexity in a multi‐fault system. TheMw6.4 quake initiates on a 5‐km‐long NW‐trending segment, then ruptures the primary SW‐trending fault at the speed of ∼1.3 km/s. TheMw7.1 quake ruptures bilaterally for 10 and 22 km, on the NW and SE portion of the fault, respectively, at the speed of 1–1.6 km/s. The rupture paths agree with aftershock distributions and surface rupture estimated from satellite imagery. The slow rupture propagation may be driven by the low structural maturity of the fault. This case study demonstrates the effectiveness of MLBP for earthquake source imaging and rapid hazard assessment.
The Assimilation of Temperature and Salinity Profile Observations for Forecasting the River–Estuary–Shelf Waters
Authors: Liu Ye , Xie Jiping , Liu Zhiqiang , Gan Jianping , Zhu Jiang
Published: September 2021

Current down‐scaling numerical modeling system around Hong Kong achieved a considerable prediction skill for the estuarine–shelf circulation off the Pearl River Estuary without data assimilation (DA). In order to further improve the reliability of this modeling system, the cost‐effective Ensemble optimal interpolation approach is implemented to test the potential benefits from assimilating the cruise temperature and salinity (T/S) profiles to reproduce the variable coast waters. Regarding assimilation parameters (e.g., assimilation window, observation spatiotemporal scales, and ensemble composition), four parallel experiments are conducted in summer 2015. Against the assimilated T/S profiles, the vertical structures of the analyzed T/S are improved by the DA, although the waters experience strong mixing on the shelf. Compared with the run without DA, the root mean square errors of the predicted T/S are generally reduced by 9.8%–23.5% and 4.2%–14.0% in the assimilation runs. The results also show the salinity stratification is improved in the shelf by the assimilation of T/S profiles, although the improvement is sensitive to the selected ensemble and the assimilation window. Further, we investigate the impact of the temporal scales of the river‐estuary‐shelf (RES) waters on the assimilation results by the sampling of the model‐state ensemble. The water exchanges between the estuary and the shelf are also better captured through this assimilation. The assimilation impact analysis shows that DA has advantages in reproducing the distribution of water masses of the RES waters, although the quality of the reproduced water mass distribution is related to the adopted sample ensemble in DA.
Evaluation of Site Errors in LLS Magnetic Direction Finding Caused by Large Hills Using the 3D‐FDTD Technique
Authors: Kohlmann Hannes , Schulz Wolfgang , Rachidi Farhad
Published: September 2021

Angle and amplitude estimation errors in magnetic direction finding, called site errors, are important sensor‐specific errors in lightning location systems (LLS). They are known to be caused by nearby cables and overhead lines due to induced currents. Due to the reflection and diffraction of electromagnetic waves, hills and mountains are also expected to generate these effects. In this paper, numerical computations applying the finite‐difference time‐domain (FDTD) method are performed to analyze the impact of hills or mountains on the angle and amplitude estimation of LLS sensors for typical first and subsequent return strokes (RS). The influence of hill size, the distance of sensors to the hill, ground parameters, and sensor bandwidth, are evaluated. The results show that on top of low ridges of only 125 m elevation, up to ±10° angle site error and +50% amplitude site error occur. A key finding is that due to field attenuation caused by lossy ground and sensor bandwidth limitations, there is practically no difference in the angle site errors for first and subsequent RS. For two sensors, the average site errors obtained from real sensor measurements are compared to results from 3D‐FDTD simulations, modeling the real terrain based on a digital elevation model. The simulation results are in good agreement with the observed, average angle site errors.
Household CH4 and N2O Footprints of Major Economies
Authors: Yan Caihui , Han Mengyao , Liu Ying , Zhang Bo
Published: September 2021

Reducing CH4 and N2O emissions plays an essential role in tackling global warming. Most previous studies focused on the direct CH4 and N2O emissions of an economy, while ignoring the CH4 and N2O emissions induced by household consumption in the final consumption of an economy. This study analyzed household CH4 and N2O footprints of the major economies and identified the decoupling and inequality of household CH4 and N2O emissions based on the multi‐regional input‐output analysis and structural path analysis from 1995 to 2014. Results demonstrated that global household CH4 and N2O emissions increased by 8.4% in 2014 compared to 1995. Developing economies such as China, Brazil, India, and Indonesia witnessed a rapid growth of household CH4 and N2O emissions, but the opposite could be observed in developed economies such as Germany, Japan, the UK, and the US. A large amount of CH4 and N2O emissions related to household consumption were transferred from developed economies to developing economies. In terms of the relationship between economic development and household CH4 and N2O emissions, the US, the UK, and Japan showed a strong decoupling status in 2014, while China and Indonesia showed a weak decoupling status. Meanwhile, the household emission inequality in developing economies was higher than that in developed economies. By exploring the relationship between economy and household CH4 and N2O emissions, it is helpful to assist developed and developing economies to adopt household CH4 and N2O emission reduction policies in line with their economic development stages.
Preservation and Destruction of Holocene Marine Terraces: The Effects of Episodic Versus Gradual Relative Sea Level Change
Authors: Matsumoto Hironori , Dickson Mark E. , Kench Paul S.
Published: September 2021

Holocene marine terraces occur globally and record information about the timing and magnitude of past coseismic events. Staircased terraces develop through repetitive coseismic uplift of shore platforms, but are also subject to destruction from subsequent wave erosion and rock weathering. In this study we calibrate a rock coast evolution model using terrace field data from Mahia Peninsula, New Zealand, and use it to investigate how relative sea level (RSL) change influences Holocene terrace development. Analyses of 10,002 simulations reveal time periods of extremely rapid terrace creation and destruction as a result of shore platform development processes that are modulated both by episodic and gradual RSL change scenarios. Subtle differences in these scenarios give rise to completely different terrace sequences, even if coseismic event timing is held constant. Improved interpretation of Holocene terrace sequences require higher resolution paleo RSL data and chronological data on shore platform development.
Quantifying Contributions of Magnetic Inclusions Within Silicates to Marine Sediments: A Dissolution Approach to Isolating Volcanic Signals for Improved Paleoenvironmental Reconstruction
Authors: Jiang X. D. , Zhao X. Y. , Zhao X. , Jiang Z. X. , Chou Y. M. , Zhang T. W. , Yang X. Q. , Liu Q. S.
Published: September 2021

Silicate‐hosted magnetic inclusions are a widespread fine grained magnetic component in marine sediments. However, their paleomagnetic and paleoenvironmental significance remains elusive as they are often overshadowed by unprotected detrital and biogenic magnetic components. We developed a protocol to extract silicate inclusions from sediments sampled from the central Pacific and the Okhotsk Sea. Our results show that the threshold condition (hydrochloric acid 10 mol/L with a reaction time of 24 h) can efficiently remove biogenic and unprotected magnetic phases and preserve silicate hosted magnetic inclusions that manifest a wide coercivity spectrum ranging between 10 and 300 mT with a median coercivity of ∼100 mT based on systematic rock magnetic analyses. This approach was applied to the Okhotsk Sea sediments, whose magnetic phases are dominantly derived from surrounding volcanic formations, spanning the last interglacial period. The residues after dissolution present a similar temporal variation compared to the bulk magnetic signal despite significant drops in amplitude. This suggests that the preserved signals of silicate inclusions can qualitatively represent the volcanic component. We suggest that when applied to sediments with complex magnetic components, this approach has the potential to extract volcanic components for paleoenvironmental reconstructions.
Soil Carbon Dioxide Flux Partitioning in a Calcareous Watershed With Agricultural Impacts
Authors: Hodges Caitlin , Brantley Susan L. , Sharifironizi Melika , Forsythe Brandon , Tang Qicheng , Carpenter Nathan , Kaye Jason
Published: September 2021

Predicting the partitioning between aqueous and gaseous C across landscapes is difficult because many factors interact to control carbon dioxide (CO2) concentrations and removal as dissolved inorganic carbon (DIC). For example, carbonate minerals buffer soil pH and allow CO2 dissolution in porewaters, but nitrification of fertilizers may decrease pH so that carbonate weathering results in a gaseous CO2 efflux. Here, we investigate CO2 partitioning in an agricultural, first‐order, mixed‐lithology humid, temperate watershed. We quantified soil mineralogy and measured porewater chemistry, soil moisture, and soil pCO2 and pO2 as a function of depth at three hillslope positions. Variation of soil moisture along the hillslope was the dominant control on the concentration of soil CO2, but mineralogy acted as a secondary control on the partitioning of CO2 between gaseous and aqueous phases. Regression slopes of pCO2 versus pO2 in the carbonate‐bearing soils indicate a deficit of aerobically respired CO2 relative to O2 (p < 0.05). Additionally, nitrification of upslope fertilizers did not lower soil pH and therefore did not cause a gaseous CO2 flux from carbonate weathering. We concluded that in the calcareous soils, up to 43% of respired C potentially dissolves and drains from the soil rather than diffusing out to the atmosphere. To explore the possible implications of the reactions we evaluated, we used databases of carbonate minerals and land uses to map types of soil degassing behaviors. Based on our maps, the partitioning of respired soil CO2 to the aqueous phase could be important in estimating ecosystem C budgets and models.
Enhancing Understanding of the Hydrological Cycle via Pairing of Process‐Oriented and Isotope Ratio Tracers
Authors: Fiorella Richard P. , Siler Nicholas , Nusbaumer Jesse , Noone David C.
Published: September 2021

The hydrologic cycle couples the Earth's energy and carbon budgets through evaporation, moisture transport, and precipitation. Despite a wealth of observations and models, fundamental limitations remain in our capacity to deduce even the most basic properties of the hydrological cycle, including the spatial pattern of the residence time (RT) of water in the atmosphere and the mean distance traveled from evaporation sources to precipitation sinks. Meanwhile, geochemical tracers such as stable water isotope ratios provide a tool to probe hydrological processes, yet their interpretation remains equivocal despite several decades of use. As a result, there is a need for new mechanistic tools that link variations in water isotope ratios to underlying hydrological processes. Here we present a new suite of “process‐oriented tags,” which we use to explicitly trace hydrological processes within the isotopically enabled Community Atmosphere Model, version 6 (iCAM6). Using these tags, we test the hypotheses that precipitation isotope ratios respond to parcel rainout, variations in atmospheric RT, and preserve information regarding meteorological conditions during evaporation. We present results for a historical simulation from 1980 to 2004, forced with winds from the ERA5 reanalysis. We find strong evidence that precipitation isotope ratios record information about atmospheric rainout and meteorological conditions during evaporation, but little evidence that precipitation isotope ratios vary with water vapor RT. These new tracer methods will enable more robust linkages between observations of isotope ratios in the modern hydrologic cycle or proxies of past terrestrial environments and the environmental processes underlying these observations.
Prefrontal contributions to the stability and variability of thought and conscious experience
Authors: Zamani Andre , Carhart-Harris Robin , Christoff Kalina
Published: September 2021

The human prefrontal cortex is a structurally and functionally heterogenous brain region, including multiple subregions that have been linked to different large-scale brain networks. It contributes to a broad range of mental phenomena, from goal-directed thought and executive functions to mind-wandering and psychedelic experience. Here we review what is known about the functions of different prefrontal subregions and their affiliations with large-scale brain networks to examine how they may differentially contribute to the diversity of mental phenomena associated with prefrontal function. An important dimension that distinguishes across different kinds of conscious experience is the stability or variability of mental states across time. This dimension is a central feature of two recently introduced theoretical frameworks—the dynamic framework of thought (DFT) and the relaxed beliefs under psychedelics (REBUS) model—that treat neurocognitive dynamics as central to understanding and distinguishing between different mental phenomena. Here, we bring these two frameworks together to provide a synthesis of how prefrontal subregions may differentially contribute to the stability and variability of thought and conscious experience. We close by considering future directions for this work.
Genetic and epigenetic basis of hepatoblastoma diversity
Authors: Nagae Genta , Yamamoto Shogo , Fujita Masashi , Fujita Takanori , Nonaka Aya , Umeda Takayoshi , Fukuda Shiro , Tatsuno Kenji , Maejima Kazuhiro , Hayashi Akimasa , Kurihara Sho , Kojima Masato , Hishiki Tomoro , Watanabe Kenichiro , Ida Kohmei , Yano Michihiro , Hiyama Yoko , Tanaka Yukichi , Inoue Takeshi , Ueda Hiroki , Nakagawa Hidewaki , Aburatani Hiroyuki , Hiyama Eiso
Published: September 2021

Hepatoblastoma (HB) is the most common pediatric liver malignancy; however, hereditary predisposition and acquired molecular aberrations related to HB clinicopathological diversity are not well understood. Here, we perform an integrative genomic profiling of 163 pediatric liver tumors (154 HBs and nine hepatocellular carcinomas) based on the data acquired from a cohort study (JPLT-2). The total number of somatic mutations is precious low (0.52/Mb on exonic regions) but correlated with age at diagnosis. Telomerase reverse transcriptase (TERT)promoter mutations are prevalent in the tween HBs, selective in the transitional liver cell tumor (TLCT, > 8 years old). DNA methylation profiling reveals that classical HBs are characterized by the specific hypomethylated enhancers, which are enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. Prolonged upregulation of ASCL2, as well as fetal-liver-like methylation patterns ofIGF2promoters, suggests their “cell of origin” derived from the premature hepatoblast, similar to intestinal epithelial cells, which are highly proliferative. Systematic molecular profiling of HB is a promising approach for understanding the epigenetic drivers of hepatoblast carcinogenesis and deriving clues for risk stratification.
Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines
Authors: Kuseyri Hübschmann Oya , Horvath Gabriella , Cortès-Saladelafont Elisenda , Yıldız Yılmaz , Mastrangelo Mario , Pons Roser , Friedman Jennifer , Mercimek-Andrews Saadet , Wong Suet-Na , Pearson Toni S. , Zafeiriou Dimitrios I. , Kulhánek Jan , Kurian Manju A. , López-Laso Eduardo , Oppebøen Mari , Kılavuz Sebile , Wassenberg Tessa , Goez Helly , Scholl-Bürgi Sabine , Porta Francesco , Honzík Tomáš , Santer René , Burlina Alberto , Sivri H. Serap , Leuzzi Vincenzo , Hoffmann Georg F. , Jeltsch Kathrin , Hübschmann Daniel , Garbade Sven F. ,   iNTD Registry Study Group, Assmann Birgit , Fung Cheuk-Wing , Guder Philipp , Hong Stacey Tay Kiat , Karall Daniela , Kato Mitsuhiro , Kavecan Ivana , Koht Jeanette Aimee , Kuster Alice , Lücke Thomas , Manti Filippo , Mir Pablo , Mühlhausen Chris , Önenli Mungan Halise Neslihan , Palacios Natalia Alexandra Julia , Ramos Joaquín Alejandro Fernández , Steel Dora , Stevanović Galina , Sykut-Cegielska Jolanta , Verbeek Marcel M. , García-Cazorla Angeles , Opladen Thomas
Published: September 2021

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.
HIV reprograms host m6Am RNA methylome by viral Vpr protein-mediated degradation of PCIF1
Authors: Zhang Qiong , Kang Yuqi , Wang Shaobo , Gonzalez Gwendolyn Michelle , Li Wanyu , Hui Hui , Wang Yinsheng , Rana Tariq M.
Published: September 2021

N6,2′-O-dimethyladenosine (m6Am) is an abundant RNA modification located adjacent to the 5′-end of the mRNA 7-methylguanosine (m7G) cap structure. m6A methylation on 2′-O-methylated A at the 5′-ends of mRNAs is catalyzed by the methyltransferase Phosphorylated CTD Interacting Factor 1 (PCIF1). The role of m6Am and the function of PCIF1 in regulating host–pathogens interactions are unknown. Here, we investigate the dynamics and reprogramming of the host m6Am RNA methylome during HIV infection. We show that HIV infection induces a dramatic decrease in m6Am of cellular mRNAs. By using PCIF1 depleted T cells, we identify 2237 m6Am genes and 854 are affected by HIV infection. Strikingly, we find that PCIF1 methyltransferase function restricts HIV replication. Further mechanism studies show that HIV viral protein R (Vpr) interacts with PCIF1 and induces PCIF1 ubiquitination and degradation. Among the m6Am genes, we find that PCIF1 inhibits HIV infection by enhancing a transcription factor ETS1 (ETS Proto-Oncogene 1, transcription factor) stability that binds HIV promoter to regulate viral transcription. Altogether, our study discovers the role of PCIF1 in HIV–host interactions, identifies m6Am modified genes in T cells which are affected by viral infection, and reveals how HIV regulates host RNA epitranscriptomics through PCIF1 degradation.
Topological phase transition in chiral graphene nanoribbons: from edge bands to end states
Authors: Li Jingcheng , Sanz Sofia , Merino-Díez Nestor , Vilas-Varela Manuel , Garcia-Lekue Aran , Corso Martina , de Oteyza Dimas G. , Frederiksen Thomas , Peña Diego , Pascual Jose Ignacio
Published: September 2021

Precise control over the size and shape of graphene nanostructures allows engineering spin-polarized edge and topological states, representing a novel source of non-conventional π-magnetism with promising applications in quantum spintronics. A prerequisite for their emergence is the existence of robust gapped phases, which are difficult to find in extended graphene systems. Here we show that semi-metallic chiral GNRs (chGNRs) narrowed down to nanometer widths undergo a topological phase transition. We fabricated atomically precise chGNRs of different chirality and size by on surface synthesis using predesigned molecular precursors. Combining scanning tunneling microscopy (STM) measurements and theory simulations, we follow the evolution of topological properties and bulk band gap depending on the width, length, and chirality of chGNRs. Our findings represent a new platform for producing topologically protected spin states and demonstrate the potential of connecting chiral edge and defect structure with band engineering.
Peak learning of mass spectrometry imaging data using artificial neural networks
Authors: Abdelmoula Walid M. , Lopez Begona Gimenez-Cassina , Randall Elizabeth C. , Kapur Tina , Sarkaria Jann N. , White Forest M. , Agar Jeffrey N. , Wells William M. , Agar Nathalie Y. R.
Published: September 2021

Mass spectrometry imaging (MSI) is an emerging technology that holds potential for improving, biomarker discovery, metabolomics research, pharmaceutical applications and clinical diagnosis. Despite many solutions being developed, the large data size and high dimensional nature of MSI, especially 3D datasets, still pose computational and memory complexities that hinder accurate identification of biologically relevant molecular patterns. Moreover, the subjectivity in the selection of parameters for conventional pre-processing approaches can lead to bias. Therefore, we assess if a probabilistic generative model based on a fully connected variational autoencoder can be used for unsupervised analysis and peak learning of MSI data to uncover hidden structures. The resulting msiPL method learns and visualizes the underlying non-linear spectral manifold, revealing biologically relevant clusters of tissue anatomy in a mouse kidney and tumor heterogeneity in human prostatectomy tissue, colorectal carcinoma, and glioblastoma mouse model, with identification of underlying m/z peaks. The method is applied for the analysis of MSI datasets ranging from 3.3 to 78.9 GB, without prior pre-processing and peak picking, and acquired using different mass spectrometers at different centers.
Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function
Authors: Špírek Mário , Taylor Martin R. G. , Belan Ondrej , Boulton Simon J. , Krejci Lumir
Published: September 2021

The RAD51 recombinase assembles as helical nucleoprotein filaments on single-stranded DNA (ssDNA) and mediates invasion and strand exchange with homologous duplex DNA (dsDNA) during homologous recombination (HR), as well as protection and restart of stalled replication forks. Strand invasion by RAD51-ssDNA complexes depends on ATP binding. However, RAD51 can bind ssDNA in non-productive ADP-bound or nucleotide-free states, and ATP-RAD51-ssDNA complexes hydrolyse ATP over time. Here, we define unappreciated mechanisms by which the RAD51 paralog complex RFS-1/RIP-1 limits the accumulation of RAD-51-ssDNA complexes with unfavorable nucleotide content. We find RAD51 paralogs promote the turnover of ADP-bound RAD-51 from ssDNA, in striking contrast to their ability to stabilize productive ATP-bound RAD-51 nucleoprotein filaments. In addition, RFS-1/RIP-1 inhibits binding of nucleotide-free RAD-51 to ssDNA. We propose that ‘nucleotide proofreading’ activities of RAD51 paralogs co-operate to ensure the enrichment of active, ATP-bound RAD-51 filaments on ssDNA to promote HR.
Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity
Authors: Haro Endika , Petit Florence , Pira Charmaine U. , Spady Conor D. , Lucas-Toca Sara , Yorozuya Lauren I. , Gray Austin L. , Escande Fabienne , Jourdain Anne-Sophie , Nguyen Andy , Fellmann Florence , Good Jean-Marc , Francannet Christine , Manouvrier-Hanu Sylvie , Ros Marian A. , Oberg Kerby C.
Published: September 2021

LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in mice, Lmx1b has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of Lmx1b appears adequate for development, Lmx1b null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In Lmx1b functional knockouts (KOs), Lmx1b transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) that are bound by Lmx1b, amplify Lmx1b expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal LMX1B coding sequence, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis.
Intranasal vaccination with a recombinant protein CTA1-DD-RBF protects mice against hRSV infection
Authors: Li Hai , Ren Hu , Zhang Yan , Cao Lei , Xu Wenbo
Published: September 2021

Human respiratory syncytial virus (hRSV) infection is a major pediatric health concern worldwide. Despite more than half a century of efforts, there is still no commercially available vaccine. In this study, we constructed and purified the recombinant protein CTA1-DD-RBF composed of a CTA1-DD mucosal adjuvant and prefusion F protein (RBF) usingEscherichia coliBL21 cells. We studied the immunogenicity of CTA1-DD-RBF in mice. Intranasal immunization with CTA1-DD-RBF stimulated hRSV F-specific IgG1, IgG2a, sIgA, and neutralizing antibodies as well as T cell immunity without inducing lung immunopathology upon hRSV challenge. Moreover, the protective immunity of CTA1-DD-RBF was superior to that of the RBF protein, as confirmed by the assessment of serum-neutralizing activity and viral clearance after challenge. Compared to formalin-inactivated hRSV (FI-RSV), intranasal immunization with CTA1-DD-RBF induced a Th1 immune response. In summary, intranasal immunization with CTA1-DD-RBF is safe and effective in mice. Therefore, CTA1-DD-RBF represents a potential mucosal vaccine candidate for the prevention of human infection with hRSV.
Insights into the origin of the invasive populations of Trioza erytreae in Europe using microsatellite markers and mtDNA barcoding approaches
Authors: Ruíz-Rivero Omar , Garcia-Lor Andrés , Rojas-Panadero Borja , Franco José Carlos , Khamis Fathiya M. , Kruger Kerstin , Cifuentes Dina , Bielza Pablo , Tena Alejandro , Urbaneja Alberto , Pérez-Hedo Meritxell
Published: September 2021

The African citrus psyllid Trioza erytreae is one of the major threats to citrus industry as the vector of the incurable disease known as huanglongbing (HLB) or citrus greening. The psyllid invaded the northwest of the Iberian Peninsula 6 years ago. The invasion alarmed citrus growers in the Mediterranean basin, the largest citrus producing area in Europe, which is still free of HLB. Before our study, no research had been carried out on the genetic diversity of T. erytreae populations that have invaded the Iberian Peninsula and the archipelagos of the Macaronesia (Madeira and the Canary Islands). In this study, combining microsatellites markers and mtDNA barcoding analysis, we characterize the genetic diversity, structure and maternal relationship of these new invasive populations of T. erytreae and those from Africa. Our results suggest that the outbreaks of T. erytreae in the Iberian Peninsula may have derived from the Canary Islands. The populations of T. erytreae that invaded Macaronesia and the Iberian Peninsula are likely to have originated from southern Africa. We anticipate our results to be a starting point for tracking the spread of this invasive pest outside of Africa and to be important for optimizing contingency and eradication plans in newly invaded and free areas.
Body and wing size, but not wing shape, vary along a large-scale latitudinal gradient in a damselfly
Authors: Outomuro David , Golab Maria J. , Johansson Frank , Sniegula Szymon
Published: September 2021

Large-scale latitudinal studies that include both north and south edge populations and address sex differences are needed to understand how selection has shaped trait variation. We quantified the variation of flight-related morphological traits (body size, wing size, ratio between wing size and body size, and wing shape) along the whole latitudinal distribution of the damselflyLestes sponsa, spanning over 2700 km. We tested predictions of geographic variation in the flight-related traits as a signature of: (1) stronger natural selection to improve dispersal in males and females at edge populations; (2) stronger sexual selection to improve reproduction (fecundity in females and sexual behaviors in males) at edge populations. We found that body size and wing size showed a U-shaped latitudinal pattern, while wing ratio showed the inverse shape. However, wing shape varied very little along the latitudinal gradient. We also detected sex-differences in the latitudinal patterns of variation. We discuss how latitudinal differences in natural and sexual selection regimes can lead to the observed quadratic patterns of variation in body and wing morphology via direct or indirect selection. We also discuss the lack of latitudinal variation in wing shape, possibly due to aerodynamic constraints.
Heart failure clinical care analysis uncovers risk reduction opportunities for preserved ejection fraction subtype
Authors: Levinson Rebecca T. , Vaitinidin Nataraja Sarma , Farber-Eger Eric , Roden Dan M. , Lasko Thomas A. , Wells Quinn S. , Mosley Jonathan D.
Published: September 2021

Heart failure (HF) has no cure and, for HF with preserved ejection fraction (HFpEF), no life-extending treatments. Defining the clinical epidemiology of HF could facilitate earlier identification of high-risk individuals. We define the clinical epidemiology of HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]), identified among 2.7 million individuals receiving routine clinical care. Differences in patterns and rates of accumulation of comorbidities, frequency of hospitalization, use of specialty care, were defined for each HF subtype. Among 28,156 HF cases, 8322 (30%) were HFpEF and 11,677 (42%) were HFrEF. HFpEF was the more prevalent subtype among older women. 177 Phenotypes differentially associated with HFpEF versus HFrEF. HFrEF was more frequently associated with diagnoses related to ischemic cardiac injury while HFpEF was associated more with non-cardiac comorbidities and HF symptoms. These comorbidity patterns were frequently present 3 years prior to a HFpEF diagnosis. HF subtypes demonstrated distinct patterns of clinical co-morbidities and disease progression. For HFpEF, these comorbidities were often non-cardiac and manifested prior to the onset of a HF diagnosis. Recognizing these comorbidity patterns, along the care continuum, may present a window of opportunity to identify individuals at risk for developing incident HFpEF.
Reproducibility in the UK biobank of genome-wide significant signals discovered in earlier genome-wide association studies
Authors: O’Sullivan Jack W. , Ioannidis John P. A.
Published: September 2021

With the establishment of large biobanks, discovery of single nucleotide variants (SNVs, also known as single nucleotide polymorphisms (SNVs)) associated with various phenotypes has accelerated. An open question is whether genome-wide significant SNVs identified in earlier genome-wide association studies (GWAS) are replicated in later GWAS conducted in biobanks. To address this, we examined a publicly available GWAS database and identified two, independent GWAS on the same phenotype (an earlier, “discovery” GWAS and a later, “replication” GWAS done in the UK biobank). The analysis evaluated 136,318,924 SNVs (of which 6289 reached P < 5e−8 in the discovery GWAS) from 4,397,962 participants across nine phenotypes. The overall replication rate was 85.0%; although lower for binary than quantitative phenotypes (58.1% versus 94.8% respectively). There was a 18.0% decrease in SNV effect size for binary phenotypes, but a 12.0% increase for quantitative phenotypes. Using the discovery SNV effect size, phenotype trait (binary or quantitative), and discovery P value, we built and validated a model that predicted SNV replication with area under the Receiver Operator Curve = 0.90. While non-replication may reflect lack of power rather than genuine false-positives, these results provide insights about which discovered associations are likely to be replicated across subsequent GWAS.
Linear unmixing protocol for hyperspectral image fusion analysis applied to a case study of vegetal tissues
Authors: Gómez-Sánchez Adrián , Marro Mónica , Marsal Maria , Zacchetti Sara , Rocha de Oliveira Rodrigo , Loza-Alvarez Pablo , de Juan Anna
Published: September 2021

Hyperspectral imaging (HSI) is a useful non-invasive technique that offers spatial and chemical information of samples. Often, different HSI techniques are used to obtain complementary information from the sample by combining different image modalities (Image Fusion). However, issues related to the different spatial resolution, sample orientation or area scanned among platforms need to be properly addressed. Unmixing methods are helpful to analyze and interpret the information of HSI related to each of the components contributing to the signal. Among those, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) offers very suitable features for image fusion, since it can easily cope with multiset structures formed by blocks of images coming from different samples and platforms and allows the use of optional and diverse constraints to adapt to the specific features of each HSI employed. In this work, a case study based on the investigation of cross-sections from rice leaves by Raman, synchrotron infrared and fluorescence imaging techniques is presented. HSI of these three different techniques are fused for the first time in a single data structure and analyzed by MCR-ALS. This example is challenging in nature and is particularly suitable to describe clearly the necessary steps required to perform unmixing in an image fusion context. Although this protocol is presented and applied to a study of vegetal tissues, it can be generally used in many other samples and combinations of imaging platforms.
The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study
Authors: Chen Jiaqi , Qu Wenqiang , Sun Li , Chen Jiansheng , Kong Wei , Wang Fan , Pan Wenyou , Liu Lin , Wu Min , Ding Fuwan , Hu Huaixia , Ding Xiang , Wei Hua , Zou Yaohong , Qian Xian , Wang Meimei , Wu Jian , Tao Juan , Tan Jun , Da Zhanyun , Zhang Miaojia , Li Jing , Liang Jun , Feng Xuebing , Geng Linyu , Sun Lingyun
Published: September 2021

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.
Evaluation of antigenicity and nutritional properties of enzymatically hydrolyzed cow milk
Authors: Liang Xiaona , Qian Guanlin , Sun Jing , Yang Mei , Shi Xinyang , Yang Hui , Wu Junrui , Wang Zongzhou , Zheng Yan , Yue Xiqing
Published: September 2021

While enzymatic hydrolysis is an effective method for lowering the antigenicity of cow milk (CM), research regarding the antigenicity and nutritional traits of CM hydrolysate is limited. Here, we evaluated the protein content, amino acid composition, sensory traits, color, flow behavior, and antigenicity of CM following enzymatic hydrolysis. The results showed that enzymatic hydrolysis increased the degree of hydrolysis, destroyed allergenic proteins, including casein, β-lactoglobulin, and ɑ-lactalbumin, and significantly increased the content of free amino acids and nutritional quality. In particular, the antigenicity of CM was significantly reduced from 44.05 to 86.55% (P < 0.5). Simultaneously, the taste, color, and flow behavior of CM were altered, the sweetness and richness intensity decreased significantly (P < 0.5), and astringency and bitterness were produced. A slightly darker and more yellow color was observed in CM hydrolysate. In addition, apparent viscosity decreased and shear stress significantly increased with increasing shear rate intensity. The results will provide a solid theoretical foundation for the development of high-quality hypoallergenic dairy products.
Low dose inocula of SARS-CoV-2 Alpha variant transmits more efficiently than earlier variants in hamsters
Authors: Mok Bobo Wing-Yee , Liu Honglian , Deng Shaofeng , Liu Jiayan , Zhang Anna Jinxia , Lau Siu-Ying , Liu Siwen , Tam Rachel Chun-Yee , Cremin Conor J. , Ng Timothy Ting-Leung , Leung Jake Siu-Lun , Lee Lam-Kwong , Wang Pui , To Kelvin Kai-Wang , Chan Jasper Fuk-Woo , Chan Kwok-Hung , Yuen Kwok-Yung , Siu Gilman Kit-Hang , Chen Honglin
Published: September 2021

Emerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than existing strains of SARS-CoV-2 in transmission. We found that the Alpha variant (B.1.1.7) increased competitive fitness over earlier parental D614G lineages in in-vitro and in-vivo systems. Using hamster transmission model, we further demonstrated that the Alpha variant is able to replicate and shed more efficiently in the nasal cavity of hamsters than other variants with low dose and short duration of exposure. The capability to initiate effective infection with low inocula may be one of the key factors leading to the rapid transmission of emerging variants of SARS-CoV-2.
Ab initio thermodynamics reveals the nanocomposite structure of ferrihydrite
Authors: Sassi Michel , Chaka Anne M. , Rosso Kevin M.
Published: September 2021

Ferrihydrite is a poorly crystalline iron oxyhydroxide nanomineral that serves a critical role as the most bioavailable form of ferric iron for living systems. However, its atomic structure and composition remain unclear due in part to ambiguities in interpretation of X-ray scattering results. Prevailing models so far have not considered the prospect that at the level of individual nanoparticles multiple X-ray indistinguishable phases could coexist. Using ab initio thermodynamics we show that ferrihydrite is likely a nanocomposite of distinct structure types whose distribution depends on particle size, temperature, and hydration. Nanoparticles of two contrasting single-phase ferrihydrite models of Michel and Manceau are here shown to be thermodynamically equivalent across a wide range of temperature and pressure conditions despite differences in their structural water content. Higher temperature and water pressure favor the formation of the former, while lower temperature and water pressure favor the latter. For aqueous suspensions at ambient conditions, their coexistence is maximal for particle sizes up to 12 nm. The predictions inform and help resolve different observations in various experiments.
Enhanced coherence of all-nitride superconducting qubits epitaxially grown on silicon substrate
Authors: Kim Sunmi , Terai Hirotaka , Yamashita Taro , Qiu Wei , Fuse Tomoko , Yoshihara Fumiki , Ashhab Sahel , Inomata Kunihiro , Semba Kouichi
Published: September 2021

Improving the coherence of superconducting qubits is a fundamental step towards the realization of fault-tolerant quantum computation. However, coherence times of quantum circuits made from conventional aluminum-based Josephson junctions are limited by the presence of microscopic two-level systems in the amorphous aluminum oxide tunnel barriers. Here, we have developed superconducting qubits based on NbN/AlN/NbN epitaxial Josephson junctions on silicon substrates which promise to overcome the drawbacks of qubits based on Al/AlOx/Al junctions. The all-nitride qubits have great advantages such as chemical stability against oxidation, resulting in fewer two-level fluctuators, feasibility for epitaxial tunnel barriers that reduce energy relaxation and dephasing, and a larger superconducting gap of ~5.2 meV for NbN, compared to ~0.3 meV for aluminum, which suppresses the excitation of quasiparticles. By replacing conventional MgO by a silicon substrate with a TiN buffer layer for epitaxial growth of nitride junctions, we demonstrate a qubit energy relaxation time $${T}_{1}=16.3\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

1

=
16.3

μ
s
and a spin-echo dephasing time $${T}_{2}=21.5\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

2

=
21.5

μ
s
. These significant improvements in quantum coherence are explained by the reduced dielectric loss compared to the previously reported $${T}_{1}\approx {T}_{2}\approx 0.5\;{{\upmu }}{{{{{\rm{s}}}}}}$$

T

1

≈

T

2

≈
0.5

μ
s
of NbN-based qubits on MgO substrates. These results are an important step towards constructing a new platform for superconducting quantum hardware.
Performing sequential forward selection and variational autoencoder techniques in soil classification based on laser-induced breakdown spectroscopy
Authors: Harefa Edward , Zhou Weidong
Published: September 2021

Twelve soil samples were tested using LIBS and the acquired spectra were analyzed to classify the soil. Sequential feature selection, variational autoencoder, and multivariate classification methods were employed.