bluuebunny/crossref_metadata_2025 huggingface dataset:
GOLD MEDAL LECTURE GIVEN AT THE ACADEMIA EUROPAEA BUILDING BRIDGES CONFERENCE 2022
Authors: Cloetingh Sierd
Published: August 2023

The quantitative understanding of processes operating in the earth system has advanced significantly over the last few decades. This has led to the realization that a close interaction between deep earth and surface processes is a key element in earth dynamics and its impact on geo-environment, geo-energy, geo-resources and geo-hazards in general. The European continent and its ocean-continent margins provide an excellent natural laboratory to examine the impact of geodynamics and climate on topography at the earth’s surface. The overview presented here demonstrates the need for a further understanding of the earth system across space and timescales. Cross-border scientific cooperation on a full pan-European scale, benefiting from funding opportunities offered by the European Commission and a pro-active role in bottom-up self-organization involving members of the Earth and Cosmic Sciences section of Academia Europaea, is needed more than ever.
The prognostic value of clinical frailty and American Society of Anesthesiology score in patients with chronic limb threatening ischaemia
Authors: Walter Amy , Bradley Nicholas , Flett Murray , Nagy John , Suttie Stuart , Guthrie Graeme
Published: August 2023

Summary: Background: Frailty is a complex multisystem syndrome associated with increased comorbidity and decreased physiological reserve. There are associations between frailty and adverse outcome in surgical patients. Chronic limb threatening ischemia (CLTI) is increasingly prevalent, with a typically frail patient population. Existing frailty scoring systems focus on functional measures and do not reliably assess comorbidities. The present study aims to describe the prognostic value of multimodal frailty assessment in patients with CLTI. Patients and methods: Patients >50 years old admitted as an emergency with CLTI between May 2020 to June 2021 were included. Frailty was measured using Clinical Frailty Score (CFS), and comorbidities with American Society of Anesthiologists score (ASA). A composite score combining CFS and ASA was derived and the prognostic value compared with each component score. The primary outcome was overall survival. Results: There were 249 eligible patients, 53.4% (n=133) had CFS>4. The mean (95% CI) overall survival for the CFS>4 cohort was 15.9 (13.6–18.3) months vs. 28.5 (26.1–30.9) months for CFS≤4 cohort ( p<0.001). Increasing CFS-ASA score was associated with inferior survival on univariate (HR=2.84, 95% CI [1.96–4.11], p<0.001) and multivariate (HR=1.78, 95% CI [1.20–2.64], p<0.01) analyses. ROC-analysis showed comparable prognostic value of CFS and CFS-ASA to predict one-year survival.  Conclusions: Frailty is highly prevalent and a poor prognostic indicator in patients with CLTI admitted as an emergency. Our results suggest that incorporating assessment of comorbidities into frailty assessment may offer prognostic value, but comparable to existing clinical frailty assessment. Further work to identify patients with inferior prognosis is required.
School Greenness and Student‐Level Academic Performance: Evidence From the Global South
Authors: Jimenez Raquel B. , Bozigar Matthew , Janulewicz Patricia , Lane Kevin J. , Hutyra Lucy R. , Fabian M. Patricia
Published: August 2023

Greenspace in schools might enhance students' academic performance. However, the literature—dominated by ecological studies at the school level in countries from the Northern Hemisphere—presents mixed evidence of a beneficial association. We evaluated the association between school greenness and student‐level academic performance in Santiago, Chile, a capital city of the Global South. This cross‐sectional study included 281,695 fourth‐grade students attending 1,498 public, charter, and private schools in Santiago city between 2014 and 2018. Student‐level academic performance was assessed using standardized test scores and indicators of attainment of learning standards in mathematics and reading. School greenness was estimated using Normalized Difference Vegetation Index (NDVI). Linear and generalized linear mixed‐effects models were fit to evaluate associations, adjusting for individual‐ and school‐level sociodemographic factors. Analyses were stratified by school type. In fully adjusted models, a 0.1 increase in school greenness was associated with higher test scores in mathematics (36.9 points, 95% CI: 2.49; 4.88) and in reading (1.84 points, 95% CI: 0.73; 2.95); as well as with higher odds of attaining learning standards in mathematics (OR: 1.20, 95% CI: 1.12; 1.28) and reading (OR: 1.07, 95% CI: 1.02; 1.13). Stratified analysis showed differences by school type, with associations of greater magnitude and strength for students attending public schools. No significant associations were detected for students in private schools. Higher school greenness was associated with improved individual‐level academic outcomes among elementary‐aged students in a capital city in South America. Our results highlight the potential of greenness in the school environment to moderate educational and environmental inequalities in urban areas.
An Approach to Link Climate Model Tropical Cyclogenesis Bias to Large‐Scale Wind Circulation Modes
Authors: Feng Xiangbo , Toumi Ralf , Roberts Malcolm , Hodges Kevin I. , Vidale Pier Luigi
Published: August 2023

Attributing sources of tropical cyclogenesis (TCG) bias to large‐scale circulation in global circulation models is challenging. Here, we propose the use of empirical orthogonal functions as an approach to understand model bias of TCG. Two leading modes of large‐scale wind circulations in the West Pacific can explain the TCG frequency and location in both climate reanalysis and the MetUM model. In the reanalysis, the two modes distinguish the summer monsoon trough position and the strength of the north Pacific subtropical high. However, in the model, the wind circulations are biased toward the positive phase of simulated modes thus overestimating TCG in the entire Main Development Region. This bias is further related to the north‐eastward shifted monsoon trough and a weakened subtropical high, and overly strong tropics‐subtropics connections. This approach could be deployed more widely to other basins and models to diagnose the causes of TCG bias.
Magnetospheric Response to a Pressure Pulse in a Three‐Dimensional Hybrid‐Vlasov Simulation
Authors: Horaites K. , Rintamäki E. , Zaitsev I. , Turc L. , Grandin M. , Cozzani G. , Zhou H. , Alho M. , Suni J. , Kebede F. , Gordeev E. , George H. , Battarbee M. , Bussov M. , Dubart M. , Ganse U. , Papadakis K. , Pfau‐Kempf Y. , Tarvus V. , Palmroth M.
Published: August 2023

Vlasiator is a high‐performance ion‐kinetic code that is now conducting 3D hybrid‐Vlasov simulations of the global magnetosphere. We use Vlasiator to investigate the impact of a pressure pulse with southward‐oriented magnetic field on the Earth's magnetosphere. The simulation driving parameters are comparable to conditions that have led to geomagnetic storms. Our pressure pulse simulation reproduces many physical effects, namely the expansion of the auroral oval, the development of field‐aligned currents, enhanced particle precipitation near the open/closed field line boundary, and compression of Earth's magnetopause. This demonstrates the effectiveness of the hybrid‐Vlasov approach for moderate driving conditions. Our investigation of the time‐dependent magnetopause compression motivates a generalization of the existing theory. Specifically, we find that accounting for the finite transition time of the solar wind dynamic pressure improves the model's description of the magnetopause oscillations.
Global Gridded Aerosol Models Established for Atmospheric Correction Over Inland and Nearshore Coastal Waters
Authors: Zhao Dan , Feng Lian , He Xianqiang
Published: August 2023

The use of standard aerosol models for atmospheric correction over inland and nearshore coastal waters generates large uncertainties due to their inability to appropriately characterize aerosols in those regions. To address this problem, we developed new aerosol models using data acquired from 1,475 Aerosol Robotic Network (AERONET) sites distributed in inland and coastal regions throughout the globe. We established spatially gridded (5° × 5°) aerosol models on a climatological monthly scale, with a total of 3,207 new aerosol models developed for 310 grid cells worldwide. The monthly aerosol model for each grid was derived using mean monthly values of microphysical aerosol properties from AERONET data. The optical properties (i.e., single scattering albedo and Ångström coefficient) of our global gridded aerosol models demonstrated considerable spatial and seasonal dynamics and deviated substantially from the aerosol models currently utilized by the National Aeronautics and Space Administration (NASA). We built associated lookup tables for all aerosol models and incorporated them into two atmospheric correction algorithms: the combined near‐infrared and shortwave infrared algorithm (NIR‐SWIR) and the Atmospheric Correction algorithm for inLand and Nearshore Coastal waters (ACLANC). For both algorithms, the accuracies of atmospherically corrected satellite remote sensing reflectance (Rrs) improved markedly when the new aerosol models were used, and improvements were noted across all spectral bands and across all six inland and nearshore water bodies used in this study. Our new aerosol models can be easily applied to all ocean color satellite missions to obtain accurate Rrs products for inland and coastal waters worldwide.
Strong Evidence of Heterogeneous Processing on Stratospheric Sulfate Aerosol in the Extrapolar Southern Hemisphere Following the 2022 Hunga Tonga‐Hunga Ha'apai Eruption
Authors: Santee M. L. , Lambert A. , Froidevaux L. , Manney G. L. , Schwartz M. J. , Millán L. F. , Livesey N. J. , Read W. G. , Werner F. , Fuller R. A.
Published: August 2023

The January 2022 eruption of Hunga Tonga‐Hunga Ha'apai (HT‐HH) caused the largest enhancement in stratospheric aerosol loading in decades and produced an unprecedented enhancement in stratospheric water vapor, leading to strong stratospheric cooling that in turn induced changes in the large‐scale circulation. Here we use satellite measurements of gas‐phase constituents together with aerosol extinction to investigate the extent to which the thick aerosol, excess moisture, and strong cooling enabled heterogeneous chemical processing. In the southern tropics, unambiguous signatures of substantial chlorine and nitrogen repartitioning appear over a broad vertical domain almost immediately after the eruption, with depletion of N2O5, NOx, and HCl accompanied by enhancement of HNO3, ClO, and ClONO2. After initially rising steeply, HNO3 and ClO plateau, maintaining fairly constant abundances for several months. These patterns are consistent with the saturation of N2O5 hydrolysis, suggesting that this reaction is the primary mechanism for the observed composition changes. The southern midlatitudes and subtropics show similar but weaker enhancements in ClO and ClONO2. In those regions, however, effects of anomalous transport dominate the evolution of HNO3 and HCl, obscuring the signs of heterogeneous processing. Perturbations in chlorine species are considerably weaker than those measured in the southern midlatitude stratosphere in 2020 following the Australian New Year's fires. The moderate HT‐HH‐induced enhancements in reactive chlorine seen throughout the southern middle and low‐latitude stratosphere, far smaller than those in typical winter polar vortices, do not lead to appreciable chemical ozone loss; rather, extrapolar lower‐stratospheric ozone remains primarily controlled by dynamical processes.
Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression
Authors: Suri Deepika , Zanni Giulia , Mahadevia Darshini , Chuhma Nao , Saha Rinki , Spivack Stephen , Pini Nicolò , Stevens Gregory S. , Ziolkowski-Blake Annette , Simpson Eleanor H. , Balsam Peter , Rayport Stephen , Ansorge Mark S.
Published: August 2023

Sensitive developmental periods shape neural circuits and enable adaptation. However, they also engender vulnerability to factors that can perturb developmental trajectories. An understanding of sensitive period phenomena and mechanisms separate from sensory system development is still lacking, yet critical to understanding disease etiology and risk. The dopamine system is pivotal in controlling and shaping adolescent behaviors, and it undergoes heightened plasticity during that time, such that interference with dopamine signaling can have long-lasting behavioral consequences. Here we sought to gain mechanistic insight into this dopamine-sensitive period and its impact on behavior. In mice, dopamine transporter (DAT) blockade from postnatal (P) day 22 to 41 increases aggression and sensitivity to amphetamine (AMPH) behavioral stimulation in adulthood. Here, we refined this sensitive window to P32-41 and identified increased firing of dopaminergic neurons in vitro and in vivo as a neural correlate to altered adult behavior. Aggression can result from enhanced impulsivity and cognitive dysfunction, and dopamine regulates working memory and motivated behavior. Hence, we assessed these behavioral domains and found that P32-41 DAT blockade increases impulsivity but has no effect on cognition, working memory, or motivation in adulthood. Lastly, using optogenetics to drive dopamine neurons, we find that increased VTA but not SNc dopaminergic activity mimics the increase in impulsive behavior in the Go/NoGo task observed after adolescent DAT blockade. Together our data provide insight into the developmental origins of aggression and impulsivity that may ultimately improve diagnosis, prevention, and treatment strategies for related neuropsychiatric disorders.
Gold nanoparticles combat enveloped RNA virus by affecting organelle dynamics
Authors: Li Fangzhou , Huang Qianqian , Zhou Ziran , Guan Qiongge , Ye Fei , Huang Baoying , Guo Weisheng , Liang Xing-Jie
Published: August 2023

Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid (RNA). These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles. However, the interaction between viruses and host organelles may be disrupted by nanomaterials, such as gold nanoparticles (AuNPs) with unique physical and chemical properties. In this study, we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells, and their effects on two representative enveloped RNA viruses: lentivirus and human coronavirus OC43 (HCoV- OC43) antiviral potential. By comparing the subcellular effects of AuNPs with different surface charge properties, we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs, mainly manifested in lysosomes and Cytoskeletal disorders. The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43. The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects. In conclusion, our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems, while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.
Transcranial random noise stimulation combined with cognitive training for treating ADHD: a randomized, sham-controlled clinical trial
Authors: Dakwar-Kawar Ornella , Mairon Noam , Hochman Shachar , Berger Itai , Cohen Kadosh Roi , Nahum Mor
Published: August 2023

Non-invasive brain stimulation has been suggested as a potential treatment for improving symptomology and cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD), the most common childhood neurodevelopmental disorder. Here, we examined whether a novel form of stimulation, high-frequency transcranial random noise stimulation (tRNS), applied with cognitive training (CT), may impact symptoms and neural oscillations in children with ADHD. We conducted a randomized, double-blind, sham-controlled trial in 23 unmedicated children with ADHD, who received either tRNS over the right inferior frontal gyrus (rIFG) and left dorsolateral prefrontal cortex (lDLPFC) or sham stimulation for 2 weeks, combined with CT. tRNS + CT yielded significant clinical improvements (reduced parent-reported ADHD rating-scale scores) following treatment, compared to the control intervention. These improvements did not change significantly at a 3-week follow-up. Moreover, resting state (RS)-EEG periodic beta bandwidth of the extracted peaks was reduced in the experimental compared to control group immediately following treatment, with further reduction at follow-up. A lower aperiodic exponent, which reflects a higher cortical excitation/inhibition (E/I) balance and has been related to cognitive improvement, was seen in the experimental compared to control group. This replicates previous tRNS findings in adults without ADHD but was significant only when using a directional hypothesis. The experimental group further exhibited longer sleep onset latencies and more wake-up times following treatment compared to the control group. No significant group differences were seen in executive functions, nor in reported adverse events. We conclude that tRNS + CT has a lasting clinical effect on ADHD symptoms and on beta activity. These results provide a preliminary direction towards a novel intervention in pediatric ADHD.
Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma
Authors: Xiang Chan , Zhang Min , Shang Zhanxian , Chen Shengnan , Zhao Jikai , Ding Bowen , Jiang Dong , Zhu Qian , Teng Haohua , Zhu Lei , Shao Jinchen , Zhao Ruiying , Ye Min , Yu Yang , Han Yuchen
Published: August 2023

An immunosuppressive microenvironment enriched with regulatory CD4+ T lymphocytes (Tregs) facilitates the progression of lung adenocarcinoma (LUAD). This study aims to investigate the cellular mechanism underlying the formation of the immunosuppressive microenvironment in LUAD. LUAD samples (n = 12) and normal lung samples (n = 3) were obtained from patients with different pathological stages of LUAD. Single-cell RNA sequencing was performed to classify cellular components and analyze the transcriptomes, including transcription factors/targets and chemokine ligands/receptors, followed by bioinformatics study such as pseudotime analysis. Myeloid cells and T cells were the most abundant cell types in tumors and normal lung tissues, while tumor-associated macrophage-folate receptor 2 (TAM-FOLR2) and CD4+ nuclear receptor subfamily 4 group A member 3 (NR4A3) exhibited sharp increases in invasive adenocarcinoma (IA). The enrichment of TAM-FOLR2 in IA might result from alveolar resident macrophage-resistin (ARM-RETN) transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential expression profiles of chemokine ligands/receptors versus those in the early stages of tumors. High expression of CCL17/19/22 was observed in IA as well as in DCs, along with the strong interaction of TAM-FOLR2 with DCs. The results of pseudotime analysis suggested that CD4+NR4A3 might potentially convert to CD4+FOXP3, further supported by the high expression of NR4A3 target genes in CD4+FOXP3 cells. This study provides a single-cell transcriptome atlas from preinvasive to invasive LUAD and reveals a potential ARM-RETN/TAM-FOLR2/DCs/CD4+NR4A3/CD4+FOXP3 trajectory in shaping the immune suppressive microenvironment along the pathogenesis of LUAD.
Circ_0000235 targets MCT4 to promote glycolysis and progression of bladder cancer by sponging miR-330-5p
Authors: Zhong Jianye , Xu Abai , Xu Peng , Su Minhong , Wang Peng , Liu Zhe , Li Boping , Liu Chunxiao , Jiang Ning
Published: August 2023

Warburg effect plays a crucial role in bladder cancer (Bca) development. However, the mechanism by which glycolysis is involved in Bca remains poorly understood. CircRNAs commonly play a regulatory role in tumor progression. Our study discovered and identified a novel circRNA, hsa_circ_0000235 (circ235), and investigated its role in the glycolytic process, which further results in the progression of Bca. We applied qRT-PCR to assess its clinicopathological relevance and evaluated its proliferation, migration, and glycolytic capacity. We investigated its mechanism using RNA immunoprecipitation, dual-luciferase reporters, and fluorescence in situ hybridization. The findings demonstrated that circ235 was dramatically increased in Bca tissues and was related to a worse prognosis. In vitro studies revealed that circ235 accelerated the rate of extracellular acidification and promoted glucose uptake and lactate manufacture in Bca cells. Additionally, it strengthened the proliferative and migratory capacities. Experiments on animals revealed that downregulating circ235 dramatically reduced carcinogenesis and tumor growth. Circ235 activates monocarboxylate transporter 4 (MCT4) by sponging miR-330-5p, which promotes glycolysis and tumor growth. In conclusion, these findings suggest that circ235 may be a viable molecular marker and therapeutic target for Bca.
Energetic robustness to large scale structural fluctuations in a photosynthetic supercomplex
Authors: Harris Dvir , Toporik Hila , Schlau-Cohen Gabriela S. , Mazor Yuval
Published: August 2023

Photosynthetic organisms transport and convert solar energy with near-unity quantum efficiency using large protein supercomplexes held in flexible membranes. The individual proteins position chlorophylls to tight tolerances considered critical for fast and efficient energy transfer. The variability in protein organization within the supercomplexes, and how efficiency is maintained despite variability, had been unresolved. Here, we report on structural heterogeneity in the 2-MDa cyanobacterial PSI-IsiA photosynthetic supercomplex observed using Cryo-EM, revealing large-scale variances in the positions of IsiA relative to PSI. Single-molecule measurements found efficient IsiA-to-PSI energy transfer across all conformations, along with signatures of transiently decoupled IsiA. Structure based calculations showed that rapid IsiA-to-PSI energy transfer is always maintained, and even increases by three-fold in rare conformations via IsiA-specific chls. We postulate that antennae design mitigates structural fluctuations, providing a mechanism for robust energy transfer in the flexible membrane.
Deterministic early endosomal maturations emerge from a stochastic trigger-and-convert mechanism
Authors: York Harrison M. , Joshi Kunaal , Wright Charles S. , Kreplin Laura Z. , Rodgers Samuel J. , Moorthi Ullhas K. , Gandhi Hetvi , Patil Abhishek , Mitchell Christina A. , Iyer-Biswas Srividya , Arumugam Senthil
Published: August 2023

Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves a phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole cell-level measurements of absolute numbers of maturation events. Here, we use lattice light-sheet imaging and bespoke automated analysis to track individual very early (APPL1-positive) and early (EEA1-positive) endosomes over the entire population, demonstrating that direct inter-endosomal contact drives maturation between these populations. Using fluorescence lifetime, we show that this endosomal interaction is underpinned by asymmetric binding of EEA1 to very early and early endosomes through its N- and C-termini, respectively. In combination with agent-based simulation which supports a ‘trigger-and-convert’ model, our findings indicate that APPL1- to EEA1-positive maturation is driven not by autonomous events but by heterotypic EEA1-mediated interactions, providing a mechanism for temporal and population-level control of maturation.
Study on the oxidation resistance mechanism of self-healable NiAl coating deposited by atmospheric plasma spraying
Authors: Zhang Li , Wang Di , Liao Xian-Jin , Chen Rui , Luo Xiao-Tao , Li Chang-Jiu
Published: August 2023

A dense NiAl coating with low oxide content was deposited on the GH4202 superalloy substrate by atmospheric plasma spraying (APS) using carbon-containing Ni/Al composite powders. Compared with traditional APS NiAl coatings with high oxide content, this coating exhibits better long-term oxidation resistance at 900 °C in air. For the NiAl coating with low oxide content, it was found that the improved inter-splat bonding, due to limited oxide inclusions, promotes the formation of a continuous protective Al2O3 layer on the coating surface during oxidation. During long-term oxidation, the dispersion of oxide scales within the coating and element diffusion across splats result in the in-situ healing of unbonded inter-splat interfaces.
cGAS–STING drives ageing-related inflammation and neurodegeneration
Authors: Gulen Muhammet F. , Samson Natasha , Keller Alexander , Schwabenland Marius , Liu Chong , Glück Selene , Thacker Vivek V. , Favre Lucie , Mangeat Bastien , Kroese Lona J. , Krimpenfort Paul , Prinz Marco , Ablasser Andrea
Published: August 2023

Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease1. Multiple factors can contribute to ageing-associated inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling and their impact in natural ageing remain unclear. Here we show that the cGAS–STING signalling pathway, which mediates immune sensing of DNA3, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglial transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia, defining a mechanism by which cGAS–STING signalling is engaged in the ageing brain. Single-nucleus RNA-sequencing analysis of microglia and hippocampi of a cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglial states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS–STING pathway as a driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS–STING signalling as a potential strategy to halt neurodegenerative processes during old age.
TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP
Authors: Arseni Diana , Chen Renren , Murzin Alexey G. , Peak-Chew Sew Y. , Garringer Holly J. , Newell Kathy L. , Kametani Fuyuki , Robinson Andrew C. , Vidal Ruben , Ghetti Bernardino , Hasegawa Masato , Ryskeldi-Falcon Benjamin
Published: August 2023

The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases of amyotrophic lateral sclerosis (ALS) and around half of cases of frontotemporal lobar degeneration (FTLD)1,2. A causal role for TDP-43 assembly in neurodegeneration is evidenced by dominantly inherited missense mutations in TARDBP, the gene encoding TDP-43, that promote assembly and give rise to ALS and FTLD3–7. At least four types (A–D) of FTLD with TDP-43 pathology (FTLD-TDP) are defined by distinct brain distributions of assembled TDP-43 and are associated with different clinical presentations of frontotemporal dementia8. We previously showed, using cryo-electron microscopy, that TDP-43 assembles into amyloid filaments in ALS and type B FTLD-TDP9. However, the structures of assembled TDP-43 in FTLD without ALS remained unknown. Here we report the cryo-electron microscopy structures of assembled TDP-43 from the brains of three individuals with the most common type of FTLD-TDP, type A. TDP-43 formed amyloid filaments with a new fold that was the same across individuals, indicating that this fold may characterize type A FTLD-TDP. The fold resembles a chevron badge and is unlike the double-spiral-shaped fold of ALS and type B FTLD-TDP, establishing that distinct filament folds of TDP-43 characterize different neurodegenerative conditions. The structures, in combination with mass spectrometry, led to the identification of two new post-translational modifications of assembled TDP-43, citrullination and monomethylation of R293, and indicate that they may facilitate filament formation and observed structural variation in individual filaments. The structures of TDP-43 filaments from type A FTLD-TDP will guide mechanistic studies of TDP-43 assembly, as well as the development of diagnostic and therapeutic compounds for TDP-43 proteinopathies.
Genome assembly of two diploid and one auto-tetraploid Cyclocarya paliurus genomes
Authors: Qu Yinquan , Shang Xulan , Fang Shengzuo , Zhang Xingtan , Fu Xiangxiang
Published: August 2023

Cyclocarya paliurus, an endemic species in the genus Juglandaceae with the character of heterodichogamy, is one of triterpene-rich medicinal plants in China. To uncover the genetic mechanisms behind the special characteristics, we sequenced the genomes of two diploid (protandry, PA-dip and protogyny, PG-dip) and one auto-tetraploid (PA-tetra) C. paliurus genomes. Based on 134.9 (~225x), 75.5 (~125x) and 271.8 Gb (~226x) subreads of PacBio platform sequencing data, we assembled 586.62 Mb (contig N50 = 1.9 Mb), 583.45 Mb (contig N50 = 1.4 Mb), and 2.38 Gb (contig N50 = 430.9 kb) for PA-dip, PG-dip and PA-tetra genome, respectively. Furthermore, 543.53, 553.87, and 2168.65 Mb in PA-dip, PG-dip, and PA-tetra, were respectively anchored to 16, 16, and 64 pseudo-chromosomes using over 65.4 Gb (~109x), 68 Gb (~113x), and 264 (~220x) Hi-C sequencing data. Annotation of PA-dip, PG-dip, and PA-tetra genome assembly identified 34,699, 35,221, and 34,633 protein-coding genes (90,752 gene models) or allele-defined genes, respectively. In addition, 45 accessions from nine locations were re-sequenced, and more than 10 × coverage reads were generated.
Early stage nanocrystallization as a method of enhancement of electrical properties of lead/barium titanate doped vanadium borate glasses
Authors: Harby Amany E. , Hannora Ahmed E. , Ali Atif Mossad , El-Desoky M. M.
Published: August 2023

Glass–ceramic nanocomposites (GCNs) of (10 − x) BaTiO3 (BT)–xPbTiO3 (PT)–60V2O5–30B2O3 with x = 0, 2.5, 5, 7.5 and 10 mol% were formed during heat treatment of conventional melt quenching glasses. X-ray diffraction was used to ensure glass and GCNs formation. Glasses and GCNs densities were measured by Archimedes principle. Fine polar clusters of lead titanate and/or barium titanate incorporation into vanadium borate glass matrix strongly depend on the composition. It was found out that the electrical conductivity of the initial glasses can be considerably improved by proper early stage of nanocrystallization at temperatures approaching the crystallization temperatures determined by DSC method. GCNs show massive increase in electrical conductivity (up to 6 orders of magnitude) as a function of BaTiO3 content. By increasing BaTiO3 content, the activation energy values have been found to increase. The enhancement in electrical conductivity of GCNs can be attributed to the increase in the crystalline phases in the glassy matrix which increases the concentrations of the V ion pairs.
Novel dual-function GC/MS aided ultrasound-assisted hydrodistillation for the valorization of Citrus sinensis by-products: phytochemical analysis and anti-bacterial activities
Authors: Abdel Samad Roudaina , El Darra Nada , Al Khatib Alissar , Chacra Hadi Abou , Jammoul Adla , Raafat Karim
Published: August 2023

A huge-amount of citrus by-products is being wasted every-year. There is a high-need to utilize these by-products with high-efficiency. This study focuses on the essential oil (EO) isolation from the zest of Citrus sinensis (CS) by-products, using a novel dual-function gas-chromatography mass-spectrometry optimized ultrasound-assisted hydrodistillation-prototype (DF-GC/MS-HUS). The CS-EO was GC-analyzed by MS-detector (GC/MS) and optimized by flame-ionization detector (GC/FID). Ultrasound-assisted hydrodistillation (HUS) had a dual-function in CS-EO isolation by utilizing an adequate-energy to break-open the oil-containing glands, and by functioning-as a dispersing-agent to emulsify the organic-phase. The most effective DF-GC/MS-HUS optimized-conditions were isolation under 38 °C and 10 min of 28.9 Hz sonication. The main-components of CS-EO were limonene, β-myrcene, and α-pinene (81.32%, 7.55%, and 4.20%) in prototype, compared to (60.23%, 5.33%, and 2.10%) in the conventional-method, respectively. The prototype CS-EO showed natural antibacterial-potentials, and inhibited the bio-film formation by Staphylococcus aureus, Listeria monocytogenes, and E. coli more-potent than the conventional-method. Compared to conventional-method, the prototype-method decreased the isolation-time by 83.3%, lowered energy-consumption, without carbon-dioxide production, by reducing isolation-temperatures by more-than half, which protected the thermolabile-components, and increased the quantity by 2514-folds, and improved the quality of CE-EO composition and its antibacterial-potentials. Therefore, the DF-GC/MS-HUS prototype method is considered a novel green-technique that minimized the energy-utilization with higher-efficiency.
Assessing Australia’s future solar power ramps with climate projections
Authors: Poddar Shukla , Evans Jason P. , Kay Merlinde , Prasad Abhnil , Bremner Stephen
Published: August 2023

Increasing levels of photovoltaic (PV) penetration to the electricity grid brings challenges to both design and operation of the grid due to its vulnerability to climate change. A crucial aspect of PV operation is power ramps leading to variability and instability in the grid. With notable large-scale PV deployment planned, including the world’s largest planned solar energy infrastructure in Powell Creek Australia, characterising future ramps is crucial for ensuring stable power generation to support large-scale economic development. Using CORDEX-Australasia projections under RCP8.5 and RCP4.5 emission scenarios, future solar ramps across Australia have been characterised up to 2100. Results predict a reduction in ramp magnitude across Australia, with changes in frequency and period length varying with the location. This work highlights the importance of considering future changes in climate when designing large-scale solar farms to ensure the incorporation of frequency control devices and storage plans for a reliable power supply.
CMIP6 models informed summer human thermal discomfort conditions in Indian regional hotspot
Authors: Shukla Krishna Kumar , Attada Raju
Published: August 2023

The frequency and intensity of extreme thermal stress conditions during summer are expected to increase due to climate change. This study examines sixteen models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) that have been bias-adjusted using the quantile delta mapping method. These models provide Universal Thermal Climate Index (UTCI) for summer seasons between 1979 and 2010, which are regridded to a similar spatial grid as ERA5-HEAT (available at 0.25° × 0.25° spatial resolution) using bilinear interpolation. The evaluation compares the summertime climatology and trends of the CMIP6 multi-model ensemble (MME) mean UTCI with ERA5 data, focusing on a regional hotspot in northwest India (NWI). The Pattern Correlation Coefficient (between CMIP6 models and ERA5) values exceeding 0.9 were employed to derive the MME mean of UTCI, which was subsequently used to analyze the climatology and trends of UTCI in the CMIP6 models.The spatial climatological mean of CMIP6 MME UTCI demonstrates significant thermal stress over the NWI region, similar to ERA5. Both ERA5 and CMIP6 MME UTCI show a rising trend in thermal stress conditions over NWI. The temporal variation analysis reveals that NWI experiences higher thermal stress during the summer compared to the rest of India. The number of thermal stress days is also increasing in NWI and major Indian cities according to ERA5 and CMIP6 MME. Future climate projections under different scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5) indicate an increasing trend in thermal discomfort conditions throughout the twenty-first century. The projected rates of increase are approximately 0.09 °C per decade, 0.26 °C per decade, and 0.56 °C per decade, respectively. Assessing the near (2022–2059) and far (2060–2100) future, all three scenarios suggest a rise in intense heat stress days (UTCI > 38 °C) in NWI. Notably, the CMIP6 models predict that NWI could reach deadly levels of heat stress under the high-emission (SSP5-8.5) scenario. The findings underscore the urgency of addressing climate change and its potential impacts on human well-being and socio-economic sectors.
Effect of immersive virtual mirror visual feedback on Mu suppression and coherence in motor and parietal cortex in stroke
Authors: Chang Won Kee , Lim Hyunmi , Park Seo Hyun , Lim Chaiyoung , Paik Nam-Jong , Kim Won-Seok , Ku Jeonghun
Published: August 2023

We investigated the activation pattern of the motor cortex (M1) and parietal cortex during immersive virtual reality (VR)-based mirror visual feedback (MVF) of the upper limb in 14 patients with chronic stroke and severe upper limb hemiparesis and in 21 healthy controls. Participants performed wrist extension with unaffected wrists (dominant side in controls). In the MVF condition, movement of the affected hand was synchronized with that of the unaffected hand. In the no-MVF condition, only the movement of unaffected hand was shown. Mu suppression in bilateral M1 and parietal cortex and mu coherence were analyzed. In patients with stroke, MVF induced significant mu suppression in both the ipsilesional M1 and parietal lobes (p = 0.006 and p = 0.009, respectively), while mu suppression was observed in the bilateral M1 (p = 0.003 for ipsilesional and p = 0.041 for contralesional M1, respectively) and contralesional parietal lobes in the controls (p = 0.036). The ipsilesional mu coherence between the M1 and parietal cortex in patients with stroke was stronger than controls, regardless of MVF condition (p < 0.001), while mu coherence between interhemispheric M1 cortices was significantly weaker in patients with stroke (p = 0.032). Our findings provide evidence of the neural mechanism of MVF using immersive VR in patients with stroke.
Understanding non-stationarity of hydroclimatic extremes and resilience in Peninsular catchments, India
Authors: Kumar Nikhil , Patel Piyush , Singh Shivam , Goyal Manish Kumar
Published: August 2023

Climate change significantly impacts the global hydrological cycle, leading to pronounced shifts in hydroclimatic extremes such as increased duration, occurrence, and intensity. Despite these significant changes, our understanding of hydroclimatic risks and hydrological resilience remains limited, particularly at the catchment scale in peninsular India. This study aims to address this gap by examining hydroclimatic extremes and resilience in 54 peninsular catchments from 1988 to 2011. We initially assess extreme precipitation and discharge indices and estimate design return levels using non-stationary Generalized Extreme Value (GEV) models that use global climate modes (ENSO, IOD, and AMO) as covariates. Further, hydrological resilience is evaluated using a convex model that inputs simulated discharge from the best hydrological model among SVM, RVM, random forest, and a conceptual model (abcd). Our analysis shows that the spatial patterns of mean extreme precipitation indices (R1 and R5) mostly resemble with extreme discharge indices (Q1 and Q5). Additionally, all extreme indices, including R1, Q1, R5, and Q5, demonstrate non-stationary behavior, indicating the substantial influence of global climate modes on extreme precipitation and flooding across the catchments. Our results indicate that the random forest model outperforms the others. Furthermore, we find that 68.52% of the catchments exhibit low to moderate hydrological resilience. Our findings emphasize the importance of understanding hydroclimatic risks and catchment resilience for accurate climate change impact predictions and effective adaptation strategies.
Symptom profiles of community cases infected by influenza, RSV, rhinovirus, seasonal coronavirus, and SARS-CoV-2 variants of concern
Authors: Geismar Cyril , Nguyen Vincent , Fragaszy Ellen , Shrotri Madhumita , Navaratnam Annalan M. D. , Beale Sarah , Byrne Thomas E. , Fong Wing Lam Erica , Yavlinsky Alexei , Kovar Jana , Hoskins Susan , Braithwaite Isobel , Aldridge Robert W. , Hayward Andrew C.
Published: August 2023

Respiratory viruses that were suppressed through previous lockdowns during the COVID-19 pandemic have recently started to co-circulate with SARS-CoV-2. Understanding the clinical characteristics and symptomatology of different respiratory viral infections can help address the challenges related to the identification of cases and the understanding of SARS-CoV-2 variants' evolutionary patterns. Flu Watch (2006–2011) and Virus Watch (2020–2022) are household community cohort studies monitoring the epidemiology of influenza, respiratory syncytial virus, rhinovirus, seasonal coronavirus, and SARS-CoV-2, in England and Wales. This study describes and compares the proportion of symptoms reported during illnesses infected by common respiratory viruses. The SARS-CoV-2 symptom profile increasingly resembles that of other respiratory viruses as new strains emerge. Increased cough, sore throat, runny nose, and sneezing are associated with the emergence of the Omicron strains. As SARS-CoV-2 becomes endemic, monitoring the evolution of its symptomatology associated with new variants will be critical for clinical surveillance.
Systemic inflammatory indices for predicting prognosis of myelofibrosis
Authors: Ersal Tuba , Özkocaman Vildan , Pınar İbrahim Ethem , Yalçın Cumali , Orhan Bedrettin , Candar Ömer , Çubukçu Sinem , Koca Tuba Güllü , Hunutlu Fazıl Çağrı , Yavuz Şeyma , Ali Rıdvan , Özkalemkaş Fahir
Published: August 2023

The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.
Effect of nanostructure lipid carrier of methylene blue and monoterpenes as enzymes inhibitor for Culex pipiens
Authors: Radwan Ibrahim Taha , Sayed-Ahmed Mohamed Z. , Ghazawy Nirvina AbdelRaouf , Alqahtani Saad S. , Ahmad Sarfaraz , Alam Nawazish , Alkhaibari Abeer Mousa , Ali Md Sajid , Selim Abdelfattah , AbdelFattah Eman Alaaeldin
Published: August 2023

Solid lipid nanoparticles second generation, nanostructure lipid carrier (NLC), is one of the most important biodegradable nanoparticles. Nanostructure Lipid carrier (NLC) was used to encapsulate methylene blue (MB) dye, carvacrol and citronellal and their efficacy as insecticidal against Culex pipiens (Cx. pipiens) were distinguished. The prepared nanoformulation revealed very good physicochemical properties, especially the homogeneity of the particle size. Transmission electron microscope showed spherical shaped nanoparticles within range less than 200 nm. The prepared NLC-MB-MT system showed a very competitive insecticidal activity and high virulence against the mosquito larvae with higher mortality rate of LC50 of 0.141 µl/mL, in addition to high level of Oxidative stress parameters obtained through all the tested enzymes including hydrogen peroxide (4.8 ppm), protein carbonyl amount (0.12 OD/mg protein), ascorbic acid (0.15 mg) and Superoxide dismutase (SOD) showed strong increasing (0.09 OD/mg protein/min) at 6 µg/mL, respectively. Whereas paradoxical results of the oxidative stress enzymes were obtained from different concentration of nanoformulation that introduce a convenient reason for their potential insecticidal effect. The cytotoxic effect of NLC-MB-MT was evaluated using WI38 human lung cell lines, the LC50 was 6.4 mg/mL. The low cytotoxic reactivity towards the tested cell line makes the NLC-MB-MT nanoformulation has its promising insecticidal efficacy. Molecular docking study for each component were done against acetylcholine esterase protein and accepted binding modes achieved by the three compounds.