bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations and Analysis of the Mid‐Latitude Atmospheric Electric Field During Geomagnetic Activity
Authors: Qiu Shican , Xie Yifei , Shi Mengxi , Yousof Hamad , Soon Willie , Ren Zhengyong , Jia Mingjiao , Dou Xiankang
Published: October 2022

In this study, the diurnal and seasonal variation curves of atmospheric electric field () are obtained, based on the extensive observations at Mohe station (Geographical coordinates: 22.357°E, 53.482°N and geomagnetic coordinates: 195.5°E, 48.8°N) of the Chinese Meridian Project. The results show that the diurnal variation of conforms to the “Carnegie” pattern, and the value of in winter is higher than the summer. The coupling effect of the solar wind–magnetosphere with the atmospheric electric field is established. In total, 15 cases of magnetic storms are selected while Mohe is under fair weather condition throughout the storm period. The analyzed results reveal that exhibits the same characteristics during the 15 storms, that is, decreases sharply and changes simultaneously with the interplanetary magnetic field (IMF) component and solar wind proton number density. When the IMF– shifts to south, presents a large decrease with magnitudes of about 100 V/m–600 V/m.
Fingering Convection in the Stably Stratified Layers of Planetary Cores
Authors: Guervilly Céline
Published: October 2022

Stably stratified layers may be present at the top of the electrically conducting fluid layers of many planets either because the temperature gradient is locally subadiabatic or because a stable composition gradient is maintained by the segregation of chemical elements. Here we study the double‐diffusive processes taking place in such a stable layer, considering the case of Mercury's core where the temperature gradient is stable but the composition gradient is unstable over a 800 km‐thick layer. The large difference in the molecular diffusivities leads to the development of buoyancy‐driven instabilities that drive radial flows known as fingering convection. We model fingering convection using hydrodynamical simulations in a rotating spherical shell and varying the rotation rate and the stratification strength. For small Rayleigh numbers (i.e., weak background temperature and composition gradients), fingering convection takes the form of columnar flows aligned with the rotation axis and with an azimuthal size comparable with the layer thickness. For larger Rayleigh numbers, the flows retain a columnar structure but the azimuthal size is drastically reduced leading to thin sheet‐like structures that are elongated in the meridional direction. The azimuthal size decreases when the thermal stratification increases, following closely the scaling law expected from the linear planar theory (Stern, 1960, https://doi.org/10.1111/j.2153-3490.1960.tb01295.x). We find that the radial flows always remain laminar with local Reynolds number of order 1–10. Equatorially symmetric zonal flows form due to latitudinal variations of the axisymmetric composition. The zonal velocity exceeds the non‐axisymmetric velocities at the largest Rayleigh numbers. We discuss plausible implications for planetary magnetic fields.
In the Weeds: Aquatic Plant Biomarker Sources to Arctic Lake Sediments
Authors: Daniels William C.
Published: October 2022

In reconstructing past changes in precipitation or evaporation from the geologic record, paleoclimatologists sometimes employ the dual‐biomarker isotope method. This method requires that two co‐occurring sedimentary lipids are derived from different biological sources, and that their compound‐specific 2H/1H ratios record different aspects of the hydrologic cycle. Several studies have used this approach, typically by comparing the 2H/1H ratios of n‐alkyl lipids (δ2Hwax) thought to be sourced from aquatic versus terrestrial plants that gain their hydrogen atoms from lake water and soil water, respectively. Yet confidently fingerprinting n‐alkyl lipid sources continues to be a challenge because the wax inputs of different plant types vary across biomes, lake types, and time. New research in the Journal of Geophysical Research‐Biogeosciences by Hollister et al. (2022, https://doi.org/10.1029/2022jg006903) utilizes a combination of three independent metrics to demonstrate that for Arctic lakes, mid‐chain n‐alkanoic acids can be sourced principally from aquatic plants whereas long‐chain n‐alkanoic acids derive from a mixture of aquatic and terrestrial plants. By cataloging wax compound distributions and compound‐specific H and C isotopes of many new plant species, their efforts will strengthen future biomarker paleoclimatology and reinforce previous applications of the dual‐biomarker approach in high‐latitude lakes. The identification of a lake system with a strong aquatic plant wax signal in the sediments should motivate future targeting of similar lakes for reconstructing past moisture with the dual‐biomarker method.
A Vine Copula‐Based Ensemble Projection of Precipitation Intensity–Duration–Frequency Curves at Sub‐Daily to Multi‐Day Time Scales
Authors: Zhang Boen , Wang Shuo , Moradkhani Hamid , Slater Louise , Liu Jiafeng
Published: October 2022

Precipitation intensity–duration–frequency (IDF) curves play a crucial role in the design and planning of urban infrastructure to reduce the risk of urban flooding and rainfall‐triggered landslides. However, changing rainfall characteristics in a warming climate render conventional IDF curves inappropriate due to the statistical assumption of stationarity. In this study, we develop vine copula‐based projections of future IDF curves at sub‐daily to multi‐day time scales with a multi‐model ensemble of five regional climate simulations over China. Stochastic spatiotemporal downscaling of precipitation is achieved to generate extreme precipitation simulations at a high spatial (0.1°) and temporal (3 hourly) resolution. These downscaled simulations are combined by the vine copula to improve the reliability and accuracy of climate‐model‐based IDF curves relative to historical observations. Our findings reveal that climate‐model‐based stochastic downscaling of precipitation reproduces the IDF curves well based on historical observations in China. The vine copula multi‐model ensemble approach outperforms Bayesian model averaging by generating more accurate and reliable IDF curves. The urban areas of 196 Chinese cities are projected to experience an increase in extreme precipitation of up to 30% in intensity and nearly two times the frequency of historical events under a high emission scenario (RCP8.5). The current urban infrastructure of more than half of the 196 cities would thus be inadequate to prevent losses caused by rainfall‐triggered hazards if designed solely based on historical precipitation observations. Compared to the climate‐model‐based IDF curves, we find that statistical IDF curves based on a nonstationary time covariate (i.e., extrapolating historical trends) are likely to underestimate the risk of urban infrastructure failures under a warming climate. This work highlights that urban infrastructure design guidelines in China should be upgraded to adapt existing IDF curves to the changing climate.
Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis
Authors: Susai Subash Raj , Healy Colm , Mongan David , Heurich Meike , Byrne Jonah F. , Cannon Mary , Cagney Gerard , Wynne Kieran , Markulev Connie , Schäfer Miriam R. , Berger Maximus , Mossaheb Nilufar , Schlögelhofer Monika , Smesny Stefan , Hickie Ian B. , Berger Gregor E. , Chen Eric Y. H. , de Haan Lieuwe , Nieman Dorien H. , Nordentoft Merete , Riecher-Rössler Anita , Verma Swapna , Street Rebekah , Thompson Andrew , Yung Alison Ruth , Nelson Barnaby , McGorry Patrick D. , Föcking Melanie , Amminger G. Paul , Cotter David
Published: October 2022

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.
Neurexin1α knockout rats display oscillatory abnormalities and sensory processing deficits back-translating key endophenotypes of psychiatric disorders
Authors: Janz Philipp , Bainier Marie , Marashli Samuel , Schoenenberger Philipp , Valencia Miguel , Redondo Roger L.
Published: October 2022

Neurexins are presynaptic transmembrane proteins crucial for synapse development and organization. Deletion and missense mutations in all three Neurexin genes have been identified in psychiatric disorders, with mutations in the NRXN1 gene most strongly linked to schizophrenia (SZ) and autism spectrum disorder (ASD). While the consequences of NRXN1 deletion have been extensively studied on the synaptic and behavioral levels, circuit endophenotypes that translate to the human condition have not been characterized yet. Therefore, we investigated the electrophysiology of cortico-striatal-thalamic circuits in Nrxn1α−/−rats and wildtype littermates focusing on a set of translational readouts, including spontaneous oscillatory activity, auditory-evoked oscillations and potentials, as well as mismatch negativity-like (MMN) responses and responses to social stimuli. On the behavioral level Nrxn1α−/−rats showed locomotor hyperactivity. In vivo freely moving electrophysiology revealed pronounced increases of spontaneous oscillatory power within the gamma band in all studied brain areas and elevation of gamma coherence in cortico-striatal and thalamocortical circuits of Nrxn1α−/−rats. In contrast, auditory-evoked oscillations driven by chirp-modulated tones showed reduced power in cortical areas confined to slower oscillations. Finally, Nrxn1α−/−rats exhibited altered auditory evoked-potentials and profound deficits in MMN-like responses, explained by reduced prediction error. Despite deficits for auditory stimuli, responses to social stimuli appeared intact. A central hypothesis for psychiatric and neurodevelopmental disorders is that a disbalance of excitation-to-inhibition is underlying oscillatory and sensory deficits. In a first attempt to explore the impact of inhibitory circuit modulation, we assessed the effects of enhancing tonic inhibition via δ-containing GABAAreceptors (using Gaboxadol) on endophenotypes possibly associated with network hyperexcitability. Pharmacological experiments applying Gaboxadol showed genotype-specific differences, but failed to normalize oscillatory or sensory processing abnormalities. In conclusion, our study revealed endophenotypes in Nrxn1α−/−rats that could be used as translational biomarkers for drug development in psychiatric disorders.
Prognostic impact of ASXL1 mutations in chronic phase chronic myeloid leukemia
Authors: Bidikian Aram , Kantarjian Hagop , Jabbour Elias , Short Nicholas J. , Patel Keyur , Ravandi Farhad , Sasaki Koji , Issa Ghayas C.
Published: October 2022

While the clinical impact of mutations in the ABL1 gene on response to therapy in chronic phase chronic myeloid leukemia (CP-CML) is well established, less is known about how other mutations affect prognosis. In a retrospective analysis, we identified 115 patients with CML (71 chronic, 15 accelerated and 29 blast phase) where targeted next-generation sequencing of genes recurrently mutated in myeloid leukemias was performed. ASXL1 was the most frequently mutated gene in the chronic (14%) and accelerated phase (40%) CML patients, whereas RUNX1 (20%) was the most common mutation in blast phase. Compared with wild-type ASXL1, CP-CML with mutant ASXL1 was associated with worse event-free survival (EFS) (median of 32.8 vs 88.3 months; P = 0.002) and failure-free survival (median of 13.8 vs 57.8 months; P = 0.04). In a multivariate analysis, ASXL1 mutation was the only independent risk factor associated with worse EFS in chronic phase CML with a hazard ratio of 4.25 (95% CI 1.59–11.35, P = 0.004). In conclusion, mutations in ASXL1 are associated with worse outcomes when detected in chronic phase CML.
Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer
Authors: Coelho Ricardo , Tozzi Alessandra , Disler Muriel , Lombardo Flavio , Fedier André , López Mónica Núñez , Freuler Florian , Jacob Francis , Heinzelmann-Schwarz Viola
Published: October 2022

PARP inhibitors (PARPi) have revolutionized the therapeutic landscape of epithelial ovarian cancer (EOC) treatment with outstanding benefits in regard to progression-free survival, especially in patients either carrying BRCA1/2 mutations or harboring defects in the homologous recombination repair system. Yet, it remains uncertain which PARPi to apply and how to predict responders when platinum sensitivity is unknown. To shed light on the predictive power of genes previously suggested to be associated with PARPi response, we systematically reviewed the literature and identified 79 publications investigating a total of 93 genes. The top candidate genes were further tested using a comprehensive CRISPR-Cas9 mutagenesis screening in combination with olaparib treatment. Therefore, we generated six constitutive Cas9+ EOC cell lines and profiled 33 genes in a CRISPR-Cas9 cell competition assay using non-essential (AAVS1) and essential (RPA3 and PCNA) genes for cell fitness as negative and positive controls, respectively. We identified only ATM, MUS81, NBN, BRCA2, and RAD51B as predictive markers for olaparib response. As the major survival benefit of PARPi treatment was reported in platinum-sensitive tumors, we next assessed nine top candidate genes in combination with three PARPi and carboplatin. Interestingly, we observed similar dropout rates in a gene and compound independent manner, supporting the strong correlation of cancer cell response to compounds that rely on DNA repair for their effectiveness. In addition, we report on CDK12 as a common vulnerability for EOC cell survival and proliferation without altering the olaparib response, highlighting its potential as a therapeutic target in EOC.
The interplay of transcriptional coregulator NUPR1 with SREBP1 promotes hepatocellular carcinoma progression via upregulation of lipogenesis
Authors: Wang Yongjia , Zhang Yuqin , Wang Zixuan , Yu Lu , Chen Keli , Xie Yuwen , Liu Yang , Liang Weijie , Zheng Yilin , Zhan Yizhi , Ding Yi
Published: October 2022

Nuclear protein 1 (NUPR1) is a transcriptional coregulator that has been implicated in the development of various cancer types. In addition, de novo fatty acid synthesis plays a pivotal role in hepatocellular carcinoma (HCC) development. However, little is currently known on the role of NUPR1 in hepatocellular carcinoma. In this study, bioinformatics analysis was conducted to analyze the expression level, prognosis value and enriched pathways of NUPR1 in Liver Hepatocellular Carcinoma (LIHC). We found that NUPR1 was significantly upregulated in human hepatocellular carcinoma cells compared with normal hepatocytes from LIHC patients in TCGA cohorts and our patients. Kaplan–Meier analysis and COX proportional hazard progression model showed that high expression of NUPR1 was correlated with a poor prognosis of LIHC patients. CCK-8, EdU and colony formation assays were performed to explore the effect of NUPR1 on the proliferation of HCC cells, then wound healing and transwell migration assays were performed to evaluate the effects of NUPR1 on cell migration. Furthermore, subcutaneous xenograft models were established to study tumor growth. Results showed that NUPR1 overexpression correlated with a highly proliferative and aggressive phenotype. In addition, NUPR1 knockdown significantly inhibited hepatocellular carcinoma cell proliferation and migration in vitro and hindered tumorigenesis in vivo. Mechanistically, endogenous NUPR1 could interact with sterol regulatory element binding protein 1 (SREBP1) and upregulated lipogenic gene expression of fatty acid synthase (FASN), resulting in the accumulation of lipid content. Moreover, pharmacological or genetic blockade of the NUPR1-SREBP1/FASN pathway enhanced anticancer activity in vitro and in vivo. Overall, we identified a novel function of NUPR1 in regulating hepatocellular carcinoma progression via modulation of SREBP1-mediated de novo lipogenesis. Targeting NUPR1-SREBP1/FASN pathway may be a therapeutic alternative for hepatocellular carcinoma.
Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway
Authors: Shen Kunyu , Miao Jinhua , Gao Qiongdan , Ling Xian , Liang Ye , Zhou Qin , Song Qirong , Luo Yuxin , Wu Qinyu , Shen Weiwei , Wang Xiaonan , Li Xiaolong , Liu Youhua , Zhou Shan , Tang Ying , Zhou Lili
Published: October 2022

Acute kidney injury (AKI) is in high prevalence in the world. However, the therapeutic strategies for AKI are still in mystery. Studies have shown to improve autophagy and lysosomal function could inhibit AKI. But their modulators need to be explored in detail. Annexin A2 (ANXA2) is a phospholipid-binding protein involving in organelle membrane integrity function, suggesting its important role in autophagy and lysosome homeostasis. It implicates ANXA2 potentially protects against AKI. However, this has not been elucidated. Herein, we found that ANXA2 is increased in renal tubules in cisplatin-induced AKI mice. Ectopic expression of ANXA2 improved lysosomal functions and enhanced autophagic flux, further protecting against renal tubular cell apoptosis and kidney injury. Conversely, knockdown of ANXA2 inhibited lysosomal function and autophagy, which aggravated the progression of AKI. Transcriptome sequencing revealed β-catenin signaling is highly responsible for this process. In vitro, we found ANXA2 induced β-catenin activation, further triggering T-cell factor-4 (TCF4)-induced transcription factor EB (TFEB). Furthermore, TFEB promoted lysosome biogenesis to enhance autophagic flux, resulting in the alleviation of AKI. Our new findings underline ANXA2 is a new therapeutic potential for AKI through modulating autophagy and lysosomal function. The underlying mechanism is associated with its inductive effects on β-catenin/TFEB pathway.
Direct observations of energy transfer from resonant electrons to whistler-mode waves in magnetosheath of Earth
Authors: Kitamura N. , Amano T. , Omura Y. , Boardsen S. A. , Gershman D. J. , Miyoshi Y. , Kitahara M. , Katoh Y. , Kojima H. , Nakamura S. , Shoji M. , Saito Y. , Yokota S. , Giles B. L. , Paterson W. R. , Pollock C. J. , Barrie A. C. , Skeberdis D. G. , Kreisler S. , Le Contel O. , Russell C. T. , Strangeway R. J. , Lindqvist P.-A. , Ergun R. E. , Torbert R. B. , Burch J. L.
Published: October 2022

Electromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA’s Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations.
A slit-diaphragm-associated protein network for dynamic control of renal filtration
Authors: Kocylowski Maciej K. , Aypek Hande , Bildl Wolfgang , Helmstädter Martin , Trachte Philipp , Dumoulin Bernhard , Wittösch Sina , Kühne Lukas , Aukschun Ute , Teetzen Carolin , Kretz Oliver , Gaal Botond , Kulik Akos , Antignac Corinne , Mollet Geraldine , Köttgen Anna , Göcmen Burulca , Schwenk Jochen , Schulte Uwe , Huber Tobias B. , Fakler Bernd , Grahammer Florian
Published: October 2022

The filtration of blood in the kidney which is crucial for mammalian life is determined by the slit-diaphragm, a cell-cell junction between the foot processes of renal podocytes. The slit-diaphragm is thought to operate as final barrier or as molecular sensor of renal filtration. Using high-resolution proteomic analysis of slit-diaphragms affinity-isolated from rodent kidney, we show that the native slit-diaphragm is built from the junction-forming components Nephrin, Neph1 and Podocin and a co-assembled high-molecular weight network of proteins. The network constituents cover distinct classes of proteins including signaling-receptors, kinases/phosphatases, transporters and scaffolds. Knockout or knock-down of either the core components or the selected network constituents tyrosine kinase MER (MERTK), atrial natriuretic peptide-receptor C (ANPRC), integral membrane protein 2B (ITM2B), membrane-associated guanylate-kinase, WW and PDZ-domain-containing protein1 (MAGI1) and amyloid protein A4 resulted in target-specific impairment or disruption of the filtration process. Our results identify the slit-diaphragm as a multi-component system that is endowed with context-dependent dynamics via a co-assembled protein network.
Laboratory evidence of magnetic reconnection hampered in obliquely interacting flux tubes
Authors: Bolaños Simon , Sladkov Andrey , Smets Roch , Chen Sophia N. , Grisollet Alain , Filippov Evgeny , Henares Jose-Luis , Nastasa Viorel , Pikuz Sergey , Riquier Raphël , Safronova Maria , Severin Alexandre , Starodubtsev Mikhail , Fuchs Julien
Published: October 2022

Magnetic reconnection can occur when two plasmas, having anti-parallel components of the magnetic field, encounter each other. In the reconnection plane, the anti-parallel component of the field is annihilated and its energy released in the plasma. Here, we investigate through laboratory experiments the reconnection between two flux tubes that are not strictly anti-parallel. Compression of the anti-parallel component of the magnetic field is observed, as well as a decrease of the reconnection efficiency. Concomitantly, we observe delayed plasma heating and enhanced particle acceleration. Three-dimensional hybrid simulations support these observations and highlight the plasma heating inhibition and reconnection efficiency reduction for these obliquely oriented flux tubes.
Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase
Authors: Lei Ruipeng , Tan Timothy J. C. , Hernandez Garcia Andrea , Wang Yiquan , Diefenbacher Meghan , Teo Chuyun , Gopan Gopika , Tavakoli Dargani Zahra , Teo Qi Wen , Graham Claire S. , Brooke Christopher B. , Nair Satish K. , Wu Nicholas C.
Published: October 2022

Neuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories of NA remain largely elusive. Here, we show that among 70 natural mutations that are present in the NA of a recent human H3N2 strain, >10% are deleterious for an ancestral strain. By mapping the permissive mutations using combinatorial mutagenesis and next-generation sequencing, an extensive epistatic network is revealed. Biophysical and structural analyses further demonstrate that certain epistatic interactions can be explained by non-additive stability effect, which in turn modulates membrane trafficking and enzymatic activity of NA. Additionally, our results suggest that other biophysical mechanisms also contribute to epistasis in NA evolution. Overall, these findings not only provide mechanistic insights into the evolution of human influenza NA and elucidate its sequence-structure-function relationship, but also have important implications for the development of next-generation influenza vaccines.
The N6-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity
Authors: Yoshinaga Masanori , Han Kyuho , Morgens David W. , Horii Takuro , Kobayashi Ryosuke , Tsuruyama Tatsuaki , Hia Fabian , Yasukura Shota , Kajiya Asako , Cai Ting , Cruz Pedro H. C. , Vandenbon Alexis , Suzuki Yutaka , Kawahara Yukio , Hatada Izuho , Bassik Michael C. , Takeuchi Osamu
Published: October 2022

During erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N6-methyladenosine (m6A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m6A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis.
Critical role of water structure around interlayer ions for ion storage in layered double hydroxides
Authors: Sudare Tomohito , Yamaguchi Takuro , Ueda Mizuki , Shiiba Hiromasa , Tanaka Hideki , Tipplook Mongkol , Hayashi Fumitaka , Teshima Katsuya
Published: October 2022

Water-containing layered materials have found various applications such as water purification and energy storage. The highly structured water molecules around ions under the confinement between the layers determine the ion storage ability. Yet, the relationship between the configuration of interlayer ions and water structure in high ion storage layered materials is elusive. Herein, using layered double hydroxides, we demonstrate that the water structure is sensitive to the filling density of ions in the interlayer space and governs the ion storage. For ion storage of dilute nitrate ions, a 24% decrease in the filling density increases the nitrate storage capacity by 300%. Quartz crystal microbalance with dissipation monitoring studies, combined with multimodal ex situ experiments and theoretical calculations, reveal that the decreasing filling density effectively facilitates the 2D hydrogen-bond networking structure in water around interlayer nitrate ions along with minimal change in the layered structure, leading to the high storage capacity.
Effective screening of Coulomb repulsions in water accelerates reactions of like-charged compounds by orders of magnitude
Authors: Kowalski Adam , Bielec Krzysztof , Bubak Grzegorz , Żuk Pawel J. , Czajkowski Maciej , Sashuk Volodymyr , Huck Wilhelm T. S. , Antosiewicz Jan M. , Holyst Robert
Published: October 2022

The reaction kinetics between like-charged compounds in water is extremely slow due to Coulomb repulsions. Here, we demonstrate that by screening these interactions and, in consequence, increasing the local concentration of reactants, we boost the reactions by many orders of magnitude. The reaction between negatively charged Coenzyme A molecules accelerates ~5 million-fold using cationic micelles. That is ~104 faster kinetics than in 0.5 M NaCl, although the salt is ~106 more concentrated. Rate enhancements are not limited to micelles, as evidenced by significant catalytic effects (104–105-fold) of other highly charged species such as oligomers and polymers. We generalize the observed phenomenon by analogously speeding up a non-covalent complex formation—DNA hybridization. A theoretical analysis shows that the acceleration is correlated to the catalysts’ surface charge density in both experimental systems and enables predicting and controlling reaction rates of like-charged compounds with counter-charged species.
Coexisting divergent and convergent plate boundary assemblages indicate plate tectonics in the Neoarchean
Authors: Huang Bo , Johnson Tim E. , Wilde Simon A. , Polat Ali , Fu Dong , Kusky Timothy
Published: October 2022

The coexistence of divergent (spreading ridge) and convergent (subduction zone) plate boundaries at which lithosphere is respectively generated and destroyed is the hallmark of plate tectonics. Here, we document temporally- and spatially-associated Neoarchean (2.55–2.51 Ga) rock assemblages with mid-ocean ridge and supra-subduction-zone origins from the Angou Complex, southern North China Craton. These assemblages record seafloor spreading and contemporaneous subduction initiation and mature arc magmatism, respectively, analogous to modern divergent and convergent plate boundary processes. Our results provide direct evidence for lateral plate motions in the late Neoarchean, and arguably the operation of plate tectonics, albeit with warmer than average Phanerozoic subduction geotherms. Further, we surmise that plate tectonic processes played an important role in shaping Earth’s surficial environments during the Neoarchean and Paleoproterozoic.
Genetically-informed prediction of short-term Parkinson’s disease progression
Authors: Sadaei Hossein J. , Cordova-Palomera Aldo , Lee Jonghun , Padmanabhan Jaya , Chen Shang-Fu , Wineinger Nathan E. , Dias Raquel , Prilutsky Daria , Szalma Sandor , Torkamani Ali
Published: October 2022

Parkinson’s disease (PD) treatments modify disease symptoms but have not been shown to slow progression, characterized by gradual and varied motor and non-motor changes overtime. Variation in PD progression hampers clinical research, resulting in long and expensive clinical trials prone to failure. Development of models for short-term PD progression prediction could be useful for shortening the time required to detect disease-modifying drug effects in clinical studies. PD progressors were defined by an increase in MDS-UPDRS scores at 12-, 24-, and 36-months post-baseline. Using only baseline features, PD progression was separately predicted across all timepoints and MDS-UPDRS subparts in independent, optimized, XGBoost models. These predictions plus baseline features were combined into a meta-predictor for 12-month MDS UPDRS Total progression. Data from the Parkinson’s Progression Markers Initiative (PPMI) were used for training with independent testing on the Parkinson’s Disease Biomarkers Program (PDBP) cohort. 12-month PD total progression was predicted with an F-measure 0.77, ROC AUC of 0.77, and PR AUC of 0.76 when tested on a hold-out PPMI set. When tested on PDBP we achieve a F-measure 0.75, ROC AUC of 0.74, and PR AUC of 0.73. Exclusion of genetic predictors led to the greatest loss in predictive accuracy; ROC AUC of 0.66, PR AUC of 0.66–0.68 for both PPMI and PDBP testing. Short-term PD progression can be predicted with a combination of survey-based, neuroimaging, physician examination, and genetic predictors. Dissection of the interplay between genetic risk, motor symptoms, non-motor symptoms, and longer-term expected rates of progression enable generalizable predictions.
Sustainable plant-based ingredients as wheat flour substitutes in bread making
Authors: Wang Yaqin , Jian Ching
Published: October 2022

Bread as a staple food has been predominantly prepared from refined wheat flour. The world’s demand for food is rising with increased bread consumption in developing countries where climate conditions are unsuitable for wheat cultivation. This reliance on wheat increases the vulnerability to wheat supply shocks caused by force majeure or man-made events, in addition to negative environmental and health consequences. In this review, we discuss the contribution to the sustainability of food systems by partially replacing wheat flour with various types of plant ingredients in bread making, also known as composite bread. The sustainable sources of non-wheat flours, their example use in bread making and potential health and nutritional benefits are summarized. Non-wheat flours pose techno-functional challenges due to significantly different properties of their proteins compared to wheat gluten, and they often contain off-favor compounds that altogether limit the consumer acceptability of final bread products. Therefore, we detail recent advances in processing strategies to improve the sensory and nutritional profiles of composite bread. A special focus is laid on fermentation, for its accessibility and versatility to apply to different ingredients and scenarios. Finally, we outline research needs that require the synergism between sustainability science, human nutrition, microbiomics and food science.
Genome-scale metabolic modeling reveals increased reliance on valine catabolism in clinical isolates of Klebsiella pneumoniae
Authors: Jenior Matthew L. , Dickenson Mary E. , Papin Jason A.
Published: October 2022

Infections due to carbapenem-resistant Enterobacteriaceae have recently emerged as one of the most urgent threats to hospitalized patients within the United States and Europe. By far the most common etiological agent of these infections is Klebsiella pneumoniae, frequently manifesting in hospital-acquired pneumonia with a mortality rate of ~50% even with antimicrobial intervention. We performed transcriptomic analysis of data collected previously from in vitro characterization of both laboratory and clinical isolates which revealed shifts in expression of multiple master metabolic regulators across isolate types. Metabolism has been previously shown to be an effective target for antibacterial therapy, and genome-scale metabolic network reconstructions (GENREs) have provided a powerful means to accelerate identification of potential targets in silico. Combining these techniques with the transcriptome meta-analysis, we generated context-specific models of metabolism utilizing a well-curated GENRE of K. pneumoniae (iYL1228) to identify novel therapeutic targets. Functional metabolic analyses revealed that both composition and metabolic activity of clinical isolate-associated context-specific models significantly differs from laboratory isolate-associated models of the bacterium. Additionally, we identified increased catabolism of L-valine in clinical isolate-specific growth simulations. These findings warrant future studies for potential efficacy of valine transaminase inhibition as a target against K. pneumoniae infection.
Amphiphile-CpG vaccination induces potent lymph node activation and COVID-19 immunity in mice and non-human primates
Authors: Seenappa Lochana M. , Jakubowski Aniela , Steinbuck Martin P. , Palmer Erica , Haqq Christopher M. , Carter Crystal , Fontenot Jane , Villinger Francois , McNeil Lisa K. , DeMuth Peter C.
Published: October 2022

Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
HiFi chromosome-scale diploid assemblies of the grape rootstocks 110R, Kober 5BB, and 101–14 Mgt
Authors: Minio Andrea , Cochetel Noé , Massonnet Mélanie , Figueroa-Balderas Rosa , Cantu Dario
Published: October 2022

Cultivated grapevines are commonly grafted on closely related species to cope with specific biotic and abiotic stress conditions. The three North American Vitis species V. riparia, V. rupestris, and V. berlandieri, are the main species used for breeding grape rootstocks. Here, we report the diploid chromosome-scale assembly of three widely used rootstocks derived from these species: Richter 110 (110R), Kober 5BB, and 101–14 Millardet et de Grasset (Mgt). Draft genomes of the three hybrids were assembled using PacBio HiFi sequences at an average coverage of 53.1 X-fold. Using the tool suite HaploSync, we reconstructed the two sets of nineteen chromosome-scale pseudomolecules for each genome with an average haploid genome size of 494.5 Mbp. Residual haplotype switches were resolved using shared-haplotype information. These three reference genomes represent a valuable resource for studying the genetic basis of grape adaption to biotic and abiotic stresses, and designing trait-associated markers for rootstock breeding programs.
Assessing the costs of GHG emissions of multi-product agricultural systems in Vietnam
Authors: Yamamoto Aito , Huynh Thi Kim Uyen , Saito Yoko , Matsuishi Takashi Fritz
Published: October 2022

Besides a vital sector of the economy, agriculture is a primary source of greenhouse gas (GHG) emissions. The present paper investigates the impact of carbon tax policy on Vietnamese agriculture by focusing on multi-product systems such as rice, livestock, and aquaculture, traditionally called the Vuon (Garden)–Ao (Pond)–Chuong (livestock pen) system (VAC). In it, farmers use garden, pond, and pen by-products as fertilizer and feed. We use shadow prices and Morishima substitution elasticities as greenhouse gas emissions indicators, estimated with directional output distance function. Farmers in the Mekong Delta region are found to be technologically less efficient than in other regions of Vietnam, though the shadow prices of GHG emissions are lower there too. This indicates that farmers in the Mekong Delta, generally concentrating either on livestock or aquaculture, have greater potential for reducing GHG emissions by way of improvements in technical efficiency than do those in other regions. However, Morishima elasticity estimates show that policy impacts diminish more quickly in the Mekong than elswhere. We suggest the Vietnamese government encourage Mekong Delta farmers to employ technologically more efficient methods or shift to more balanced farming to reduce the shadow price of GHG emissions, encouraging more efficient emissions reduction.
Influence of energy loss function to the Monte Carlo simulated electron backscattering coefficient
Authors: Chen Haotian , Zou Yanbo , Mao Shifeng , Khan M. S. S. , Tőkési Károly , Ding Z. J.
Published: October 2022

We report an improved calculation of the electron backscattering coefficients (BSCs) for beryllium, molybdenum and tungsten at electron energies of 0.1–100 keV based on an up-to-date Monte Carlo simulation method with different input of energy loss function (ELF) data. The electron inelastic cross-section is derived from the relativistic dielectric functional formalism, where the full Penn’s algorithm is applied for the extension of the ELF from the optical limit of $$q \to 0$$

q
→
0

into the $$\left( {q,\omega } \right)$$

q
,
ω

-plane. We have found that the accuracy of energy loss function may affect largely the calculated BSC. We also show that this has close relationship with the f- and ps-sum rules.
Effects of oligo-fucoidan on the immune response, inflammatory status and pulmonary function in patients with asthma: a randomized, double-blind, placebo-controlled trial
Authors: Yeh Chia-wei , Shih Chia-Ju , Liu Tu-Chen , Chiou Ya-ling
Published: October 2022

Asthma is a common disease occurring worldwide. The clinical treatment of asthma is constantly revised and updated; however, it is associated with side effects. Our previous in vitro and ex vivo studies found that oligo-fucoidan can improve allergic immune responses and reduce airway inflammation. The purpose of this clinical trial was to investigate the effects of oligo-fucoidan on the immune status, inflammatory response, and pulmonary function of patients with asthma. Twenty asthmatic patients were randomly divided into two groups: (1) control group: receiving regular asthma treatment and supplementation with placebo; (2) fucoidan group: receiving regular asthma treatment and supplementation with oligo-fucoidan. Pulmonary function tests, the "Asthma Control Questionnaire" survey, biochemical data, inflammatory factors, and immune cell subtypes were detected. During treatment, the levels of WBC (p = 0.038) and creatinine (p = 0.012 and p = 0.008 at 12th and 24th weeks) were significantly decreased in the fucoidan group. Lung function (FEV1/FVC pr) significantly increased in the fucoidan group (p = 0.046). Regarding the proportion of immune cells, the level of IFN+ and CD4+IFN+cells in the fucoidan group was significantly increased during the treatment period (P < 0.05), while the proportions of CD3+CD4+ cells (p = 0.048) and CD3+CD8+ cells (p = 0.009) in the fucoidan group were significantly decreased during the treatment period. Regarding cytokines, the level of interleukin-8 (IL-8) was also significantly reduced in the fucoidan group during the treatment period.
RETRACTED ARTICLE: Conceptualising a channel-based overlapping CNN tower architecture for COVID-19 identification from CT-scan images
Authors: Tiwari Ravi Shekhar , D Lakshmi , Das Tapan Kumar , Srinivasan Kathiravan , Chang Chuan-Yu
Published: October 2022

Convolutional Neural Network (CNN) has been employed in classifying the COVID cases from the lungs’ CT-Scan with promising quantifying metrics. However, SARS COVID-19 has been mutated, and we have many versions of the virus B.1.1.7, B.1.135, and P.1, hence there is a need for a more robust architecture that will classify the COVID positive patients from COVID negative patients with less training. We have developed a neural network based on the number of channels present in the images. The CNN architecture is developed in accordance with the number of the channels present in the dataset and are extracting the features separately from the channels present in the CT-Scan dataset. In the tower architecture, the first tower is dedicated for only the first channel present in the image; the second CNN tower is dedicated to the first and second channel feature maps, and finally the third channel takes account of all the feature maps from all three channels. We have used two datasets viz. one from Tongji Hospital, Wuhan, China and another SARS-CoV-2 dataset to train and evaluate our CNN architecture. The proposed model brought about an average accuracy of 99.4%, F1 score 0.988, and AUC 0.99.
Transcriptome analysis of mulberry (Morus alba L.) leaves to identify differentially expressed genes associated with post-harvest shelf-life elongation
Authors: Das Dipayan , Bhattacharyya Subires , Bhattacharyya Monidipa , Sashankar Puja , Ghosh Arindam , Mandal Palash
Published: October 2022

Present study deals with molecular expression patterns responsible for post-harvest shelf-life extension of mulberry leaves. Quantitative profiling showed retention of primary metabolite and accumulation of stress markers in NS7 and CO7 respectively. The leaf mRNA profiles was sequenced using the Illumina platform to identify DEGs. A total of 3413 DEGs were identified between the treatments. Annotation with Arabidopsis database has identified 1022 DEGs unigenes. STRING generated protein–protein interaction, identified 1013 DEGs nodes with p < 1.0e−16. KEGG classifier has identified genes and their participating biological processes. MCODE and BiNGO detected sub-networking and ontological enrichment, respectively at p ≤ 0.05. Genes associated with chloroplast architecture, photosynthesis, detoxifying ROS and RCS, and innate-immune response were significantly up-regulated, responsible for extending shelf-life in NS7. Loss of storage sucrose, enhanced activity of senescence-related hormones, accumulation of xenobiotics, and development of osmotic stress inside tissue system was the probable reason for tissue deterioration in CO7. qPCR validation of DEGs was in good agreement with RNA sequencing results, indicating the reliability of the sequencing platform. Present outcome provides a molecular insight regarding involvement of genes in self-life extension, which might help the sericulture industry to overcome their pre-existing problems related to landless farmers and larval feeding during monsoon.