bluuebunny/crossref_metadata_2025 huggingface dataset:
Atmospheric Circulation Constraints on 21st Century Seasonal Precipitation Storylines for the Southwestern United States
Authors: Grise Kevin M.
Published: August 2022

Precipitation is vital for the water‐limited region of the southwestern United States. Coupled Model Intercomparison Project Phase 6 global climate models project 21st century precipitation trends of varying sign for this region, even if forced by an identical anthropogenic emissions scenario. This study investigates the role of the present‐day and future atmospheric circulation in driving the disparity in precipitation trends among models. The wettest model projections are linked to the development of an anomalous mid‐tropospheric trough over the eastern North Pacific Ocean, which depends in part on future unpredictable internal variability. By contrast, future precipitation trends are also linked to models' representation of the present‐day climatological mid‐tropospheric ridge over western North America. Models that fail to properly simulate this ridge in the present‐day climatology are responsible for the most extreme outlier precipitation scenarios for the Southwest for the 21st century: extreme drying in winter and extreme wetting in summer.
Evidence for Anthropogenic Organic Aerosols Contributing to Ice Nucleation
Authors: Tian Ping , Liu Dantong , Bi Kai , Huang Mengyu , Wu Yangzhou , Hu Kang , Li Ruijie , He Hui , Ding Deping , Hu Yaqiong , Liu Quan , Zhao Delong , Qiu Yan , Kong Shaofei , Xue Huiwen
Published: August 2022

The role of organic aerosols (OA) as ice nucleating particles (INPs) deserves attention because of their high atmospheric abundance. The low concentration of INPs poses challenges in identifying the ice nucleation (IN) of OA among a mix of aerosol types in ambient environment. This study coupled a catalytic stripper system (350°C heating) with a continuous flow diffusion chamber to online investigate the immersion INPs of ambient particles at −30°C at a suburban site. Significant reduction (71 ± 25%) of INP concentrations after evaporation suggested that INPs can be significantly contributed by volatile OA. In addition, nonvolatile OA were more efficient INPs than black carbon. Oxygenated OA by photooxidation and lower ambient promoted the IN activity at noon, when the OA may be more viscous. These results hereby present the first field evidence that OA in anthropogenically influenced regions can be efficient INPs well above the homogeneous IN temperature.
Kinematic Representations of Linear and Power‐Law Viscoelastic Deformation Through the Earthquake Cycle
Authors: Meade Brendan J. , Mallick Rishav , Carrero‐Mustelier Emily
Published: August 2022

Viscoelastic deformation below the Earth's elastic crust is modulated by stresses generated by both plate tectonic and earthquake cycle processes. Rapid near‐fault deformation following large earthquakes has been interpreted as the signature of viscoelastic stress diffusion in the upper mantle and earthquake cycle models have been developed that integrated this effect throughout the duration of the earthquake cycle. Here we develop a surrogate method to approximate the upper crustal kinematics associated with time‐dependent viscoelastic deformation that does not require knowledge of nor provide constraints on subcrustal rheology. To do this we show how the effects of deformation in the viscoelastic upper mantle can be emulated by introducing a set of effective dislocations at crust‐mantle interface. The approach is shown to approximate both linear and power‐law viscoelastic rheologies and offers a way to accurately represent viscoelastic kinematics even in the case where upper mantle rheology is poorly constrained.
Generalization of Runoff Risk Prediction at Field Scales to a Continental‐Scale Region Using Cluster Analysis and Hybrid Modeling
Authors: Ford Chanse M. , Hu Yao , Ghosh Chirantan , Fry Lauren M. , Malakpour‐Estalaki Siamak , Mason Lacey , Fitzpatrick Lindsay , Mazrooei Amir , Goering Dustin C.
Published: August 2022

As surface water resources in the U.S. continue to be pressured by excess nutrients carried by agricultural runoff, the need to assess runoff risk at the field scale continues to grow in importance. Most landscape hydrologic models developed at regional scales have limited applicability at finer spatial scales. Hybrid models can be used to address the scale mismatch between model simulation and applicability, but could be limited by their ability to generalize over a large domain with heterogeneous hydrologic characteristics. To assist the generalization, we develop a regionalization approach based on the principal component analysis and K‐means clustering to identify the clusters with similar runoff potential over the Great Lakes region. For each cluster, hybrid models are developed by combining National Oceanic and Atmospheric Administration's National Water Model and a data‐driven model, eXtreme gradient boosting with field‐scale measurements, enabling prediction of daily runoff risk level at the field scale over the entire region.
Observations of the First Harmonic of Saturn Kilometric Radiation During Cassini's Grand Finale
Authors: Wu Siyuan , Zarka Philippe , Lamy Laurent , Taubenschuss Ulrich , Cecconi Baptiste , Ye Shengyi , Fischer Georg , Kurth William S. , Francez Théo
Published: August 2022

Clear first harmonic emissions of Saturn Kilometric Radiation are discovered during the Cassini Grand Finale orbits. Both ordinary (O) and extraordinary (X) mode fundamental emissions accompanied by X mode harmonics are observed. Analysis shows that the frequency ratio between the fundamental and harmonic emissions is 2.01 ± 0.08, and the harmonic emissions display weaker intensities than the fundamental, by 30–40 dB for the X‐X (fundamental‐harmonic) type harmonic and 10–30 dB for the O‐X type harmonic. The intensity relations between the two types of harmonics, that is, O‐X and X‐X show different patterns that we attribute to different conditions of emission at the source. Direction‐finding results shows that the fundamental and harmonic emissions are plausibly generated in the same source region. In agreement with previous studies at Earth, the generation of the two types of harmonics can be attributed to the cyclotron maser instability operating with different plasma density and electron energy distributions in the source region.
The Influence of Pine Island Ice Shelf Calving on Basal Melting
Authors: Bradley A. T. , Bett D. T. , Dutrieux P. , De Rydt J. , Holland P. R.
Published: August 2022

The combination of the Pine Island Ice Shelf (PIIS) draft and a seabed ridge beneath it form a topographic barrier, restricting access of warm Circumpolar Deep Water to a cavity inshore of the ridge, thus exerting an important control on PIIS basal ablation. In addition, PIIS has recently experienced several large calving events and further calving could significantly alter the cavity geometry. Changes in the ice front location, together with changes in ice thickness, might relax the topographic barrier and thus significantly change basal melt rates. Here, we consider the impact of past, and possible future, calving events on PIIS melt rates. We use a high‐resolution ocean model to simulate melt rates in both an idealized domain whose geometry captures the salient features of Pine Island Glacier, and a realistic geometry accurately resembling it, to explore how calving affects melt rates. The idealized simulations reveal that the melt response to calving has a sensitive dependence on the thickness of the gap between PIIS and the seabed ridge and inform our interpretation of the realistic simulations, which suggest that PIIS melt rates did not respond significantly to recent calving. However, the mean melt rate increases approximately linearly with further calving, and is amplified by approximately 10% relative to present day once the ice front reaches the ridge‐crest, taking less than one decade if calving maintains its present rate. This provides strong evidence that calving may represent an important, but as yet unexplored, contribution to the ice‐ocean sensitivity of the West Antarctic Ice Sheet.
Rates of Future Climate Change in the Gulf of Mexico and the Caribbean Sea: Implications for Coral Reef Ecosystems
Authors: Lawman A. E. , Dee S. G. , DeLong K. L. , Correa A. M. S.
Published: August 2022

Rising temperatures and ocean acidification due to anthropogenic climate change pose ominous threats to coral reef ecosystems in the Gulf of Mexico (GoM) and the western Caribbean Sea. Unfortunately, the once structurally complex coral reefs in the GoM and Caribbean have dramatically declined since the 1970s; relatively few coral reefs still exhibit a mean live coral cover of >10%. Additional work is needed to characterize future climate stressors on coral reefs in the GoM and the Caribbean Sea. Here, we use climate model simulations spanning the period of 2015–2100 to partition and assess the individual impacts of climate stressors on corals in the GoM and the western Caribbean Sea. We use a top‐down modeling framework to diagnose future projected changes in thermal stress and ocean acidification and discuss its implications for coral reef ecosystems. We find that ocean temperatures increase by 2°C–3°C over the 21st century, and surpass reported regional bleaching thresholds by mid‐century. Whereas ocean acidification occurs, the rate and magnitude of temperature changes outpace and outweigh the impacts of changes in aragonite saturation state. A framework for quantifying and communicating future risks in the GoM and Caribbean using reef risk projection maps is discussed. Without substantial mitigation efforts, the combined impact of increasing ocean temperatures and acidification are likely to stress most existing corals in the GoM and the Caribbean, with widespread economic and ecological consequences.
Associations of body mass index, fasting insulin, and inflammation with mortality: a prospective cohort study
Authors: Wiebe Natasha , Muntner Paul , Tonelli Marcello
Published: August 2022

Background/objectives

Obesity is often considered to increase the risk for premature mortality. Higher fasting insulin and c-reactive protein are associated with higher body mass index (BMI) and all-cause mortality, so may confound the association between obesity and mortality. Our objective was to determine the independent associations between BMI, fasting insulin, c-reactive protein, and all-cause mortality in a general population sample.

Methods

This prospective cohort study included non-institutionalized US adults (≥20 years) from the National Health and Nutrition Examination Surveys 1999–2000 to 2013–2014. The main exposures of interest were BMI, fasting insulin, c-reactive protein. Mortality data were obtained through linking participants to the National Death Index (ending December 31, 2015).

Results

There were 12,563 participants with a median age of 45 years (range 20–85) and 47.9% were male. The median BMI was 27 kg/m2 (IQR 24–32), median fasting insulin was 54 pmol/L (IQR 35–87), and median c-reactive protein was 1.9 mg/L (IQR 0.8–4.4). In a Cox model adjusted for age, biological sex, cigarette smoking, and ten chronic conditions, higher BMI parameterized with quadratic and linear terms was not associated with mortality. When fasting insulin and the natural logarithm of c-reactive protein were included in the model, an inverse association between BMI and mortality was present (compared to the referent category of 5th percentile: 1st percentile, HR 1.10, 95% CI 1.06-1.13; 99th percentile, HR 0.48, 95% CI 0.34–0.69). In contrast, higher levels of fasting insulin and c-reactive protein were associated with an increased risk of mortality (for fasting insulin: 1st percentile, HR 0.98, 95% CI 0.97–0.99; 99th percentile, HR 1.83, 95% CI 1.48–2.26; for c-reactive protein, 1st percentile, HR 0.87, 95% CI 0.84–0.90; 99th percentile, HR 2.77, 95% CI 2.12–3.62).

Conclusions

Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.
Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients
Authors: André Sonia , Azarias da Silva Marne , Picard Morgane , Alleaume-Buteau Aurélie , Kundura Lucy , Cezar Renaud , Soudaramourty Calaiselvy , André Santa Cruz , Mendes-Frias Ana , Carvalho Alexandre , Capela Carlos , Pedrosa Jorge , Gil Castro António , Loubet Paul , Sotto Albert , Muller Laurent , Lefrant Jean-Yves , Roger Claire , Claret Pierre-Géraud , Duvnjak Sandra , Tran Tu-Anh , Zghidi-Abouzid Ouafa , Nioche Pierre , Silvestre Ricardo , Corbeau Pierre , Mammano Fabrizio , Estaquier Jérôme
Published: August 2022

In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that the propensity of CD4 T cells to die may impact the quantity and quality of the humoral response in acutely infected individuals. In addition to specific immunoglobulins (Ig)A, IgM, and IgG against SARS-CoV-2 nucleocapsid (N), membrane (M), and spike (S1) proteins, we assessed the quality of IgG response by measuring the avidity index. Because the S protein represents the main target for neutralization and antibody-dependent cellular cytotoxicity responses, we also analyzed anti-S-specific IgG using S-transfected cells (S-Flow). Our results demonstrated that most COVID-19 patients have a predominant IgA anti-N humoral response during the early phase of infection. This specific humoral response preceded the anti-S1 in time and magnitude. The avidity index of anti-S1 IgG was low in acutely infected individuals compared to convalescent patients. We showed that the percentage of apoptotic CD4 T cells is inversely correlated with the levels of specific IgG antibodies. These lower levels were also correlated positively with plasma levels of CXCL10, a marker of disease severity, and soluble Fas ligand that contributes to T-cell death. Finally, we found lower S-Flow responses in patients with higher CD4 T-cell apoptosis. Altogether, these results demonstrate that individuals with high levels of CD4 T-cell apoptosis and CXCL10 have a poor ability to build an efficient anti-S response. Consequently, preventing CD4 T-cell death might be a strategy for improving humoral response during the acute phase, thereby reducing COVID-19 pathogenicity.
Hypoxic human proximal tubular epithelial cells undergo ferroptosis and elicit an NLRP3 inflammasome response in CD1c+ dendritic cells
Authors: Giuliani Kurt T. K. , Grivei Anca , Nag Purba , Wang Xiangju , Rist Melissa , Kildey Katrina , Law Becker , Ng Monica S. , Wilkinson Ray , Ungerer Jacobus , Forbes Josephine M. , Healy Helen , Kassianos Andrew J.
Published: August 2022

Inflammasomes are multiprotein platforms responsible for the release of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Mouse studies have identified inflammasome activation within dendritic cells (DC) as pivotal for driving tubulointerstitial fibrosis and inflammation, the hallmarks of chronic kidney disease (CKD). However, translation of this work to human CKD remains limited. Here, we examined the complex tubular cell death pathways mediating inflammasome activation in human kidney DC and, thus, CKD progression. Ex vivo patient-derived proximal tubular epithelial cells (PTEC) cultured under hypoxic (1% O2) conditions modelling the CKD microenvironment showed characteristics of ferroptotic cell death, including mitochondrial dysfunction, reductions in the lipid repair enzyme glutathione peroxidase 4 (GPX4) and increases in lipid peroxidation by-product 4-hydroxynonenal (4-HNE) compared with normoxic PTEC. The addition of ferroptosis inhibitor, ferrostatin-1, significantly reduced hypoxic PTEC death. Human CD1c+ DC activated in the presence of hypoxic PTEC displayed significantly increased production of inflammasome-dependent cytokines IL-1β and IL-18. Treatment of co-cultures with VX-765 (caspase-1/4 inhibitor) and MCC950 (NLRP3 inflammasome inhibitor) significantly attenuated IL-1β/IL-18 levels, supporting an NLRP3 inflammasome-dependent DC response. In line with these in vitro findings, in situ immunolabelling of human fibrotic kidney tissue revealed a significant accumulation of tubulointerstitial CD1c+ DC containing active inflammasome (ASC) specks adjacent to ferroptotic PTEC. These data establish ferroptosis as the primary pattern of PTEC necrosis under the hypoxic conditions of CKD. Moreover, this study identifies NLRP3 inflammasome signalling driven by complex tubulointerstitial PTEC-DC interactions as a key checkpoint for therapeutic targeting in human CKD.
Neutrophil extracellular traps-triggered impaired autophagic flux via METTL3 underlies sepsis-associated acute lung injury
Authors: Qu Mengdi , Chen Zhaoyuan , Qiu Zhiyun , Nan Ke , Wang Yanghanzhao , Shi Yuxin , Shao Yuwen , Zhong Ziwen , Zhu Shuainan , Guo Kefang , Chen Wankun , Lu Xihua , Wang Zhiping , Zhang Hao , Miao Changhong
Published: August 2022

Neutrophil extracellular traps (NETs) assist pathogen clearance, while excessive NETs formation is associated with exacerbated inflammatory responses and tissue injury in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Autophagy is generally considered to be a protective process, but autophagy dysfunction is harmful. Whether and how NETs affect autophagic flux during sepsis-induced ALI are currently unknown. Here, we confirmed that the level of NETs was increased in ARDS patients and mice models, which led to impairment of autophagic flux and deterioration of the disease. Mechanistically, NETs activated METTL3 mediated m6A methylation of Sirt1 mRNA in alveolar epithelial cells, resulting in abnormal autophagy. These findings provide new insights into how NETs contribute to the development of sepsis-associated ALI/ARDS.
Long term complications and vision loss in HLA-B27 uveitis
Authors: Al-Ani Haya H. , Sims Joanne L. , Niederer Rachael L.
Published: August 2022

Objectives

To evaluate the long term complications and vision loss in HLA-B27 uveitis.

Methods

Retrospective review of subjects with HLA-B27 uveitis in a public tertiary centre between January 2008 and 2020.

Results

562 HLA-B27-positive subjects (834 eyes) had mean follow-up of 9.8 years (8173.2 eye-years). Median visual acuity at ten years was 0.1 logMAR (IQR 0.0–0.1). Complications occurred in 404 eyes (48.4%): posterior synechiae (39.7%), cataract (22.1%), elevated intraocular pressure (15.5%), cystoid macular oedema (6.0%). Permanent moderate vision loss ( ≤ 0.4 logMAR) due to uveitis occurred in 14 eyes (1.7%) and severe vision loss (≤ 1.0 logMAR) in 7 eyes (0.8%). Complications were more common with older age (OR 1.017 p = 0.016), chronic inflammation (OR 5.272 p < 0.001) and intermediate uveitis (OR 5.982 p < 0.001).

Conclusions

Complications are frequent in HLA-B27 uveitis, especially in older subjects, chronic inflammation and intermediate uveitis. Despite this, the majority of subjects maintain good visual prognosis.
Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes
Authors: Li Jiahong , Shami Gerald J. , Cho Ellie , Liu Boyin , Hanssen Eric , Dixon Matthew W. A. , Tilley Leann
Published: August 2022

The sexual stage gametocytes of the malaria parasite, Plasmodium falciparum, adopt a falciform (crescent) shape driven by the assembly of a network of microtubules anchored to a cisternal inner membrane complex (IMC). Using 3D electron microscopy, we show that a non-mitotic microtubule organizing center (MTOC), embedded in the parasite’s nuclear membrane, orients the endoplasmic reticulum and the nascent IMC and seeds cytoplasmic microtubules. A bundle of microtubules extends into the nuclear lumen, elongating the nuclear envelope and capturing the chromatin. Classical mitotic machinery components, including centriolar plaque proteins, Pfcentrin-1 and −4, microtubule-associated protein, End-binding protein-1, kinetochore protein, PfNDC80 and centromere-associated protein, PfCENH3, are involved in the nuclear microtubule assembly/disassembly process. Depolymerisation of the microtubules using trifluralin prevents elongation and disrupts the chromatin, centromere and kinetochore organisation. We show that the unusual non-mitotic hemispindle plays a central role in chromatin organisation, IMC positioning and subpellicular microtubule formation in gametocytes.
Co-benefits of CO2 emission reduction from China’s clean air actions between 2013-2020
Authors: Shi Qinren , Zheng Bo , Zheng Yixuan , Tong Dan , Liu Yang , Ma Hanchen , Hong Chaopeng , Geng Guannan , Guan Dabo , He Kebin , Zhang Qiang
Published: August 2022

Climate change mitigation measures can yield substantial air quality improvements while emerging clean air measures in developing countries can also lead to CO2 emission mitigation co-benefits by affecting the local energy system. Here, we evaluate the effect of China’s stringent clean air actions on its energy use and CO2 emissions from 2013-2020. We find that widespread phase-out and upgrades of outdated, polluting, and inefficient combustion facilities during clean air actions have promoted the transformation of the country’s energy system. The co-benefits of China’s clean air measures far outweigh the additional CO2 emissions of end-of-pipe devices, realizing a net accumulative reduction of 2.43 Gt CO2 from 2013-2020, exceeding the accumulated CO2 emission increase in China (2.03 Gt CO2) during the same period. Our study indicates that China’s efforts to tackle air pollution induce considerable climate benefit, and measures with remarkable CO2 reduction co-benefits deserve further attention in future policy design.
Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau
Authors: Asadzadeh Jamshid , Ruchti Evelyne , Jiao Wei , Limoni Greta , MacLachlan Catherine , Small Scott A. , Knott Graham , Santa-Maria Ismael , McCabe Brian D.
Published: August 2022

Alteration of the levels, localization or post-translational processing of the microtubule associated protein Tau is associated with many neurodegenerative disorders. Here we develop adult-onset models for human Tau (hTau) toxicity in Drosophila that enable age-dependent quantitative measurement of central nervous system synapse loss and axonal degeneration, in addition to effects upon lifespan, to facilitate evaluation of factors that may contribute to Tau-dependent neurodegeneration. Using these models, we interrogate the interaction of hTau with the retromer complex, an evolutionarily conserved cargo-sorting protein assembly, whose reduced activity has been associated with both Parkinson’s and late onset Alzheimer’s disease. We reveal that reduction of retromer activity induces a potent enhancement of hTau toxicity upon synapse loss, axon retraction and lifespan through a specific increase in the production of a C-terminal truncated isoform of hTau. Our data establish a molecular and subcellular mechanism necessary and sufficient for the depletion of retromer activity to exacerbate Tau-dependent neurodegeneration.
Organic matter composition and greenhouse gas production of thawing subsea permafrost in the Laptev Sea
Authors: Wild Birgit , Shakhova Natalia , Dudarev Oleg , Ruban Alexey , Kosmach Denis , Tumskoy Vladimir , Tesi Tommaso , Grimm Hanna , Nybom Inna , Matsubara Felipe , Alexanderson Helena , Jakobsson Martin , Mazurov Alexey , Semiletov Igor , Gustafsson Örjan
Published: August 2022

Subsea permafrost represents a large carbon pool that might be or become a significant greenhouse gas source. Scarcity of observational data causes large uncertainties. We here use five 21-56 m long subsea permafrost cores from the Laptev Sea to constrain organic carbon (OC) storage and sources, degradation state and potential greenhouse gas production upon thaw. Grain sizes, optically-stimulated luminescence and biomarkers suggest deposition of aeolian silt and fluvial sand over 160 000 years, with dominant fluvial/alluvial deposition of forest- and tundra-derived organic matter. We estimate an annual thaw rate of 1.3 ± 0.6 kg OC m−2 in subsea permafrost in the area, nine-fold exceeding organic carbon thaw rates for terrestrial permafrost. During 20-month incubations, CH4 and CO2 production averaged 1.7 nmol and 2.4 µmol g−1 OC d−1, providing a baseline to assess the contribution of subsea permafrost to the high CH4 fluxes and strong ocean acidification observed in the region.
Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques
Authors: Pino Maria , Pagliuzza Amélie , Pampena M. Betina , Deleage Claire , Viox Elise G. , Nguyen Kevin , Shim Inbo , Zhang Adam , Harper Justin L. , Samer Sadia , King Colin T. , Cervasi Barbara , Gill Kiran P. , Ehnert Stephanie , Jean Sherrie M. , Freeman Michael L. , Lifson Jeffrey D. , Kulpa Deanna , Betts Michael R. , Chomont Nicolas , Lederman Michael M. , Paiardini Mirko
Published: August 2022

Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes. This increase of cytolytic cells, however, does not limit measures of viral persistence during ART, including intact proviral genomes. After ART interruption, a subset of animals that initially receives FTY720 displays a modest delay in viral rebound, with reduced plasma viremia and frequencies of infected T follicular helper cells. Further research is needed to optimize the potential utility of FTY720 when coupled with strategies that boost the antiviral function of T-cells in lymphoid tissues.
NODULIN HOMEOBOX is required for heterochromatin homeostasis in Arabidopsis
Authors: Karányi Zsolt , Mosolygó-L Ágnes , Feró Orsolya , Horváth Adrienn , Boros-Oláh Beáta , Nagy Éva , Hetey Szabolcs , Holb Imre , Szaker Henrik Mihály , Miskei Márton , Csorba Tibor , Székvölgyi Lóránt
Published: August 2022

Arabidopsis NODULIN HOMEOBOX (NDX) is a nuclear protein described as a regulator of specific euchromatic genes within transcriptionally active chromosome arms. Here we show that NDX is primarily a heterochromatin regulator that functions in pericentromeric regions to control siRNA production and non-CG methylation. Most NDX binding sites coincide with pericentromeric het-siRNA loci that mediate transposon silencing, and are antagonistic with R-loop structures that are prevalent in euchromatic chromosomal arms. Inactivation of NDX leads to differential siRNA accumulation and DNA methylation, of which CHH/CHG hypomethylation colocalizes with NDX binding sites. Hi-C analysis shows significant chromatin structural changes in the ndx mutant, with decreased intrachromosomal interactions at pericentromeres where NDX is enriched in wild-type plants, and increased interchromosomal contacts between KNOT-forming regions, similar to those observed in DNA methylation mutants. We conclude that NDX is a key regulator of heterochromatin that is functionally coupled to het-siRNA loci and non-CG DNA methylation pathways.
Construction of azaheterocycles via Pd-catalyzed migratory cycloannulation reaction of unactivated alkenes
Authors: Wang Jin-Ping , Song Shuo , Wu Yichen , Wang Peng
Published: August 2022

Azahetereocycles constitute important structural components in many biologically active natural compounds and marketed drugs, and represent the most promising scaffolds in drug discovery. Accordingly, the development of efficient and general synthetic methods for the construction of diverse azaheterocycles is the major goal in synthetic chemistry. Herein, we report the efficient construction of a wide range of azaheterocycles via a Pd-catalyzed migratory cycloannulation strategy with unactivated alkenes. This strategy enables the rapid synthesis of a series of 6-, 7- and 8-membered azaheterocycles in high efficiency, and features a broad substrate scope, excellent functional group tolerance under redox-neutral conditions. The significance of this finding is demonstrated by the efficient synthesis of drug-like molecules with high step-economy. Preliminary mechanistic investigations reveal that this reaction underwent a sequentially migratory insertion to alkenes, metal migration process, and the aza-Michael addition to a quinone methide intermediate.
Early postnatal serotonin modulation prevents adult-stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming
Authors: Kim Hyosang , Kim Doyoun , Cho Yisul , Kim Kyungdeok , Roh Junyeop Daniel , Kim Yangsik , Yang Esther , Kim Seong Soon , Ahn Sunjoo , Kim Hyun , Kang Hyojin , Bae Yongchul , Kim Eunjoon
Published: August 2022

Autism spectrum disorder is characterized by early postnatal symptoms, although little is known about the mechanistic deviations that produce them and whether correcting them has long-lasting preventive effects on adult-stage deficits. ARID1B, a chromatin remodeler implicated in neurodevelopmental disorders, including autism spectrum disorder, exhibits strong embryonic- and early postnatal-stage expression. We report here thatArid1b-happloinsufficient (Arid1b+/–) mice display autistic-like behaviors at juvenile and adult stages accompanied by persistent decreases in excitatory synaptic density and transmission. Chronic treatment ofArid1b+/–mice with fluoxetine, a selective serotonin-reuptake inhibitor, during the first three postnatal weeks prevents synaptic and behavioral deficits in adults. Mechanistically, these rescues accompany transcriptomic changes, including upregulation of FMRP targets and normalization of HDAC4/MEF2A-related transcriptional regulation of the synaptic proteins, SynGAP1 and Arc. These results suggest that chronic modulation of serotonergic receptors during critical early postnatal periods prevents synaptic and behavioral deficits in adultArid1b+/–mice through transcriptional reprogramming.
The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1
Authors: Dhoonmoon Ashna , Nicolae Claudia M. , Moldovan George-Lucian
Published: August 2022

Suppression of nascent DNA degradation has emerged as an essential role of the BRCA pathway in genome protection. In BRCA-deficient cells, the MRE11 nuclease is responsible for both resection of reversed replication forks, and accumulation of single stranded DNA gaps behind forks. Here, we show that the mono-ADP-ribosyltransferase PARP14 is a critical co-factor of MRE11. PARP14 is recruited to nascent DNA upon replication stress in BRCA-deficient cells, and through its catalytic activity, mediates the engagement of MRE11. Loss or inhibition of PARP14 suppresses MRE11-mediated fork degradation and gap accumulation, and promotes genome stability and chemoresistance of BRCA-deficient cells. Moreover, we show that the KU complex binds reversed forks and protects them against EXO1-catalyzed degradation. KU recruits the PARP14-MRE11 complex, which initiates partial resection to release KU and allow long-range resection by EXO1. Our work identifies a multistep process of nascent DNA processing at stalled replication forks in BRCA-deficient cells.
Replicative manufacturing of metal moulds for low surface roughness polymer replication
Authors: Kluck Sebastian , Hambitzer Leonhard , Luitz Manuel , Mader Markus , Sanjaya Mario , Balster Andreas , Milich Marcel , Greiner Christian , Kotz-Helmer Frederik , Rapp Bastian E.
Published: August 2022

Tool based manufacturing processes like injection moulding allow fast and high-quality mass-market production, but for optical polymer components the production of the necessary tools is time-consuming and expensive. In this paper a process to fabricate metal-inserts for tool based manufacturing with smooth surfaces via a casting and replication process from fused silica templates is presented. Bronze, brass and cobalt-chromium could be successfully replicated from shaped fused silica replications achieving a surface roughnesses of Rq8 nm and microstructures in the range of 5 µm. Injection moulding was successfully performed, using a commercially available injection moulding system, with thousands of replicas generated from the same tool. In addition, three-dimensional bodies in metal could be realised with 3D-Printing of fused silica casting moulds. This work thus represents an approach to high-quality moulding tools via a scalable facile and cost-effective route surpassing the currently employed cost-, labour- and equipment-intensive machining techniques.
Glassy thermal conductivity in Cs3Bi2I6Cl3 single crystal
Authors: Acharyya Paribesh , Ghosh Tanmoy , Pal Koushik , Rana Kewal Singh , Dutta Moinak , Swain Diptikanta , Etter Martin , Soni Ajay , Waghmare Umesh V. , Biswas Kanishka
Published: August 2022

As the periodic atomic arrangement of a crystal is made to a disorder or glassy-amorphous system by destroying the long-range order, lattice thermal conductivity, κL, decreases, and its fundamental characteristics changes. The realization of ultralow and unusual glass-like κL in a crystalline material is challenging but crucial to many applications like thermoelectrics and thermal barrier coatings. Herein, we demonstrate an ultralow (~0.20 W/m·K at room temperature) and glass-like temperature dependence (2–400 K) of κL in a single crystal of layered halide perovskite, Cs3Bi2I6Cl3. Acoustic phonons with low cut-off frequency (20 cm−1) are responsible for the low sound velocity in Cs3Bi2I6Cl3 and make the structure elastically soft. While a strong anharmonicity originates from the low energy and localized rattling-like vibration of Cs atoms, synchrotron X-ray pair-distribution function evidence a local structural distortion in the Bi-halide octahedra and Cl vacancy. The hierarchical chemical bonding and soft vibrations from selective sublattice leading to low κL is intriguing from lattice dynamical perspective as well as have potential applications.
In-situ growth of robust superlubricated nano-skin on electrospun nanofibers for post-operative adhesion prevention
Authors: Wang Yi , Xu Yuanhang , Zhai Weijie , Zhang Zhinan , Liu Yuhong , Cheng Shujie , Zhang Hongyu
Published: August 2022

It is a great challenge to achieve robustly bonded, fully covered, and nanoscaled coating on the surface of electrospun nanofibers. Herein, we develop a controllable, facile, and versatile strategy to in-situ grow superlubricated nano-skin (SLNS) on the single electrospun nanofiber. Specifically, zwitterionic polymer chains are generated from the nanofiber subsurface in an inside-out way, which consequently form a robust network interpenetrating with the polymeric chains of the nanofiber matrix. The nanofibers with SLNS are superlubricated with the coefficient of friction (COF) lower than 0.025, which is about 16-fold of reduction than the original nanofibers. The time-COF plot is very stable after 12, 000 cycles of friction test, and no abrasion is observed. Additionally, the developed nanofibrous membranes possess favorable tensile property and biocompatibility. Furthermore, the nanofibrous membranes with SLNS achieve prevention of post-operative adhesion, which is confirmed in both rat tendon adhesion model and abdominal adhesion model. Compared with clinically-used antiadhesive membranes such as Interceed and DK-film, our nanofibrous membranes are not only more effective but also have the advantage of lower production cost. Therefore, this study demonstrates a potential of the superlubricated nanofibrous membranes in-situ grown based on a SLNS strategy for achieving prevention of post-operative adhesion in clinics.
Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER
Authors: Jhund Pardeep S. , Kondo Toru , Butt Jawad H. , Docherty Kieran F. , Claggett Brian L. , Desai Akshay S. , Vaduganathan Muthiah , Gasparyan Samvel B. , Bengtsson Olof , Lindholm Daniel , Petersson Magnus , Langkilde Anna Maria , de Boer Rudolf A. , DeMets David , Hernandez Adrian F. , Inzucchi Silvio E. , Kosiborod Mikhail N. , Køber Lars , Lam Carolyn S. P. , Martinez Felipe A. , Sabatine Marc S. , Shah Sanjiv J. , Solomon Scott D. , McMurray John J. V.
Published: August 2022

Whether the sodium–glucose cotransporter 2 inhibitor dapagliflozin reduces the risk of a range of morbidity and mortality outcomes in patients with heart failure regardless of ejection fraction is unknown. A patient-level pooled meta-analysis of two trials testing dapagliflozin in participants with heart failure and different ranges of left ventricular ejection fraction (≤40% and >40%) was pre-specified to examine the effect of treatment on endpoints that neither trial, individually, was powered for and to test the consistency of the effect of dapagliflozin across the range of ejection fractions. The pre-specified endpoints were: death from cardiovascular causes; death from any cause; total hospital admissions for heart failure; and the composite of death from cardiovascular causes, myocardial infarction or stroke (major adverse cardiovascular events (MACEs)). A total of 11,007 participants with a mean ejection fraction of 44% (s.d. 14%) were included. Dapagliflozin reduced the risk of death from cardiovascular causes (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76–0.97; P = 0.01), death from any cause (HR 0.90, 95% CI 0.82–0.99; P = 0.03), total hospital admissions for heart failure (rate ratio 0.71, 95% CI 0.65–0.78; P < 0.001) and MACEs (HR 0.90, 95% CI 0.81–1.00; P = 0.045). There was no evidence that the effect of dapagliflozin differed by ejection fraction. In a patient-level pooled meta-analysis covering the full range of ejection fractions in patients with heart failure, dapagliflozin reduced the risk of death from cardiovascular causes and hospital admissions for heart failure (PROSPERO: CRD42022346524).
Dasymetric population mapping based on US census data and 30-m gridded estimates of impervious surface
Authors: Swanwick Rachel H. , Read Quentin D. , Guinn Steven M. , Williamson Matthew A. , Hondula Kelly L. , Elmore Andrew J.
Published: August 2022

Assessment of socio-environmental problems and the search for solutions often require intersecting geospatial data on environmental factors and human population densities. In the United States, Census data is the most common source for information on population. However, timely acquisition of such data at sufficient spatial resolution can be problematic, especially in cases where the analysis area spans urban-rural gradients. With this data release, we provide a 30-m resolution population estimate for the contiguous United States. The workflow dasymetrically distributes Census block level population estimates across all non-transportation impervious surfaces within each Census block. The methodology is updatable using the most recent Census data and remote sensing-based observations of impervious surface area. The dataset, known as the U.G.L.I (updatable gridded lightweight impervious) population dataset, compares favorably against other population data sources, and provides a useful balance between resolution and complexity.
ADTC-InSAR: a tropospheric correction database for Andean volcanoes
Authors: Lopez-Pozo Fernanda , Abarca-del-Rio Rodrigo , Lara Luis E.
Published: August 2022

Monitoring geophysical hazards requires a near real-time response and precise interpretation of InSAR data, typically recording minute surface deformations. Accurate tropospheric adjustment is an essential aspect of InSAR processing. This study provides a free database of ready-to-use Tropospheric Correction for InSAR for the three volcanic zones from north to south of the Andes. Average Daily Tropospheric Correction for InSAR (ADTC-InSAR) is a collection of average daily tropospheric delay matrices created using ECMWF re-analysis of the global atmosphere and surface conditions (ERA5) as atmospheric data and TRAIN software. The construction method and annual variation according to the climatic zones are provided, and its effectiveness is evaluated. ADTC-InSAR facilitates the generation of tropospheric corrections in InSAR with easy access, fast application, and accuracy comparable to TRAIN. Its purpose is to serve as a starting point for tropospheric correction in the event of emergency response to extreme occurrences and as a reference for other research and academic objectives.
Global inventory of suitable, cultivable and available cropland under different scenarios and policies
Authors: Schneider Julia M. , Zabel Florian , Mauser Wolfram
Published: August 2022

Where land-use change and particularly the expansion of cropland could potentially take place in the future is a central research question to investigate emerging trade-offs between food security, climate protection and biodiversity conservation. We provide consistent global datasets of land potentially suitable, cultivable and available for agricultural use for historic and future time periods from 1980 until 2100 under RCP2.6 and RCP8.5, available at 30 arc-seconds spatial resolution and aggregated at country level. Based on the agricultural suitability of land for 23 globally important food, feed, fiber and bioenergy crops, and high resolution land cover data, our dataset indicates where cultivation is possible and how much land could potentially be used as cropland when biophysical constraints and different assumptions on land-use regulations are taken into account. By serving as an input for land-use models, the produced data could improve the comparability of the models and their output, and thereby contribute to a better understanding of potential land-use trade-offs.
Real-world behavioral dataset from two fully remote smartphone-based randomized clinical trials for depression
Authors: Pratap Abhishek , Homiar Ava , Waninger Luke , Herd Calvin , Suver Christine , Volponi Joshua , Anguera Joaquin A. , Areán Pat
Published: August 2022

Most people with mental health disorders cannot receive timely and evidence-based care despite billions of dollars spent by healthcare systems. Researchers have been exploring using digital health technologies to measure behavior in real-world settings with mixed results. There is a need to create accessible and computable digital mental health datasets to advance inclusive and transparently validated research for creating robust real-world digital biomarkers of mental health. Here we share and describe one of the largest and most diverse real-world behavior datasets from over two thousand individuals across the US. The data were generated as part of the two NIMH-funded randomized clinical trials conducted to assess the effectiveness of delivering mental health care continuously remotely. The longitudinal dataset consists of self-assessment of mood, depression, anxiety, and passively gathered phone-based behavioral data streams in real-world settings. This dataset will provide a timely and long-term data resource to evaluate analytical approaches for developing digital behavioral markers and understand the effectiveness of mental health care delivered continuously and remotely.
Mass spectrometry data on specialized metabolome of medicinal plants used in East Asian traditional medicine
Authors: Kang Kyo Bin , Jeong Eunah , Son Seungju , Lee Eunjin , Lee Seungjin , Choi Seong Yeon , Kim Hyun Woo , Yang Heejung , Shim Sang Hee
Published: August 2022

Traditional East Asian medicine not only serves as a potential source of drug discovery, but also plays an important role in the healthcare systems of Korea, China, and Japan. Tandem mass spectrometry (MS/MS)-based untargeted metabolomics is a key methodology for high-throughput analysis of the complex chemical compositions of medicinal plants used in traditional East Asian medicine. This Data Descriptor documents the deposition to a public repository of a re-analyzable raw LC-MS/MS dataset of 337 medicinal plants listed in the Korean Pharmacopeia, in addition to a reference spectral library of 223 phytochemicals isolated from medicinal plants. Enhanced by recently developed repository-level data analysis pipelines, this information can serve as a reference dataset for MS/MS-based untargeted metabolomic analysis of plant specialized metabolites.
On controlled Hamilton and Hamilton–Jacobi differential equations of higher-order
Authors: Treanţă Savin , Nonlaopon Kamsing , Khan Muhammad Bilal
Published: August 2022

In this paper, we investigate the nonlinear dynamics associated with controlled Lagrangians involving higher-order derivatives. More precisely, we establish the controlled higher-order Hamilton ordinary differential equations (ODEs) and Hamilton–Jacobi partial differential equation (PDE) for the considered class of Lagrangians governed by higher-order derivatives of the state variables. Moreover, we formulate and prove an invariance result with respect to the state variable. In addition, in order to validate the theoretical results and to highlight their effectiveness, some illustrative applications are presented.
Spheroid co-culture of BMSCs with osteocytes yields ring-shaped bone-like tissue that enhances alveolar bone regeneration
Authors: Zhou Ying-Hui , Guo Yue , Zhu Jia-Yu , Tang Chen-Yi , Zhao Ya-Qiong , Zhou Hou-De
Published: August 2022

Oral and maxillofacial bone defects severely impair appearance and function, and bioactive materials are urgently needed for bone regeneration. Here, we spheroid co-cultured green fluorescent protein (GFP)-labeled bone marrow stromal cells (BMSCs) and osteocyte-like MLO-Y4 cells in different ratios (3:1, 2:1, 1:1, 1:2, 1:3) or as monoculture. Bone-like tissue was formed in the 3:1, 2:1, and 1:1 co-cultures and MLO-Y4 monoculture. We found a continuous dense calcium phosphate structure and spherical calcium phosphate similar to mouse femur with the 3:1, 2:1, and 1:1 co-cultures, along with GFP-positive osteocyte-like cells encircled by an osteoid-like matrix similar to cortical bone. Flake-like calcium phosphate, which is more mature than spherical calcium phosphate, was found with the 3:1 and 2:1 co-cultures. Phosphorus and calcium signals were highest with 3:1 co-culture, and this bone-like tissue was ring-shaped. In a murine tooth extraction model, implantation of the ring-shaped bone-like tissue yielded more bone mass, osteoid and mineralized bone, and collagen versus no implantation. This tissue fabricated by spheroid co-culturing BMSCs with osteocytes yields an internal structure and mineral composition similar to mouse femur and could promote bone formation and maturation, accelerating regeneration. These findings open the way to new strategies in bone tissue engineering.