bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractRising 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

Abstract
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

AbstractIn 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

AbstractInflammasomes 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

AbstractNeutrophil 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

Abstract
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

AbstractThe 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

AbstractClimate 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

AbstractAlteration 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

AbstractSubsea 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

AbstractAntiretroviral 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

AbstractArabidopsis 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

AbstractAzahetereocycles 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

AbstractAutism 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

AbstractSuppression 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.