bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased circulating lipid peroxides in severe preeclampsia activate NF‐κΒ and upregulate ICAM‐1 in vascular endothelial cells
Authors: Takacs P. , Kauma S. W. , Sholley M. M. , Walsh S. W. , Dinsmoor M. J. , Green K. 
Published: July 2002

ABSTRACTPreeclampsia is a systemic disease of pregnancy characterized by maternal hypertension, proteinuria, and edema. These clinical pathological findings may be attributed to abnormalities in vascular endothelial activation secondary to increased oxidative stress. To test the hypothesis that increased circulating lipid peroxides in preeclamptic women activate vascular endothelial cells, we determined NF‐κΒ transcriptional activity and ICAM‐1 expression in human umbilical vein endothelial cells (HUVEC) cultured with plasma from women with severe preeclampsia (preeclamptic plasma, N = 12) or plasma from normal pregnancies (normal plasma, N = 12). Preeclamptic women had increased circulating lipid peroxides compared with normal pregnant women, as demonstrated by a 4.5‐fold higher concentration of plasma malondialdehyde (P<0.001). By using a NF‐κΒ luciferase reporter construct transfected into HUVEC, preeclamptic plasma was found to up‐regulate HUVEC NF‐κΒ activity by 2.5‐fold when compared with normal plasma (P<0.001). Inhibition of lipid peroxides with both vitamin E and N‐acetyl‐cysteine significantly reduced NF‐κΒ activation in response to preeclamptic‐plasma by 77% (P<0.005) and 76% (P<0.01), respectively. Flow cytometric analysis revealed that preeclamptic‐plasma also up‐regulated HUVEC ICAM‐1 expression by 30% (P<0.001) compared with normal‐plasma, while both vitamin E (P<0.005) and N‐acetyl‐cysteine (P<0.0001) significantly inhibited this effect. In summary, elevated plasma levels of lipid peroxides in preeclampsia are associated with increased NF‐κΒ activation and ICAM‐1 expression on HUVEC, which can be inhibited by vitamin E and N‐acetyl‐cysteine.
Predicting protein decomposition: the case of aspartic–acid racemization kinetics
Authors: Collins M. J. , Waite E. R. , van Duin A. C. T. 
Published: July 2002

The increase in proportion of the non–biological (D–) isomer of aspartic–acid (Asp) relative to the L–isomer has been widely used in archaeology and geochemistry as a tool for dating. The method has proved controversial, particularly when used for bones. The non–linear kinetics of Asp racemization have prompted a number of suggestions as to the underlying mechanism(s) and have led to the use of mathematical transformations which linearize the increase in D–Asp with respect to time. Using one example, a suggestion that the initial rapid phase of Asp racemization is due to a contribution from asparagine (Asn), we demonstrate how a simple model of the degradation and racemization of Asn can be used to predict the observed kinetics. A more complex model of peptide bound Asx (Asn + Asp) racemization, which occurs via the formation of a cyclic succinimide (Asu), can be used to correctly predict Asx racemization kinetics in proteins at high temperatures (95–140°C). The model fails to predict racemization kinetics in dentine collagen at 37°C. The reason for this is that Asu formation is highly conformation dependent and is predicted to occur extremely slowly in triple helical collagen. As conformation strongly influences the rate of Asu formation and hence Asx racemization, the use of extrapolation from high temperatures to estimate racemization kinetics of Asx in proteins below their denaturation temperature is called into question.In the case of archaeological bone, we argue that the D:L ratio of Asx reflects the proportion of non–helical to helical collagen, overlain by the effects of leaching of more soluble (and conformationally unconstrained) peptides. Thus, racemization kinetics in bone are potentially unpredictable, and the proposed use of Asx racemization to estimate the extent of DNA depurination in archaeological bones is challenged.
Comparative Sequence Analysis of the Imprinted Dlk1–Gtl2 Locus in Three Mammalian Species Reveals Highly Conserved Genomic Elements and Refines Comparison with the Igf2–H19 Region
Authors: Paulsen Martina , Takada Shuji , Youngson Neil A. , Benchaib Mehdi , Charlier Carole , Segers Karin , Georges Michel , Ferguson-Smith Anne C. 
Published: July 2002

The Dlk1–Gtl2 domain on mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced this conserved region in the mouse and sheep and included the human sequence in a three species comparison. This analysis resulted in a precise conservation map and identification of highly conserved sequence elements, some of which we have shown previously to be differentially methylated in the mouse. Additionally, this analysis facilitated identification of a CpG-rich tandem repeat array located ∼13–15 kb upstream of Gtl2. Furthermore, we have identified a third imprinted transcript that overlaps with the last Dlk1 exon in the mouse. This transcript lacks a conserved open reading frame and is probably generated by cleavage of extendedDlk1 transcripts. Because Dlk1 and Gtl2share many of the imprinting properties of the well-characterizedIgf2–H19 domain, it has been proposed that the two regions may be regulated in the same way. Comparative genomic examination of the two domains indicates that although there are similarities, other features are very different, including the location of conserved CTCF-binding sites, and the level of conservation at regulatory regions.[The sequence data described in this paper have been submitted to the GenBank data library under accession no. AJ320506.]
High-Throughput Gene Mapping in Caenorhabditis elegans
Authors: Swan Kathryn A. , Curtis Damian E. , McKusick Kathleen B. , Voinov Alexander V. , Mapa Felipa A. , Cancilla Michael R. 
Published: July 2002

Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 ± 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.[The sequence data described in this paper have been submitted to the NCBI dbSNP data library under accession nos. 4388625–4389689 and GenBank dbSTS under accession nos. 973810–974874. The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: The C. elegans Sequencing Consortium and TheCaenorhabditis Genetics Center.]
Engineering a Reduced Escherichia coli Genome
Authors: Kolisnychenko Vitaliy , Plunkett Guy , Herring Christopher D. , Fehér Tamás , Pósfai János , Blattner Frederick R. , Pósfai György 
Published: July 2002

Our goal is to construct an improved Escherichia coli to serve both as a better model organism and as a more useful technological tool for genome science. We developed techniques for precise genomic surgery and applied them to deleting the largest K-islands of E. coli, identified by comparative genomics as recent horizontal acquisitions to the genome. They are loaded with cryptic prophages, transposons, damaged genes, and genes of unknown function. Our method leaves no scars or markers behind and can be applied sequentially. Twelve K-islands were successfully deleted, resulting in an 8.1% reduced genome size, a 9.3% reduction of gene count, and elimination of 24 of the 44 transposable elements ofE. coli. These are particularly detrimental because they can mutagenize the genome or transpose into clones being propagated for sequencing, as happened in 18 places of the draft human genome sequence. We found no change in the growth rate on minimal medium, confirming the nonessential nature of these islands. This demonstration of feasibility opens the way for constructing a maximally reduced strain, which will provide a clean background for functional genomics studies, a more efficient background for use in biotechnology applications, and a unique tool for studies of genome stability and evolution.[Sequence data described in this paper have been submitted to the DNA Data Bank of Japan, European Molecular Biology Laboratory, and GenBank databases under accession nos. AF402780,AF402779, and AF406953, respectively.]
Improved detection of homologous membrane proteins by inclusion of information from topology predictions
Authors: Hedman Maria , Deloof Hans , Von Heijne Gunnar , Elofsson Arne 
Published: July 2002

AbstractA total of 20%–25% of the proteins in a typical genome are helical membrane proteins. The transmembrane regions of these proteins have markedly different properties when compared with globular proteins. This presents a problem when homology search algorithms optimized for globular proteins are applied to membrane proteins. Here we present modifications of the standard Smith‐Waterman and profile search algorithms that significantly improve the detection of related membrane proteins. The improvement is based on the inclusion of information about predicted transmembrane segments in the alignment algorithm. This is done by simply increasing the alignment score if two residues predicted to belong to transmembrane segments are aligned with each other. Benchmarking over a test set of G‐protein‐coupled receptor sequences shows that the number of false positives is significantly reduced in this way, both when closely related and distantly related proteins are searched for.
Association of Sialic Acid–Binding Immunoglobulin-Like Lectin 15 With Phenotypes in Esophageal Squamous Cell Carcinoma in the Setting of Neoadjuvant Chemoradiotherapy
Authors: Zhou Sha , Wang Yuting , Zhang Rui , Zeng Weian , Liu Shiliang , Liu Songran , Liu Mengzhong , Yang Hong , Xi Mian 
Published: January 2023

ImportanceSialic acid–binding immunoglobulin-like lectin 15 (Siglec-15) is a novel immune checkpoint molecule that is highly homologous to programmed cell death ligand 1 (PD-L1), but information remains limited about its role in esophageal squamous cell carcinoma (ESCC).ObjectiveTo explore the expression pattern and association of Siglec-15 with outcomes among patients with ESCC who received neoadjuvant chemoradiotherapy (CRT).Design, Setting, and ParticipantsThis retrospective cohort study was conducted at an academic institution in China. Participants included patients with ESCC who underwent neoadjuvant CRT and esophagectomy between June 2002 and December 2018. Multiplexed immunofluorescence staining was used to evaluate the expression of Siglec-15 and PD-L1 in tumor cells (TCs) or tumor-associated macrophages based on pre-CRT biopsies. Different immune phenotypes have been proposed and further validated in an independent cohort. Data analysis was conducted from January to May 2021.ExposuresSiglec-15 or PD-L1 positivity vs negativity.Main Outcomes and MeasuresPathologic complete response (pCR), overall survival (OS), and recurrence-free survival (RFS).ResultsOf 130 participants (median [range] age, 56 [42-73] years; 108 [83.1%] male participants) in the primary cohort, 58 patients (44.6%) achieved a pCR after neoadjuvant CRT. Siglec-15 and PD-L1 were detected in both TCs and macrophages. The percentage of Siglec-15–positive macrophages was notably higher than that of Siglec-15–positive TCs (median [IQR]: 34.4% [12.7%-64.3%] vs 4.8% [0.7%-25.6%]; P &amp;lt; .001). TC–Siglec-15 expression was significantly and positively associated with macrophage–Siglec-15 expression (r = 0.78; P &amp;lt; .001). Siglec-15 positivity was significantly associated with a higher rate of pCR (37 of 70 [52.9%] vs 21 of 60 [35.0%]; P = .04), more favorable OS (hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01), and RFS (HR, 0.48; 95% CI, 0.26–0.88; P = .02). However, PD-L1 positivity in TCs was negatively associated with survival. Stratification analysis further revealed that patients with combined Siglec-15 positivity and PD-L1 negativity had better survival than those with other phenotypes. Major findings were reproducible in a validation cohort with 55 patients.Conclusions and RelevanceIn this cohort study of patients with ESCC receiving neoadjuvant CRT, Siglec-15 positivity was associated with a better pathological response and more favorable survival. Siglec-15 could serve as a novel biomarker to identify potential candidates that may benefit from immunotherapy combined with CRT.
Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong
Authors: Au Philip C. M. , Tan Kathryn C. B. , Lam David C. L. , Cheung Bernard M. Y. , Wong Ian C. K. , Kwok Wang Chun , Sing Chor-Wing , Cheung Ching-Lung 
Published: January 2023

ImportancePatients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted.ObjectiveThis study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes.Design, Setting, and ParticipantsThis retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics.ExposuresPatients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator).Main Outcomes and MeasuresThe main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022.ResultsThis study included 30 385 patients. The propensity score–matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P &amp;lt; .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis.Conclusions and RelevanceThe findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted.
Association Between Neonatal Intensive Care Unit Type and Quality of Care in Moderate and Late Preterm Infants
Authors: Salazar Elizabeth G. , Handley Sara C. , Greenberg Lucy T. , Edwards Erika M. , Lorch Scott A. 
Published: January 2023

ImportanceA higher level of care improves outcomes in extremely and very preterm infants, yet the impact of neonatal intensive care unit (NICU) level on moderate and late preterm (MLP) care quality is unknown.ObjectiveTo examine the association between NICU type and care quality in MLP (30-36 weeks’ gestation) and extremely and very preterm (25-29 weeks’ gestation) infants.Design, Setting, and ParticipantsThis cohort study was a prospective analysis of 433 814 premature infants born in 465 US hospitals between January 1, 2016, and December 31, 2020, without anomalies and who survived more than 12 hours and were transferred no more than once. Data were from the Vermont Oxford Network all NICU admissions database.ExposuresNICU types were defined as units with ventilation restrictions without surgery (type A with restrictions, similar to American Academy of Pediatrics [AAP] level 2 NICUs), without surgery (type A) and with surgery not requiring cardiac bypass (type B, similar to AAP level 3 NICUs), and with all surgery (type C, similar to AAP level 4 NICUs).Main Outcomes and MeasuresThe primary outcome was gestational age (GA)–specific composite quality measures using Baby-Measure of Neonatal Intensive Care Outcomes Research (Baby-MONITOR) for extremely and very preterm infants and an adapted MLP quality measure for MLP infants. Secondary outcomes were individual component measures of each scale. Composite scores were standardized observed minus expected scores, adjusted for patient characteristics, averaged, and expressed with a mean of 0 and SD of 1. Between May 2021 and October 2022, Kruskal-Wallis tests were used to compare scores by NICU type.ResultsAmong the 376 219 MLP (204 181 [54.3%] male, 172 038 [45.7%] female; mean [SD] GA, 34.2 [1.7] weeks) and 57 595 extremely and very preterm (30 173 [52.4%] male, 27 422 [47.6%] female; mean [SD] GA, 27.7 [1.4] weeks) infants included, 6.6% received care in type A NICUs with restrictions, 29.3% in type A NICUs without restrictions, 39.7% in type B NICUs, and 24.4% in type C NICUs. The MLP infants had lower MLP-QM scores in type C NICUs (median [IQR]: type A with restrictions, 0.4 [−0.1 to 0.8]; type A, 0.4 [−0.4 to 0.9]; type B, 0.1 [−0.7 to 0.7]; type C, −0.7 [−1.6 to 0.4]; P &amp;lt; .001). No significant differences were found in extremely and very preterm Baby-MONITOR scores by NICU type. In type C NICUs, MLP infants had lower scores in no extreme length of stay and change-in-weight z score.Conclusions and RelevanceIn this cohort study, composite quality scores were lower for MLP infants in type C NICUs, whereas extremely and very preterm composite quality scores were similar across NICU types. Policies facilitating care for MLP infants at NICUs with less complex subspecialty services may improve care quality delivered to this prevalent, at-risk population.
Enhancement of Out‐of‐Plane Spin–Orbit Torque by Interfacial Modification
Authors: Zhao Tieyang , Liu Liang , Zhou Chenghang , Zheng Zhenyi , Li Huihui , Xie Qidong , Yao Bingqing , Ren Lizhu , Chai Jianwei , Dong Zhili , Zhao Chao , Chen Jingsheng 
Published: January 2023

AbstractSpin–orbit torque (SOT)‐induced switching of perpendicular magnetization in the absence of magnetic field is crucial for the application of SOT‐based spintronic devices. Recent works have demonstrated that the low‐symmetry crystal structure in CuPt/CoPt can give rise to an out‐of‐plane (OOP) spin torque and lead to deterministic magnetization switching without an external field. However, it is essential to improve OOP effective field for the efficient switching. In this work, the impact of interface oxidation on the generation of OOP effective field in a CuPt/ferromagnet heterostructure is systematically studied. By introducing an oxidized CuPt surface, it is found that the field‐free switching performance shows remarkable improvement. OOP effective field measurement indicates that the oxidation treatment can enhance the OOP effective field by more than two times. It is also demonstrated that this oxidation‐induced OOP SOT efficiency enhancement is independent of the device shapes, magnetic materials, or magnetization easy axis. This work contributes to improve the performance of SOT devices and provides an effective fabrication guidance for future spintronic devices that utilize OOP SOT.
Resolution of MoS2 Nanosheets‐Induced Pulmonary Inflammation Driven by Nanoscale Intracellular Transformation and Extracellular‐Vesicle Shuttles
Authors: Ortiz Peña Nathaly , Cherukula Kondareddy , Even Benjamin , Ji Ding‐Kun , Razafindrakoto Sarah , Peng Shiyuan , Silva Amanda K. A. , Ménard‐Moyon Cécilia , Hillaireau Hervé , Bianco Alberto , Fattal Elias , Alloyeau Damien , Gazeau Florence 
Published: January 2023

AbstractPulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among 2D nanomaterials and graphene, MoS2 has received tremendous attention in optoelectronics and nanomedicine. Here an integrated approach is proposed to follow up the transformation of MoS2 nanosheets at the nanoscale and assesss their impact on lung inflammation status over 1 month after a single inhalation in mice. Analysis of immune cells, alveolar macrophages, extracellular vesicles, and cytokine profiling in bronchoalveolar lavage fluid (BALF) shows that MoS2 nanosheets induced initiation of lung inflammation. However, the inflammation is rapidly resolved despite the persistence of various biotransformed molybdenum‐based nanostructures in the alveolar macrophages and the extracellular vesicles for up to 1 month. Using in situ liquid phase transmission electron microscopy experiments, the dynamics of MoS2 nanosheets transformation triggered by reactive oxygen species could be evidenced. Three main transformation mechanisms are observed directly at the nanoscale level: 1) scrolling of the dispersed sheets leading to the formation of nanoscrolls and folded patches, 2) etching releasing soluble MoO4−, and 3) oxidation generating oxidized sheet fragments. Extracellular vesicles released in BALF are also identified as a potential shuttle of MoS2 nanostructures and their degradation products and more importantly as mediators of inflammation resolution.
Solvent‐in‐Gas System for Promoted Photocatalytic Ammonia Synthesis on Porous Framework Materials
Authors: Liu Sisi , Wang Mengfan , Ji Haoqing , Zhang Lifang , Ni Jiajie , Li Najun , Qian Tao , Yan Chenglin , Lu Jianmei 
Published: January 2023

AbstractPhotocatalytic nitrogen reduction reaction (PNRR) is emerging as a sustainable ammonia synthesis approach to meet global carbon neutrality. Porous framework materials with well‐designed structures have great opportunities in PNRR; however, they suffer from unsatisfactory activity in the conventional gas‐in‐solvent system (GIS), owing to the hindrance of nitrogen utilization and strong competing hydrogen evolution caused by overwhelming solvent. In this study, porous framework materials are combined with a novel “solvent‐in‐gas” system, which can bring their superiority into full play. This system enables photocatalysts to directly operate in a gas‐dominated environment with a limited proton source uniformly suspended in it, achieving the accumulation of high‐concentrated nitrogen within porous framework while efficiently restricting the solvent‐photocatalyst contact. An over eightfold increase in ammonia production rate (1820.7 µmol g−1 h−1) compared with the conventional GIS and an apparent quantum efficiency as high as ≈0.5% at 400 nm are achieved. This system‐level strategy further finds applicability in photocatalytic CO2 reduction, featuring it as a staple for photosynthetic methodology.