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"Abstract": {
"AbstractText": "Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow-sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAA), but not subcutaneous adipose arteries (SAA), exhibit endothelial dysfunction."
},
"ArticleTitle": "Differential effects of obesity on visceral vs. subcutaneous adipose arteries: role of shear activated Kir2.1 and alterations to the glycocalyx.",
"AuthorList": {
"Author": {
"LastName": [
"Ahn",
"Le Master",
"Lee",
"Phillips",
"Levitan",
"Fancher"
],
"ForeName": [
"Sang Joon",
"Elizabeth",
"James C",
"Shane A",
"Irena",
"Ibra S"
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"NA"
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"HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)",
"HHS | NIH | National Institute on Aging (NIA)",
"University of Delaware (UD)"
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"Abstract": {
"AbstractText": "Obesity is associated with higher risks of cardiac arrhythmias. Although this may be partly explained by concurrent cardiometabolic ill-health, growing evidence suggests that increasing adiposity independently confers risk for arrhythmias. Amongst fat depots, epicardial adipose tissue (EAT) exhibits a proinflammatory secretome, and given the lack of fascial separation, has been implicated as a transducer of inflammation to the underlying myocardium. The present review explores the mechanisms underpinning adverse electrophysiological remodelling as a consequence of EAT accumulation and the consequent inflammation. We first describe the physiological and pathophysiological function of EAT and its unique secretome, and subsequently discuss the evidence for ionic channel and connexin expression modulation as well as fibrotic remodelling induced by cytokines and free fatty acids that are secreted by EAT. Finally, we highlight how weight reduction and regression of EAT volume may cause reverse remodelling to ameliorate arrhythmic risk."
},
"ArticleTitle": "Epicardial adipose tissue as a mediator of cardiac arrhythmias.",
"AuthorList": {
"Author": {
"LastName": [
"Patel",
"Hwang",
"Se Liebers",
"Ng"
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"ForeName": [
"Kiran Haresh Kumar",
"Taesoon",
"Curtis",
"Fu Siong"
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"British Heart Foundation (BHF)"
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""
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"PMID": 34890280,
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"AbstractText": "Consumption of diets high in fat, sugar and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Obese women are more prone to develop arterial stiffening leading to more frequent and severe CVD compared to men. As tissue transglutaminase (TG2) has been implicated in vascular stiffening, our goal herein was to determine the efficacy of cystamine, a non-specific TG2 inhibitor, at reducing vascular stiffness in female mice chronically fed a WD. Three experimental groups of female mice were created. One was fed regular chow diet (CD) for 43 weeks starting at four weeks of age. The second was fed a WD for the same 43 weeks, whereas a third cohort was fed WD, but also received cystamine (216 mg/kg/d) in the drinking water during the last eight weeks on the diet (WD+C). All vascular stiffness parameters assessed, including aortic pulse wave velocity and the incremental modulus of elasticity of isolated femoral and mesenteric arteries, were significantly increased in WD- vs. CD-fed mice, and reduced in WD+C vs. WD-fed mice. These changes coincided with respectively augmented and diminished vascular wall collagen and F-actin content, with no associated effect in blood pressure. In cultured human vascular smooth muscle cells, cystamine reduced TG2 activity, F-actin/G-actin ratio, collagen compaction capacity and cellular stiffness. We conclude that cystamine treatment represents an effective approach to reduce vascular stiffness in female mice in the setting of WD consumption, likely due to its TG2 inhibitory capacity."
},
"ArticleTitle": "Cystamine reduces vascular stiffness in Western diet-fed female mice.",
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"Author": {
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"Ramirez-Perez",
"Cabral-Amador",
"Whaley-Connell",
"Aroor",
"Morales-Quinones",
"Woodford",
"Ghiarone",
"Ferreira-Santos",
"Jurrissen",
"Manrique-Acevedo",
"Jia",
"Demarco",
"Padilla",
"Martinez-Lemus",
"Lastra"
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"Francisco I",
"Francisco J",
"Adam T",
"Annayya R",
"Mariana",
"Makenzie L",
"Thaysa",
"Larissa",
"Thomas J",
"Camila M",
"Guanghong",
"Vincent G",
"Jaume",
"Luis A",
"Guido"
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"K08HL132012",
"DK124329",
"R01HL137769",
"2018/18854-0",
"5I01BX001981",
"I01BX003391",
"Truman VA Medical Research Foundation"
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"HHS | National Institutes of Health (NIH)",
"HHS | National Institutes of Health (NIH)",
"HHS | National Institutes of Health (NIH)",
"HHS | National Institutes of Health (NIH)",
"HHS | National Institutes of Health (NIH)",
"Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)",
"U.S. Department of Veterans Affairs (VA)",
"U.S. Department of Veterans Affairs (VA)",
"U.S. Department of Veterans Affairs (VA)"
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"Abstract": {
"AbstractText": "Organizing and annotating biological sample data is critical in data-intensive bioinformatics. Unfortunately, metadata formats from a data provider are often incompatible with requirements of a processing tool. There is no broadly accepted standard to organize metadata across biological projects and bioinformatics tools, restricting the portability and reusability of both annotated datasets and analysis software."
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"ArticleTitle": "Linking big biomedical datasets to modular analysis with Portable Encapsulated Projects.",
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"Author": {
"LastName": [
"Sheffield",
"Stolarczyk",
"Reuter",
"Rendeiro"
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"Nathan C",
"Michał",
"Vincent P",
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"PMID": 34890456,
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"AbstractText": "Under anaerobic stress, Arabidopsis thaliana induces the expression of a collection of core hypoxia genes that encode proteins for an adaptive response. Among these genes is NIP2;1, which encodes a member of the \"Nodulin 26-like Intrinsic Protein\" (NIP) subgroup of the aquaporin superfamily of membrane channel proteins. NIP2;1 expression is limited to the \"anoxia core\" region of the root stele under normal growth conditions, but shows substantial induction (up to 1,000-fold by 2-4 h of hypoxia) by low oxygen stress, and accumulation in all root tissues. During hypoxia, NIP2;1-GFP accumulates predominantly on the plasma membrane by 2 h, is distributed between the plasma and internal membranes during sustained hypoxia, and remains elevated in root tissues through 4 h of reoxygenation recovery. In response to hypoxia challenge, T-DNA insertion mutant nip2;1 plants exhibit elevated lactic acid within root tissues, reduced efflux of lactic acid, and reduced acidification of the external medium compared to wild-type plants. Previous biochemical evidence demonstrates that NIP2;1 has lactic acid channel activity, and our work supports the hypothesis that NIP2;1 prevents lactic acid toxicity by facilitating release of cellular lactic acid from the cytosol to the apoplast, supporting eventual efflux to the rhizosphere. In evidence, nip2;1 plants demonstrate poorer survival during argon-induced hypoxia stress. Expressions of the ethanolic fermentation transcript Alcohol Dehydrogenase1 and the core hypoxia-induced transcript Alanine Aminotransferase1 are elevated in nip2;1, and expression of the Glycolate Oxidase3 transcript is reduced, suggesting NIP2;1 lactic acid efflux regulates other pyruvate and lactate metabolism pathways."
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"ArticleTitle": "Aquaporin family lactic acid channel NIP2;1 promotes plant survival under low oxygen stress in Arabidopsis.",
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"Routray",
"Choi",
"Spangler",
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"AbstractText": "Homeostasis in living cells refers to the steady state of internal, physical, and chemical conditions. It is sustained by self-regulation of the dynamic cellular system. To gain insight into the homeostatic mechanisms that maintain cytosolic nutrient concentrations in plant cells within a homeostatic range, we performed computational cell biology experiments. We mathematically modeled membrane transporter systems and simulated their dynamics. Detailed analyses of 'what-if' scenarios demonstrated that a single transporter type for a nutrient, irrespective of whether it is a channel or a cotransporter, is not sufficient to calibrate a desired cytosolic concentration. A cell cannot flexibly react to different external conditions. Rather, at least two different transporter types for the same nutrient, which are energized differently, are required. The gain of flexibility in adjusting a cytosolic concentration was accompanied by the establishment of energy-consuming cycles at the membrane, suggesting that these putatively \"futile\" cycles are not as futile as they appear. Accounting for the complex interplay of transporter networks at the cellular level may help design strategies for increasing nutrient use efficiency of crop plants."
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"ArticleTitle": "Nutrient cycling is an important mechanism for homeostasis in plant cells.",
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"Author": {
"LastName": [
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"Ingo"
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"AbstractText": "Formation of pollen wall exine is preceded by the development of several transient layers of extracellular materials deposited on the surface of developing pollen grains. One such layer is primexine (PE), a thin, ephemeral structure that is present only for a short period of time and is difficult to visualize and study. Recent genetic studies suggested that PE is a key factor in the formation of exine, making it critical to understand its composition and the dynamics of its formation. In this study, we used high-pressure frozen/freeze-substituted samples of developing Arabidopsis (Arabidopsis thaliana) pollen for a detailed transmission electron microscopy analysis of the PE ultrastructure throughout the tetrad stage of pollen development. We also analyzed anthers from wild-type Arabidopsis and three mutants defective in PE formation by immunofluorescence, carefully tracing several carbohydrate epitopes in PE and nearby anther tissues during the tetrad and the early free-microspore stages. Our analyses revealed likely sites where these carbohydrates are produced and showed that the distribution of these carbohydrates in PE changes significantly during the tetrad stage. We also identified tools for staging tetrads and demonstrate that components of PE undergo changes resembling phase separation. Our results indicate that PE behaves like a much more dynamic structure than has been previously appreciated and clearly show that Arabidopsis PE creates a scaffolding pattern for formation of reticulate exine."
},
"ArticleTitle": "Dynamic changes in primexine during the tetrad stage of pollen development.",
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"Author": {
"LastName": [
"Wang",
"Owen",
"Dobritsa"
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"Heather A",
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"PMID": 34890459,
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"AbstractText": "Systemic acquired resistance (SAR) is a plant immune response established in uninfected leaves after colonization of local leaves with biotrophic or hemibiotrophic pathogens. The amino acid-derived metabolite N-hydroxypipecolic acid (NHP) travels from infected to systemic leaves, where it activates salicylic acid (SA) biosynthesis through the isochorismate pathway. The resulting increased SA levels are essential for induction of a large set of SAR marker genes and full SAR establishment. In this study, we show that pharmacological treatment of Arabidopsis thaliana with NHP induces a subset of SAR-related genes even in the SA induction-deficient2 (sid2/isochorismate synthase1) mutant, which is devoid of NHP-induced SA. NHP-mediated induction is abolished in sid2-1 NahG plants, in which basal SA levels are degraded. The SA receptor NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) and its interacting TGACG SEQUENCE-SPECIFIC BINDING PROTEIN (TGA) transcription factors are required for the NHP-mediated induction of SAR genes at resting SA levels. Isothermal titration analysis determined a KD of 7.9 ± 0.5 µM for the SA/NPR1 complex, suggesting that basal levels of SA would not bind to NPR1 unless yet unknown potentially NHP-induced processes increase the affinity. Moreover, the nucleocytoplasmic protein PHYTOALEXIN DEFICIENT4 is required for a slight NHP-mediated increase in NPR1 protein levels and NHP-induced expression of SAR-related genes. Our experiments have unraveled that NHP requires basal SA and components of the SA signaling pathway to induce SAR genes. Still, the mechanism of NHP perception remains enigmatic."
},
"ArticleTitle": "N-hydroxypipecolic acid-induced transcription requires the salicylic acid signaling pathway at basal SA levels.",
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"Voß",
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"AbstractText": "Several effectors from phytopathogens usually target various cell organelles to interfere with plant defenses, and they generally contain sequences that direct their translocation into organelles, such as chloroplasts. In this study, we characterized a different mechanism for effectors to attack chloroplasts in wheat (Triticum aestivum). Two effectors from Puccinia striiformis f. sp. tritici (Pst), Pst_4, and Pst_5, inhibit Bax-mediated cell death and plant immune responses, such as callose deposition and reactive oxygen species (ROS) accumulation. Gene silencing of the two effectors induced significant resistance to Pst, demonstrating that both effectors function as virulence factors of Pst. Although these two effectors have low sequence similarities and lack chloroplast transit peptides, they both interact with TaISP (wheat cytochrome b6-f complex iron-sulfur subunit, a chloroplast protein encoded by nuclear gene) in the cytoplasm. Silencing of TaISP impaired wheat resistance to avirulent Pst and resulted in less accumulation of ROS. Heterogeneous expression of TaISP enhanced chloroplast-derived ROS accumulation in Nicotiana benthamiana. Co-localization in N. benthamiana and western blot assay of TaISP content in wheat chloroplasts show that both effectors suppressed TaISP from entering chloroplasts. We conclude that these biotrophic fungal effectors suppress plant defenses by disrupting the sorting of chloroplast protein, thereby limiting host ROS accumulation and promoting fungal pathogenicity."
},
"ArticleTitle": "Two stripe rust effectors impair wheat resistance by suppressing import of host Fe-S protein into chloroplasts.",
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"Zhai",
"Zhang",
"Tang",
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"Wang",
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"Xingmin",
"Chunlei",
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"Jianfeng",
"Sébastien",
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"Abstract": {
"AbstractText": "Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens in a synergistic and interdependent manner, while JA and ET also have independent roles in certain processes, e.g. in responses to wounding and flooding, respectively. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, of which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. We previously demonstrated that Arabidopsis (Arabidopsis thaliana) GDSL LIPASE 1 (GLIP1) depends on ET for gene expression and pathogen resistance. Here, promoter analysis of GLIP1 revealed ERELEE4 as the critical cis-element for ET-responsive GLIP1 expression. In a yeast one-hybrid screening, ORA59 was isolated as a specific transcription factor that binds to the ERELEE4 element, in addition to the well-characterized GCC box. We found that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in gene promoters. Notably, ORA59 exhibited a differential preference for GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. JA and ET induced ORA59 phosphorylation, which was required for both activity and specificity of ORA59. Furthermore, RNA-seq and virus-induced gene silencing analyses led to the identification of ORA59 target genes of distinct functional categories in JA and ET pathways. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways."
},
"ArticleTitle": "The transcription factor ORA59 exhibits dual DNA binding specificity that differentially regulates ethylene- and jasmonic acid-induced genes in plant immunity.",
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"Hyeri",
"Su Jin",
"Kwang-Moon",
"Yerin",
"Dong Sook",
"Myoung-Hoon",
"Soo Young",
"Jong Chan",
"Sun Jae",
"Jungmin",
"Ohkmae K"
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"Abstract": {
"AbstractText": "The mechanical properties of guard cell (GC) walls are important for stomatal development and stomatal response to external stimuli. However, the molecular mechanisms of pectin synthesis and pectin composition controlling stomatal development and dynamics remain poorly explored. Here, we characterized the role of two Arabidopsis (Arabidopsis thaliana) galacturonosyltransferases, GAUT10 and GAUT11, in plant growth, stomatal development, and stomatal dynamics. GAUT10 and GAUT11 double mutations reduced pectin synthesis and promoted homogalacturonan (HG) demethylesterification and demethylesterified HG degradation, resulting in larger stomatal complexes and smaller pore areas, increased stomatal dynamics, and enhanced drought tolerance of plants. In contrast, increased GAUT10 or GAUT11 expression impaired stomatal dynamics and drought sensitivity. Genetic interaction analyses together with immunolabeling analyses suggest that the methylesterified HG level is important in stomatal dynamics, and pectin abundance with the demethylesterified HG level controls stomatal dimension and stomatal size. Our results provide insight into the molecular mechanism of GC wall properties in stomatal dynamics, and highlight the role of GAUT10 and GAUT11 in stomatal dimension and dynamics through modulation of pectin biosynthesis and distribution in GC walls."
},
"ArticleTitle": "Two galacturonosyltransferases function in plant growth, stomatal development, and dynamics.",
"AuthorList": {
"Author": {
"LastName": [
"Guo",
"Xiao",
"Liu",
"Li",
"Yan",
"Yao",
"Hu"
],
"ForeName": [
"Huimin",
"Chuanlei",
"Qing",
"Ruiying",
"Zhiqiang",
"Xuan",
"Honghong"
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"2016YFD0100606"
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"Article": {
"Abstract": {
"AbstractText": "In tip-growing plant cells, growth results from myosin XI and F-actin-mediated deposition of cell wall polysaccharides contained in secretory vesicles. Previous evidence showed that myosin XI anticipates F-actin accumulation at the cell's tip, suggesting a mechanism where vesicle clustering via myosin XI increases F-actin polymerization. To evaluate this model, we used a conditional loss-of-function strategy by generating moss (Physcomitrium patens) plants harboring a myosin XI temperature-sensitive allele. We found that loss of myosin XI function alters tip cell morphology, vacuolar homeostasis, and cell viability but not following F-actin depolymerization. Importantly, our conditional loss-of-function analysis shows that myosin XI focuses and directs vesicles at the tip of the cell, which induces formin-dependent F-actin polymerization, increasing F-actin's local concentration. Our findings support the role of myosin XI in vesicle focusing, possibly via clustering and F-actin organization, necessary for tip growth, and deepen our understanding of additional myosin XI functions."
},
"ArticleTitle": "Myosin XI drives polarized growth by vesicle focusing and local enrichment of F-actin in Physcomitrium patens.",
"AuthorList": {
"Author": {
"LastName": [
"Galotto",
"Wisanpitayakorn",
"Bibeau",
"Liu",
"Furt",
"Pierce",
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"Tüzel",
"Vidali"
],
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"Giulia",
"Pattipong",
"Jeffrey P",
"Yen-Chun",
"Fabienne",
"Ellen C",
"Parker J",
"Erkan",
"Luis"
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"National Science Foundation and the National Institutes of Health (NSF-MCB"
],
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"Abstract": {
"AbstractText": "Males have worse outcomes after hip fracture than female counterparts. Cognitive impairment (CI) also increases the risk of poor recovery from hip fracture; however, CI is under-recognized. Patient sex may contribute to this under-recognition through differential misclassification. The objective of this study was to measure under-recognition and differential misclassification of CI by patient sex."
},
"ArticleTitle": "Differential misclassification of cognitive impairment by sex among hip fracture patients.",
"AuthorList": {
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"LastName": [
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"Year": 2021,
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"Day": 10
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"Article": {
"Abstract": {
"AbstractText": "Involvement of end-users in research can enhance its quality, relevance, credibility and legitimacy; however, the processes through which these changes occur are unclear. Our aim was to explore a coproduction research team's experiences of their involvement in research about young people with type 1 diabetes mellitus (T1DM)."
},
"ArticleTitle": "A framework for involving coproduction partners in research about young people with type 1 diabetes.",
"AuthorList": {
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"Fiona",
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"Michelle",
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"Article": {
"Abstract": {
"AbstractText": "Patient engagement in research agenda setting is increasingly being seen as a strategy to improve the responsiveness of healthcare to patient priorities. Implementation of low-dose computed tomography (LDCT) screening for lung cancer is suboptimal, suggesting that research is needed."
},
"ArticleTitle": "Engaging veteran stakeholders to identify patient-centred research priorities for optimizing implementation of lung cancer screening.",
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"Author": {
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"Article": {
"Abstract": {
"AbstractText": "Patients with immune-mediated diseases treated with anti-CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID-19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown."
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"ArticleTitle": "Coronavirus Disease 2019 Outcomes Among Recipients of Anti-CD20 Monoclonal Antibodies for Immune-Mediated Diseases: A Comparative Cohort Study.",
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"Tiffany Y-T",
"Michael",
"Xiaoqing",
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"Lauren",
"Lily",
"Kathleen M M",
"Alessandra",
"Yuqing",
"Jeffrey A",
"Zachary S"
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"NIAMS NIH HHS",
"NIAMS NIH HHS",
"NIAMS NIH HHS",
"NIAMS NIH HHS",
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"AbstractText": "Recent studies have identified at least 20 different kidney cell types based upon chromatin structure and gene expression. Histone deacetylases (HDACs) are epigenetic transcriptional repressors via deacetylation of histone lysines resulting in inaccessible chromatin. We reported that kidney epithelial HDAC1 and HDAC2 activity is critical for maintaining a healthy kidney and preventing fluid-electrolyte abnormalities. However, to what extent does Hdac1/Hdac2 knockdown affect chromatin structure and subsequent transcript expression in the kidney? To answer this question, we used single nucleus Assay for Transposase-Accessible Chromatin-sequencing (snATAC-seq) and snRNA-seq to profile kidney nuclei from male and female, control and littermate kidney epithelial Hdac1/Hdac2 knockdown mice. Hdac1/Hdac2 knockdown resulted in significant changes in the chromatin structure predominantly within the promoter region of gene loci involved in fluid-electrolyte balance such as the aquaporins, with both increased and decreased accessibility captured. Moreover, Hdac1/Hdac2 knockdown resulted different gene loci being accessible with a corresponding increased transcript number in the kidney, but among all mice only 24-30% of chromatin accessibility agreed with transcript expression (e.g. open chromatin, increased transcript). To conclude, although chromatin structure does affect transcription, ~70% of the differentially expressed genes cannot be explained by changes in chromatin accessibility and HDAC1/HDAC2 had a minimal effect on these global patterns. Yet, the genes that are targets of HDAC1 and HDAC2 are critically important for maintaining kidney function."
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"AbstractText": "Low vitamin D status is associated with a higher risk for cardiovascular diseases (CVDs). Although most existing linear Mendelian randomization (MR) studies reported a null effect of vitamin D on CVD risk, a non-linear effect cannot be excluded. Our aim was to apply the non-linear MR design to investigate the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with CVD risk."
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"AbstractText": "Bacterial whole-genome sequencing based on short-read technologies often results in a draft assembly formed by contiguous sequences. The introduction of long-read sequencing technologies permits those contiguous sequences to be unambiguously bridged into complete genomes. However, the elevated costs associated with long-read sequencing frequently limit the number of bacterial isolates that can be long-read sequenced. Here we evaluated the recently released 96 barcoding kit from Oxford Nanopore Technologies (ONT) to generate complete genomes on a high-throughput basis. In addition, we propose an isolate selection strategy that optimizes a representative selection of isolates for long-read sequencing considering as input large-scale bacterial collections."
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"Gladstone",
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"AbstractText": "Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non-poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints."
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"AbstractText": "Early diagnosis of mild cognitive impairment (MCI) fascinates screening high-risk Alzheimer's disease (AD). White matter is found to degenerate earlier than gray matter and functional connectivity during MCI. Although studies reveal white matter degenerates in the limbic system for MCI, how other white matter degenerates during MCI remains unclear. In our method, regions of interest with a high level of resting-state functional connectivity with hippocampus were selected as seeds to track fibers based on diffusion tensor imaging (DTI). In this way, hippocampus-temporal and thalamus-related fibers were selected, and each fiber's DTI parameters were extracted. Then, statistical analysis, machine learning classification, and Pearson's correlations with behavior scores were performed between MCI and normal control (NC) groups. Results show that: 1) the mean diffusivity of hippocampus-temporal and thalamus-related fibers are significantly higher in MCI and could be used to classify 2 groups effectively. 2) Compared with normal fibers, the degenerated fibers detected by the DTI indexes, especially for hippocampus-temporal fibers, have shown significantly higher correlations with cognitive scores. 3) Compared with the hippocampus-temporal fibers, thalamus-related fibers have shown significantly higher correlations with depression scores within MCI. Our results provide novel biomarkers for the early diagnoses of AD."
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"AbstractText": "During natural vision, objects rarely appear in isolation, but often within a semantically related scene context. Previous studies reported that semantic consistency between objects and scenes facilitates object perception and that scene-object consistency is reflected in changes in the N300 and N400 components in EEG recordings. Here, we investigate whether these N300/400 differences are indicative of changes in the cortical representation of objects. In two experiments, we recorded EEG signals, while participants viewed semantically consistent or inconsistent objects within a scene; in Experiment 1, these objects were task-irrelevant, while in Experiment 2, they were directly relevant for behavior. In both experiments, we found reliable and comparable N300/400 differences between consistent and inconsistent scene-object combinations. To probe the quality of object representations, we performed multivariate classification analyses, in which we decoded the category of the objects contained in the scene. In Experiment 1, in which the objects were not task-relevant, object category could be decoded from ~100 ms after the object presentation, but no difference in decoding performance was found between consistent and inconsistent objects. In contrast, when the objects were task-relevant in Experiment 2, we found enhanced decoding of semantically consistent, compared with semantically inconsistent, objects. These results show that differences in N300/400 components related to scene-object consistency do not index changes in cortical object representations but rather reflect a generic marker of semantic violations. Furthermore, our findings suggest that facilitatory effects between objects and scenes are task-dependent rather than automatic."
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"Abstract": {
"AbstractText": "Identifying new indications for drugs plays an essential role at many phases of drug research and development. Computational methods are regarded as an effective way to associate drugs with new indications. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering the biological knowledge of drugs and diseases, which are believed to be useful for improving the accuracy of drug repositioning. To this end, a novel heterogeneous information network (HIN) based model, namely HINGRL, is proposed to precisely identify new indications for drugs based on graph representation learning techniques. More specifically, HINGRL first constructs a HIN by integrating drug-disease, drug-protein and protein-disease biological networks with the biological knowledge of drugs and diseases. Then, different representation strategies are applied to learn the features of nodes in the HIN from the topological and biological perspectives. Finally, HINGRL adopts a Random Forest classifier to predict unknown drug-disease associations based on the integrated features of drugs and diseases obtained in the previous step. Experimental results demonstrate that HINGRL achieves the best performance on two real datasets when compared with state-of-the-art models. Besides, our case studies indicate that the simultaneous consideration of network topology and biological knowledge of drugs and diseases allows HINGRL to precisely predict drug-disease associations from a more comprehensive perspective. The promising performance of HINGRL also reveals that the utilization of rich heterogeneous information provides an alternative view for HINGRL to identify novel drug-disease associations especially for new diseases."
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"AbstractText": "Trypanosoma cruzi/HIV coinfection has been described as a relevant clinical event and an emerging public health problem. Here, we describe the epidemiological patterns of deaths related to Chagas disease and HIV/AIDS coinfection in Brazil from 2000 to 2019."
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"Abstract": {
"AbstractText": "Label=\"OBJECTIVE\" NlmCategory=\"OBJECTIVE\"> The aim of this <i>in vitro</i> experiment was to see how the operator's manual skills, polishing equipment, and abrasive materials affected the surface roughness of denture base resins."
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"ArticleTitle": "Comparative Analysis of Abrasive Materials and Polishing System on the Surface Roughness of Heat-Polymerized Acrylic Resins.",
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"AbstractText": "To evaluate whether participation in CenteringPregnancy group prenatal care is associated with decreased risk of an interpregnancy interval (IPI) ≤6 months."
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"Abstract": {
"AbstractText": "Metabolic diseases are often associated with lipid and glucose metabolism abnormalities, which increase the risk of cardiovascular disease. Diabetic cardiomyopathy (DCM) is an important development of metabolic diseases and a major cause of death. Lipids are the main fuel for energy metabolism in the heart. The increase of circulating lipids affects the uptake and utilization of fatty acids and glucose in the heart, and also affects mitochondrial function. In this paper, the mechanism of lipid overload in metabolic diseases leading to cardiac energy metabolism disorder is discussed."
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"ArticleTitle": "Effects of Lipid Overload on Heart in Metabolic Diseases.",
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"Yan",
"Xie",
"Ding",
"Wang",
"Guo"
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"Xinya",
"Yi",
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"AbstractText": "Diabetes confers an increased risk of microvascular complications, including retinopathy. However, whether prediabetes is also related to retinopathy has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and retinopathy. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship. Nine cross-sectional studies including 14 751 community dwelling adult participants were included; 3847 (26.1%) of them were prediabetic. Results showed that prediabetes was associated with a higher prevalence of retinopathy compared to normoglycemia [odds ratio (OR): 1.55, 95% confidence interval (CI): 1.10-2.20, p=0.01, I<sup>2</sup>=34%]. Sensitivity analysis by excluding one study at a time showed consistent result (OR: 1.35 to 1.73, p all<0.05). Subgroup analysis showed study characteristics such as definition of prediabetes, country of study, sample size, mean age of participants, or univariate or multivariate analyses may not significantly affect the association (p for subgroup difference all>0.05). Current evidence suggests that patients with prediabetes may be associated with higher prevalence of retinopathy as compared to those with normoglycemia. Although prospective cohort studies are needed to validate these findings, results of our meta-analysis highlighted the importance of early prevention of retinopathy in patients with prediabetes."
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"AbstractText": "There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses."
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"AbstractText": "Brain Magnetic Resonance Imaging (MRI) examination of cerebral small vessel disease (CSVD) may help screen vascular cognitive impairment. A recently estimated CSVD score system was suggested to capture the overall CSVD burden. The study aimed to detect the association between systemic evaluation score of cerebral vascular imaging parameters with cognitive functions."
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"ArticleTitle": "Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis.",
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"AbstractText": "Label=\"PURPOSE\" NlmCategory=\"OBJECTIVE\">While marked reductions in neural activity and mitochondrial function have been reported in Alzheimer's disease (AD), the degree of mitochondrial activity in mild cognitive impairment (MCI) or early-stage AD remains unexplored. Here, we used positron emission tomography (PET) to examine the direct relationship between mitochondrial activity (<sup>18</sup>F-BCPP-EF) and β-amyloid (Aβ) deposition (<sup>11</sup>C-PiB) in the same brains of senescence-accelerated mouse prone 10 (SAMP10) mice, an Aβ-developing neuroinflammatory animal model showing accelerated senescence with deterioration in cognitive functioning similar to that in MCI."
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"LastName": [
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"Iga",
"Ikegaya",
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"Ohba",
"Nishiyama",
"Fukomoto",
"Kanazawa",
"Harada",
"Tsukada",
"Sato",
"Ouchi"
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"Satoru",
"Yurika",
"Shunsuke",
"Takeharu",
"Hiroyuki",
"Shingo",
"Daisuke",
"Masakatsu",
"Norihiro",
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"AbstractText": "TREM2 is a microglial receptor genetically linked to the risk for Alzheimer's disease (AD). The cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2) have emerged as a valuable biomarker for the disease progression in AD and higher CSF levels of sTREM2 are linked to slower cognitive decline. Increasing sTREM2 in mouse models of amyloidosis reduces amyloid-related pathology through modulating microglial functions, suggesting a beneficial role of sTREM2 in microglia biology and AD pathology."
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"Ying",
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"AbstractText": "To improve the developmental competence of in vitro cultured oocytes, extensive literature focused on maturation rate improvement with different additives in culture medium, while studies investigating the maturation dynamics of oocytes during in vitro maturation (IVM) and the influencing factors on oocyte viability are scarce."
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"Abstract": {
"AbstractText": "HIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition among African, Caribbean, and other Black (ACB) women has been associated with the higher prevalence of bacterial vaginosis (BV) in these communities, wherein the vaginal microbiota is predominated by diverse pro-inflammatory anaerobic bacteria. However, while the vaginal microbiota in BV-free women is typically predominated by one of several different Lactobacillus spp., the degree of HIV protection afforded by a Lactobacillus-predominant vaginal microbiota also varies considerably. Specifically, L. crispatus is associated with an immunoregulatory genital immune environment, exclusion of BV-associated bacteria, and reduced HIV risk. In contrast, less HIV protection or exclusion of BV-associated bacteria and fewer immune benefits have been associated with L. iners-which is unfortunately the most common Lactobacillus species among ACB women. These species-specific clinical differences are underpinned by substantial genomic differences between Lactobacillus species: for instance, the much smaller genome of L. iners lacks the coding sequence for D-lactic acid dehydrogenase and cannot produce the D-lactate isomer that enhances HIV trapping in mucus but encodes for epithelial cell toxins and stress resistance proteins that may enhance bacterial survival in the context of microbiota and environmental fluctuations. While more studies are needed to elucidate whether differences in HIV protection between Lactobacillus species are due to direct genital immune effects or the exclusion of proinflammatory BV-associated bacteria, the current body of work suggests that for BV treatment to succeed as an HIV prevention strategy, it may be necessary to induce a vaginal microbiota that is predominated by specific (non-iners) Lactobacillus species. Video abstract."
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"AbstractText": "The risk of outbreaks escalating into pandemics has soared with globalization. Therefore, understanding transmission mechanisms of infectious diseases has become critical to formulating global public health policy. This systematic review assessed evidence in the medical and public health literature for the military as a disease vector."
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"Abstract": {
"AbstractText": "micro(mi)RNAs are short noncoding RNAs that through their seed sequence (pos. 2-7/8 of the guide strand) regulate cell function by targeting complementary sequences (seed matches) located mostly in the 3' untranslated region (3' UTR) of mRNAs. Any short RNA that enters the RNA induced silencing complex (RISC) can kill cells through miRNA-like RNA interference when its 6mer seed sequence (pos. 2-7 of the guide strand) has a G-rich nucleotide composition. G-rich seeds mediate 6mer Seed Toxicity by targeting C-rich seed matches in the 3' UTR of genes critical for cell survival. The resulting Death Induced by Survival gene Elimination (DISE) predominantly affects cancer cells but may contribute to cell death in other disease contexts. This review summarizes recent findings on the role of DISE/6mer Seed Tox in cancer; its therapeutic potential; its contribution to therapy resistance; its selectivity, and why normal cells are protected. In addition, we explore the connection between 6mer Seed Toxicity and aging in relation to cancer and certain neurodegenerative diseases."
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"AbstractText": "Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer's disease (AD) and their clinical utility in predicting disease progression."
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"AbstractText": "Previous studies have confirmed that the microglial activation and subsequent inflammatory responses in the trigeminal nucleus caudalis (TNC) are involved in the central sensitization of chronic migraine (CM). MicroRNA-155-5p has been shown to modulate the polarization of microglia and participate in inflammatory processes in a variety of neurological diseases. However, its role in CM remains unclear. The purpose of this study was to determine the precise role of miR-155-5p in CM."
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"AbstractText": "Loneliness is a relatively common problem in young people (14-24 years) and predicts the onset of depression and anxiety. Interventions to reduce loneliness thus have significant potential as active ingredients in strategies to prevent or alleviate anxiety and depression among young people. Previous reviews have focused on quantitative evidence and have not examined potential mechanisms that could be targets for intervention strategies. To build on this work, in this review we aimed to combine qualitative and quantitative evidence with stakeholder views to identify interventions that appear worth testing for their potential effectiveness in reducing loneliness, anxiety and depression in young people aged 14-24 years, and provide insights into the potential mechanisms of action. We conducted a Critical Interpretative Synthesis, a systematic review method that iteratively synthesises qualitative and quantitative evidence and is explicitly focused on building theory through a critical approach to the evidence that questions underlying assumptions. Literature searches were performed using nine databases, and eight additional databases were searched for theses and grey literature. Charity and policy websites were searched for content relevant to interventions for youth loneliness. We incorporated elements of Rapid Realistic Review approaches by consulting with young people and academic experts to feed into search strategies and the resulting conceptual framework, in which we aimed to set out which interventions appear potentially promising in terms of theoretical and empirical underpinnings and which fit with stakeholder views. We reviewed effectiveness data and quality ratings for the included randomised controlled trials only. Through synthesising 27 studies (total participants n = 105,649; range 1-102,072 in different studies) and grey literature, and iteratively consulting with stakeholders, a conceptual framework was developed. A range of 'Intrapersonal' (e.g. therapy that changes thinking and behaviour), 'Interpersonal' (e.g. improving social skills), and 'Social' Strategies (e.g. enhancing social support, and providing opportunities for social contact) seem worth testing further for their potential to help young people address loneliness, thereby preventing or alleviating depression and/or anxiety. Such strategies should be co-designed with young people and personalised to fit individual needs. Plausible mechanisms of action are facilitating sustained social support, providing opportunities for young people to socialise with peers who share similar experiences, and changing thinking and behaviour, for instance through building positive attitudes to themselves and others. The most convincing evidence of effectiveness was found in support of Intrapersonal Strategies: two randomised controlled studies quality-rated as 'good' found decreases in loneliness associated with different forms of therapy (Cognitive Behavioural Therapy or peer network counselling), although power calculations were not reported, and effect sizes were small or missing. Strategies to address loneliness and prevent or alleviate anxiety and depression need to be co-designed and personalised. Promising elements to incorporate into these strategies are social support, including from peers with similar experiences, and psychological therapy."
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"Abstract": {
"AbstractText": "The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity."
},
"ArticleTitle": "Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.",
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"Ruhl",
"Pink",
"Kühne",
"Beushausen",
"Keil",
"Christoph",
"Sauer",
"Boblitz",
"Schmidt",
"David",
"Jäck",
"Roth",
"Cornberg",
"Schulz",
"Welte",
"Höper",
"Falk"
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"Isabell",
"Jenny F",
"Kerstin",
"Jana",
"Stella",
"Andrea",
"Lennart",
"Julius",
"Sascha",
"Hans-Martin",
"Edith",
"Markus",
"Thomas F",
"Tobias",
"Marius M",
"Christine S"
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"DZIF TTU-IICH 07_913",
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"ImProVIT",
"01KI2043"
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"Deutsche Forschungsgemeinschaft (German Research Foundation)",
"Deutsches Zentrum für Infektionsforschung (German Center for Infection Research)",
"Deutsches Zentrum für Infektionsforschung (German Center for Infection Research)",
"Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)",
"Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)",
"Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)"
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"Abstract": {
"AbstractText": "Gene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using \"circtools\". Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment."
},
"ArticleTitle": "Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder.",
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"LastName": [
"Lin",
"Lopez",
"Cruceanu",
"Pierotti",
"Fiori",
"Squassina",
"Chillotti",
"Dieterich",
"Mellios",
"Turecki"
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"Rixing",
"Juan Pablo",
"Cristiana",
"Caroline",
"Laura M",
"Alessio",
"Caterina",
"Christoph",
"Nikolaos",
"Gustavo"
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"Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)",
"Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)",
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"AbstractText": "Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells."
},
"ArticleTitle": "Depletion of NK6 Homeobox 3 (NKX6.3) causes gastric carcinogenesis through copy number alterations by inducing impairment of DNA replication and repair regulation.",
"AuthorList": {
"Author": {
"LastName": [
"Yoon",
"Eun",
"Ashktorab",
"Smoot",
"Kim",
"Nam",
"Park"
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"ForeName": [
"Jung Hwan",
"Jung Woo",
"Hassan",
"Duane T",
"Jeong Kyu",
"Suk Woo",
"Won Sang"
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"National Research Foundation of Korea (NRF)"
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"Abstract": {
"AbstractText": "Osteosarcoma (OS) is the most common primary bone tumor. Its high mortality rate and metastasis rate seriously threaten human health. Currently, the treatment has reached a plateau, hence we urgently need to explore new therapeutic directions. In this paper, we found that Trio was highly expressed in osteosarcoma than normal tissues and promoted the proliferation, migration, and invasion of osteosarcoma cells. Furthermore, Trio inhibited osteosarcoma cells' osteogenic differentiation in vitro and accelerated the growth of osteosarcoma in vivo. Given Trio contains two GEF domains, which have been reported as the regulators of RhoGTPases, we further discovered that Trio could regulate osteosarcoma progression and osteogenic differentiation through activating RhoGTPases. In summary, all our preliminary results showed that Trio could be a potential target and prognostic marker of osteosarcoma."
},
"ArticleTitle": "Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.",
"AuthorList": {
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"Yuan",
"Xu",
"Zhang",
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"Hong",
"Ma"
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"Lichan",
"Xiaohong",
"Zhongyin",
"Yuhuan",
"Leilei",
"Junqing"
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"82170911",
"82170911"
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"National Natural Science Foundation of China (National Science Foundation of China)",
"National Natural Science Foundation of China (National Science Foundation of China)",
"National Natural Science Foundation of China (National Science Foundation of China)",
"National Natural Science Foundation of China (National Science Foundation of China)",
"National Natural Science Foundation of China (National Science Foundation of China)"
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"Abstract": {
"AbstractText": "Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in stromal tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure and function. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through a collagen receptor. Discoidin domain receptor tyrosine kinase 1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells via Notch signaling to differentiate and form lobules. These findings demonstrate how human breast tissue regeneration is triggered by transmission of signals from the extracellular matrix through an epithelial bilayer to coordinate structural changes that lead to formation of a complex ductal-lobular network."
},
"ArticleTitle": "Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1.",
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"Author": {
"LastName": [
"Rauner",
"Jin",
"Miller",
"Gierahn",
"Li",
"Sokol",
"Feng",
"Mathis",
"Love",
"Gupta",
"Kuperwasser"
],
"ForeName": [
"Gat",
"Dexter X",
"Daniel H",
"Todd M",
"Carman M",
"Ethan S",
"Yu-Xiong",
"Robert A",
"J Christopher",
"Piyush B",
"Charlotte"
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"1122374",
"7R01GM124491-02"
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"National Science Foundation (NSF)",
"U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)"
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{
"PMID": 34893590,
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"Year": 2021,
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"Day": 11
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"Abstract": {
"AbstractText": "CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals."
},
"ArticleTitle": "Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive.",
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"Author": {
"LastName": [
"Gamez",
"Chaverra-Rodriguez",
"Buchman",
"Kandul",
"Mendez-Sanchez",
"Bennett",
"Sánchez C",
"Yang",
"Antoshechkin",
"Duque",
"Papathanos",
"Marshall",
"Akbari"
],
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"Stephanie",
"Duverney",
"Anna",
"Nikolay P",
"Stelia C",
"Jared B",
"Héctor M",
"Ting",
"Igor",
"Jonny E",
"Philippos A",
"John M",
"Omar S"
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"R01AI151004"
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"Agency": [
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"Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)"
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"Abstract": {
"AbstractText": "Metastasis is the main cause of carcinoma-related death, yet we know little about how it initiates due to our inability to visualize stochastic invasion events. Classical models suggest that cells accumulate mutations that first drive formation of a primary mass, and then downregulate epithelia-specific genes to cause invasion and metastasis. Here, using transparent zebrafish epidermis to model simple epithelia, we can directly image invasion. We find that KRas-transformation, implicated in early carcinogenesis steps, directly drives cell invasion by hijacking a process epithelia normally use to promote death-cell extrusion. Cells invading by basal cell extrusion simultaneously pinch off their apical epithelial determinants, endowing new plasticity. Following invasion, cells divide, enter the bloodstream, and differentiate into stromal, neuronal-like, and other cell types. Yet, only invading KRas<sup>V12</sup> cells deficient in p53 survive and form internal masses. Together, we demonstrate that KRas-transformation alone causes cell invasion and partial dedifferentiation, independently of mass formation."
},
"ArticleTitle": "KRas-transformed epithelia cells invade and partially dedifferentiate by basal cell extrusion.",
"AuthorList": {
"Author": {
"LastName": [
"Fadul",
"Zulueta-Coarasa",
"Slattum",
"Redd",
"Jin",
"Redd",
"Daetwyler",
"Hedeen",
"Huisken",
"Rosenblatt"
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"ForeName": [
"John",
"Teresa",
"Gloria M",
"Nadja M",
"Mauricio Franco",
"Michael J",
"Stephan",
"Danielle",
"Jan",
"Jody"
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"1078-2015",
"R01GM102169",
"55108560",
"CA042014"
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"European Molecular Biology Organization (EMBO)",
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"AbstractText": "Carbon nanodots with opposite chirality possess the same major physicochemical properties such as optical features, hydrodynamic diameter, and colloidal stability. Here, a detailed analysis about the comparison of the concentration of both carbon nanodots is carried out, putting a threshold to when differences in biological behavior may be related to chirality and may exclude effects based merely on differences in exposure concentrations due to uncertainties in concentration determination. The present study approaches this comparative analysis evaluating two basic biological phenomena, the protein adsorption and cell internalization. We find how a meticulous concentration error estimation enables the evaluation of the differences in biological effects related to chirality."
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"EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)",
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"AbstractText": "Understanding the genetic basis of climatic adaptation is essential for predicting species' responses to climate change. However, intraspecific variation of these responses arising from local adaptation remains ambiguous for most species. Here, we analyze genomic data from diamondback moth (Plutella xylostella) collected from 75 sites spanning six continents to reveal that climate-associated adaptive variation exhibits a roughly latitudinal pattern. By developing an eco-genetic index that combines genetic variation and physiological responses, we predict that most P. xylostella populations have high tolerance to projected future climates. Using genome editing, a key gene, PxCad, emerged from our analysis as functionally temperature responsive. Our results demonstrate that P. xylostella is largely capable of tolerating future climates in most of the world and will remain a global pest beyond 2050. This work improves our understanding of adaptive variation along environmental gradients, and advances pest forecasting by highlighting the genetic basis for local climate adaptation."
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"Jacques",
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"National Natural Science Foundation of China (National Science Foundation of China)",
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"AbstractText": "Prior research indicates that lower resting-state functional coupling between two brain networks, lateral frontoparietal network (LFPN) and default mode network (DMN), relates to cognitive test performance, for children and adults. However, most of the research that led to this conclusion has been conducted with non-representative samples of individuals from higher-income backgrounds, and so further studies including participants from a broader range of socioeconomic backgrounds are required. Here, in a pre-registered study, we analyzed resting-state fMRI from 6839 children ages 9-10 years from the ABCD dataset. For children from households defined as being above poverty (family of 4 with income > $25,000, or family of 5+ with income > $35,000), we replicated prior findings; that is, we found that better performance on cognitive tests correlated with weaker LFPN-DMN coupling. For children from households defined as being in poverty, the direction of association was reversed, on average: better performance was instead directionally related to stronger LFPN-DMN connectivity, though there was considerable variability. Among children in households below poverty, the direction of this association was predicted in part by features of their environments, such as school type and parent-reported neighborhood safety. These results highlight the importance of including representative samples in studies of child cognitive development."
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"AbstractText": "Potassium (K) metal is a promising alkali metal anode for its high abundance. However, dendrite on K anode is a serious problem which is even worse than Li. Artificial SEI (ASEI) is one of effective routes for suppressing dendrite. However, there are still some issues of the ASEI made by the traditional methods, e.g. weak adhesion, insufficient/uneven reaction, which deeply affects the ionic diffusion kinetics and the effect of inhibiting dendrites. Herein, through a unique self-catalysis tribo-electrochemistry reaction, a continuous and compact protective layer is successfully constructed on K metal anode in seconds. Such a continuous and compact protective layer can not only improve the K<sup>+</sup> diffusion kinetics, but also strongly suppress K dendrite formation by its hard mechanical properties derived from rigid carbon system, as well as the improved K<sup>+</sup> conductivity and lowered electronic conductivity from the amorphous KF. As a result, the potassium symmetric cells exhibit stable cycles last more than 1000 h, which is almost 500 times that of pristine K."
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"ArticleTitle": "Tribo-electrochemistry induced artificial solid electrolyte interface by self-catalysis.",
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"Liu",
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"Xie",
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"21805079"
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"National Natural Science Foundation of China (National Science Foundation of China)",
"National Natural Science Foundation of China (National Science Foundation of China)"
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"AbstractText": "Sustained ryanodine receptor (RyR) Ca<sup>2+</sup> leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca<sup>2+</sup> content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca<sup>2+</sup> uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca<sup>2+</sup> leak or preventing mitochondrial Ca<sup>2+</sup> uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca<sup>2+</sup> leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise."
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"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)",
"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)",
"Université de Lausanne (University of Lausanne)",
"Universidade de Brasília (University of Brasília)",
"Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)",
"Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)",
"Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)",
"Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)",
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"AbstractText": "The rational design of high-temperature endurable Cu-based catalysts is a long-sought goal since they are suffering from significant sintering. Establishing a barrier on the metal surface by the classical strong metal-support interaction (SMSI) is supposed to be an efficient way for immobilizing nanoparticles. However, Cu particles were regarded as impossible to form classical SMSI before irreversible sintering. Herein, we fabricate the SMSI between sputtering reconstructed Cu and flame-made LaTiO<sub>2</sub> support at a mild reduction temperature, exhibiting an ultra-stable performance for more than 500 h at 600 °C. The sintering of Cu nanoparticles is effectively suppressed even at as high as 800 °C. The critical factors to success are reconstructing the electronic structure of Cu atoms in parallel with enhancing the support reducibility, which makes them adjustable by sputtering power or decorated supports. This strategy will extremely broaden the applications of Cu-based catalysts at more severe conditions and shed light on establishing SMSI on other metals."
},
"ArticleTitle": "Ultra-high thermal stability of sputtering reconstructed Cu-based catalysts.",
"AuthorList": {
"Author": {
"LastName": [
"Yu",
"Sun",
"Tong",
"Zhang",
"Li",
"Li",
"Liu",
"Tsubaki",
"Abe",
"Sun"
],
"ForeName": [
"Jiafeng",
"Xingtao",
"Xin",
"Jixin",
"Jie",
"Shiyan",
"Yuefeng",
"Noritatsu",
"Takayuki",
"Jian"
],
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"X",
"X",
"J",
"J",
"S",
"Y",
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"Language": "eng",
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"Grant": {
"GrantID": [
"22078315"
],
"Agency": [
"National Natural Science Foundation of China (National Science Foundation of China)"
],
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""
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}
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"Abstract": {
"AbstractText": "The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution. Liquid sulphur dioxide proves to be a superior alternative for copper-catalyzed peptide condensations. Compared to water, amino acids are activated in sulphur dioxide, leading to the incorporation of all 20 proteinogenic amino acids into proteins. Strikingly, even extremely low initial reactant concentrations of only 50 mM are sufficient for extensive peptide formation, yielding up to 2.9% of dialanine in 7 days. The reactions carried out at room temperature and the successful use of the Hadean mineral covellite (CuS) as a catalyst, suggest a volcanic environment for the formation of the peptide world on early Earth."
},
"ArticleTitle": "From amino acid mixtures to peptides in liquid sulphur dioxide on early Earth.",
"AuthorList": {
"Author": {
"LastName": [
"Sauer",
"Haas",
"Sydow",
"Siegle",
"Lauer",
"Trapp"
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"ForeName": [
"Fabian",
"Maren",
"Constanze",
"Alexander F",
"Christoph A",
"Oliver"
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"M",
"C",
"AF",
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"O"
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"Initiating Molecular Life",
"TRR 235, Emergence of Life"
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"Volkswagen Foundation (VolkswagenStiftung)",
"Deutsche Forschungsgemeinschaft (German Research Foundation)"
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"Abstract": {
"AbstractText": "Molecules with a nitrogen-nitrogen (N-N) bond in their structures exhibit various biological activities and other unique properties. A few microbial proteins are recently emerging as dedicated N-N bond forming enzymes in natural product biosynthesis. However, the details of these biochemical processes remain largely unknown. Here, through in vitro biochemical characterization and computational studies, we report the molecular basis of hydrazine bond formation by a family of di-domain enzymes. These enzymes are widespread in bacteria and sometimes naturally exist as two standalone enzymes. We reveal that the methionyl-tRNA synthase-like domain/protein catalyzes ATP-dependent condensation of two amino acids substrates to form a highly unstable ester intermediate, which is subsequently captured by the zinc-binding cupin domain/protein and undergoes redox-neutral intramolecular rearrangement to give the N-N bond containing product. These results provide important mechanistic insights into enzymatic N-N bond formation and should facilitate future development of novel N-N forming biocatalyst."
},
"ArticleTitle": "Molecular basis of enzymatic nitrogen-nitrogen formation by a family of zinc-binding cupin enzymes.",
"AuthorList": {
"Author": {
"LastName": [
"Zhao",
"Peng",
"Song",
"Shi",
"Lu",
"Wang",
"Du"
],
"ForeName": [
"Guiyun",
"Wei",
"Kaihui",
"Jingkun",
"Xingyu",
"Binju",
"Yi-Ling"
],
"Initials": [
"G",
"W",
"K",
"J",
"X",
"B",
"YL"
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"Language": "eng",
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"31872625",
"LR19C010001"
],
"Agency": [
"National Natural Science Foundation of China (National Science Foundation of China)",
"Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)"
],
"Country": [
"",
""
]
}
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"Article": {
"Abstract": {
"AbstractText": "Candida auris is an emerging healthcare-associated pathogen of global concern. Recent reports have identified C. auris isolates that grow in cellular aggregates or filaments, often without a clear genetic explanation. To investigate the regulation of C. auris morphogenesis, we applied an Agrobacterium-mediated transformation system to all four C. auris clades. We identified aggregating mutants associated with disruption of chitin regulation, while disruption of ELM1 produced a polarized, filamentous growth morphology. We developed a transiently expressed Cas9 and sgRNA system for C. auris that significantly increased targeted transformation efficiency across the four C. auris clades. Using this system, we confirmed the roles of C. auris morphogenesis regulators. Morphogenic mutants showed dysregulated chitinase expression, attenuated virulence, and altered antifungal susceptibility. Our findings provide insights into the genetic regulation of aggregating and filamentous morphogenesis in C. auris. Furthermore, the genetic tools described here will allow for efficient manipulation of the C. auris genome."
},
"ArticleTitle": "Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains.",
"AuthorList": {
"Author": {
"LastName": [
"Santana",
"O'Meara"
],
"ForeName": [
"Darian J",
"Teresa R"
],
"Initials": [
"DJ",
"TR"
],
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]
}
},
"Language": "eng",
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"U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)"
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"Year": 2021,
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"Article": {
"Abstract": {
"AbstractText": "Electric field-induced changes in the electrical resistance of a material are considered essential and enabling processes for future efficient large-scale computations. However, the underlying physical mechanisms of electroresistance are currently remain largely unknown. Herein, an electrically reversible resistance change has been observed in the thermoelectric α-Cu<sub>2</sub>Se. The spontaneous electric dipoles formed by Cu<sup>+</sup> ions displaced from their positions at the centers of Se-tetrahedrons in the ordered α-Cu<sub>2</sub>Se phase are examined, and α-Cu<sub>2</sub>Se phase is identified to be a multipolar antiferroelectric semiconductor. When exposed to the applied voltage, a reversible switching of crystalline domains aligned parallel to the polar axis results in an observed reversible resistance change. The study expands on opportunities for semiconductors with localized polar symmetry as the hardware basis for future computational architectures."
},
"ArticleTitle": "Electroresistance in multipolar antiferroelectric Cu<sub>2</sub>Se semiconductor.",
"AuthorList": {
"Author": {
"LastName": [
"Bai",
"Wu",
"Su",
"Peng",
"Li",
"Yang",
"Zhang",
"Uher",
"Tang"
],
"ForeName": [
"Hui",
"Jinsong",
"Xianli",
"Haoyang",
"Zhi",
"Dongwang",
"Qingjie",
"Ctirad",
"Xinfeng"
],
"Initials": [
"H",
"J",
"X",
"H",
"Z",
"D",
"Q",
"C",
"X"
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"52072282"
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"Agency": [
"National Natural Science Foundation of China (National Science Foundation of China)"
],
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""
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}
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"PMID": 34893624,
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"DateRevised": {
"Year": 2021,
"Month": 12,
"Day": 11
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"Article": {
"Abstract": {
"AbstractText": "To improve understanding of Alzheimer's disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p < 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-β in MCI APOE-ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses."
},
"ArticleTitle": "Using imputation to provide harmonized longitudinal measures of cognition across AIBL and ADNI.",
"AuthorList": {
"Author": {
"LastName": [
"Shishegar",
"Cox",
"Rolls",
"Bourgeat",
"Doré",
"Lamb",
"Robertson",
"Laws",
"Porter",
"Fripp",
"Tosun",
"Maruff",
"Savage",
"Rowe",
"Masters",
"Weiner",
"Villemagne",
"Burnham"
],
"ForeName": [
"Rosita",
"Timothy",
"David",
"Pierrick",
"Vincent",
"Fiona",
"Joanne",
"Simon M",
"Tenielle",
"Jurgen",
"Duygu",
"Paul",
"Greg",
"Christopher C",
"Colin L",
"Michael W",
"Victor L",
"Samantha C"
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"D",
"P",
"V",
"F",
"J",
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"T",
"J",
"D",
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"G",
"CC",
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"GNT1191535"
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"Agency": [
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"Commonwealth Scientific and Industrial Research Organisation"
],
"Country": [
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"PMID": 34893625,
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"Month": 12,
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"Article": {
"Abstract": {
"AbstractText": "Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap<sup>+</sup> cells and Fsp1<sup>+</sup> cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap<sup>+</sup> cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1<sup>+</sup> cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta."
},
"ArticleTitle": "Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta.",
"AuthorList": {
"Author": {
"LastName": [
"Chen",
"Yang",
"Lovisa",
"Ambrose",
"McAndrews",
"Sugimoto",
"Kalluri"
],
"ForeName": [
"Yang",
"Sujuan",
"Sara",
"Catherine G",
"Kathleen M",
"Hikaru",
"Raghu"
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"S",
"CG",
"KM",
"H",
"R"
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"Agency": [
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{
"PMID": 34893627,
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"Article": {
"Abstract": {
"AbstractText": "The pedestrian-induced instability of the London Millennium Bridge is a widely used example of Kuramoto synchronisation. Yet, reviewing observational, experimental, and modelling evidence, we argue that increased coherence of pedestrians' foot placement is a consequence of, not a cause of the instability. Instead, uncorrelated pedestrians produce positive feedback, through negative damping on average, that can initiate significant lateral bridge vibration over a wide range of natural frequencies. We present a simple general formula that quantifies this effect, and illustrate it through simulation of three mathematical models, including one with strong propensity for synchronisation. Despite subtle effects of gait strategies in determining precise instability thresholds, our results show that average negative damping is always the trigger. More broadly, we describe an alternative to Kuramoto theory for emergence of coherent oscillations in nature; collective contributions from incoherent agents need not cancel, but can provide positive feedback on average, leading to global limit-cycle motion."
},
"ArticleTitle": "Emergence of the London Millennium Bridge instability without synchronisation.",
"AuthorList": {
"Author": {
"LastName": [
"Belykh",
"Bocian",
"Champneys",
"Daley",
"Jeter",
"Macdonald",
"McRobie"
],
"ForeName": [
"Igor",
"Mateusz",
"Alan R",
"Kevin",
"Russell",
"John H G",
"Allan"
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"I",
"M",
"AR",
"K",
"R",
"JHG",
"A"
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"0729-2020-0036"
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"Agency": [
"National Science Foundation (NSF)",
"Ministry of Education and Science of the Russian Federation (Minobrnauka)"
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"AbstractText": "While aldehydes represent a classic class of electrophilic synthons, the corresponding acyl radicals are inherently nucleophilic, which exhibits umpolung reactivity. Generation of acyl radicals typically requires noble metal catalysts or excess oxidants to be added. Herein, we report a convenient and green approach to access acyl radicals, capitalizing on neutral eosin Y-enabled hydrogen atom transfer (HAT) photocatalysis with aldehydes. The generated acyl radicals underwent SOMOphilic substitutions with various functionalized sulfones (X-SO<sub>2</sub>R') to deliver value-added acyl products. The merger of eosin Y photocatalysis and sulfone-based SOMOphiles provides a versatile platform for a wide array of aldehydic C-H functionalizations, including fluoromethylthiolation, arylthiolation, alkynylation, alkenylation and azidation. The present protocol features green characteristics, such as being free of metals, harmful oxidants and additives; step-economic; redox-neutral; and amenable to scale-up assisted by continuous-flow technology."
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"ArticleTitle": "Divergent functionalization of aldehydes photocatalyzed by neutral eosin Y with sulfone reagents.",
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"AbstractText": "Natural environments are recognized as complex heterogeneous structures thus requiring numerous multi-scale observations to yield a comprehensive description. To monitor the current state and identify negative impacts of human activity, fast and precise instruments are in urgent need. This work provides an automated approach to the assessment of spatial variability of water quality using guideline values on the example of 1526 water samples comprising 21 parameters at 448 unique locations across the New Moscow region (Russia). We apply multi-task Gaussian process regression (GPR) to model the measured water properties across the territory, considering not only the spatial but inter-parameter correlations. GPR is enhanced with a Spectral Mixture Kernel to facilitate a hyper-parameter selection and optimization. We use a 5-fold cross-validation scheme along with [Formula: see text]-score to validate the results and select the best model for simultaneous prediction of water properties across the area. Finally, we develop a novel Probabilistic Substance Quality Index (PSQI) that combines probabilistic model predictions with the regulatory standards on the example of the epidemiological rules and hygienic regulations established in Russia. Moreover, we provide an interactive map of experimental results at 100 m<sup>2</sup> resolution. The proposed approach contributes significantly to the development of flexible tools in environment quality monitoring, being scalable to different standard systems, number of observation points, and region of interest. It has a strong potential for adaption to environmental and policy changes and non-unified assessment conditions, and may be integrated into support-decision systems for the rapid estimation of water quality spatial distribution."
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