| 1. |
- Zhou, Suhan, et al.
(author)
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ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function
- 2019
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In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:1, s. F134-F145
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Journal article (peer-reviewed)abstract
- Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Set(473) and eNOS at Ser(1177). Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis. and improving microvascular endothelial dysfunction. rhADAMIS13 could be a promising strategy to treat AKI in clinical settings.
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| 2. |
- Chen, Mei-Qin, et al.
(author)
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Arabidopsis NMD3 is required for nuclear export of 60S ribosomal subunits and affects secondary cell wall thickening
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4, s. 35904-35904
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Journal article (peer-reviewed)abstract
- NMD3 is required for nuclear export of the 60S ribosomal subunit in yeast and vertebrate cells, but no corresponding function of NMD3 has been reported in plants. Here we report that Arabidopsis thaliana NMD3 (AtNMD3) showed a similar function in the nuclear export of the 60S ribosomal subunit. Interference with AtNMD3 function by overexpressing a truncated dominant negative form of the protein lacking the nuclear export signal sequence caused retainment of the 60S ribosomal subunits in the nuclei. More interestingly, the transgenic Arabidopsis with dominant negative interference of AtNMD3 function showed a striking failure of secondary cell wall thickening, consistent with the altered expression of related genes and composition of cell wall components. Observation of a significant decrease of rough endoplasmic reticulum (RER) in the differentiating interfascicular fiber cells of the transgenic plant stems suggested a link between the defective nuclear export of 60S ribosomal subunits and the abnormal formation of the secondary cell wall. These findings not only clarified the evolutionary conservation of NMD3 functions in the nuclear export of 60S ribosomal subunits in yeast, animals and plants, but also revealed a new facet of the regulatory mechanism underlying secondary cell wall thickening in Arabidopsis. This new facet is that the nuclear export of 60S ribosomal subunits and the formation of RER may play regulatory roles in coordinating protein synthesis in cytoplasm and transcription in nuclei.
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| 3. |
- Eisenhofer, Graeme, et al.
(author)
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Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma
- 2011
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In: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 18:1, s. 97-111
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Journal article (peer-reviewed)abstract
- Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with PPGLs and 846 subjects without PPGLs examined how catecholamine metabolomic profiles are impacted by hereditary background and relate to variable hormone secretion. Catecholamine secretion was assessed in a subgroup of 156 patients from whom tumour tissue was available for measurements of catecholamine contents. Among all analytes, the free catecholamine O-methylated metabolites measured in plasma showed the largest tumour-related increases relative to the reference group. Patients with tumours due to multiple endocrine neoplasia type 2 and neurofibromatosis type 1 (NF1) showed similar catecholamine metabolite and secretory profiles to patients with adrenaline-producing tumours and no evident hereditary background. Tumours from these three patient groups contained higher contents of catecholamines, but secreted the hormones at lower rates than tumours that did not contain appreciable adrenaline, the latter including PPGLs due to von Hippel - Lindau (VHL) and succinate dehydrogenase (SDH) gene mutations. Large increases of plasma dopamine and its metabolites additionally characterised patients with PPGLs due to the latter mutations, whereas patients with NF1 were characterised by large increases in plasma dihydroxyphenylglycol and dihydroxyphenylacetic acid, the deaminated metabolites of noradrenaline and dopamine. This analysis establishes the utility of comprehensive catecholamine metabolite profiling for characterising the distinct and highly diverse catecholamine metabolomic and secretory phenotypes among different groups of patients with PPGLs. The data further suggest developmental origins of PPGLs from different populations of chromaffin cell progenitors. © 2011 Society for Endocrinology Printed in Great Britain.
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| 4. |
- Han, Zixuan, et al.
(author)
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Evaluating the large-scale hydrological cycle response within the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) ensemble
- 2021
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:6, s. 2537-2558
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Journal article (peer-reviewed)abstract
- The mid-Pliocene (∼3 Ma) is one of the most recent warm periods with high CO2 concentrations in the atmosphere and resulting high temperatures, and it is often cited as an analog for near-term future climate change. Here, we apply a moisture budget analysis to investigate the response of the large-scale hydrological cycle at low latitudes within a 13-model ensemble from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). The results show that increased atmospheric moisture content within the mid-Pliocene ensemble (due to the thermodynamic effect) results in wetter conditions over the deep tropics, i.e., the Pacific intertropical convergence zone (ITCZ) and the Maritime Continent, and drier conditions over the subtropics. Note that the dynamic effect plays a more important role than the thermodynamic effect in regional precipitation minus evaporation (PmE) changes (i.e., northward ITCZ shift and wetter northern Indian Ocean). The thermodynamic effect is offset to some extent by a dynamic effect involving a northward shift of the Hadley circulation that dries the deep tropics and moistens the subtropics in the Northern Hemisphere (i.e., the subtropical Pacific). From the perspective of Earth's energy budget, the enhanced southward cross-equatorial atmospheric transport (0.22 PW), induced by the hemispheric asymmetries of the atmospheric energy, favors an approximately 1∘ northward shift of the ITCZ. The shift of the ITCZ reorganizes atmospheric circulation, favoring a northward shift of the Hadley circulation. In addition, the Walker circulation consistently shifts westward within PlioMIP2 models, leading to wetter conditions over the northern Indian Ocean. The PlioMIP2 ensemble highlights that an imbalance of interhemispheric atmospheric energy during the mid-Pliocene could have led to changes in the dynamic effect, offsetting the thermodynamic effect and, hence, altering mid-Pliocene hydroclimate.
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| 5. |
- Kyrpides, Nikos C, et al.
(author)
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Genomic encyclopedia of bacteria and archaea: sequencing a myriad of type strains.
- 2014
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In: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 12:8
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Journal article (peer-reviewed)abstract
- Microbes hold the key to life. They hold the secrets to our past (as the descendants of the earliest forms of life) and the prospects for our future (as we mine their genes for solutions to some of the planet's most pressing problems, from global warming to antibiotic resistance). However, the piecemeal approach that has defined efforts to study microbial genetic diversity for over 20 years and in over 30,000 genome projects risks squandering that promise. These efforts have covered less than 20% of the diversity of the cultured archaeal and bacterial species, which represent just 15% of the overall known prokaryotic diversity. Here we call for the funding of a systematic effort to produce a comprehensive genomic catalog of all cultured Bacteria and Archaea by sequencing, where available, the type strain of each species with a validly published name (currently∼11,000). This effort will provide an unprecedented level of coverage of our planet's genetic diversity, allow for the large-scale discovery of novel genes and functions, and lead to an improved understanding of microbial evolution and function in the environment.
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| 6. |
- Lubong Sabado, Rachel, et al.
(author)
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Evidence of dysregulation of dendritic cells in primary HIV infection
- 2010
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In: BLOOD. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:19, s. 3839-3852
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Journal article (peer-reviewed)abstract
- Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV infection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation.
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| 7. |
- Moretti, Rocco, et al.
(author)
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Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
- 2013
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In: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987
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Journal article (peer-reviewed)abstract
- Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
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| 8. |
- Qin, Nan, et al.
(author)
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Effects of selective attention on the C1 ERP component : A systematic review and meta-analysis
- 2022
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In: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986. ; 59:12
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Research review (peer-reviewed)abstract
- The C1 event-related potential (ERP) captures the earliest stage of feedforward processing in the primary visual cortex (V1). An ongoing debate is whether top-down selective attention can modulate the C1. One side of the debate pointed out that null findings appear to outnumber positive findings; thus, selective attention does not seem to influence the C1. However, this suggestion is not based on a valid approach to summarizing evidence across studies. Therefore, we conducted a systematic review and meta-analysis investigating the effects of selective attention on the C1, involving 47 experiments and 794 subjects in total. Despite heterogeneity across studies, results suggested that attention has a moderate effect on the C1 (Cohen's $$ dz= 0.33, p < .0001); that is, C1 amplitude is larger for visual stimuli that are attended than unattended. These results suggest that C1 is affected by top-down selective attention.
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| 9. |
- Qin, Shuang-Jian, et al.
(author)
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Neurotoxicity of fine and ultrafine particulate matter : a comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework
- 2024
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 947
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Research review (peer-reviewed)abstract
- Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.
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| 10. |
- Zhang, Suping, et al.
(author)
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Osthole Ameliorates Renal Fibrosis in Mice by Suppressing Fibroblast Activation and Epithelial-Mesenchymal Transition
- 2018
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
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Journal article (peer-reviewed)abstract
- Renal fibrosis is a common pathway of virtually all progressive kidney diseases. Osthole (OST, 7-Methoxy-8-(3-methylbut-2-enyl)-2-chromenone), a derivative of coumarin mainly found in plants of the Apiaceae family, has shown inhibitory effects on inflammation, oxidative stress, fibrosis and tumor progression. The present study investigated whether OST mediates its effect via suppressing fibroblast activation and epithelial-mesenchymal transition (EMT) in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Herein, we found that OST inhibited fibroblast activation in a dose-dependent manner by inhibiting the transforming growth factor-beta 1 (TGF beta 1)-Smad pathway. OST also blocked fibroblast proliferation by reducing DNA synthesis and downregulating the expressions of proliferation- and cell cycle-related proteins including proliferating cell nuclear antigen (PCNA), CyclinD1 and p21 Waf1/Cip1. Meanwhile, in the murine model of renal interstitial fibrosis induced by UUO, myofibroblast activation with increased expression of alpha-smooth muscle actin (alpha-SMA) and proliferation were attenuated by OST treatment. Additionally, we provided in vivo evidence suggesting that OST repressed EMT with preserved E-cadherin and reduced Vimentin expression in obstructed kidney. UUO injury-induced upregulation of EMT-related transcription factors, Snail family transcriptional repressor-1(Snail 1) and Twist family basic helix-loop-helix (BHLH) transcription factor (Twist) as well as elevated G2/M arrest of tubular epithelial cell, were rescued by OST treatment. Further, OST treatment reversed aberrant expression of TGF beta 1-Smad signaling pathway, increased level of proinflammatory cytokines and NF-kappaB (NF-kappa B) activation in kidneys with obstructive nephropathy. Taken together, these findings suggest that OST hinder renal fibrosis in UUO mouse mainly through inhibition of fibroblast activation and EMT.
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| 11. |
- Zhang, Xin, et al.
(author)
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Enhancing the Photovoltaic Performance of Triplet Acceptors Enabled by Side-Chain Engineering
- 2021
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In: Solar RRL. - : WILEY-V C H VERLAG GMBH. - 2367-198X. ; 5:10
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Journal article (peer-reviewed)abstract
- Triplet excitons have both longer lifetimes and diffusion lengths than singlet excitons due to the nature of triplet excitons, which is expected to increase the photocurrent and further improve the performance of organic solar cells (OSCs). However, the working mechanism of triplet excitons in OSCs is not clearly clarified. Therefore, it is urgent to develop new triplet acceptors for in-depth understanding. Herein, a series of acceptors (BTn-4Cl) are synthesized by fine-tuning of the side-chain branch positions. The generation of triplet excitons of BTn-4Cl is confirmed by the time-resolved photoluminescence (TRPL) spectra, magnetophotocurrent (MPC) experiment, and electron paramagnetic resonance (EPR) spectra. The effects of side-chain engineering on the optoelectronic properties, packing behaviors, energy losses, charge transport properties, spin lifetimes of triplet polarons, and blend film morphologies are systematically studied. These results show that D18:BT3-4Cl-based OSCs possess the best power conversion efficiency (PCE) of 17.31% due to lower energy losses, less recombination losses, more balanced charge carrier mobilities, longer spin-lattice (T-1) relaxation time, and more favorable morphology. This work enhances the understanding of the structure-property relationship for high-performance triplet acceptors.
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