bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parameterizing Wave‐Driven Vertical Constituent Transport in the Upper Atmosphere
Authors: Gardner Chester S. , Guo Yafang , Liu Alan Z. 
Published: May 2019

AbstractDissipating waves contribute to vertical mixing of the atmosphere, alter molecular and eddy diffusion, and induce chemical transport of reactive species. These processes induce strong vertical transport of atmospheric constituents in regions where wave dissipation is significant. The effective wave diffusivity is proportional to the Stokes drift velocity imparted by the spectrum of vertically propagating waves, which is related to the vertical heat and wave energy fluxes. Because the heat flux cannot be derived from wave parameterization schemes employed in most atmospheric models, wave‐driven constituent transport has not been fully incorporated. However, we show in this paper that wave diffusivity can also be expressed in terms of the eddy diffusivity and variances of the temperature and lapse rate fluctuations, quantities that are readily derived from many wave parameterizations. The theory is in good agreement with lidar measurements of heat fluxes in the mesopause region. Total dynamical diffusivity associated with dissipating waves and turbulence can exceed 300 m2/s near the mesopause.
Estimating the time-varying generation rate of acetic acid from an all-purpose floor cleaner
Authors: Arnold Susan , Ramachandran Gurumurthy , Kaup Hannah , Servadio Joseph 
Published: May 2019

AbstractUnderstanding the relationship between consumer product use and risk of adverse health outcomes facilitates appropriate risk management and product stewardship. A preferred method for estimating the systemic and respiratory tract exposure and dose tailored to cleaning products use has been proposed, refining previously issued exposure guidance. Consistent with other exposure and risk-assessment frameworks, it is dependent upon high-quality exposure determinant data that also serve as model inputs. However, as publicly available exposure determinant data are scarce, the risk assessor is left with the option of estimating determinants such as the generation rate or employing empirical methods to estimate them. When the exposure scenario involves a chemical mixture, estimating the generation rate may not be feasible. We present an approach for estimating the time-varying generation rate of an aqueous acetic acid mixture representative of the base formulation for many consumer and DIY cleaning products that was previously assessed in a screening-level assessment. The approach involved measuring the evaporation rate for a reasonable worst-case scenario under controlled conditions. Knowing the mass applied, a time-varying generation rate was estimated. To evaluate its portability, a field study was conducted in a home where measurements were collected in an all-purpose room with the exterior door open (Room 1) and closed (Room 2), and a bathroom (Room 3) using a portable Fourier Transform Infrared (FTIR) spectrophotometer. Acetic acid concentrations were modeled using two common indoor air models, the Well Mixed Room model. Measured and modeled acetic acid concentrations were compared, with the WMR 95% confidence intervals encompassing measured concentrations for all three rooms, supporting the utility of the approach used and portability of the generation rate derived from it.
Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma
Authors: Lupino Lauren , Perry Tracey , Margielewska Sandra , Hollows Robert , Ibrahim Maha , Care Matthew , Allegood Jeremy , Tooze Reuben , Sabbadini Roger , Reynolds Gary , Bicknell Roy , Rudzki Zbigniew , Lin Hock Ye , Zanetto Ulises , Wei Wenbin , Simmons William , Spiegel Sarah , Woodman Ciaran B. J. , Rowe Martin , Vrzalikova Katerina , Murray Paul G. 
Published: May 2019

AbstractAlthough the over-expression of angiogenic factors is reported in diffuse large B-cell lymphoma (DLBCL), the poor response to anti-VEGF drugs observed in clinical trials suggests that angiogenesis in these tumours might be driven by VEGF-independent pathways. We show that sphingosine kinase-1 (SPHK1), which generates the potent bioactive sphingolipid sphingosine-1-phosphate (S1P), is over-expressed in DLBCL. A meta-analysis of over 2000 cases revealed that genes correlated with SPHK1 mRNA expression in DLBCL were significantly enriched for tumour angiogenesis meta-signature genes; an effect evident in both major cell of origin (COO) and stromal subtypes. Moreover, we found that S1P induces angiogenic signalling and a gene expression programme that is present within the tumour vasculature of SPHK1-expressing DLBCL. Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL.
Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer
Authors: Zhu Liyuan , Zhu Yiran , Han Shuting , Chen Miaoqin , Song Ping , Dai Dongjun , Xu Wenxia , Jiang Tingting , Feng Lifeng , Shin Vivian Y. , Wang Xian , Jin Hongchuan 
Published: May 2019

AbstractChemoresistance remains the uppermost disincentive for cancer treatment on account of many genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) are emerging players in promoting cancer initiation and progression. However, the regulation and function in chemoresistance are largely unknown. Herein, we identified ARHGAP5-AS1 as a lncRNA upregulated in chemoresistant gastric cancer cells and its knockdown reversed chemoresistance. Meanwhile, high ARHGAP5-AS1 expression was associated with poor prognosis of gastric cancer patients. Intriguingly, its abundance is affected by autophagy and SQSTM1 is responsible for transporting ARHGAP5-AS1 to autophagosomes. Inhibition of autophagy in chemoresistant cells, thus, resulted in the upregulation of ARHGAP5-AS1. In turn, it activated the transcription of ARHGAP5 in the nucleus by directly interacting with ARHGAP5 promoter. Interestingly, ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of ARHGAP5 mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. In summary, impaired autophagic degradation of lncRNA ARHGAP5-AS1 in chemoresistant cancer cells promoted chemoresistance. It can activate the transcription of ARHGAP5 in the nucleus and stimulate m6A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA in the cytoplasm by recruiting METTL3. Therefore, targeting ARHGAP5-AS1/ARHGAP5 axis might be a promising strategy to overcome chemoresistance in gastric cancer.
RETRACTED ARTICLE: FABP4 contributes to renal interstitial fibrosis via mediating inflammation and lipid metabolism
Authors: Qiao Yujie , Liu Liping , Yin Lianhong , Xu Lina , Tang Zeyao , Qi Yan , Mao Zhang , Zhao Yanyan , Ma Xiaodong , Peng Jinyong 
Published: May 2019

AbstractFatty acid binding protein 4 (FABP4), a subtype of fatty acid-binding protein family, shows critical roles in metabolism and inflammation. However, its roles on regulating renal interstitial fibrosis (RIF) remain unclear. In this work, LPS-stimulated in vitro models on NRK-52E and NRK-49F cells, and in vivo UUO models in rats and mice were established. The results showed that comparing with control groups or sham groups, the expression levels of α-SMA, COL1A, COL3A, IL-1β, IL-6, and TNF-α in LPS-stimulated cells or UUO animals were significantly increased. Meanwhile, the levels of TC, TG, and free fatty acid were also significantly increased as well as the obvious lipid droplets, and the serum levels of BUN, Cr were significantly increased with large amounts of collagen deposition in renal tissues. Further investigation showed that compared with control groups or sham groups, the expression levels of FABP4 in LPS-stimulated cells and UUO animals were significantly increased, resulting in down- regulating the expression levels of PPARγ, upregulating the levels of p65 and ICAM-1, and decreasing the expression levels of ACADM, ACADL, SCP-2, CPT1, EHHADH, and ACOX1. To deeply explore the mechanism of FABP4 in RIF, FABP4 siRNA and inhibitor interfered cell models, and UUO model on FABP4 knockout (KO) mice were used. The results showed that the expression levels of α-SMA, COL1A, and COL3A were significantly decreased, the deposition of lipid droplets decreased, and the contents of TC, TG, and free fatty acids were significantly decreased after gene silencing. Meanwhile, the expression levels of PPAR-γ, ACADM, ACADL, SCP-2, CPT1, EHHADH, and ACOX1 were upregulated, the levels of p65 and ICAM-1 were downregulated, and the mRNA levels of IL-1β, IL-6, and TNF-α were decreased. Our results supported that FABP4 contributed to RIF via promoting inflammation and lipid metabolism, which should be considered as one new drug target to treat RIF.
TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice
Authors: Wang Zhouqing , Zhou Li , An Dong , Xu Weixing , Wu Chunfeng , Sha Sha , Li Yingchun , Zhu Yichao , Chen Aidong , Du Yimei , Chen Lei , Chen Ling 
Published: May 2019

AbstractActivation of transient receptor potential vanilloid 4 (TRPV4) induces neuronal injury. TRPV4 activation enhances inflammatory response and promotes the proinflammatory cytokine release in various types of tissue and cells. Hyperneuroinflammation contributes to neuronal damage in epilepsy. Herein, we examined the contribution of neuroinflammation to TRPV4-induced neurotoxicity and its involvement in the inflammation and neuronal damage in pilocarpine model of temporal lobe epilepsy in mice. Icv. injection of TRPV4 agonist GSK1016790A (GSK1016790A-injected mice) increased ionized calcium binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) protein levels and Iba-1-positive (Iba-1+) and GFAP-positive (GFAP+) cells in hippocampi, which indicated TRPV4-induced microglial cell and astrocyte activation. The protein levels of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome components NLRP3, apoptosis-related spotted protein (ASC) and cysteinyl aspartate-specific protease-1 (caspase-1) were increased in GSK1016790A-injected mice, which indicated NLRP3 inflammasome activation. GSK1016790A also increased proinflammatory cytokine IL-1β, TNF-α and IL-6 protein levels, which were blocked by caspase-1 inhibitor Ac-YVAD-cmk. GSK1016790A-induced neuronal death was attenuated by Ac-YVAD-cmk. Icv. injection of TRPV4-specific antagonist HC-067047 markedly increased the number of surviving cells 3 d post status epilepticus in pilocarpine model of temporal lobe epilepsy in mice (pilocarpine-induced status epilepticus, PISE). HC-067047 also markedly blocked the increase in Iba-1 and GFAP protein levels, as well as Iba-1+ and GFAP+ cells 3 d post-PISE. Finally, the increased protein levels of NLRP3, ASC and caspase-1 as well as IL-1β, TNF-α and IL-6 were markedly blocked by HC-067047. We conclude that TRPV4-induced neuronal death is mediated at least partially by enhancing the neuroinflammatory response, and this action is involved in neuronal injury following status epilepticus.
Cyclin-dependent kinase 1-mediated phosphorylation of SET at serine 7 is essential for its oncogenic activity
Authors: Yin Ling , Zeng Yongji , Xiao Yi , Chen Yuanhong , Shen Hong , Dong Jixin 
Published: May 2019

AbstractSE translocation (SET), an inhibitor of protein phosphatase 2A (PP2A), plays important roles in mitosis and possesses oncogenic activity in several types of cancer. However, little is known regarding its regulation. Here we reveal a novel phosphorylation site of SET isoform 1, and we have determined its biological significance in tumorigenesis. We found that the mitotic kinase cyclin-dependent kinase 1 (CDK1) phosphorylates SET isoform 1 in vitro and in vivo at serine 7 during antitubulin drug-induced mitotic arrest and normal mitosis. SET deletion resulted in massive multipolar spindles, chromosome misalignment and missegregation, and centrosome amplification during mitosis. Moreover, mitotic phosphorylation of SET isoform 1 is required for cell migration, invasion, and anchorage-independent growth in vitro and tumorigenesis in xenograft animal models. We further documented that SET phosphorylation affects Akt activity. Collectively, our findings suggest that SET isoform 1 promotes oncogenesis in a mitotic phosphorylation-dependent manner.
Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage
Authors: Simonich Cassandra A. , Doepker Laura , Ralph Duncan , Williams James A. , Dhar Amrit , Yaffe Zak , Gentles Lauren , Small Christopher T. , Oliver Brian , Vigdorovich Vladimir , Mangala Prasad Vidya , Nduati Ruth , Sather D. Noah , Lee Kelly K. , Matsen IV Frederick A. , Overbaugh Julie 
Published: May 2019

AbstractHIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine targets. Here we reconstruct the developmental lineage of BF520.1, an infant-derived HIV-specific broadly neutralizing antibody (bnAb), using computational methods developed specifically for this purpose. We find that the BF520.1 inferred naive precursor binds HIV Env. We also show that heterologous cross-clade neutralizing activity evolved in the infant within six months of infection and that, ultimately, only 2% SHM is needed to achieve the full breadth of the mature antibody. Mutagenesis and structural analyses reveal that, for this infant bnAb, substitutions in the kappa chain were critical for activity, particularly in CDRL1. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses.
miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate
Authors: Ji Yun , Fioravanti Jessica , Zhu Wei , Wang Hongjun , Wu Tuoqi , Hu Jinhui , Lacey Neal E. , Gautam Sanjivan , Le Gall John B. , Yang Xia , Hocker James D. , Escobar Thelma M. , He Shan , Dell’Orso Stefania , Hawk Nga V. , Kapoor Veena , Telford William G. , Di Croce Luciano , Muljo Stefan A. , Zhang Yi , Sartorelli Vittorio , Gattinoni Luca 
Published: May 2019

AbstractT cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8+ T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. miR-155 enhances Polycomb repressor complex 2 (PRC2) activity indirectly by promoting the expression of the PRC2-associated factor Phf19 through downregulation of the Akt inhibitor, Ship1. Phf19 orchestrates a transcriptional program extensively shared with miR-155 to restrain T cell senescence and sustain CD8+ T cell antitumor responses. These effects rely on Phf19 histone-binding capacity, which is critical for the recruitment of PRC2 to the target chromatin. These findings establish the miR-155–Phf19–PRC2 as a pivotal axis regulating CD8+ T cell differentiation, thereby paving new ways for potentiating cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate.
Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration
Authors: Keller Laetitia , Pijnenburg Luc , Idoux-Gillet Ysia , Bornert Fabien , Benameur Laila , Tabrizian Maryam , Auvray Pierrick , Rosset Philippe , María Gonzalo-Daganzo Rosa , Gómez Barrena Enrique , Gentile Luca , Benkirane-Jessel Nadia 
Published: May 2019

AbstractThe extended life expectancy and the raise of accidental trauma call for an increase of osteoarticular surgical procedures. Arthroplasty, the main clinical option to treat osteoarticular lesions, has limitations and drawbacks. In this manuscript, we test the preclinical safety of the innovative implant ARTiCAR for the treatment of osteoarticular lesions. Thanks to the combination of two advanced therapy medicinal products, a polymeric nanofibrous bone wound dressing and bone marrow-derived mesenchymal stem cells, the ARTiCAR promotes both subchondral bone and cartilage regeneration. In this work, the ARTiCAR shows 1) the feasibility in treating osteochondral defects in a large animal model, 2) the possibility to monitor non-invasively the healing process and 3) the overall safety in two animal models under GLP preclinical standards. Our data indicate the preclinical safety of ARTiCAR according to the international regulatory guidelines; the ARTiCAR could therefore undergo phase I clinical trial.
Host diet and evolutionary history explain different aspects of gut microbiome diversity among vertebrate clades
Authors: Youngblut Nicholas D. , Reischer Georg H. , Walters William , Schuster Nathalie , Walzer Chris , Stalder Gabrielle , Ley Ruth E. , Farnleitner Andreas H. 
Published: May 2019

AbstractMultiple factors modulate microbial community assembly in the vertebrate gut, though studies disagree as to their relative contribution. One cause may be a reliance on captive animals, which can have very different gut microbiomes compared to their wild counterparts. To resolve this disagreement, we analyze a new, large, and highly diverse animal distal gut 16 S rRNA microbiome dataset, which comprises 80% wild animals and includes members of Mammalia, Aves, Reptilia, Amphibia, and Actinopterygii. We decouple the effects of host evolutionary history and diet on gut microbiome diversity and show that each factor modulates different aspects of diversity. Moreover, we resolve particular microbial taxa associated with host phylogeny or diet and show that Mammalia have a stronger signal of cophylogeny. Finally, we find that environmental filtering and microbe-microbe interactions differ among host clades. These findings provide a robust assessment of the processes driving microbial community assembly in the vertebrate intestine.
Evaluation of lipid oxidation mechanisms in beverages and cosmetics via analysis of lipid hydroperoxide isomers
Authors: Ito Junya , Komuro Marina , Parida Isabella Supardi , Shimizu Naoki , Kato Shunji , Meguro Yasuhiro , Ogura Yusuke , Kuwahara Shigefumi , Miyazawa Teruo , Nakagawa Kiyotaka 
Published: May 2019

AbstractUnderstanding of lipid oxidation mechanisms (e.g., auto-oxidation and photo-oxidation) in foods and cosmetics is deemed essential to maintain the quality of such products. In this study, the oxidation mechanisms in foods and cosmetics were evaluated through analysis of linoleic acid hydroperoxide (LAOOH) and linoleic acid ethyl ester hydroperoxide (ELAOOH) isomers. Based on our previous method for analysis of LAOOH isomers, in this study, we developed a new HPLC-MS/MS method that enables analysis of ELAOOH isomers. The HPLC-MS/MS methods to analyze LAOOH and ELOOH isomers were applied to food (liquor) and cosmetic (skin cream) samples. As a result, LAOOH and ELAOOH isomers specific to photo-oxidation, and ELAOOH isomers characteristic to auto-oxidation were detected in some marketed liquor samples, suggesting that lipid oxidation of marketed liquor proceeds by both photo- and auto-oxidation during the manufacturing process and/or sales. In contrast, because only LAOOH and ELAOOH isomers specific to auto-oxidation were detected in skin cream stored under dark at different temperatures (−5 °C–40 °C) for different periods (2–15 months), auto-oxidation was considered to be the major oxidation mechanism in such samples. Therefore, our HPLC-MS/MS methods appear to be powerful tools to elucidate lipid oxidation mechanisms in food and cosmetic products.
Contribution of frustules and mucilage trails to the mobility of diatom Navicula sp.
Authors: Chen Lei , Weng Ding , Du Chuan , Wang Jiadao , Cao Shan 
Published: May 2019

AbstractThe secreted mucilage trails of the diatom Navicula sp. in the process of motility were studied by scanning electron microscopy (SEM), transmission electron microscope (TEM), atomic force microscopy (AFM) and Raman spectra etc. Contrary to previous studies, force measurement was taken directly on the mucilage trails of live cells using the method of in situ force mapping by AFM. The retraction force curve presented an increased tip-substrate peak and a small saw-tooth pattern tip-mucilage peak. Especially, same measurements on various substrates with different surface energy revealed that the mucilage trails actually functioned as a medium increasing the adhesive force between the diatom and substrates, which is crucial to diatom’s adhesion and locomotion. In addition, the mechanical properties of mucilage trails were quite different from mucilage strands in the maximum adhesive force and the maximum polymer extension length. Raman spectra indicated the difference in compositions that both of the two kinds of mucilages had proteins and polysaccharide, but the mucilage strands contained some other components with C=O, —CH2— and —CH3 asymmetric and symmetric stretches. This research hammers out more precise information about mucilage trails which would be useful in terms of diatom motility and biofouling prevention.
Structural and free energy landscape of novel mutations in ribosomal protein S1 (rpsA) associated with pyrazinamide resistance
Authors: Khan Muhammad Tahir , Khan Abbas , Rehman Ashfaq Ur , Wang Yanjie , Akhtar Khalid , Malik Shaukat Iqbal , Wei Dong-Qing 
Published: May 2019

AbstractResistance to key first-line drugs is a major hurdle to achieve the global end tuberculosis (TB) targets. A prodrug, pyrazinamide (PZA) is the only drug, effective in latent TB, recommended in drug resistance and susceptible Mycobacterium tuberculosis (MTB) isolates. The prodrug conversion into active form, pyrazinoic acid (POA), required the activity of pncA gene encoded pyrazinamidase (PZase). Although pncA mutations have been commonly associated with PZA resistance but a small number of resistance cases have been associated with mutationss in RpsA protein. Here in this study a total of 69 PZA resistance isolates have been sequenced for pncA mutations. However, samples that were found PZA resistant but pncA wild type (pncAWT), have been sequenced for rpsA and panD genes mutation. We repeated a drug susceptibility testing according to the WHO guidelines on 18 pncAWT MTB isolates. The rpsA and panD genes were sequenced. Out of total 69 PZA resistant isolates, 51 harbored 36 mutations in pncA gene (GeneBank Accession No. MH46111) while, fifteen different mutations including seven novel, were detected in the fourth S1 domain of RpsA known as C-terminal (MtRpsACTD) end. We did not detect any mutations in panD gene. Among the rpsA mutations, we investigated the molecular mechanism of resistance behind mutations, D342N, D343N, A344P, and I351F, present in the MtRpsACTD through molecular dynamic simulations (MD). WT showed a good drug binding affinity as compared to mutants (MTs), D342N, D343N, A344P, and I351F. Binding pocket volume, stability, and fluctuations have been altered whereas the total energy, protein folding, and geometric shape analysis further explored a significant variation between WT and MTs. In conclusion, mutations in MtRpsACTD might be involved to alter the RpsA activity, resulting in drug resistance. Such molecular mechanism behind resistance may provide a better insight into the resistance mechanism to achieve the global TB control targets.