1,761,104 research outputs found
Synthesis and Structure–Activity Studies of β‑Barrel Assembly Machine Complex Inhibitor MRL-494
No full textIn the hunt for new
antibiotics with activity against Gram-negative
pathogens, the outer membrane β-barrel assembly machine (BAM)
complex has become an increasingly interesting target. The recently
reported BAM complex inhibitor, MRL-494, was discovered via a screening
campaign for molecules that target the outer membrane. Notably, MRL-494
was reported to be an unintended byproduct generated during the synthesis
of an unrelated compound, and as such no synthesis of the compound
was disclosed. We here present a convenient and reliable route for
the synthesis of MRL-494 that scales well. The antibacterial activity
measured for synthesized MRL-494 matches that reported in the literature.
Furthermore, MRL-494 was found to exhibit potent synergistic activity
with rifampicin against Gram-negative bacteria, including E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. MRL-494 was also found to cause
outer membrane disruption and induction of the Rcs stress response
pathway. In addition, we undertook a focused structure–activity
study specifically aimed at elucidating the roles played by the two
guanidine moieties contained within the structure of MRL-494
Participant 494 Community Conversations Interview
No full textIn this interview, Participant 494 shares their perspective on the COVID-19 pandemic, and says that it brought a bit of peace into their life. The participant describes that it feels good to take a break from the hustle and bustle of everyday life. The participant has been able to keep in touch with family members by using technology. They share that they wish there was more leadership from politicians during the pandemic.New Jersey Department of Healt
Image_2_Host MicroRNA hsa-miR-494-3p Promotes EV71 Replication by Directly Targeting PTEN.JPEG
No full textMany cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases.</p
Image_3_Host MicroRNA hsa-miR-494-3p Promotes EV71 Replication by Directly Targeting PTEN.JPEG
No full textMany cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases.</p
Image_1_Host MicroRNA hsa-miR-494-3p Promotes EV71 Replication by Directly Targeting PTEN.JPEG
No full textMany cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases.</p
Image_4_Host MicroRNA hsa-miR-494-3p Promotes EV71 Replication by Directly Targeting PTEN.JPEG
No full textMany cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases.</p
Additional file 1 of CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis
No full textAdditional file 1: Figure S1. (a) The relative expression of circVAPA, CircHIPK3 and 18S rRNA in SCLC cells were detected by RT-qPCR after RNase R treatment. CircHIPK3 was a positive control, while 18S rRNA was a negative control. (b-c) Quantification of circVAPA copy numbers in DMS273 and H82 cell lines. The red and blue dots indicate the Ct value and the amount of RNA in DMS273 and H82 SCLC cells, respectively. More experimental details are provided in the Methods section. (d) Prediction of the potential translation ability of circVAPA. An interaction model shows that circVAPA harbors potential internal ribosome entry site (IRES), but not open reading frame (ORF), which is analyzed by the circRNADb and ORFfinder databases. (All data are presented as the mean ± SD; ns, no significance; ***P 1 and p-value < 0.001 were selected. NC, negative control cells for overexpressing or suppressing miR-377-3p/miR-494-3p; miR-377 mimic/miR-494 mimic, transiently overexpressing miR-377-3p/miR-494-3p, respectively; miR-377 inhibitor/miR-494 inhibitor, transiently suppressing miR-377-3p/miR-494-3p, respectively. (All data are presented as the mean ± SD; **P < 0.01; ***P <0.001 by two-tailed Student’s t-test). Three independent assays were performed in the above assays. Figure S5. (a) RT-qPCR analysis of miR-377-3p/miR-494-3p expression in DMS273 cells transiently transfecting the indicated mimics. (b) RT-qPCR analysis of the effects of miR-377-3p/miR-494-3p on IGF1R in SCLC cells. (c-f) Quantification of miR-377-3p, miR-494-3p, and IGF1R copy numbers in DMS273 and H82 cell lines. The red and blue dots indicate the Ct value and the amount of RNA in DMS273 and H82 SCLC cells, respectively. More experimental details are provided in the Methods section. NC, negative control cells for overexpressing or suppressing miR-377-3p/miR-494-3p; miR-377 mimic/miR-494 mimic, transiently overexpressing miR-377-3p/miR-494-3p, respectively; miR-377 inhibitor/miR-494 inhibitor, transiently suppressing miR-377-3p/miR-494-3p, respectively. (All data are presented as the mean ± SD; ***P < 0.001 by two-tailed Student’s t-test). Three independent assays were performed in the above assays. Figure S6. (a) Cell viability analysis of the effect of circVAPA overexpression or IGF1R inhibitor (drug BMS-536924) on SCLC cells. (b) Western blot analysis of the effects of circVAPA depletion or IGF1R inhibitor (drug BMS-536924) addition on S6RP and p-S6RP protein expression in H82 cells. (c and d) Cell viability (c) and colony formation (d) analysis of the H82 cells with circVAPA knockdown or the control with or without IGF1R inhibitor. (e) RT-qPCR analysis of circVAPA and VAPA mRNA expression in stable DMS273 cells transfected with the lentivirus-shRNA. Vector was the negative control for knocking down circVAPA. (f) Immunohistochemistry analysis of ki67 in tumors. Scale bar, 50 μm. si-circVAPA, the co-transfection of two independent siRNAs target circVAPA; IGF1Ri, the addition of IGF1R inhibitor (drug BMS-536924). (All data are presented as the mean ± SD; ns, no significance; ***P < 0.001 by two-tailed Student’s t-test). Three independent assays were performed in the above assays
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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