| 491. |
- Mukherjee, Sourav P., et al.
(författare)
-
Next-Generation Sequencing Reveals Differential Responses to Acute versus Long-Term Exposures to Graphene Oxide in Human Lung Cells
- 2020
-
Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 16:21
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have addressed the biological impact of graphene-based materials including graphene oxide (GO), yet few have focused on long-term effects. Here, RNA sequencing is utilized to unearth responses of human lung cells to GO. To this end, the BEAS-2B cell line derived from normal human bronchial epithelium is subjected to repeated, low-dose exposures of GO (1 or 5 mu g mL(-1)) for 28 days or to the equivalent, cumulative amount of GO for 48 h. Then, samples are analyzed by using the NovaSeq 6000 sequencing system followed by pathway analysis and gene ontology enrichment analysis of the differentially expressed genes. Significant differences are seen between the low-dose, long-term exposures and the high-dose, short-term exposures. Hence, exposure to GO for 48 h results in mitochondrial dysfunction. In contrast, exposure to GO for 28 days is characterized by engagement of apoptosis pathways with downregulation of genes belonging to the inhibitor of apoptosis protein (IAP) family. Validation experiments confirm that long-term exposure to GO affects the apoptosis threshold in lung cells, accompanied by a loss of IAPs. These studies reveal the sensitivity of RNA-sequencing approaches and show that acute exposure to GO is not a good predictor of the long-term effects of GO.
|
|
| 492. |
- Murray, Alison E., et al.
(författare)
-
Roadmap for naming uncultivated Archaea and Bacteria
- 2020
-
Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
-
Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
|
|
| 493. |
- Nadeem, Aftab, et al.
(författare)
-
Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA
- 2021
-
Ingår i: PLoS Pathogens. - : Public Library of Science. - 1553-7366 .- 1553-7374. ; 17:3
-
Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae is a noninvasive intestinal pathogen extensively studied as the causative agent of the human disease cholera. Our recent work identified MakA as a potent virulence factor of V. cholerae in both Caenorhabditis elegans and zebrafish, prompting us to investigate the potential contribution of MakA to pathogenesis also in mammalian hosts. In this study, we demonstrate that the MakA protein could induce autophagy and cytotoxicity of target cells. In addition, we observed that phosphatidic acid (PA)-mediated MakA-binding to the host cell plasma membranes promoted macropinocytosis resulting in the formation of an endomembrane-rich aggregate and vacuolation in intoxicated cells that lead to induction of autophagy and dysfunction of intracellular organelles. Moreover, we functionally characterized the molecular basis of the MakA interaction with PA and identified that the N-terminal domain of MakA is required for its binding to PA and thereby for cell toxicity. Furthermore, we observed that the ΔmakA mutant outcompeted the wild-type V. cholerae strain A1552 in the adult mouse infection model. Based on the findings revealing mechanistic insights into the dynamic process of MakA-induced autophagy and cytotoxicity we discuss the potential role played by the MakA protein during late stages of cholera infection as an anti-colonization factor.
|
|
| 494. |
- Nan, Jun-hu, et al.
(författare)
-
Air-core characteristics in a swirling tunnel flow
- 2022
-
Ingår i: Journal of Hydrodynamics. - : Springer Nature. - 1001-6058 .- 1000-4874 .- 1878-0342. ; 34:4, s. 634-646
-
Tidskriftsartikel (refereegranskat)abstract
- A cost-effective technique to dissipate the energy in hydropower systems is the formation of a swirling flow within a tunnel. In such flows, an air core with a significant cross section usually occurs. To reveal the air-core features in the horizontal tunnel of a high-head shaft spillway, laboratory tests, numerical modeling, and prototype observations are performed, to examine issues such as the formation of the air core, the interjacent air motion, the air-carrying capacity, and the scale effects. It is shown that the shape of the air core varies greatly in the axial and radial directions along the tunnel and that the center of the core deviates from the axis of the tunnel. The motion of the air within the core is caused by the combined action of the water entrainment on the inner surface of the swirling flow and the axial pressure difference in the air core. The aeration process can be divided into five processes with respect to the changes of the gate openings. A theoretical expression is established for the air-carrying capacity of the swirling flow. The vacuum degree is the similarity condition of the air-carrying capacity of the swirling flow between the model and prototype tests based on the Froude law of the similitude, and this similarity condition is verified by both the model and prototype results. This work provides a reference for the application of the swirling flows in horizontal hydropower tunnels.
|
|
| 495. |
- Nazli, Aisha, et al.
(författare)
-
Enterocyte cytoskeleton changes are crucial for enhanced translocation of nonpathogenic Escherichia coli across metabolically stressed gut epithelia
- 2006
-
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:1, s. 192-201
-
Tidskriftsartikel (refereegranskat)abstract
- Substantial data implicate the commensal flora as triggers for the initiation of enteric inflammation or inflammatory disease relapse. We have shown that enteric epithelia under metabolic stress respond to non-pathogenic bacteria by increases in epithelial paracellular permeability and bacterial translocation. Here we assessed the structural basis of these findings. Confluent filter-grown monolayers of the human colonic T84 epithelial cell line were treated with 0.1 mM dinitrophenol (which uncouples oxidative phosphorylation) and noninvasive, nonpathogenic Escherichia coli (strain HB101, 106 CFU) with or without pretreatment with various pharmacological agents. At 24 h later, apoptosis, tight-junction protein expression, transepithelial resistance (TER, a marker of paracellular permeability), and bacterial internalization and translocation were assessed. Treatment with stabilizers of microtubules (i.e., colchicine), microfilaments (i.e., jasplakinolide) and clathrin-coated pit endocytosis (i.e., phenylarsine oxide) all failed to block DNP+E. coli HB101-induced reductions in TER but effectively prevented bacterial internalization and translocation. Neither the TER defect nor the enhanced bacterial translocations were a consequence of increased apoptosis. These data show that epithelial paracellular and transcellular (i.e., bacterial internalization) permeation pathways are controlled by different mechanisms. Thus, epithelia under metabolic stress increase their endocytotic activity that can result in a microtubule-, microfilament-dependent internalization and transcytosis of bacteria. We speculate that similar events in vivo would allow excess unprocessed antigen and bacteria into the mucosa and could evoke an inflammatory response by, for example, the activation of resident or recruited immune cells. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
|
|
| 496. |
- Nedfors, Nils, et al.
(författare)
-
Characterization of magnetron sputtered Cr-B and Cr-B-C thin films for electrical contact applications
- 2015
-
Ingår i: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 266, s. 167-176
-
Tidskriftsartikel (refereegranskat)abstract
- We have deposited Cr-B and Cr-B-C thin films by co-sputtering from chromium boride and carbon targets. The binary Cr-B films consist of nanocrystalline and substoichiometric CrB2 - x grains (B/Cr atomic ratio <= 1.5) with a (101)-texture, where B segregates to the grain boundaries forming a B-rich tissue phase. A hardness of 25 GPa is measured for these films. They have a low wear resistance, attributed to a (101)-texture and limited adhesion. As a consequence, wear debris in the CrB2 - x wear track from delaminated film and steel-to-steel contact between the exposed substrate and the counter surface result in a high friction (0.52-0.78 against stainless steel) making the Cr-B films unsuitable as sliding electric contacts. Cr-B-C films, on the other hand, form a two phase amorphous structure at >17 at.% C consisting of an amorphous Cr-rich phase containing both B and C and an amorphous matrix phase containing mainly B and C. The addition of C improves the adhesion and tribological properties and a coefficient of friction of 0.12 is obtained at 38 at.% C. The improved tribological properties are explained by the formation of the matrix phase, which acts as a solid lubricant forming a graphite-like tribofilm during ball-on-disc test. However, the formation of an amorphous structure is not beneficial for the electrical contact resistance, which increases from 0.5 Omega for the Cr-B film to 1.5 and 2.3 Omega for the Cr-B-C films containing 17 and 26 at% C, respectively. Finally, the importance of a chemical analysis of the chromium boride sputtering target composition is discussed.
|
|
| 497. |
- Newell, Felicity, et al.
(författare)
-
Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
|
|
| 498. |
- Nguyen-Vu, Trang, et al.
(författare)
-
Estrogen receptor beta reduces colon cancer metastasis through a novel miR-205-PROX1 mechanism
- 2016
-
Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 7:27, s. 42159-42171
-
Tidskriftsartikel (refereegranskat)abstract
- Colon cancer is a common cause of cancer death in the Western world. Accumulating evidence supports a protective role of estrogen via estrogen receptor beta (ER beta) but the mechanism of action is not known. Here, we elucidate a molecular mechanism whereby ER beta represses the oncogenic prospero homebox 1 (PROX1) through the upregulation of miR-205. We show that PROX1 is a potential target of miR-205 and that in clinical specimens from The Cancer Genome Atlas data, ER beta and miR-205 are decreased in colorectal cancer tissue compared to non-tumorous colon, while PROX1 levels are increased. Through mechanistic studies in multiple colorectal cancer cell lines, we show that ER beta upregulates miR-205, and that miR-205 targets and represses PROX1 through direct interaction with its 3' UTR. Through the generation of intestine-specific ER beta knockout mice, we establish that this pathway is correspondingly regulated in normal intestinal epithelial cells in vivo. Functionally, we demonstrate that miR-205 decreases cell proliferation and decreases migratory and invasive potential of colon cancer cells, leading to a reduction of micrometastasis in vivo. In conclusion, ER beta in both normal and cancerous colon epithelial cells upregulates miRNA-205, which subsequently reduces PROX1 through direct interaction with its 3' UTR. This results in reduced proliferative and metastatic potential of the cells. Our study proposes a novel pathway that may be exploited using ER beta-selective agonists and/or miR-205-replacement therapy in order to improve preventive and therapeutic approaches against colon cancer.
|
|
| 499. |
- Nie, Huizhen, et al.
(författare)
-
The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
- 2021
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
-
Tidskriftsartikel (refereegranskat)abstract
- Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
|
|
| 500. |
- Nie, Li Ying, et al.
(författare)
-
High-Isolation Two-Port UWB Antenna Based on Shared Structure
- 2020
-
Ingår i: IEEE Transactions on Antennas and Propagation. - 0018-926X. ; 68:12, s. 8186-8191
-
Tidskriftsartikel (refereegranskat)abstract
- In this communication, a novel planar structure-shared diverse two-port ultrawideband (UWB) antenna with high isolation and common ground is proposed based on a new slot-loaded method. A tapered slot with an end-fire radiation pattern is etched in the top middle section of a coplanar waveguide (CPW)-fed printed monopole antenna to reduce its effects on the monopole mode. The two-port UWB antenna features diverse patterns which can fully cover the upper space. A nonuniformly symmetric-coupled coplanar waveguide (NSC-CPW) is introduced to enable the two sets of the feeding structures sharing a ground plane with minimum interaction. Due to the modal orthogonality, high isolation between the two ports is obtained without additional decoupling structures. The experimental results of the proposed multiple-input multiple-output (MIMO) antenna indicate that the isolation is higher than 31.4 dB and the diversity gain is approximately 10 dB within a wide frequency range from 2.98 to 10 GHz. Meanwhile, high realized peak gain (>2.5 dB) and good efficiency (>80%) are also obtained for both the ports.
|
|
