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https://www.readbyqxmd.com/read/29352139/mitochondrial-glutamine-metabolism-via-got2-supports-pancreatic-cancer-growth-through-senescence-inhibition
#1
Seungyeon Yang, Sunsook Hwang, Minjoong Kim, Sung Bin Seo, Jeong-Hwa Lee, Seung Min Jeong
Cellular senescence, which leads to a cell cycle arrest of damaged or dysfunctional cells, is an important mechanism to restrain the malignant progression of cancer cells. Because metabolic changes underlie many cell-fate decisions, it has been suggested that cell metabolism might play key roles in senescence pathways. Here, we show that mitochondrial glutamine metabolism regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells. Glutamine deprivation or inhibition of mitochondrial aspartate transaminase (GOT2) results in a profound induction of senescence and a suppression of PDAC growth...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348665/pcdhga9-acts-as-a-tumor-suppressor-to-induce-tumor-cell-apoptosis-and-autophagy-and-inhibit-the-emt-process-in-human-gastric-cancer
#2
Junyong Weng, Jingbo Xiao, Yushuai Mi, Xu Fang, Yahuang Sun, Shanbao Li, Zhiwei Qin, Xu Li, Tingting Liu, Senlin Zhao, Lisheng Zhou, Yugang Wen
The results of a cDNA  array revealed that protocadherin gamma subfamily A, 9 (PCDHGA9) was significantly decreased in SGC-7901 gastric cancer (GC) cells compared with GES-1 normal gastric cells and was strongly associated with the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. As a member of the cadherin family, PCDHGA9 functions in both cell-cell adhesion and nuclear signaling. However, its role in tumorigenicity or metastasis has not been reported. In the present study, we found that PCDHGA9 was decreased in GC tissues compared with corresponding normal mucosae and its expression was correlated with the GC TNM stage, the UICC stage, differentiation, relapse, and metastasis (p < 0...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#3
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348327/genome-instability-as-a-consequence-of-defects-in-the-resolution-of-recombination-intermediates
#4
Stephen C West, Ying Wai Chan
The efficient processing of homologous recombination (HR) intermediates, which often contain four-way structures known as Holliday junctions (HJs), is required for proper chromosome segregation at mitosis. Eukaryotic cells possess three distinct pathways of resolution: (i) HJ dissolution mediated by BLM-topoisomerase IIIα-RMI1-RMI2 (BTR) complex, and HJ resolution catalyzed by either (ii) SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex) or (iii) GEN1. The BTR pathway acts at all times throughout the cell cycle, whereas the actions of SMX and GEN1 are restrained in S phase and become elevated late in the cell cycle to ensure the resolution of persistent recombination intermediates before mitotic division...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29347155/laser-opacity-in-underdense-preplasma-of-solid-targets-due-to-quantum-electrodynamics-effects
#5
W-M Wang, P Gibbon, Z-M Sheng, Y-T Li, J Zhang
We investigate how next-generation laser pulses at 10-200PW interact with a solid target in the presence of a relativistically underdense preplasma produced by amplified spontaneous emission (ASE). Laser hole boring and relativistic transparency are strongly restrained due to the generation of electron-positron pairs and γ-ray photons via quantum electrodynamics (QED) processes. A pair plasma with a density above the initial preplasma density is formed, counteracting the electron-free channel produced by hole boring...
July 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346764/sgk1-governs-the-reciprocal-development-of-th17-and-regulatory-t-cells
#6
Chuan Wu, Zuojia Chen, Sheng Xiao, Theresa Thalhamer, Asaf Madi, Timothy Han, Vijay Kuchroo
A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346751/the-brain-compass-a-perspective-on-how-self-motion-updates-the-head-direction-cell-attractor
#7
REVIEW
Jean Laurens, Dora E Angelaki
Head direction cells form an internal compass signaling head azimuth orientation even without visual landmarks. This property is generated by a neuronal ring attractor that is updated using rotation velocity cues. The properties and origin of this velocity drive remain, however, unknown. We propose a quantitative framework whereby this drive represents a multisensory self-motion estimate computed through an internal model that uses sensory prediction errors of vestibular, visual, and somatosensory cues to improve on-line motor drive...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#8
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343646/role-of-boundary-conditions-in-determining-cell-alignment-in-response-to-stretch
#9
Kellen Chen, Andrea Vigliotti, Mattia Bacca, Robert M McMeeking, Vikram S Deshpande, Jeffrey W Holmes
The ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotransduction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29342483/-fitness-to-drive-after-stroke
#10
Peter Marx
In Germany, patient information and expert testimony on driving ability requires knowledge of the corresponding legislation and the Guideline for expertises on driver aptitude. The testimony should clearly identify handicaps with regard to driving, give estimates on the future risks of a sudden loss of control, and also consider personal attitudes such as inadequate behavior, lack of insight etc. Physical handicaps often can be compensated for by restrains or restrictions such as vehicle modifications, daylight driving only etc...
January 2018: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29340087/identification-of-antipsychotic-drug-fluspirilene-as-a-potential-anti-glioma-stem-cell-drug
#11
Yu Dong, Takuya Furuta, Hemragul Sabit, Tomohiro Kitabayashi, Shabierjiang Jiapaer, Masahiko Kobayashi, Yasushi Ino, Tomoki Todo, Lei Teng, Atsushi Hirao, Shi-Guang Zhao, Mitsutoshi Nakada
Glioma stem cell (GSC)-targeted therapy is expected to be one of the most innovative approaches to treat patients with glioblastoma (GBM). A number of the drugs that restrain the signaling pathway essential for GSC maintenance have been under clinical trials. Here, we identified fluspirilene, a traditional antipsychotic drug, as a GSC-targeting agent, selected from thousands of existing drugs, and investigated its therapeutic effects against GBM with the purpose of drug repositioning. To develop novel therapeutics targeting GSCs, we initially screened drug libraries for small-molecule compounds showing a greater efficacy, compared to that of controls, in inhibiting the proliferation and survival of different GSC lines using cell proliferation assay...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340060/assessment-of-antimicrobial-and-wound-healing-effects-of-brevinin-2ta-against-the-bacterium-klebsiella-pneumoniae-in-dermally-wounded-rats
#12
Siqin Liu, Qilin Long, Yang Xu, Jun Wang, Zhongwei Xu, Lei Wang, Mei Zhou, Yuxin Wu, Tianbao Chen, Chris Shaw
Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339572/three-dimensional-cross-linking-composite-of-graphene-carbon-nanotube-and-si-nanoparticles-for-lithium-ion-batteries-anode
#13
Suyun Tian, Guannan Zhu, Yanping Tang, Xiaohua Xie, Qian Wang, Yufei Ma, Gu Qiao Ding, Xiaoming Xie
Various graphene-based Si nanocomposites have been reported to improve the performance of active materials in Li ion battery. However, these candidates still yield severe capacity fading due to the electrical disconnection and fracture caused by huge volume changes with extended cycles.Therefore, we design a novel three-dimensional cross-linking structure of graphene and single-wall carbon nanotube to encapsulate Si nanoparticles. The synthesized three-dimensional structure is ascribed to the excellent self-assembly of carbon nanotube with graphene oxide and a thermal treatment process at 900 ºC...
January 17, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29335648/rapid-chromatin-repression-by-aire-provides-precise-control-of-immune-tolerance
#14
Andrew S Koh, Erik L Miller, Jason D Buenrostro, David M Moskowitz, Jing Wang, William J Greenleaf, Howard Y Chang, Gerald R Crabtree
Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance against self-reactive T lymphocytes. However, the mechanism that allows expression of tissue-specific genes at levels that prevent harm is unknown. Here we show that Brg1 generates accessibility at tissue-specific loci to impose central tolerance. We found that Aire has an intrinsic repressive function that restricts chromatin accessibility and opposes Brg1 across the genome. Aire exerted this repressive influence within minutes after recruitment to chromatin and restrained the amplitude of active transcription...
January 15, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29335647/aged-polymorphonuclear-leukocytes-cause-fibrotic-interstitial-lung-disease-in-the-absence-of-regulation-by-b-cells
#15
Jung Hwan Kim, John Podstawka, Yuefei Lou, Lu Li, Esther K S Lee, Maziar Divangahi, Björn Petri, Frank R Jirik, Margaret M Kelly, Bryan G Yipp
Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via β2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs...
January 15, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29335523/mir-139-5p-inhibits-aerobic-glycolysis-cell-proliferation-migration-and-invasion-in-hepatocellular-carcinoma-via-a-reciprocal-regulatory-interaction-with-ets1
#16
Shengni Hua, Ling Lei, Ling Deng, Xie Weng, Chengdong Liu, Xiaolong Qi, Shuang Wang, Dongyan Zhang, Xuejing Zou, Chuanhui Cao, Li Liu, Dehua Wu
Cancer cells have metabolic features that allow them to preferentially metabolize glucose through aerobic glycolysis, providing them with a progression advantage. However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has not been extensively investigated. We addressed this in the present study by examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model. We found that overexpressing miR-139-5p restrained aerobic glycolysis, suppressing proliferation, migration, and invasion in HCC cells...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29335415/usp48-restrains-resection-by-site-specific-cleavage-of-the-brca1-ubiquitin-mark-from-h2a
#17
Michael Uckelmann, Ruth M Densham, Roy Baas, Herrie H K Winterwerp, Alexander Fish, Titia K Sixma, Joanna R Morris
BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of the DNA damage response, priming chromatin for repair by homologous recombination. However, no specific deubiquitinating enzymes (DUBs) are known to antagonize this function. Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334459/development-of-charmm-compatible-force-field-parameters-for-cobalamin-and-related-cofactors-from-quantum-mechanical-calculations
#18
Anna Pavlova, Jerry M Parks, James C Gumbart
Corrinoid cofactors such as cobalamin are used by many enzymes and are essential for most living organisms. Therefore, there is broad interest in investigating cobalamin-protein interactions with molecular dynamics simulations. Previously developed parameters for cobalamins are based mainly on crystal structure data. Here, we report CHARMM-compatible force field parameters for several corrinoids developed from quantum mechanical calculations. We provide parameters for corrinoids in three oxidation states, Co3+, Co2+ and Co1+, and with various axial ligands...
January 15, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29333928/phosphorylation-of-stat3-promotes-vasculogenic-mimicry-by-inducing-epithelial-to-mesenchymal-transition-in-colorectal-cancer
#19
Cong Han, Baocun Sun, Xiulan Zhao, Yanhui Zhang, Qiang Gu, Fang Liu, Nan Zhao, Lili Wu
Vasculogenic mimicry refers to the process by which highly invasive cancer cells mimic endothelial cells by forming blood channels. Vasculogenic mimicry is important for the invasion and metastasis of tumor cells in colorectal cancer. STAT3 was initially identified as a mediator of the inflammation-associated acute phase response. The phosphorylation of Signal Transducers and Activators of Transcription 3 (p-STAT3) is closely related to tumor invasion and migration. We analyzed the relationship between p-STAT3 and vasculogenic mimicry formation in 65 human colorectal cancer samples, and the results showed that the expression of p-STAT3 is significantly correlated with vasculogenic mimicry, tumor metastasis, Tumor, Lymph Node and Metastasis Stage (TNM Stage), and poor prognosis...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29333658/in-situ-shrna-synthesis-on-dna-polylactide-nanoparticles-to-treat-multidrug-resistant-breast-cancer
#20
Qianqian Ni, Fuwu Zhang, Yunlei Zhang, Guizhi Zhu, Zhe Wang, Zhaogang Teng, Chunyan Wang, Bryant C Yung, Gang Niu, Guangming Lu, Longjiang Zhang, Xiaoyuan Chen
Nanomedicine has shown unprecedented potential for cancer theranostics. Nucleic acid (e.g., DNA and RNA) nanomedicines are of particular interest for combination therapy with chemotherapeutics. However, current nanotechnologies to construct such nucleic acid nanomedicines, which rely on chemical conjugation or physical complexation of nucleic acids with chemotherapeutics, have restrained their clinical translation due to limitations such as low drug loading efficiency and poor biostability. Herein, in situ rolling circle transcription (RCT) is applied to synthesize short hairpin RNA (shRNA) on amphiphilic DNA-polylactide (PLA) micelles...
January 15, 2018: Advanced Materials
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