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https://www.readbyqxmd.com/read/28928749/foxo1-regulates-bacteria-induced-neutrophil-activity
#1
Guangyu Dong, Liang Song, Chen Tian, Yu Wang, Fang Miao, Jiabao Zheng, Chanyi Lu, Sarah Alsadun, Dana T Graves
Neutrophils play an essential role in the innate immune response to microbial infection and are particularly important in clearing bacterial infection. We investigated the role of the transcription factor FOXO1 in the response of neutrophils to bacterial challenge with Porphyromonas gingivalis in vivo and in vitro. In these experiments, the effect of lineage-specific FOXO1 deletion in LyzM.Cre(+)FOXO1(L/L) mice was compared with matched littermate controls. FOXO1 deletion negatively affected several critical aspects of neutrophil function in vivo including mobilization of neutrophils from the bone marrow (BM) to the vasculature, recruitment of neutrophils to sites of bacterial inoculation, and clearance of bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28925396/mig-6-negatively-regulates-stat3-phosphorylation-in-uterine-epithelial-cells
#2
J-Y Yoo, W S Yang, J H Lee, B G Kim, R R Broaddus, J M Lim, T H Kim, J-W Jeong
Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4-resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28916732/il-4-producing-b-cells-regulate-t-helper-cell-dichotomy-in-type-1-and-type-2-controlled-diseases
#3
Ramona Hurdayal, Hlumani H Ndlovu, Mélanie Revaz-Breton, Suraj P Parihar, Justin Komguep Nono, Melissa Govender, Frank Brombacher
Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major, while conferring immunity to the intestinal trematode Schistosoma mansoni Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (mb1(cre)IL-4Rα(-/lox)) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28878021/ck1%C3%AE-ablation-in-keratinocytes-induces-p53-dependent-sunburn-protective-skin-hyperpigmentation
#4
Chung-Hsing Chang, Che-Jung Kuo, Takamichi Ito, Yu-Ya Su, Si-Tse Jiang, Min-Hsi Chiu, Yi-Hsiung Lin, Andrea Nist, Marco Mernberger, Thorsten Stiewe, Shosuke Ito, Kazumasa Wakamatsu, Yi-An Hsueh, Sheau-Yann Shieh, Irit Snir-Alkalay, Yinon Ben-Neriah
Casein kinase 1α (CK1α), a component of the β-catenin destruction complex, is a critical regulator of Wnt signaling; its ablation induces both Wnt and p53 activation. To characterize the role of CK1α (encoded by Csnk1a1) in skin physiology, we crossed mice harboring floxed Csnk1a1 with mice expressing K14-Cre-ER(T2) to generate mice in which tamoxifen induces the deletion of Csnk1a1 exclusively in keratinocytes [single-knockout (SKO) mice]. As expected, CK1α loss was accompanied by β-catenin and p53 stabilization, with the preferential induction of p53 target genes, but phenotypically most striking was hyperpigmentation of the skin, importantly without tumorigenesis, for at least 9 mo after Csnk1a1 ablation...
September 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28870520/loss-of-nrf2-promotes-alveolar-type-2-cell-loss-in-irradiated-fibrotic-lung
#5
Geri Traver, Stacey Mont, David Gius, William E Lawson, George X Ding, Konjeti R Sekhar, Michael L Freeman
The development of radiation-induced pulmonary fibrosis represents a critical clinical issue limiting delivery of therapeutic doses of radiation to non-small cell lung cancer. Identification of the cell types whose injury initiates a fibrotic response and the underlying biological factors that govern that response are needed for developing strategies that prevent or mitigate fibrosis. C57BL/6 mice (wild type, Nrf2 null, Nrf2(flox/flox), and Nrf2(Δ/Δ); SPC-Cre) were administered a thoracic dose of 12Gy and allowed to recover for 250 days...
September 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28867552/connexin-43-mediated-astroglial-metabolic-networks-contribute-to-the-regulation-of-the-sleep-wake-cycle
#6
Jerome Clasadonte, Eliana Scemes, Zhongya Wang, Detlev Boison, Philip G Haydon
Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28861005/murine-myocardial-transcriptome-analysis-reveals-a-critical-role-of-cops8-in-the-gene-expression-of-cullin-ring-ligase-substrate-receptors-and-redox-and-vesicle-trafficking-pathways
#7
Ammara Abdullah, Kathleen M Eyster, Travis Bjordahl, Peng Xiao, Erliang Zeng, Xuejun Wang
Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases. Supported primarily by the decrease of substrate receptor (SR) proteins of CRLs in cells deficient of a CSN subunit, CSN-mediated cullin deneddylation is believed to prevent autoubiquitination and self-destruction of the SR in active CRLs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28855262/transposable-elements-are-the-primary-source-of-novelty-in-primate-gene-regulation
#8
Marco Trizzino, YoSon Park, Marcia Holsbach-Beltrame, Katherine Aracena, Katelyn Mika, Minal Caliskan, George H Perry, Vincent J Lynch, Christopher D Brown
Gene regulation shapes the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac and H3K4me1) to profile cis-regulatory elements (CREs) and using RNA-seq to characterize gene expression in the same individuals. To quantify regulatory divergence, we compared CRE activity across species by testing differential ChIP-seq read depths directly measured for orthologous sequences. We show that the primate regulatory landscape is largely conserved across the lineage, with 63% of the tested human liver CREs showing similar activity across species...
August 30, 2017: Genome Research
https://www.readbyqxmd.com/read/28841687/a-trp53fl-flptenfl-fl-mouse-model-of-undifferentiated-pleomorphic-sarcoma-mediated-by-adeno-cre-injection-and-in-vivo-bioluminescence-imaging
#9
Marisa R Buchakjian, Nicole M Merritt, Devon L Moose, Adam J Dupuy, Munir R Tanas, Michael D Henry
Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection...
2017: PloS One
https://www.readbyqxmd.com/read/28827130/activation-of-tlr4-stat3-signaling-in-vta-contributes-to-the-acquisition-and-maintenance-of-morphine-induced-conditioned-place-preference
#10
Jia-Xin Chen, Kang-Mei Huang, Meng Liu, Jin-Xiang Jiang, Jian-Peng Liu, Yu-Xiang Zhang, Chen Yang, Wen-Jun Xin, Xue-Qin Zhang
Morphine, commonly used to relieve the acute or chronic pain, has a high potential for addiction and exerts rewarding effects via a critical role for mesolimbic dopamine system. Studies suggest that addiction-related behavior is highly associated with inflammatory immune response, but the mechanisms are poorly understood. The present study showed that intra-VTA microinjection of TLR4 antagonist LPS-RS prevented the acquisition and maintenance, but not the expression, of morphine-induced CPP in rats. In addition, chronic morphine treatment significantly activated STAT3 on day 6 and 11 in VTA, and bilateral microinjection of STAT3 inhibitor S3I-201 into the VTA suppressed the acquisition and maintenance of morphine-induced CPP in rats...
August 18, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#11
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28816086/inducible-knockout-of-mouse-zfhx3-emphasizes-its-key-role-in-setting-the-pace-and-amplitude-of-the-adult-circadian-clock
#12
Ashleigh G Wilcox, Lucie Vizor, Michael J Parsons, Gareth Banks, Patrick M Nolan
The transcription factor zinc finger homeobox 3 (ZFHX3) plays a key role in coupling intracellular transcriptional-translational oscillations with intercellular synchrony in mouse suprachiasmatic nucleus (SCN). However, like many key players in central nervous system function, ZFHX3 serves an important role in neurulation and neuronal terminal differentiation while retaining discrete additional functions in the adult SCN. Recently, using a dominant missense mutation in mouse Zfhx3, we established that this gene can modify circadian period and sleep in adult animals...
August 1, 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28815492/building-cre-knockin-rat-lines-using-crispr-cas9
#13
Yuanwu Ma, Lianfeng Zhang, Xingxu Huang
Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815491/direct-generation-of-conditional-alleles-using-crispr-cas9-in-mouse-zygotes
#14
Colin E J Pritchard, Lona J Kroese, Ivo J Huijbers
Conditional alleles in genetically modified mice allow for the deletion of a gene of interest in a target tissue when combined with a tissue-specific Cre recombinase. A conditional allele is achieved by introducing LoxP sites around a critical exon, a gene, or a cluster of genes. Previously, conditional alleles were introduced in the mouse germline by classic gene targeting in embryonic stem cells, a challenging and time-consuming procedure. Now, conditional alleles can be generated directly in fertilized mouse eggs (zygotes) using the CRISPR/Cas9 technology...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807982/c-ebp%C3%AE-is-required-for-survival-of-ly6c-monocytes
#15
Akihiro Tamura, Hideyo Hirai, Asumi Yokota, Naoka Kamio, Atsushi Sato, Tsukimi Shoji, Takahiro Kashiwagi, Yusuke Torikoshi, Yasuo Miura, Daniel G Tenen, Taira Maekawa
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis. Further subdivision of monocytes revealed that Cebpb mRNA was highly upregulated in Ly6C(-) monocytes in bone marrow. Accordingly, Ly6C(-) monocytes were significantly reduced in Cebpb(-/-) mice. Bone marrow chimera experiments and Mx1-Cre-mediated deletion of Cebpb revealed the cell-intrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28794157/suppressor-of-fused-restraint-of-hedgehog-activity-level-is-critical-for-osteogenic-proliferation-and-differentiation-during-calvarial-bone-development
#16
Jianying Li, Ying Cui, Jie Xu, Qihui Wang, Xueqin Yang, Yan Li, Xiaoyun Zhang, Mengsheng Qiu, Ze Zhang, Zunyi Zhang
Hedgehog signaling plays crucial roles in the development of calvarial bone, relying on the activation of Gli transcription factors. However, the molecular mechanism of the role of regulated Gli protein level in osteogenic specification of mesenchyme still remains elusive. Here, we show by conditionally inactivating Suppressor of Fused (Sufu), a critical repressor of Hedgehog signaling, in Wnt1-Cre mediated cranial neural crest (CNC), or Dermo1-Cre mediated mesodermal lineages, that Sufu restraint of Hedgehog activity level is critical for differentiation of pre-osteogenic mesenchyme...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28793320/microsomal-triglyceride-transfer-protein-contributes-to-lipid-droplet-maturation-in-adipocytes
#17
Larry L Swift, Joseph D Love, Carla M Harris, Benny H Chang, W Gray Jerome
Previous studies in our laboratory have established the presence of MTP in both white and brown adipose tissue in mice as well as in 3T3-L1 cells. Additional studies demonstrated an increase in MTP levels as 3T3-L1 cells differentiate into adipocytes concurrent with the movement of MTP from the juxtanuclear region of the cell to the surface of lipid droplets. This suggested a role for MTP in lipid droplet biogenesis and/or maturation. To probe the role of MTP in adipocytes, we used a Cre-Lox approach with aP2-Cre and Adipoq-Cre recombinase transgenic mice to knock down MTP expression in brown and white fat of mice...
2017: PloS One
https://www.readbyqxmd.com/read/28777492/gankyrin-induces-stat3-activation-in-tumour-microenvironment-and-sorafenib-resistance-in-hepatocellular-carcinoma
#18
Toshiharu Sakurai, Norihisa Yada, Satoru Hagiwara, Tadaaki Arizumi, Kosuke Minaga, Ken Kamata, Mamoru Takenaka, Yasunori Minami, Tomohiro Watanabe, Naoshi Nishida, Masatoshi Kudo
Most hepatocellular carcinomas (HCCs) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumourigenesis in the colon. Although the in vitro function of gankyrin is well known, its role in vivo remains to be elucidated. We investigated the effect of gankyrin in tumour microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrin(f/f) ) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrin(f/f) )...
August 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28770041/stromal-senp1-promotes-mouse-early-folliculogenesis-by-regulating-bmp4-expression
#19
Shu Tan, Boya Feng, Mingzhu Yin, Huanjiao Jenny Zhou, Ge Lou, Weidong Ji, Yonghao Li, Wang Min
BACKGROUND: Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. However, the mechanism by which stromal cells and derived factors regulate oocyte development remains unclear. RESULTS: We observed that SENP1, a small ubiquitin-related modifier (SUMO)-specific isopeptidase, was expressed in sm22α-positive stromal cells of mouse ovary. The sm22α-positive stromal cells tightly associated with follicle maturation...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28768723/lamtor1-is-critically-required-for-cd4-t-cell-proliferation-and-regulatory-t-cell-suppressive-function
#20
Takashi Hosokawa, Tetsuya Kimura, Shigeyuki Nada, Tatsusada Okuno, Daisuke Ito, Sujin Kang, Satoshi Nojima, Kazuya Yamashita, Takeshi Nakatani, Yoshitomo Hayama, Yasuhiro Kato, Yuhei Kinehara, Masayuki Nishide, Norihisa Mikami, Syohei Koyama, Hyota Takamatsu, Daisuke Okuzaki, Naganari Ohkura, Shimon Sakaguchi, Masato Okada, Atsushi Kumanogoh
Mechanistic target of rapamycin complex (mTORC)1 integrates intracellular sufficiency of nutrients and regulates various cellular functions. Previous studies using mice with conditional knockout of mTORC1 component proteins (i.e., mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4(+) T cells. Lamtor1 is the protein that is required for amino acid sensing and activation of mTORC1; however, the roles of Lamtor1 in T cells have not been investigated. In this article, we show that Lamtor1-deficient CD4(+) T cells exhibited marked reductions in proliferation, IL-2 production, mTORC1 activity, and expression of purine- and lipid-synthesis genes...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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