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https://www.readbyqxmd.com/read/28347132/radiolabeled-peptides-current-and-new-perspectives
#1
Marta Opalinska, Alicja Hubalewska-Dydejczyk, Anna Sowa-Staszczak
Radiolabeled peptides have been the subject of research for over 20 years and during that time possibility/variety of peptide receptor imaging and later targeted radiotherapy increased significantly. The targeted receptors belong to the large family of G-protein-coupled receptors or tyrosine kinases receptors partially connected with them. They both regulate large signaling networks, control multiple cell functions and are implicated in many diseases including cancers. The essential feature of peptides used in nuclear medicine involves their ability to binding with high affinity and specify to their receptors overexpressed on tumor cells...
June 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28346798/priming-adipose-stem-cells-with-tumor-necrosis-factor-alpha-preconditioning-potentiates-their-exosome-efficacy-for-bone-regeneration
#2
ZuFu Lu, YongJuan Chen, Colin Dunstan, Seyediman Roohani-Esfahani, Hala Zreiqat
Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration. We showed that adipose tissue-derived MSC (ASC)-derived exosomes (ASC-EXO) were able to promote the proliferation and osteogenic differentiation in HOBs; and the trophic effects of ASC-EXO on HOBs were further harnessed when ASCs were preconditioned with tumor necrosis factor-alpha (TNF-α) for 3 days, which mimics the acute inflammatory phase upon bone injury...
March 23, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346728/nubpl-a-novel-metastasis-related-gene-promotes-colorectal-carcinoma-cell-motility-by-inducing-emt
#3
Yuhui Wang, Nan Wu, Donglin Sun, Haiming Sun, Dandan Tong, Duo Liu, Bo Pang, Su Li, Jia Wei, Jialin Dai, Yang Liu, Jing Bai, Jingshu Geng, Songbin Fu, Yan Jin
NUBPL is an assembly factor for human mitochondrial complex I, which is the biggest member of mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n=197) from Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and nontumorous tissues demonstrated that expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P=0...
March 27, 2017: Cancer Science
https://www.readbyqxmd.com/read/28346614/crosstalk-between-transforming-growth-factor-beta-2-and-toll-like-receptor-4-in-the-trabecular-meshwork
#4
Humberto Hernandez, Wanda E Medina-Ortiz, Tomi Luan, Abbot F Clark, Colleen M McDowell
Purpose: The trabecular meshwork (TM) is involved in the outflow of aqueous humor and intraocular pressure (IOP) regulation. Regulation of the extracellular matrix (ECM) by TGFβ2 signaling pathways in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in liver, kidney, lung, and skin. Here, we investigated the role of TGFβ2-TLR4 signaling crosstalk in the regulation of the ECM in the TM and ocular hypertension...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28346521/hiv-1-gp120-envelope-glycoprotein-determinants-for-cytokine-burst-in-human-monocytes
#5
Benoît Levast, Lucie Barblu, Mathieu Coutu, Jérémie Prévost, Nathalie Brassard, Adam Peres, Camille Stegen, Joaquín Madrenas, Daniel E Kaufmann, Andrés Finzi
The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28346517/cd22-is-required-for-formation-of-memory-b-cell-precursors-within-germinal-centers
#6
Craig P Chappell, Kevin E Draves, Edward A Clark
CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations...
2017: PloS One
https://www.readbyqxmd.com/read/28346502/ebv-induces-persistent-nf-%C3%AE%C2%BAb-activation-and-contributes-to-survival-of-ebv-positive-neoplastic-t-or-nk-cells
#7
Honami Takada, Ken-Ichi Imadome, Haruna Shibayama, Mayumi Yoshimori, Ludan Wang, Yasunori Saitoh, Shin Uota, Shoji Yamaoka, Takatoshi Koyama, Norio Shimizu, Kouhei Yamamoto, Shigeyoshi Fujiwara, Osamu Miura, Ayako Arai
Epstein-Barr virus (EBV) has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV). However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV...
2017: PloS One
https://www.readbyqxmd.com/read/28346501/a-tissue-specific-role-for-intraflagellar-transport-genes-during-craniofacial-development
#8
Elizabeth N Schock, Jaime N Struve, Ching-Fang Chang, Trevor J Williams, John Snedeker, Aria C Attia, Rolf W Stottmann, Samantha A Brugmann
Primary cilia are nearly ubiquitous, cellular projections that function to transduce molecular signals during development. Loss of functional primary cilia has a particularly profound effect on the developing craniofacial complex, causing several anomalies including craniosynostosis, micrognathia, midfacial dysplasia, cleft lip/palate and oral/dental defects. Development of the craniofacial complex is an intricate process that requires interactions between several different tissues including neural crest cells, neuroectoderm and surface ectoderm...
2017: PloS One
https://www.readbyqxmd.com/read/28346496/overlapping-setbp1-gain-of-function-mutations-in-schinzel-giedion-syndrome-and-hematologic-malignancies
#9
Rocio Acuna-Hidalgo, Pelagia Deriziotis, Marloes Steehouwer, Christian Gilissen, Sarah A Graham, Sipko van Dam, Julie Hoover-Fong, Aida B Telegrafi, Anne Destree, Robert Smigiel, Lindsday A Lambie, Hülya Kayserili, Umut Altunoglu, Elisabetta Lapi, Maria Luisa Uzielli, Mariana Aracena, Banu G Nur, Ercan Mihci, Lilia M A Moreira, Viviane Borges Ferreira, Dafne D G Horovitz, Katia M da Rocha, Aleksandra Jezela-Stanek, Alice S Brooks, Heiko Reutter, Julie S Cohen, Ali Fatemi, Martin Smitka, Theresa A Grebe, Nataliya Di Donato, Charu Deshpande, Anthony Vandersteen, Charles Marques Lourenço, Andreas Dufke, Eva Rossier, Gwenaelle Andre, Alessandra Baumer, Careni Spencer, Julie McGaughran, Lude Franke, Joris A Veltman, Bert B A De Vries, Albert Schinzel, Simon E Fisher, Alexander Hoischen, Bregje W van Bon
Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346477/disruption-of-sorcs2-reveals-differences-in-the-regulation-of-stereociliary-bundle-formation-between-hair-cell-types-in-the-inner-ear
#10
Andrew Forge, Ruth R Taylor, Sally J Dawson, Michael Lovett, Daniel J Jagger
Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346462/wnt-tcf1-pathway-restricts-embryonic-stem-cell-cycle-through-activation-of-the-ink4-arf-locus
#11
Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#12
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346441/altering-the-threshold-of-an-excitable-signal-transduction-network-changes-cell-migratory-modes
#13
Yuchuan Miao, Sayak Bhattacharya, Marc Edwards, Huaqing Cai, Takanari Inoue, Pablo A Iglesias, Peter N Devreotes
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346439/hippo-signalling-governs-cytosolic-nucleic-acid-sensing-through-yap-taz-mediated-tbk1-blockade
#14
Qian Zhang, Fansen Meng, Shasha Chen, Steven W Plouffe, Shiying Wu, Shengduo Liu, Xinran Li, Ruyuan Zhou, Junxian Wang, Bin Zhao, Jianming Liu, Jun Qin, Jian Zou, Xin-Hua Feng, Kun-Liang Guan, Pinglong Xu
The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#15
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
March 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28346426/mrl-proteins-cooperate-with-activated-ras-in-glia-to-drive-distinct-oncogenic-outcomes
#16
E Taylor, N Alqadri, L Dodgson, D Mason, E Lyulcheva, G Messina, D Bennett
The Mig10/RIAM/Lpd (MRL) adapter protein Lpd regulates actin dynamics through interactions with Scar/WAVE and Ena/VASP proteins to promote the formation of cellular protrusions and to stimulate invasive migration. However, the ability of MRL proteins to interact with multiple actin regulators and to promote serum response factor (SRF) signalling has raised the question of whether MRL proteins employ alternative downstream mechanisms to drive oncogenic processes in a context-dependent manner. Here, using a Drosophila model, we show that overexpression of either human Lpd or its Drosophila orthologue Pico can promote growth and invasion of Ras(V12)-induced cell tumours in the brain...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346422/the-metastatic-suppressor-ndrg1-inhibits-emt-migration-and-invasion-through-interaction-and-promotion-of-caveolin-1-ubiquitylation-in-human-colorectal-cancer-cells
#17
L Mi, F Zhu, X Yang, J Lu, Y Zheng, Q Zhao, X Wen, A Lu, M Wang, M Zheng, J Ji, J Sun
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346420/hepatic-cyclooxygenase-2-overexpression-induced-spontaneous-hepatocellular-carcinoma-formation-in-mice
#18
H Chen, W Cai, E S H Chu, J Tang, C-C Wong, S H Wong, W Sun, Q Liang, J Fang, Z Sun, J Yu
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346410/quality-of-tcr-signaling-determined-by-differential-affinities-of-enhancers-for-the-composite-batf-irf4-transcription-factor-complex
#19
Arifumi Iwata, Vivek Durai, Roxane Tussiwand, Carlos G Briseño, Xiaodi Wu, Gary E Grajales-Reyes, Takeshi Egawa, Theresa L Murphy, Kenneth M Murphy
Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expression of genes in the TH2 subset of helper T cells to enhancer occupancy by the BATF-IRF4 transcription factor complex at varying strengths of TCR stimulation. Genes dependent on BATF-IRF4 clustered into groups with distinct TCR sensitivities...
March 27, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346402/large-scale-design-of-robust-genetic-circuits-with-multiple-inputs-and-outputs-for-mammalian-cells
#20
Benjamin H Weinberg, N T Hang Pham, Leidy D Caraballo, Thomas Lozanoski, Adrien Engel, Swapnil Bhatia, Wilson W Wong
Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance...
March 27, 2017: Nature Biotechnology
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