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https://www.readbyqxmd.com/read/28174173/the-apc-c-e3-ligase-complex-activator-fzr1-restricts-braf-oncogenic-function
#1
Lixin Wan, Ming Chen, Juxiang Cao, Xiangpeng Dai, Qing Yin, Jinfang Zhang, Su-Jung Song, Ying Lu, Jing Liu, Hiroyuki Inuzuka, Jesse M Katon, Kelsey Berry, Jacqueline Fung, Christopher Ng, Pengda Liu, Min Sup Song, Lian Xue, Roderick T Bronson, Marc W Kirschner, Rutao Cui, Pier Paolo Pandolfi, Wenyi Wei
BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APC(FZR1), APC(FZR1) earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases...
February 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28147277/regulation-of-serine-threonine-kinase-akt-activation-by-nad-dependent-deacetylase-sirt7
#2
Jia Yu, Bo Qin, Fengying Wu, Sisi Qin, Somaira Nowsheen, Shan Shan, Jacqueline Zayas, Huadong Pei, Zhenkun Lou, Liewei Wang
The Akt pathway is a central regulator that promotes cell survival in response to extracellular signals. Depletion of SIRT7, an NAD(+)-dependent deacetylase that is the least-studied sirtuin, is known to significantly increase Akt activity in mice through unknown mechanisms. In this study, we demonstrate that SIRT7 depletion in breast cancer cells results in Akt hyper-phosphorylation and increases cell survival following genotoxic stress. Mechanistically, SIRT7 specifically interacts with and deacetylates FKBP51 at residue lysines 28 and 155 (K28 and K155), resulting in enhanced interactions among FKBP51, Akt, and PHLPP, as well as Akt dephosphorylation...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28121425/biosensor-based-evolution-and-elucidation-of-a-biosynthetic-pathway-in-escherichia-coli
#3
Yongfei Liu, Yinyin Zhuang, Dongqin Ding, Yiran Xu, Jibin Sun, Dawei Zhang
The successful evolution of metabolite-producing microbes requires a high throughput screening method to obtain the desired properties within a short time. In this study, we developed a transcription factor-driven device that combined a metabolite-responsive element and a selection module. This device was able to specifically sense intracellular L-phenylalanine (L-Phe) and convert this signal into an observable phenotype. Applying this device, we successfully improved L-Phe production by screening hyper-producing phenotypes from an RBS library and a random mutagenesis library...
January 25, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28065737/osmoregulatory-role-of-vasotocinergic-and-isotocinergic-systems-in-the-gilthead-sea-bream-sparus-aurata-l
#4
Juan Miguel Mancera, Gonzalo Martínez-Rodríguez, Arleta Krystyna Skrzynska, Juan Antonio Martos-Sitcha
Gilthead sea bream, Sparus aurata L., is an important fish species for the Mediterranean aquaculture and is considered a good model for studying the osmoregulatory process, due to its capacity to cope with great changes in environmental salinity (5-60‰). Our group studied the osmoregulatory role of different endocrine systems in this species, focusing on the vasotocinergic and isotocinergic systems over several years. For this purpose, the cDNAs coding for pro-vasotocin (pro-vt), pro-isotocin (pro-it), two arginine vasotocin (AVT) receptors (avtr v1a2- and v2-types) and one IT receptor (itr) were cloned...
January 5, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28061745/large-scale-transcriptome-comparison-of-sunflower-genes-responsive-to-verticillium-dahliae
#5
Shuchun Guo, Yongchun Zuo, Yanfang Zhang, Chengyan Wu, Wenxia Su, Wen Jin, Haifeng Yu, Yulin An, Qianzhong Li
BACKGROUND: Sunflower Verticillium wilt (SVW) is a vascular disease caused by root infection with Verticillium dahliae (V. dahlia). It is a serious threat to the yield and quality of sunflower. However, chemical and agronomic measures for controlling this disease are not effective. The selection of more resistant genotypes is a desirable strategy to reduce contamination. A deeper knowledge of the molecular mechanisms and genetic basis underlying sunflower Verticillium wilt is necessary to accelerate breeding progress...
January 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/27995987/intrinsic-photosensitivity-enhances-motility-of-t-lymphocytes
#6
Thieu X Phan, Barbara Jaruga, Sandeep C Pingle, Bidhan C Bandyopadhyay, Gerard P Ahern
Sunlight has important biological effects in human skin. Ultraviolet (UV) light striking the epidermis catalyzes the synthesis of Vitamin D and triggers melanin production. Although a causative element in skin cancers, sunlight is also associated with positive health outcomes including reduced incidences of autoimmune diseases and cancers. The mechanisms, however, by which light affects immune function remain unclear. Here we describe direct photon sensing in human and mouse T lymphocytes, a cell-type highly abundant in skin...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886185/hyper-il-6-a-potent-and-efficacious-stimulator-of-rgc-regeneration
#7
D Fischer
Mature retinal ganglion cells (RGCs) normally fail to regenerate injured axons and die soon after optic nerve injury. Research over the last two decades has demonstrated that application of IL-6-like cytokines or activation of respective downstream signaling pathways promote neuroprotection and optic nerve regeneration. However, the overall beneficial effects of natural cytokines remain usually rather moderate, possibly due to intrinsic signaling pathway inhibitors, such as PTEN or SOCS3, or a limited expression of specific cytokine receptors in RGCs...
February 2017: Eye
https://www.readbyqxmd.com/read/27874229/exopolysaccharides-promote-myxococcus-xanthus-social-motility-by-inhibiting-cellular-reversals
#8
Tianyi Zhou, Beiyan Nan
The biofilm-forming bacterium Myxococcus xanthus moves on surfaces as structured swarms utilizing type IV pili-dependent social (S) motility. In contrast to isolated cells that reverse their moving direction frequently, individual cells within swarms rarely reverse. The regulatory mechanisms that inhibit cellular reversal and promote the formation of swarms are not well understood. Here we show that exopolysaccharides (EPS), the major extracellular components of M. xanthus swarms, inhibit cellular reversal in a concentration-dependent manner...
November 22, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27751503/the-role-of-dopamine-in-positive-and-negative-prediction-error-utilization-during-incidental-learning-insights-from-positron-emission-tomography-parkinson-s-disease-and-huntington-s-disease
#9
David Mathar, Leonora Wilkinson, Anna K Holl, Jane Neumann, Lorenz Deserno, Arno Villringer, Marjan Jahanshahi, Annette Horstmann
Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task - WPT) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [(11)C]raclopride Positron Emission Tomography (PET), allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway...
September 19, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/27596138/the-effect-of-the-nmda-receptor-dependent-signaling-pathway-on-cell-morphology-and-melanosome-transfer-in-melanocytes
#10
Jing Ni, Nan Wang, Lili Gao, Lili Li, Siwen Zheng, Yuejian Liu, Molu Ozukum, Anna Nikiforova, Guangming Zhao, Zhiqi Song
BACKGROUND: The pigmentation of skin and hair in mammals is driven by the intercellular transfer of melanosome from the melanocyte to surrounding keratinocytes However, the detailed molecular mechanism is still a subject of investigation. OBJECTIVE: To investigate the effects of N-methyl-d-aspartate (NMDA) receptor-dependent signaling pathway on melanocyte morphologic change and melanosome transfer between melanocytes and keratinocytes. METHODS: The expression and the intracellular distribution of NMDA receptor in human melanocyte were analyzed by Western blot and immunofluorescence staining...
December 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27559126/menainv-mediates-synergistic-cross-talk-between-signaling-pathways-driving-chemotaxis-and-haptotaxis
#11
Madeleine J Oudin, Miles A Miller, Joelle A Z Klazen, Tatsiana Kosciuk, Alisha Lussiez, Shannon K Hughes, Jenny Tadros, James E Bear, Douglas A Lauffenburger, Frank B Gertler
Directed cell migration, a key process in metastasis, arises from the combined influence of multiple processes, including chemotaxis-the directional movement of cells to soluble cues-and haptotaxis-the migration of cells on gradients of substrate-bound factors. However, it is unclear how chemotactic and haptotactic pathways integrate with each other to drive overall cell behavior. Mena(INV) has been implicated in metastasis by driving chemotaxis via dysregulation of phosphatase PTP1B and more recently in haptotaxis via interaction with integrin α5β1...
October 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27531891/wnt-signalling-is-a-bi-directional-vulnerability-of-cancer-cells
#12
David J Duffy, Aleksandar Krstic, Thomas Schwarzl, Melinda Halasz, Kristiina Iljin, Dirk Fey, Bridget Haley, Jenny Whilde, Saija Haapa-Paananen, Vidal Fey, Matthias Fischer, Frank Westermann, Kai-Oliver Henrich, Steffen Bannert, Desmond G Higgins, Walter Kolch
Wnt signalling is involved in the formation, metastasis and relapse of a wide array of cancers. However, there is ongoing debate as to whether activation or inhibition of the pathway holds the most promise as a therapeutic treatment for cancer, with conflicting evidence from a variety of tumour types. We show that Wnt/β-catenin signalling is a bi-directional vulnerability of neuroblastoma, malignant melanoma and colorectal cancer, with hyper-activation or repression of the pathway both representing a promising therapeutic strategy, even within the same cancer type...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27527558/integration-of-renal-sensory-afferents-at-the-level-of-the-paraventricular-nucleus-dictating-sympathetic-outflow
#13
REVIEW
Hong Zheng, Kaushik P Patel
The sympathetic nervous system has been identified as a major contributor to the pathophysiology of chronic heart failure (CHF) and other diseases such as hypertension and diabetes, both in experimental animal models and patients. The kidneys have a dense afferent sensory innervation positioning it to be the origin of multimodal input to the central nervous system. Afferent renal nerve (ARN) signals are centrally integrated, and their activation results in a general increase in sympathetic tone, which is directed toward the kidneys as well as other peripheral organs innervated by the sympathetic nerves...
August 6, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27515486/systems-level-analysis-of-the-yeast-osmo-stat
#14
Soheil Rastgou Talemi, Carl-Fredrik Tiger, Mikael Andersson, Roja Babazadeh, Niek Welkenhuysen, Edda Klipp, Stefan Hohmann, Jörg Schaber
Adaptation is an important property of living organisms enabling them to cope with environmental stress and maintaining homeostasis. Adaptation is mediated by signaling pathways responding to different stimuli. Those signaling pathways might communicate in order to orchestrate the cellular response to multiple simultaneous stimuli, a phenomenon called crosstalk. Here, we investigate possible mechanisms of crosstalk between the High Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways in yeast, which mediate adaptation to hyper- and hypo-osmotic challenges, respectively...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27495129/laser-acupuncture-causes-thermal-changes-in-small-intestine-meridian-pathway
#15
Regina Célia de Souza, Mario Pansini, Gisele Arruda, Caroline Valente, Marcos Leal Brioschi
The acupuncture meridians represent the flow of corporal energy which contains the acupuncture points. Laser acupuncture is a form of acupuncture stimulation by the use of laser. Thermographic images represent the propagation of heat in micro-environmental systems. The objective of this study was to investigate the use of thermographic images to document the changes on the small intestine meridian (S.I.M.) when submitted to laser acupuncture. Another important issue regards to the analysis of the flow direction if it is upward when stimulated by acupuncture points...
November 2016: Lasers in Medical Science
https://www.readbyqxmd.com/read/27460695/vascular-effects-of-linagliptin-in-non-obese-diabetic-mice-are-glucose-independent-and-involve-positive-modulation-of-the-endothelial-nitric-oxide-synthase-enos-caveolin-1-cav-1-pathway
#16
Valentina Vellecco, Emma Mitidieri, Antonella Gargiulo, Vincenzo Brancaleone, Danilo Matassa, Thomas Klein, Franca Esposito, Giuseppe Cirino, Mariarosaria Bucci
AIM: To test the effect of linagliptin in non-obese diabetic (NOD) mice, a murine model of type 1 diabetes, to unveil a possible direct cardiovascular action of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond glycaemia control. METHODS: NOD mice were grouped according to glycosuria levels as NODI: none; NODII: high; NODIII: severe. Linagliptin treatment was initiated once they reached NODII levels. Vascular reactivity was assessed ex vivo on aorta harvested from mice upon reaching NODIII level...
December 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27409410/prostaglandin-d2-receptor-antagonists-in-early-development-as-potential-therapeutic-options-for-asthma
#17
REVIEW
Pierachille Santus, Dejan Radovanovic
INTRODUCTION: Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that interfere with the innate inflammatory response in asthma have been identified. Promising preliminary results concern the signaling cascade promoted by prostaglandin D2 (PGD2) and its receptor antagonists...
September 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27396242/effects-of-thrombin-on-insulin-signalling-and-glucose-uptake-in-cultured-human-myotubes
#18
Ali Al-Bayati, Dhanisha Lukka, Audrey E Brown, Mark Walker
BACKGROUND: Hyper-coagulability (elevated thrombin) is a feature of type 2 diabetes and contributes to an increased risk of thrombotic and vascular events. Skeletal muscle is the key peripheral tissue site of insulin resistance in type 2 diabetes. Cultured human skeletal muscle cells were used to explore the effects of thrombin on insulin signalling and glucose uptake. We hypothesized that thrombin affects insulin activity in human skeletal muscle cells which could link the hypercoagulability and insulin resistance in type 2 diabetes...
September 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27290643/selection-pressure-on-human-str-loci-and-its-relevance-in-repeat-expansion-disease
#19
Makoto K Shimada, Ryoko Sanbonmatsu, Yumi Yamaguchi-Kabata, Chisato Yamasaki, Yoshiyuki Suzuki, Ranajit Chakraborty, Takashi Gojobori, Tadashi Imanishi
Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs...
October 2016: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/27203446/boosting-central-nervous-system-axon-regeneration-by-circumventing-limitations-of-natural-cytokine-signaling
#20
Marco Leibinger, Anastasia Andreadaki, Philipp Gobrecht, Evgeny Levin, Heike Diekmann, Dietmar Fischer
Retinal ganglion cells (RGCs) do not normally regenerate injured axons, but die upon axotomy. Although IL-6-like cytokines are reportedly neuroprotective and promote optic nerve regeneration, their overall regenerative effects remain rather moderate. Here, we hypothesized that direct activation of the gp130 receptor by the designer cytokine hyper-IL-6 (hIL-6) might induce stronger RGC regeneration than natural cytokines. Indeed, hIL-6 stimulated neurite growth of adult cultured RGCs with significantly higher efficacy than CNTF or IL-6...
October 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
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