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https://www.readbyqxmd.com/read/28855209/therapeutic-targeting-of-oncogenic-tyrosine-phosphatases
#1
Rochelle Frankson, Zhi-Hong Yu, Yunpeng Bai, Qinglin Li, Ruo-Yu Zhang, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTPs) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTKs) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions...
August 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28679948/prl2-links-magnesium-flux-and-sex-dependent-circadian-metabolic-rhythms
#2
Noriko Uetani, Serge Hardy, Simon-Pierre Gravel, Silke Kiessling, Adam Pietrobon, Nau Nau Wong, Valérie Chénard, Nicolas Cermakian, Julie St-Pierre, Michel L Tremblay
Magnesium (Mg2+) plays pleiotropic roles in cellular biology, and it is essentially required for all living organisms. Although previous studies demonstrated intracellular Mg2+ levels were regulated by the complex of phosphatase of regenerating liver 2 (PRL2) and Mg2+ transporter of cyclin M (CNNMs), physiological functions of PRL2 in whole animals remain unclear. Interestingly, Mg2+ was recently identified as a regulator of circadian rhythm-dependent metabolism; however, no mechanism was found to explain the clock-dependent Mg2+ oscillation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28652133/acute-salinity-tolerance-and-the-control-of-two-prolactins-and-their-receptors-in-the-nile-tilapia-oreochromis-niloticus-and-mozambique-tilapia-o-mossambicus-a-comparative-study
#3
Yoko Yamaguchi, Jason P Breves, Maria C Haws, Darren T Lerner, E Gordon Grau, Andre P Seale
Osmoregulation in vertebrates is largely controlled by the neuroendocrine system. Prolactin (PRL) is critical for the survival of euryhaline teleosts in fresh water by promoting ion retention. In the euryhaline Mozambique tilapia (Oreochromis mossambicus), pituitary PRL cells release two PRL isoforms, PRL188 and PRL177, in response to a fall in extracellular osmolality. Both PRLs function via two PRL receptors (PRLRs) denoted PRLR1 and PRLR2. We conducted a comparative study using the Nile tilapia (O. niloticus), a close relative of Mozambique tilapia that is less tolerant to increases in environmental salinity, to investigate the regulation of PRLs and PRLRs upon acute hyperosmotic challenges in vivo and in vitro...
June 23, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28649267/evidence-for-a-postreproductive-phase-in-female-false-killer-whales-pseudorca-crassidens
#4
Theoni Photopoulou, Ines M Ferreira, Peter B Best, Toshio Kasuya, Helene Marsh
BACKGROUND: A substantial period of life after reproduction ends, known as postreproductive lifespan (PRLS), is at odds with classical life history theory and its causes and mechanisms have puzzled evolutionary biologists for decades. Prolonged PRLS has been confirmed in only two non-human mammals, both odontocete cetaceans in the family Delphinidae. We investigate the evidence for PRLS in a third species, the false killer whale, Pseudorca crassidens, using a quantitative measure of PRLS and morphological evidence from reproductive tissues...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28365912/multimodal-analysis-of-the-preferred-retinal-location-and-the-transition-zone-in-patients-with-stargardt-disease
#5
Tommaso Verdina, Vivienne C Greenstein, Andrea Sodi, Stephen H Tsang, Tomas R Burke, Ilaria Passerini, Rando Allikmets, Gianni Virgili, Gian Maria Cavallini, Stanislao Rizzo
PURPOSE: The purpose of our study was to investigate morpho-functional features of the preferred retinal location (PRL) and the transition zone (TZ) in a series of patients with recessive Stargardt disease (STGD1). METHODS: Fifty-two STGD1 patients with at least one ABCA4 mutation, atrophy of the central macula (MA) and an eccentric PRL were recruited for the study. Microperimetry, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) were performed...
July 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28246390/prl3-phosphatase-active-site-is-required-for-binding-the-putative-magnesium-transporter-cnnm3
#6
Huizhi Zhang, Guennadi Kozlov, Xinlu Li, Howie Wu, Irina Gulerez, Kalle Gehring
The phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28245492/a-preferred-retinal-location-of-fixation-can-be-induced-when-systematic-stimulus-relocations-are-applied
#7
Maria J Barraza-Bernal, Katharina Rifai, Siegfried Wahl
Patients with central vision loss obtain visual information by fixating on an object eccentrically with a preferred retinal locus of fixation (PRL). Patients do not always choose the most efficient PRL position, and as a consequence, visual performance is not always fully exploited. This study investigates whether PRLs can be induced by applying systematic stimulus relocations. The PRL was trained using a central scotoma simulation in 15 healthy subjects. They performed different visual tasks during four sessions, after which their reading performance was evaluated...
February 1, 2017: Journal of Vision
https://www.readbyqxmd.com/read/28114373/does-vertical-reading-help-people-with-macular-degeneration-an-exploratory-study
#8
Aurélie Calabrèse, Tingting Liu, Gordon E Legge
Individuals with macular degeneration often develop a Preferred Retinal Locus (PRL) used in place of the impaired fovea. It is known that many people adopt a PRL left of the scotoma, which is likely to affect reading by occluding text to the right of fixation. For such individuals, we examined the possibility that reading vertical text, in which words are rotated 90° with respect to the normal horizontal orientation, would be beneficial for reading. Vertically oriented words would be tangential to the scotoma instead of being partially occluded by it...
2017: PloS One
https://www.readbyqxmd.com/read/27899452/structural-basis-of-the-oncogenic-interaction-of-phosphatase-prl-1-with-the-magnesium-transporter-cnnm2
#9
Paula Giménez-Mascarell, Iker Oyenarte, Serge Hardy, Tilman Breiderhoff, Marchel Stuiver, Elie Kostantin, Tammo Diercks, Angel L Pey, June Ereño-Orbea, María Luz Martínez-Chantar, Reham Khalaf-Nazzal, Felix Claverie-Martin, Dominik Müller, Michel L Tremblay, Luis Alfonso Martínez-Cruz
Phosphatases of regenerating liver (PRLs), the most oncogenic of all protein-tyrosine phosphatases (PTPs), play a critical role in metastatic progression of cancers. Recent findings established a new paradigm by uncovering that their association with magnesium transporters of the cyclin M (CNNM) family causes a rise in intracellular magnesium levels that promote oncogenic transformation. Recently, however, essential roles for regulation of the circadian rhythm and reproduction of the CNNM family have been highlighted...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27856537/phosphocysteine-in-the-prl-cnnm-pathway-mediates-magnesium-homeostasis
#10
Irina Gulerez, Yosuke Funato, Howie Wu, Meng Yang, Guennadi Kozlov, Hiroaki Miki, Kalle Gehring
PRLs (phosphatases of regenerating liver) are frequently overexpressed in human cancers and are prognostic markers of poor survival. Despite their potential as therapeutic targets, their mechanism of action is not understood in part due to their weak enzymatic activity. Previous studies revealed that PRLs interact with CNNM ion transporters and prevent CNNM4-dependent Mg(2+) transport, which is important for energy metabolism and tumor progression. Here, we report that PRL-CNNM complex formation is regulated by the formation of phosphocysteine...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27811525/fixation-stability-and-viewing-distance-in-patients-with-amd
#11
Luminita Tarita-Nistor, Esther G González, Taylor Brin, Mark S Mandelcorn, Anne-Catherine Scherlen, Efrem D Mandelcorn, Martin J Steinbach
PURPOSE: People with normal vision perform activities of daily living binocularly, while changing viewing distance frequently and effortlessly. Typically, in patients with age-related macular degeneration (AMD), fixation stability is recorded with monocular instruments at a fixed viewing distance (i.e. optical infinity) to determine the location and precision of the preferred retinal loci (PRLs)-the part of the functional retina that fulfills the role of a pseudo-fovea. Fixation stability recorded with these instruments has been related to performance on visual tasks at shorter viewing distances, although it is not known how viewing distance affects the precision of ocular motor control in these patients...
February 2017: Optometry and Vision Science: Official Publication of the American Academy of Optometry
https://www.readbyqxmd.com/read/27769327/characteristics-of-the-preferred-retinal-loci-of-better-and-worse-seeing-eyes-of-patients-with-a-central-scotoma
#12
Eli Kisilevsky, Luminita Tarita-Nistor, Esther G González, Mark S Mandelcorn, Michael H Brent, Samuel N Markowitz, Martin J Steinbach
OBJECTIVE: Patients with central vision loss develop preferred retinal loci (PRLs) in the eccentric retina. The characteristics of the PRLs for the better eye (BE) are well studied, but not those of the worse eye (WE). We examined the distribution of monocular PRLs in the visual field (VF), as well as visual acuity, fixation stability, and PRL eccentricity for the BE and WE of patients with central vision loss. DESIGN: Retrospective consecutive case series. PARTICIPANTS: A total of 87 BE and 50 WE of patients with central vision loss...
October 2016: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/27666520/role-of-phosphatase-of-regenerating-liver-1-prl1-in-spermatogenesis
#13
Yunpeng Bai, Hong-Ming Zhou, Lujuan Zhang, Yuanshu Dong, Qi Zeng, Weinian Shou, Zhong-Yin Zhang
The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and reproductive ability of male mice, likely due to functional compensation by the relatively higher expression of PRL2 in the testes. However, PRL1(-/-)/PRL2(+/-) male mice show testicular atrophy phenotype similar to PRL2(-/-) mice...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27594860/comparative-transcriptome-analysis-of-primary-roots-of-brassica-napus-seedlings-with-extremely-different-primary-root-lengths-using-rna-sequencing
#14
Xiaoling Dun, Zhangsheng Tao, Jie Wang, Xinfa Wang, Guihua Liu, Hanzhong Wang
Primary root (PR) development is a crucial developmental process that is essential for plant survival. The elucidation of the PR transcriptome provides insight into the genetic mechanism controlling PR development in crops. In this study, we performed a comparative transcriptome analysis to investigate the genome-wide gene expression profiles of the seedling PRs of four Brassica napus genotypes that were divided into two groups, short group (D43 and D61), and long group (D69 and D72), according to their extremely different primary root lengths (PRLs)...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27523456/relationship-between-primary-restless-legs-syndrome-and-migraine-with-aura
#15
Bilgehan Atılgan Acar, Türkan Acar, Aybala Neslihan Alagöz, Alper Karacan, Ceyhun Varım, Mehmet Şevki Uyanık, Tezcan Kaya, Ramazan Akdemir
In this study, the prevalence and characteristics of definite migraine in primary restless legs syndrome (pRLS) patients and matched control patients (CPs) were investigated. We evaluated 63 consecutive adult pRLS patients and 141 age- and sex-matched controls in this case-control study. The diagnosis of migraine and its subtypes were defined based on The International Classification of Headache Disorders-II. Only those with "definite" migraine were included in the study. The mean age of 63 adult pRLS patients (15 men and 48 women) who participated in the study was 49...
August 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27514804/discovery-and-evaluation-of-prl-trimer-disruptors-for-novel-anticancer-agents
#16
Yunpeng Bai, Zhi-Hong Yu, Zhong-Yin Zhang
Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a variety of late-stage tumors and their distant metastatic sites. Therefore, the oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There is considerable interest in identifying small molecule inhibitors targeting PRLs as novel anticancer agents. However, it has been difficult to acquire phosphatase activity-based PRL inhibitors due to the unusual wide and shallow catalytic pockets of PRLs revealed by crystal structure studies...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27402066/hormonal-regulation-of-aquaporin-3-opposing-actions-of-prolactin-and-cortisol-in-tilapia-gill
#17
Jason P Breves, Mayu Inokuchi, Yoko Yamaguchi, Andre P Seale, Bethany L Hunt, Soichi Watanabe, Darren T Lerner, Toyoji Kaneko, E Gordon Grau
Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW)...
September 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27379370/autocrine-positive-feedback-regulation-of-prolactin-release-from-tilapia-prolactin-cells-and-its-modulation-by-extracellular-osmolality
#18
Yoko Yamaguchi, Shunsuke Moriyama, Darren T Lerner, E Gordon Grau, Andre P Seale
Prolactin (PRL) is a vertebrate hormone with diverse actions in osmoregulation, metabolism, reproduction, and in growth and development. Osmoregulation is fundamental to maintaining the functional structure of the macromolecules that conduct the business of life. In teleost fish, PRL plays a critical role in osmoregulation in fresh water. Appropriately, PRL cells of the tilapia are directly osmosensitive, with PRL secretion increasing as extracellular osmolality falls. Using a model system that employs dispersed PRL cells from the euryhaline teleost fish, Oreochromis mossambicus, we investigated the autocrine regulation of PRL cell function...
September 2016: Endocrinology
https://www.readbyqxmd.com/read/27114589/benefit-of-surveillance-for-pancreatic-cancer-in-high-risk-individuals-outcome-of-long-term-prospective-follow-up-studies-from-three-european-expert-centers
#19
MULTICENTER STUDY
Hans Vasen, Isaura Ibrahim, Carmen Guillen Ponce, Emily P Slater, Elvira Matthäi, Alfredo Carrato, Julie Earl, Kristin Robbers, Anneke M van Mil, Thomas Potjer, Bert A Bonsing, Wouter H de Vos Tot Nederveen Cappel, Wilma Bergman, Martin Wasser, Hans Morreau, Günter Klöppel, Christoph Schicker, Martin Steinkamp, Jens Figiel, Irene Esposito, Evelina Mocci, Enrique Vazquez-Sequeiros, Alfonso Sanjuanbenito, Maria Muñoz-Beltran, José Montans, Peter Langer, Volker Fendrich, Detlef K Bartsch
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis. PATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC...
June 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/26968909/subsistence-patterns-gender-roles-effective-temperature-and-the-evolutionary-timing-of-a-post-reproductive-life-span
#20
German Loffler
Evolutionary anthropologists explain menopause and the start of a post reproductive lifespan (PRLS), as beneficiary for older women who can now help contribute to their children/grandchildren's wellbeing. This paper presents a new model with the aim to elucidate when, where, and for whom, such benefits may have arisen. In foraging societies, women contribute nutrients to their social groups/family units to a greater degree as overall effective temperatures (ETs) rise. Where the ET is favorable for women's contributions (ETs between 15 and 20), selection does lengthen the PRLS of women because women contribute sufficiently to enhance their own inclusive fitness...
April 2016: Medical Hypotheses
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