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https://www.readbyqxmd.com/read/29167404/a-critical-role-for-dopamine-d5-receptors-in-pain-chronicity-in-male-mice
#1
Salim Megat, Stephanie Shiers, Jamie K Moy, Paulino Barragan-Iglesias, Grishma Pradhan, Rebecca P Seal, Gregory Dussor, Theodore J Price
Dopaminergic modulation of spinal cord plasticity has long been recognized but circuits affected by this system and the precise receptor subtypes involved in this modulation have not been defined. Dopaminergic modulation from the A11 nucleus of the hypothalamus contributes to plasticity in a model of chronic pain called hyperalgesic priming. Here we tested the hypothesis that the key receptor subtype mediating this effect is the D5 receptor (D5R). We find that a spinally-directed lesion of dopaminergic neurons reverses hyperalgesic priming in both sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29149443/migration-of-interneuron-precursors-in-the-nascent-cerebellar-cortex
#2
Annika K Wefers, Christian Haberlandt, Lachezar Surchev, Christian Steinhäuser, Ronald Jabs, Karl Schilling
The cerebellum arguably constitutes one of the best characterized central nervous circuits, and its structure, cellular function, and histogenesis have been described in exceptional quantitative detail. A notable exception to this is the development of its inhibitory interneurons, and in particular the extensive migrations of future basket and stellate cells. Here, we used acute slices from 8-day-old mice to assess the migration of Pax2-EGFP-tagged precursors of these cells en route to the molecular layer during their transit through the nascent cerebellar cortex...
November 17, 2017: Cerebellum
https://www.readbyqxmd.com/read/29138573/matrine-suppresses-the-migration-and-invasion-of-nsclc-cells-by-inhibiting-pax2-induced-epithelial-mesenchymal-transition
#3
Jun Yang, Du He, Yan Peng, Hongzhen Zhong, Yuhong Deng, Zhonghua Yu, Chengnong Guan, Yufang Zuo, Zumin Xu
Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29135049/functional-characterization-of-e2f3b-in-human-hepg2-liver-cancer-cell-line
#4
Yujia Lu, Wei Li
E2F3 is a transcription factor that has been shown to be overexpressed in hepatocellular carcinoma (HCC). It is well-known that the E2F3 gene encodes two proteins E2F3a and E2F3b. Therefore, the functions of the two distinct isoforms need to be clarified separately. To characterize the function of E2F3b in HCC, the effects of ectopic expression of E2F3b on cell proliferation, cell cycle, apoptosis and gene expression were investigated. E2F3b promoted G1/S phase transition and markedly increased cell proliferation, but had minor effect on apoptosis...
November 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29107072/ectopic-phosphorylated-creb-marks-dedifferentiated-proximal-tubules-in-cystic-kidney-disease
#5
Pawan Puri, Caitlin M Schaefer, Daniel Bushnell, Mary E Taglienti, Jordan A Kreidberg, Bradley K Yoder, Carlton M Bates
Ectopic cAMP signaling is pathological in polycystic kidney disease; however, its spatio-temporal actions are unclear. We characterized expression of phosphorylated Creb (p-Creb), a target and mediator of cAMP signaling, in developing and cystic kidney models. We also examined tubule-specific effects of cAMP analogs in cystogenesis in embryonic kidney explants. In wild-type mice, p-Creb marked nephron progenitors (NP), early epithelial NP derivatives, ureteric bud, and cortical stroma; p-Creb was present in differentiated thick ascending limb of Henle, collecting duct, and stroma; however, it disappeared in mature NP-derived proximal tubules...
October 26, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29100356/pax2-maintains-the-differentiation-of-mouse-oviductal-epithelium-and-inhibits-the-transition-to-a-stem-cell-like-state
#6
Kholoud Alwosaibai, Atefeh Abedini, Ensaf M Al-Hujaily, Yong Tang, Kenneth Garson, Olga Collins, Barbara C Vanderhyden
Recent studies have provided evidence that the secretory cells of the fallopian tube (oviduct) are a probable origin for high-grade serous ovarian carcinoma. In addition to secretory cells, the fallopian tube epithelium consists of ciliated cells and CD44+ undifferentiated stem-like cells. Loss of PAX2 expression is recognized as an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown. The aim of this study was to define the role of PAX2 in oviductal epithelial (OVE) cells and its response to transforming growth factor β1 (TGFβ), characterizing specifically its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061636/synaptic-input-as-a-directional-cue-for-migrating-interneuron-precursors
#7
Annika K Wefers, Christian Haberlandt, Nuriye B Tekin, Dmitry A Fedorov, Aline Timmermann, Johannes J L van der Want, Farrukh A Chaudhry, Christian Steinhäuser, Karl Schilling, Ronald Jabs
During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron / projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video-microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue. We found that cerebellar interneuronal precursors regularly show spontaneous postsynaptic currents, indicative of synaptic innervation, well before settling in the molecular layer...
October 23, 2017: Development
https://www.readbyqxmd.com/read/29060967/-significance-and-expression-of-pax8-pax2-p53-and-ras-in-ovary-and-fallopian-tubes-to-origin-of-ovarian-high-grade-serous-carcinoma
#8
Y N Mao, L X Zeng, Y H Li, Y Z Liu, J Y Wu, L Li, Q Wang
Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods: A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016...
October 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29054766/rethinking-genotype-phenotype-correlations-in-papillorenal-syndrome-a-case-report-on-an-unusual-congenital-camptodactyly-and-skeletal-deformity-with-a-heterogeneous-pax2-mutation-of-hexanucleotide-duplication
#9
Jiewei Liu, Ping Wang, Juan Huang, Zihua Yu
Papillorenal syndrome (PRS), an autosomal dominant inherited condition, is clinically featured by renal hypoplasia and optic nerve dysplasia. Based on current knowledge of genotype-phenotype correlations in PRS, mutations in the Paired box 2 (PAX2) gene have been recognized as a critical pathogenesis of typical renal and optic disease manifestations. However, little information is currently available on the skeletal abnormalities of PRS and the potential contribution of PAX2 mutations. Here, we present a case of a 10-year-old female PRS patient with the typical features of chronic renal failure and severe myopia, but was unexpectedly discovered camptodactyly of her left middle finger which affects the proximal interphalangeal joint...
October 17, 2017: Gene
https://www.readbyqxmd.com/read/29038743/mature-induced-pluripotent-stem-cell-derived-human-podocytes-reconstitute-kidney-glomerular-capillary-wall-function-on-a-chip
#10
Samira Musah, Akiko Mammoto, Thomas C Ferrante, Sauveur S F Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, James C Weaver, George M Church, Donald E Ingber
An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#11
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but because of a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: To establish an in vitro method for studying differentiation of bipotential gonadal progenitors by using human embryonic stem cells (hESCs) and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28931330/sequential-molecular-changes-and-dynamic-oxidative-stress-in-high-grade-serous-ovarian-carcinogenesis
#12
Hiroshi Kobayashi, Kenji Ogawa, Naoki Kawahara, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada
The mechanism of high-grade serous ovarian cancer (HGSC) development remains elusive. This review outlines recent advances in the understanding of sequential molecular changes associated with the development of HGSC, as well as describes oxidative stress-induced genomic instability and carcinogenesis. This article reviews the English language literature between 2005 and 2017. Clinicopathological features analysis provides a sequential progression of fallopian tubal epithelium to precursor lesions to type 2 HGSC...
October 2017: Free Radical Research
https://www.readbyqxmd.com/read/28918284/new-insights-into-human-female-reproductive-tract-development
#13
Stanley J Robboy, Takeshi Kurita, Laurence Baskin, Gerald R Cunha
We present a detailed review of the embryonic and fetal development of the human female reproductive tract utilizing specimens from the 5th through the 22nd gestational week. Hematoxylin and eosin (H&E) as well as immunohistochemical stains were used to study the development of the human uterine tube, endometrium, myometrium, uterine cervix and vagina. Our study revisits and updates the classical reports of Koff (1933) and Bulmer (1957) and presents new data on development of human vaginal epithelium. Koff proposed that the upper 4/5ths of the vagina is derived from Müllerian epithelium and the lower 1/5th derived from urogenital sinus epithelium, while Bulmer proposed that vaginal epithelium derives solely from urogenital sinus epithelium...
August 11, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28912684/distinct-activities-of-tfap2a-and-tfap2b-in-the-specification-of-gabaergic-interneurons-in-the-developing-cerebellum
#14
Norliyana Zainolabidin, Sandhya P Kamath, Ayesha R Thanawalla, Albert I Chen
GABAergic inhibitory neurons in the cerebellum are subdivided into Purkinje cells and distinct subtypes of interneurons from the same pool of progenitors, but the determinants of this diversification process are not well defined. To explore the transcriptional regulation of the development of cerebellar inhibitory neurons, we examined the role of Tfap2A and Tfap2B in the specification of GABAergic neuronal subtypes in mice. We show that Tfap2A and Tfap2B are expressed in inhibitory precursors during embryonic development and that their expression persists into adulthood...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28875951/effects-of-cyclosporine-a-on-the-development-of-metanephros-in-the-pregnant-balb-c-mice
#15
Yu-Jie Liao, Rong-Shuang Huang, Wei-Jing Lai, Fang Liu, Liang Ma, Yuan-Sheng Xie, Stephen Salerno, Yi Li, Ping Fu
Background: Cyclosporine A (CsA) is a commonly used clinical immunosuppressant. However, CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons, with the effects remaining unknown. In this study, we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice. Methods: Pregnant mice were randomly divided into two groups, and CsA (10 mg·kg(-1)·d(-1)) was subcutaneously injected from gestation day 10...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28873352/immunophenotypic-comparison-of-testicular-sclerosing-sertoli-cell-tumors-and-sertoli-cell-tumors-not-otherwise-specified
#16
Hector Mesa, Chen Zhang, Juan C Manivel, Thomas M Ulbright
Testicular Sertoli cell tumors (SCT) are rare and most fall into the category of SCT-not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), originally described in 1991, comprises a small fraction of SCTs and was considered a specific entity until the 2016 revision of the World Health Organization classification of non-germ cell tumors, where it was classified as a morphologic variant of SCT-NOS. In a recent study, differences in expression of PAX2/PAX8, inhibin, androgen receptor and S100 protein between SCT-NOS and S-SCT were noted in a small number of cases...
September 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/28855599/functional-non-coding-polymorphism-in-an-epha2-promoter-pax2-binding-site-modifies-expression-and-alters-the-mapk-and-akt-pathways
#17
Xiaoyin Ma, Zhiwei Ma, Xiaodong Jiao, J Fielding Hejtmancik
To identify possible genetic variants influencing expression of EPHA2 (Ephrin-receptor Type-A2), a tyrosine kinase receptor that has been shown to be important for lens development and to contribute to both congenital and age related cataract when mutated, the extended promoter region of EPHA2 was screened for variants. SNP rs6603883 lies in a PAX2 binding site in the EPHA2 promoter region. The C (minor) allele decreased EPHA2 transcriptional activity relative to the T allele by reducing the binding affinity of PAX2...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852936/down-regulation-of-pax2-promotes-in-vitro-differentiation-of-podocytes-from-human-cd34-cells
#18
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Podocytes are major kidney cells that help in glomerular filtration and any damage or loss is a major event in the progression of kidney diseases. Understanding podocytes development will help in designing therapeutic strategies against these renal diseases. Therefore, in vitro generation of podocytes from adult hematopoietic CD34(+) stem cells is explored in the present study. Apheretically, isolated human HSCs from peripheral blood showed the presence of CD34 surface glycoprotein through immunocytochemistry (ICC) and flowcytometry...
August 29, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28837644/prickle1-regulates-neurite-outgrowth-of-apical-spiral-ganglion-neurons-but-not-hair-cell-polarity-in-the-murine-cochlea
#19
Tian Yang, Jennifer Kersigo, Shu Wu, Bernd Fritzsch, Alexander G Bassuk
In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC...
2017: PloS One
https://www.readbyqxmd.com/read/28820764/severe-case-of-renal-coloboma-syndrome-in-long-term-follow-up
#20
Lise Sels, Werner Dirven, Koenraad Devriendt, Anita Leys
PURPOSE: To characterize the ocular features of a severe case of renal coloboma syndrome in a long-term follow-up. METHODS: Observational case report over a period of 45 years. Examination under anesthesia at the age of 3 months, repeated ophthalmologic examination (age 7, 14, 25, 45 years), fluorescein and indocyanine green angiography, electroretinography, ocular ultrasound, optical coherence tomography, computed tomography scan orbits, and magnetic resonance imaging of the brain...
August 17, 2017: Retinal Cases & Brief Reports
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