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https://www.readbyqxmd.com/read/28640708/medulloblastoma-from-myth-to-molecular
#1
Vijay Ramaswamy, Michael D Taylor
Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640243/in-depth-investigations-of-adolescents-and-adults-with-holoprosencephaly-identify-unique-characteristics
#2
Karin Weiss, Paul Kruszka, Maria J Guillen Sacoto, Yonit A Addissie, Donald W Hadley, Casey K Hadsall, Bethany Stokes, Ping Hu, Erich Roessler, Beth Solomon, Edythe Wiggs, Audrey Thurm, Robert B Hufnagel, Wadih M Zein, Jin S Hahn, Elaine Stashinko, Eric Levey, Debbie Baldwin, Nancy J Clegg, Mauricio R Delgado, Maximilian Muenke
PurposeWith improved medical care, some individuals with holoprosencephaly (HPE) are surviving into adulthood. We investigated the clinical manifestations of adolescents and adults with HPE and explored the underlying molecular causes.MethodsParticipants included 20 subjects 15 years of age and older. Clinical assessments included dysmorphology exams, cognitive testing, swallowing studies, ophthalmic examination, and brain magnetic resonance imaging. Genetic testing included chromosomal microarray, Sanger sequencing for SHH, ZIC2, SIX3, and TGIF, and whole-exome sequencing (WES) of 10 trios...
June 22, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28639704/genome-wide-association-analysis-identifies-potential-regulatory-genes-for-eumelanin-pigmentation-in-chicken-plumage
#3
L Yang, X Du, S Wei, L Gu, N Li, Y Gong, S Li
Plumage color in chicken is determined by the proportion of eumelanin and pheomelanin pigmentation. As the main ingredient in plumage melanin, eumelanin plays a key role in the dark black, brown and grey coloration. However, very few studies have been performed to identify the related genes and mutations on a genome-wide scale. Herein, a resource family consisting of one backcross population and two F2 cross populations between a black roster and Yukou Brown I parent stockbreed was constructed for identification of genes related to eumelanin pigmentation...
June 22, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28637687/inhibition-of-cdk4-6-by-palbociclib-significantly-extends-survival-in-medulloblastoma-patient-derived-xenograft-mouse-models
#4
Michelle L Cook Sangar, Laura A Genovesi, Madison W Nakamoto, Melissa J Davis, Sue E Knoblaugh, Pengxiang Ji, Amanda Millar, Brandon Wainwright, James M Olson
  <p>Bioinformatics analysis followed by in vivo studies in patient-derived xenograft models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly Group 3 MYC-amplified tumors which have the worst clinical prognosis.</p> <br />Experimental Design: <p>A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets.  The top hit from this analysis was validated in vivo using patient-derived xenograft models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#5
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28633965/phosphoproteome-analysis-reveals-a-critical-role-for-hedgehog-signalling-in-osteoblast-morphological-transitions
#6
Ariane Marumoto, Renato Milani, Rodrigo A da Silva, Célio Junior da Costa Fernandes, José Mauro Granjeiro, Carmen V Ferreira, Maikel P Peppelenbosch, Willian F Zambuzzi
The reciprocal and adaptive interactions between cells and substrates governing morphological transitions in the osteoblast compartment remain largely obscure. Here we show that osteoblast cultured in basement membrane matrix (Matrigel™) exhibits significant morphological changes after ten days of culture, and we decided to exploit this situation to investigate the molecular mechanisms responsible for guiding osteoblast morphological transitions. As almost all aspects of cellular physiology are under control of kinases, we generated more or less comprehensive cellular kinome profiles employing PepChip peptide arrays that contain over 1000 consensus substrates of kinase peptide...
June 17, 2017: Bone
https://www.readbyqxmd.com/read/28633908/dynamics-of-the-cell-division-orientation-of-granule-cell-precursors-during-cerebellar-development
#7
Satoshi Miyashita, Toma Adachi, Mariko Yamashita, Takayuki Sota, Mikio Hoshino
The cerebellar granule cell (GC) system provides a good model for studying neuronal development. In the external granule layer (EGL), granule cell precursors (GCPs) rapidly and continuously divide to produce numerous GCs as well as GCPs. In some brain regions, the orientation of cell division affects daughter cell fate, thus the direction of GCP division is related to whether it produces a GCP or a GC. Therefore, we tried to characterize the orientation of GCP division from embryonic to postnatal stages and to identify an environmental cue that regulates the orientation...
June 17, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28631844/sonic-hedgehog-wnt-and-brain-derived-neurotrophic-factor-cell-signaling-pathway-crosstalk-potential-therapy-for-depression
#8
REVIEW
Mohd Tayyab, Mehdi H Shahi, Shirin Farheen, Mubeena P M Mariyath, Nabeela Khanam, Javier S Castresana, M Mobarak Hossain
There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#9
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
Transcriptional output of the Sonic hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1-3, which undergo extensive post-translational modifications, including ubiquitination and SUMOylation. Here, we report that sentrin-specific peptidase SENP1 is the specific de-SUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues, and SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28627590/activation-of-sonic-hedgehog-signal-by-purmorphamine-in-a-mouse-model-of-parkinson-s-disease-protects-dopaminergic-neurons-and-attenuates-inflammatory-response-by-mediating-pi3k-akt-signaling-pathway
#10
Shuai Shao, Guang-Liang Wang, Cespuglio Raymond, Xue-Hua Deng, Xiao-Lan Zhu, Di Wang, Le-Peng Hong
In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626955/expression-profile-of-urothelial-transcription-factors-in-bladder-biopsies-with-interstitial-cystitis
#11
Kanya Kaga, Ken-Ichi Inoue, Mayuko Kaga, Tomohiko Ichikawa, Tomonori Yamanishi
OBJECTIVES: To characterize interstitial cystitis pathology based on the expression profile of urothelial tissue-specific master transcription factors. METHODS: Bladder carcinoma cell lines derived from the urothelial stem cells (epithelial or mesenchymal) were used to identify candidate urothelial master transcription factors. Gene expression was measured with quantitative reverse transcription polymerase chain reaction. From the initial screening of 170 transcription factors (human homologs of Drosophila segmentation genes and known master transcription factors from a database), 28 transcription factors were selected...
June 18, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#12
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28620819/cellular-growth-and-tube-formation-of-htr8-svneo-trophoblast-effects-of-exogenously-added-fatty-acid-binding-protein-4-and-its-inhibitor
#13
Sanjay Basak, Arnab Sarkar, Santosh Mathapati, Asim K Duttaroy
Adequate placental angiogenesis is critical for the establishment of the placental circulation and thus for normal feto-placental growth and development. Fatty acid-binding protein-4 (FABP4) plays a pro-angiogenic role in endothelial cells; however, very little information is available in placental first trimester trophoblast cells. Here we report that exogenously added FABP4 (exo-FABP4) stimulated tube formation (as a measure of in vitro angiogenesis) in HTR8/SVneo trophoblastic cells. HTR-8/SVneo cells were incubated in the presence of exogenously added FABP4 at different concentrations and time points...
June 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28619821/convergence-of-signaling-pathways-underlying-habenular-formation-and-axonal-outgrowth
#14
Sara Roberson, Marnie E Halpern
The habenular nuclei are a conserved integrating center in the vertebrate epithalamus where they modulate diverse behaviors. Despite their importance, our understanding of habenular development is incomplete. Time-lapse imaging and fate mapping demonstrate that the dorsal habenulae (dHb) of zebrafish are derived from dbx1b-expressing (dbx1b(+)) progenitors, which transition into cxcr4b-expressing neuronal precursors. The precursors give rise to differentiated neurons whose axons innervate the midbrain interpeduncular nucleus (IPN)...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28615294/pituitary-stem-cell-regulation-who-is-pulling-the-strings
#15
Benoit Cox, Heleen Roose, Annelies Vennekens, Hugo Vankelecom
The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury, and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory...
June 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28607372/enhanced-derivation-of-human-pluripotent-stem-cell-derived-cortical-glutamatergic-neurons-by-a-small-molecule
#16
Shi-Ying Cao, Yao Hu, Cheng Chen, Fang Yuan, Min Xu, Qi Li, Kai-Heng Fang, Yaoyu Chen, Yan Liu
Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28603898/getting-to-the-root-of-scales-feather-and-hair-as-deep-as-odontodes
#17
Danielle Dhouailly, Pascal Godefroit, Thomas Martin, Stefan Nonchev, Flavien Caraguel, Olav Oftedal
While every jawed vertebrate, or its recent ancestor, possesses teeth, skin appendages are characteristic of the living clades: skin denticles (odontodes) in chondrichthyians, dermal scales in teleosts, ducted multicellular glands in amphibians, epidermal scales in squamates, feathers in birds, and hair-gland complexes in mammals, all of them showing a dense periodic patterning. While the odontode origin of teleost scales is generally accepted, the origin of both feather and hair is still debated. They appear long before mammals and birds, at least in Jurassic in mammaliaforms and in ornithodires (pterosaurs and dinosaurs), and are contemporary to scales of early squamates...
June 11, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28600817/il17a-dependent-asymmetric-stem-cell-divisions-are-increased-in-human-psoriasis-a-mechanism-underlying-benign-hyperproliferation
#18
Alexandra Charruyer, Stephen Fong, Giselle Vitcov, Samuel Sklar, Leah Tabernik, Monica Taneja, Melinda Caputo, Catherine Soeung, Lili Yue, Yoshi Uchida, Sarah T Arron, Karen Horton, Robert Foster, Shigetoshi Sano, Jeffrey North, Ruby Ghadially
The balance between asymmetric and symmetric stem cell (SC) divisions is key to tissue homeostasis and dysregulation of this balance has been shown in cancers. We hypothesized that the balance between asymmetric SC divisions (ACDs) and symmetric cell divisions (SCDs) would be dysregulated in the benign hyperproliferation of psoriasis. We found that, whereas SCDs were increased in squamous cell carcinoma (SCC) (human and murine), ACDs were increased in the benign hyperproliferation of psoriasis (human and murine)...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600143/involvement-of-pi3k-akt-pathway-in-the-inhibition-of-hepatocarcinoma-cell-invasion-and-metastasis-induced-by-sash1-through-downregulating-shh-gli1-signaling
#19
Changyu Sun, Zhihao Zhang, Ping He, Yan Zhou, Xuhua Xie
The SASH1 gene is discovered as a tumor suppressor recently. However, the molecular mechanisms of SASH1 in hepatocarcinoma (HCC) remain unclear. In present studies, we investigated the molecular mechanisms of SASH1 on cell invasion and metastasis of hepatocarcinoma in vivo and in vitro. In this study, SASH1 overexpression HCC cell lines were treated with purmorphamine (0, 0.5, 1, 2μmol/l). Western blot and qRT-PCR were used to examine the related gene expression of EMT markers and the Shh-Gli1 and PI3K/Akt-dependent pathway...
June 7, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28598258/the-epidemiology-of-supernumerary-teeth-and-the-associated-molecular-mechanism
#20
Xi Lu, Fang Yu, Junjun Liu, Wenping Cai, Yumei Zhao, Shouliang Zhao, Shangfeng Liu
Supernumerary teeth are common clinical dental anomalies. Although various studies have provided abundant information regarding genes and signalling pathways involved in tooth morphogenesis, which include Wnt, FGF, BMP, and Shh, the molecular mechanism of tooth formation, especially for supernumerary teeth, is still unclear. In the population, some cases of supernumerary teeth are sporadic, while others are syndrome-related with familial hereditary. The prompt and accurate diagnosis of syndrome related supernumerary teeth is quite important for some distinctive disorders...
June 9, 2017: Organogenesis
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