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https://www.readbyqxmd.com/read/28931407/the-emerging-roles-of-phosphatases-in-hedgehog-pathway
#1
REVIEW
Long Zhao, Liguo Wang, Chunli Chi, Wenwen Lan, Ying Su
Hedgehog signaling is evolutionarily conserved and plays a pivotal role in cell fate determination, embryonic development, and tissue renewal. As aberrant Hedgehog signaling is tightly associated with a broad range of human diseases, its activities must be precisely controlled. It has been known that several core components of Hedgehog pathway undergo reversible phosphorylations mediated by protein kinases and phosphatases, which acts as an effective regulatory mechanism to modulate Hedgehog signal activities...
September 20, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28930454/chemical-bypass-of-general-base-catalysis-in-hedgehog-protein-cholesterolysis-using-a-hyper-nucleophilic-substrate
#2
Daniel Ciulla, Michael Jorgensen, Jose-Luis Giner, Brian P Callahan
Proteins in the hedgehog family undergo self-catalyzed endoproteolysis involving nucleophilic attack by a molecule of cholesterol. Recently, a conserved aspartate residue (D303, or D46) of hedgehog was identified as the general base that activates cholesterol during this unusual autoprocessing event; mutation of the catalyzing functional group (D303A) reduces activity by >104 fold. Here we report near total rescue of this ostensibly dead general base mutant by a synthetic substrate, 3ß-hydroperoxycholestane (3HPC) in which the sterol -OH group is replaced by the hyper nucleophilic -OOH group...
September 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28929469/chondrocyte-expansion-is-associated-with-loss-of-primary-cilia-and-disrupted-hedgehog-signalling
#3
C L Thompson, J C Plant, A K Wann, C L Bishop, P Novak, H M Mitchison, P L Beales, J P Chapple, M M Knight
Tissue engineering-based therapies targeting cartilage diseases, such as osteoarthritis, require in vitro expansion of articular chondrocytes. A major obstacle for these therapies is the dedifferentiation and loss of phenotype accompanying chondrocyte expansion. Recent studies suggest that manipulation of hedgehog signalling may be used to promote chondrocyte re-differentiation. Hedgehog signalling requires the primary cilium, a microtubule-based signalling compartment, the integrity of which is linked to the cytoskeleton...
September 20, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28929109/genetic-variants-in-the-hedgehog-interacting-protein-gene-are-associated-with-the-fev1-fvc-ratio-in-southern-han-chinese-subjects-with-chronic-obstructive-pulmonary-disease
#4
Zili Zhang, Jian Wang, Zeguang Zheng, Xindong Chen, Xiansheng Zeng, Yi Zhang, Defu Li, Jiaze Shu, Kai Yang, Ning Lai, Lian Dong, Wenju Lu
BACKGROUND: Convincing evidences have demonstrated the associations between HHIP and FAM13a polymorphisms and COPD in non-Asian populations. Here genetic variants in HHIP and FAM13a were investigated in Southern Han Chinese COPD. METHODS: A case-control study was conducted, including 989 cases and 999 controls. The associations between SNPs genotypes and COPD were performed by a logistic regression model; for SNPs and COPD-related phenotypes such as lung function, COPD severity, pack-year of smoking, and smoking status, a linear regression model was employed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28928250/coexistent-duplication-of-urethra-and-a-refluxing-ectopic-ureter-presenting-as-recurrent-epididymo-orchitis-in-a-child
#5
Ferzine Mohamed, Susan Jehangir
Congenital anomalies of the kidney and urinary tract (CAKUTs) occur in 3-6 per 1000 live births, accounting for most cases of paediatric end-stage kidney disease.(1) However, the molecular basis of CAKUT and anomalies of the external genitalia is poorly understood. We, herein, describe a case with left recurrent epididymo-orchitis with a coexistent urethral duplication and an ectopic ureter with an ipsilateral non-functioning kidney, which is, to the best of our knowledge, the first reported case of its kind...
September 19, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28927025/repurposing-itraconazole-for-the-treatment-of-cancer
#6
Rachel Pounds, Sarah Leonard, Christopher Dawson, Sean Kehoe
The repurposing of drugs is becoming increasingly attractive as it avoids the lengthy process and cost implications associated with bringing a novel drug to market. Itraconazole is a broad-spectrum anti-fungal agent. An emerging body of in vivo, in vitro and clinical evidence have confirmed that it also possesses antineoplastic activities and has a synergistic action when combined with other chemotherapeutic agents. It acts via several mechanisms to prevent tumour growth, including inhibition of the Hedgehog pathway, prevention of angiogenesis, decreased endothelial cell proliferation, cell cycle arrest and induction of auto-phagocytosis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925352/bmps-direct-sensory-interneuron-identity-in-the-developing-spinal-cord-using-signal-specific-not-morphogenic-activities
#7
Madeline G Andrews, Lorenzo M Del Castillo, Eliana Ochoa-Bolton, Ken Yamauchi, Jan Smogorzewski, Samantha J Butler
The Bone Morphogenetic Protein (BMP) family reiteratively signals to direct disparate cellular fates throughout embryogenesis. In the developing dorsal spinal cord, multiple BMPs are required to specify sensory interneurons (INs). Previous studies suggested that the BMPs act as concentration-dependent morphogens to direct IN identity, analogous to the manner in which sonic hedgehog patterns the ventral spinal cord. However, it remains unresolved how multiple BMPs would cooperate to establish a unified morphogen gradient...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28923910/a-transposon-screen-identifies-loss-of-primary-cilia-as-a-mechanism-of-resistance-to-smo-inhibitors
#8
Xuesong Zhao, Ekaterina Pak, Kimberly J Ornell, Maria F Pazyra-Murphy, Ethan L MacKenzie, Emily J Chadwick, Tatyana Ponomaryov, Joseph F Kelleher, Rosalind A Segal
Drug resistance poses a great challenge to targeted cancer therapies. In Hedgehog pathway-dependent cancers, the scope of mechanisms enabling resistance to Smo-inhibitors is not known. Here, we performed a transposon mutagenesis screen in medulloblastoma and identified multiple modes of resistance. Surprisingly, mutations in ciliogenesis genes represent a frequent cause of resistance, and patient datasets indicate that cilia loss constitutes a clinically relevant category of resistance. Conventionally, primary cilia are thought to enable oncogenic Hedgehog signaling...
September 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28921619/alcohol-reduces-arterial-remodeling-by-inhibiting-sonic-hedgehog-stimulated-sca1-progenitor-stem-cell-expansion
#9
Emma Fitzpatrick, Xu Han, Weimin Liu, Eoin Corcoran, Denise Burtenshaw, Maryam Alshamrani, David Morrow, Jay-Christian Helt, Paul A Cahill, Eileen M Redmond
BACKGROUND: Cell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate Ethanol (EtOH) on Sonic Hedgehog (SHh) signaling in regulating possible Sca1(+) progenitor stem cell involvement during pathologic arterial remodeling. METHODS AND RESULTS: Partial ligation or sham-operation of the left carotid artery was performed in transgenic Sca1-eGFP mice gavaged with or without 'daily moderate' EtOH...
September 18, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28916586/actrt1-inhibits-hedgehog-signaling-to-suppress-basal-cell-carcinoma
#10
(no author information available yet)
Coding or enhancer mutations in ACTRT1 reduce its expression to drive basal cell carcinoma.
September 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28915250/multi-layered-mutation-in-hedgehog-related-genes-in-gorlin-syndrome-may-affect-the-phenotype
#11
Shoko Onodera, Akiko Saito, Daigo Hasegawa, Nana Morita, Katsuhito Watanabe, Takeshi Nomura, Takahiko Shibahara, Shinsuke Ohba, Akira Yamaguchi, Toshifumi Azuma
Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28915233/the-utility-of-stem-cells-in-pediatric-urinary-bladder-regeneration
#12
REVIEW
Philip M Iannaccone, Vasil Galat, Matthew I Bury, Yongchao C Ma, Arun K Sharma
Pediatric patients with a neurogenic urinary bladder caused by developmental abnormalities including spina bifida exhibit chronic urological problems. Surgical management in the form of enterocystoplasty is used to enlarge the bladder but is associated with significant clinical complications. Thus, alternative methods to enterocystoplasty have been explored through the incorporation of stem cells with tissue engineering strategies. Within the context of this review, we will examine the use of bone marrow stem cells and induced pluripotent stem cells (iPSCs) as they relate to bladder regeneration at the anatomic and molecular levels...
September 15, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28914635/clinical-genetics-of-craniosynostosis
#13
Andrew O M Wilkie, David Johnson, Steven A Wall
PURPOSE OF REVIEW: When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis. RECENT FINDINGS: Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases...
September 14, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#14
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901252/the-origin-and-identification-of-mesenchymal-stem-cells-in-teeth-from-odontogenic-to-non-odontogenic
#15
Dixin Cui, Hongyu Li, Mian Wan, Yiran Peng, Xin Xu, Xuedong Zhou, Liwei Zheng
Mesenchymal stem cells (MSCs) in teeth have been exploited as vital seed cells for stem cell-based dental medicine. To date, several mesenchymal stem cell populations originated from odontogenic tissue have been isolated and characterized by their expression of MSC surface markers and capacity of multi-lineage differentiation, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP) and so on. However, their identity in vivo remains elusive, which hinders further understanding of their application in stem cell-based tooth regeneration...
September 13, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28900135/hedgehog-signalling-is-required-for-cell-survival-in-drosophila-wing-pouch-cells
#16
Juan Lu, Dan Wang, Jie Shen
An appropriate balance between cell survival and cell death is essential for correct pattern formation in the animal tissues and organs. Previous studies have shown that the short-range signalling molecule Hedgehog (Hh) is required for cell proliferation and pattern formation in the Drosophila central wing discs. Signal transduction by one of the Hh targets, the morphogen Decapentaplegic (Dpp), is required for not only cell proliferation, but also cell survival in the pouch cells. However, Hh function in cell survival and cell death has not been revealed...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899410/nucleolar-and-spindle-associated-protein-1-promotes-the-aggressiveness-of-astrocytoma-by-activating-the-hedgehog-signaling-pathway
#17
Xianqiu Wu, Benke Xu, Chao Yang, Wentao Wang, Dequan Zhong, Zhan Zhao, Longshuang He, Yuanjun Hu, Lili Jiang, Jun Li, Libing Song, Wei Zhang
BACKGROUND: The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. METHODS: The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry to demonstrate the correlation between the NUSAP1 expression and clinicopathological characteristics...
September 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28894158/biophysical-characterisation-of-the-novel-zinc-binding-property-in-suppressor-of-fused
#18
Amira Jabrani, Staëlle Makamte, Emilie Moreau, Yasmine Gharbi, Anne Plessis, Lucia Bruzzone, Matthieu Sanial, Valérie Biou
Suppressor of Fused (SUFU) is a highly conserved protein that acts as a negative regulator of the Hedgehog (HH) signalling pathway, a major determinant of cell differentiation and proliferation. Therefore, SUFU deletion in mammals has devastating effects on embryo development. SUFU is part of a multi-protein cytoplasmic signal-transducing complex. Its partners include the Gli family of transcription factors that function either as repressors, or as transcription activators according to the HH activation state...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893568/endocrine-and-physiological-regulation-of-neutral-fat-storage-in-drosophila
#19
REVIEW
Michael Lehmann
After having revolutionized our understanding of the mechanisms of animal development, Drosophila melanogaster has more recently emerged as an equally valid genetic model in the field of animal metabolism. An increasing number of studies have revealed that many signaling pathways that control metabolism in mammals, including pathways controlled by nutrients (insulin, TOR), steroid hormone, glucagon, and hedgehog, are functionally conserved between mammals and Drosophila. In fact, genetic screens and analyses in Drosophila have identified new players and filled in gaps in the signaling networks that control metabolism...
September 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28892064/a-mouse-model-for-embryonal-tumors-with-multilayered-rosettes-uncovers-the-therapeutic-potential-of-sonic-hedgehog-inhibitors
#20
Julia E Neumann, Annika K Wefers, Sander Lambo, Edoardo Bianchi, Marie Bockstaller, Mario M Dorostkar, Valerie Meister, Pia Schindler, Andrey Korshunov, Katja von Hoff, Johannes Nowak, Monika Warmuth-Metz, Marlon R Schneider, Ingrid Renner-Müller, Daniel J Merk, Mehdi Shakarami, Tanvi Sharma, Lukas Chavez, Rainer Glass, Jennifer A Chan, M Mark Taketo, Philipp Neumann, Marcel Kool, Ulrich Schüller
Embryonal tumors with multilayered rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with a fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh and Wnt signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin...
September 11, 2017: Nature Medicine
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