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https://www.readbyqxmd.com/read/29050204/irreversible-growth-plate-fusions-in-children-with-medulloblastoma-treated-with-a-targeted-hedgehog-pathway-inhibitor
#1
Giles W Robinson, Sue C Kaste, Wassim Chemaitilly, Daniel C Bowers, Stephen Laughton, Amy Smith, Nicholas G Gottardo, Sonia Partap, Anne Bendel, Karen D Wright, Brent A Orr, William C Warner, Arzu Onar-Thomas, Amar Gajjar
The permanent defects in bone growth observed in preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated in early phase clinical studies of vismodegib in children. Consequently, vismodegib advanced into pediatric trials for malignancies suspected of being driven by aberrant activation of the Hh pathway. In one multicenter phase II trial, vismodegib was added to the therapy regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we report on 3 children (2 on trial and one off trial) treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044603/comorbid-masticatory-impairment-delays-recovery-from-acute-cerebral-ischemia-and-locomotor-hypoactivity-after-subarachnoid-hemorrhage-in-mice
#2
Ikuho Kojima, Tatsushi Mutoh, Kazumasu Sasaki, Yasuko Tatewaki, Yasuyuki Taki, Tatsuya Ishikawa
Tooth loss and related changes in the functionality may lead to worse outcome of stroke patients, but the link involved in this pathway remains unclear. This study aimed to determine the effect of comorbid masticatory impairment on acute cerebral ischemia and neurobehavioral outcome after experimental subarachnoid hemorrhage (SAH). Thirty C57BL/6 mice with (molar-less) or without (control) prior treatment of cutting off the upper molars (separated by at least one week), were subjected to SAH by endovascular perforation...
October 17, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29044104/mining-drives-extensive-deforestation-in-the-brazilian-amazon
#3
Laura J Sonter, Diego Herrera, Damian J Barrett, Gillian L Galford, Chris J Moran, Britaldo S Soares-Filho
Mining poses significant and potentially underestimated risks to tropical forests worldwide. In Brazil's Amazon, mining drives deforestation far beyond operational lease boundaries, yet the full extent of these impacts is unknown and thus neglected in environmental licensing. Here we quantify mining-induced deforestation and investigate the aspects of mining operations, which most likely contribute. We find mining significantly increased Amazon forest loss up to 70 km beyond mining lease boundaries, causing 11,670 km(2) of deforestation between 2005 and 2015...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/29043142/costimulation-pathway-blockade-in-kidney-transplant-recipients-with-de-novo-rheumatoid-arthritis
#4
Mohamed Sheta, Samy Riad, Udayakumar Deepak, Naim Issa, Mark Birkenbach, Hassan N Ibrahim, Aleksandra Kukla
The best approach to treatment of de-novo rheumatoid arthritis in solid organ transplant recipients on typical immunosuppression is not well established. The use of biologics targeting specific cell types, cytokines, and immunological pathways has been gaining interest in the treatment of both, auto- and alloimmunity. We present a case of de-novo rheumatoid arthritis in a kidney transplant recipient 10 years post-transplant while receiving cyclosporine, mycophenolate mofetil, and also prednisone. Initial presentation included features of polymyalgia rheumatica and nephrotic range proteinuria...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29042811/optical-inactivation-of-the-anterior-cingulate-cortex-modulate-descending-pain-pathway-in-a-rat-model-of-trigeminal-neuropathic-pain-created-via-chronic-constriction-injury-of-the-infraorbital-nerve
#5
Hyeong Cheol Moon, Won Ik Heo, Yon Ji Kim, Daae Lee, So Yoon Won, Hong Rae Kim, Seung Man Ha, Youn Joo Lee, Young Seok Park
PURPOSE: The anterior cingulate cortex (ACC) plays a critical role in the initiation, development, and maintenance of neuropathic pain. Recently, the effects of optical stimulation on pain have been investigated, but the therapeutic effects of optical stimulation on trigeminal neuralgia (TN) have not been clearly shown. Here, we investigated the effects of optical inhibition of the ACC on TN lesions to determine whether the alleviation of pain affects behavior performance and thalamic neuron signaling...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29042286/protein-kinase-and-lipase-inhibitors-of-inositide-metabolism-deplete-ip7-indirectly-in-pancreatic-%C3%AE-cells-off-target-effects-on-cellular-bioenergetics-and-direct-effects-on-ip6k-activity
#6
Subu Surendran Rajasekaran, Christopher Illies, Stephen B Shears, Huanchen Wang, Thais S Ayala, Joilson O Martins, Elisabetta Daré, Per-Olof Berggren, Christopher J Barker
Inositol pyrophosphates have emerged as important regulators of many critical cellular processes from vesicle trafficking and cytoskeletal rearrangement to telomere length regulation and apoptosis. We have previously demonstrated that 5-di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic β-cells and is important for insulin exocytosis. To better understand IP7 regulation in β-cells, we used an insulin secreting cell line, HIT-T15, to screen a number of different pharmacological inhibitors of inositide metabolism for their impact on cellular IP7...
October 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29041414/pump-induced-lasing-suppression-in-yb-er-doped-microlasers
#7
Fuchuan Lei, Yong Yang, Jonathan M Ward, Síle Nic Chormaic
A pump source is one of the essential prerequisites in order to achieve lasing in a system, and, in most cases, a stronger pump leads to higher laser power at the output. However, this behavior may be suppressed if two pump beams are used. In this work, we show that lasing around the 1600 nm band can be suppressed completely if two pumps, at wavelengths of 980 nm and 1550 nm, are applied simultaneously to an Yb:Er-doped microlaser, whereas it can be revived by switching one of them off. This phenomenon can be explained by assuming that the presence of one pump (980 nm) changes the role of the other pump (1550 nm); more specifically, the 1550 nm pump starts to consume the population inversion instead of increasing it when the 980 nm pump power exceeds a certain value...
October 2, 2017: Optics Express
https://www.readbyqxmd.com/read/29040496/changes-in-platelet-bax-levels-contribute-to-impaired-platelet-response-to-thrombin-after-cardiopulmonary-bypass-prospective-observational-clinical-and-laboratory-investigations
#8
M Murase, Y Nakayama, D I Sessler, N Mukai, S Ogawa, Y Nakajima
Background: Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery (n=20 each)...
October 10, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29038542/store-operated-ca-2-entry-facilitates-the-lipopolysaccharide-induced-cyclooxygenase-2-expression-in-gastric-cancer-cells
#9
Jhen-Hong Wong, Kuo-Hao Ho, Sean Nam, Wen-Li Hsu, Chia-Hsien Lin, Che-Mai Chang, Jaw-Yuan Wang, Wei-Chiao Chang
Helicobacter pylori has been identified as one of the major causes of chronic gastritis, gastric and duodenal ulcers, and gastric cancer. Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria, and H. pylori LPS might play an exclusively important role in activating inflammatory pathways in monocytes and macrophages. To study the role of LPS in the underlying mechanism of inflammatory responses, we established an in vitro model using the human AGS gastric cancer cell line...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29036751/-diagnosis-and-management-of-vestibular-schwannomas-an-interdisciplinary-challenge
#10
Steffen Rosahl, Christopher Bohr, Michael Lell, Klaus Hamm, Heinrich Iro
Vestibular schwannomas expand slowly in the internal auditory canal, in the cerebellopontine angle, inside the cochlear and the labyrinth. Larger tumors can displace and compress the brainstem. With an annual incidence of 1:100 000 vestibular schwannoma represent 6-7% of all intracranial tumors. In the cerebellopontine angle they are by far the most neoplasm with 90% of all lesions located in this region. Magnetic resonance imaging (MRI), audiometry, and vestibular diagnostics are the mainstays of the clinical workup for patients harboring tumors...
April 2017: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/29035735/transcriptome-profiling-identifies-genes-pathways-associated-with-experimental-resistance-to-paromomycin-in-leishmania-donovani
#11
Aditya Verma, Vasundhra Bhandari, Deepak Kumar Deep, Shyam Sundar, Jean Claude Dujardin, Ruchi Singh, Poonam Salotra
Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage...
October 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29035005/living-supramolecular-polymerization-of-a-perylene-bisimide-dye-into-fluorescent-j-aggregates
#12
Wolfgang Wagner, Marius Wehner, Vladimir Stepanenko, Soichiro Ogi, Frank Würthner
Self-assembly of a new, in bay-position 1,7- dimethoxy-substituted perylene bisimide (PBI) organogelator affords non-fluorescent H-aggregates at fast cooling rates and fluorescent J-aggregates at slow cooling rates. Under properly adjusted conditions the kinetically trapped "off-pathway" H-aggregates transform into the thermodynamically favored J-aggregates, a process that can be accelerated by the addition of J-aggregate seeds. Spectroscopic studies revealed a subtle interplay of pi-pi interactions and intra- and intermolecular hydrogen bonding for monomeric, H- and J-aggregated PBIs...
October 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29034085/amp-activated-protein-kinase-not-just-an-energy-sensor
#13
REVIEW
David Grahame Hardie, Sheng-Cai Lin
Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy...
2017: F1000Research
https://www.readbyqxmd.com/read/29033800/stimulation-of-cortico-subthalamic-projections-amplifies-resting-motor-circuit-activity-and-leads-to-increased-locomotion-in-dopamine-depleted-mice
#14
Teresa H Sanders
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in patients with Parkinson's disease (PD). STN-DBS enables similar improved motor function, including increased movement speed (reduced bradykinesia), in the 6-OHDA dopamine-depletion mouse model of PD. Previous analyses of electrophysiological recordings from STN and motor cortex (M1) have explored signaling changes that correspond to PD and amelioration of PD symptoms. The most common results show an increase in beta frequency power during 'off' states and a reduction in beta during 'on' states...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29032247/specifications-of-targeting-heterochromatin-modifications-in-plants
#15
REVIEW
Jered M Wendte, Robert J Schmitz
Plants encode a diverse repertoire of DNA methyltransferases that have specialized to target cytosines for methylation in specific sequence contexts. These include the de novo methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which methylates cytosines in all sequence contexts through an RNA guided process, the CHROMOMETHYLASES (CMTs), which methylate CHH and CHG cytosines (where H is A, T, or C), and the maintenance methyltransferase, METHYLTRANSFERASE 1 (MET1), which maintains methylation of symmetrical CG contexts...
October 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29029395/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#16
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028415/crispr-cas9-mediated-noncoding-rna-editing-in-human-cancers
#17
Jie Yang, Xiaodan Meng, Jinchang Pan, Nan Jiang, Chengwei Zhou, Zhenhua Wu, Zhaohui Gong
Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system...
October 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/29020946/the-transcriptome-of-the-developing-grain-a-resource-for-understanding-seed-development-and-the-molecular-control-of-the-functional-and-nutritional-properties-of-wheat
#18
Parimalan Rangan, Agnelo Furtado, Robert J Henry
BACKGROUND: Wheat is one of the three major cereals that have been domesticated to feed human populations. The composition of the wheat grain determines the functional properties of wheat including milling efficiency, bread making, and nutritional value. Transcriptome analysis of the developing wheat grain provides key insights into the molecular basis for grain development and quality. RESULTS: The transcriptome of 35 genotypes was analysed by RNA-Seq at two development stages (14 and 30 days-post-anthesis, dpa) corresponding to the mid stage of development (stage Z75) and the almost mature seed (stage Z85)...
October 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29020041/how-will-climate-change-pathways-and-mitigation-options-alter-incidence-of-vector-borne-diseases-a-framework-for-leishmaniasis-in-south-and-meso-america
#19
Bethan V Purse, Dario Masante, Nicholas Golding, David Pigott, John C Day, Sergio Ibañez-Bernal, Melanie Kolb, Laurence Jones
The enormous global burden of vector-borne diseases disproportionately affects poor people in tropical, developing countries. Changes in vector-borne disease impacts are often linked to human modification of ecosystems as well as climate change. For tropical ecosystems, the health impacts of future environmental and developmental policy depend on how vector-borne disease risks trade off against other ecosystem services across heterogeneous landscapes. By linking future socio-economic and climate change pathways to dynamic land use models, this study is amongst the first to analyse and project impacts of both land use and climate change on continental-scale patterns in vector-borne diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28993468/a-ragulator-borc-interaction-controls-lysosome-positioning-in-response-to-amino-acid-availability
#20
Jing Pu, Tal Keren-Kaplan, Juan S Bonifacino
Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood...
October 9, 2017: Journal of Cell Biology
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