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https://www.readbyqxmd.com/read/28822119/five-questions-answered-a-review-of-autologous-hematopoietic-stem-cell-transplantation-for-the-treatment-of-multiple-sclerosis
#1
REVIEW
Harold L Atkins, Mark S Freedman
Multiple sclerosis (MS) is thought to be an autoimmune disease targeting the central nervous system leading to demyelination, and axonal and neuronal damage, resulting in progressive disability. More intensive therapies such as immunodepletion with hematopoietic stem-cell rescue are being used at a time prior to patients becoming irreversibly disabled. Over the last 15 years, there has been a shift away from using autologous hematopoietic stem-cell transplants (aHSCT) to treat patients with progressive MS, towards treating those with active inflammation and relapses...
August 18, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28821796/cathepsin-k-knockout-protects-against-cardiac-dysfunction-in-diabetic-mice
#2
Rui Guo, Yinan Hua, Olivia Rogers, Travis E Brown, Jun Ren, Sreejayan Nair
Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca(2+) handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821660/contribution-of-astroglial-cx43-hemichannels-to-the-modulation-of-glutamatergic-currents-by-d-serine-in-the-mouse-prefrontal-cortex
#3
Claire Meunier, Nan Wang, Chenju Yi, Glenn Dallerac, Pascal Ezan, Annette Koulakoff, Luc Leybaert, Christian Giaume
Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine co-agonist of the NMDA receptor at the glycine binding site, can be released by astrocytes in a calcium [Ca(2+)]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821638/fluorescent-probes-for-selective-protein-labeling-in-lysosomes-a-case-of-%C3%AE-galactosidase-a
#4
Cornelius Bohl, Adam Pomorski, Susanne Seemann, Anne-Marie Knospe, Chaonan Zheng, Artur Krężel, Arndt Rolfs, Jan Lukas
Fluorescence-based live-cell imaging (LCI) of lysosomal glycosidases is often hampered by unfavorable pH and redox conditions that reduce fluorescence output. Moreover, most lysosomal glycosidases are low-mass soluble proteins that do not allow for bulky fluorescent protein fusions. We selected α-galactosidase A (GALA) as a model lysosomal glycosidase involved in Anderson-Fabry disease (AFD) for the current LCI approach. Examination of the subcellular localization of AFD-causing mutants can reveal the mechanism underlying cellular trafficking deficits...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821555/p53-non-genotoxic-activation-and-mtorc1-inhibition-lead-to-effective-combination-for-neuroblastoma-therapy
#5
Myrthala Moreno-Smith, Anna Lakoma, Zaowen Chen, Ling Tao, Kathleen A Scorsone, Linda Schild, Kevin Aviles-Padilla, Rana Nikzad, Yankai Zhang, Rikhia Chakraborty, Jan J Molenaar, Sanjeev Vasudevan, Vivien Sheehan, Eugene S Kim, Silke Paust, Jason M Shohet, Eveline Barbieri
mTORC1 inhibitors are promising agents for neuroblastoma therapy, however they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. <br /><br />Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the anti-tumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first and second generation MDM2 inhibitors to reactivate p53...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821541/targeting-mir-423-5p-reverses-exercise-training-induced-hcn4-channel-remodeling-and-sinus-bradycardia
#6
Alicia D'Souza, Charles M Pearman, Yanwen Wang, Shu Nakao, Sunil Jit R Logantha, Charlotte Cox, Hayley J Bennett, Yu Zhang, Anne Berit Johnsen, Nora Linscheid, Pi C Poulsen, Jonathan Elliott, Jessica Coulson, Jamie S McPhee, Abigail C Robertson, Paula A da Costa Martins, Ashraf Kitmitto, Ulrik Wisloff, Elizabeth J Cartwright, Oliver Monfredi, Alicia Lundby, Halina Dobrzynski, Delvac Oceandy, Gwilym M Morris, Mark R Boyett
Rationale: Downregulation of the pacemaking ion channel, HCN4, and the corresponding ionic current, If, underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes and it will be important to understand the underlying processes. Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of micro-RNAs (miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than non-athletes and in all subjects the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes...
August 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28821490/serca-directs-cell-migration-and-branching-across-species-and-germ-layers
#7
Danielle V Bower, Nick Lansdale, Sonia Navarro, Thai V Truong, Dan J Bower, Neil C Featherstone, Marilyn G Connell, Denise Al-Alam, Mark R Frey, Le A Trinh, G Esteban Fernandez, David Warburton, Scott E Fraser, Daimark Bennett, Edwin C Jesudason
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca(2+) reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca(2+) levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca(2+) differential, aborting both cell migration and new branching...
August 17, 2017: Biology Open
https://www.readbyqxmd.com/read/28821460/long-term-effects-of-hydrogen-sulfide-on-the-anabolic-catabolic-balance-of-articular-cartilage-in-vitro
#8
A Vela-Anero, T Hermida-Gomez, L Gato-Calvo, C Vaamonde-García, S Diaz-Prado, R Meijide-Faílde, F J Blanco, E F Burguera
Healthy cartilage maintenance relies on an equilibrium among the anabolic and catabolic processes in chondrocytes. With the onset of osteoarthritis (OA), increased interleukin (IL)-1β levels induce an inhibition of the synthesis of extracellular matrix (ECM) proteins, as well as an increase in proteases. This eventually leads to a predominance of the catabolic phenotype and the progressive loss of articular cartilage. Hydrogen sulfide (H2S) is a small gaseous molecule recognized as the third endogenous gasotransmitter...
August 15, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#9
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28820873/ubiquitin-proteasome-system-rescuing-ebv-latency
#10
Mirella Bucci
No abstract text is available yet for this article.
August 18, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28820818/reply-blood-congestion-can-be-rescued-by-hemodilution-in-a-random-pattern-skin-flap
#11
Koji Kanayama, Takanobu Mashiko, Rintaro Asahi, Ataru Sunaga, Kotaro Yoshimura
No abstract text is available yet for this article.
August 9, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28820811/blood-congestion-can-be-rescued-by-hemodilution-in-a-random-pattern-skin-flap-letter
#12
Sara Di Lorenzo, Giovanni Zabbia, Roberto Pirrello, Bartolo Corradino
No abstract text is available yet for this article.
August 9, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28820333/protease-dead-separase-inhibits-chromosome-segregation-and-rab-11-vesicle-trafficking
#13
Xiaofei Bai, Joshua N Bembenek
Separase cleaves cohesin to allow chromosome segregation. Separase also regulates cortical granule exocytosis and vesicle trafficking during cytokinesis, both of which involve RAB-11. We investigated whether separase regulates exocytosis through a proteolytic or non-proteolytic mechanism. In C. elegans, protease-dead separase (SEP-1(PD)::GFP) is dominant negative. Consistent with its role in cohesin cleavage, SEP-1(PD)::GFP causes chromosome segregation defects. As expected, partial depletion of cohesin rescues this defect, confirming that SEP-1(PD)::GFP acts through a substrate trapping mechanism...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820331/polo-like-kinase-1-plk1-dependent-phosphorylation-of-methylenetetrahydrofolate-reductase-mthfr-regulates-replication-via-histone-methylation
#14
Xueyan Li, Shanshan Nai, Yuehe Ding, Qizhi Geng, Bingtao Zhu, Kai Yu, Wei-Guo Zhu, Meng-Qiu Dong, Xiao-Dong Su, Xingzhi Xu, Jing Li
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the folate cycle and its genetic variations have been associated with various human diseases. Previously we identified that MTHFR is phosphorylated by cyclin-dependent kinase 1 (CDK1) at T34 and MTHFR underlies heterochromatin maintenance marked by H3K9me3 levels. Herein we demonstrate that pT34 creates a binding motif that docks MTHFR to the polo-binding domain (PBD) of polo-like kinase 1 (PLK1), a fundamental kinase that orchestrates many cell cycle events...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820284/bnip3l-nix-mediated-mitophagy-protects-against-ischemic-brain-injury-independent-of-park2
#15
Yang Yuan, Yanrong Zheng, Xiangnan Zhang, Ying Chen, Xiaoli Wu, Jiaying Wu, Zhe Shen, Lei Jiang, Lu Wang, Wei Yang, Jianhong Luo, Zhenghong Qin, Weiwei Hu, Zhong Chen
Cerebral ischemia induces massive mitochondrial damage. These damaged mitochondria are cleared, thus attenuating brain injury, by mitophagy. Here, we identified the involvement of BNIP3L/NIX in cerebral ischemia-reperfusion (I-R)-induced mitophagy. Bnip3l knockout (bnip3l(-/-)) impaired mitophagy and aggravated cerebral I-R injury in mice, which can be rescued by BNIP3L overexpression. The rescuing effects of BNIP3L overexpression can be observed in park2(-/-) mice, which showed mitophagy deficiency after I-R...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819432/silencing-of-hjurp-induces-dysregulation-of-cell-cycle-and-ros-metabolism-in-bladder-cancer-cells-via-ppar%C3%AE-sirt1-feedback-loop
#16
Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Guofeng Qian, Conghua Xie, Han C Dan, Wei Jiang, Min Wu, Chin-Lee Wu, Yu Xiao, Xinghuan Wang
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819043/increased-acetylation-of-microtubules-rescues-human-tau-induced-microtubule-defects-and-neuromuscular-junction-abnormalities-in-drosophila
#17
Chuan-Xi Mao, Xue Wen, Shan Jin, Yong Q Zhang
Tau normally associates with and stabilizes microtubules (MTs), but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we show that inhibition of histone deacetylase 6 (HDAC6), which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression...
August 17, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28818757/expression-of-a-na-h-antiporter-rtnhx1-from-a-recretohalophyte-reaumuria-trigyna-improved-salt-tolerance-of-transgenic-arabidopsis-thaliana
#18
Ningning Li, Xue Wang, Binjie Ma, Chao Du, Linlin Zheng, Yingchun Wang
Reaumuria trigyna is an endangered recretohalophyte and a small xeric shrub that is endemic to the eastern Alxa and western Ordos areas of Inner Mongolia, China. Using transcriptome data, we identified a 1662-bp open reading frame encoding a 553-amino-acid protein corresponding to a Na(+)/H(+) antiporter (RtNHX1) from R. trigyna. RtNHX1 was rapidly up-regulated by NaCl and exogenous abscisic acid treatment and had different tissue-specific expression patterns before and after salt-stress treatment. Overexpression of RtNHX1 enhanced seed germination, biomass accumulation, chlorophyll content, and root elongation in transgenic Arabidopsis plants under salt stress and rescued the salt-sensitive deficiencies of the nhx1 mutant...
July 25, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28817740/influence-of-microtextured-implant-surfaces-on-peri-implantitis-and-its-treatment-a-preclinical-trial
#19
Juan C Rodriguez, Tapan Koticha, Diana L Eubanks, Ivan Rudek, Fred J Molz, Ludovica Chiavaccini, Andrew Claude, Steven Elder, Hom-Lay Wang
PURPOSE: The prevalence of peri-implantitis has increased significantly, forcing clinicians to search for ways to prevent it. Laser-microtextured surfaces promote soft tissue attachment and provide a tight seal around implants. Hence, the aim of this study was to examine the clinical, radiographic, and histologic features of ligature-induced peri-implantitis, as well as the effect of surgical treatment of these induced peri-implantitis lesions on laser-microtextured implants in a controlled animal model...
August 17, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28817668/titanium-biomaterials-with-complex-surfaces-induced-aberrant-peripheral-circadian-rhythms-in-bone-marrow-mesenchymal-stromal-cells
#20
Nathaniel Hassan, Kirstin McCarville, Kenzo Morinaga, Cristiane M Mengatto, Peter Langfelder, Akishige Hokugo, Yu Tahara, Christopher S Colwell, Ichiro Nishimura
Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated...
2017: PloS One
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