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https://www.readbyqxmd.com/read/28423296/eltrombopag-added-to-standard-immunosuppression-for-aplastic-anemia
#1
Danielle M Townsley, Phillip Scheinberg, Thomas Winkler, Ronan Desmond, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Janet Valdez, Jennifer Lotter, Xingmin Feng, Marie Desierto, Harshraj Leuva, Margaret Bevans, Colin Wu, Andre Larochelle, Katherine R Calvo, Cynthia E Dunbar, Neal S Young
Background Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28414301/striatopallidal-dysfunction-underlies-repetitive-behavior-in-shank3-deficient-model-of-autism
#2
Wenting Wang, Chenchen Li, Qian Chen, Marie-Sophie van der Goes, James Hawrot, Annie Y Yao, Xian Gao, Congyi Lu, Ying Zang, Qiangge Zhang, Katherine Lyman, Dongqing Wang, Baolin Guo, Shengxi Wu, Charles R Gerfen, Zhanyan Fu, Guoping Feng
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28403174/exercise-in-vivo-marks-human-myotubes-in-vitro-training-induced-increase-in-lipid-metabolism
#3
Jenny Lund, Arild C Rustan, Nils G Løvsletten, Jonathan M Mudry, Torgrim M Langleite, Yuan Z Feng, Camilla Stensrud, Mari G Brubak, Christian A Drevon, Kåre I Birkeland, Kristoffer J Kolnes, Egil I Johansen, Daniel S Tangen, Hans K Stadheim, Hanne L Gulseth, Anna Krook, Eili T Kase, Jørgen Jensen, G Hege Thoresen
BACKGROUND AND AIMS: Physical activity has preventive as well as therapeutic benefits for overweight subjects. In this study we aimed to examine effects of in vivo exercise on in vitro metabolic adaptations by studying energy metabolism in cultured myotubes isolated from biopsies taken before and after 12 weeks of extensive endurance and strength training, from healthy sedentary normal weight and overweight men. METHODS: Healthy sedentary men, aged 40-62 years, with normal weight (body mass index (BMI) < 25 kg/m2) or overweight (BMI ≥ 25 kg/m2) were included...
2017: PloS One
https://www.readbyqxmd.com/read/28399408/eradication-of-tumors-through-simultaneous-ablation-of-cd276-b7-h3-positive-tumor-cells-and-tumor-vasculature
#4
Steven Seaman, Zhongyu Zhu, Saurabh Saha, Xiaoyan M Zhang, Mi Young Yang, Mary Beth Hilton, Karen Morris, Christopher Szot, Holly Morris, Deborah A Swing, Lino Tessarollo, Sean W Smith, Sylvia Degrado, Dmitry Borkin, Nareshkumar Jain, Julia Scheiermann, Yang Feng, Yanping Wang, Jinyu Li, Dean Welsch, Gary DeCrescenzo, Amit Chaudhary, Enrique Zudaire, Kimberly D Klarmann, Jonathan R Keller, Dimiter S Dimitrov, Brad St Croix
Targeting the tumor vasculature with antibody-drug conjugates (ADCs) is a promising anti-cancer strategy that in order to be realized must overcome several obstacles, including identification of suitable targets and optimal warheads. Here, we demonstrate that the cell-surface protein CD276/B7-H3 is broadly overexpressed by multiple tumor types on both cancer cells and tumor-infiltrating blood vessels, making it a potentially ideal dual-compartment therapeutic target. In preclinical studies CD276 ADCs armed with a conventional MMAE warhead destroyed CD276-positive cancer cells, but were ineffective against tumor vasculature...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28384226/inhibition-of-prenylated-kras-in-a-lipid-environment
#5
Johanna M Jansen, Charles Wartchow, Wolfgang Jahnke, Susan Fong, Tiffany Tsang, Keith Pfister, Tatiana Zavorotinskaya, Dirksen Bussiere, Jan Marie Cheng, Kenneth Crawford, Yumin Dai, Jeffrey Dove, Eric Fang, Yun Feng, Jean-Michel Florent, John Fuller, Alvar D Gossert, Mohammad Hekmat-Nejad, Chrystèle Henry, Julia Klopp, William P Lenahan, Andreas Lingel, Sylvia Ma, Arndt Meyer, Yuji Mishina, Jamie Narberes, Gwynn Pardee, Savithri Ramurthy, Sebastien Rieffel, Darrin Stuart, Sharadha Subramanian, Laura Tandeske, Stephania Widger, Armin Widmer, Aurelie Winterhalter, Isabel Zaror, Stephen Hardy
RAS mutations lead to a constitutively active oncogenic protein that signals through multiple effector pathways. In this chemical biology study, we describe a novel coupled biochemical assay that measures activation of the effector BRAF by prenylated KRASG12V in a lipid-dependent manner. Using this assay, we discovered compounds that block biochemical and cellular functions of KRASG12V with low single-digit micromolar potency. We characterized the structural basis for inhibition using NMR methods and showed that the compounds stabilized the inactive conformation of KRASG12V...
2017: PloS One
https://www.readbyqxmd.com/read/28367502/an-overdetermined-system-of-transform-equations-in-support-of-robust-dce-mri-registration-with-outlier-rejection
#6
Adam Johansson, James Balter, Mary Feng, Yue Cao
Quantitative hepatic perfusion parameters derived by fitting dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of liver to a pharmacokinetic model are prone to errors if the dynamic images are not corrected for respiratory motion by image registration. The contrast-induced intensity variations in pre- and postcontrast phases pose challenges for the accuracy of image registration. We propose an overdetermined system of transformation equations between the image volumes in the DCE-MRI series to achieve robust alignment...
September 2016: Tomography: a Journal for Imaging Research
https://www.readbyqxmd.com/read/28334750/ctc1-mediated-c-strand-fill-in-is-an-essential-step-in-telomere-length-maintenance
#7
Xuyang Feng, Shih-Jui Hsu, Christopher Kasbek, Mary Chaiken, Carolyn M Price
To prevent progressive telomere shortening as a result of conventional DNA replication, new telomeric DNA must be added onto the chromosome end. The de novo DNA synthesis involves elongation of the G-rich strand of the telomere by telomerase. In human cells, the CST complex (CTC1-STN1-TEN1) also functions in telomere replication. CST first aids in duplication of the telomeric dsDNA. Then after telomerase has extended the G-rich strand, CST facilitates fill-in synthesis of the complementary C-strand. Here, we analyze telomere structure after disruption of human CTC1 and demonstrate that functional CST is essential for telomere length maintenance due to its role in mediating C-strand fill-in...
February 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334037/ang1-treatment-reduces-muscle-pathology-and-prevents-a-decline-in-perfusion-in-dmd-mice
#8
Kelly M Gutpell, Nikola Tasevski, Boaz Wong, William Thomas Hrinivich, Feng Su, Jennifer Hadway, Lise Desjardins, Ting-Yim Lee, Lisa Marie Hoffman
Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD...
2017: PloS One
https://www.readbyqxmd.com/read/28331230/dentin-sialoprotein-facilitates-dental-mesenchymal-cell-differentiation-and-dentin-formation
#9
Wentong Li, Lei Chen, Zhuo Chen, Lian Wu, Junsheng Feng, Feng Wang, Lisa Shoff, Xin Li, Kevin J Donly, Mary MacDougall, Shuo Chen
Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its target gene expression. DSP mutations cause dentin genetic diseases. However, mechanisms of DSP in controlling dental mesenchymal cell differentiation are unknown. Using DSP as bait, we screened a protein library from mouse odontoblastic cells and found that DSP is a ligand and binds to cell surface receptor, occludin. Further study identified that the C-terminal DSP domain(aa 363-458) interacts with the occludin extracellular loop 2(aa 194-241)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28306547/synthetic-ct-for-mri-based-liver-stereotactic-body-radiotherapy-treatment-planning
#10
Jeremy S Bredfeldt, Lianli Liu, Mary Feng, Yue Cao, James M Balter
A technique for generating MRI-derived synthetic CT volumes (MRCTs) is demonstrated in support of adaptive liver stereotactic body radiation therapy (SBRT). Under IRB approval, 16 subjects with hepatocellular carcinoma were scanned using a single MR pulse sequence (T1 Dixon). Air-containing voxels were identified by intensity thresholding on T1-weighted, water and fat images. The envelope of the anterior vertebral bodies was segmented from the fat image and fuzzy-C-means (FCM) was used to classify each non-air voxel as mid-density, lower-density, bone, or marrow in the abdomen, with only bone and marrow classified within the vertebral body envelope...
April 21, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28306506/crystal-structure-of-the-minimal-cas9-from-campylobacter-jejuni-reveals-the-molecular-diversity-in-the-crispr-cas9-systems
#11
Mari Yamada, Yuto Watanabe, Jonathan S Gootenberg, Hisato Hirano, F Ann Ran, Takanori Nakane, Ryuichiro Ishitani, Feng Zhang, Hiroshi Nishimasu, Osamu Nureki
The RNA-guided endonuclease Cas9 generates a double-strand break at DNA target sites complementary to the guide RNA and has been harnessed for the development of a variety of new technologies, such as genome editing. Here, we report the crystal structures of Campylobacter jejuni Cas9 (CjCas9), one of the smallest Cas9 orthologs, in complex with an sgRNA and its target DNA. The structures provided insights into a minimal Cas9 scaffold and revealed the remarkable mechanistic diversity of the CRISPR-Cas9 systems...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28270689/dna-methyltransferase-dnmt3a-contributes-to-neuropathic-pain-by-repressing-kcna2-in-primary-afferent-neurons
#12
Jian-Yuan Zhao, Lingli Liang, Xiyao Gu, Zhisong Li, Shaogen Wu, Linlin Sun, Fidelis E Atianjoh, Jian Feng, Kai Mo, Shushan Jia, Brianna Marie Lutz, Alex Bekker, Eric J Nestler, Yuan-Xiang Tao
Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262027/bis-15-crown-5-ether-pillar-5-arene-k-responsive-channels
#13
Wei-Xu Feng, Zhanhu Sun, Yan Zhang, Yves-Marie Legrand, Eddy Petit, Cheng-Yong Su, Mihail Barboiu
An artificial selective K(+) channel is formed from the supramolecular organization on bis(benzo-15-crown-5- ether-ureido)-pillar[5]arene compound. This channel achieves a selectivity of SK(+)/Na(+) = 5 for an initial transport rate of kK(+) = 3.2 × 10(-3) s(-1). The cation-file diffusion occurs via selective macrocyclic-filters anchored on inactive supporting pillar[5]arene relays. The sandwich-type binding geometry of the K(+) cation by two 15-crown-5 moieties sites is a key feature influencing channel efficiency...
March 6, 2017: Organic Letters
https://www.readbyqxmd.com/read/28241136/tirr-regulates-53bp1-by-masking-its-histone-methyl-lysine-binding-function
#14
Pascal Drané, Marie-Eve Brault, Gaofeng Cui, Khyati Meghani, Shweta Chaubey, Alexandre Detappe, Nishita Parnandi, Yizhou He, Xiao-Feng Zheng, Maria Victoria Botuyan, Alkmini Kalousi, William T Yewdell, Christian Münch, J Wade Harper, Jayanta Chaudhuri, Evi Soutoglou, Georges Mer, Dipanjan Chowdhury
P53-binding protein 1 (53BP1) is a multi-functional double-strand break repair protein that is essential for class switch recombination in B lymphocytes and for sensitizing BRCA1-deficient tumours to poly-ADP-ribose polymerase-1 (PARP) inhibitors. Central to all 53BP1 activities is its recruitment to double-strand breaks via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2). Here we identify an uncharacterized protein, Tudor interacting repair regulator (TIRR), that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif...
March 9, 2017: Nature
https://www.readbyqxmd.com/read/28217772/dielectrowetting-manipulation-for-digital-microfluidics-creating-transporting-splitting-and-merging-of-droplets
#15
Hongyao Geng, Jian Feng, Lisa Marie Stabryla, Sung Kwon Cho
Generating, splitting, transporting, and merging droplets are fundamental and critical unit operations for digital (droplet-based) microfluidics. State-of-the-art digital microfluidics performs such operations commonly using electrowetting-on-dielectric (EWOD) in the typical configuration of two parallel channel plates. This paper presents such operations using dielectrowetting (derived from liquid dielectrophoresis), not EWOD, with an array of interdigitated electrodes. The major and unique feature is that the present droplet manipulations are effective for conductive (water with/without surfactant) and non-conductive (propylene carbonate) fluids...
March 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28202755/low-pathogenic-influenza-a-viruses-in-north-american-diving-ducks-contribute-to-the-emergence-of-a-novel-highly-pathogenic-influenza-a-h7n8-virus
#16
Yifei Xu, Andrew M Ramey, Andrew S Bowman, Thomas J DeLiberto, Mary L Killian, Scott Krauss, Jacqueline M Nolting, Mia Kim Torchetti, Andrew B Reeves, Richard J Webby, David E Stallknecht, Xiu-Feng Wan
Introductions of low pathogenic avian influenza (LPAI) viruses of subtypes H5 and H7 into poultry from wild birds have the potential to mutate to highly pathogenic avian influenza (HPAI), but such viruses' origins are often unclear. In January 2016, a novel H7N8 HPAI virus caused an outbreak in turkeys in Indiana, USA. To determine the virus's origin, we sequenced genomes of 441 wild bird-origin influenza A viruses (IAVs) from North America and subjected them to evolutionary analyses. Results showed that the H7N8 LPAI virus most likely circulated among diving ducks in the Mississippi flyway during autumn 2015 and was subsequently introduced to Indiana turkeys, in which it evolved high pathogenicity...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28196607/development-of-a-model-web-based-system-to-support-a-statewide-quality-consortium-in-radiation-oncology
#17
Jean M Moran, Mary Feng, Lisa A Benedetti, Robin Marsh, Kent A Griffith, Martha M Matuszak, Michael Hess, Matthew McMullen, Jennifer H Fisher, Teamour Nurushev, Margaret Grubb, Stephen Gardner, Daniel Nielsen, Reshma Jagsi, James A Hayman, Lori J Pierce
PURPOSE: A database in which patient data are compiled allows analytic opportunities for continuous improvements in treatment quality and comparative effectiveness research. We describe the development of a novel, web-based system that supports the collection of complex radiation treatment planning information from centers that use diverse techniques, software, and hardware for radiation oncology care in a statewide quality collaborative, the Michigan Radiation Oncology Quality Consortium (MROQC)...
October 20, 2016: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28195206/dentin-sialoprotein-is-a-novel-substrate-of-matrix-metalloproteinase-9-in-vitro-and-in-vivo
#18
Guohua Yuan, Lei Chen, Junsheng Feng, Guobin Yang, Qingwen Ni, Xiaoping Xu, Chunyan Wan, Merry Lindsey, Kevin J Donly, Mary MacDougall, Zhi Chen, Shuo Chen
Dentin sialoprotein (DSP) is essential for dentinogenesis and processed into fragments in the odontoblast-like cells and the tooth compartments. Matrix metalloproteinase 9 (MMP9) is expressed in teeth from early embryonic to adult stage. Although MMP9 has been reported to be involved in some physiological and pathological conditions through processing substrates, its role in tooth development and whether DSP is a substrate of MMP9 remain unknown. In this study, the function of MMP9 in the tooth development was examined by observation of Mmp9 knockout (Mmp9-/-) mouse phenotype, and whether DSP is a substrate of MMP9 was explored by in vitro and in vivo experiments...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187864/relation-of-household-income-to-incidence-of-sudden-unexpected-death-in-wake-county-north-carolina
#19
Louisa A Mounsey, Feng-Chang Lin, Irion Pursell, Golsa Joodi, Mary Elizabeth Lewis, Anthony Nwosu, Chani Hodonsky, Ross J Simpson, J Paul Mounsey
The incidence of out-of-hospital sudden unexpected death (OHSUD) in a racially and socioeconomically diverse population has been inadequately studied. We collated all OHSUDs over a 24-month period among 18- to 64-year olds in Wake County, North Carolina, to investigate geographic and socioeconomic disparity in incidence of OHSUD. An electronic query of Wake County Emergency Medical Services (EMS) identified all EMS attended out-of-hospital deaths. After excluding trauma, expected deaths, and deaths occurring in non-free-living subjects, medical records and medical examiner's reports were reviewed by a committee of cardiologists to make the determination of OHSUD...
April 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28179375/quantitative-prediction-of-human-renal-clearance-and-drug-drug-interactions-of-organic-anion-transporter-substrates-using-in-vitro-transport-data
#20
Sumathy Mathialagan, Mary A Piotrowski, David A Tess, Bo Feng, John Litchfiled, Manthena V Varma
Organic anion transporters (OATs) play an important role in the renal secretion of drugs, and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir) and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance to in vivo secretory clearance...
February 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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