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https://www.readbyqxmd.com/read/28822103/current-progress-in-innovative-engineered-antibodies
#1
REVIEW
William R Strohl
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year...
August 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28822027/impact-of-orientation-and-flexibility-of-peptide-linkers-on-t-maritima-lipase-tm1350-displayed-on-bacillus-subtilis-spores-surface-using-cotb-as-fusion-partner
#2
Jawad Ullah, Huayou Chen, Ake Vastermark, Jinru Jia, Bangguo Wu, Zhong Ni, Yilin Le, Hongcheng Wang
Fusion protein construction often requires peptide linkers for prolonged conformation, extended stability and enzyme activity. In this study a series of fusion between Thermotoga maritima lipase Tm1350 and Bacillus subtillis coat protein CotB, comprising of several peptide linkers, with different length, flexibility and orientations were constructed. Effects of temperature, pH and chemicals were examined, on the activity of displayed enzyme. The fusion protein with longer flexible linkers L9 [(GGGGS)4] and L7 (GGGGS-GGGGS-EAAAK-EAAAK-GGGGS-GGGGS) possess 1...
August 18, 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#3
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28821793/molecular-mechanisms-of-atlastin-mediated-er-membrane-fusion-revealed-by-a-fret-based-single-vesicle-fusion-assay
#4
Kyung Tae Kim, Yeojin Moon, Yunsu Jang, Kang Taek Lee, Changwook Lee, Youngsoo Jun, Sanghwa Lee
Homotypic fusion of endoplasmic reticulum membranes is driven by atlastin GTPases; however, the underlying mechanism remains largely unknown. Here, using a FRET-based single-vesicle fusion assay with liposomes bearing the yeast atlastin Sey1p, we investigated the molecular mechanisms of atlastin-mediated membrane tethering and fusion. Although Sey1p-bearing proteoliposomes frequently underwent membrane tethering in a GTP hydrolysis-dependent manner as reported in studies using bulk assays, only a small fraction of the tethered liposomes proceeded to fusion...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821767/identification-of-candidate-genes-for-devil-facial-tumour-disease-tumourigenesis
#5
Robyn L Taylor, Yiru Zhang, Jennifer P Schöning, Janine E Deakin
Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821709/assessment-of-the-announced-north-korean-nuclear-test-using-long-range-atmospheric-transport-and-dispersion-modelling
#6
Pieter De Meutter, Johan Camps, Andy Delcloo, Piet Termonia
On 6 January 2016, the Democratic People's Republic of Korea announced to have conducted its fourth nuclear test. Analysis of the corresponding seismic waves from the Punggye-ri nuclear test site showed indeed that an underground man-made explosion took place, although the nuclear origin of the explosion needs confirmation. Seven weeks after the announced nuclear test, radioactive xenon was observed in Japan by a noble gas measurement station of the International Monitoring System. In this paper, atmospheric transport modelling is used to show that the measured radioactive xenon is compatible with a delayed release from the Punggye-ri nuclear test site...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821673/unc-18-and-tomosyn-antagonistically-control-synaptic-vesicle-priming-downstream-of-unc-13-in-c-elegans
#7
Seungmee Park, Na-Ryum Bin, Bin Yu, Raymond Wong, Ewa Sitarska, Kyoko Sugita, Ke Ma, Junjie Xu, Chi-Wei Tien, Arash Algouneh, Ekaterina Turlova, Siyan Wang, Pranay Siriya, Waleed Shahid, Lorraine Kalia, Zhong-Ping Feng, Philippe P Monnier, Hong-Shuo Sun, Mei Zhen, Shangbang Gao, Josep Rizo, Shuzo Sugita
Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examined how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in C...
August 8, 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
#8
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/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#9
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821551/coordinated-regulation-of-the-eii-man-and-frurki-operons-of-streptococcus-mutans-by-global-and-fructose-specific-pathways
#10
Lin Zeng, Brinta Chakraborty, Tanaz Farivar, Robert A Burne
The glucose/mannose-PTS permease EII(Man) encoded by manLMN in the dental caries pathogen Streptococcus mutans has a dominant influence on sugar-specific, CcpA-independent catabolite repression (CR). Mutations in manL affect energy metabolism and virulence-associated traits, including biofilm formation, acid tolerance and competence. Using promoter:reporter fusions, expression of the manLMN and the fruRKI operons, encoding a transcriptional regulator, a fructose-1-P kinase and a fructose-PTS permease EII(Fru), respectively, was monitored in response to carbohydrate source and in mutants lacking CcpA, FruR, and components of EII(Man) Expression of genes for EII(Man) and EII(Fru) was directly regulated by CcpA and CR, as evinced by in vivo and in vitro methods...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28821444/circumferential-fusion-a-comparative-analysis-between-anterior-lumbar-interbody-fusion-with-posterior-pedicle-screw-fixation-and-transforaminal-lumbar-interbody-fusion-for-l5-s1-isthmic-spondylolisthesis
#11
Erik Y Tye, Joseph E Tanenbaum, Andrea S Alonso, Roy Xiao, Michael P Steinmetz, Thomas E Mroz, Jason W Savage
BACKGROUND CONTEXT: Transforaminal lumbar interbody fusion (TLIF) or anterior lumbar interbody fusion with percutaneous pedicle screws (ALIFPS) offer significantly higher radiographic fusion rates than other fusion techniques for L5-S1 isthmic spondylolisthesis (IS). As it stands, there is a relative paucity of comparative data of the two techniques. PURPOSE: To define the clinical, radiographic, and financial differences between TLIF and ALIFPS for L5-S1 IS. STUDY DESIGN/SETTING: A retrospective cohort study conducted at a single-tertiary care center...
August 15, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28821194/primary-benign-and-malignant-thyroid-neoplasms-with-signet-ring-cells-cytologic-histologic-and-molecular-features
#12
Nada A Farhat, Ayse M Onenerk, Jeffrey F Krane, Dora Dias-Santagata, Peter M Sadow, William C Faquin
Objectives: Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs. Methods: A search was performed of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28820949/association-between-patient-factors-and-outcome-of-synthetic-cartilage-implant-hemiarthroplasty-vs-first-metatarsophalangeal-joint-arthrodesis-in-advanced-hallux-rigidus
#13
Andy Goldberg, Dishan Singh, Mark Glazebrook, Chris M Blundell, Gwyneth De Vries, Ian L D Le, Dominic Nielsen, M Elizabeth Pedersen, Anthony Sakellariou, Matthew Solan, Alastair S E Younger, Timothy R Daniels, Judith F Baumhauer
BACKGROUND: We evaluated data from a clinical trial of first metatarsophalangeal joint (MTPJ1) implant hemiarthroplasty and arthrodesis to determine the association between patient factors and clinical outcomes. METHODS: Patients ≥18 years with hallux rigidus grade 2, 3, or 4 were treated with synthetic cartilage implant MTPJ1 hemiarthroplasty or arthrodesis. Pain visual analog scale (VAS), Foot and Ankle Ability Measure (FAAM) sports and activities of daily living (ADL) scores, and Short Form-36 Physical Function (SF-36 PF) subscore were obtained preoperatively, and at 2, 6, 12, 24, 52, and 104 weeks postoperatively...
August 1, 2017: Foot & Ankle International
https://www.readbyqxmd.com/read/28820900/secy-seca-fusion-protein-retains-the-ability-to-mediate-protein-transport
#14
Yasunori Sugano, Arata Furukawa, Osamu Nureki, Yoshiki Tanaka, Tomoya Tsukazaki
In bacteria, the membrane protein complex SecY/E/G and SecA ATPase are essential for protein translocation. About 30% of newly synthesized proteins in the cytosol are targeted to and translocated across the cytoplasmic membrane by the Sec factors. Although a number of single-molecule analyses and structural studies, including the crystal structure of SecYEG complexed with SecA, have been published, the underlying molecular mechanisms and the functional oligomer states remain elusive. In this study, we constructed a fusion protein SecY-SecA, which induces the formation of the SecY-A/SecE/SecG complex (SecYAEG), to enable investigation of the molecular mechanisms by advanced single-molecule analyses...
2017: PloS One
https://www.readbyqxmd.com/read/28820890/history-based-forward-and-feedback-mechanism-in-cooperative-spectrum-sensing-including-malicious-users-in-cognitive-radio-network
#15
Noor Gul, Ijaz Mansoor Qureshi, Adnan Omar, Atif Elahi, Sajjad Khan
In cognitive radio communication, spectrum sensing plays a vital role in sensing the existence of the primary user (PU). The sensing performance is badly affected by fading and shadowing in case of single secondary user(SU). To overcome this issue, cooperative spectrum sensing (CSS) is proposed. Although the reliability of the system is improved with cooperation but existence of malicious user (MU) in the CSS deteriorates the performance. In this work, we consider the Kullback-Leibler (KL) divergence method for minimizing spectrum sensing data falsification (SSDF) attack...
2017: PloS One
https://www.readbyqxmd.com/read/28820363/incidence-of-perioperative-medical-complications-and-mortality-among-elderly-patients-undergoing-surgery-for-spinal-deformity-analysis-of-3519-patients
#16
Amit Jain, Hamid Hassanzadeh, Varun Puvanesarajah, Eric O Klineberg, Daniel M Sciubba, Michael P Kelly, D Kojo Hamilton, Virginie Lafage, Aaron J Buckland, Peter G Passias, Themistocles S Protopsaltis, Renaud Lafage, Justin S Smith, Christopher I Shaffrey, Khaled M Kebaish
OBJECTIVE Using 2 complication-reporting methods, the authors investigated the incidence of major medical complications and mortality in elderly patients after surgery for adult spinal deformity (ASD) during a 2-year follow-up period. METHODS The authors queried a multicenter, prospective, surgeon-maintained database (SMD) to identify patients 65 years or older who underwent surgical correction of ASD from 2008 through 2014 and had a minimum 2 years of follow-up (n = 153). They also queried a Centers for Medicare & Medicaid Services claims database (MCD) for patients 65 years or older who underwent fusion of 8 or more vertebral levels from 2005 through 2012 (n = 3366)...
August 18, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28820234/halide-welding-for-silver-nanowires-network-electrode
#17
Hyungseok Kang, Yeon Tae Kim, Siuk Cheon, Gi-Ra Yi, Jeong Ho Cho
We developed a method of chemically welding silver nanowires (AgNWs) using an aqueous solution containing sodium halide salts (NaF, NaCl, NaBr, or NaI). The halide welding was performed simply by immersing the as-coated AgNW film into the sodium halide solution, and the resulting material was compared with that obtained using two typical thermal and plasmonic welding techniques. The halide welding dramatically reduced the sheet resistance of the AgNW electrode due to the strong fusion among nanowires at each junction while preserving the optical transmittance...
August 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28820008/radioscapholunate-fusion-with-triquetrum-and-distal-pole-of-scaphoid-excision-long-term-follow-up
#18
Ngoc B Ha, Joideep Phadnis, Simon B M MacLean, Gregory I Bain
The purpose of this study was to assess the long-term outcomes of radioscapholunate fusion, with and without distal pole of scaphoid excision and excision of the triquetrum. These compromised three operative groups. Seventeen patients were identified with a minimum of 10 years follow-up, with a mean of 15 years (range 10-19). Fifteen of the 17 patients were satisfied with their outcome. Two were converted to total wrist fusion. The mean outcomes scores were; pain visual analogue scale score 2.1/10, Quick Disabilities of the Arm, Shoulder, and Hand 29 and Modified Mayo Wrist score 60...
August 1, 2017: Journal of Hand Surgery, European Volume
https://www.readbyqxmd.com/read/28819706/generation-of-a-functional-humanized-delta-like-ligand-4-transgenic-mouse-model
#19
John Wiseman, Pernilla Gregersson, Johan Johansson, Kerstin Magnell, Fernanda Pilataxi, Chris Morehouse, Philip Brohawn, Nicholas Holoweckyj, Patrick Strout, Song Cho
Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form...
August 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28819671/fullerenol-nanoparticles-suppress-rankl-induced-osteoclastogenesis-by-inhibiting-differentiation-and-maturation
#20
Huan Geng, Ya-Nan Chang, Xue Bai, Shuitao Liu, Qing Yuan, Weihong Gu, Juan Li, Kui Chen, Gengyan Xing, Gengmei Xing
Bone health requires regulation of homeostatic equilibrium between osteoblasts and osteoclasts. The over-activation of osteoclasts can disrupt bone metabolism, resulting in osteoporosis and other bone-loss diseases. Fullerenol, a polyhydroxy derivative of fullerene, exhibits excellent biocompatibility. Here we show that fullerenol nanoparticles exert two functions: inhibition of osteoclastic differentiation and blockage of pre-osteoclast fusion to restructure osteoclast maturation and function. Experimentally, the nanoparticles reduced pre-osteoclast migration and inhibited ruffled border formation to block their maturation...
August 18, 2017: Nanoscale
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