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https://www.readbyqxmd.com/read/29773891/assessing-the-feasibility-of-neutralizing-osteopontin-with-various-therapeutic-antibody-modalities
#1
Vahid Farrokhi, Jeffrey R Chabot, Hendrik Neubert, Zhiyong Yang
Osteopontin is a secreted glycophosphoprotein that is highly implicated in many physiological and pathological processes such as biomineralization, cell-mediated immunity, inflammation, fibrosis, cell survival, tumorigenesis and metastasis. Antibodies against osteopontin have been actively pursued as potential therapeutics for various diseases by pharmaceutical companies and academic laboratories. Many studies have demonstrated the efficacy of osteopontin inhibition in a variety of preclinical models of diseases such as rheumatoid arthritis, cancer, nonalcoholic steatohepatitis, but clinical utility has not yet been demonstrated...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29733200/temporal-profiling-establishes-a-dynamic-s-palmitoylation-cycle
#2
Sang Joon Won, Brent R Martin
S-palmitoylation is required for membrane anchoring, proper trafficking, and the normal function of hundreds of integral and peripheral membrane proteins. Previous bioorthogonal pulse-chase proteomics analyses identified Ras family GTPases, polarity proteins, and G proteins as rapidly cycling S-palmitoylated proteins sensitive to depalmitoylase inhibition, yet the breadth of enzyme regulated dynamic S-palmitoylation largely remains a mystery. Here we present a pulsed bioorthogonal S-palmitoylation assay for temporal analysis of S-palmitoylation dynamics...
May 7, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29724458/interspecific-comparison-of-radiocesium-trophic-transfer-in-two-tropical-fish-species
#3
Simon Pouil, Jean-Louis Teyssié, Scott W Fowler, Marc Metian, Michel Warnau
The trophic transfer of radiocesium (134 Cs) was investigated in two tropical fish, the silver moony Monodactylus argenteus and the spotted scat Scatophagus argus. Juveniles of both species were exposed to dietary 134 Cs using the pulse-chase feeding methodology. The food was brine shrimp (Artemia salina) previously exposed to the dissolved radiotracer. Depuration kinetics of 134 Cs were followed for 45 d. Results showed that Cs was similarly efficiently assimilated by both species (AE > 50%). The estimated trophic transfer factors in the two species ranked from 1 to 2, suggesting that 134 Cs could be biomagnified in both omnivorous species...
April 30, 2018: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/29721083/targeting-cpt1a-mediated-fatty-acid-oxidation-sensitizes-nasopharyngeal-carcinoma-to-radiation-therapy
#4
Zheqiong Tan, Lanbo Xiao, Min Tang, Fang Bai, Jiangjiang Li, Liling Li, Feng Shi, Namei Li, Yueshuo Li, Qianqian Du, Jingchen Lu, Xinxian Weng, Wei Yi, Hanwen Zhang, Jia Fan, Jian Zhou, Qiang Gao, José N Onuchic, Ann M Bode, Xiangjian Luo, Ya Cao
Nasopharyngeal carcinoma (NPC) has a particularly high prevalence in southern China, southeastern Asia and northern Africa. Radiation resistance remains a serious obstacle to successful treatment in NPC. This study aimed to explore the metabolic feature of radiation-resistant NPC cells and identify new molecular-targeted agents to improve the therapeutic effects of radiotherapy in NPC. Methods : Radiation-responsive and radiation-resistant NPC cells were used as the model system in vitro and in vivo . Metabolomics approach was used to illustrate the global metabolic changes...
2018: Theranostics
https://www.readbyqxmd.com/read/29717623/aortic-sca-1-sup-sup-progenitor-cells-arise-from-the-somitic-mesoderm-lineage-in-mouse
#5
Sarah K Steinbach, Tao Wang, Martha H Carruthers, Angela Li, Rickvinder Besla, Adam P Johnston, Clinton S Robbins, Mansoor Husain
Sca-1<sup>+</sup> progenitor cells in the adult mouse aorta are known to generate vascular smooth muscle cells (VSMC), but their embryological origins and temporal abundance are not known. Using tamoxifen-inducible <i>Myf5-Cre</i><sup>ER</sup> mice, we demonstrate that Sca-1<sup>+</sup> adult aortic cells arise from the somitic mesoderm beginning at E8.5 and continue throughout somitogenesis. <i>Myf5</i> lineage-derived Sca-1<sup>+</sup> cells greatly expand in situ starting at 4 weeks of age and become a major source of aortic Sca-1<sup>+</sup> cells by 6 weeks of age...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29707441/genetic-requirement-of-talin1-for-proliferation-of-cranial-neural-crest-cells-during-palate-development
#6
Kana Ishii, Kusumika Mukherjee, Takashi Okada, Eric C Liao
Background: Craniofacial malformations are among the most common congenital anomalies. Cranial neural crest cells (CNCCs) form craniofacial structures involving multiple cellular processes, perturbations of which contribute to craniofacial malformations. Adhesion of cells to the extracellular matrix mediates bidirectional interactions of the cells with their extracellular environment that plays an important role in craniofacial morphogenesis. Talin (tln) is crucial in cell-matrix adhesion between cells, but its role in craniofacial morphogenesis is poorly understood...
March 2018: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/29704548/toxicity-and-aggregation-of-the-polyglutamine-disease-protein-ataxin-3-is-regulated-by-its-binding-to-vcp-p97-in-drosophila-melanogaster
#7
Gorica Ristic, Joanna R Sutton, Kozeta Libohova, Sokol V Todi
Among the nine dominantly inherited, age-dependent neurodegenerative diseases caused by abnormal expansion in the polyglutamine (polyQ) repeat of otherwise unrelated proteins is Spinocerebellar Ataxia Type 3 (SCA3). SCA3 is caused by polyQ expansion in the deubiquitinase (DUB), ataxin-3. Molecular sequelae related to SCA3 remain unclear. Here, we sought to understand the role of protein context in SCA3 by focusing on the interaction between this DUB and Valosin-Containing Protein (VCP). VCP is bound directly by ataxin-3 through an arginine-rich area preceding the polyQ repeat...
April 25, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29700288/atp-depletion-during-mitotic-arrest-induces-mitotic-slippage-and-apc-c-cdh1-dependent-cyclin-b1-degradation
#8
Yun Yeon Park, Ju-Hyun Ahn, Min-Guk Cho, Jae-Ho Lee
ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29695488/characterization-of-lamp1-labeled-nondegradative-lysosomal-and-endocytic-compartments-in-neurons
#9
Xiu-Tang Cheng, Yu-Xiang Xie, Bing Zhou, Ning Huang, Tamar Farfel-Becker, Zu-Hang Sheng
Despite widespread distribution of LAMP1 and the heterogeneous nature of LAMP1-labeled compartments, LAMP1 is routinely used as a lysosomal marker, and LAMP1-positive organelles are often referred to as lysosomes. In this study, we use immunoelectron microscopy and confocal imaging to provide quantitative analysis of LAMP1 distribution in various autophagic and endolysosomal organelles in neurons. Our study demonstrates that a significant portion of LAMP1-labeled organelles do not contain detectable lysosomal hydrolases including cathepsins D and B and glucocerebrosidase...
April 25, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29685227/formation-of-high-order-oligomers-is-required-for-functional-bioactivity-of-an-african-bat-henipavirus-surface-glycoprotein
#10
Laura Behner, Louisa Zimmermann, Marc Ringel, Michael Weis, Andrea Maisner
Hendra virus (HeV) and Nipah virus (NiV) are highly pathogenic henipaviruses originating from fruit bats in Australia and Asia that can cause severe infections in livestock and humans. In recent years, also African bat henipaviruses were identified at the nucleic acid level. To assess their potential to replicate in non-bat species, several studies were performed to characterize the two surface glycoproteins required for virus entry and spread by cell-cell fusion. It has been shown that surface expression and fusion-helper function of the receptor-binding G protein of Kumasi virus (KV), the prototypic Ghanaian bat henipavirus, is reduced compared to other non-African henipavirus G proteins...
May 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29617903/spermatogonial-stem-cells
#11
Hiroshi Kubota, Ralph L Brinster
Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis and have an essential role to maintain highly productive spermatogenesis by self-renewal and continuous generation of daughter spermatogonia that differentiate into spermatozoa, transmitting genetic information to the next generation. Since the 1950s, many experimental methods, including histology, immunostaining, whole-mount analyses, and pulse-chase labeling had been used in attempts to identify SSCs, but without success. In 1994, a spermatogonial transplantation method was reported that established a quantitative functional assay to identify SSCs by evaluating their ability to both self-renew and differentiate to spermatozoa...
March 30, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29610302/identification-of-long-lived-synaptic-proteins-by-proteomic-analysis-of-synaptosome-protein-turnover
#12
Seok Heo, Graham H Diering, Chan Hyun Na, Raja Sekhar Nirujogi, Julia L Bachman, Akhilesh Pandey, Richard L Huganir
Memory formation is believed to result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a subset of long-lived proteins (LLPs). While it is known that LLPs exist, whether such proteins are present at synapses is unknown. We performed an unbiased screen using metabolic pulse-chase labeling in vivo in mice and in vitro in cultured neurons combined with quantitative proteomics...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29555761/dimeric-sorting-code-for-concentrative-cargo-selection-by-the-copii-coat
#13
Chao Nie, Huimin Wang, Rui Wang, David Ginsburg, Xiao-Wei Chen
The flow of cargo vesicles along the secretory pathway requires concerted action among various regulators. The COPII complex, assembled by the activated SAR1 GTPases on the surface of the endoplasmic reticulum, orchestrates protein interactions to package cargos and generate transport vesicles en route to the Golgi. The dynamic nature of COPII, however, hinders analysis with conventional biochemical assays. Here we apply proximity-dependent biotinylation labeling to capture the dynamics of COPII transport in cells...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29547696/piperidinyl-ureas-chemically-control-defective-in-cullin-neddylation-1-dcn1-mediated-cullin-neddylation
#14
Jared T Hammill, Daniel C Scott, Jaeki Min, Michele C Connelly, Gloria Holbrook, Fangyi Zhu, Amy Matheny, Lei Yang, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29540753/micro-scale-fusion-in-dense-relativistic-nanowire-array-plasmas
#15
Alden Curtis, Chase Calvi, James Tinsley, Reed Hollinger, Vural Kaymak, Alexander Pukhov, Shoujun Wang, Alex Rockwood, Yong Wang, Vyacheslav N Shlyaptsev, Jorge J Rocca
Nuclear fusion is regularly created in spherical plasma compressions driven by multi-kilojoule pulses from the world's largest lasers. Here we demonstrate a dense fusion environment created by irradiating arrays of deuterated nanostructures with joule-level pulses from a compact ultrafast laser. The irradiation of ordered deuterated polyethylene nanowires arrays with femtosecond pulses of relativistic intensity creates ultra-high energy density plasmas in which deuterons (D) are accelerated up to MeV energies, efficiently driving D-D fusion reactions and ultrafast neutron bursts...
March 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29540503/integrin-%C3%AE-2-marks-a-niche-of-trophoblast-progenitor-cells-in-first-trimester-human-placenta
#16
Cheryl Q E Lee, Margherita Y Turco, Lucy Gardner, Benjamin D Simons, Myriam Hemberger, Ashley Moffett
During pregnancy the trophoblast cells of the placenta are the only fetal cells in direct contact with maternal blood and decidua. Their functions include transport of nutrients and oxygen, secretion of pregnancy hormones, remodelling of the uterine arteries, and communicating with maternal cells. Despite the importance of trophoblast cells in placental development and successful pregnancy, little is known about the identity, location and differentiation of human trophoblast progenitors. We identify a proliferative trophoblast niche at the base of the cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression...
April 16, 2018: Development
https://www.readbyqxmd.com/read/29515998/quantitative-ex-vivo-mri-changes-due-to-progressive-formalin-fixation-in-whole-human-brain-specimens-longitudinal-characterization-of-diffusion-relaxometry-and-myelin-water-fraction-measurements-at-3t
#17
Anwar S Shatil, Md Nasir Uddin, Kant M Matsuda, Chase R Figley
Purpose: Postmortem MRI can be used to reveal important pathologies and establish radiology-pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this study was to investigate time-dependent effects of formalin fixation on MRI relaxometry (T1 and T2 ), diffusion tensor imaging (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens. Methods: Two whole, neurologically-healthy human brains were immersed in 10% formalin solution and scanned at 13 time points between 0 and 1,032 h...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29492374/surface-functionalization-dependent-subcellular-localization-of-superparamagnetic-nanoparticle-in-plasma-membrane-and-endosome
#18
Deepak B Thimiri Govinda Raj, Niamat Ali Khan
In this article, we elaborate the application of thermal decomposition based synthesis of Fe3 O4 superparamagnetic nanoparticle (SPMNP) in subcellular fractionation context. Here, we performed surface functionalization of SPMNP with phospholipids and dimercaptosuccinic acid. Surprisingly, we observed surface functionalization dependent SPMNP localization in subcellular compartments such as plasma membrane, endosomes and lysosomes. By using SPMNP based subcellular localization with pulse-chase methodology, we could use SPMNP for high pure-high yield organelle (plasma membrane, endosomes and lysosome) fractionation...
2018: Nano Convergence
https://www.readbyqxmd.com/read/29474059/a-halotag-based-multicolor-fluorogenic-sensor-visualizes-and-quantifies-proteome-stress-in-live-cells-using-solvatochromic-and-molecular-rotor-based-fluorophores
#19
Yu Liu, Kun Miao, Yinghao Li, Matthew Fares, Shuyuan Chen, Xin Zhang
Protein homeostasis, or proteostasis, is essential for cellular fitness and viability. Many environmental factors compromise proteostasis, induce global proteome stress, and cause diseases. The proteome stress sensor is a powerful tool for dissecting the mechanism of cellular stress and finding therapeutics that ameliorate these diseases. In this work, we present a multicolor HaloTag-based sensor (named AgHalo) to visualize and quantify proteome stresses in live cells. The current AgHalo sensor is equipped with three fluorogenic probes that turn on fluorescence when the sensor forms either soluble oligomers or insoluble aggregates upon exposure to stress conditions, both in vitro and in cellulo...
February 28, 2018: Biochemistry
https://www.readbyqxmd.com/read/29465310/dietary-starch-breakdown-product-sensing-mobilizes-and-apically-activates-%C3%AE-glucosidases-in-small-intestinal-enterocytes
#20
Mohammad Chegeni, Mahdi Amiri, Buford L Nichols, Hassan Y Naim, Bruce R Hamaker
Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa)...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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