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https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#1
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445759/pulsatile-lipid-vesicles-under-osmotic-stress
#2
Morgan Chabanon, James C S Ho, Bo Liedberg, Atul N Parikh, Padmini Rangamani
The response of lipid bilayers to osmotic stress is an important part of cellular function. Recent experimental studies showed that when cell-sized giant unilamellar vesicles (GUVs) are exposed to hypotonic media, they respond to the osmotic assault by undergoing a cyclical sequence of swelling and bursting events, coupled to the membrane's compositional degrees of freedom. Here, we establish a fundamental and quantitative understanding of the essential pulsatile behavior of GUVs under hypotonic conditions by advancing a comprehensive theoretical model of vesicle dynamics...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445757/action-of-antimicrobial-peptides-on-bacterial-and-lipid-membranes-a-direct-comparison
#3
Joseph E Faust, Pei-Yin Yang, Huey W Huang
The bacterial membrane represents an attractive target for the design of new antibiotics to combat widespread bacterial resistance. Understanding how antimicrobial peptides (AMPs) and other membrane-active agents attack membranes could facilitate the design of new, effective antimicrobials. Despite intense study of AMPs on model membranes, we do not know how well the mechanism of attack translates to real biological membranes. To that end, we have characterized the attack of AMPs on Escherichia coli cytoplasmic membranes and directly compared this action to model membranes...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445756/membrane-mechanics-of-primary-afferent-neurons-in-the-dorsal-root-ganglia-of-rats
#4
Hirosato Kanda, Jianguo G Gu
Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG)...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28444900/lactosylceramide-induced-phosphorylation-signaling-to-group-iva-phospholipase-a2-via-reactive-oxygen-species-in-tumor-necrosis-factor-%C3%AE-treated-cells
#5
Hiroyuki Nakamura, Yuta Moriyama, Kazuaki Watanabe, Satoshi Tomizawa, Risa Yamazaki, Hiromasa Takahashi, Toshihiko Murayama
The activity of α-type cytosolic phospholipase A2 (cPLA2 α, group IVA PLA2 ), which releases arachidonic acid (AA), is mainly regulated by the Ca(2+) -induced intracellular translocation/attachment of the enzyme to substrate membranes and its phosphorylation. We previously reported that tumor necrosis factor-α (TNFα) stimulated the formation of lactosylceramide (LacCer) in L929 fibroblast cells, and this lipid directly bound with and activated cPLA2 α [Nakamura et al., J. Biol. Chem. 2013;288:23264-23272]...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28443362/effect-of-the-side-chain-spacer-structure-on-the-ph-responsive-properties-of-polycarboxylates
#6
Atsushi Harada, Ryoma Teranishi, Eiji Yuba, Kenji Kono
The properties of stimuli-responsive polymers change significantly with changes to their environment, such as temperature and pH. This behavior can be utilized for the preparation of stimuli-responsive carriers for efficient cytosolic delivery of active drugs. Among the possible environmental conditions, pH is one of the most useful stimuli because the pH in an endosome is lower than under physiological conditions, depending on endosomal development. This pH difference is an important factor in the design of pH-responsive polymers, which can be used to enhance the transport of endocytosed drugs from the endosomal compartment to the cytoplasm...
April 26, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28443331/coupling-between-the-dynamics-of-water-and-surfactants-in-lyotropic-liquid-crystals
#7
Jesse Gatten McDaniel, Arun Yethiraj
Bilayers composed of lipid or surfactant molecules are central to biological membranes and lamellar lyotropic liquid crystalline (LLC) phases. Common to these systems are phases that exhibit either ordered or disordered packing of the hydrophobic tails. In this work, we study the impact of surfactant ordering, i.e., disordered Lα and ordered Lβ LLC phases, on the dynamics of water in the lamellar phases of dicarboxylate gemini surfactants. We study the different phases at identical hydration levels by changing the length of the hydrophobic tails; surfactants with shorter tails form Lα phases and those with longer tails form Lβ phases...
April 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28443114/tadir1-2-a-wheat-ortholog-of-lipid-transfer-protein-atdir1-contributes-to-negative-regulation-of-wheat-resistance-against-puccinia-striiformis-f-sp-tritici
#8
Soyed M Ahmed, Peng Liu, Qinghe Xue, Changan Ji, Tuo Qi, Jia Guo, Jun Guo, Zhensheng Kang
Very few LTPs have been shown to act through plasma membrane receptors or to be involved in the hypersensitive response (HR). DIR1, a new type of plant LTP interacts with lipids in vitro, moves to distant tissues during systemic acquired resistance (SAR) and therefore is thought to be involved in long-distance signaling during SAR. However, the exact functions of DIR1 orthologs in cereal species under biotic and abiotic stresses have not been thoroughly defined. In this study, a novel wheat ortholog of the DIR1 gene, TaDIR1-2, was isolated from Suwon11, a Chinese cultivar of wheat and functionally characterized...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442922/inhibition-of-pcsk9-protects-against-radiation-induced-damage-of-prostate-cancer-cells
#9
Si-Shun Gan, Jian-Qing Ye, Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating low-density lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442766/nanoscale-membrane-domain-formation-driven-by-cholesterol
#10
Matti Javanainen, Hector Martinez-Seara, Ilpo Vattulainen
Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442719/chlamydia-trachomatis-neither-exerts-deleterious-effects-on-spermatozoa-nor-impairs-male-fertility
#11
Jenniffer Puerta Suarez, Leonardo R Sanchez, Florencia C Salazar, Hector A Saka, Rosa Molina, Andrea Tissera, Virginia E Rivero, Walter D Cardona Maya, Ruben D Motrich
Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection. However, whether Chlamydia trachomatis has a negative impact on sperm quality and male fertility is still controversial. Herein, we report the effects on sperm quality of the in vitro exposure of spermatozoa to Chlamydia trachomatis, and also the effects of male genital infection on male fertility using an animal model. Human and mouse sperm were obtained from healthy donors and cauda epididimys from C57BL/6 mice, respectively...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442546/modeled-structural-basis-for-the-recognition-of-%C3%AE-2-3-sialyllactose-by-soluble-klotho
#12
Jon D Wright, Sung-Wan An, Jian Xie, Joonho Yoon, Nicole Nischan, Jennifer J Kohler, Noelynn Oliver, Carmay Lim, Chou-Long Huang
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of actions. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28442379/peripheral-membrane-associations-of-matrix-metalloproteinases
#13
REVIEW
Steven R Van Doren, Tara C Marcink, Rama K Koppisetti, Alexander Jurkevich, Yan G Fulcher
Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing freely in the extracellular matrix. Yet multiple MMPs are also observed at cell surfaces. Their membrane-proximal activities include sheddase activities, collagenolysis, bacterial killing, and intracellular trafficking reaching as far as the nucleus. The catalytic domains of MMP-7 and MMP-12 bind bilayers peripherally, each in two different orientations, by presenting positive charges and a few hydrophobic groups to the surface. Related peripheral membrane associations are predicted for other soluble MMPs...
April 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#14
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28442061/effect-of-docosahexanoic-acid-on-quality-of-frozen-thawed-bull-semen-in-bioxcell-extender
#15
Asmatullah Kaka, Wahid Haron, Rosnina Yusoff, Nurhusien Yimer, A M Khumran, Kazhal Sarsaifi, Atique Ahmed Behan, Ubedullah Kaka, Akeel Ahmed Memon, Mahdi Ebrahimi
This study was conducted to investigate the effect of docosahexanoic acid (DHA) supplementation in BioXcell extender on the quality of frozen-thawed bull semen. Twenty-four ejaculates were collected from three bulls (eight from each bull). Ejaculates with motility ≥70% and normal morphology ≥80% were extended into BioXcell extender to which 0 (control), 3, 5, 10 or 15ngmL(-1) DHA was added. The supplemented semen samples were incubated at 37°C for 15min for DHA uptake by spermatozoa. Later, samples were cooled for 2h at 5°C and packaged into 0...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28441781/dengue-virus-non-structural-protein-5
#16
REVIEW
Abbas El Sahili, Julien Lescar
The World Health Organization estimates that the yearly number of dengue cases averages 390 million. This mosquito-borne virus disease is endemic in over 100 countries and will probably continue spreading, given the observed trend in global warming. So far, there is no antiviral drug available against dengue, but a vaccine has been recently marketed. Dengue virus also serves as a prototype for the study of other pathogenic flaviviruses that are emerging, like West Nile virus and Zika virus. Upon viral entry into the host cell and fusion of the viral lipid membrane with the endosomal membrane, the viral RNA is released and expressed as a polyprotein, that is then matured into three structural and seven non-structural (NS) proteins...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28441593/a-comprehensive-evaluation-of-the-environmental-quality-of-a-coastal-lagoon-ravenna-italy-integrating-chemical-and-physiological-analyses-in-mussels-as-a-biomonitoring-strategy
#17
Marco Capolupo, Silvia Franzellitti, Alisar Kiwan, Paola Valbonesi, Enrico Dinelli, Emanuela Pignotti, Manfred Birke, Elena Fabbri
This study aimed at evaluating the environmental quality of a coastal lagoon (Pialassa Piomboni, NW-Adriatic, Italy) by combining analyses of biomarkers of environmental stress and bioaccumulation of contaminants in marine mussels (Mytilus galloprovincialis) transplanted for 28days to six selected sites. Assessed biomarkers encompassed lysosomal endpoints, oxidative stress and detoxification parameters, specific responses to metals, neuro- and genotoxic substances; chemical analyses focused on PAHs, metals, pesticide and pharmaceuticals...
April 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28441577/membrane-vesicles-and-horizontal-gene-transfer-in-prokaryotes
#18
REVIEW
Sara Domingues, Kaare M Nielsen
Membrane vesicles (MVs) are released from all living cells. MVs are lumen-containing spheres of lipid-bilayers derived from the cell surface. MVs are biologically active and contain various components, including genetic material. Both chromosomal and plasmid DNA, as well as different types of RNA have been detected in MVs. Vesicle-mediated transfer of genes coding for antibiotic resistance, virulence and metabolic traits has been reported in Gram-negative and Gram-positive bacteria and in Archaea. MVs can persist over time in natural environments...
April 22, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28440865/generation-of-wavy-structure-on-lipid-membrane-by-peripheral-proteins-a-linear-elastic-analysis
#19
Paritosh Mahata, Sovan Lal Das
We carry out a linear elastic analysis to study wavy structure generation on lipid membrane by peripheral membrane proteins. We model the lipid membrane as linearly elastic and anisotropic material. The hydrophobic insertion by proteins into the lipid membrane has been idealized as penetration of rigid rodlike inclusions into the membrane and the electrostatic interaction between protein and membrane has been modeled by a distributed surface traction acting on the membrane surface. With the proposed model we study curvature generation by several binding domains of peripheral membrane proteins containing BAR domains and amphipathic alpha-helices...
April 25, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28439282/overexpression-of-cucumber-phospholipase-d-alpha-gene-cspld%C3%AE-in-tobacco-enhanced-salinity-stress-tolerance-by-regulating-na-k-balance-and-lipid-peroxidation
#20
Tuo Ji, Shuzhen Li, Meili Huang, Qinghua Di, Xiufeng Wang, Min Wei, Qinghua Shi, Yan Li, Biao Gong, Fengjuan Yang
Plant phospholipase D (PLD), which can hydrolyze membrane phospholipids to produce phosphatidic acid (PA), a secondary signaling molecule, has been proposed to function in diverse plant stress responses. In this research, we characterized the roles of the cucumber phospholipase D alpha gene (PLDα, GenBank accession number EF363796) in growth and tolerance to short- and long-term salt stress in transgenic tobacco (Nicotiana tabacum). Fresh and dry weights of roots, PLD activity and content, mitogen activated protein kinase (MAPK) gene expression, Na(+)-K(+) homeostasis, expression of genes encoding ion exchange, reactive oxygen species (ROS) metabolism and osmotic adjustment substances were investigated in wild type (WT) and CsPLDα-overexpression tobacco lines grown under short- and long-term high salt (250 mM) stress...
2017: Frontiers in Plant Science
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