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https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#1
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the post-fusion glycoprotein (RSV sF) of RSV, which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to Alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-Alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28544275/recessive-mutations-in-msto1-cause-mitochondrial-dynamics-impairment-leading-to-myopathy-and-ataxia
#2
Alessia Nasca, Chiara Scotton, Irina Zaharieva, Marcella Neri, Rita Selvatici, Olafur Thor Magnusson, Aniko Gal, David Weaver, Rachele Rossi, Annarita Armaroli, Marika Pane, Rahul Phadke, Anna Sarkozy, Francesco Muntoni, Imelda Hughes, Antonella Cecconi, György Hajnóczky, Alice Donati, Eugenio Mercuri, Massimo Zeviani, Alessandra Ferlini, Daniele Ghezzi
We report here the first families carrying recessive variants in the MSTO1 gene: compound heterozygous mutations were identified in two sisters and in an unrelated singleton case, who presented a multisystem complex phenotype mainly characterized by myopathy and cerebellar ataxia. Human MSTO1 is a poorly studied protein, suggested to have mitochondrial localization and to regulate morphology and distribution of mitochondria. As for other mutations affecting genes involved in mitochondrial dynamics, no biochemical defects typical of mitochondrial disorders were reported...
May 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28544270/localization-and-domain-characterization-of-the-sfla-regulator-of-flagellar-formation-in-vibrio-alginolyticus
#3
Satoshi Inaba, Takehiko Nishigaki, Norihiro Takekawa, Seiji Kojima, Michio Homma
Many swimming bacteria use flagella as locomotive organelles. The spatial and numerical regulation of flagellar biosynthesis differs by bacterial species. The marine bacteria Vibrio alginolyticus use a single polar flagellum whose number is regulated positively by FlhF and negatively by FlhG. Cells lacking FlhF and FlhG have no flagellum. The motility defect in an flhFG deletion was suppressed by a mutation in the sflA gene that resulted in the production of multiple, peritrichous flagella. SflA is a Vibrio-specific protein...
May 22, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28544109/express-with-caution-epitope-tags-and-cdna-variants-effects-on-herg-channel-trafficking-half-life-and-function
#4
Marika L Osterbur Badhey, Alexander C Bertalovitz, Thomas V McDonald
INTRODUCTION: Genetic mutations in KCNQ2 which encodes hERG, the alpha subunit of the potassium channel responsible for the IKr current, cause Long QT Syndrome, an inherited cardiac arrhythmia disorder. Electrophysiology techniques are used to correlate genotype with molecular phenotype to determine which mutations identified in patients diagnosed Long QT Syndrome are disease causing, and which are benign. These investigations are usually done using heterologous expression in cell lines, and often, epitope fusion tags are used to enable isolation and identification of the protein of interest...
May 24, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28543743/detection-and-localization-of-regucalcin-in-spermatozoa-of-water-buffalo-bubalus-bubalis-a-calcium-regulating-multifunctional-protein
#5
H Pillai, A M Shende, M S Parmar, J Thomas, H S Kartha, G Taru Sharma, S K Ghosh, S K Bhure
Regucalcin (RGN) is a calcium-regulating, anti-apoptotic, antioxidative and antiproliferative multifunctional protein predominantly seen in liver and kidney. All these functions are very crucial during spermatogenesis and sperm maturation process until fertilization of the ovum. Although many studies have reported the wide distribution of regucalcin in the male reproductive tract of the rat, human and bovine, its presence in spermatozoa is yet to be demonstrated wherein calcium has a pivotal role in the transport, capacitation, acrosomal reaction and further fusion with ova...
May 24, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28543534/a-chimeric-protein-of-cfa-i-cs6-subunits-and-ltb-sta-toxoid-could-protect-immunized-mice-against-enterotoxigenic-escherichia-coli
#6
Narges Zeinalzadeh, Ali Hatef Salmanian, Goli Goujani, Jafar Amani, Ghasem Ahangari, Asal Akhavian, Mahyat Jafari
Enterotoxigenic Escherichia Coli (ETEC) strains are the most common bacteria causing diarrhea in children in developing countries and travelers to these areas. Colonization factors (CFs) and enterotoxins are the main virulence determinants in ETEC pathogenesis. Heterogeneity of CFs commonly considered as the bottleneck to achieve an effective vaccine. On the other hand, it is believed that a broad spectrum protection against ETEC would be available when the anti-CF and anti-enterotoxin immunity were induced simultaneously...
May 23, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28542501/a-rho-associated-coiled-coil-containing-kinases-rock-inhibitor-y-27632-enhances-adhesion-viability-and-differentiation-of-human-term-placenta-derived-trophoblasts-in-vitro
#7
Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, Kenji Matsumoto
Although human term placenta-derived primary cytotrophoblasts (pCTBs) represent a good human syncytiotrophoblast (STB) model, in vitro culture of pCTBs is not always easily accomplished. Y-27632, a specific inhibitor of Rho-associated coiled-coil containing kinases (ROCK), reportedly prevented apoptosis and improved cell-to-substrate adhesion and culture stability of dissociated cultured human embryonic stem cells and human corneal endothelial cells. The Rho kinase pathway regulates various kinds of cell behavior, some of which are involved in pCTB adhesion and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28542452/the-role-of-aspartyl-aminopeptidase-ape4-in-cryptococcus-neoformans-virulence-and-authophagy
#8
Fabiano de Assis Gontijo, Amanda Teixeira de Melo, Renata C Pascon, Larissa Fernandes, Hugo Costa Paes, J Andrew Alspaugh, Marcelo A Vallim
In order to survive and cause disease, microbial pathogens must be able to proliferate at the temperature of their infected host. We identified novel microbial features associated with thermotolerance in the opportunistic fungal pathogen Cryptococcus neoformans using a random insertional mutagenesis strategy, screening for mutants with defective growth at 37°C. Among several thermosensitive mutants, we identified one bearing a disruption in a gene predicted to encode the Ape4 aspartyl aminopeptidase protein...
2017: PloS One
https://www.readbyqxmd.com/read/28542388/targeted-dna-methylation-in-pericentromeres-with-genome-editing-based-artificial-dna-methyltransferase
#9
Taiga Yamazaki, Yu Hatano, Tetsuya Handa, Sakiko Kato, Kensuke Hoida, Rui Yamamura, Takashi Fukuyama, Takayuki Uematsu, Noritada Kobayashi, Hiroshi Kimura, Kazuo Yamagata
To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI...
2017: PloS One
https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#10
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28542141/an-enhanced-bioluminescence-based-annexin-v-probe-for-apoptosis-detection-in-vitro-and-in-vivo
#11
Trajen Head, Peter Dau, Stephanie Duffort, Pirouz Daftarian, Pratibha M Joshi, Roberto Vazquez-Padron, Sapna K Deo, Sylvia Daunert
The process of controlled cellular death known as apoptosis has an important central role not only in normal homeostatic maintenance of tissues, but also in numerous diseases such as cancer, neurodegenerative, autoimmune, and cardiovascular diseases. As a result, new technologies with the capability to selectively detect apoptotic cells represent a central focus of research for the study of these conditions. We have developed a new biosensor for the detection of apoptotic cells, incorporating the targeted selectivity for apoptotic cells from Annexin V with the sensitivity of bioluminescence signal generation from a serum-stable mutant of Renilla luciferase (RLuc8)...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539870/a-select-subset-of-electron-transport-chain-genes-associated-with-optic-atrophy-link-mitochondria-to-axon-regeneration-in-caenorhabditis-elegans
#12
Wendy M Knowlton, Thomas Hubert, Zilu Wu, Andrew D Chisholm, Yishi Jin
The role of mitochondria within injured neurons is an area of active interest since these organelles are vital for the production of cellular energy in the form of ATP. Using mechanosensory neurons of the nematode Caenorhabditis elegans to test regeneration after neuronal injury in vivo, we surveyed genes related to mitochondrial function for effects on axon regrowth after laser axotomy. Genes involved in mitochondrial transport, calcium uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28539819/dexamethasone-treatment-at-the-myoblast-stage-enhanced-c2c12-myocyte-differentiation
#13
Der-Sheng Han, Wei-Shiung Yang, Tung-Wei Kao
Background: Glucocorticoids induce skeletal muscle atrophy in many clinical situations; however, their hypertrophic and pro-differentiation effects on myotubes have rarely been reported. We hypothesized that dexamethasone (DEX) has a dual effect on muscle differentiation, and aimed to develop a new differentiation protocol for C2C12 cell line. Methods: Dose- and time-dependent effect of DEX on C2C12 myoblast cell line was analyzed at myoblast and myotube stage, respectively. The level of differentiation was determined by myh1, pax7, atrogin-1, and myostatin mRNA expression and fusion index...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539478/a-novel-epigenetic-aml1-eto-thap10-mir-383-mini-circuitry-contributes-to-t-8-21-leukaemogenesis
#14
Yonghui Li, Qiaoyang Ning, Jinlong Shi, Yang Chen, Mengmeng Jiang, Li Gao, Wenrong Huang, Yu Jing, Sai Huang, Anqi Liu, Zhirui Hu, Daihong Liu, Lili Wang, Clara Nervi, Yun Dai, Michael Q Zhang, Li Yu
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML...
May 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28539444/improved-prefusion-stability-optimized-codon-usage-and-augmented-virion-packaging-enhance-the-immunogenicity-of-respiratory-syncytial-virus-rsv-fusion-protein-in-a-vectored-vaccine-candidate
#15
Bo Liang, Joan O Ngwuta, Sonja Surman, Barbora Kabatova, Xiang Liu, Matthias Lingemann, Xueqiao Liu, Lijuan Yang, Richard Herbert, Joanna Swerczek, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but lacks a licensed vaccine or suitable antiviral drug. A live-attenuated chimeric bovine/human parainfluenza virus type-3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naïve children, rB/HPIV3 was well-tolerated but the immunogenicity of wildtype RSV F was unsatisfactory...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539432/golgi-associated-protein-kinase-c-%C3%AE%C2%B5-is-delivered-to-phagocytic-cups-role-of-phosphatidylinositol-4-phosphate
#16
Cheryl M Hanes, Anna E D'Amico, Takehiko Ueyama, Alexander C Wong, Xuexin Zhang, W Frederick Hynes, Margarida M Barroso, Nathaniel C Cady, Mohamed Trebak, Naoaki Saito, Michelle R Lennartz
Protein kinase C-ε (PKC-ε) at phagocytic cups mediates the membrane fusion necessary for efficient IgG-mediated phagocytosis. The C1B and pseudosubstrate (εPS) domains are necessary and sufficient for this concentration. C1B binds diacylglycerol; the docking partner for εPS is unknown. Liposome assays revealed that the εPS binds phosphatidylinositol 4-phosphate (PI4P) and PI(3,5)P2 Wortmannin, but not LY294002, inhibits PKC-ε concentration at cups and significantly reduces the rate of phagocytosis. As Wortmannin inhibits PI4 kinase, we hypothesized that PI4P mediates the PKC-ε concentration at cups and the rate of phagocytosis...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28539418/loss-of-doc2-dependent-spontaneous-neurotransmission-augments-glutamatergic-synaptic-strength
#17
Denise M O Ramirez, Devon C Crawford, Natali L Chanaday, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali
Action potential-evoked vesicle fusion comprises the majority of neurotransmission within chemical synapses, but action potential-independent spontaneous neurotransmission also contributes to the collection of signals sent to the postsynaptic cell. Previous work has implicated spontaneous neurotransmission in homeostatic synaptic scaling, but few studies have selectively manipulated spontaneous neurotransmission without substantial changes in evoked neurotransmission to study this function in detail. Here we used a quadruple knockdown strategy to reduce levels of proteins within the soluble calcium-binding double C2 domain (Doc2)-like protein family to selectively reduce spontaneous neurotransmission in cultured mouse and rat neurons...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28539405/tumor-susceptibility-gene-101-tsg101-regulates-predisposition-towards-apoptosis-via-escrt-machinery-accessory-proteins
#18
Zenia Kaul, Oishee Chakrabarti
ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes and apoptosis. The role played by these proteins in either facilitating or protecting against apoptosis is still unclear. In this study, while trying to understand how deficiency of Mahogunin RING Finger 1 (MGRN1) affects cell viability, we uncover a novel role for its interactor, the ESCRT-I protein, TSG101 - it directly participates in mitigating ER stress mediated apoptosis...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539390/mfn2-deletion-in-brown-adipose-tissue-protects-from-insulin-resistance-and-impairs-thermogenesis
#19
Kiana Mahdaviani, Ilan Y Benador, Shi Su, Raffi A Gharakhanian, Linsey Stiles, Kyle M Trudeau, Maria Cardamone, Violeta Enríquez-Zarralanga, Eleni Ritou, Tamar Aprahamian, Marcus F Oliveira, Barbara E Corkey, Valentina Perissi, Marc Liesa, Orian S Shirihai
BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained...
May 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28539286/-expression-purification-and-activity-analysis-of-ggdef-and-eal-domain-containing-proteins-from-lactobacillus-acidophilus
#20
Jia-Hui He, Jie-Li Sun, Wen-Juan Yan, Fang Wang
OBJECTIVE: To identify the functions of the proteins containing the GGDEF or EAL domain in Lactobacillus acidophilus for investigation of the regulatory mechanism of c-di-GMP in this strain. METHODS: The DNA fragments of NH13_07045-GGDEF, NH13_07050 and NH13_07055 from Lactobacillus acidophilus ATCC4356 were amplified by PCR and cloned into the expression vector pMAL-His-c2. After sequencing, the recombinant plasmids were transformed into competent Escherichia coli cells, which were induced by IPTG to express the recombinant proteins fused with maltose binding protein (MBP)...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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