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https://www.readbyqxmd.com/read/28436959/peptide-mhc-based-nanomedicines-for-autoimmunity-function-as-t-cell-receptor-microclustering-devices
#1
Santiswarup Singha, Kun Shao, Yang Yang, Xavier Clemente-Casares, Patricia Solé, Antonio Clemente, Jesús Blanco, Qin Dai, Fayi Song, Shang Wan Liu, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Roopa Hebbandi Nanjundappa, Pascal Detampel, Matthias Amrein, César Fandos, Robert Tanguay, Susan Newbigging, Pau Serra, Anmar Khadra, Warren C W Chan, Pere Santamaria
We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28416692/immunomodulation-accelerated-neuronal-regeneration-following-selective-rod-photoreceptor-cell-ablation-in-the-zebrafish-retina
#2
David T White, Sumitra Sengupta, Meera T Saxena, Qingguo Xu, Justin Hanes, Ding Ding, Hongkai Ji, Jeff S Mumm
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28398466/novel-nesprin-1-mutations-associated-with-dilated-cardiomyopathy-cause-nuclear-envelope-disruption-and-defects-in-myogenesis
#3
Can Zhou, Chen Li, Bin Zhou, Huaqin Sun, Victoria Koullourou, Ian Holt, Megan J Puckelwartz, Derek T Warren, Robert Hayward, Ziyuan Lin, Lin Zhang, Glenn E Morris, Elizabeth M McNally, Sue Shackleton, Li Rao, Catherine M Shanahan, Qiuping Zhang
Nesprins-1 and -2 are highly expressed in skeletal and cardiac muscle and together with SUN (Sad1p/UNC84)-domain containing proteins and lamin A/C form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) bridging complex at the nuclear envelope (NE). Mutations in nesprin-1/2 have previously been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM). In this study, three novel rare variants (R8272Q, S8381C and N8406K) in the C-terminus of the SYNE1 gene (nesprin-1) were identified in seven DCM patients by mutation screening...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28397687/a-metabolic-switch-controls-intestinal-differentiation-downstream-of-adenomatous-polyposis-coli-apc
#4
Imelda T Sandoval, Richard Glenn C Delacruz, Braden N Miller, Shauna Hill, Kristofor A Olson, Ana E Gabriel, Kevin Boyd, Christeena Satterfield, Holly Van Remmen, Jared Rutter, David A Jones
Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28382297/candida-parapsilosis-protects-premature-intestinal-epithelial-cells-from-invasion-and-damage-by-candida-albicans
#5
Sara Gonia, Linda Archambault, Margaret Shevik, Marie Altendahl, Emily Fellows, Joseph M Bliss, Robert T Wheeler, Cheryl A Gale
Candida is a leading cause of late-onset sepsis in premature infants and is thought to invade the host via immature or damaged epithelial barriers. We previously showed that the hyphal form of Candida albicans invades and causes damage to premature intestinal epithelial cells (pIECs), whereas the non-hyphal Candida parapsilosis, also a fungal pathogen of neonates, has less invasion and damage abilities. In this study, we investigated the potential for C. parapsilosis to modulate pathogenic interactions of C...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28375163/triazole-fungicides-inhibit-zebrafish-hatching-by-blocking-the-secretory-function-of-hatching-gland-cells
#6
Javiera F De la Paz, Natalia Beiza, Susana Paredes-Zúñiga, Misque S Hoare, Miguel L Allende
In animals, hatching represents the transition point from a developing embryo to a free-living individual, the larva. This process is finely regulated by many endogenous and environmental factors and has been shown to be sensitive to a variety of chemical agents. It is commonly evaluated in bioassays in order to establish the effects of different agents on early development and reproductive capabilities in fish and other aquatic animals. In fish, the breakdown of the chorion is achieved by the secretion of choriolysin by hatching gland cells (HGCs) into the perivitelline space (PVS), coupled with spontaneous movements of the developing larva...
April 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28366621/rescue-of-pink1-deficiency-by-stress-dependent-activation-of-autophagy
#7
Yuxi Zhang, David T Nguyen, Ellen M Olzomer, Gin P Poon, Nicholas J Cole, Anita Puvanendran, Brigitte R Phillips, Daniel Hesselson
Stimulating autophagy is a promising therapeutic strategy for slowing the progression of neurodegenerative disease. Neurons are insensitive to current approaches based on mTOR inhibition for activating autophagy, and instead may rely on the Parkinson's disease-associated proteins PINK1 and PARKIN to activate the autophagy-lysosomal pathway in response to mitochondrial damage. We developed a multifactorial zebrafish drug-screening platform combining Pink1 deficiency with an environmental toxin to compromise mitochondrial function and trigger dopaminergic neuron loss...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28365195/zebrafish-foxp3-is-required-for-the-maintenance-of-immune-tolerance
#8
Kotaro Sugimoto, Subhra P Hui, Delicia Z Sheng, Maki Nakayama, Kazu Kikuchi
Regulatory T (Treg) cells play a central role in the suppression of excessive immune responses against both self and non-self antigens. The development and function of Treg cells are controlled by a master regulatory gene encoding the forkhead box P3 (FOXP3) protein in mammals. However, little is known regarding the functions of Treg cells and FOXP3 in non-mammalian vertebrates. In this study, we generated mutant zebrafish lacking a functional FOXP3 ortholog, and demonstrated a significant reduction in survival accompanied by a marked increase in inflammatory gene expression, mononuclear cell infiltration, and T cell proliferation in peripheral tissues...
March 30, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28334933/disrupted-in-schizophrenia-1is-essential-for-normal-hypothalamic-pituitary-interrenal-hpi-axis-function
#9
Helen Eachus, Charlotte Bright, Vincent T Cunliffe, Marysia Placzek, Jonathan D Wood, Penelope J Watt
Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331079/characterization-and-vaccine-potential-of-membrane-vesicles-produced-by-francisella-noatunensis-sup-orientalis-in-an-adult-zebrafish-model
#10
Leidy Lagos, Julia I Tandberg, Urska Repnik, Preben Boysen, Erik Ropstad, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen
Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. Francisella noatunensis subspecies orientalis (Fno) are Gram-negative, facultative intracellular bacteria that cause the disease francisellosis in fish. Francisellosis is commonly characterized as a chronic granulomatous disease with high morbidity and can result in high mortality depending on the host...
March 22, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28304369/the-role-of-adaptive-immunity-as-an-ecological-filter-on-the-gut-microbiota-in-zebrafish
#11
Keaton Stagaman, Adam R Burns, Karen Guillemin, Brendan Jm Bohannan
All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1(-) zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota...
March 17, 2017: ISME Journal
https://www.readbyqxmd.com/read/28279710/satellite-like-cells-contribute-to-pax7-dependent-skeletal-muscle-repair-in-adult-zebrafish
#12
Michael A Berberoglu, Thomas L Gallagher, Zachary T Morrow, Jared C Talbot, Kimberly J Hromowyk, Inês M Tenente, David M Langenau, Sharon L Amacher
Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle...
April 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28266617/a-missense-mutation-in-zbtb17-blocks-the-earliest-steps-of-t-cell-differentiation-in-zebrafish
#13
Divine-Fondzenyuy Lawir, Norimasa Iwanami, Michael Schorpp, Thomas Boehm
T cells are an evolutionarily conserved feature of the adaptive immune systems of vertebrates. Comparative studies using evolutionarily distant species hold great promise for unraveling the genetic landscape underlying this process. To this end, we used ENU mutagenesis to generate mutant zebrafish with specific aberrations in early T cell development. Here, we describe the identification of a recessive missense mutation in the transcriptional regulator zbtb17 (Q562K), which affects the ninth zinc finger module of the protein...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263972/the-pre-rrna-processing-factor-def-is-rate-limiting-for-the-pathogenesis-of-mycn-driven-neuroblastoma
#14
T Tao, S B Sondalle, H Shi, S Zhu, A R Perez-Atayde, J Peng, S J Baserga, A T Look
The nucleolar factor, digestive organ expansion factor (DEF), has a key role in ribosome biogenesis, functioning in pre-ribosomal RNA (pre-rRNA) processing as a component of the small ribosomal subunit (SSU) processome. Here we show that the peripheral sympathetic nervous system (PSNS) is very underdeveloped in def-deficient zebrafish, and that def haploinsufficiency significantly decreases disease penetrance and tumor growth rate in a MYCN-driven transgenic zebrafish model of neuroblastoma that arises in the PSNS...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28249360/heart-function-and-hemodynamics-analysis-for-zebrafish-embryos
#15
REVIEW
Huseyin C Yalcin, Armin Amindari, Jonathan T Butcher, Asma Althani, Magdi Yacoub
The zebrafish has emerged to become a powerful vertebrate animal model for cardiovascular research in recent years. Its advantages include easy genetic manipulation, transparency, small size, low cost, and the ability to survive without active circulation at early stages of development. Sequencing the whole genome and identifying orthologue genes with human genome enabled to induce clinically relevant cardiovascular defects via genetic approaches. Heart function and disturbed hemodynamics need to be assessed in a reliable manner for these disease models in order to reveal mechanobiology of induced defects...
March 1, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28247754/small-sized-mpeg-plga-nanoparticles-of-schisantherin-a-with-sustained-release-for-enhanced-brain-uptake-and-anti-parkinsonian-activity
#16
Tongkai Chen, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson's disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG-PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of ∼91% and drug loading of ∼28%...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28242612/fgf-and-canonical-wnt-signaling-cooperate-to-induce-paraxial-mesoderm-from-tailbud-neuromesodermal-progenitors-through-regulation-of-a-two-step-emt
#17
Hana Goto, Samuel C Kimmey, Richard H Row, David Q Matus, Benjamin L Martin
Mesoderm induction begins during gastrulation. Recent evidence from several vertebrate species indicates mesoderm induction continues after gastrulation in neuromesodermal progenitor cells (NMPs) within the posterior-most embryonic structure called the tailbud. It is unclear to what extent the molecular mechanisms of mesoderm induction are conserved between gastrula and post-gastrula stages of development. Fibroblast growth factor (FGF) signaling is required for mesoderm induction during gastrulation through positive transcriptional regulation of the t-box transcription factor brachyury (ntla in zebrafish)...
February 27, 2017: Development
https://www.readbyqxmd.com/read/28237116/methods-to-study-autophagy-in-zebrafish
#18
E Fodor, T Sigmond, E Ari, K Lengyel, K Takács-Vellai, M Varga, T Vellai
Autophagy (cellular self-eating) is a highly regulated degradation process of the eukaryotic cell during which parts of the cytoplasm are delivered into, and broken down within, the lysosomal compartment. The process serves as a main route for the elimination of superfluous and damaged cellular constituents, thereby mediating macromolecular and organellar turnover. In addition to maintaining cellular homeostasis, autophagy is involved in various other cellular and developmental processes by degrading specific regulatory proteins, and contributing to the clearance of intracellular pathogens...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28208665/effect-of-photon-hormesis-on-dose-responses-to-alpha-particles-in-zebrafish-embryos
#19
Candy Yuen Ping Ng, Shuk Han Cheng, Kwan Ngok Yu
Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET) value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio) as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf) revealed through acridine orange (AO) staining...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207787/hyaluronic-acid-synthesis-is-required-for-zebrafish-tail-fin-regeneration
#20
Xiaohu Ouyang, Nicholas J Panetta, Maya D Talbott, Alexander Y Payumo, Caroline Halluin, Michael T Longaker, James K Chen
Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation...
2017: PloS One
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