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https://www.readbyqxmd.com/read/28728075/immunological-tolerance-as-a-barrier-to-protective-hiv-humoral-immunity
#1
REVIEW
Kristin Ms Schroeder, Amanda Agazio, Raul M Torres
HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28727987/associations-of-autoimmunity-immunodeficiency-lymphomagenesis-and-gut-microbiota-in-mice-with-knockins-for-a-pathogenic-autoantibody
#2
Shweta Jain, Jerrold M Ward, Dong-Mi Shin, Hongsheng Wang, Zohreh Naghashfar, Alexander L Kovalchuk, Herbert C Morse
A number of mouse strains transgenic for B-cell receptors specific for nucleic acids or other autoantigens have been generated to understand how autoreactive B cells are regulated in normal and autoimmune mice. Previous studies of nonautoimmune C57BL/6 mice heterozygous for both the IgH and IgL knockins of the polyreactive autoantibody, 564, produced high levels of autoantibodies in a largely Toll-like receptor 7-dependent manner. Herein, we describe studies of mice homozygous for the knockins that also expressed high levels of autoantibodies but, unlike the heterozygotes, exhibited a high incidence of mature B-cell lymphomas and enhanced susceptibility to bacterial infections...
July 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28723571/emi2-is-essential-for-mouse-spermatogenesis
#3
Lakshmi Gopinathan, Radoslaw Szmyd, Diana Low, M Kasim Diril, Heng-Yu Chang, Vincenzo Coppola, Kui Liu, Lino Tessarollo, Ernesto Guccione, Ans M M van Pelt, Philipp Kaldis
The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2-in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28716990/proof-of-principle-for-a-novel-class-of-antihypertensives-that-target-the-oxidative-activation-of-protein-kinase-g-i%C3%AE
#4
Joseph R Burgoyne, Oleksandra Prysyazhna, Daniel A Richards, Philip Eaton
Arterial hypertension continues to be a major health burden. Development of new antihypertensive drugs that engage vasodilatory mechanisms not harnessed by available therapies offer therapeutic potential. Oxidants induce an interprotein disulfide in protein kinase G Iα (PKG Iα) at C42, which is associated with its targeting and activation, resulting in vasodilation and blood pressure lowering. Consequently, we developed an assay and screened for electrophilic drugs that activate PKG Iα by selectively targeting C42, as such compounds have potential as novel antihypertensives with a mechanism of action that differs from current therapies...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28714144/cerebellins-are-differentially-expressed-in-selective-subsets-of-neurons-throughout-the-brain
#5
Erica Seigneur, Thomas C Südhof
Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer' (DCC), and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion...
July 16, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28710355/high-resolution-imaging-of-dna-methylation-dynamics-using-a-zebrafish-reporter
#6
Ranran Zhang, Lian Liu, Yuxiao Yao, Fei Fei, Feng Wang, Qian Yang, Yonghao Gui, Xu Wang
As one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684956/knockin-out-the-spasms
#7
COMMENT
Libor Velíšek
No abstract text is available yet for this article.
May 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28675425/foxc2-influences-alveolar-epithelial-cell-differentiation-during-lung-development
#8
Mayoko Tsuji, Masae Morishima, Kazuhiko Shimizu, Shunichi Morikawa, Mikael Heglind, Sven Enerbäck, Taichi Ezaki, Jun Tamaoki
FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2(+/-) mice and then analyzed...
July 4, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28671867/knockin-on-heaven-s-door-end-of-life-decisions-and-discussions
#9
Curt Tribble Md
More than 2.5 million people die in the United States each year. For the majority who live out their final days in various institutions or in hospice care, decisions must be made about which treatments to administer, which treatments to stop, which treatments to continue, and which treatments to back off of. Thus, while death remains inevitable, its timing is often very much a function of human agency. Once it was common to speak of "nature taking its course," but now it has become as common to view death as something about which people have some control [Meisel 2008]...
June 29, 2017: Heart Surgery Forum
https://www.readbyqxmd.com/read/28654070/generation-of-genetically-modified-mice-through-the-microinjection-of-oocytes
#10
Fabien Delerue, Lars M Ittner
The use of genetically modified mice has significantly contributed to studies on both physiological and pathological in vivo processes. The pronuclear injection of DNA expression constructs into fertilized oocytes remains the most commonly used technique to generate transgenic mice for overexpression. With the introduction of CRISPR technology for gene targeting, pronuclear injection into fertilized oocytes has been extended to the generation of both knockout and knockin mice. This work describes the preparation of DNA for injection and the generation of CRISPR guides for gene targeting, with a particular emphasis on quality control...
June 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#11
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28645528/long-term-sustainable-dendritic-cell-specific-depletion-murine-model-for-periodontitis-research
#12
Amanda Finger Stadler, Mitulkumar Patel, Rafal Pacholczyk, Christopher W Cutler, Roger M Arce
Dendritic cells (DCs) are specialized antigen-presenting cells that play a pivotal role in the pathogenesis of periodontitis. The use of animal models to study the role of DCs in periodontitis has been limited by lack of a method for sustained depletion of DCs. Hence, the objectives of this study were to validate the zDC-DTR knockin mouse model of conventional DCs (cDCs) depletion, as well as to investigate whether this depletion could be sustained long enough to induce alveolar bone loss in this model. zDC-DTR mice were treated with different dose regimens of diphtheria toxin (DT) to determine survival rate...
June 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28643262/genome-editing-in-the-cricket-gryllus-bimaculatus
#13
Takahito Watanabe, Sumihare Noji, Taro Mito
Hemimetabolous, or incompletely metamorphosing, insects are phylogenetically basal and include many beneficial and deleterious species. The cricket, Gryllus bimaculatus, is an emerging model for hemimetabolous insects, based on the success of RNA interference (RNAi)-based gene-functional analyses and transgenic technology. Taking advantage of genome editing technologies in this species would greatly promote functional genomics studies. Genome editing has proven to be an effective method for site-specific genome manipulation in various species...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643258/crispr-cas9-mediated-targeted-knockin-of-exogenous-reporter-genes-in-zebrafish
#14
Atsuo Kawahara
Genome editing technologies such as ZFN, TALEN, and CRISPR/Cas9 efficiently induce DNA double-stranded breaks (DSBs) at a targeted genomic locus, often resulting in a frameshift-mediated target gene disruption. It remains difficult to perform targeted integration of exogenous genes by genome editing technologies. DSBs can be restored through DNA repair mechanisms, such as non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination (HR). It is well known that HR facilitates homology-dependent integration of donor DNA template into a targeted locus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28628038/crispr-cas9-mediated-gene-editing-ameliorates-neurotoxicity-in-mouse-model-of-huntington-s-disease
#15
Su Yang, Renbao Chang, Huiming Yang, Ting Zhao, Yan Hong, Ha Eun Kong, Xiaobo Sun, Zhaohui Qin, Peng Jin, Shihua Li, Xiao-Jiang Li
Huntington's disease is a neurodegenerative disorder caused by a polyglutamine repeat in the Huntingtin gene (HTT). Although suppressing the expression of mutant HTT (mHTT) has been explored as a therapeutic strategy to treat Huntington's disease, considerable efforts have gone into developing allele-specific suppression of mHTT expression, given that loss of Htt in mice can lead to embryonic lethality. It remains unknown whether depletion of HTT in the adult brain, regardless of its allele, could be a safe therapy...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625919/c1q-tnf-related-protein-1-promotes-endothelial-barrier-dysfunction-under-disturbed-flow
#16
Zhu Hui Liu, Chang Li, Jia Wei Chen, Ying Shen, Jie Gao, Wei Feng Shen, Rui Yan Zhang, Xiao Qun Wang, Lin Lu
Endothelial hyper-permeability is a major determinant factor that contributes to the accelerated development of atherosclerotic lesions at hemodynamically disturbed sites. Previously, we showed that C1q/TNF related protein (CTRP) 1 promotes endothelium-leukocyte interactions and inflammatory responses in vascular cells. Here, we sought to investigate the role of CTRP1 in modulation of endothelial permeability under disturbed flow condition. By using en face staining of mouse aorta, we found CTRP1 expression was significantly increased in vascular endothelial cells under disturbed flow as compared to steady laminar flow...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623169/mutation-of-the-inhibitory-ethanol-site-in-gabaa-%C3%AF-1-receptors-promotes-tolerance-to-ethanol-induced-motor-incoordination
#17
Yuri A Blednov, Cecilia M Borghese, Carlos I Ruiz, Madeline A Cullins, Adriana Da Costa, Elizabeth A Osterndorff-Kahanek, Gregg E Homanics, R Adron Harris
Genes encoding the ρ1/2 subunits of GABAA receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine)...
June 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28605434/a-knockin-mouse-model-of-spinocerebellar-ataxia-type-3-exhibits-prominent-aggregate-pathology-and-aberrant-splicing-of-the-disease-gene-transcript
#18
Biswarathan Ramani, Ginny M Harris, Rogerio Huang, Takahiro Seki, Geoffrey G Murphy, Maria do Carmo Costa, Svetlana Fischer, Thomas L Saunders, Guangbin Xia, Richard C McEachin, Henry L Paulson
No abstract text is available yet for this article.
June 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28593137/msk1-regulates-transcriptional-induction-of-arc-arg3-1-in-response-to-neurotrophins
#19
Chris J Hunter, Judit Remenyi, Sonia A Correa, Lucia Privitera, Kathleen M S E Reyskens, Kirsty J Martin, Rachel Toth, Bruno G Frenguelli, J Simon C Arthur
The immediate early gene activity-regulated cytoskeletal protein (Arc)/Arg3.1 and the neurotrophin brain-derived neurotrophic factor (BDNF) play important roles in synaptic plasticity and learning and memory in the mammalian brain. However, the mechanisms by which BDNF regulates the expression of Arc/Arg3.1 are unclear. In this study, we show that BDNF acts via the ERK1/2 pathway to activate the nuclear kinase mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 then induces Arc/Arg3.1 expression via the phosphorylation of histone H3 at the Arc/Arg3...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28589361/the-aid-cre-ert2-model-a-tool-for-monitoring-b-cell-immune-responses-and-generating-selective-hybridomas
#20
Simon Le Gallou, Takuya Nojima, Daisuke Kitamura, Jean-Claude Weill, Claude-Agnès Reynaud
Expression of activation-induced cytidine deaminase (AID) is the hallmark of B cells engaged in an immune response in germinal centers. We designed an inducible fate-mapping reporter mouse in which AID-expressing B cells could be timely and irreversibly marked, by knockin at the Aicda locus of a tamoxifen-inducible Cre recombinase. This mouse model allows notably for the long-term follow-up of memory B cells and plasma cells engaged in an immune response. We describe here a protocol to generate hybridomas from small memory subsets that can be easily traced and identified in this mouse line through Cre-activated fluorescent reporters...
2017: Methods in Molecular Biology
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