Development of schemas revealed by prior experience and NMDA receptor knock-out by Dragoi, George, Tonegawa, Susumu

Get full text
Get full text

Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity by Regev, Aviv

“…CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-Ag7 These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. …”
Get full text

A Modular Assembly Platform for Rapid Generation of DNA Constructs by Tammela, Tuomas, Chang, Gregory P., Wagner, Bethany L., Lee, Da-Yae, Papagiannakopoulos, Thales, Xue, Wen, Joshi, Nik, Akama-Garren, Elliot, Rideout, William M., Jacks, Tyler E

“…Our data demonstrate the applicability of GMAP toward the validation of synthetic promoters, identification of potent RNAi constructs, establishment of inducible lentiviral systems, tumor initiation in genetically engineered mouse models, and gene-targeting for the generation of knock-in mice. GMAP represents a recombinant DNA technology designed for widespread circulation and easy adaptation for other uses, such as synthetic biology, genetic screens, and CRISPR-Cas9.…”
Get full text
Get full text
Get full text
Get full text
Get full text

SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10 by Donmez Yalcin, Gizem, Cohen, Dena E., Wang, Diana G., Guarente, Leonard Pershing

“…Here we show that production of β-amyloid and plaques in a mouse model of AD are reduced by overexpressing the NAD-dependent deacetylase SIRT1 in brain, and are increased by knocking out SIRT1 in brain. SIRT1 directly activates the transcription of the gene encoding the α-secretase, ADAM10. …”
Get full text
Get full text

Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter Jejuni by Ciulli, Alessio, De Schutter, Joris, Morrison, James P., Morrison, Michael James, Imperiali, Barbara

“…In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. …”
Get full text
Get full text
Get full text

Caldag-Gefi Down-Regulation in the Striatum as a Neuroprotective Change in Huntington's Disease. by Dunn, Denise E., Merali, Farhan I., Woodman, Ben, Yim, Michael, Borkowska, Anna E., Frosch, Matthew P., Bates, Gillian P., Lo, Donald C., Crittenden, Jill R, Housman, David E, Graybiel, Ann M

“…In a brain-slice explant model of HD, knock-down of CalDAG-GEFI expression rescues striatal neurons from pathology induced by transfection of polyglutamine-expanded Htt exon 1. …”
Get full text
Get full text
Get full text

Integrin beta(1)-focal adhesion kinase signaling directs the proliferation of metastatic cancer cells disseminated in the lungs by Shibue, Tsukasa, Weinberg, Robert A

“…Activation of FAK in these metastatic cells depends on expression of the β1 subunit of integrins, and proliferation of these cells after extravasation in the lungs is diminished by knocking down the expression of either FAK or integrin β1. …”
Get full text
Get full text

Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function by Tao, Jifang, Hu, Keping, Chang, Qiang, Wu, Hao, Sherman, Nicholas E., Martinowich, Keri, Klose, Robert J., Schanen, Carolyn, Jaenisch, Rudolf, Wang, Weidong, Sun, Yi Eve

“…We demonstrate that serine 80 (S80) phosphorylation of MeCP2 is critical as its mutation into alanine (S80A) in transgenic knock-in mice leads to locomotor deficits. S80A mutation attenuates MeCP2 chromatin association at several gene promoters in resting neurons and leads to transcription changes of a small number of genes. …”
Get full text

Growth landscape formed by perception and import of glucose in yeast by Youk, Hyun, van Oudenaarden, Alexander

“…Disrupting this interaction by knocking out two key glucose sensors significantly changes the cell’s growth rate, yet uptake rates are unchanged. …”
Get full text

SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin by Simic, Petra, Zainabadi, Kayvan, Sykes, David B., Saez, Borja, Lotinun, Sutada, Baron, Roland, Scadden, David, Schipani, Ernestina, Bell, Eric L., Guarente, Leonard Pershing

“…We investigated whether the sirtuin SIRT1 had a function in MSCs by creating MSC specific SIRT1 knock‐out (MSCKO) mice. Aged MSCKO mice (2.2 years old) showed defects in tissues derived from MSCs; i.e. a reduction in subcutaneous fat, cortical bone thickness and trabecular volume. …”
Get full text
Get full text

Distinct EMT programs control normal mammary stem cells and tumour-initiating cells by Ye, Xin, Tam, Wai Leong, Shibue, Tsukasa, Kaygusuz, Yasemin, Ng Eaton, Elinor, Reinhardt, Ferenc, Weinberg, Robert A

“…Using genetically engineered knock-in reporter mouse lines, here we show that normal gland-reconstituting mammary stem cells residing in the basal layer of the mammary epithelium and breast TICs originating in the luminal layer exploit the paralogous EMT-TFs Slug and Snail, respectively, which induce distinct EMT programs. …”
Get full text
Get full text

Histone deacetylase 2 is required for chromatin condensation and subsequent enucleation of cultured mouse fetal erythroblasts by Ji, Peng, Yeh, Victor, Ramirez, Tzutzuy, Murata-Hori, Maki, Lodish, Harvey F

“…Short hairpin RNA down-regulation of histone deacetylase 2, but not of the other histone deacetylases, phenotypically mimicked the effect of trichostatin A or valproic acid treatment, causing significant inhibition of chromatin condensation and enucleation. Importantly, knock-down of histone deacetylase 2 did not affect erythroblast proliferation, differentiation, or apoptosis. …”
Get full text
Get full text

Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration by Horvitz, Howard Robert

“…In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: −0.49, P = 1.83 × 10−12 (start codon morpholino) and −0.46, P = 4.05 × 10−9 (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P = 0.01). …”
Get full text
Get full text

T-cell death following immune activation is mediated by mitochondria-localized SARM by Panneerselvam, P., Singh, L. P., Selvarajan, V., Chng, W. J., Ng, S. B., Tan, N. S., Ho, B., Ding, Jeak Ling, Chen, Jianzhu

“…SARM expression is significantly reduced in natural killer (NK)/T lymphoma patients compared with healthy individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T cells knocked down of SARM survived and proliferated more significantly compared with wild-type T cells following influenza infection in vivo. …”
Get full text
Get full text

Invasive breast carcinoma cells from patients exhibit Mena[superscript INV]- and macrophage-dependent transendothelial migration by Gertler, Frank, Pignatelli, Jeanine, Goswami, Sumanta, Jones, Joan G., Rohan, Thomas E., Pieri, Evan, Chen, Xiaoming, Adler, Esther, Cox, Dianne, Maleki, Sara, Bresnick, Anne, Condeelis, John S., Oktay, Maja H.

“…The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena[superscript INV] or adding an antibody that blocks CSF-1R function prevented transendothelial migration. …”
Get full text
Get full text

Dose-Response Analysis of Chemotactic Signaling Response in Salmonella typhimurium LT2 upon Exposure to Cysteine / Cystine Redox Pair by Rosier, Bob T., Lazova, Milena

“…In contrast to S. typhimurium 14028, where no response to cystine was observed in a knockout strain of chemoreceptor genes mcpB and mcpC, here we showed that McpB / McpC-independent responses to cystine existed in the strain S. typhimurium LT2 even at nanomolar concentrations. Additionally, knocking out mcpB and mcpC did not affect the linear dose-response dependence, whereas enhanced responses were only observed to solutions that where not pH neutral ( > 100 μM cystine) in the case of McpC overexpression. …”
Get full text
Get full text

Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4′-Deoxyflavones in Scutellaria baicalensis by Zhao, Qing, Cui, Meng-Ying, Levsh, Olesya, Yang, Dongfeng, Liu, Jie, Li, Jie, Hill, Lionel, Hu, Yonghong, Weng, Jing-Ke, Chen, Xiao-Ya, Martin, Cathie, Yang, Lei,S.M.Massachusetts Institute of Technology.

“…When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. …”
Get full text
Get full text

Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen by Bienvenu, Frederic, Jirawatnotai, Siwanon, Elias, Joshua E., Meyer, Clifford A., Mizeracka, Karolina, Marson, Alexander, Frampton, Garrett M., Cole, Megan F., Odom, Duncan, Odajima, Junko, Geng, Yan, Zagozdzon, Agnieszka, Jecrois, Marie, Young, Richard A., Liu, X. Shirley, Cepko, Constance L., Gygi, Steven P., Sicinski, Piotr

Get full text
Get full text

Enhancing tumor cell response to chemotherapy through nanoparticle-mediated codelivery of siRNA and cisplatin prodrug by Xu, Xiaoyang, Xie, Kun, Zhang, Xue-Qing, Pridgen, Eric M., Park, Ga Young, Cui, Danica S., Shi, Jinjun, Kantoff, Philip W., Lippard, Stephen J., Walker, Graham C., Farokhzad, Omid C., Langer, Robert S, Wu, Jun

“…We demonstrated the potency of the siRNA-containing NPs to knock down target genes efficiently both in vitro and in vivo. …”
Get full text
Get full text
Get full text
Get full text
Get full text

A CRISPR Interference System for Efficient and Rapid Gene Knockdown in Caulobacter crescentus by Guzzo, Mathilde, Castro, Lennice K., Reisch, Christopher R., Guo, Monica S., Laub, Michael T.

“…CRISPR interference (CRISPRi) is a powerful new tool used in different organisms that provides a fast, specific, and reliable way to knock down gene expression. Caulobacter crescentus is a well-studied model bacterium, and although a variety of genetic tools have been developed, it currently takes several weeks to delete or deplete individual genes, which significantly limits genetic studies. …”
Get full text