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https://www.readbyqxmd.com/read/27936496/simultaneous-stimulation-of-the-sbpase-fbp-aldolase-and-the-photorespiratory-gdc-h-protein-increases-co2-assimilation-vegetative-biomass-and-seed-yield-in-arabidopsis
#1
Andrew J Simkin, Patricia E Lopez-Calcagno, Philip A Davey, Lauren R Headland, Tracy Lawson, Stefan Timm, Hermann Bauwe, Christine A Raines
In this paper we have altered the levels of three different enzymes involved in the Calvin Benson cycle and photorespiratory pathway. We have generated transgenic Arabidopsis plants with altered combinations of sedoheptulose 1,7-bisphosphatase (SBPase), fructose 1,6-bisphophate aldolase (FBPA) and the glycine decarboxylase H-protein (GDC-H) gene identified as targets to improve photosynthesis based on previous studies. Here, we show that increasing the levels of the three corresponding proteins, either independently or in combination, significantly increases the quantum efficiency of PSII...
December 9, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27936493/new-additions-to-the-cluspro-server-motivated-by-capri
#2
Sandor Vajda, Christine Yueh, Dmitri Beglov, Tanggis Bohnuud, Scott E Mottarella, Bing Xia, David R Hall, Dima Kozakov
The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for Small Angle X-ray Scattering (SAXS) data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936492/lncrna-a-versatile-regulator-of-the-nf-%C3%AE%C2%BAb-signaling-circuit
#3
REVIEW
Xiaohua Mao, Zhenyi Su, Adnan K Mookhtiar
The Nuclear Factor-κB (NF-κB) family of transcription factors play an essential role for the regulation of inflammatory responses, immune function and malignant transformation. Aberrant activity of this signaling pathway may lead to inflammation, autoimmune diseases and oncogenesis. Over the last two decades great progress has been made in the understanding of NF-κB activation and how the response is counteracted for maintaining tissue homeostasis. Therapeutic targeting of this pathway has largely remained ineffective due to the widespread role of this vital pathway and the lack of specificity of the therapies currently available...
December 9, 2016: Immunology
https://www.readbyqxmd.com/read/27936466/dpp4-cd26-overexpression-in-urothelial-carcinoma-confers-an-independent-prognostic-impact-and-correlates-with-intrinsic-biological-aggressiveness
#4
Peir-In Liang, Bi-Wen Yeh, Wei-Ming Li, Ti-Chun Chan, I-Wei Chang, Chun-Nung Huang, Ching-Chia Li, Hung-Lung Ke, Hsin-Chih Yeh, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC) is common cancer worldwide. The molecular aberrations regarding tumor progression remain unclear. Pericellular proteolysis is crucial in tumorigenesis, but its significance is unexplored in UC. By data mining the datasets in Gene Expression Omnibus, specifically focus on the proteolysis pathway, and followed by a preliminary validation in a pilot batch of tumor samples, we identified that the upregulation of dipeptidyl peptidase 4 (DPP4) was most significantly associated with clinical aggressiveness of UCs...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936456/1%C3%AE-25-dihydroxyvitamin-d-inhibits-de-novo-fatty-acid-synthesis-and-lipid-accumulation-in-metastatic-breast-cancer-cells-through-down-regulation-of-pyruvate-carboxylase
#5
Tomasz Wilmanski, Kimberly Buhman, Shawn S Donkin, John R Burgess, Dorothy Teegarden
Both increased de novo fatty acid synthesis and higher neutral lipid accumulation are a common phenotype observed in aggressive breast cancer cells, making lipid metabolism a promising target for breast cancer prevention. In the present studies, we demonstrate a novel effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)₂D) on lipid metabolism in malignant breast epithelial cells. Treatment of MCF10CA1a breast epithelial cells with 1,25(OH)₂D (10 nM) for 5 and 7 days decreased the level of triacylglycerol, the most abundant form of neutral lipids, by 20%(±3...
December 1, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27936446/design-synthesis-and-evaluation-of-4-aminoquinoline-purine-hybrids-as-potential-antiplasmodial-agents
#6
P Linga Reddy, Shabana I Khan, Prija Ponnan, Mohit Tripathi, Diwan S Rawat
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P...
December 1, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27936416/antigen-recognition-triggered-drug-delivery-mediated-by-nanocapsule-functionalized-cytotoxic-t-cells
#7
R Brad Jones, Stephanie Mueller, Sudha Kumari, Vlad Vrbanac, Shy Genel, Andrew M Tager, Todd M Allen, Bruce D Walker, Darrell J Irvine
Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27936412/contribution-of-cellular-autolysis-to-tissular-functions-during-plant-development
#8
REVIEW
Sacha Escamez, Hannele Tuominen
Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it appears biologically meaningful to distinguish between the modules of PCD and autolysis during plant development...
December 6, 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/27936408/biased-mu-opioid-receptor-ligands-a-promising-new-generation-of-pain-therapeutics
#9
REVIEW
Edward R Siuda, Richard Carr, David H Rominger, Jonathan D Violin
Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events...
December 6, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27936398/microrna138-regulates-keratin-17-protein-expression-to-affect-hacat-cell-proliferation-and-apoptosis-by-targeting-htert-in-psoriasis-vulgaris
#10
Shi-Jun Feng, Rui-Qi Chu, Jing Ma, Zheng-Xiang Wang, Guang-Jing Zhang, Xiu-Fang Yang, Zhi Song, Yun-Yi Ma
The purpose of this study is to explore the how microRNA-138 (miR-138) affects the expression of keratin 17 (K17) and psoriasis development. Twenty-eight skin lesions from patients with psoriasis vulgaris and twenty-four normal skin tissues from healthy controls were collected. The HaCaT cells were assigned into blank, negative control (NC), miR-138 mimic, miR-138 inhibitor, hTERT siRNA and miR-138 inhibitor+hTERT siRNA groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the miR-138 expression...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27936285/what-do-reactive-fragments-actually-do-in-cells
#11
Oliver Plettenburg
Covalently binding molecules are frequently regarded as being generally promiscuous. In a recent study, binding selectivities and cellular target proteins of a wide variety of reactive fragments are examined in a proteome-wide context.
December 9, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27936133/polyglycine-acts-as-a-rejection-signal-for-protein-transport-at-the-chloroplast-envelope
#12
Joshua K Endow, Agostinho Gomes Rocha, Amy J Baldwin, Rebecca L Roston, Toshio Yamaguchi, Hironari Kamikubo, Kentaro Inoue
PolyGly is present in many proteins in various organisms. One example is found in a transmembrane β-barrel protein, translocon at the outer-envelope-membrane of chloroplasts 75 (Toc75). Toc75 requires its N-terminal extension (t75) for proper localization. t75 comprises signals for chloroplast import (n75) and envelope sorting (c75) in tandem. n75 and c75 are removed by stromal processing peptidase and plastidic type I signal peptidase 1, respectively. PolyGly is present within c75 and its deletion or substitution causes mistargeting of Toc75 to the stroma...
2016: PloS One
https://www.readbyqxmd.com/read/27936065/kinase-screening-in-pichia-pastoris-identified-promising-targets-involved-in-cell-growth-and-alcohol-oxidase-1-promoter-paox1-regulation
#13
Wei Shen, Chuixing Kong, Ying Xue, Yiqi Liu, Menghao Cai, Yuanxing Zhang, Tianyi Jiang, Xiangshan Zhou, Mian Zhou
As one of the most commonly used eukaryotic recombinant protein expression systems, P. pastoris relies heavily on the AOX1 promoter (PAOX1), which is strongly induced by methanol but strictly repressed by glycerol and glucose. However, the complicated signaling pathways involved in PAOX1 regulation when supplemented with different carbon sources are poorly understood. Here we constructed a kinase deletion library in P. pastoris and identified 27 mutants which showed peculiar phenotypes in cell growth or PAOX1 regulation...
2016: PloS One
https://www.readbyqxmd.com/read/27935997/endoplasmic-reticulum-targeted-subunit-toxins-provide-a-new-approach-to-rescue-misfolded-mutant-proteins-and-revert-cell-models-of-genetic-diseases
#14
Humaira Adnan, Zhenbo Zhang, Hyun-Joo Park, Chetankumar Tailor, Clare Che, Mustafa Kamani, George Spitalny, Beth Binnington, Clifford Lingwood
Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology...
2016: PloS One
https://www.readbyqxmd.com/read/27935965/bypass-of-candida-albicans-filamentation-biofilm-regulators-through-diminished-expression-of-protein-kinase-cak1
#15
Carol A Woolford, Katherine Lagree, Wenjie Xu, Tatyana Aleynikov, Hema Adhikari, Hiram Sanchez, Paul J Cullen, Frederick Lanni, David R Andes, Aaron P Mitchell
Biofilm formation on implanted medical devices is a major source of lethal invasive infection by Candida albicans. Filamentous growth of this fungus is tied to biofilm formation because many filamentation-associated genes are required for surface adherence. Cell cycle or cell growth defects can induce filamentation, but we have limited information about the coupling between filamentation and filamentation-associated gene expression after cell cycle/cell growth inhibition. Here we identified the CDK activating protein kinase Cak1 as a determinant of filamentation and filamentation-associated gene expression through a screen of mutations that diminish expression of protein kinase-related genes implicated in cell cycle/cell growth control...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27935964/gw182-free-microrna-silencing-complex-controls-post-transcriptional-gene-expression-during-caenorhabditis-elegans-embryogenesis
#16
Guillaume Jannot, Pascale Michaud, Miguel Quévillon Huberdeau, Louis Morel-Berryman, James A Brackbill, Sandra Piquet, Katherine McJunkin, Kotaro Nakanishi, Martin J Simard
MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27935957/intracellular-zn-ii-intoxication-leads-to-dysregulation-of-the-perr-regulon-resulting-in-heme-toxicity-in-bacillus-subtilis
#17
Pete Chandrangsu, John D Helmann
Transition metal ions (Zn(II), Cu(II)/(I), Fe(III)/(II), Mn(II)) are essential for life and participate in a wide range of biological functions. Cellular Zn(II) levels must be high enough to ensure that it can perform its essential roles. Yet, since Zn(II) binds to ligands with high avidity, excess Zn(II) can lead to protein mismetallation. The major targets of mismetallation, and the underlying causes of Zn(II) intoxication, are not well understood. Here, we use a forward genetic selection to identify targets of Zn(II) toxicity...
December 9, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#18
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935862/targeting-of-interleukin-il-17a-inhibits-pdl1-expression-in-tumor-cells-and-induces-anticancer-immunity-in-an-estrogen-receptor-negative-murine-model-of-breast-cancer
#19
Yun-Feng Ma, Chen Chen, Dongqing Li, Min Liu, Zhuang-Wei Lv, Yanhong Ji, Jiru Xu
The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935847/structure-based-development-of-pde%C3%AE-inhibitors
#20
Pablo Martín-Gago, Eyad Kalawy Fansa, Alfred Wittinghofer, Herbert Waldmann
The prenyl binding protein PDEδ enhances the diffusion of farnesylated Ras proteins in the cytosol, ultimately affecting their correct localization and signaling. This has turned PDEδ into a promising target to prevent oncogenic KRas signaling. In this review we summarize and describe the structure-guided-development of the three different PDEδ inhibitor chemotypes that have been documented so far. We also compare both their potency for binding to the PDEδ pocket and their in vivo efficiency in suppressing oncogenic KRas signaling, as a result of the inhibition of the PDEδ/KRas interaction...
November 17, 2016: Biological Chemistry
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