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On and Off Pathways

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https://www.readbyqxmd.com/read/29155285/parasite-infection-of-specific-host-genotypes-relates-to-changes-in-prevalence-in-two-natural-populations-of-bumblebees
#1
Oliver Manlik, Regula Schmid-Hempel, Paul Schmid-Hempel
The antagonistic relationship between parasites and their hosts is strongly influenced by genotype-by-genotype interactions. Defense against parasitism is commonly studied in the context of immune system-based mechanisms and, thus, the focus in the search for candidate genes in host-parasite interactions is often on immune genes. In this study, we investigated the association between prevalence of parasite infection and host mitochondrial DNA (mtDNA) haplotypes in two natural populations of bumblebees (Bombus terrestris)...
November 16, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29155145/differential-effects-of-the-nrf2-activators-tbhq-and-cddo-im-on-the-early-events-of-t-cell-activation
#2
Joseph W Zagorski, Alexandra E Turley, Robert A Freeborn, Kelly R VanDenBerg, Heather E Dover, Brian R Kardell, Karen T Liby, Cheryl E Rockwell
We previously demonstrated that activation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) promotes CD4+ Th2 differentiation. In the current study, we assessed the role of Nrf2 in early events following T cell activation. The Nrf2 activators, tBHQ (tert-butylhydroquinone) and CDDO-Im (the imidazolide derivative of the triterpenoid CDDO), were used in conjunction with splenocytes derived from wild-type and Nrf2-null mice to distinguish between Nrf2-specific and off-target effects...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29153163/a-100-year-review-methods-and-impact-of-genetic-selection-in-dairy-cattle-from-daughter-dam-comparisons-to-deep-learning-algorithms
#3
K A Weigel, P M VanRaden, H D Norman, H Grosu
In the early 1900s, breed society herdbooks had been established and milk-recording programs were in their infancy. Farmers wanted to improve the productivity of their cattle, but the foundations of population genetics, quantitative genetics, and animal breeding had not been laid. Early animal breeders struggled to identify genetically superior families using performance records that were influenced by local environmental conditions and herd-specific management practices. Daughter-dam comparisons were used for more than 30 yr and, although genetic progress was minimal, the attention given to performance recording, genetic theory, and statistical methods paid off in future years...
December 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29150846/cancer-stem-cells-as-targets-for-immunotherapy
#4
REVIEW
Amy S Codd, Takayuki Kanaseki, Toshihiko Torigo, Zsuzsanna Tabi
Current cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasise to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypic and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarise some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression...
November 18, 2017: Immunology
https://www.readbyqxmd.com/read/29148752/substituent-effects-on-the-reactivity-of-cyclic-tertiary-sulfamidates
#5
Claudio D Navo, Nuria Mazo, Alberto Avenoza, Jesús H Busto, Jesús M Peregrina, Gonzalo Jiménez-Osés
The reactivity of cyclic tertiary sulfamidates derived from α-methylisoserine strongly depends on the substitution at the C and N termini. These substrates are one of the very few examples able to undergo nucleophilic ring-opening at a quaternary carbon with complete inversion of the configuration, as demonstrated both experimentally and computationally. When the sulfonamide is unprotected, the characteristic ring-opening reaction is completely silenced, which explains that the majority of the ring-opening reactions reported in the literature invoke N-alkyl or N-acyl-protected sulfamidates...
November 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#6
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#7
Chao Zhang, Xin Zhang, Ran Xu, Bin Huang, An-Jing Chen, Chao Li, Jian Wang, Xin-Gang Li
BACKGROUND: Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29141603/detect-i-detect-ii-a-study-protocol-for-a-prospective-multicentre-observational-study-to-validate-the-uromark-assay-for-the-detection-of-bladder-cancer-from-urinary-cells
#8
Wei Shen Tan, Andrew Feber, Liqin Dong, Rachael Sarpong, Sheida Rezaee, Simon Rodney, Pramit Khetrapal, Patricia de Winter, Frelyn Ocampo, Rumana Jalil, Norman R Williams, Chris Brew-Graves, John D Kelly
BACKGROUND: Haematuria is a common finding in general practice which requires visual inspection of the bladder by cystoscopy as well as upper tract imaging. In addition, patients with non-muscle invasive bladder cancer (NMIBC) often require surveillance cystoscopy as often as three monthly depending on disease risk. However, cystoscopy is an invasive procedure which is uncomfortable, requires hospital attendance and is associated with a risk of urinary tract infection. We have developed the UroMark assay, which can detect 150 methylation specific alteration specific to bladder cancer using DNA from urinary sediment cells...
November 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29141117/tunable-energy-landscapes-to-control-pathway-complexity-in-self-assembled-n-heterotriangulenes-living-and-seeded-supramolecular-polymerization
#9
Jorge S Valera, Rafael Gómez, Luis Sánchez
Herein, the synthesis and self-assembling features of N-heterotriangulenes 1-3 decorated in their periphery with 3,4,5-trialkoxy-N-(alkoxy)benzamide moieties that enable kinetic control of the supramolecular polymerization process are described. The selection of an appropriate solvent results in a tunable energy landscape in which the relative energy of the different monomeric or aggregated species can be regulated. Thus, in a methylcyclohexane/toluene (MCH/Tol) mixture, intramolecular hydrogen-bonding interactions in the peripheral side units favor the formation of metastable inactivated monomers that evolve with time at precise conditions of concentration and temperature...
November 15, 2017: Small
https://www.readbyqxmd.com/read/29136467/equilibrating-l-fe-iii-ooac-and-l-fe-v-o-species-in-hydrocarbon-oxidations-by-bio-inspired-nonheme-iron-catalysts-using-h2o2-and-acoh
#10
Williamson N Oloo, Rahul Banerjee, John D Lipscomb, Lawrence Que
Inspired by the remarkable chemistry of the family of Rieske oxygenase enzymes, nonheme iron complexes of tetradentate N4 ligands have been developed to catalyze hydrocarbon oxidation reactions using H2O2 in the presence of added carboxylic acids. The observation that the stereo- and enantioselectivity of the oxidation products can be modulated by the electronic and steric properties of the acid implicates an oxidizing species that incorporates the carboxylate moiety. Frozen solutions of these catalytic mixtures generally afford two S = ½ intermediates, a highly anisotropic g2...
November 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29136139/rad-seq-reveals-patterns-of-additive-polygenic-variation-caused-by-spatially-varying-selection-in-the-american-eel-anguilla-rostrata
#11
Charles Babin, Pierre-Alexandre Gagnaire, Scott A Pavey, Louis Bernatchez
The American Eel (Anguilla rostrata) has an exceptional life cycle characterized by panmictic reproduction at the species scale, random dispersal, and selection in a highly heterogeneous habitat extending from subtropical to subarctic latitudes. The genetic consequences of spatially-varying selection in this species have been investigated for decades, revealing subtle clines in allele frequency at a few loci that contrast with complete panmixia on the vast majority of the genome. Because reproduction homogenizes allele frequencies every generation, sampling size, and genomic coverage are critical to reach sufficient power to detect selected loci in this context...
November 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29133936/the-rho-gtpase-signalling-pathway-in-urothelial-carcinoma
#12
REVIEW
Solomon L Woldu, Ryan C Hutchinson, Laura-Maria Krabbe, Oner Sanli, Vitaly Margulis
Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29133761/reduction-on-off-responses-of-electroretinogram-in-monkeys-with-long-term-high-intraocular-pressure
#13
Ke-Gao Liu, Xiao-Yan Peng, Zheng Zhang, Hua Sun, Di-Ya Yang, Ning-Li Wang
BACKGROUND: There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram (ERG) are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure (IOP) might cause dysfunction of cone-dominated photopic negative response (PhNR) in monkeys with high IOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high IOP...
November 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29131578/optically-detected-magnetic-resonance-for-selective-imaging-of-diamond-nanoparticles
#14
Margaret E Robinson, James D Ng, Huilong Zhang, Joseph T Buchman, Olga A Shenderova, Christy L Haynes, Zhenqiang Ma, Randall H Goldsmith, Robert J Hamers
While there is great interest in understanding the fate and transport of nanomaterials in the environment and in biological systems, the detection of nanomaterials in complex matrices by fluorescence methods is complicated by photodegradation, blinking, and by the presence of natural organic material and other fluorescent background signals that hamper detection of fluorescent nanomaterials of interest. Optically detected magnetic resonance (ODMR) of nitrogen-vacancy (NV) centers in diamond nanoparticles provides a pathway toward background-free fluorescence measurements, as the application of a resonant microwave field can selectively modulate the intensity from NV centers in the diamond in nanodiamonds of various diameters in complex materials systems using on-resonance and off-resonance microwave fields...
November 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29128684/mapk-p38-regulates-inflammatory-gene-expression-via-tristetraprolin-doing-good-by-stealth
#15
J D O'Neil, A J Ammit, A R Clark
Tristetraprolin (TTP) is an RNA-destabilizing protein that exerts profound anti-inflammatory effects by inhibiting the expression of tumour necrosis factor and many other inflammatory mediators. The mitogen-activated protein kinase (MAPK) p38 signaling pathway controls the strength and duration of inflammatory responses by regulating both the expression and function of TTP. The kinase MK2 (MAPK activated kinase 2) is activated by MAPK p38, and in turn phosphorylates TTP at two critical serine residues. One consequence of these phosphorylations is the protection of TTP from proteasome-mediated degradation...
November 8, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29126317/inflammation-friend-or-foe-for-animal-production
#16
Leon J Broom, Michael H Kogut
Inflammation is an essential immune response that seeks to contain microbial infection and repair damaged tissue. Increased pro-inflammatory mediators have been associated with enhanced resistance to a range of important poultry and pig pathogens. However, inflammation may also have undesirable consequences, including potentially exacerbating tissue damage and diverting nutrients away from productive purposes. The negative effects of inflammation have led to the active pursuit of anti-inflammatory feed additives and/or strategies...
November 4, 2017: Poultry Science
https://www.readbyqxmd.com/read/29122629/long-term-cilostazol-administration-prevents-age-related-decline-of-hippocampus-dependent-memory-in-mice
#17
Shuichi Yanai, Hideki Ito, Shogo Endo
Phosphodiesterases (PDEs) are enzymes that hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and/or 3', 5'-cyclic guanosine monophosphate (cGMP). The regulation of intracellular signaling pathways mediated by cyclic nucleotides is imperative to synaptic plasticity and memory in animals. Because PDEs play an important role in this regulation, PDE inhibitors are considered as candidate compounds for treating cognitive and memory disorders. In the present study, we tested whether cilostazol, a selective PDE3 inhibitor, prevents the cognitive deterioration that occurs during the course of normal aging in mice...
November 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29120630/how-well-can-implicit-solvent-simulations-explore-folding-pathway-a-quantitative-analysis-of-%C3%AE-helix-bundle-proteins
#18
Qiang Shao, Weiliang Zhu
Protein folding has been posing challenges for molecular simulation for decades. Implicit solvent models are sought as routes to increase the capability of simulation, with trade-offs between computational speed and accuracy. Here, we systematically investigate the folding of a variety of α-helix bundle proteins ranging in size from 46 to 102 amino acids using state-of-the-art force field and implicit solvent model. The accurate all-atom simulated folding is enabled for six proteins, including for the first time a successful folding of protein with >100 amino acids in implicit solvent...
November 9, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29117317/superior-retinal-gene-transfer-and-biodistribution-profile-of-subretinal-versus-intravitreal-delivery-of-aav8-in-nonhuman-primates
#19
Immanuel P Seitz, Stylianos Michalakis, Barbara Wilhelm, Felix F Reichel, G Alex Ochakovski, Eberhart Zrenner, Marius Ueffing, Martin Biel, Bernd Wissinger, Karl U Bartz-Schmidt, Tobias Peters, M Dominik Fischer
Purpose: To investigate shedding and biodistribution characteristics of recombinant adeno-associated virus serotype 8 (rAAV8) after single-dose subretinal or intravitreal injection in nonhuman primates (NHP, Macaca fascicularis) as a surrogate for environmental hazard and patient safety. Methods: In a study for regulatory submission, 22 NHP were divided into four cohorts receiving either single subretinal injections of vehicle or clinical grade rAAV8 (1 × 1011 or 1 × 1012 vector genomes [vg]) versus single intravitreal application of 1 × 1012 vg...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29115427/abnormal-dna-methylation-may-contribute-to-the-progression-of-osteosarcoma
#20
Xiao-Gang Chen, Liang Ma, Jia-Xin Xu
The identification of optimal methylation biomarkers to achieve maximum diagnostic ability remains a challenge. The present study aimed to elucidate the potential molecular mechanisms underlying osteosarcoma (OS) using DNA methylation analysis. Based on the GSE36002 dataset obtained from the Gene Expression Omnibus database, differentially methylated genes were extracted between patients with OS and controls using t‑tests. Subsequently, hierarchical clustering was performed to segregate the samples into two distinct clusters, OS and normal...
October 25, 2017: Molecular Medicine Reports
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