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https://www.readbyqxmd.com/read/28630333/boosting-cns-axon-regeneration-by-harnessing-antagonistic-effects-of-gsk3-activity
#1
Marco Leibinger, Anastasia Andreadaki, Renate Golla, Evgeny Levin, Alexander M Hilla, Heike Diekmann, Dietmar Fischer
Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3(S/A) knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630130/how-a-genetically-stable-extremophile-evolves-modes-of-genome-diversification-in-the-archaeon-sulfolobus-acidocaldarius
#2
Dominic Mao, Dennis W Grogan
In order to analyze in molecular terms how Sulfolobus genomes diverge, damage-induced mutations and natural polymorphisms (PMs) were identified in laboratory constructs and wild-type isolates, respectively, of Sulfolobus acidocaldarius Among wild-type isolates drawn from one local population, pairwise nucleotide divergence averaged 4 x 10(-6), which is about 0.15% of the corresponding divergence reported for Sulfolobus islandicus The most variable features of wild-type S. acidocaldarius genomes were homopolymer (mononucleotide) tracts and longer tandem repeats, consistent with the spontaneous mutations that occur under laboratory conditions...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28630042/the-glutamate-cystine-antiporter-slc7a11-xct-enhances-cancer-cell-dependency-on-glucose-by-exporting-glutamate
#3
Pranavi Koppula, Yilei Zhang, Jiejun Shi, Wei Li, Boyi Gan
Cancer cells with specific genetic alterations may be highly dependent on certain nutrients for survival, which can inform therapeutic strategies to target these cancer-specific metabolic vulnerabilities. The glutamate/cystine antiporter solute carrier family 7 member 11 (SLC7A11, also called xCT) is overexpressed in several cancers. Contrasting the established pro-survival roles of SLC7A11 under other stress conditions, here we report an unexpected finding that SLC7A11 overexpression enhances cancer cell dependency on glucose and renders cancer cells more sensitive to glucose starvation-induced cell death, and conversely, that SLC7A11 deficiency by either knockdown or pharmacological inhibition promotes cancer cell survival upon glucose starvation...
June 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28629740/seasonal-dynamics-spatial-distribution-and-genetic-analysis-of-anaplasma-species-infecting-small-ruminants-from-northern-tunisia
#4
Hanène Belkahia, Mourad Ben Said, Narjesse El Mabrouk, Mariem Saidani, Chayma Cherni, Mariem Ben Hassen, Ali Bouattour, Lilia Messadi
To date, there have been no reports on seasonal variations of Anaplasma spp. in South Mediterranean small ruminants. In this longitudinal field study, single and mixed Anaplasma spp. infections in small ruminants from five different governorates belonging to three bioclimatic zones from the North of Tunisia were evaluated according to seasons. A total of 1685 blood small ruminant samples were collected in spring (355 sheep and 241 goats), summer (249 sheep and 202 goats), autumn (236 sheep and 186 goats) and winter (132 sheep and 84 goats)...
June 16, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28629478/genetic-epigenetic-interactions-in-cis-a-major-focus-in-the-post-gwas-era
#5
REVIEW
Catherine Do, Alyssa Shearer, Masako Suzuki, Mary Beth Terry, Joel Gelernter, John M Greally, Benjamin Tycko
Studies on genetic-epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS)...
June 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#6
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28625990/bioavailability-of-carbohydrate-content-in-natural-and-transgenic-switchgrasses-for-the-extreme-thermophile-caldicellulosiruptor-bescii
#7
Jeffrey V Zurawski, Piyum A Khatibi, Hannah O Akinosho, Christopher T Straub, Scott H Compton, Jonathan M Conway, Laura L Lee, Arthur J Ragauskas, Brian H Davison, Michael W W Adams, Robert M Kelly
Improving access to the carbohydrate content of lignocellulose is key to reducing recalcitrance for microbial deconstruction and conversion to fuels and chemicals. Caldicellulosiruptor bescii completely solubilizes naked microcrystalline cellulose, yet this transformation is impeded within the context of the plant cell wall by a network of lignin and hemicellulose. Here, the bioavailability of carbohydrates to C. bescii at 70°C was examined for reduced lignin transgenic switchgrass lines COMT3(+) and MYB Trans, their corresponding parental lines (cultivar Alamo) COMT3(-) and MYB WT, and natural variant cultivar Cave-in-Rock (CR)...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28625987/metabolic-engineering-of-actinobacillus-succinogenes-provides-insights-into-succinic-acid-biosynthesis
#8
Michael T Guarnieri, Yat-Chen Chou, Davinia Salvachúa, Ali Mohagheghi, Peter C St John, Darren J Peterson, Yannick J Bomble, Gregg T Beckham
Actinobacillus succinogenes, a gram-negative, facultative anaerobe, exhibits the native capacity to convert pentose and hexose sugars to succinic acid (SA) with high yield as a tricarboxylic acid (TCA) cycle intermediate. In addition, A. succinogenes is capnophilic, incorporating CO2 into SA, making this organism an ideal candidate host for conversion of lignocellulosic sugars and CO2 to an emerging commodity bioproduct sourced from renewable feedstocks. In this work, we report the development of facile metabolic engineering capabilities in A...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28625476/feedback-loops-interlocked-at-competitive-binding-sites-amplify-and-facilitate-genetic-oscillations
#9
Koichiro Uriu, Hajime Tei
Positive and negative feedback loops are often present in regulatory networks for genetic oscillations. Relative time scales and integration of these feedback loops are key to robust oscillations in expression levels. Using examples from the circadian clock and synthetic genetic oscillators, we study positive and negative feedback loops interlocked at competitive binding sites. In the mammalian circadian clock, a key clock gene Bmal1 is regulated by the activator ROR and the repressor REV-ERB. Conversely, Bmal1 activates both of them, forming interlocked feedback loops...
June 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28624618/a-sample-to-answer-real-time-convective-polymerase-chain-reaction-system-for-point-of-care-diagnostics
#10
Bowen Shu, Chunsun Zhang, Da Xing
Timely and accurate molecular diagnostics at the point-of-care (POC) level is critical to global health. To this end, we propose a handheld convective-flow real-time polymerase chain reaction (PCR) system capable of direct sample-to-answer genetic analysis for the first time. Such a system mainly consists of a magnetic bead-assisted photothermolysis sample preparation, a closed-loop convective PCR reactor, and a wireless video camera-based real-time fluorescence detection. The sample preparation exploits the dual functionality of vancomycin-modified magnetic beads (VMBs) for bacteria enrichment and photothermal conversion, enabling cell pre-concentration and lysis to be finished in less than 3min...
June 8, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28623042/corneocyte-lipid-envelope-cle-the-key-structure-for-skin-barrier-function-and-ichthyosis-pathogenesis
#11
REVIEW
Masashi Akiyama
Research on the genetic abnormalities and pathogenetic processes of ichthyoses has progressed remarkably, and many causative genes and molecules have been identified in ichthyoses and ichthyosis syndromes. Most of the genes/molecules causative of ichthyosis are associated with the barrier function of the stratum corneum, and defects in the skin barrier play important roles in the pathogenesis of various ichthyosis phenotypes. It has been elucidated that, of the ichthyosis-causative genes, ABCA12, ALOXE3, ALOX12B, CYP4F22, CERS3, ABHD5, PNPLA1 and ELOVL4 work in the formation of the corneocyte lipid envelope (CLE), a structure that is essential to sound skin barrier function...
June 8, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28620583/engineering-of-genetically-arrested-parasites-gaps-for-a-precision-malaria-vaccine
#12
REVIEW
Oriana Kreutzfeld, Katja Müller, Kai Matuschewski
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#13
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28615445/iron-sulfur-cluster-biogenesis-and-trafficking-in-mitochondria
#14
Joseph J Braymer, Roland Lill
The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a multi-stage, multi-compartment process that is essential for a broad range of cellular functions including genome maintenance, protein translation, energy conversion, and the antiviral response. Genetic and cell biological studies over almost two decades have revealed some thirty proteins involved in the synthesis of cellular [2Fe 2S] and [4Fe-4S] clusters and their incorporation into numerous apoproteins. Mechanistic aspects of Fe/S protein biogenesis continue to be elucidated by biochemical and ultrastructural investigations...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28611790/saccharification-performances-of-miscanthus-at-the-pilot-and-miniaturized-assay-scales-genotype-and-year-variabilities-according-to-the-biomass-composition
#15
Nassim Belmokhtar, Stéphanie Arnoult, Brigitte Chabbert, Jean-Paul Charpentier, Maryse Brancourt-Hulmel
HIGHLIGHTS Biomass production and cell wall composition are differentially impacted by harvesting year and genotypes, influencing then cellulose conversion in miniaturized assay.Using a high-throughput miniaturized and semi-automated method for performing the pretreatment and saccharification steps at laboratory scale allows for the assessment of these factors on the biomass potential for producing bioethanol before moving to the industrial scale. The large genetic diversity of the perennial grass miscanthus makes it suitable for producing cellulosic ethanol in biorefineries...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28608936/a-photo-responsive-f-box-protein-fof2-regulates-floral-initiation-by-promoting-flc-expression-in-arabidopsis
#16
Reqing He, Xinmei Li, Ming Zhong, Jindong Yan, Ronghuan Ji, Xu Li, Qin Wang, Dan Wu, Mengsi Sun, Dongying Tang, Jianzhong Lin, Hongyu Li, Bin Liu, Hongtao Liu, Xuanming Liu, Xiaoying Zhao, Chentao Lin
Floral initiation is regulated by various genetic pathways in response to light, temperature, hormones, and developmental status. However, the molecular mechanisms underlying the interactions between different genetic pathways are not fully understood. Here, we show that the photoresponsive gene FOF2 (F-box of flowering 2) negatively regulates flowering. FOF2 encodes a putative F-box protein that interacts specifically with ASK14, and its overexpression results in later flowering under both long-day and short-day photoperiods...
June 13, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28607440/an-arabidopsis-mutant-with-high-operating-efficiency-of-photosystem-ii-and-low-chlorophyll-fluorescence
#17
Niels van Tol, Martijn Rolloos, Dieuwertje Augustijn, A Alia, Huub J de Groot, Paul J J Hooykaas, Bert J van der Zaal
The overall light energy to biomass conversion efficiency of plant photosynthesis is generally regarded as low. Forward genetic screens in Arabidopsis have yielded very few mutants with substantially enhanced photochemistry. Here, we report the isolation of a novel Arabidopsis mutant with a high operating efficiency of Photosystem II (φPSII) and low chlorophyll fluorescence from a library of lines harboring T-DNA constructs encoding artificial transcription factors. This mutant was named Low Chlorophyll Fluorescence 1 (LCF1)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607166/unique-vs-redundant-functions-of-neuroligin-genes-in-shaping-excitatory-and-inhibitory-synapse-properties
#18
Soham Chanda, William D Hale, Bo Zhang, Marius Wernig, Thomas C Südhof
Neuroligins are evolutionarily conserved postsynaptic cell-adhesion molecules that interact with presynaptic neurexins. Neurons express multiple neuroligin isoforms that are targeted to specific synapses, but their synaptic functions and mechanistic redundancy are not completely understood. Overexpression or RNAi-mediated knockdown of neuroligins respectively causes dramatic increase or decrease in synapse density, whereas genetic deletions of neuroligins impair synapse function with only minor effects on synapse numbers, raising fundamental questions about the overall physiological role of neuroligins...
June 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28606623/the-interaction-between-alpha-7-nicotinic-acetylcholine-receptor-and-nuclear-peroxisome-proliferator-activated-receptor-%C3%AE-represents-a-new-antinociceptive-signaling-pathway-in-mice
#19
Giulia Donvito, Deniz Bagdas, Wisam Toma, Elnaz Rahimpour, Asti Jackson, Julie A Meade, Shakir AlSharari, Abhijit R Kulkarni, F Ivy Carroll, Aron H Lichtman, Roger L Papke, Ganesh A Thakur, M Imad Damaj
Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca(2+)-dependent manner...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28606094/what-is-the-impact-of-pcsk9-rs505151-and-rs11591147-polymorphisms-on-serum-lipids-level-and-cardiovascular-risk-a-meta-analysis
#20
Chengfeng Qiu, Pingyu Zeng, Xiaohui Li, Zhen Zhang, Bingjie Pan, Zhou Y F Peng, Yapei Li, Yeshuo Ma, Yiping Leng, Ruifang Chen
BACKGROUND: PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. METHODS: In this meta-analysis, we explored the association of PCSK9 rs505151 and rs11591147 polymorphisms with serum lipid levels and cardiovascular risk by calculating the standardized mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CI)...
June 12, 2017: Lipids in Health and Disease
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