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"Lloyd, Stephen"
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The string diaries
A family is hunted by a centuries-old monster: a man with a relentless obsession who can take on any identity. The String Diaries is a sweeping thriller that extends from the present day, to Oxford in the 1970s, to Hungary at the turn of the 19th century, all tracing back to a man from an ancient royal family with a consuming passion--a boy who can change his shape, insert himself into the intimate lives of his victims, and destroy them. If Hannah fails to end the chase now, her daughter is next in line. Only Hannah can decide how much she is willing to sacrifice to finally put a centuries-old curse to rest.
Book
OGG1 deficiency alters the intestinal microbiome and increases intestinal inflammation in a mouse model
OGG1-deficient (Ogg1-/-) animals display increased propensity to age-induced and diet-induced metabolic diseases, including insulin resistance and fatty liver. Since the intestinal microbiome is increasingly understood to play a role in modulating host metabolic responses, we examined gut microbial composition in Ogg1-/- mice subjected to different nutritional challenges. Interestingly, Ogg1-/- mice had a markedly altered intestinal microbiome under both control-fed and hypercaloric diet conditions. Several microbial species that were increased in Ogg1-/- animals were associated with increased energy harvest, consistent with their propensity to high-fat diet induced weight gain. In addition, several pro-inflammatory microbes were increased in Ogg1-/- mice. Consistent with this observation, Ogg1-/- mice were significantly more sensitive to intestinal inflammation induced by acute exposure to dextran sulfate sodium. Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice.
Journal Article
Written in the blood
\"See the girl. Leah Wilde is twenty-four, a runaway on a black motorbike, hunting for answers while changing her identity with each new Central European town. See the man, having come of age in extraordinary suffering and tragedy in nineteenth-century Budapest, witness to horror, to love, to death, and the wrath of a true monster. Izsak still lives in the present day, impossibly middle-aged. He's driven not only to hunt this immortal evil but to find his daughter, stolen from an Arctic cabin and grown into the thing Izsak has sworn to kill. See the monster, a beautiful, seemingly young woman who stalks the American West, seeking the young and the strong to feed upon, desperate to return to Europe where her coven calls\"--Dust jacket flap.
Book
8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle
Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1) recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Here, we report that OGG1-deficient mice also display skeletal muscle pathologies, including increased muscle lipid deposition and alterations in genes regulating lipid uptake and mitochondrial fission in skeletal muscle. In addition, expression of genes of the TCA cycle and of carbohydrate and lipid metabolism are also significantly altered in muscle of OGG1-deficient mice. These tissue changes are accompanied by marked reductions in markers of muscle function in OGG1-deficient animals, including decreased grip strength and treadmill endurance. Collectively, these data indicate a role for skeletal muscle OGG1 in the maintenance of optimal tissue function.
Journal Article
8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction
Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that is catalyzed by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report a novel role for OGG1 in altering cellular and whole body energy homeostasis. OGG1-deficient (Ogg1(-/-)) mice have increased adiposity and hepatic steatosis following exposure to a high-fat diet (HFD), compared to wild-type (WT) animals. Ogg1(-/-) animals also have higher plasma insulin levels and impaired glucose tolerance upon HFD feeding, relative to WT counterparts. Analysis of energy expenditure revealed that HFD-fed Ogg1(-/-) mice have a higher resting VCO(2) and consequently, an increased respiratory quotient during the resting phase, indicating a preference for carbohydrate metabolism over fat oxidation in these mice. Additionally, microarray and quantitative PCR analyses revealed that key genes of fatty acid oxidation, including carnitine palmitoyl transferase-1, and the integral transcriptional co-activator Pgc-1α were significantly downregulated in Ogg1(-/-) livers. Multiple genes involved in TCA cycle metabolism were also significantly reduced in livers of Ogg1(-/-) mice. Furthermore, hepatic glycogen stores were diminished, and fasting plasma ketones were significantly reduced in Ogg1(-/-) mice. Collectively, these data indicate that OGG1 deficiency alters cellular substrate metabolism, favoring a fat sparing phenotype, that results in increased susceptibility to obesity and related pathologies in Ogg1(-/-) mice.
Journal Article
The Cyril Scott companion : unity in diversity
This Companion explores the life and work of this remarkably creative man. It provides a comprehensive analysis and appraisal of all the available music and includes a complete catalogue of his musical works, along with a discography. Several works...both music and literary are here newly catalogued and discussed. Altogether, the volume gives a broad picture of Scott's entire output in literary, dramatic and philosophical genres.--Publisher
Book
Stereosonic vision: Exploring visual-to-auditory sensory substitution mappings in an immersive virtual reality navigation paradigm
Sighted people predominantly use vision to navigate spaces, and sight loss has negative consequences for independent navigation and mobility. The recent proliferation of devices that can extract 3D spatial information from visual scenes opens up the possibility of using such mobility-relevant information to assist blind and visually impaired people by presenting this information through modalities other than vision. In this work, we present two new methods for encoding visual scenes using spatial audio: simulated echolocation and distance-dependent hum volume modulation. We implemented both methods in a virtual reality (VR) environment and tested them using a 3D motion-tracking device. This allowed participants to physically walk through virtual mobility scenarios, generating data on real locomotion behaviour. Blindfolded sighted participants completed two tasks: maze navigation and obstacle avoidance. Results were measured against a visual baseline in which participants performed the same two tasks without blindfolds. Task completion time, speed and number of collisions were used as indicators of successful navigation, with additional metrics exploring detailed dynamics of performance. In both tasks, participants were able to navigate using only audio information after minimal instruction. While participants were 65% slower using audio compared to the visual baseline, they reduced their audio navigation time by an average 21% over just 6 trials. Hum volume modulation proved over 20% faster than simulated echolocation in both mobility scenarios, and participants also showed the greatest improvement with this sonification method. Nevertheless, we do speculate that simulated echolocation remains worth exploring as it provides more spatial detail and could therefore be more useful in more complex environments. The fact that participants were intuitively able to successfully navigate space with two new visual-to-audio mappings for conveying spatial information motivates the further exploration of these and other mappings with the goal of assisting blind and visually impaired individuals with independent mobility.
Journal Article
The best horror of the year. Volume ten
A group of mountain climbers, caught in the dark, fights to survive their descent; An American band finds more than they bargained for in Mexico while scouting remote locations for a photo shoot; A young student's exploration into the origins of a mysterious song leads him on a winding, dangerous path through the US's deep south; A group of kids scaring each other with ghost stories discovers alarming consequences. The Best Horror of the Year showcases the previous year's best offerings in horror short fiction. This edition includes award-winning and critically acclaimed authors Mark Morris, Kaaron Warren, John Langan, Carole Johnstone, Brian Hodge, and others. For more than three decades, award-winning editor and anthologist Ellen Datlow has had her finger on the pulse of the latest and most terrifying in horror writing. Night Shade Books is proud to present the tenth volume in this annual series, a new collection of stories to keep you up at night.
BOOK
Inhibition of DNA Glycosylases via Small Molecule Purine Analogs
Following the formation of oxidatively-induced DNA damage, several DNA glycosylases are required to initiate repair of the base lesions that are formed. Recently, NEIL1 and other DNA glycosylases, including OGG1 and NTH1 were identified as potential targets in combination chemotherapeutic strategies. The potential therapeutic benefit for the inhibition of DNA glycosylases was validated by demonstrating synthetic lethality with drugs that are commonly used to limit DNA replication through dNTP pool depletion via inhibition of thymidylate synthetase and dihydrofolate reductase. Additionally, NEIL1-associated synthetic lethality has been achieved in combination with Fanconi anemia, group G. As a prelude to the development of strategies to exploit the potential benefits of DNA glycosylase inhibition, it was necessary to develop a reliable high-throughput screening protocol for this class of enzymes. Using NEIL1 as the proof-of-principle glycosylase, a fluorescence-based assay was developed that utilizes incision of site-specifically modified oligodeoxynucleotides to detect enzymatic activity. This assay was miniaturized to a 1536-well format and used to screen small molecule libraries for inhibitors of the combined glycosylase/AP lyase activities. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of damaged purines. Although a subset of these small molecules could inhibit other DNA glycosylases that excise oxidatively-induced DNA adducts, they could not inhibit a pyrimidine dimer-specific glycosylase.
Journal Article