Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
679
result(s) for
"Scott, Graham R."
Sort by:
Batman, Knightsend
\"Bruce Wayne returns to Gotham City only to find that his replacement, Jean-Paul Valley, has become increasingly violent and reckless. Now he must confront and defeat Jean-Paul in order to win back the mantle of the Bat. Following the events of Batman: Knightquest: The Search, Bruce Wayne is ready to return to his role as Gotham's greatest protector, Batman. Including never-before-collected material! Bruce Wayne completes his improbable recovery from his broken back and is ready to resume his role as Gotham's protector. But Jean-Paul Valley, the man who now patrols the night as a vicious and violent Batman, is not willing to give up his new identity. Driven to the brink of madness by inner demons, the new Batman seeks to destroy Bruce as they meet in mortal combat.\"-- Provided by publisher.
Book
Temperature during embryonic development has persistent effects on thermal acclimation capacity in zebrafish
Global warming is intensifying interest in the mechanisms enabling ectothermic animals to adjust physiological performance and cope with temperature change. Here we show that embryonic temperature can have dramatic and persistent effects on thermal acclimation capacity at multiple levels of biological organization. Zebrafish embryos were incubated until hatching at control temperature (T E = 27 °C) or near the extremes for normal development (T E = 22 °C or 32 °C) and were then raised to adulthood under common conditions at 27 °C. Short-term temperature challenge affected aerobic exercise performance (U cᵣᵢₜ), but each T E group had reduced thermal sensitivity at its respective T E. In contrast, unexpected differences arose after long-term acclimation to 16 °C, when performance in the cold was ∼20% higher in both 32 °C and 22 °C T E groups compared with 27 °C T E controls. Differences in performance after acclimation to cold or warm (34 °C) temperatures were partially explained by variation in fiber type composition in the swimming muscle. Cold acclimation changed the abundance of 3,452 of 19,712 unique and unambiguously identified transcripts detected in the fast muscle using RNA-Seq. Principal components analysis differentiated the general transcriptional responses to cold of the 27 °C and 32 °C T E groups. Differences in expression were observed for individual genes involved in energy metabolism, angiogenesis, cell stress, muscle contraction and remodeling, and apoptosis. Therefore, thermal acclimation capacity is not fixed and can be modified by temperature during early development. Developmental plasticity may thus help some ectothermic organisms cope with the more variable temperatures that are expected under future climate-change scenarios.
Journal Article
Batman Knightfall omnibus
\"This classic storyline that led to the birth of a new Batman begins as the Dark Knight's greatest enemies have all simultaneously escaped from Arkham Asylum and are preying on Gotham City. With his city under siege, Batman pushes his body to its physical breaking point as he takes on the Joker, the Mad Hatter, Poison Ivy, Killer Croc, the Riddler and the Scarecrow, one after another. But things get much worse, when Bane, the man behind all of this madness, confronts an exhausted Batman and cripples him by breaking his back.\"-- Provided by publisher.
Book
Physiological and genomic evidence that selection on the transcription factor Epas1 has altered cardiovascular function in high-altitude deer mice
Evolutionary adaptation to extreme environments often requires coordinated changes in multiple intersecting physiological pathways, but how such multi-trait adaptation occurs remains unresolved. Transcription factors, which regulate the expression of many genes and can simultaneously alter multiple phenotypes, may be common targets of selection if the benefits of induced changes outweigh the costs of negative pleiotropic effects. We combined complimentary population genetic analyses and physiological experiments in North American deer mice (Peromyscus maniculatus) to examine links between genetic variation in transcription factors that coordinate physiological responses to hypoxia (hypoxia-inducible factors, HIFs) and multiple physiological traits that potentially contribute to high-altitude adaptation. First, we sequenced the exomes of 100 mice sampled from different elevations and discovered that several SNPs in the gene Epas1, which encodes the oxygen sensitive subunit of HIF-2α, exhibited extreme allele frequency differences between highland and lowland populations. Broader geographic sampling confirmed that Epas1 genotype varied predictably with altitude throughout the western US. We then discovered that Epas1 genotype influences heart rate in hypoxia, and the transcriptomic responses to hypoxia (including HIF targets and genes involved in catecholamine signaling) in the heart and adrenal gland. Finally, we used a demographically-informed selection scan to show that Epas1 variants have experienced a history of spatially varying selection, suggesting that differences in cardiovascular function and gene regulation contribute to high-altitude adaptation. Our results suggest a mechanism by which Epas1 may aid long-term survival of high-altitude deer mice and provide general insights into the role that highly pleiotropic transcription factors may play in the process of environmental adaptation.
Journal Article
Convergent changes in muscle metabolism depend on duration of high-altitude ancestry across Andean waterfowl
High-altitude environments require that animals meet the metabolic O 2 demands for locomotion and thermogenesis in O 2 -thin air, but the degree to which convergent metabolic changes have arisen across independent high-altitude lineages or the speed at which such changes arise is unclear. We examined seven high-altitude waterfowl that have inhabited the Andes (3812–4806 m elevation) over varying evolutionary time scales, to elucidate changes in biochemical pathways of energy metabolism in flight muscle relative to low-altitude sister taxa. Convergent changes across high-altitude taxa included increased hydroxyacyl-coA dehydrogenase and succinate dehydrogenase activities, decreased lactate dehydrogenase, pyruvate kinase, creatine kinase, and cytochrome c oxidase activities, and increased myoglobin content. ATP synthase activity increased in only the longest established high-altitude taxa, whereas hexokinase activity increased in only newly established taxa. Therefore, changes in pathways of lipid oxidation, glycolysis, and mitochondrial oxidative phosphorylation are common strategies to cope with high-altitude hypoxia, but some changes require longer evolutionary time to arise.
Journal Article
ASCC3 promotes chemosensitivity in colorectal cancer cells
The activating signal co-integrator 1 complex subunit 3 (ASCC3), a multifunctional protein, has been implicated as a prognostic marker in several types of cancer. However, mechanisms underlying its prognostic value are not fully understood. Here, we report that ASCC3 promotes sensitivity to chemotherapeutic drugs that induce replication stress, such as 5-fluorouracil, cisplatin, and hydroxyurea, in colorectal cancer (CRC) cells, likely in a cancer type dependent manner. Increased chemoresistance resulting from ASCC3 loss is not due to reduced genomic instability as evidenced by enhanced accumulation of DNA damage and micronuclei following exposure to these drugs. RNA-seq analysis reveals that ASCC3 stimulates the expression of gene sets associated with mTORC1 signaling, glycolysis, and protein folding pathways in CRC cells. While promoting the serine biosynthesis pathway, we demonstrate, through extracellular flux assays and stable isotopes tracer analysis, that ASCC3 reprograms energy metabolism, favoring glycolysis over oxidative phosphorylation. Furthermore, we find that ASCC3 is required for PERK production upon ER stress. Impaired PERK production is associated with reduced levels of CHOP and caspase 3 following treatment with 5-fluorouracil, indicating that ASCC3 promotes PERK production to enhance cell death upon chemotherapy. Collectively, our work reveals an unexpected role of ASCC3 in connecting replication stress to both metabolic reprogramming and PERK-mediated signaling in CRC cells.
Journal Article
Counter-gradient variation and the expensive tissue hypothesis explain parallel brain size reductions at high elevation in cricetid and murid rodents
To better understand functional morphological adaptations to high elevation (> 3000 m above sea level) life in both North American and African mountain-associated rodents, we used microCT scanning to acquire 3D images and a 3D morphometric approach to calculate endocranial volumes and skull lengths. This was done on 113 crania of low-elevation and high-elevation populations in species of North American cricetid mice (two
Peromyscus
species, n = 53), and African murid rodents of two tribes, Otomyini (five species, n = 49) and Praomyini (four species, n = 11). We tested two distinct hypotheses for how endocranial volume might vary in high-elevation populations: the expensive tissue hypothesis, which predicts that brain and endocranial volumes will be reduced to lessen the costs of growing and maintaining a large brain; and the brain-swelling hypothesis, which predicts that endocranial volumes will be increased either as a direct phenotypic effect or as an adaptation to accommodate brain swelling and thus minimize pathological symptoms of altitude sickness. After correcting for general allometric variation in cranial size, we found that in both North American
Peromyscus
mice and African laminate-toothed (
Otomys
) rats, highland rodents had smaller endocranial volumes than lower-elevation rodents, consistent with the expensive tissue hypothesis. In the former group,
Peromyscus
mice, crania were obtained not just from wild-caught mice from high and low elevations but also from those bred in common-garden laboratory conditions from parents caught from either high or low elevations. Our results in these mice showed that brain size responses to elevation might have a strong genetic basis, which counters an opposite but weaker environmental effect on brain volume. These results potentially suggest that selection may act to reduce brain volume across small mammals at high elevations but further experiments are needed to assess the generality of this conclusion and the nature of underlying mechanisms.
Journal Article
The trans-Himalayan flights of bar-headed geese (Anser indicus)
Birds that fly over mountain barriers must be capable of meeting the increased energetic cost of climbing in low-density air, even though less oxygen may be available to support their metabolism. This challenge is magnified by the reduction in maximum sustained climbing rates in large birds. Bar-headed geese (Anser indicus) make one of the highest and most iconic transmountain migrations in the world. We show that those populations of geese that winter at sea level in India are capable of passing over the Himalayas in 1 d, typically climbing between 4,000 and 6,000 m in 7–8 h. Surprisingly, these birds do not rely on the assistance of upslope tailwinds that usually occur during the day and can support minimum climb rates of 0.8–2.2 km·h –1 , even in the relative stillness of the night. They appear to strategically avoid higher speed winds during the afternoon, thus maximizing safety and control during flight. It would seem, therefore, that bar-headed geese are capable of sustained climbing flight over the passes of the Himalaya under their own aerobic power.
Journal Article
Inferring TLB Configuration with Performance Tools
Modern computing systems are primarily designed for maximum performance, which inadvertently introduces vulnerabilities at the micro-architecture level. While cache side-channel analysis has received significant attention, other Central Processing Units (CPUs) components like the Translation Lookaside Buffer (TLB) can also be exploited to leak sensitive information. This paper focuses on the TLB, a micro-architecture component that is vulnerable to side-channel attacks. Despite the coarse granularity at the page level, advancements in tools and techniques have made TLB information leakage feasible. The primary goal of this study is not to demonstrate the potential for information leakage from the TLB but to establish a comprehensive framework to reverse engineer the TLB configuration, a critical aspect of side-channel analysis attacks that have previously succeeded in extracting sensitive data. The methodology involves detailed reverse engineering efforts on Intel CPUs, complemented by analytical tools to support TLB reverse engineering. This study successfully reverse-engineered the TLB configurations for Intel CPUs and introduced visual tools for further analysis. These results can be used to explore TLB vulnerabilities in greater depth. However, when attempting to apply the same methodology to the IBM Power9, it became clear that the methodology was not transferable, as mapping functions and performance counters vary across different vendors.
Journal Article
The adaptive benefit of evolved increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice
Background
Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O
2
consumption,
V̇
O
2
max, during acute cold exposure) in high-altitude deer mice (
Peromyscus maniculatus
). We crossed highland and lowland deer mice to produce F
2
inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O
2
affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O
2
transport pathway to examine the links between cardiorespiratory traits and
V̇
O
2
max.
Results
Physiological experiments revealed that increases in Hb-O
2
affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in
V̇
O
2
max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O
2
affinity on
V̇
O
2
max in hypoxia was contingent on the capacity for O
2
diffusion in active tissues.
Conclusions
These results suggest that increases in Hb-O
2
affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O
2
diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O
2
affinity is contingent on the capacity to extract O
2
from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.
Journal Article