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"Brown, Kim"
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Uncharted : a couple's epic empty-nest adventure sailing from one life to another
\"A narrative memoir about the particular midlife crisis that comes when children leave home. Author Kim Brown Seely and her husband (Seattle residents who did time in NYC) decide somewhat spontaneously to acquire a 54-foot sailboat, learn how to sail, then set off to find a spirit bear (the rare white Kermode bear) in the forest that on the BC mainland north of the tip of Vancouver Island. The looming life change for them is that the youngest of their two sons is about ship off to college on the east coast, and their eldest is already living in San Francisco. How better to face this end of parenting than demonstrate to themselves that there's more living and adventure to be had, especially with a sailboat. This author is a wonderful storyteller, and she can capture the mood swings of a marital spat in a most appealing way\"-- Provided by publisher.
Book
Sleep deprivation impairs cAMP signalling in the hippocampus
Lost sleep, found memories
It is well known that sleep deprivation can have cognitive consequences, including learning and memory deficits, but the mechanisms by which sleep deprivation affects brain function remain unknown. New experiments identify the cyclic AMP pathway as a functional target of sleep deprivation, specifically the impairment of cAMP/PKA-based plasticity in the hippocampus. Rescuing cAMP signalling using phosphodiesterase inhibitors also rescues the memory deficits, pointing to cAMP/PKA signalling enhancers as a possible therapeutic approach to counteract the cognitive effects of lost sleep.
Sleep deprivation can have adverse cognitive effects, with one of the major consequences on the brain being memory deficits in learning models that are dependent on the hippocampus. A molecular mechanism by which brief sleep deprivation alters hippocampal function is now identified in mice; it involves the impairment of cyclic-AMP- and protein-kinase-A-dependent forms of synaptic plasticity.
Millions of people regularly obtain insufficient sleep
1
. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus
2
,
3
,
4
,
5
. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3′, 5′-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity
6
in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.
Journal Article
Baseline mRNA expression differs widely between common laboratory strains of zebrafish
Common strains of wildtype zebrafish (
Danio rerio
) have unique genomic features including SNPs and CNV, but strain information often goes unreported in the literature. As a result, the confounding effects of interstrain variation makes repetition of studies in zebrafish challenging. Here we analyze hepatic mRNA expression patterns between three common zebrafish strains (AB, Tuebingen (TU), and WIK) using Agilent 4 × 44 K gene expression microarrays to establish baseline mRNA expression across strains and between sexes. We observed wide variation in sex-specific gene expression within AB and WIK strains (141 genes in AB and 67 genes in WIK), but no significant variation between sexes within TU. After partitioning the dataset into male and female subsets, we detected 421 unique mRNA transcripts with statistically significant differential expression; 269 mRNA transcripts varied between males, 212 mRNA transcripts varied between females, and 59 mRNA transcripts varied across the three strains, regardless of sex. It is not surprising that mRNA expression profiles differ between sexes and strains, but it is imperative to characterize the differences. These results highlight the complexity of variation within zebrafish and underscore the value of this model system as a valid representation of normal variation present in other species, including humans.
Journal Article
Beyond notation : the music of Earle Brown
Earle Brown (1926-2002) was a crucial part of the seminal group of experimental composers known as the New York School, and his work intersects in fascinating ways with that of his colleagues John Cage, Morton Feldman, and Christian Wolff. This book seeks to expand our view of Brown's work, addressing his practices as a painter and composer as well as his collaborations with visual artists Alexander Calder, Robert Rauschenberg, and the American abstract expressionists. The essays collected here explore Brown's compositional methods and their historical place in depth: not only his influential experiments with open form composition and graphic notation, but his interest in collaboration, mixed media, and his engagement with the European avant-garde. The volume includes several short essays by Brown that shed new light on his relationships with colleagues and the ideas that drove his work.
Book
Implementation science and the Health Resources and Services Administration’s Ryan White HIV/AIDS Program’s work towards ending the HIV epidemic in the United States
Introduction Implementation science has emerged as an essential field for HIV treatment and prevention, providing crucial insights for clinical effectiveness and efficacy trials, bench-to-bedside translation of clinical trial evidence into real-world intervention strategies, and routine program monitoring and evaluation [1,2,3,4,5]. Funded at $2.3 billion in 2019, with more than 2,000 providers across the US, the RWHAP delivers a comprehensive system of high-quality HIV care and treatment, including direct medical care and support services for more than half a million people with HIV—more than 50% of all people living with diagnosed HIV in the US [9]. Since 1990, the RHWAP has played a pivotal role in supporting state and county health departments as well as faith- and community-based organizations to implement effective intervention strategies to improve the health and well-being of people with HIV. According to the Centers for Disease Control and Prevention (CDC), when taken daily, PrEP is highly effective for preventing HIV infection [17]. Trying to rigorously account for the messiness of the real world, however, can require elaborate, resource-intensive evaluation frameworks that are hard to replicate. [...]studies that are highly tailored to, and therefore relevant for, a specific context may have reduced external validity, hindering the production of generalizable knowledge that could support broader implementation [7].
Journal Article
Venom : the complete collection
One of comics' wildest writers takes on the symbiotic super hero! Flash Thompson, the Secret Avenger called Agent Venom, faces Daimon Hellstrom and the Monsters of Evil in a battle to save his soul! But when Venom's psychopathic off spring targets the Microverse, Flash and the new Scarlet Spider must put their rivalries aside to handle the madness of Carnage! Venom says farewell to New York and heads to Philadelphia - but Toxin follows soon after. And the pair of lethal symbiotes may unwittingly unleash something even more deadly! Can Flash battle side-by-side with the original Venom, Eddie Brock, to save the City of Brotherly Love? Plus underworld boss Lord Ogre! The killer called Crossbones! And...a symbiotic sidekick?! Cullen Bunn's explosive Venom run is collected in full!
Book
Grasping Cybersecurity Leadership as It Relates to Critical Infrastructure Protection
Leadership growth is a contemporaneous approach to learning. Developing healthcare leadership and decision-making concerning protecting U.S. critical infrastructure from a framework of sound cybersecurity protection approaches in the age of COVID-19 is the latest development for cybersecurity healthcare leaders. Examined is the creation of this framework from the leadership viewpoint to investigate arguments, practices, and how this information explains the assembly and effects of cybersecurity consciousness, skill, experience, behaviors, aims, agreement, and knowledge absorption. This examination concentrates on the development of the framework and focus group results as this framework is reasoned the suitable tool to expose how diverse backgrounds can be realized to blend new knowledge, the age of COVID-19, U.S. critical infrastructure, protection, variation, and diversity into enhanced knowledge, skill, and abilities. This data adds to the body of knowledge regarding cybersecurity leadership knowledge development for academics, practitioners, and learners.
Journal Article
Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis
Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNV elements exhibited strain specificity, with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen's large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and substructure of these commonly used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype and, if not properly addressed, such extensive levels of germ-line variation and population substructure in this commonly used model organism can potentially confound studies intended for translation to human diseases.
Journal Article
Cross-Species Array Comparative Genomic Hybridization Identifies Novel Oncogenic Events in Zebrafish and Human Embryonal Rhabdomyosarcoma
Human cancer genomes are highly complex, making it challenging to identify specific drivers of cancer growth, progression, and tumor maintenance. To bypass this obstacle, we have applied array comparative genomic hybridization (array CGH) to zebrafish embryonal rhabdomyosaroma (ERMS) and utilized cross-species comparison to rapidly identify genomic copy number aberrations and novel candidate oncogenes in human disease. Zebrafish ERMS contain small, focal regions of low-copy amplification. These same regions were commonly amplified in human disease. For example, 16 of 19 chromosomal gains identified in zebrafish ERMS also exhibited focal, low-copy gains in human disease. Genes found in amplified genomic regions were assessed for functional roles in promoting continued tumor growth in human and zebrafish ERMS--identifying critical genes associated with tumor maintenance. Knockdown studies identified important roles for Cyclin D2 (CCND2), Homeobox Protein C6 (HOXC6) and PlexinA1 (PLXNA1) in human ERMS cell proliferation. PLXNA1 knockdown also enhanced differentiation, reduced migration, and altered anchorage-independent growth. By contrast, chemical inhibition of vascular endothelial growth factor (VEGF) signaling reduced angiogenesis and tumor size in ERMS-bearing zebrafish. Importantly, VEGFA expression correlated with poor clinical outcome in patients with ERMS, implicating inhibitors of the VEGF pathway as a promising therapy for improving patient survival. Our results demonstrate the utility of array CGH and cross-species comparisons to identify candidate oncogenes essential for the pathogenesis of human cancer.
Journal Article