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Articles 1 - 24 of 24

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter Dec 2015

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1 ...


Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros Oct 2015

Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros

Victor R. Ambros

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms ...


Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke Oct 2015

Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke

Victor R. Ambros

Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in ...


Drug-Resistant Hiv-1 Protease Regains Functional Dynamics Through Cleavage Site Coevolution, Nevra Ozer, Aysegul Ozen, Celia Schiffer, Turkan Haliloglu May 2015

Drug-Resistant Hiv-1 Protease Regains Functional Dynamics Through Cleavage Site Coevolution, Nevra Ozer, Aysegul Ozen, Celia Schiffer, Turkan Haliloglu

Celia A. Schiffer

Drug resistance is caused by mutations that change the balance of recognition favoring substrate cleavage over inhibitor binding. Here, a structural dynamics perspective of the regained wild-type functioning in mutant HIV-1 proteases with coevolution of the natural substrates is provided. The collective dynamics of mutant structures of the protease bound to p1-p6 and NC-p1 substrates are assessed using the Anisotropic Network Model (ANM). The drug-induced protease mutations perturb the mechanistically crucial hinge axes that involve key sites for substrate binding and dimerization and mainly coordinate the intrinsic dynamics. Yet with substrate coevolution, while the wild-type dynamic behavior is restored in ...


Evolution Of The Influenza A Virus Genome During Development Of Oseltamivir Resistance In Vitro, Nicholas Renzette, Daniel Caffrey, Konstantin Zeldovich, Ping Liu, Glen Gallagher, Daniel Aiello, Alyssa Porter, Evelyn Kurt-Jones, Daniel Bolon, Yu-Ping Poh, Jeffrey Jensen, Celia Schiffer, Timothy Kowalik, Robert Finberg, Jennifer Wang Mar 2015

Evolution Of The Influenza A Virus Genome During Development Of Oseltamivir Resistance In Vitro, Nicholas Renzette, Daniel Caffrey, Konstantin Zeldovich, Ping Liu, Glen Gallagher, Daniel Aiello, Alyssa Porter, Evelyn Kurt-Jones, Daniel Bolon, Yu-Ping Poh, Jeffrey Jensen, Celia Schiffer, Timothy Kowalik, Robert Finberg, Jennifer Wang

Glen R. Gallagher

Influenza A virus (IAV) is a major cause of morbidity and mortality throughout the world. Current antiviral therapies include oseltamivir, a neuraminidase inhibitor that prevents the release of nascent viral particles from infected cells. However, the IAV genome can evolve rapidly, and oseltamivir resistance mutations have been detected in numerous clinical samples. Using an in vitro evolution platform and whole-genome population sequencing, we investigated the population genomics of IAV during the development of oseltamivir resistance. Strain A/Brisbane/59/2007 (H1N1) was grown in Madin-Darby canine kidney cells with or without escalating concentrations of oseltamivir over serial passages. Following drug ...


Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs Oct 2014

Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs

Elizabeth J. Luna

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and ...


A Phylogenetic Analysis Of The Correlates Of Sleep In Birds, Timothy Roth, John Lesku, Charles Amlaner, Steven Lima Nov 2006

A Phylogenetic Analysis Of The Correlates Of Sleep In Birds, Timothy Roth, John Lesku, Charles Amlaner, Steven Lima

Charles J. Amlaner

Quantitative comparative studies of sleep have focused exclusively on mammals. Such studies have repeatedly found strong relationships between the time spent in various sleep states and constitutive variables related to morphology, physiology, and life history. These studies influenced the development of several prominent hypotheses for the functions of sleep, but the applicability of these patterns and hypotheses to non-mammalian taxa is unclear. Here, we present the first quantitative analysis of sleep in a non-mammalian taxon (birds), focusing on the daily amount of time spent in slow-wave sleep (SWS) and rapid-eye movement (REM) sleep as determined by electrophysiological methods. We examined ...


A Phylogenetic Analysis Of Sleep Architecture In Mammals: The Integration Of Anatomy, Physiology, And Ecology, John Lesku, Timothy Roth, Charles Amlaner, Steven Lima Sep 2006

A Phylogenetic Analysis Of Sleep Architecture In Mammals: The Integration Of Anatomy, Physiology, And Ecology, John Lesku, Timothy Roth, Charles Amlaner, Steven Lima

Charles J. Amlaner

Among mammalian species, the time spent in the two main "architectural" states of sleep-slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep-varies greatly. Previous comparative studies of sleep architecture found that larger mammals, those with bigger brains, and those with higher absolute basal metabolic rates (BMR) tended to engage in less SWS and REM sleep. Species experiencing a greater risk of predation also exhibited less SWS and REM sleep. In all cases, however, these studies lacked a formal phylogenetic and theoretical framework and used mainly correlational analyses. Using independent contrasts and an updated data set, we extended existing approaches with path analysis ...


Asynchronous Eye Closure As An Anti-Predator Behavior In The Western Fence Lizard (Sceloporus Occidentalis), Christian Mathews, John Lesku, Stephen Lima, Charles Amlaner Feb 2006

Asynchronous Eye Closure As An Anti-Predator Behavior In The Western Fence Lizard (Sceloporus Occidentalis), Christian Mathews, John Lesku, Stephen Lima, Charles Amlaner

Charles J. Amlaner

Asynchronous eye closure (ASEC), one eye open while the other is closed, is a behavior observed in birds, some aquatic mammals, and reptiles. In birds and aquatic mammals, ASEC is associated with unihemispheric sleep wherein the cerebral hemisphere contralateral to (i.e. neurologically connected to) the closed eye sleeps while the other cerebral hemisphere remains awake with its associated eye open and functional. Evidence from birds suggests that ASEC is an important anti-predator adaptation to mediate the trade-off between the need to remain vigilant and the need to sleep. However, the anti-predator correlates of ASEC remain largely unstudied in other ...


Sleeping Under Risk Of Predation, Steven Lima, John Lesku, Neil Rattenborg, Charles Amlaner Sep 2005

Sleeping Under Risk Of Predation, Steven Lima, John Lesku, Neil Rattenborg, Charles Amlaner

Charles J. Amlaner

Every studied animal engages in sleep, and many animals spend much of their lives in this vulnerable behavioural state. We believe that an explicit description of this vulnerability will provide many insights into both the function and architecture (or organization) of sleep. Early studies of sleep recognized this idea, but it has been largely overlooked during the last 20 years. We critically evaluate early models that suggested that the function of sleep is antipredator in nature, and outline a new model in which we argue that whole-brain or 'blackout' sleep may be the safest way to sleep given a functionally ...


Unilateral Eye Closure And Interhemispheric Eeg Asymmetry During Sleep In The Pigeon (Columba Livia), Niels Rattenborg, Charles Amlaner, Steven Lima Dec 2000

Unilateral Eye Closure And Interhemispheric Eeg Asymmetry During Sleep In The Pigeon (Columba Livia), Niels Rattenborg, Charles Amlaner, Steven Lima

Charles J. Amlaner

Aquatic mammals (i.e., Cetaceans, eared seals and manatees) and birds show interhemispheric asymmetries (IA) in slow-wave sleep-related electroencephalographic (EEG) activity, suggesting that the depth of sleep differs between hemispheres. In birds, an association between unilateral eye closure and IA has been reported in five species from three orders (i.e., Galliformes, Charadriiformes, and Anseriformes). Moreover, unilateral eye closure has been observed during behaviorally defined sleep in 29 species from 13 avian orders, suggesting that birds in general display IA during sleep. Despite the apparent prevalence of unilateral eye closure and IA in birds, previous work did not detect A ...


Behavioral, Neurophysiological And Evolutionary Perspectives On Unihemispheric Sleep, Niels Rattenborg, Charles Amlaner, Steven Lima Nov 2000

Behavioral, Neurophysiological And Evolutionary Perspectives On Unihemispheric Sleep, Niels Rattenborg, Charles Amlaner, Steven Lima

Charles J. Amlaner

Several animals mitigate the fundamental conflict between sleep and wakefulness by engaging in unihemispheric sleep, a unique state during which one cerebral hemisphere sleeps while the other remains awake. Among mammals, unihemispheric sleep is restricted to aquatic species (Cetaceans, cared seals and manatees). in contrast to mammals, unihemispheric sleep is widespread in birds, and may even occur in reptiles. Unihemispheric sleep allows surfacing to breathe in aquatic mammals and predator detection in birds. Despite the apparent utility in being able to sleep unihemispherically, very few mammals sleep in this manner. This is particularly interesting since the reptilian ancestors to mammals ...


Eye States And Postures Of The Western Fence Lizard (Sceloporus Occidentalis), With Special Reference To Asynchronous Eye Closure And Behavioral Sleep, Christian Mathews, Charles Amlaner Aug 2000

Eye States And Postures Of The Western Fence Lizard (Sceloporus Occidentalis), With Special Reference To Asynchronous Eye Closure And Behavioral Sleep, Christian Mathews, Charles Amlaner

Charles J. Amlaner

No abstract provided.


Half-Awake To The Risk Of Predation, Niels Rattenborg, Steven Lima, Charles Amlaner Feb 1999

Half-Awake To The Risk Of Predation, Niels Rattenborg, Steven Lima, Charles Amlaner

Charles J. Amlaner

Birds have overcome the problem of sleeping in risky situations by developing the ability to sleep with one eye open and one hemisphere of the brain awake. Such unihemispheric slow-wave sleep is in direct contrast to the typical situation in which sleep and wakefulness are mutually exclusive states of the whole brain. We have found that birds can detect approaching predators during unihemispheric slow-wave sleep, and that they can increase their use of unihemispheric sleep as the risk of predation increases. We believe this is the first evidence for an animal behaviourally controlling sleep and wakefulness simultaneously in different regions ...


Facultative Control Of Avian Unihemispheric Sleep Under The Risk Of Predation, Niels Rattenborg, Steven Lima, Charles Amlaner Dec 1998

Facultative Control Of Avian Unihemispheric Sleep Under The Risk Of Predation, Niels Rattenborg, Steven Lima, Charles Amlaner

Charles J. Amlaner

Birds and aquatic mammals are the only taxonomic groups known to exhibit unihemispheric slow-wave sleep (USWS). In aquatic mammals, USWS permits sleep and breathing to occur concurrently in water. However, the function of avian USWS has been unclear. Our study is based on the premise that avian USWS serves a predator detection function, since the eye contralateral to the awake hemisphere remains open during USWS. If USWS functions as a form of predator detection, then birds should be able to control both the proportion of slow-wave sleep composed of USWS and the orientation of the open eye in response to ...


Sleep, Sleep Disorders, And Biological Rhythms, Charles Amlaner, Robert Greene, Michael Hanson, Greg Greg Nichols, Naomi Rogers, Carol Thibodeau Dec 1998

Sleep, Sleep Disorders, And Biological Rhythms, Charles Amlaner, Robert Greene, Michael Hanson, Greg Greg Nichols, Naomi Rogers, Carol Thibodeau

Charles J. Amlaner

A module to help students to understand the nature and function of sleep and its effects on human health; to experience the process of scientific inquiry; and to recognize the role of science in society and the relationship of basic science and human health.


Harvest: A Generalized Animal Population Growth Simulation, David Stewart, Charles Amlaner, Claude Barnett Jun 1992

Harvest: A Generalized Animal Population Growth Simulation, David Stewart, Charles Amlaner, Claude Barnett

Charles J. Amlaner

We present a general purpose discrete-event, stochastic simulation model (HARVEST) which can be used to model the population growth of a wide variety of animal species. A complete example is given with validation, to show how it can be used for managing the Eastern wild turkey. The structure of the simulation system (micro Passim) is described, and the implementation of the model is discussed as an example of how the process-interaction simulation protocol may be used to represent a complex natural system. The model is designed to be used by state and federal wildlife agencies for exploration of the effects ...


Turning Eggs To Fossils: A Natural Experiment In Taphonomy, James Hayward, Charles Amlaner, Karen Young May 1989

Turning Eggs To Fossils: A Natural Experiment In Taphonomy, James Hayward, Charles Amlaner, Karen Young

Charles J. Amlaner

Ashfall from Mount St. Helens' May 18, 1980 eruption covered eggs and nests of two species of colonial, ground-nesting gulls. While some members of both species excavated their eggs from beneath the ash, most eggs and nests remained buried. One year after the ashfall, habitats known to contain pre-ashfall nests were transected and the ash layer was measured and removed. Eggs, nests, and associated materials were counted. Entire hollow eggshells and eggshell fragments were found, as well as rodent bones and teeth, bird bones, beetle carapaces, and vegetation. No fetal bones were found with eggs. Fossilization potential for nests and ...


Thermoregulation And Sleep: Effects Of Thermal Stress On Sleep Patterns Of Glaucous-Winged Gulls (Larus Glaucescens), Mark Opp, Nigel Ball, Don Miller, Charles Amlaner Jul 1987

Thermoregulation And Sleep: Effects Of Thermal Stress On Sleep Patterns Of Glaucous-Winged Gulls (Larus Glaucescens), Mark Opp, Nigel Ball, Don Miller, Charles Amlaner

Charles J. Amlaner

1. To determine effects of thermal stress on avian sleep patterns, incubating Glaucous-winged gulls were subjected to conditions of heat loss and heat gain via conduction from hollow copper eggs.

2. Heated manipulations resulted in significant reductions in sleep and rest relative to controls, whereas cooled manipulations had little effect.

3. The resilience of sleep to thermal stress is greater than that of rest. We suggest that the incompatability of sleep with conductive processes to off-load heat from the eggs is responsible in this case.

4. Pant Sleep, the behaviour in which birds appear to maintain some the benefits of ...


Sleeping Gulls And Predator Avoidance, Nigel Ball, James Shaffer, Charles Amlaner Oct 1984

Sleeping Gulls And Predator Avoidance, Nigel Ball, James Shaffer, Charles Amlaner

Charles J. Amlaner

No abstract provided.


A Synthesis Of Sleep In Wild Birds, Charles Amlaner, Nigel Ball Dec 1982

A Synthesis Of Sleep In Wild Birds, Charles Amlaner, Nigel Ball

Charles J. Amlaner

No abstract provided.


Sleep In The Herring Gull (Larus Argentatus), Charles Amlaner, David Mcfarland Apr 1981

Sleep In The Herring Gull (Larus Argentatus), Charles Amlaner, David Mcfarland

Charles J. Amlaner

Sleep postures and eye state of free-ranging herring gulls (Larus argentatus) were studied during the breeding season. Three mutually exclusive behaviours were observed, namely sleep, rest-sleep and rest postures. Arousal thresholds, eye blink rates and eye closure time were obtained during these behaviours. Significant relationships existed between eye blinking, eye closure, and a raised threshold of arousal when birds were in the sleep and rest-sleep postures. During a natural disturbance, birds in the sleep posture remained in this posture but did not blink their eyes: this is called pseudo sleep. Male gulls also exhibited a lower threshold of arousal while ...


Increases In A Population Of Nesting Glaucous-Winged Gulls Disturbed By Humans, Charles Amlaner, James Hayward, Ernest Schwab, John Stout Dec 1976

Increases In A Population Of Nesting Glaucous-Winged Gulls Disturbed By Humans, Charles Amlaner, James Hayward, Ernest Schwab, John Stout

Charles J. Amlaner

No abstract provided.


Predation On Nesting Gulls By A River Otter In Washington State, James Hayward, Charles Amlaner, W. Gillett, John Stout Apr 1975

Predation On Nesting Gulls By A River Otter In Washington State, James Hayward, Charles Amlaner, W. Gillett, John Stout

Charles J. Amlaner

No abstract provided.