79717 research outputs found
Sort by
ParkBoPharmacyMetalloproteaseSecretedType.pdf
No full textVibrio cholerae is autochthonous to various aquatic niches and is the etiological agent of the life-threatening diarrheal disease
cholera. The persistence of V. cholerae in natural habitats is a crucial factor in the epidemiology of cholera. In contrast to the
well-studied V. cholerae-chitin connection, scarce information is available about the factors employed by the bacteria for the
interaction with collagens. Collagens might serve as biologically relevant substrates, because they are the most abundant protein
constituents of metazoan tissues and V. cholerae has been identified in association with invertebrate and vertebrate marine animals,
as well as in a benthic zone of the ocean where organic matter, including collagens, accumulates. Here, we describe the
characterization of the V. cholerae putative collagenase, VchC, encoded by open reading frame VC1650 and belonging to the
subfamily M9A peptidases. Our studies demonstrate that VchC is an extracellular collagenase degrading native type I collagen of
fish and mammalian origin. Alteration of the predicted catalytic residues coordinating zinc ions completely abolished the protein
enzymatic activity but did not affect the translocation of the protease by the type II secretion pathway into the extracellular
milieu. We also show that the protease undergoes a maturation process with the aid of a secreted factor(s). Finally, we propose
that V. cholerae is a collagenovorous bacterium, as it is able to utilize collagen as a sole nutrient source. This study initiates new
lines of investigations aiming to uncover the structural and functional components of the V. cholerae collagen utilization
program
AlderJayCEOASGlobalClimateSimulations_SupplementalMaterial.pdf
No full textWe apply GENMOM, a coupled atmosphere–ocean climate model, to simulate eight equilibrium time
slices at 3000-year intervals for the past 21,000 years forced
by changes in Earth–Sun geometry, atmospheric greenhouse
gases (GHGs), continental ice sheets, and sea level. Simulated
global cooling during the Last Glacial Maximum
(LGM) is 3.8°C and the rate of post-glacial warming is in
overall agreement with recently published temperature reconstructions.
The greatest rate of warming occurs between
15 and 12 ka (2.4°C over land, 0.7°C over oceans, and
1.4°C globally) in response to changes in radiative forcing
from the diminished extent of the Northern Hemisphere (NH)
ice sheets and increases in GHGs and NH summer insolation.
The modeled LGM and 6 ka temperature and precipitation
climatologies are generally consistent with proxy reconstructions,
the PMIP2 and PMIP3 simulations, and other paleoclimate
data–model analyses. The model does not capture the
mid-Holocene “thermal maximum” and gradual cooling to
preindustrial (PI) global temperature found in the data. Simulated
monsoonal precipitation in North Africa peaks between
12 and 9 ka at values ~50% greater than those of the PI,
and Indian monsoonal precipitation peaks at 12 and 9 ka at
values ~45% greater than the PI. GENMOM captures the
reconstructed LGM extent of NH and Southern Hemisphere
(SH) sea ice. The simulated present-day Antarctica Circumpolar
Current (ACC) is ~48% weaker than the observed (62
versus 119 Sv). The simulated present-day Atlantic Meridional
Overturning Circulation (AMOC) of 19:3 ± 1:4 Sv on
the Bermuda Rise (33°N) is comparable with observed value
of 18:7 ± 4:8 Sv. AMOC at 33°N is reduced by ~15% during
the LGM, and the largest post-glacial increase (~11 %)
occurs during the 15 ka time slice
BioEarth: Envisioning and developing a new regional earth system model to inform natural and agricultural resource management
Get PDFAs managers of agricultural and natural resources are confronted with uncertainties in global change impacts, the complexities associated with the interconnected cycling of nitrogen, carbon, and water present daunting management challenges. Existing models provide detailed information on specific sub-systems (e.g., land, air, water, and economics). An increasing awareness of the unintended consequences of management decisions resulting from interconnectedness of these sub-systems, however, necessitates coupled regional earth system models (EaSMs). Decision makers’ needs and priorities can be integrated into the model design and development processes to enhance decision-making relevance and “usability” of EaSMs. BioEarth is a research initiative currently under development with a focus on the U.S. Pacific Northwest region that explores the coupling of multiple stand-alone EaSMs to generate usable information for resource decision-making. Direct engagement between model developers and non-academic stakeholders involved in resource and environmental management decisions throughout the model development process is a critical component of this effort. BioEarth utilizes a bottom-up approach for its land surface model that preserves fine spatial-scale sensitivities and lateral hydrologic connectivity, which makes it unique among many regional EaSMs. This paper describes the BioEarth initiative and highlights opportunities and challenges associated with coupling multiple stand-alone models to generate usable information for agricultural and natural resource decision-making
Intertidal zone particulate organic carbon redistribution by low-tide rainfall
Get PDFWe present field data and data from the literature to highlight the effects of low-tide rainfall on particulate organic carbon (POC) redistribution in intertidal landscapes. The POC exchanges reported from disparate but related studies were standardized to a storm-induced exchange rate (gPOC m⁻² mmRain⁻¹) and compared. Results show that these intertidal areas have a characteristic response to rainfall with an average flux of 0.040 ± 0.038 gPOC m⁻² mmRain⁻¹. Further, low-tide rainfall can entrain and redistribute 7–54% of annual sedimentary POC accumulation, or 12–75% of annual POC export, based on current outwelling assessments. Finally, we provide a conceptual model describing the variability of rainfall-driven POC exchange through the hierarchical structure of intertidal landscapes and how observations of POC flux can be expected to change across the intertidal landscape. This information should be used to guide sampling strategies for continued intertidal zone rainfall work.This is the publisher’s final pdf. The article is copyrighted by the Association for the Sciences of Limnology and Oceanography (ASLO) and published by John Wiley & Sons, Ltd. It can be found at: http://www.aslo.org/lo/index.htm
IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSlideSet.pptx
No full textBACKGROUND:
AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined.
METHODS:
We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized, multiple-ascending-dose study in which 40 healthy humans (8 humans per dose group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or 16 mg per kilogram of body weight) or placebo, in a 3: 1 ratio. We estimated the protective dose in humans by comparing pharmacokinetic variables in infected nonhuman primates, uninfected nonhuman primates, and uninfected humans.
RESULTS:
Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P < 0.001 with the use of the log-rank test for the comparison of survival across groups). No safety concern was identified at doses up to 16 mg per kilogram per day in humans. No serious adverse events were reported. Drug exposure (the area under the curve) was dose-dependent in both nonhuman primates and humans; drug clearance was independent of dose but was higher in nonhuman primates than in humans. The protective dose in humans was initially estimated, on the basis of exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to 12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram per day to match the geometric mean protective exposure in nonhuman primates.
CONCLUSIONS:
This study shows that, on the basis of efficacy in nonhuman primates and pharmacokinetic data in humans, AVI-7288 has potential as postexposure prophylaxis for MARV infection in humans
Solutions for Recovering and Sustaining the Bounty of the Ocean Combining Fishery Reforms, Rights-Based Fisheries Management, and Marine Reserves
Get PDFFood security, economic opportunities, and other benefits provided by a healthy ocean are in jeopardy because of years of overexploitation of many fisheries, and the challenges will intensify in many locales as climate and the environment continue to change. The good news is that solutions are gaining traction. Mandates to end overfishing that use scientifically determined catch limits and rights-based approaches to fishery management have produced impressive results in ending overfishing and recovering depleted stocks. Similarly, spatial protections, such as fully protected marine reserves, are increasing the diversity, size, and abundance of species within reserves; some of that bounty reaches fished areas outside of them. We review the effects of combining catch limits, rights-based fisheries approaches, and establishment of marine reserves and discuss additional advantages of these combined solutions in securing sustainable and profitable fisheries, community goals, and healthy ecosystems. This paper highlights the contribution of emerging science-based solutions and the steps needed to replicate and scale these successes. Triple-wins for the environment, the economy, and society can be achieved through integrated fisheries management and protection as conscious steps toward reversing the current degradation of our ocean’s living resources.This manuscript is based on a keynote lecture given by Jane Lubchenco at One Planet, One Ocean: The 2nd International Ocean Research Conference, Barcelona, Spain, November 17–21, 2014. This is the publisher’s final pdf. The published article is copyrighted by the Oceanography Society and can be found at: http://www.tos.org/oceanography/archive/28-2_barner.htm
UllmanDavidCEOASLaurentideIce-SheetSuppData.zip
No full textChanges in the amount of summer incoming solar radiation (insolation) reaching the Northern Hemisphere are the underlying pacemaker of glacial cycles. However, not all rises in boreal summer insolation over the past 800,000 years resulted in deglaciation to present-day ice volumes, suggesting that there may be a climatic threshold for the disappearance of land-based ice. Here we assess the surface mass balance stability of the Laurentide ice sheet—the largest glacial ice mass in the Northern Hemisphere—during the last deglaciation (24,000 to 9,000 years ago). We run a surface energy balance model with climate data from simulations with a fully coupled atmosphere–ocean general circulation model for key time slices during the last deglaciation. We find that the surface mass balance of the Laurentide ice sheet was positive throughout much of the deglaciation, and suggest that dynamic discharge was mainly responsible for mass loss during this time. Total surface mass balance became negative only in the early Holocene, indicating the transition to a new state where ice loss occurred primarily by surface ablation. We conclude that the Laurentide ice sheet remained a viable ice sheet before the Holocene and began to fully deglaciate only once summer temperatures and radiative forcing over the ice sheet increased by 6–7 °C and 16–20 W m⁻², respectively, relative to full glacial conditions
Accelerated food source location in aging Drosophila
Get PDFAdequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila melanogaster, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with a decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than young ones. Robust food search behavior was associated with significantly lower fat reserves and lower starvation resistance in old flies. Food-finding latency (FFL) was shortened in young wild-type flies that were starved until their fat was depleted but also in heterozygous chico mutants with reduced insulin receptor activity and higher fat deposits. Conversely, food trap entry was delayed in old flies with increased insulin signaling. Our results suggest that the difference in FFL between young and old flies is linked to age-dependent differences in metabolic status and may be mediated by reduced insulin signaling.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by John Wiley & Sons, Ltd. on behalf of the Anatomical Society. The published article can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291474-9726
KamvarZBotanyPlantPathSpatialTemporalAnalysisSupplementaryFigureS1.pdf
No full textSudden oak death caused by the oomycete Phytophthora ramorum was first discovered in California toward the end of the 20th century and subsequently emerged on tanoak forests in Oregon before its first detection in 2001 by aerial surveys. The Oregon Department of Forestry has since monitored the epidemic and sampled symptomatic tanoak trees from 2001 to the present. Populations sampled over this period were genotyped using microsatellites and studied to infer the population genetic history. To date, only the NA1 clonal lineage is established in this region, although three lineages exist on the North American west coast. The original introduction into the Joe Hall area eventually spread to several regions: mostly north but also east and southwest. A new introduction into Hunter Creek appears to correspond to a second introduction not clustering with the early introduction. Our data are best explained by both introductions originating from nursery populations in California or Oregon and resulting from two distinct introduction events. Continued vigilance and eradication of nursery populations of P. ramorum are important to avoid further emergence and potential introduction of other clonal lineages
Toward energy-efficient cloud computing: Prediction, consolidation, and overcommitment
Get PDFEnergy consumption has become a significant concern for cloud service providers due to financial as well as environmental factors. As a result, cloud service providers are seeking innovative ways that allow them to reduce the amount of energy that their data centers consume. They are calling for the development of new energy-efficient techniques that are suitable for their data centers. The services offered by the cloud computing paradigm have unique characteristics that distinguish them from traditional services, giving rise to new design challenges as well as opportunities when it comes to developing energy-aware resource allocation techniques for cloud computing data centers. In this article we highlight key resource allocation challenges, and present some potential solutions to reduce cloud data center energy consumption. Special focus is given to power management techniques that exploit the virtualization technology to save energy. Several experiments, based on real traces from a Google cluster, are also presented to support some of the claims we make in this article.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by IEEE-Institute of Electrical and Electronics Engineers and can be found at: http://www.comsoc.org/netmag,©2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works