584 research outputs found
The persistence and ecological impacts of a cyanobacterium genetically engineered to express mosquitocidal Bacillus thuringiensis toxins.
Background: The cyanobacterium Anabaena PCC 7120#11 has been genetically engineered to act as a delivery vehicle for Bacillus thuringiensis subspecies israelensis mosquitocidal toxins. To address ecological concerns about releasing this genetically engineered microorganism into the environment for mosquito larva control, the persistence and ecological impacts of PCC 7120#11 was evaluated using multi-species, standardized aquatic microcosms. Methods: The microcosms were set up as described in ASTM E1366-02 (Standard Practice for Standardized Aquatic Microcosms: Fresh Water), with a few modifications. The treatment group microcosms were inoculated with PCC 7120#11 and key water quality parameters and non-target effects were compared between the treatment and control groups over a period of 35 days. Results: PCC 7120#11 decreased from a concentration of 4.50 Ă 106 cells/ml (at inoculation) to 1.32 Ă 103 cells/ml after 4 weeks and larvicidal activity against third instar larvae of Anopheles arabiensis was only evident for two weeks after treatment. Both treatment and the interaction of treatment and time had a significant effect on nitrate, phosphate and photosynthetic microorganism concentrations. Treatment with PCC 7120#11 caused a temporary spike in ammonia in the microcosms a week after treatment, but the concentrations were well below acute and chronic criteria values for ammonia in freshwater ecosystems. Cyprinotus vidua concentrations were not significantly different between PCC 7120#11 and control microcosms. In PCC 7120#11 microcosms, Daphnia pulex concentrations were significantly lower than control concentrations between days 18 and 25. By the end of the experiment, none of the measured variables were significantly different between the treatment groups. Conclusions: The standard aquatic microcosm experiments provided more data on the ecological impacts of PCC 7120#11 than single-organism assessments would have. On the basis of the relatively minor, short-term effects that PCC 7120#11 had on water quality parameters and non-target invertebrates, further evaluation of PCC 7120#11 for use in integrated vector management is warranted.SP201
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Potassium dependent structural changes in the selectivity filter of HERG potassium channels
The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to the role they play in regulating cardiac electrical activity. Here, we exploit the K+ sensitivity of HERG inactivation to determine structures of both a conductive and non-conductive selectivity filter structure of HERG. The conductive state has a canonical cylindrical shaped selectivity filter. The non-conductive state is characterized by flipping of the selectivity filter valine backbone carbonyls to point away from the central axis. The side chain of S620 on the pore helix plays a central role in this process, by coordinating distinct sets of interactions in the conductive, non-conductive, and transition states. Our model represents a distinct mechanism by which ion channels fine tune their activity and could explain the uniquely rapid inactivation kinetics of HERG
Managed Aquifer Recharge as a Tool to Enhance Sustainable Groundwater Management in California
A growing population and an increased demand for water resources have resulted in a global trend of groundwater depletion. Arid and semi-arid climates are particularly susceptible, often relying on groundwater to support large population centers or irrigated agriculture in the absence of sufficient surface water resources. In an effort to increase the security of groundwater resources, managed aquifer recharge (MAR) programs have been developed and implemented globally. MAR is the approach of intentionally harvesting and infiltrating water to recharge depleted aquifer storage. California is a prime example of this growing problem, with three cities that have over a million residents and an agricultural industry that was valued at 47 billion dollars in 2015. The present-day groundwater overdraft of over 100 km3 (since 1962) indicates a clear disparity between surface water supply and water demand within the state. In the face of groundwater overdraft and the anticipated effects of climate change, many new MAR projects are being constructed or investigated throughout California, adding to those that have existed for decades. Some common MAR types utilized in California include injection wells, infiltration basins (also known as spreading basins, percolation basins, or recharge basins), and low-impact development. An emerging MAR type that is actively being investigated is the winter flooding of agricultural fields using existing irrigation infrastructure and excess surface water resources, known as agricultural MAR. California therefore provides an excellent case study to look at the historical use and performance of MAR, ongoing and emerging challenges, novel MAR applications, and the potential for expansion of MAR. Effective MAR projects are an essential tool for increasing groundwater security, both in California and on a global scale. This chapter aims to provide an overview of the most common MAR types and applications within the State of California and neighboring semi-arid regions
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Flood risk and climate change: global and regional perspectives
A holistic perspective on changing rainfall-driven flood risk is provided for the late 20th and early 21st centuries. Economic losses from floods have greatly increased, principally driven by the expanding exposure of assets at risk. It has not been possible to attribute rain-generated peak streamflow trends to anthropogenic climate change over the past several decades. Projected increases in the frequency and intensity of heavy rainfall, based on climate models, should contribute to increases in precipitation-generated local flooding (e.g. flash flooding and urban flooding). This article assesses the literature included in the IPCC SREX report and new literature published since, and includes an assessment of changes in flood risk in seven of the regions considered in the recent IPCC SREX report-Africa, Asia, Central and South America, Europe, North America, Oceania and Polar regions. Also considering newer publications, this article is consistent with the recent IPCC SREX assessment finding that the impacts of climate change on flood characteristics are highly sensitive to the detailed nature of those changes and that presently we have only low confidence1 in numerical projections of changes in flood magnitude or frequency resulting from climate change
The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction
We investigated the effect of trastuzumab on cardiac function in a realâworld historic cohort of patients with HER2âpositive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirtyâseven patients with HER2âpositive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%â48%) and median followâup was 18âmonths (IQR 9â34âmonths). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF 5%âpoints below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase 5%âpoints below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardioâprotective medications (CPM), including ACEâinhibitors, betaâblockers and angiotensineâ2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, PÂ =Â .091). Sixtyâfive percent of patients who received trastuzumab for HER2âpositive MBC did not develop severe cardiotoxicity during a median followâup of 18âmonths, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than twoâthirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population
Climate change and increased risk for the insurance sector: A global perspective and an assessment for the Netherlands.
Climate change is projected to increase the frequency and severity of extreme weather events. As a consequence, economic losses caused by natural catastrophes could increase significantly. This will have considerable consequences for the insurance sector. On the one hand, increased risk from weather extremes requires assessing expected changes in damage and including adequate climate change projections in risk management. On the other hand, climate change can also bring new business opportunities for insurers. This paper gives an overview of the consequences of climate change for the insurance sector and discusses several strategies to cope with and adapt to increased risks. The particular focus is on the Dutch insurance sector, as the Netherlands is extremely vulnerable to climate change, especially with regard to extreme precipitation and flooding. Current risk sharing arrangements for weather risks are examined while potential new business opportunities, adaptation strategies, and public-private partnerships are identified. © The Author(s) 2009
A pilot study using tactile cueing for gait rehabilitation following stroke
Recovery of walking function is a vital goal of post-stroke rehabilitation. Cueing using audio metronomes has been shown to improve gait, but can be impractical when interacting with others, particularly outdoors where awareness of vehicles and bicycles is essential. Audio is also unsuitable in environments with high background noise, or for those with a hearing impairment. If successful, lightweight portable tactile cueing has the potential to take the benefits of cueing out of the laboratory and into everyday life. The Haptic Bracelets are lightweight wireless devices containing a computer, accelerometers and low-latency vibrotactiles with a wide dynamic range. In this paper we review gait rehabilitation problems and existing solutions, and present an early pilot in which the Haptic Bracelets were applied to post-stroke gait rehabilitation. Tactile cueing during walking was well received in the pilot, and analysis of motion capture data showed immediate improvements in gait
Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features
Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns. Thirteen out of fifteen MYC - R+ samples showed a non-classical cytology including pleomorphic (centroblastic, immunoblastic), anaplastic or blastoid. MYC translocation partners were IG-loci in 4/11 and non-IG loci in 7/11 analysed cases. The involved IG-loci included IGH in 3 cases and IGL in one case. PAX5 was the non-IG partner in 2/7 patients. The MYC - R+ MCL reported herein frequently displayed characteristics associated with an aggressive clinical course including high genomic-complexity (6/7 samples), frequent deletions involving the CDKN2A locus (7/10 samples), high Ki-67 proliferation index (12/13 samples) and frequent P53 expression (13/13 samples). Of note, in 4/14 samples, SOX11 was not or only focally expressed and 3/13 samples showed focal or diffuse TdT-positivity presenting a diagnostic challenge as these features could point to a differential diagnosis of diffuse large B-cell lymphoma and/or lymphoblastic lymphoma/leukaemia
Floods and climate: emerging perspectives for flood risk assessment and management
Flood estimation and flood management have traditionally been the domain of
hydrologists, water resources engineers and statisticians, and disciplinary
approaches abound. Dominant views have been shaped; one example is the
catchment perspective: floods are formed and influenced by the interaction
of local, catchment-specific characteristics, such as meteorology,
topography and geology. These traditional views have been beneficial, but
they have a narrow framing. In this paper we contrast traditional views with
broader perspectives that are emerging from an improved understanding of the
climatic context of floods. We come to the following conclusions: (1) extending the traditional
system boundaries (local catchment, recent decades, hydrological/hydraulic
processes) opens up exciting possibilities for better understanding and
improved tools for flood risk assessment and management. (2) Statistical
approaches in flood estimation need to be complemented by the search for the
causal mechanisms and dominant processes in the atmosphere, catchment and
river system that leave their fingerprints on flood characteristics.
(3) Natural climate variability leads to time-varying flood characteristics, and
this variation may be partially quantifiable and predictable, with the
perspective of dynamic, climate-informed flood risk management.
(4) Efforts are needed to fully account for factors that contribute to changes
in all three risk components (hazard, exposure, vulnerability) and to
better understand the interactions between society and floods. (5) Given the
global scale and societal importance, we call for the organization of an
international multidisciplinary collaboration and data-sharing initiative to
further understand the links between climate and flooding and to advance
flood research
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