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Find video protocols related to scientific articles indexed in Pubmed.
Biopesticides: State of the Art and Future Opportunities.
J. Agric. Food Chem.
PUBLISHED: 11-19-2014
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The use of biopesticides and related alternative management products is increasing. New tools, including semiochemicals and plant-incorporated protectants (PIPs), as well as botanical and microbially derived chemicals, are playing an increasing role in pest management, along with plant and animal genetics, biological control, cultural methods, and newer synthetics. The goal of this Perspective is to highlight promising new biopesticide research and development (R&D), based upon recently published work and that presented in the American Chemical Society (ACS) symposium "Biopesticides: State of the Art and Future Opportunities," as well as the authors' own perspectives. Although the focus is on biopesticides, included in this Perspective is progress with products exhibiting similar characteristics, namely those naturally occurring or derived from natural products. These are target specific, of low toxicity to nontarget organisms, reduced in persistence in the environment, and potentially usable in organic agriculture. Progress is being made, illustrated by the number of biopesticides and related products in the registration pipeline, yet major commercial opportunities exist for new bioherbicides and bionematicides, in part occasioned by the emergence of weeds resistant to glyphosate and the phase-out of methyl bromide. The emergence of entrepreneurial start-up companies, the U.S. Environmental Protection Agency (EPA) fast track for biopesticides, and the availability of funding for registration-related R&D for biorational pesticides through the U.S. IR-4 program provide incentives for biopesticide development, but an expanded effort is warranted both in the United States and worldwide to support this relatively nascent industry.
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Recent Trends in Global Emissions of Hydrochlorofluorocarbons and Hydrofluorocarbons-reflecting on the 2007 Adjustments to the Montreal Protocol.
J Phys Chem A
PUBLISHED: 11-19-2014
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Global-scale atmospheric measurements are used to investigate the effectiveness of recent adjustments to production and consumption controls on hydrochlorofluorocarbons (HCFCs) under the Montreal Protocol on Substances that Deplete the Ozone Layer (Montreal Protocol) and to assess recent projections of large increases in hydrofluorocarbon (HFC) production and emission. The results show that aggregate global HCFC emissions did not increase appreciably during 2007-2012 and suggest that the 2007 Adjustments to the Montreal Protocol played a role in limiting HCFC emissions well in advance of the 2013 cap on global production. HCFC emissions varied between 27 and 29 kt CFC-11-equivalent (eq)/yr or 0.76 and 0.79 GtCO2-eq/yr during this period. Despite slower than projected increases in aggregate HCFC emissions since 2007, total emissions of HFCs used as substitutes for HCFCs and chlorofluorocarbons (CFCs) have not increased more rapidly than rates projected for 2007-2012. HFC global emission magnitudes related to this substitution totaled 0.51 (-0.03, +0.04) GtCO2-eq/yr in 2012, a magnitude about two times larger than emissions reported to the United Nations Framework Convention on Climate Change (UNFCCC) for these HFCs. Assuming accurate reporting to the UNFCCC, the results imply that developing countries (non-Annex I Parties) not reporting to the UNFCCC now account for nearly 50% of global HFC emissions used as substitutes for ozone-depleting substances (ODSs). Global HFC emissions (as CO2-eq) from ODS substitution can be attributed approximately equally to mobile air conditioning, commercial refrigeration, and the sum of all other applications.
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Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-12-2014
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Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.
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Hand Hygiene Knowledge and Perceptions Among Anesthesia Providers.
Anesth. Analg.
PUBLISHED: 11-11-2014
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Health care worker compliance with hand hygiene guidelines is an important measure for health care-associated infection prevention, yet overall compliance across all health care arenas remains low. A correct answer to 4 of 4 structured questions pertaining to indications for hand decontamination (according to types of contact) has been associated with improved health care provider hand hygiene compliance when compared to those health care providers answering incorrectly for 1 or more questions. A better understanding of knowledge deficits among anesthesia providers may lead to hand hygiene improvement strategies. In this study, our primary aims were to characterize and identify predictors for hand hygiene knowledge deficits among anesthesia providers.
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Intestinal Expression of Fas and Fas Ligand Is Upregulated by Bacterial Signaling through TLR4 and TLR5, with Activation of Fas Modulating Intestinal TLR-Mediated Inflammation.
J. Immunol.
PUBLISHED: 11-08-2014
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TLRs play an important role in mediating intestinal inflammation and homeostasis. Fas is best studied in terms of its function in apoptosis, but recent studies demonstrate that Fas signaling may mediate additional functions such as inflammation. The role of Fas, and the Fas ligand (FasL), in the intestine is poorly understood. The aim of this study was to evaluate potential cross-talk between TLRs and Fas/FasL system in intestinal epithelial cells (IECs). IECs were stimulated with TLR ligands, and expression of Fas and FasL was investigated. Treatment with TLR4 and TLR5 ligands, but not TLR2 and 9 ligands, increased expression of Fas and FasL in IECs in vitro. Consistent with this finding, expression of intestinal Fas and FasL was reduced in vivo in the epithelium of TLR4 knockout (KO), 5KO, and germ-free mice, but not in TLR2KO mice. Modulating Fas signaling using agonistic anti-Fas augmented TLR4- and TLR5-mediated TNF-? and IL-8 production by IECs. In addition, suppression of Fas in IECs reduced the ability of TLR4 and TLR5 ligands and the intestinal pathogens Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL-8. In conclusion, this study demonstrates that extensive cross-talk in IECs occurs between the Fas and TLR signaling pathways, with the FasL/Fas system playing a role in TLR-mediated inflammatory responses in the intestine.
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The use of metabolomics in population-based research.
Adv Nutr
PUBLISHED: 11-01-2014
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The NIH has made a significant commitment through the NIH Common Fund's Metabolomics Program to build infrastructure and capacity for metabolomics research, which should accelerate the field. Given this investment, it is the ideal time to start planning strategies to capitalize on the infrastructure being established. An obvious gap in the literature relates to the effective use of metabolomics in large-population studies. Although published reports from population-based studies are beginning to emerge, the number to date remains relatively small. Yet, there is great potential for using metabolomics in population-based studies to evaluate the effects of nutritional, pharmaceutical, and environmental exposures (the "exposome"); conduct risk assessments; predict disease development; and diagnose diseases. Currently, the majority of the metabolomics studies in human populations are in nutrition or nutrition-related fields. This symposium provided a timely venue to highlight the current state-of-science on the use of metabolomics in population-based research. This session provided a forum at which investigators with extensive experience in performing research within large initiatives, multi-investigator grants, and epidemiology consortia could stimulate discussion and ideas for population-based metabolomics research and, in turn, improve knowledge to help devise effective methods of health research.
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PTCH1 expression at diagnosis predicts imatinib failure in chronic myeloid leukaemia patients in chronic phase.
Am. J. Hematol.
PUBLISHED: 09-17-2014
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The tyrosine kinase inhibitor (TKI) imatinib has revolutionized the management of chronic myeloid leukaemia (CML). However, around 25% of patients fail to sustain an adequate response. We sought to identify gene-expression biomarkers that could be used to predict imatinib response. The expression of 29 genes, previously implicated in CML pathogenesis, were measured by TaqMan Low Density Array in 73 CML patient samples. Patients were divided into low and high expression for each gene and imatinib failure (IF), probability of achieving CCyR, progression free survival and CML related OS were compared by Kaplan-Meier and log-rank. Results were validated in a second cohort of 56 patients, with a further technical validation using custom gene-expression assays in a conventional RT-qPCR in a sub-cohort of 37 patients. Patients with low PTCH1 expression showed a worse clinical response for all variables in all cohorts. PTCH1 was the most significant predictor in the multivariate analysis compared with Sokal, age and EUTOS. PTCH1 expression assay showed the adequate sensitivity, specificity and predictive values to predict for IF. Given the different treatments available for CML, measuring PTCH1 expression at diagnosis may help establish who will benefit best from imatinib and who is better selected for second generation TKI. Am. J. Hematol., 2014. © 2014 Wiley Periodicals, Inc.
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Hollandites as a new class of multiferroics.
Sci Rep
PUBLISHED: 08-27-2014
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Discovery of new complex oxides that exhibit both magnetic and ferroelectric properties is of great interest for the design of functional magnetoelectrics, in which research is driven by the technologically exciting prospect of controlling charges by magnetic fields and spins by applied voltages, for sensors, 4-state logic, and spintronics. Motivated by the notion of a tool-kit for complex oxide design, we developed a chemical synthesis strategy for single-phase multifunctional lattices. Here, we introduce a new class of multiferroic hollandite Ba-Mn-Ti oxides not apparent in nature. BaMn3Ti4O14.25, designated BMT-134, possesses the signature channel-like hollandite structure, contains Mn(4+) and Mn(3+) in a 1:1 ratio, exhibits an antiferromagnetic phase transition (TN ~ 120?K) with a weak ferromagnetic ordering at lower temperatures, ferroelectricity, a giant dielectric constant at low frequency and a stable intrinsic dielectric constant of ~200 (1-100?MHz). With evidence of correlated antiferromagnetic and ferroelectric order, the findings point to an unexplored family of structures belonging to the hollandite supergroup with multifunctional properties, and high potential for developing new magnetoelectric materials.
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Evaluation and integration of genetic signature for prediction risk of nasopharyngeal carcinoma in Southern China.
Biomed Res Int
PUBLISHED: 08-10-2014
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Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC).
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Annotated features of domestic cat - Felis catus genome.
Gigascience
PUBLISHED: 08-05-2014
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Domestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors.
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Endogenous Retrovirus Insertion in the KIT Oncogene Determines White and White spotting in Domestic Cats.
G3 (Bethesda)
PUBLISHED: 08-03-2014
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The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. We performed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1) as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and white spotting. A full-length (7125 bp) FERV1 element is associated with white spotting, whereas a FERV1 long terminal repeat (LTR) is associated with all Dominant White individuals. For purposes of statistical analysis, the alternatives of wild-type sequence, FERV1 element, and LTR-only define a triallelic marker. Taking into account pedigree relationships, deafness is genetically linked and associated with this marker; estimated P values for association are in the range of 0.007 to 0.10. The retrotransposition interrupts a DNAase I hypersensitive site in KIT intron 1 that is highly conserved across mammals and was previously demonstrated to regulate temporal and tissue-specific expression of KIT in murine hematopoietic and melanocytic cells. A large-population genetic survey of cats (n = 270), representing 30 cat breeds, supports our findings and demonstrates statistical significance of the FERV1 LTR and full-length element with Dominant White/blue iris (P < 0.0001) and white spotting (P < 0.0001), respectively.
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The Global Invertebrate Genomics Alliance (GIGA): developing community resources to study diverse invertebrate genomes.
J. Hered.
PUBLISHED: 07-30-2014
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Over 95% of all metazoan (animal) species comprise the "invertebrates," but very few genomes from these organisms have been sequenced. We have, therefore, formed a "Global Invertebrate Genomics Alliance" (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major challenges (e.g., species selection, sample collection and storage, sequence assembly, annotation, analytical tools) associated with genome/transcriptome sequencing across a large taxonomic spectrum. We aim to promote standards that will facilitate comparative approaches to invertebrate genomics and collaborations across the international scientific community. Candidate study taxa include species from Porifera, Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida, Bryozoa, and Platyhelminthes, among others. GIGA will target 7000 noninsect/nonnematode species, with an emphasis on marine taxa because of the unrivaled phyletic diversity in the oceans. Priorities for selecting invertebrates for sequencing will include, but are not restricted to, their phylogenetic placement; relevance to organismal, ecological, and conservation research; and their importance to fisheries and human health. We highlight benefits of sequencing both whole genomes (DNA) and transcriptomes and also suggest policies for genomic-level data access and sharing based on transparency and inclusiveness. The GIGA Web site (http://giga.nova.edu) has been launched to facilitate this collaborative venture.
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Timing of enteral nutrition in acute pancreatitis: meta-analysis of individuals using a single-arm of randomised trials.
Pancreatology
PUBLISHED: 07-23-2014
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In acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of admission might further reduce complications.
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HIV in (and out of) the clinic: Biomedicine, traditional medicine and spiritual healing in Harare.
SAHARA J
PUBLISHED: 07-15-2014
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Abstract Contemporary lived experiences of the human immunodeficiency virus (HIV) are shaped by clinical and cultural encounters with illness. In sub-Saharan countries such as Zimbabwe, HIV is treated in very different ways in various therapeutic contexts including by biomedical experts, traditional medicine and faith healers. The co-existence of such expertise raises important questions around the potencies and limits of medicalisation and alternative healing practices in promoting HIV recovery. First, in this study, drawing on in-depth qualitative interviews with 60 people from poor urban areas in Harare, we explore the experiences of people living with and affected by HIV. Specifically, we sought to document, interrogate and reflect on their perceptions and experiences of biomedicine in relation to traditional medicine and spiritual healing. Their accounts indicate that traditional medicine and spiritual beliefs continue to significantly influence the way in which HIV is understood, and the forms of help and care people seek. Second, we observe the dramatic and overwhelmingly beneficial impact of Antiretroviral Therapy and conclude through Zimbabwean's own stories that limitations around delivery and wider structural inequalities impede its potential. Lastly, we explore some practical implications of the biomedical clinic (and alternative healing practices) being understood as sites of ideological and expert contestation. This paper aimed to add to our knowledge of the relationships between traditional medicine and spiritual healing in connection with biomedicine and how this may influence HIV treatment and prevention.
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Perspectives on Transgenic, Herbicide-Resistant Crops in the USA Almost 20 Years after Introduction.
Pest Manag. Sci.
PUBLISHED: 06-18-2014
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Herbicide-resistant crops have had profound impacts on weed management. Most of the impact has been by glyphosate-resistant maize, cotton, soybean, and canola. Significant economic savings, yield increases, and more efficacious and simplified weed management resulted in widespread adoption of the technology. Initially, glyphosate-resistant crops enabled significantly reduced tillage and reduced the environmental impact of weed management. Continuous use of glyphosate with glyphosate-resistant crops over broad areas facilitated the evolution of glyphosate-resistant weeds, which have resulted in increases in the use of tillage and other herbicides with glyphosate, reducing some of the initial environmental benefits of glyphosate-resistant crops. Transgenic crops with resistance to auxinic herbicides, as well as to herbicides that inhibit acetolactate synthase, acetyl-CoA carboxylase, and hydroxyphenylpyruvate dioxygenase, stacked with glyphosate and/or glufosinate resistance, will become available in the next few years. These technologies will provide additional weed management options for farmers, but will not have all of the positive impacts (reduced cost, simplified weed management, lowered environmental impact, and reduced tillage) that glyphosate-resistant crops had initially. In the more distant future, other herbicide-resistant crops (including non-transgenic ones), herbicides with new modes of action, and technologies that are currently in their infancy (e.g., bioherbicides, sprayable herbicidal RNAi, and/or robotic weeding) may impact the role of transgenic, herbicide-resistant crops in weed management.
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The Dynamics of Enterococcus Transmission from Bacterial Reservoirs Commonly Encountered by Anesthesia Providers.
Anesth. Analg.
PUBLISHED: 06-18-2014
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Enterococci, the second leading cause of health care-associated infections, have evolved from commensal and harmless organisms to multidrug-resistant bacteria associated with a significant increase in patient morbidity and mortality. Prevention of ongoing spread of this organism within and between hospitals is important. In this study, we characterized Enterococcus transmission dynamics for bacterial reservoirs commonly encountered by anesthesia providers during the routine administration of general anesthesia.
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The Epidemiology of Staphylococcus aureus Transmission in the Anesthesia Work Area.
Anesth. Analg.
PUBLISHED: 06-18-2014
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Little is known regarding the epidemiology of intraoperative Staphylococcal aureus transmission. The primary aim of this study was to examine the mode of transmission, reservoir of origin, transmission locations, and antibiotic susceptibility for frequently encountered S aureus strains (phenotypes) in the anesthesia work area. Our secondary aims were to examine phenotypic associations with 30-day postoperative patient cultures, phenotypic growth rates, and risk factors for phenotypic isolation.
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The biomechanics of throwing: simplified and cogent.
Sports Med Arthrosc
PUBLISHED: 05-03-2014
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The majority of shoulder injuries occur due to repetitive overhead movements, with baseball pitching being the most common mechanism for overuse injury. Before studying the treatment of these shoulder injuries, it is paramount that the health professional have an understanding of the etiology of and the underlying mechanisms for shoulder pathology. The act of overhead throwing is an eloquent full-body motion that requires tremendous coordination from the time of force generation to follow-through. The shoulder complex is a crucial component of the upper body kinetic chain as it transmits force created in the lower body to the arm and hand to produce velocity and accuracy with ball release. The focus of this article is on the biomechanics of the throwing motion, with emphasis on the kinematics of the shoulder. The established phases of the throwing motion will be reviewed in a stepwise manner and the contributions of osseous and soft-tissue structures to the successful completion of each phase will be discussed.
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Natural compounds as next-generation herbicides.
Plant Physiol.
PUBLISHED: 04-30-2014
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Herbicides with new modes of action (MOAs) are badly needed due to the rapidly evolving resistance to commercial herbicides, but a new MOA has not been introduced in over 20 years. The greatest pest management challenge for organic agriculture is the lack of effective natural product herbicides. The structural diversity and evolved biological activity of natural phytotoxins offer opportunities for the development of both directly used natural compounds and synthetic herbicides with new target sites based on the structures of natural phytotoxins. Natural phytotoxins are also a source for the discovery of new herbicide target sites that can serve as the focus of traditional herbicide discovery efforts. There are many examples of strong natural phytotoxins with MOAs other than those used by commercial herbicides, which indicates that there are molecular targets of herbicides that can be added to the current repertoire of commercial herbicide MOAs.
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Allergy/hypersensitivity reactions as a predisposing factor to complex regional pain syndrome I in orthopedic patients.
Orthopedics
PUBLISHED: 04-26-2014
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Several predisposing conditions have been associated with complex regional pain syndrome I (CRPS I). The purpose of this study was to determine the relationship between a history of allergy/hypersensitivity reactions and CRPS I in orthopedic patients. Orthopedic patients with CRPS I (n=115) who experienced pain relief after a successful sympathetic nerve blockade were identified for study inclusion; a control group (n=115) matched to the CRPS I group by age, sex, and location of injury was also included. All patients in the study had an average age of 42 years. In the CRPS I group, all participants were Caucasian and the majority (80.8%) were women. The skin of patients with CRPS I was described as fair (57.7%), mottled (57.7%), or sensitive (80.8%). Of the patients with CRPS I, 78 (67.8%) reported a statistically significant history of allergies compared with the 39 (33.9%) patients in the control group (P<.0001). Patients with CRPS I who experienced complete pain relief for at least 1 month following a single sympathetic nerve block were asked to answer a questionnaire (n=35), and some then underwent immediate hypersensitivity testing using a skin puncture technique (n=26). Skin hypersensitivity testing yielded an 83.3% positive predictive value with an accuracy of 76.9%. Based on these results, a positive history for allergy/hypersensitivity reactions is a predisposing condition for CRPS I in this subset of orthopedic patients. These hypersensitivity reactions may prove important in gaining a better understanding in the pathophysiology of CRPS I as a regional pain syndrome.
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Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology.
BMC Genomics
PUBLISHED: 04-15-2014
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Tuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome.
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Jejunal feeding in patients with pancreatitis.
Nutr Clin Pract
PUBLISHED: 04-04-2014
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Patients with severe acute pancreatitis complicated by organ failure and/or pancreatic necrosis or fluid collections should have placement of a double-lumen nasogastric-jejunal tube to be used for both gastric decompression and jejunal feeding. These patients are at risk for gastric outlet obstruction, which may be treated so that complications such as aspiration and reflux are avoided. Furthermore, early enteral feeding can prevent ileus, suppress further organ failure, and ultimately restore gut function if continued in an uninterrupted manner. Ultimately, this patient population will benefit from pancreatic rest and jejunal feeding specifically when compared with patients using nasogastric feeding tubes.
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Multistabilities and symmetry-broken one-color and two-color states in closely coupled single-mode lasers.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 03-26-2014
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We theoretically investigate the dynamics of two mutually coupled, identical single-mode semi-conductor lasers. For small separation and large coupling between the lasers, symmetry-broken one-color states are shown to be stable. In this case the light outputs of the lasers have significantly different intensities while at the same time the lasers are locked to a single common frequency. For intermediate coupling we observe stable symmetry-broken two-color states, where both lasers lase simultaneously at two optical frequencies which are separated by up to 150 GHz. Using a five-dimensional model, we identify the bifurcation structure which is responsible for the appearance of symmetric and symmetry-broken one-color and two-color states. Several of these states give rise to multistabilities and therefore allow for the design of all-optical memory elements on the basis of two coupled single-mode lasers. The switching performance of selected designs of optical memory elements is studied numerically.
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Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes.
Exp. Cell Res.
PUBLISHED: 03-25-2014
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Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: ?-, ?- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer.
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Development of MHC-Linked Microsatellite Markers in the Domestic Cat and Their Use to Evaluate MHC Diversity in Domestic Cats, Cheetahs, and Gir Lions.
J. Hered.
PUBLISHED: 03-13-2014
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Diversity within the major histocompatibility complex (MHC) reflects the immunological fitness of a population. MHC-linked microsatellite markers provide a simple and an inexpensive method for studying MHC diversity in large-scale studies. We have developed 6 MHC-linked microsatellite markers in the domestic cat and used these, in conjunction with 5 neutral microsatellites, to assess MHC diversity in domestic mixed breed (n = 129) and purebred Burmese (n = 61) cat populations in Australia. The MHC of outbred Australian cats is polymorphic (average allelic richness = 8.52), whereas the Burmese population has significantly lower MHC diversity (average allelic richness = 6.81; P < 0.01). The MHC-linked microsatellites along with MHC cloning and sequencing demonstrated moderate MHC diversity in cheetahs (n = 13) and extremely low diversity in Gir lions (n = 13). Our MHC-linked microsatellite markers have potential future use in diversity and disease studies in other populations and breeds of cats as well as in wild felid species.
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Mammalian keratin associated proteins (KRTAPs) subgenomes: disentangling hair diversity and adaptation to terrestrial and aquatic environments.
BMC Genomics
PUBLISHED: 02-19-2014
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Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.
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Sympatric Asian felid phylogeography reveals a major Indochinese-Sundaic divergence.
Mol. Ecol.
PUBLISHED: 02-19-2014
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The dynamic geological and climatological history of Southeast Asia has spawned a complex array of ecosystems and 12 of the 37 known cat species, making it the most felid-rich region in the world. To examine the evolutionary histories of these poorly studied fauna, we compared phylogeography of six species (leopard cat Prionailurus bengalensis, fishing cat P. viverrinus, Asiatic golden cat Pardofelis temminckii, marbled cat P. marmorata, tiger Panthera tigris and leopard P. pardus) by sequencing over 5 kb of DNA each from 445 specimens at multiple loci of mtDNA, Y and X chromosomes. All species except the leopard displayed significant phylogenetic partitions between Indochina and Sundaland, with the central Thai-Malay Peninsula serving as the biogeographic boundary. Concordant mtDNA and nuclear DNA genealogies revealed deep Indochinese-Sundaic divergences around 2 MYA in both P. bengalensis and P. marmorata comparable to previously described interspecific distances within Felidae. The divergence coincided with serial sea level rises during the late Pliocene and early Pleistocene, and was probably reinforced by repeated isolation events associated with environmental changes throughout the Pleistocene. Indochinese-Sundaic differentiations within P. tigris and P. temminckii were more recent at 72-108 and 250-1570 kya, respectively. Overall, these results illuminate unexpected, deep vicariance events in Southeast Asian felids and provide compelling evidence of species-level distinction between the Indochinese and Sundaic populations in the leopard cat and marbled cat. Broader sampling and further molecular and morphometric analyses of these species will be instrumental in defining conservation units and effectively preserving Southeast Asian biodiversity.
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Roots of the invasive species Carduus nutans L. and C. acanthoides L. produce large amounts of aplotaxene, a possible allelochemical.
J. Chem. Ecol.
PUBLISHED: 02-06-2014
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The invasive thistle Carduus nutans has been reported to be allelopathic, yet no allelochemicals have been identified from the species. In a search for allelochemicals from C. nutans and the closely related invasive species C. acanthoides, bioassay-guided fractionation of roots and leaves of each species were conducted. Only dichloromethane extracts of the roots of both species contained a phytotoxin (aplotaxene, (Z,Z,Z)-heptadeca-1,8,11,14-tetraene) with sufficient total activity to potentially act as an allelochemical. Aplotaxene made up 0.44 % of the weight of greenhouse-grown C. acanthoides roots (ca. 20 mM in the plant) and was not found in leaves of either species. It inhibited growth of lettuce 50 % (I 50) in soil at a concentration of ca. 0.5 mg g(-1) of dry soil (ca. 6.5 mM in soil moisture). These values gave a total activity in soil value (molar concentration in the plant divided by the molarity required for 50 % growth inhibition in soil?=?3.08) similar to those of some established allelochemicals. The aplotaxene I 50 for duckweed (Lemna paucicostata) in nutrient solution was less than 0.333 mM, and the compound caused cellular leakage of cucumber cotyledon discs in darkness and light at similar concentrations. Soil in which C. acanthoides had grown contained aplotaxene at a lower concentration than necessary for biological activity in our short-term soil bioassays, but these levels might have activity over longer periods of time and might be an underestimate of concentrations in undisturbed and/or rhizosphere soil.
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The dynamic proliferation of CanSINEs mirrors the complex evolution of Feliforms.
BMC Evol. Biol.
PUBLISHED: 02-02-2014
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Repetitive short interspersed elements (SINEs) are retrotransposons ubiquitous in mammalian genomes and are highly informative markers to identify species and phylogenetic associations. Of these, SINEs unique to the order Carnivora (CanSINEs) yield novel insights on genome evolution in domestic dogs and cats, but less is known about their role in related carnivores. In particular, genome-wide assessment of CanSINE evolution has yet to be completed across the Feliformia (cat-like) suborder of Carnivora. Within Feliformia, the cat family Felidae is composed of 37 species and numerous subspecies organized into eight monophyletic lineages that likely arose 10 million years ago. Using the Felidae family as a reference phylogeny, along with representative taxa from other families of Feliformia, the origin, proliferation and evolution of CanSINEs within the suborder were assessed.
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Arthroscopic subscapularis bankart technique as a salvage procedure for failed anterior shoulder stabilization.
HSS J
PUBLISHED: 02-01-2014
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Shoulder instability is a relatively common problem. Even with contemporary surgical techniques, instability can recur following both open and arthroscopic fixation. Surgical management of capsular insufficiency in anterior shoulder stabilization represents a significant challenge, particularly in young, active patients. There are a limited number of surgical treatment options. The Laterjet technique can present with a number of intraoperative challenges and postoperative complication.
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Midterm Clinical Outcomes for Arthroscopic Subdeltoid Transfer of the Long Head of the Biceps Tendon to the Conjoint Tendon.
Arthroscopy
PUBLISHED: 01-23-2014
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The aim of this study was to assess the midterm functional outcomes for arthroscopic subdeltoid transfer of the long head of the biceps tendon (LHBT) to the conjoint tendon.
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Potential ecological roles of artemisinin produced by Artemisia annua L.
J. Chem. Ecol.
PUBLISHED: 01-21-2014
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Artemisia annua L. (annual wormwood, Asteraceae) and its secondary metabolite artemisinin, a unique sesquiterpene lactone with an endoperoxide bridge, has gained much attention due to its antimalarial properties. Artemisinin has a complex structure that requires a significant amount of energy for the plant to synthesize. So, what are the benefits to A. annua of producing this unique compound, and what is the ecological role of artemisinin? This review addresses these questions, discussing evidence of the potential utility of artemisinin in protecting the plant from insects and other herbivores, as well as pathogens and competing plant species. Abiotic factors affecting the artemisinin production, as well as mechanisms of artemisinin release to the surroundings also are discussed, and new data are provided on the toxicity of artemisinin towards soil and aquatic organisms. The antifungal and antibacterial effects reported are not very pronounced. Several studies have reported that extracts of A. annua have insecticidal effects, though few studies have proven that artemisinin could be the single compound responsible for the observed effects. However, the pathogen(s) or insect(s) that may have provided the selection pressure for the evolution of artemisinin synthesis may not have been represented in the research thus far conducted. The relatively high level of phytotoxicity of artemisinin in soil indicates that plant/plant allelopathy could be a beneficial function of artemisinin to the producing plant. The release routes of artemisinin (movement from roots and wash off from leaf surfaces) from A. annua to the soil support the rationale for allelopathy.
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Herbicides and plant hormesis.
Pest Manag. Sci.
PUBLISHED: 01-13-2014
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Herbicide hormesis is commonly observed at subtoxic doses of herbicides and other phytotoxins. The occurrence and magnitude of this phenomenon are influenced by plant growth stage and physiological status, environmental factors, the endpoint measured and the timing between treatment and endpoint measurement. The mechanism in some cases of herbicide hormesis appears to be related to the target site of the herbicide, whereas in other examples hormesis may be by overcompensation to moderate stress induced by the herbicides or a response to disturbed homeostasis. Theoretically, herbicide hormesis could be used in crop production, but this has been practical only in the case of the use of herbicides as sugar cane 'ripeners' to enhance sucrose accumulation. The many factors that can influence the occurrence, the magnitude and the dose range of hormetic increases in yield for most crops make it too unpredictable and risky as a production practice with the currently available knowledge. Herbicide hormesis can cause undesired effects in situations in which weeds are unintentionally exposed to hormetic doses (e.g. in adjacent fields, when shielded by crop vegetation). Some weeds that have evolved herbicide resistance may have hormetic responses to recommended herbicide application rates. Little is known about such effects under field conditions. A more complete understanding of herbicide hormesis is needed to exploit its potential benefits and to minimize its potential harmful effects in crop production.
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Evolution of resistance to phytoene desaturase and protoporphyrinogen oxidase inhibitors--state of knowledge.
Pest Manag. Sci.
PUBLISHED: 01-06-2014
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Two major classes of herbicides include inhibitors of protoporphyrinogen oxidase (PPO) and phytoene desaturase (PDS). Plants can evolve resistance to PPO and PDS inhibitors via several mechanisms that include physical changes, resulting in reduced uptake, physiological changes, resulting in compartmentalization or altered translocation, and biochemical changes, resulting in enhanced metabolic degradation or alterations of protein structures, leading to loss of sensitivity to the herbicides. This review discusses the involvement of some of these mechanisms in the various cases of resistance to PDS- and PPO-inhibiting herbicides, and highlights unique aspects of target-site resistance to these herbicides.
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GWATCH: a web platform for automated gene association discovery analysis.
Gigascience
PUBLISHED: 01-01-2014
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As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations.
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Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.
PLoS ONE
PUBLISHED: 01-01-2014
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Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications.
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Evolution: a new cat species emerges.
Curr. Biol.
PUBLISHED: 12-21-2013
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The complex ongoing process of species development is highlighted by the description of a new felid species, Leopardus guttulus, from Brazil. Broad molecular genetic assessments affirm reproductive isolation and separation in nature, the hallmark of species recognition.
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The Bundle "Plus": The Effect of a Multidisciplinary Team Approach to Eradicate Central Line-Associated Bloodstream Infections.
Anesth. Analg.
PUBLISHED: 10-24-2013
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Central line-associated bloodstream infections (CLABSIs) have decreased significantly over the last decade. Further reductions in CLABSI rates should be possible. We describe a multidisciplinary approach to the reduction of CLABSIs.
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Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel syndrome subjects.
Expert Rev Gastroenterol Hepatol
PUBLISHED: 10-17-2013
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Loss of intestinal absorptive capacity from congenital defect, surgical resection or mucosal disease results in short bowel syndrome (SBS)-associated intestinal failure. In the past, few medical management options were available besides dietary modification, controlling diarrhea or high stomal output, and providing parenteral fluid, electrolyte and nutrient support (parenteral support). Recent research on strategies to enhance the intestinal absorptive capacity focused on glucagon-like peptide-2, an intestinotrophic hormone that has been shown to increase the villus height and crypt depth, and decrease gastric motility and intestinal secretory losses. STEPS is a Phase III randomized double-blinded controlled trial in which teduglutide, a recombinant analog of glucagon-like peptide-2, or placebo was given subcutaneously to SBS patients for 24 weeks. A clinically meaningful response, defined as a 20-100% reduction in parenteral support volume, was achieved in 63% of the treatment group compared with 30% in the placebo group (p = 0.002) without an increase in serious side effects. Teduglutide offers a new targeted approach to SBS-associated intestinal failure management. Its specific role in clinical practice remains to be evaluated.
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Structure and performance of dielectric films based on self-assembled nanocrystals with a high dielectric constant.
Nanotechnology
PUBLISHED: 09-24-2013
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Self-assembled films built from nanoparticles with a high dielectric constant are attractive as a foundation for new dielectric media with increased efficiency and range of operation, due to the ability to exploit nanofabrication techniques and emergent electrical properties originating from the nanoscale. However, because the building block is a discrete one-dimensional unit, it becomes a challenge to capture potential enhancements in dielectric performance in two or three dimensions, frequently due to surface effects or the presence of discontinuities. This is a recurring theme in nanoparticle film technology when applied to the realm of thin film semiconductor and device electronics. We present the use of chemically synthesized (Ba,Sr)TiO3 nanocrystals, and a novel deposition-polymerization technique, as a means to fabricate the dielectric layer. The effective dielectric constant of the film is tunable according to nanoparticle size, and effective film dielectric constants of up to 34 are enabled. Wide area and multilayer dielectrics of up to 8 cm(2) and 190 nF are reported, for which the building block is an 8 nm nanocrystal. We describe models for assessing dielectric performance, and distinct methods for improving the dielectric constant of a nanocrystal thin film. The approach relies on evaporatively driven assembly of perovskite nanocrystals with uniform size distributions in a tunable 7-30 nm size range, coupled with the use of low molecular weight monomer/polymer precursor chemistry that can infiltrate the porous nanocrystal thin film network post assembly. The intercrystal void space (low k dielectric volume fraction) is minimized, while simultaneously promoting intercrystal connectivity and maximizing volume fraction of the high k dielectric component. Furfuryl alcohol, which has good affinity to the surface of (Ba,Sr)TiO3 nanocrystals and miscibility with a range of solvents, is demonstrated to be ideal for the production of nanocomposites. The nanocrystal/furfuryl alcohol dispersions are suitable for the fabrication of thin films by chemical deposition techniques, including spin-coating, printing or a spraying process. To demonstrate the application of this technique to device fabrication, a multilayer capacitor with capacitance of 0.83 nF mm(-2) at 1 MHz is presented.
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Mosquito Repellents Based on a Natural Chromene Analogue with Longer Duration of Action than N,N-Diethyl-meta-toluamide (DEET).
J. Agric. Food Chem.
PUBLISHED: 09-23-2013
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Mosquito repellents play a major role in reducing bites and therefore mitigating transmission of mosquito-borne diseases. There is concern by some about the reported neurotoxic effects of the popular repellent DEET. Also, a product with longer effective activity after application is needed. This paper describes the synthesis and repellent activity of (2,2 dimethyl-2H-chromen-5-yl)methanol, a derivative of chromene amide that is a compound from the plant Amyris texana . This compound is more potent and provides longer duration of protection than DEET against Aedes aegypti (L.), the primary vector that transmits pathogens causing yellow and dengue fevers in humans.
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Cross talk between the Akt and p38? pathways in macrophages downstream of Toll-like receptor signaling.
Mol. Cell. Biol.
PUBLISHED: 08-26-2013
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The stimulation of Toll-like receptors (TLRs) on macrophages by pathogen-associated molecular patterns (PAMPs) results in the activation of intracellular signaling pathways that are required for initiating a host immune response. Both phosphatidylinositol 3-kinase (PI3K)-Akt and p38 mitogen-activated protein kinase (MAPK) signaling pathways are activated rapidly in response to TLR activation and are required to coordinate effective host responses to pathogen invasion. In this study, we analyzed the role of the p38-dependent kinases MK2/3 in the activation of Akt and show that lipopolysaccharide (LPS)-induced phosphorylation of Akt on Thr308 and Ser473 requires p38? and MK2/3. In cells treated with p38 inhibitors or an MK2/3 inhibitor, phosphorylation of Akt on Ser473 and Thr308 is reduced and Akt activity is inhibited. Furthermore, BMDMs deficient in MK2/3 display greatly reduced phosphorylation of Ser473 and Thr308 following TLR stimulation. However, MK2/3 do not directly phosphorylate Akt in macrophages but act upstream of PDK1 and mTORC2 to regulate Akt phosphorylation. Akt is recruited to phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the membrane, where it is activated by PDK1 and mTORC2. Analysis of lipid levels in MK2/3-deficient bone marrow-derived macrophages (BMDMs) revealed a role for MK2/3 in regulating Akt activity by affecting availability of PIP3 at the membrane. These data describe a novel role for p38?-MK2/3 in regulating TLR-induced Akt activation in macrophages.
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Involvement of facultative apomixis in inheritance of EPSPS gene amplification in glyphosate-resistant Amaranthus palmeri.
Planta
PUBLISHED: 08-20-2013
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The inheritance of glyphosate resistance in two Amaranthus palmeri populations (R1 and R2) was examined in reciprocal crosses (RC) and second reciprocal crosses (2RC) between glyphosate-resistant (R) and -susceptible (S) parents of this dioecious species. R populations and Female-R × Male-S crosses contain higher 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene copy numbers than the S population. EPSPS expression, EPSPS enzyme activity, EPSPS protein quantity, and level of resistance to glyphosate correlated positively with genomic EPSPS relative copy number. Transfer of resistance was more influenced by the female than the male parent in spite of the fact that the multiple copies of EPSPS are amplified in the nuclear genome. This led us to hypothesize that this perplexing pattern of inheritance may result from apomictic seed production in A. palmeri. We confirmed that reproductively isolated R and S female plants produced seeds, indicating that A. palmeri can produce seeds both sexually and apomictically (facultative apomixis). This apomictic trait accounts for the low copy number inheritance in the Female-S × Male-R offsprings. Apomixis may also enhance the stability of the glyphosate resistance trait in the R populations in the absence of reproductive partners.
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Molecular evidence for a recent demographic expansion in the puma (Puma concolor) (Mammalia, Felidae).
Genet. Mol. Biol.
PUBLISHED: 08-16-2013
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The puma is an iconic predator that ranges throughout the Americas, occupying diverse habitats. Previous phylogeographic analyses have revealed that it exhibits moderate levels of genetic structure across its range, with few of the classically recognized subspecies being supported as distinct demographic units. Moreover, most of the species molecular diversity was found to be in South America. To further investigate the phylogeographic structure and demographic history of pumas we analyzed mtDNA sequences from 186 individuals sampled throughout their range, with emphasis on South America. Our objectives were to refine the phylogeographic assessment within South America and to investigate the demographic history of pumas using a coalescent approach. Our results extend previous phylogeographic findings, reassessing the delimitation of historical population units in South America and demonstrating that this species experienced a considerable demographic expansion in the Holocene, ca. 8,000 years ago. Our analyses indicate that this expansion occurred in South America, prior to the hypothesized re-colonization of North America, which was therefore inferred to be even more recent. The estimated demographic history supports the interpretation that pumas suffered a severe demographic decline in the Late Pleistocene throughout their distribution, followed by population expansion and re-colonization of the range, initiating from South America.
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Stratospheric ozone, global warming, and the principle of unintended consequences--an ongoing science and policy success story.
J Air Waste Manag Assoc
PUBLISHED: 07-18-2013
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In 1974, Mario Molina and F. Sherwood Rowland warned that chlorofluorocarbons (CFCs) could destroy the stratospheric ozone layer that protects Earth from harmful ultraviolet radiation. In the decade after scientists documented the buildup and long lifetime of CFCs in the atmosphere; found the proof that CFCs chemically decomposed in the stratosphere and catalyzed the depletion of ozone; quantified the adverse effects; and motivated the public and policymakers to take action. In 1987, 24 nations plus the European Community signed the Montreal Protocol. Today, 25 years after the Montreal Protocol was agreed, every United Nations state is a party (universal ratification of 196 governments); all parties are in compliance with the stringent controls; 98% of almost 100 ozone-depleting chemicals have been phased out worldwide; and the stratospheric ozone layer is on its way to recovery by 2065. A growing coalition of nations supports using the Montreal Protocol to phase down hydrofluorocarbons, which are ozone safe but potent greenhouse gases. Without rigorous science and international consensus, emissions of CFCs and related ozone-depleting substances (ODSs) could have destroyed up to two-thirds of the ozone layer by 2065, increasing the risk of causing millions of cancer cases and the potential loss of half of global agricultural production. Furthermore, because most, ODSs are also greenhouse gases, CFCs and related ODSs could have had the effect of the equivalent of 24-76 gigatons per year of carbon dioxide. This critical review describes the history of the science of stratospheric ozone depletion, summarizes the evolution of control measures and compliance under the Montreal Protocol and national legislation, presents a review of six separate transformations over the last 100 years in refrigeration and air conditioning (A/C) technology, and illustrates government-industry cooperation in continually improving the environmental performance of motor vehicle A/C.
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Hormesis with glyphosate depends on coffee growth stage.
An. Acad. Bras. Cienc.
PUBLISHED: 07-06-2013
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Weed management systems in almost all Brazilian coffee plantations allow herbicide spray to drift on crop plants. In order to evaluate if there is any effect of the most commonly used herbicide in coffee production, glyphosate, on coffee plants, a range of glyphosate doses were applied directly on coffee plants at two distinct plant growth stages. Although growth of both young and old plants was reduced at higher glyphosate doses, low doses caused no effects on growth characteristics of young plants and stimulated growth of older plants. Therefore, hormesis with glyphosate is dependent on coffee plant growth stage at the time of herbicide application.
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Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.
PLoS Pathog.
PUBLISHED: 07-01-2013
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Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5?32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.
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Minke whale genome and aquatic adaptation in cetaceans.
Nat. Genet.
PUBLISHED: 06-18-2013
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The shift from terrestrial to aquatic life by whales was a substantial evolutionary event. Here we report the whole-genome sequencing and de novo assembly of the minke whale genome, as well as the whole-genome sequences of three minke whales, a fin whale, a bottlenose dolphin and a finless porpoise. Our comparative genomic analysis identified an expansion in the whale lineage of gene families associated with stress-responsive proteins and anaerobic metabolism, whereas gene families related to body hair and sensory receptors were contracted. Our analysis also identified whale-specific mutations in genes encoding antioxidants and enzymes controlling blood pressure and salt concentration. Overall the whale-genome sequences exhibited distinct features that are associated with the physiological and morphological changes needed for life in an aquatic environment, marked by resistance to physiological stresses caused by a lack of oxygen, increased amounts of reactive oxygen species and high salt levels.
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A common novel splice variant of SLC22A1 (OCT1) is associated with impaired responses to imatinib in patients with chronic myeloid leukaemia.
Br. J. Haematol.
PUBLISHED: 06-17-2013
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Approximately one-third of patients with chronic myeloid leukaemia will fail to achieve or maintain responses to imatinib. Changes in solute carrier family 22 (organic cation transporter), member 1 (SLC22A1, also termed OCT1), the main transporter for imatinib, have been proposed as a possible predictive factor. We analysed SLC22A1 mRNA levels and single nucleotide polymorphisms (SNPs) located in exon 7 in 153 diagnostic whole blood samples from two patient cohorts. The level of SLC22A1 expression did not significantly correlate with imatinib failure or achievement of molecular remission. The SNP 408V>M (g.1222G>A) was present in 65% of patients and was associated in all cases with an eight base-pair insertion (8(+) allele) at the 3 end of exon 7. The latter generates an alternative splice site, leading to a premature stop codon. M420del was found in 33% of patients and never in cis with 8(+) (the 3(-) allele). Significantly longer times to 1% and 0·1% molecular responses (by quantitative reverse transcription polymerase chain reaction) were seen in patients with 8(+) 8(+) or 8(+) N compared to those with the remaining four genotypes (N = no insertion or deletion). Patients lacking 8(+) and 3(-) (NN, 18%) showed the best outcomes overall. Thus, while SLC22A1 expression does not appear to affect response, alterations in its splicing or amino acid sequence may do so.
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The tiger genome and comparative analysis with lion and snow leopard genomes.
Nat Commun
PUBLISHED: 05-02-2013
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Tigers and their close relatives (Panthera) are some of the worlds most endangered species. Here we report the de novo assembly of an Amur tiger whole-genome sequence as well as the genomic sequences of a white Bengal tiger, African lion, white African lion and snow leopard. Through comparative genetic analyses of these genomes, we find genetic signatures that may reflect molecular adaptations consistent with the big cats hypercarnivorous diet and muscle strength. We report a snow leopard-specific genetic determinant in EGLN1 (Met39>Lys39), which is likely to be associated with adaptation to high altitude. We also detect a TYR260G>A mutation likely responsible for the white lion coat colour. Tiger and cat genomes show similar repeat composition and an appreciably conserved synteny. Genomic data from the five big cats provide an invaluable resource for resolving easily identifiable phenotypes evident in very close, but distinct, species.
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Magnetoelectricity in CoFe2O4 nanocrystal-P(VDF-HFP) thin films.
Nanoscale Res Lett
PUBLISHED: 05-01-2013
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Transition metal ferrites such as CoFe2O4, possessing a large magnetostriction coefficient and high Curie temperature (Tc > 600 K), are excellent candidates for creating magnetic order at the nanoscale and provide a pathway to the fabrication of uniform particle-matrix films with optimized potential for magnetoelectric coupling. Here, a series of 0-3 type nanocomposite thin films composed of ferrimagnetic cobalt ferrite nanocrystals (8 to 18 nm) and a ferroelectric/piezoelectric polymer poly(vinylidene fluoride-co-hexafluoropropene), P(VDF-HFP), were prepared by multiple spin coating and cast coating over a thickness range of 200 nm to 1.6 ?m. We describe the synthesis and structural characterization of the nanocrystals and composite films by XRD, TEM, HRTEM, STEM, and SEM, as well as dielectric and magnetic properties, in order to identify evidence of cooperative interactions between the two phases. The CoFe2O4 polymer nanocomposite thin films exhibit composition-dependent effective permittivity, loss tangent, and specific saturation magnetization (Ms). An enhancement of the effective permittivity and saturation magnetization of the CoFe2O4-P(VDF-HFP) films was observed and directly compared with CoFe2O4-polyvinylpyrrolidone, a non-ferroelectric polymer-based nanocomposite prepared by the same method. The comparison provided evidence for the observation of a magnetoelectric effect in the case of CoFe2O4-P(VDF-HFP), attributed to a magnetostrictive/piezoelectric interaction. An enhancement of Ms up to +20.7% was observed at room temperature in the case of the 10 wt.% CoFe2O4-P(VDF-HFP) sample.
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Host genomic influences on HIV/AIDS.
Genome Biol.
PUBLISHED: 01-31-2013
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ABSTRACT: The AIDS era has seen multiple advances in the power of genetics research; scores of host genetic protective factors have been nominated and several have translated to the bedside. We discuss how genomics may inform HIV/AIDS prevention, treatment and eradication.
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Omics methods for probing the mode of action of natural and synthetic phytotoxins.
J. Chem. Ecol.
PUBLISHED: 01-27-2013
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For a little over a decade, omics methods (transcriptomics, proteomics, metabolomics, and physionomics) have been used to discover and probe the mode of action of both synthetic and natural phytotoxins. For mode of action discovery, the strategy for each of these approaches is to generate an omics profile for phytotoxins with known molecular targets and to compare this library of responses to the responses of compounds with unknown modes of action. Using more than one omics approach enhances the probability of success. Generally, compounds with the same mode of action generate similar responses with a particular omics method. Stress and detoxification responses to phytotoxins can be much clearer than effects directly related to the target site. Clues to new modes of action must be validated with in vitro enzyme effects or genetic approaches. Thus far, the only new phytotoxin target site discovered with omics approaches (metabolomics and physionomics) is that of cinmethylin and structurally related 5-benzyloxymethyl-1,2-isoxazolines. These omics approaches pointed to tyrosine amino-transferase as the target, which was verified by enzyme assays and genetic methods. In addition to being a useful tool of mode of action discovery, omics methods provide detailed information on genetic and biochemical impacts of phytotoxins. Such information can be useful in understanding the full impact of natural phytotoxins in both agricultural and natural ecosystems.
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The arthroscopic "subdeltoid approach" to the anterior shoulder.
J Shoulder Elbow Surg
PUBLISHED: 01-11-2013
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Surgical management of shoulder pathologies has evolved tremendously during the past 3 decades, such that many lesions previously treated with open techniques are now addressed arthroscopically. Despite this movement, many surgeons and outcome studies continue to prefer open repairs as the gold standard, criticizing--with good reason--the reliability, reproducibility, and extended operative time of arthroscopic repairs, particularly with respect to anterior stabilizations and subscapularis repairs. With this in mind, we present the arthroscopic "subdeltoid approach," a novel standardized exposure technique for extracompartmental anterior shoulder arthroscopy. We define the subdeltoid space as the fascial plane bound superiorly by the acromion and coracoacromial ligament, medially by the coracoid and the conjoint tendon, inferiorly by the musculotendinous insertion of the pectoralis major to the humerus, and laterally by the lateral border of the humerus. When coupled with existing arthroscopic tools, this space dramatically enhances our ability to apply open techniques to some of the more challenging anterior shoulder pathoanatomy and expand the indications and efficacy of arthroscopy. This exposure technique has been used in more than 300 cases during the past decade to treat a myriad of shoulder pathologies, without any longstanding postoperative complications.
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A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
Elife
PUBLISHED: 01-01-2013
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HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the intermediate phenotype nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001.
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Serine/threonine protein phosphatases: multi-purpose enzymes in control of defense mechanisms.
Plant Signal Behav
PUBLISHED: 11-23-2011
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Depending on the threat to a plant, different pattern recognition receptors, such as receptor-like kinases, identify the stress and trigger action by appropriate defense response development. The plant immunity system primary response to these challenges is rapid accumulation of phytohormones, such as ethylene (ET), salicylic acid (SA), and jasmonic acid (JA) and its derivatives. These phytohormones induce further signal transduction and appropriate defenses against biotic threats. Phytohormones play crucial roles not only in the initiation of diverse downstream signaling events in plant defense but also in the activation of effective defenses through an essential process called signaling pathway crosstalk, a mechanism involved in transduction signals between two or more distinct, "linear signal transduction pathways simultaneously activated in the same cell."
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Teduglutide for the treatment of short bowel syndrome.
Expert Rev Gastroenterol Hepatol
PUBLISHED: 10-25-2011
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Extensive resection of the intestine impairs its absorptive capacity and results in short bowel syndrome when the nutritional equilibrium is compromised. The remnant intestine adapts structurally to compensate, but nutritional autonomy cannot be achieved in patients with intestinal failure, requiring intravenous fluids and parenteral nutrition (PN) for sustenance of life. PN is expensive and associated with serious complications. Efforts to minimize or eliminate the need for PN heralded research focusing on the therapeutic utility of intrinsic gut factors involved in the postresection adaptation process. With the breakthrough recognition of the intestinotrophic properties of glucagon-like peptide-2, teduglutide, a recombinant analogue of glucagon-like peptide-2, is being investigated as a promising hope to mitigate the requirement of PN. Clinical studies to date have demonstrated a desirable benefit-to-risk profile in regards to its safety and efficacy. If approved for marketing, it will be the first of its class in short bowel syndrome management, offering an innovative therapeutic modality for this debilitating condition.
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Timing characterization of 100 GHz passively mode-locked discrete mode laser diodes.
Opt Express
PUBLISHED: 09-22-2011
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We report on the characterization of the timing stability of passively mode-locked discrete mode diode laser sources. These are edge-emitting devices with a spatially varying refractive index profile for spectral filtering. Two devices with a mode-locking frequency of 100 GHz are characterized. The first device is designed to support a comb of six modes and generates near Fourier limited 1.9 ps pulses. The second supports four primary modes resulting in a sinusoidal modulation of the optical intensity. Using a cross-correlation technique, we measured a 20 fs pulse to pulse timing jitter for the first device, while, for the second device, a mode-beating (RF) linewidth of 1 MHz was measured using heterodyne mixing in a semiconductor optical amplifier. Comparison of these results with those obtained for an equivalent Fabry-Perot laser indicates that the spectral filtering mechanism employed does not adversely affect the timing properties of these passively mode-locked devices.
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Why have no new herbicide modes of action appeared in recent years?
Pest Manag. Sci.
PUBLISHED: 09-02-2011
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Herbicides with new modes of action are badly needed to manage the evolution of resistance of weeds to existing herbicides. Yet no major new mode of action has been introduced to the market place for about 20 years. There are probably several reasons for this. New potential products may have remained dormant owing to concerns that glyphosate-resistant (GR) crops have reduced the market for a new herbicide. The capture of a large fraction of the herbicide market by glyphosate with GR crops led to significantly diminished herbicide discovery efforts. Some of the reduced herbicide discovery research was also due to company consolidations and the availability of more generic herbicides. Another problem might be that the best herbicide molecular target sites may have already been discovered. However, target sites that are not utilized, for which there are inhibitors that are highly effective at killing plants, suggests that this is not true. Results of modern methods of target site discovery (e.g. gene knockout methods) are mostly not public, but there is no evidence of good herbicides with new target sites coming from these approaches. In summary, there are several reasons for a long dry period for new herbicide target sites; however, the relative magnitude of each is unclear. The economic stimulus to the herbicide industry caused by the evolution of herbicide-resistant weeds, especially GR weeds, may result in one or more new modes of action becoming available in the not too distant future.
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A suite of genetic markers useful in assessing wildcat (Felis silvestris ssp.)-domestic cat (Felis silvestris catus) admixture.
J. Hered.
PUBLISHED: 08-18-2011
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The wildcat (Felis silvestris ssp.) is a conservation concern largely due to introgressive hybridization with its congener F. s. catus, the common domestic cat. Because of a recent divergence and entirely overlapping ranges, hybridization is common and pervasive between these taxa threatening the genetic integrity of remaining wildcat populations. Identifying pure wildcats for inclusion in conservation programs using current morphological discriminants is difficult because of gross similarity between them and the domestic, critically hampering conservation efforts. Here, we present a vetted panel of microsatellite loci and mitochondrial polymorphisms informative for each of the 5 naturally evolved wildcat subspecies and the derived domestic cat. We also present reference genotypes for each assignment class. Together, these marker sets and corresponding reference genotypes allow for the development of a genetic rational for defining "units of conservation" within a phylogenetically based taxonomy of the entire F. silvestris species complex. We anticipate this marker panel will allow conservators to assess genetic integrity and quantify admixture in managed wildcat populations and to be a starting point for more in-depth analysis of hybridization.
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Identification of mosquito biting deterrent constituents from the Indian folk remedy plant Jatropha curcas.
J. Med. Entomol.
PUBLISHED: 08-18-2011
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An investigation of the Indian folk remedy plant Jatropha curcas L., was performed to identify the constituents responsible for the mosquito biting deterrent activity of the oil. J. curcas seed oil is burned in oil lamps in India and parts of Africa to repel biting insects, primarily mosquitoes. The seed oil was thoroughly analyzed by 1H NMR, 13C NMR, high-performance liquid chromatography-refractive index, and gas chromatography-flame ionization detection to identify the constituents in the oil. Identified constituents, both free fatty acids and triglycerides, were evaluated for activity in Aedes aegypti (L.) (Diptera: Culicidae) biting deterrent assays. Furthermore, an oil condensation trap was used to demonstrate that free fatty acids or triglycerides are partially volatilized during the combustion process. These compounds were found to be responsible for the biting deterrency of the burned oil. Specifically, oleic, palmitic, linoleic, and stearic acids were all active at 25 nmol/cm2 above that of solvent control in Ae. aegypti biting deterrent assays. Oleic, palmitic, and linoleic acids were all more active than stearic acid in the same bioassay. Evaluation of the triglycerides containing each of these fatty acids revealed that tripalmitin, tristearin, trilinolein, and triolein all demonstrated significant activity above a solvent control at 10 microg/cm2, whereas tripalmitin was the most active. Due to literature reports suggesting larvicidal activity of the oil, J. curcas seed oil and its free fatty acid constituents also were evaluated against 1-d-old Ae. aegypti larvae up to 500 ppm. Oleic acid was the only fatty acid having larvicidal activity against 1-d-old Ae. aegypti larvae, with an LD50 of 47.9 ppm.
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Design of waveguide-integrated semiconductor laser sources for optical frequency comb generation.
Opt Lett
PUBLISHED: 08-03-2011
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A numerical study of threshold gain and modal dispersion in integrated semiconductor laser optical frequency comb sources is presented. We consider an example device where one of the cleaved facets of the laser is replaced by a short Bragg grating section and show that as many as 16 modes can be selected at the first harmonic of the underlying Fabry-Perot cavity. An intracavity approach to limiting the grating-induced dispersion that can be implemented directly through the grating profile is demonstrated.
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Modes of action of microbially-produced phytotoxins.
Toxins (Basel)
PUBLISHED: 07-28-2011
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Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin.
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Calcium mediates glomerular filtration through calcineurin and mTORC2/Akt signaling.
J. Am. Soc. Nephrol.
PUBLISHED: 07-22-2011
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Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfate-induced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin- and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurin-independent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier.
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Transcriptional responses to cantharidin, a protein phosphatase inhibitor, in Arabidopsis thaliana reveal the involvement of multiple signal transduction pathways.
Physiol Plant
PUBLISHED: 07-19-2011
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Cantharidin is a natural compound isolated from the blister beetle (Epicauta spp.). It is a potent inhibitor of protein serine/threonine phosphatases (PPPs), especially PP2A and PP4. Protein phosphatases and kinases maintain a sensitive balance between dephosphorylated and phosphorylated forms of appropriate proteins, thereby playing important roles in signal transduction pathways and regulation of gene expression, cellular proliferation, cell differentiation, apoptosis and other processes. The foliage of 12-day-old Arabidopsis thaliana seedlings was treated with 200 µM (IC(30) ) of the PPP inhibitor cantharidin, and the entire transcriptome profile was determined by microarray analysis at 2, 10 and 24 h after treatment. The transcription of approximately 10% (2577) of the 24 000 genes of Arabidopsis changed significantly (P? 0.05 and signal log ratios: ?1 or ?-1) after treatment. Inhibition of PPPs significantly reduced transcription of genes associated with auxin and light signaling and induced expression of genes involved in the hypersensitive response and in flagellin and abscisic acid signaling. The great variety of up- and downregulated genes in this microarray experiment implied that cantharidin interfered with the activities of PPPs that interact directly or indirectly with receptors or are located near the beginning of signal transduction pathways. In many cases, PPPs interact with protein complexes of various receptors such as ethylene or light sensors localized in different cell compartments. They function as negative regulators modifying receptor functions, thus altering signaling that influences transcriptional responses.
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FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions.
Vet. Immunol. Immunopathol.
PUBLISHED: 06-12-2011
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Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations.
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Comparing conventional and biotechnology-based pest management.
J. Agric. Food Chem.
PUBLISHED: 05-06-2011
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Pest management has changed dramatically during the past 15 years by the introduction of transgenes into crops for the purpose of pest management. Transgenes for herbicide resistance or for production of one or more Bt toxins are the predominant pest management traits currently available. These two traits have been rapidly adopted where available because of their superior efficacy and simplification of pest management for the farmer. Furthermore, they have substantially reduced the use of environmentally and toxicologically suspect pesticides while reducing the carbon footprint of pest management as reduced tillage became more common, along with fewer trips across the field to spray pesticides. The most successful of these products have been glyphosate-resistant crops, which cover approximately 85% of all land occupied by transgenic crops. Over-reliance on glyphosate with continual use of these crops has resulted in the evolution of highly problematic glyphosate-resistant weeds. This situation has resulted in some farmers using weed management methods similar to those used with conventional crops. Evolution of resistance has not been a significant problem with Bt crops, perhaps because of a mandated resistance management strategy. Transgenic crops with multiple genes for resistance to different herbicides and resistance to additional insects will be available in the next few years. These products will offer opportunities for the kind of pest management diversity that is more sustainable than that provided by the first generation of transgenic crops.
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Genome-wide association study implicates PARD3B-based AIDS restriction.
J. Infect. Dis.
PUBLISHED: 04-20-2011
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Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression.
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Adaptive evolution of the matrix extracellular phosphoglycoprotein in mammals.
BMC Evol. Biol.
PUBLISHED: 03-31-2011
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Matrix extracellular phosphoglycoprotein (MEPE) belongs to a family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs) that play a key role in skeleton development, particularly in mineralization, phosphate regulation and osteogenesis. MEPE associated disorders cause various physiological effects, such as loss of bone mass, tumors and disruption of renal function (hypophosphatemia). The study of this developmental gene from an evolutionary perspective could provide valuable insights on the adaptive diversification of morphological phenotypes in vertebrates.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.