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Methiozolin is a new herbicide with an unknown mechanism of action (MOA) for control of annual bluegrass (Poa annua L.) in several warm- and cool-season turfgrasses. In the literature, methiozolin was proposed to be a pigment inhibitor via inhibition of tyrosine aminotransferases (TATs) or a cellulose biosynthesis inhibitor (CBI). Here, exploratory research was conducted to characterize the herbicide symptomology and MOA of methiozolin. Arabidopsis (Arabidopsis thaliana L.) and P. annua exhibited a similar level of susceptibility to methiozolin, and arrest of meristematic growth was the most characteristic symptomology. For example, methiozolin inhibited A. thaliana root growth (GR50 8 nM) and shoot emergence (GR80 ˜50 nM), and apical meristem growth was completely arrested at rates greater than 500 nM. We concluded that methiozolin was neither a TAT nor a CBI inhibitor. Methiozolin had a minor effect on chlorophyll and alpha-tocopherol content in treated seedlings (<500 nM), and supplements in the proposed TAT pathway could not lessen phytotoxicity. Examination of microscopic images of roots revealed that methiozolin-treated (100 nM) and untreated seedlings had similar root cell lengths. Thus, methiozolin inhibits cell proliferation and not elongation from meristematic tissue. Subsequently, we suspected methiozolin was an inhibitor of the mevalonic acid (MVA) pathway, because its herbicidal symptomologies were nearly indistinguishable from those caused by lovastatin. However, methiozolin did not inhibit phytosterol production, and MVA pathway metabolites did not rescue treated seedlings. Further experiments showed that methiozolin produced a physiological profile very similar to cinmethylin across a number of assays, a known inhibitor of fatty-acid synthesis through inhibition of thioesterases (FATs). Experiments with lesser duckweed (Lemna aequinoctialis Welw.; syn. Lemna paucicostata Hegelm.) showed that methiozolin also reduced fatty-acid content in Lemna with a profile similar, but not identical, to cinmethylin. However, there was no difference in fatty-acid content between treated (1 µM) and untreated A. thaliana seedlings. Methiozolin also bound to both A, thaliana and L. aequinoctialis FATs in vitro. Modeling suggested that methiozolin and cinmethylin have comparable and overlapping FAT binding sites. While there was a discrepancy in the effect of methiozolin on fatty-acid content between L. aequinoctialis and A. thaliana, the overall evidence indicates that methiozolin is a FAT inhibitor and acts in a similar manner as cinmethylin.
Catatonia is a psychomotor dysregulation syndrome of diverse aetiology, increasingly recognised as a prominent feature of N-methyl-d-aspartate receptor antibody encephalitis (NMDARE) in adults. No study to date has systematically assessed the prevalence and symptomatology of catatonia in children with NMDARE. We analysed 57 paediatric patients with NMDARE from the literature using the Bush-Francis Catatonia Rating Scale. Catatonia was common (occurring in 86% of patients), manifesting as complex clusters of positive and negative features within individual patients. It was both underrecognised and undertreated. Immunotherapy was the only effective intervention, highlighting the importance of prompt recognition and treatment of the underlying cause of catatonia.
Herbicide resistance has for decades been an increasing problem of agronomic crops such as corn and soybean. Several weed species have evolved herbicide resistance in turfgrass systems such as golf courses, sports fields, and sod production—particularly biotypes of annual bluegrass and goosegrass. Consequences of herbicide resistance in agronomic cropping systems indicate what could happen in turfgrass if herbicide resistance becomes broader in terms of species, distribution, and mechanisms of action. The turfgrass industry must take action to develop effective resistance management programs while this problem is still relatively small in scope. We propose that lessons learned from a series of national listening sessions conducted by the Herbicide Resistance Education Committee of the Weed Science Society of America to better understand the human dimensions affecting herbicide resistance in crop production provide tremendous insight into what themes to address when developing effective resistance management programs for the turfgrass industry.
The rupture of atherosclerotic plaques is the prerequisite for adverse cardiovascular events. Calcification morphology plays a critical role in plaque stability, therefore accurate calcification classification is essential for favourable patient management. Blood biomarkers may be a worthwhile approach to stratify patients based on calcification phenotype. Vitamin K-dependent Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent inhibitor of vascular calcification. Recent studies have demonstrated the potential utility of circulating non-functional MGP (dp-ucMGP) measurements to determine arterial stiffness and calcification levels. The objective of this study was to examine the relationship between circulating dp-ucMGP and calcification phenotype within symptomatic atherosclerotic lesions. Consenting patients undergoing standard endarterectomy procedures were recruited (n = 29). Fasting venous blood was collected preoperatively. Circulating plasma levels of dp-ucMGP were quantified using the inaKtif MGP (dp-ucMGP) iSYS kit. A bicinchoninic acid assay was used to standardise the total protein content present in each sample. High-resolution micro-CT imaging was conducted on the excised atherosclerotic specimens postoperatively. ImageJ post-processing was used to accurately quantify the calcification volume (≥ 130 Hounsfield Units) and determine the total number of calcified particles (3D objects counter plugin). Thirteen carotid (average age 71 years, 9 male) and fourteen peripheral lower limb (average age 65 years, 12 male) patients were examined. One patient had a carotid and a peripheral lower limb plaque (age 79, male). Peripheral lower limb specimens have larger volumes of calcification and higher numbers of calcified particles than carotid samples (472 ± 310 vs 85 ± 113mm3, p < 0.0005; 13919 ± 16034 vs 3476 ± 6208, p = 0.061.) While a higher dp-ucMGP value was noted in carotid than peripheral lower limb patients (214 ± 52 vs 169 ± 36pmol/L, p = 0.014) there was no correlation between circulating dp-ucMGP and calcification volume or number of calcified particles (rs = -0.329 and rs = 0.046). Previous research also found that peripheral lower limb lesions contain higher volumes of calcification than carotid lesions. There is currently no published data on calcified particle comparisons. Patients with symptomatic carotid disease are assumed to have a degree of peripheral arterial disease, this could explain the higher levels of circulating dp-ucMGP in carotid patients. The current study did not examine the dietary patterns of individuals with regards to Vitamin K intake or analyse other areas of the vasculature for additional calcification. This may interfere with dp-ucMGP measurements. This study serves as a preliminary investigation into the potential of dp-ucMGP as a blood based biomarker to distinguish between symptomatic atherosclerotic calcification phenotypes.
While mastery of aspects of music theory is relevant to rapid learning and understanding of a new choral part, many choirs comprise members with no formal education in music theory. Also, the language of music theory is not intuitive, with many terms having meanings different from those in common use, which can present obstacles for mature learners. The authors hypothesised that students joining an internationally recognised university choir might master aspects of music theory as a by-product of rehearsals. This was tested by having new admissions to such a choir complete a music theory test at the commencement and at the end of a year. The test evaluated the ability to name and write intervals and name notes and the duration of notes. Overall results did not reject the hypothesis. Subjects with no formal music training also showed most, and statistically significant, improvement in the questions related to intervals, which are arguably the most useful skills for choristers who do not sight-read. This appears to be a new finding: the literature shows occasional references to music theory skills, but their acquisition in a learning-by-doing style is not reported. Some insights into ways of enhancing choral performance are a by-product of the principal focus of the study.
The regeneration niche defines the specific environmental requirements of the early phases of a plant's life cycle. It is critical for the long-term persistence of plant populations, particularly for obligate seeders that are highly vulnerable to stochastic events in fire-prone ecosystems. Here, we assessed germination characteristics and the relationship between population structure, soil seed bank density and fire response in Stachystemon vinosus (Euphorbiaceae), a rare endemic shrub from Western Australia, from burnt and long unburnt habitats. Many plants in long unburnt habitat were similar in size to those in recently burnt habitat. Soil seed bank density was related to plant abundance and fire history with density lower in burnt than unburnt sites. Thus, inter-fire recruitment may play a critical role in the requirements of the study species. To assess the dormancy status and germination requirements we used a ‘move-along’ experiment with temperatures from six seasonal phases of the year. Seeds were incubated under light and dark conditions, with and without smoked water, and with and without dry after-ripening. Germination was most effective when seeds were treated with smoked water and incubated in the dark at temperatures resembling autumn/winter conditions. After-ripening increased germination in light and dark incubated seeds in the absence of smoked water but was unnecessary for optimal germination in smoked water treated seeds. Irrespective of treatment, seeds showed a requirement for cooler temperatures for germination. These results suggest that rising temperatures and changes in fire regime associated with global warming may alter future germination responses of Stachystemon vinosus.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
A comprehensive analysis of early dinosaur relationships raised the possibility that the group may have originated in Laurasia (Northern Hemisphere), rather than Gondwana (Southern Hemisphere) as often thought. However, that study focused solely on morphology and phylogenetic relationships and did not quantitatively evaluate this issue. Here, we investigate dinosaur origins using a novel Bayesian framework uniting tip-dated phylogenetics with dynamic, time-sliced biogeographic methods, which explicitly account for the age and locality of fossils and the changing interconnections of areas through time due to tectonic and eustatic change. Our analysis finds strong support for a Gondwanan origin of Dinosauria, with 99 % probability for South America (83 % for southern South America). Parsimony analysis gives concordant results. Inclusion of time-sliced biogeographic information affects ancestral state reconstructions (e.g., high connectivity between two regions increases uncertainty over which is the ancestral area) and influences tree topology (disfavouring uniting fossil taxa from localities that were widely separated during the relevant time slice). Our approach directly integrates plate tectonics with phylogenetics and divergence dating, and in doing so reaffirms southern South America as the most likely area for the geographic origin of Dinosauria.
OBJECTIVES/SPECIFIC AIMS: Accumulation of cholesterol-laden macrophages in arterial walls leads to atherosclerosis. LXRs induce expression of genes that are atheroprotective in macrophages including CCR7, a chemokine receptor that promotes their emigration from the plaque. CCR7 expression has been shown to be negatively regulated by phosphorylation of LXRα at S198 and is reduced in diabetic mice that show impaired plaque regression. I hypothesized that LXRα phosphorylation at S198 diminishes macrophage emigration from atherosclerotic plaque and contributes to impaired regression in diabetes. METHODS/STUDY POPULATION: Inducible LXRα S198A phosphorylation deficient knock in mouse were used as donors for bone marrow transplantation into mice prone to develop atherosclerosis. Plaques were developed by placing mice on western diet; and regression was induced by lowering their lipid levels. Aortic plaques were then analyzed by using morphometric, histological, and molecular analyses in control and diabetic mice expressing either LXRα WT or LXRα S198A during regression. RESULTS/ANTICIPATED RESULTS: Surprisingly, lack of phosphorylation increased plaque macrophage content and impaired regression under normoglycemic condition; however, it did not exacerbate diabetic regression. Plaques in diabetic mice were associated with increased LXRα S198 phosphorylation. Consistent with this, LXRα phosphorylation is enhanced in macrophages cultured under hyperglycemic conditions indicating glucose-dependent regulation of LXRα phosphorylation. Monocyte trafficking studies reveal that lack of phosphorylation and diabetes independently increase recruitment of monocytes in the plaque that might contribute to increased macrophage content. Importantly, I found that diabetes also increases macrophage retention in the plaque, which is reversed in the absence of phosphorylation. We predict that this increased retention results from inhibition of emigration of plaque macrophages through enhanced phosphorylation in diabetes. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that inhibiting LXRα phosphorylation could be beneficial in diabetic atherosclerosis to reverse the accumulation of macrophages in the plaque. This study imparts insight on regulation of plaque macrophage trafficking through LXRα S198 phosphorylation.
In a recent essay, Harker and coauthors stated that considering herbicide resistance as a wicked problem “without clear causes or solutions” ignores what weed scientists know about the biology and management of herbicide-resistant weeds. In this response, we argue that this misrepresents what is meant by “wicked” and that the wicked problem concept is valuable in understanding the multifaceted nature of herbicide resistance as a human-caused phenomenon.
Dr David Livingstone died on May 1st 1873. He was 60 years old and had spent much of the previous 30 years walking across large stretches of Southern Africa, exploring the terrain he hoped could provide new environments in which Europeans and Africans could cohabit on equal terms and bring prosperity to a part of the world he saw ravaged by the slave trade. Just days before he died, he wrote in his journal about the permanent stream of blood that he was emitting related to haemorrhoids and the acute intestinal pain that had left him incapable of walking. What actually killed Livingstone is unknown, yet the years spent exploring sub-Saharan Africa undoubtedly exposed him to a gamut of parasitic and other infectious diseases. Some of these we can be certain of. He wrote prolifically and described his encounters with malaria, relapsing fevers, parasitic helminths and more. His graphic writing allows us to explore his own encounters with tropical diseases and how European visitors to Africa considered them at this time. This paper outlines Livingstone's life and his contributions to understanding parasitic diseases.
Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.
Although the problem of herbicide resistance is not new, the widespread evolution of glyphosate resistance in weed species such as Palmer amaranth (Amaranthus palmeri S. Wats.), common waterhemp (Amaranthus rudis Sauer), and kochia [Kochia scoparia (L.) Schrad.] raised awareness throughout the agricultural community of herbicide resistance as a problem. Glyphosate-resistant weeds resulted in the loss of a simple, single herbicide option to control a wide spectrum of weeds that gave efficacious and economical weed management in corn (Zea mays L.), soybean [Glycine max (L.) Merr.], and cotton (Gossypium hirsutum L.) crops engineered for tolerance to this herbicide and planted over widespread areas of the South and Midwest of the United States. Beyond these crops, glyphosate is used for vegetation management in other cropping systems and in noncrop areas across the United States, and resistance to this herbicide threatens its continued utility in all of these situations. This, combined with the development of multiple herbicide-resistant weeds and the lack of commercialization of herbicides with new mechanisms of action over the past years (Duke 2012), caused the weed science community to realize that stewardship of existing herbicide resources, extending their useful life as long as possible, is imperative. Further, while additional herbicide tolerance traits are being incorporated into crops, weed management in these crops will still be based upon using existing, old, herbicide chemistries.
Microbial mats are common in polar streams and often dominate benthic biomass. Climate change may be enhancing the variability of stream flows in the Antarctic, but so far studies investigating mat responses to disturbance have been limited in this region. Mat regrowth was evaluated following disturbance by experimentally scouring rocks from an ephemeral McMurdo Dry Valley stream over two summers (2001–02 and 2012–13). Mats were sampled at the beginning and resampled at the end of the flow season. In 2012–13, mats were additionally resampled mid-season along with previously undisturbed controls. In 2001–02 rocks regained 47% of chlorophyll a and 40% of ash-free dry mass by the end of the summer, while in 2012–13 rocks regrew 18% and 27%, respectively. Mat stoichiometry differed between summers, and reflected differences in biomass and discharge. Oscillatoria spp. were greatest on scoured rocks and Phormidium spp. on undisturbed rocks. Small diatoms Humidophila and Fistulifera spp. increased throughout the summer in all mats, with the latter more abundant in scoured communities. Collectively, these data suggest that mats are variable intra-annually, responsive to hydrology and require multiple summers to regrow initial biomass once lost. These results will aid the interpretation of long-term data, as well as inform Antarctic Specially Managed Area protocols.