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Alternaria alternata is an opportunistic phytopathogen that negatively impact the growth and production of a wide variety of host plants. In this study, we evaluated the antifungal potential of biogenic ZnO, and bimetallic silver and zinc oxide (Ag/ZnO) nanoparticles synthesized using seed extract of Abrus precatorious and characterized using different analytical tools. In vitro antifungal potentials of ZnO and Ag/ZnO nanoparticles were carried out using the food poison technique. Morphological and ultrastructure of the A. alternata treated with the nanoparticles were carried out using high resolution scanning and transmission electron microscopy (HRSEM and HRTEM). In addition, changes in polysaccharide production, chitin content and enzymatic (cellulase and lipase) activities of A. alternata were assayed. Double peak signifying a UVmax of 353.88 and 417.25 nm representing Ag and ZnO respectively was formed in the bimetallic nanoparticles. HRSEM and HRTEM results shows agglomerated nanoparticles with particle and crystallite size of 23.94 and 16.84 nm for ZnO nanoparticles, 35.12 and 28.99 nm for Ag/ZnO nanoparticles respectively. In vitro antifungal assay shows a significant concentration-dependent inhibition (p

Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as biodegradation, specificity, stability and toxicity, impede their progression into clinical trials. Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy. The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.

The number and diversity of drugs in the tuberculosis (TB) drug development process has increased over the years, yet the attrition rate remains very high, signaling the need for continued research in drug discovery. In this study, crude secondary metabolites from marine fungi associated with ascidians collected from Saldanha and False Bays (South Africa) were investigated for antimycobacterial activity. Isolation of fungi was performed by sectioning thin inner-tissues of ascidians and spreading them over potato dextrose agar (PDA). Solid state fermentation of fungal isolates on PDA was then performed for 28 days to allow production of secondary metabolites. Afterwards, PDA cultures were dried and solid-liquid extraction using methanol was performed to extract fungal metabolites. Profiling of metabolites was performed using untargeted liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The broth microdilution method was used to determine antimycobacterial activity against Mycobacterium smegmatis mc2155 and Mycobacterium tuberculosis H37Rv, while in silico flexible docking was performed on selected target proteins from M. tuberculosis. A total of 16 ascidians were sampled and 46 fungi were isolated. Only 32 fungal isolates were sequenced, and their sequences submitted to GenBank to obtain accession numbers. Metabolite profiling of 6 selected fungal extracts resulted in the identification of 65 metabolites. The most interesting extract was that of Clonostachys rogersoniana MGK33 which inhibited Mycobacterium smegmatis mc2155 and Mycobacterium tuberculosis H37Rv growth with minimum inhibitory concentrations (MICs) of 0.125 and 0.2 mg/mL, respectively. These results were in accordance with those from in silico molecular docking studies which showed that bionectin F produced by C. rogersoniana MGK33 is a potential inhibitor of M. tuberculosis β-ketoacyl-acyl carrier protein reductase (MabA, PDB ID = 1UZN), with the docking score observed as −11.17 kcal/mol. These findings provided evidence to conclude that metabolites from marine-derived fungi are potential sources of bioactive metabolites with antimycobacterial activity. Even though in silico studies showed that bionectin F is a potent inhibitor of an essential enzyme, MabA, the results should be validated by performing purification of bionectin F from C. rogersoniana MGK33 and in vitro assays against MabA and whole cells (M. tuberculosis).

Ground beef is a common source of US Salmonella illnesses and outbreaks. However, the demographic and socioeconomic factors that are related to risk in ground beef-associated outbreaks of Salmonella infections are poorly understood. We describe the individual-level demographic characteristics and county-level indicators of social vulnerability for people infected with Salmonella linked to outbreaks associated with ground beef in the United States during 2012-2018. Non-Hispanic (NH) White and NH American Indian/Alaska Native persons, and people living in nonmetropolitan areas, were overrepresented among people in salmonellosis outbreaks linked to ground beef. Case patients disproportionately resided in counties with high social vulnerability, suggesting that one or more community social risk factors may contribute to or be associated with some food safety risks. Collecting and analyzing socioeconomic and demographic characteristics of people in outbreaks can help identify disparities in foodborne disease, which can be further characterized and inform equity-focused interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Foodborne illness continues to be a substantial public health concern in the United States with contaminated ground beef, chicken, and leafy greens identified as important sources of illnesses and outbreaks. These foods also have been identified by consumers as foods that are likely to carry germs that can make people sick. Food irradiation is a promising tool to enhance food safety. Despite this, there has been limited application of food irradiation in the U.S. During October 7-9, 2022, we licensed data from a Porter Novelli Public Services survey (N = 1,008) to examine consumer risk perception of contamination of ground beef, chicken, and leafy greens with pathogens, and the potential influence risk perception has on purchasing irradiated versions of these foods. Among respondents familiar with food irradiation, a higher proportion of those who believed ground beef and leafy greens were likely contaminated also indicated they were likely to consider purchasing irradiated ground beef (55.6% vs 35.4%; p = 0.0061) and leafy greens (60.8% vs 36.1%; p ≤ 0.0001) compared with those who did not; chicken was not significant (58.6% vs 45.4%; p = 0.0727). This survey demonstrated the importance of risk perception as an influencer on a consumer's decision to purchase irradiated foods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Michael Ablan reports were provided by Centers for Disease Control and Prevention (CDC). Michael Ablan reports a relationship with Centers for Disease Control and Prevention (CDC) that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper”., (Published by Elsevier Inc.)

Over 40% of all U.S. Salmonella illnesses are attributed to consumption of contaminated meat and poultry products each year. Determining which serotypes cause the most outbreak illnesses associated with specific meat and poultry types can inform prevention measures. We developed an approach to categorize serotypes using outbreak illness burden (high, moderate, low) and trajectory (increased, stable, decreased). We used data from 192 foodborne Salmonella outbreaks resulting in 7,077 illnesses, 1,330 hospitalizations, and 9 deaths associated with chicken, turkey, beef, or pork during 2012-2021. We linked each meat and poultry type to 1-3 serotypes that we categorized as high outbreak illness burden and increased trajectory during 2021. Calculation and public display of outbreak illness burden and trajectory annually could facilitate the prioritization of serotypes for prevention by federal and state health and regulatory agencies and by the meat and poultry industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Salmonella is estimated to be the leading bacterial cause of U.S. domestically acquired foodborne illness. Large outbreaks of Salmonella attributed to ground beef have been reported in recent years. The demographic and sociodemographic characteristics of infected individuals linked to these outbreaks are poorly understood. We employed a retrospective case-control design; case-patients were people with laboratory-confirmed Salmonella infections linked to ground beef-associated outbreaks between 2012 and 2019, and controls were respondents to the 2018-2019 FoodNet Population Survey who reported eating ground beef and denied recent gastrointestinal illness. We used county-level CDC/ATSDR Social Vulnerability Index (SVI) to compare case-patient and controls. Case-patient status was regressed on county-level social vulnerability and individual-level demographic characteristics. We identified 376 case-patients and 1,321 controls in the FoodNet sites. Being a case-patient was associated with increased overall county-level social vulnerability (OR: 1.21 [95% CI: 1.07-1.36]) and socioeconomic vulnerability (OR: 1.24 [1.05-1.47]) when adjusted for individual-level demographics. Case-patient status was not strongly associated with the other SVI themes of household composition and disability, minority status and language, and housing type and transportation. Data on individual-level factors such as income, poverty, unemployment, and education could facilitate further analyses to understand this relationship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Over 20% of E. coli O157 illnesses and over 5% of Salmonella illnesses are estimated to be attributable to beef consumption in the United States. Irradiating ground beef is one possible method to reduce disease burden. We simulated the effect of ground beef irradiation on illnesses, hospitalizations, deaths, and direct healthcare costs from ground beef-associated E. coli O157 and Salmonella illnesses in the United States. To estimate the fraction of illnesses, hospitalizations, deaths, and direct healthcare costs preventable by ground beef irradiation, we multiplied the disease burden attributable to ground beef; the estimated percentage of ground beef sold that is not currently irradiated; the percentage of unirradiated ground beef that would be irradiated; and the percentage reduction in risk of illness after irradiation. We multiplied this fraction by estimates of burden and direct healthcare costs to calculate the numbers or amounts averted. Model inputs were obtained from the literature and expert opinion. We used Monte Carlo simulation to incorporate uncertainty in inputs into model estimates. Simulation outcomes were summarized with means and 95% uncertainty intervals (UI). Irradiating 50% of the currently unirradiated ground beef supply would avert 3,285 (95% UI: 624-9,977) E. coli O157 illnesses, 135 (95% UI: 24-397) hospitalizations, 197 (95% UI: 34-631) hemolytic uremic syndrome cases, 2 (95% UI: 0-16) deaths, and $2,972,656 (95% UI: $254,708-$14,496,916) in direct healthcare costs annually. For Salmonella, irradiation would avert 20,308 (95% UI: 9,858-38,903) illnesses, 400 (95% UI: 158-834) hospitalizations, 6 (95% UI: 0-18) deaths, and $7,318,632 (95% UI: $1,436,141-$26,439,493) in direct healthcare costs. Increasing ground beef irradiation could reduce E. coli O157 and Salmonella burden in the United States. Additional studies should assess whether targeted irradiation of higher-risk ground beef products could prevent similar numbers of illnesses with less total product irradiated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

In the United States, there is currently no system to track donated human tissue products to individual recipients. This posed a challenge during an investigation of a nationwide tuberculosis outbreak that occurred when bone allograft contaminated with Mycobacterium tuberculosis (Lot A) was implanted into 113 patients in 18 US states, including 2 patients at 1 health care facility in Colorado. A third patient at the same facility developed spinal tuberculosis with an isolate genetically identical to the Lot A outbreak strain. However, health care records indicated this patient had received bone allograft from a different donor (Lot B). We investigated the source of this newly identified infection, including the possibilities of Lot B donor infection, product switch or contamination during manufacturing, product switch at the health care facility, person-to-person transmission, and laboratory error. The findings included gaps in tissue traceability at the health care facility, creating the possibility for a product switch at the point of care despite detailed tissue-tracking policies. Nationally, 6 (3.9%) of 155 Lot B units could not be traced to final disposition. This investigation highlights the critical need to improve tissue-tracking systems to ensure unbroken traceability, facilitating investigations of recipient adverse events and enabling timely public health responses to prevent morbidity and mortality., (Published by Elsevier Inc.)

In 2016, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state partners investigated nine Listeria monocytogenes infections linked to frozen vegetables. The investigation began with two environmental L. monocytogenes isolates recovered from Manufacturer A, primarily a processor of frozen onions, that were a match by whole genome sequencing (WGS) to eight clinical isolates and historical onion isolates with limited collection details. Epidemiologic information, product distribution, and laboratory evidence linked suspect food items, including products sourced from Manufacturer B, also a manufacturer of frozen vegetable/fruit products, with an additional illness. The environmental isolates were obtained during investigations at Manufacturers A and B. State and federal partners interviewed ill people, analyzed shopper card data, and collected household and retail samples. Nine ill persons between 2013 and 2016 were reported in four states. Of four ill people with information available, frozen vegetable consumption was reported by three, with shopper cards confirming purchases of Manufacturer B brands. Two identified outbreak strains of L. monocytogenes (Outbreak Strain 1 and Outbreak Strain 2) were a match to environmental isolates from Manufacturer A and/or isolates from frozen vegetables recovered from open and unopened product samples sourced from Manufacturer B; the investigation resulted in extensive voluntary recalls. The close genetic relationship between isolates helped investigators determine the source of the outbreak and take steps to protect public health. This is the first known multistate outbreak of listeriosis in the United States linked to frozen vegetables and highlights the significance of sampling and WGS analyses when there is limited epidemiologic information. Additionally, this investigation emphasizes the need for further research regarding food safety risks associated with frozen foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The Centers for Disease Control and Prevention (CDC) has identified nontyphoidal Salmonella as one of the top five pathogens contributing to foodborne illnesses in the United States. Beef continues to be a common source of Salmonella outbreaks, despite the implementation of interventions at slaughter and processing facilities to reduce contamination of beef. We described Salmonella outbreaks linked to beef in the United States during 2012-2019, examined trends, and identified potential targets for intervention and prevention strategies. We queried CDC's Foodborne Disease Outbreak Surveillance System (FDOSS) for all foodborne nontyphoidal Salmonella outbreaks linked to beef as the single contaminated ingredient or implicated food, with the date of first illness onset from 2012 to 2019. Information on antimicrobial resistance (AR) for outbreak-related isolates was obtained from CDC's National Antimicrobial Resistance Monitoring System (NARMS). We calculated the number of outbreaks, outbreak-related illnesses, hospitalizations, and deaths overall, by beef processing category and Salmonella serotype. During 2012-2019, 27 Salmonella outbreaks were linked to beef consumption, resulting in 1103 illnesses, 254 hospitalizations, and two deaths. The most common category of beef implicated was nonintact raw, ground beef (12 outbreaks, 44%), followed by intact raw (six outbreaks, 22%). Ground beef was responsible for the most illnesses (800, 73%), both of the reported deaths, and was the source of the largest outbreak. AR data were available for 717 isolates from 25 (93%) outbreaks. Nine (36%) of these outbreaks had isolates resistant to one or more of the antibiotics tested by NARMS, of which eight (89%) contained multidrug-resistant isolates. Several outbreaks reported highlight challenges faced during investigations, areas where further research may be warranted, and opportunities to prevent future outbreaks along the farm-to-fork continuum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Evolutionary change impacts the rate at which insect pests, pollinators, or disease vectors expand or contract their geographic ranges. Although evolutionary changes, and their ecological feedbacks, strongly affect these risks and associated ecological and economic consequences, they are often underappreciated in management efforts. Greater rigor and scope in study design, coupled with innovative technologies and approaches, facilitates our understanding of the causes and consequences of eco-evolutionary dynamics in insect range shifts. Future efforts need to ensure that forecasts allow for demographic and evolutionary change and that management strategies will maximize (or minimize) the adaptive potential of range-shifting insects, with benefits for biodiversity and ecosystem services., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Leafy greens contaminated with Shiga toxin-producing Escherichia coli have continued to cause foodborne illness outbreaks in recent years and present a threat to public health. An important component of foodborne illness outbreak investigations is determining the source of the outbreak vehicle through traceback investigations. The U.S. Food and Drug Administration is home to traceback investigation experts who use a standardized process to initiate, execute, and interpret the results of traceback investigations in collaboration with the Centers for Disease Control and Prevention and state and local partners. Traceback investigations of three outbreaks of Shiga toxin-producing E. coli infections linked to romaine lettuce in 2018 and 2019 were examined to demonstrate challenges, limitations, and opportunities for improvement. The three outbreaks resulted in a total of 474 illnesses, 215 hospitalizations, and 5 deaths. These illnesses were linked to the consumption of romaine lettuce from three distinct growing regions in Arizona and California. Some of the challenges encountered included the time it took to initiate a traceback, limited product-identifying information throughout the supply chain, lack of interoperability in record-keeping systems, and comingling of product from multiple suppliers. These challenges led to time delays in the identification of the farm source of the leafy greens and the inability to identify the root cause of contamination. Implementation of technology-enabled traceability systems, testing of these systems, and future regulations to incentivize adoption of traceability systems are some of the initiatives that will help address these challenges by improving traceback investigations and ultimately preventing foodborne illnesses and future outbreaks from occurring., (Published 2021 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Overwintering is a serious challenge for insects, and winters are rapidly changing as climate shifts. The capacity for phenotypic plasticity and evolutionary adaptation will determine which species profit or suffer from these changes. Here we discuss current knowledge on the potential and evidence for evolution in winter-relevant traits among insect species and populations. We conclude that the best evidence for evolutionary shifts in response to changing winters remain those related to changes in phenology, but all evidence points to cold hardiness as also having the potential to evolve in response to climate change. Predicting future population sizes and ranges relies on understanding to what extent evolution in winter-related traits is possible, and remains a serious challenge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Assembly of tau protein into paired helical filaments and straight filaments is a key feature of Alzheimer's disease. Aggregation of tau has been implicated in neurodegeneration, cellular toxicity and the propagation, which accompanies disease progression. We have reported previously that a region of tau (297-391), referred to as dGAE, assembles spontaneously in physiological conditions to form paired helical filament-like fibres in vitro in the absence of additives such as heparin. This provides a valuable tool with which to explore the effects of tau in cell culture. Here we have studied the cellular uptake of soluble oligomeric and fibrillar forms of dGAE and examined the downstream consequences of tau internalisation into differentiated SH-SY5Y neuroblastoma cells using fluorescence and electron microscopy alongside structural and biochemical analyses. The assembled dGAE shows more acute cytotoxicity than the soluble, non-aggregated form. Conversely, the soluble form is much more readily internalised and, once within the cell, is able to associate with endogenous tau resulting in increased phosphorylation and aggregation of endogenous tau, which accumulates in lysosomal/endosomal compartments. It appears that soluble oligomeric forms are able to propagate tau pathology without being acutely toxic. The model system we have developed now permits the molecular mechanisms of propagation of tau pathology to be studied in vitro in a more physiological manner with a view to development of novel therapeutic approaches., Competing Interests: Disclosures S.J.P. was supported by a Sussex Neuroscience doctoral grant. K.E.M. was supported by Medical Research Council (MR/K022105/1) awarded to L.C.S. L.C.S. is supported by funding from Alzheimer's Research UK and Alzheimer's Society and Biotechnology and Biological Sciences Research Council (BB/S003657/1). K.E.M. and Y.K.A. were supported by funding from WisTa Laboratories Ltd. (PAR1596). Conflict of interest CRH and CMW hold Office in TauRx Therapeutics Ltd. and are inventors on patents owned by WisTa Laboratories Ltd., an affiliate of TauRx Therapeutics Ltd. KEM and YKA are funded by WisTa Laboratories Ltd., (PAR1596)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Triacylglycerides (TAGs) are the most important stored energy reserve in eukaryotes and are regularly measured in insects. Quantitative analysis of TAGs is complicated by their diversity of structure, and there are concerns with the quantitative accuracy of commonly used analytical methods. We used thin layer chromatography coupled to a flame ionisation detector (TLC-FID), an accurate method that is not sensitive to saturation or chain length of fatty acids, to quantify TAG content in small amounts of insect tissue, and used it to validate three high-throughput lipid assays (gravimetric, vanillin, and enzymatic). The performance of gravimetric assays depended on the solvent used. Folch reagent (chloroform: methanol 2:1 v/v) was a good index of TAG content, but overestimated lipid content due to the extraction of structural lipid and non-lipid components. Diethyl ether produced reasonable quantitative measurements but lacked precision and could not produce a repeatable rank-order of samples. The vanillin assay was accurate both as a quantitative method and as an index, preferably with a standard of mixed fatty acid composition. The enzymatic assay did not accurately or precisely quantify TAGs under our assay conditions. We conclude that the vanillin assay is suitable as a high-throughput method for quantifying TAG providing fatty acid composition does not change among treatment groups. However, if samples contain significant quantities of di- or mono-acylglycerides, or the fatty acid composition differs across treatment groups, TLC-FID is recommended., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Carbon dioxide and chilling are sometimes used to immobilise insects for laboratory research. Both of these methods are known to have short-term effects on behaviour and physiology in Drosophila, but their long-term impacts are unknown. We exposed female D. melanogaster adults to high CO(2) concentrations (4h at 18,000ppm) and chronic cold (72h at 4°C). The carbon dioxide exposure increased chill coma recovery time, but did not result in changes in offspring number, sex ratio, or size. By contrast, the cold exposure resulted in fewer, smaller offspring, and resulted in a male-biased sex ratio compared to controls. There was no significant interaction between CO(2) and cold. We conclude that although caution must be used in choosing an immobilisation method, CO(2) appears to have less long-term impact than cold., (2010 Elsevier Ltd. All rights reserved.)

Insects can improve their desiccation resistance by one or more of (1) increasing their water content; (2) decreasing water loss rate; or (3) increasing the amount of water able to be lost before death. Female Drosophila melanogaster have previously been reported to increase their resistance to desiccation after a desiccation pre-treatment and recovery, but the mechanism of this increased desiccation resistance has not been explored. We show that female, but not male adult D. melanogaster increased their resistance to desiccation after 1h of recovery from a 3 to 4.5h pre-treatment that depletes them of 10% of their water content. The pre-treatment did not result in an increase in water content after recovery, and there is a slight increase in water content at death in pre-treated females (but no change in males), suggesting that the amount of water loss tolerated is not improved. Metabolic rate, measured on individual flies with flow-through respirometry, did not change with pre-treatment. However, a desiccation pre-treatment did result in a reduction in water loss rate, and further investigation indicated that a change in cuticular water loss rate accounted for this decrease. Thus, the observed increase in desiccation resistance appears to be based on a change in cuticular permeability. However, physiological changes in response to the desiccation pre-treatment were similar in male and female, which therefore does not account for the difference in rapid desiccation hardening between the sexes. We speculate that sex differences in fuel use during desiccation may account for the discrepancy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Amyloid fibril deposition is central to the pathology of more than 30 unrelated diseases including Alzheimer's disease and Type 2 diabetes. It is generally accepted that amyloid fibrils share common structural features despite each disease being characterised by the deposition of an unrelated protein or peptide. The structure of amyloid fibrils has been studied using X-ray fibre diffraction and crystallography, solid-state NMR and electron paramagnetic resonance, and many different, sometimes opposing, models have been suggested. Many of these models are based on the original interpretation of the cross-beta diffraction pattern for cross-beta silk in which beta-strands run perpendicular to the fibre axis, although alternative models include beta-helices and natively structured proteins. Here, we have analysed opposing model structures and examined the necessary structural elements within the amyloid core structure, as well as producing idealised models to test the limits of the core conformation. Our work supports the view that amyloid fibrils share a number of common structural features, resulting in characteristic diffraction patterns. This pattern may be satisfied by structures in which the strands align close to perpendicular to the fibre axis and are regularly arranged to form beta-sheet ribbons. Furthermore, the fibril structure contains several beta-sheets that associate via side-chain packing to form the final protofilament structure.