A rapid assessment framework for food system shocks: Lessons learned from COVID-19 in the Indo-Pacific region.

The frequency and severity of shocks to food systems is accelerating globally, exemplified by the current COVID-19 outbreak. In low- and middle-income countries, the impacts have exacerbated existing food system vulnerabilities and poverty. Governments and donors must respond quickly, but few tools are available that identify interventions to build food system resilience, or emerging opportunities for transformation. In this paper we reflect on the application of a systems-based rapid assessment which we applied across 11 Indo-Pacific countries in May-July 2020. Our approach was shaped by three design parameters: the integration of key informants' perspectives engaged remotely within the countries, applicability to diverse food systems and COVID-19 experiences across the region, and the consideration of food systems as complex systems. For the rapid assessment we adopted an analytical framework proposed by Allen and Prosperi (2016). To include a development lens, we added the analysis of vulnerable groups and their exposure, impacts, recovery potential and resilience, and pro-poor interventions. We concluded that the framework and approach facilitated integration and triangulation of disparate knowledge types and data to identify priority interventions and was sufficiently flexible to be applied across food systems, at both national, sub-national and commodity scales. The step-wise method was simple and enabled structured inquiry and reporting. Although the systems concepts appeared more easily transferrable to key informants in some countries than others, potentially transformational interventions were identified, and also some risks of maladaptation. We present a refined framework that emphasises analysis of political, economic and institutional drivers of exposure and vulnerability, the constraints that they pose for building recovery potential and resilience, and trade-offs amongst winners and losers inherent in proposed interventions.

COVID-19 and food systems in Pacific Island Countries, Papua New Guinea, and Timor-Leste: Opportunities for actions towards the sustainable development goals.

Context: The COVID-19 pandemic has impacted global food systems. This has led to different strategies by communities, governments, and businesses involved in food systems to mitigate and adapt to the unfolding pandemic. Small Island Developing States are particularly exposed to the conflation of risks from COVID-19 disease, economic downturns, underlying climate vulnerabilities and biosecurity risks. Objective: Our study aimed to identify the food systems vulnerabilities, impacts, and opportunities for supporting resilience and sustainable development in selected Pacific Island countries, Papua New Guinea, and Timor-Leste. The study focused on the impacts from the first six months of the pandemic (February-July 2020), with remote data collection and analysis done between May and July 2020. Methods: We conducted 67 interviews, and triangulated information with desktop and news sources emerging at the time. We present results on the effect on smallholder livelihoods, supply chains, governance, communities and employment. Overall, the major impacts of COVID-19 have been on economies, posing risks to future food security and further hampering progress towards key Sustainable Development Goals. Results and conclusions: We found that unemployment and economic contraction have been the most severe effects to date, with long-term consequences for food value chains and smallholder farmers. Disruptions to tourism, labour migration, and remittances have led to varying socio-economic impacts throughout the region. Vulnerable groups, notably women, urban poor, and youth, have been disproportionately affected by unemployment. Timor-Leste has had some social protection measures, whereas in Pacific Countries these have been varied. The lockdowns and State of Emergency initially influenced the distribution and marketing of food, but local food economies are starting to stabilise. The continued functioning of international food supply chains reduced the risk of food insecurity in high import dependent nations, notably import dependent countries like Tuvalu and Kiribati. Significance: The results have significance for three recovery pathways. The first recovery pathway relates to revisiting value chains in light of restricted travel. The second recovery pathway exists through leveraging the adaptive capacities of communities to stimulate innovative agriculture that also integrates climate adaptation and nutrition. The third recovery pathway relates to addressing the structural challenges that perpetuate inequalities and poverty while finding new ways of implementing inclusive policies and research. Our study presents a set of comparative examples of managing a food system shock that can inform future systems-oriented research and policy for sustainable development.

A blue ring nebula from a stellar merger several thousand years ago.

Stellar mergers are a brief but common phase in the evolution of binary star systems1,2. These events have many astrophysical implications; for example, they may lead to the creation of atypical stars (such as magnetic stars3, blue stragglers4 and rapid rotators5), they play an important part in our interpretation of stellar populations6 and they represent formation channels of compact-object mergers7. Although a handful of stellar mergers have been observed directly8,9, the central remnants of these events were shrouded by an opaque shell of dust and molecules10, making it impossible to observe their final state (for example, as a single merged star or a tighter, surviving binary11). Here we report observations of an unusual, ring-shaped ultraviolet ('blue') nebula and the star at its centre, TYC 2597-735-1. The nebula has two opposing fronts, suggesting a bipolar outflow of material from TYC 2597-735-1. The spectrum of TYC 2597-735-1 and its proximity to the Galactic plane suggest that it is an old star, yet it has abnormally low surface gravity and a detectable long-term luminosity decay, which is uncharacteristic for its evolutionary stage. TYC 2597-735-1 also exhibits Hα emission, radial-velocity variations, enhanced ultraviolet radiation and excess infrared emission-signatures of dusty circumstellar disks12, stellar activity13 and accretion14. Combined with stellar evolution models, the observations suggest that TYC 2597-735-1 merged with a lower-mass companion several thousand years ago. TYC 2597-735-1 provides a look at an unobstructed stellar merger at an evolutionary stage between its dynamic onset and the theorized final equilibrium state, enabling the direct study of the merging process.

MiR137 is an androgen regulated repressor of an extended network of transcriptional coregulators.

Androgens and the androgen receptor (AR) play crucial roles in male development and the pathogenesis and progression of prostate cancer (PCa). The AR functions as a ligand dependent transcription factor which recruits multiple enzymatically distinct epigenetic coregulators to facilitate transcriptional regulation in response to androgens. Over-expression of AR coregulators is implicated in cancer. We have shown that over-expression of KDM1A, an AR coregulator, contributes to PCa recurrence by promoting VEGFA expression. However the mechanism(s) whereby AR coregulators are increased in PCa remain poorly understood. In this study we show that the microRNA hsa-miR-137 (miR137) tumor suppressor regulates expression of an extended network of transcriptional coregulators including KDM1A/LSD1/AOF1, KDM2A/JHDM1A/FBXL11, KDM4A/JMJD2A, KDM5B JARID1B/PLU1, KDM7A/JHDM1D/PHF8, MED1/TRAP220/DRIP205 and NCoA2/SRC2/TIF2. We show that expression of miR137 is increased by androgen in LnCaP androgen PCa responsive cells and that the miR137 locus is epigenetically silenced in androgen LnCaP:C4-2 and PC3 independent PCa cells. In addition, we found that restoration of miR137 expression down-regulates expression of VEGFA, an AR target gene, which suggests a role of miR137 loss also in cancer angiogenesis. Finally we show functional inhibition of miR137 function enhanced androgen induction of PSA/KLK3 expression. Our data indicate that miR137 functions as an androgen regulated suppressor of androgen signaling by modulating expression of an extended network of transcriptional coregulators. Therefore, we propose that epigenetic silencing of miR137 is an important event in promoting androgen signaling during prostate carcinogenesis and progression.

Soil contamination and persistence of pollutants following organophosphate sprays and explosions to control red-billed quelea (Quelea quelea).

BACKGROUND: Red-billed quelea (Quelea quelea) are controlled at breeding colonies and roosts by organophosphate sprays or explosions. Contamination with organophosphates after sprays and with petroleum products and phthalates after explosions was assessed. RESULTS: Concentrations in soil of the organophosphate fenthion the day after sprays were uneven (0-29.5 µg g(-1)), which was attributable to excess depositions at vehicle turning points, incorrect positioning of nozzles and poor equipment maintenance. A laboratory study using field-collected samples provided an estimate of 47 days for the half-life of fenthion. After sprays, fenthion persisted in soil for up to 188 days. High concentrations were detected 5 months after negative results at the same sites, providing indirect evidence of leaching. Concentrations of total petroleum hydrocarbons (TPHs) and phthalates ranged from 0.05 to 130.81 (mean 18.69) µg g(-1) and from 0 to 1.62 (mean 0.55) µg g(-1) respectively in the craters formed by the explosions, but declined to means of 0.753 and 0.027 µg g(-1) at 10 m away. One year after an explosion, mean TPHs of 0.865 and mean phthalates of 0.609 were detected. CONCLUSION: Localisation of high concentrations of fenthion likely to have effects on soil biota could be mitigated by improved spray management. Given a half-life in the soil of 47 days for fenthion and the possibility of its leaching months after applications raises concerns about its acceptability. The pollutants left behind after explosions have been quantified for the first time, and, given their long-term persistence, their continued use poses a threat to environmental health.

Effects of the organophosphate fenthion for control of the red-billed quelea Quelea quelea on cholinesterase and haemoglobin concentrations in the blood of target and non-target birds.

The red-billed quelea bird Quelea quelea is one of sub-Saharan Africa's most damaging pests, attacking small-grain crops throughout semi-arid zones. It is routinely controlled by spraying its breeding colonies and roosts with organophosphate pesticides, actions often associated with detrimental effects on non-target organisms. Attributions of mortality and morbidity of non-targets to the sprays are difficult to confirm unequivocally but can be achieved by assessing depressions in cholinesterase activities since these are reduced by exposure to organophosphates. Here we report on surveys of birds caught before and after sprays that were examined for their blood cholinesterase activities to assess the extent to which these became depressed. Blood samples from birds were taken before and after sprays with fenthion against red-billed quelea in colonies or roosts, and at other unsprayed sites, in Botswana and Tanzania and analysed for levels of haemoglobin (Hb) and activities of whole blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Background activities of AChE, BChE and Hb concentrations varied with bird species, subspecies, mass, age and gender. Contrary to expectation, since avian erythrocytes are often reported to lack cholinesterases, acetylcholinesterase activities in pre-spray samples of adult birds were positively correlated with Hb concentrations. When these factors were taken into account there were highly significant declines (P < 0.0001) in AChE and BChE and increases in Hb after contact with fenthion in both target and non-target birds. BChE generally declined further (up to 87 % depression) from baseline levels than AChE (up to 83 % depression) but did so at a slower rate in a sample of quelea nestlings. Baseline activities of AChE and BChE and levels of Hb were higher in the East African subspecies of the red-billed quelea Q. q. aethiopica than in the southern African subspecies Q. q. lathamii, with the exception of BChE activities for adult males which were equivalent.

Healthcare impact of personalized medicine using genetic testing: an exploratory analysis for warfarin.

Warfarin, an anticoagulant commonly used to prevent and control blood clots, is complicated to use because the optimal dose varies greatly among patients. If the dose is too high, the risk of serious bleeding increases; if the dose is too low, the risk of stroke increases. We estimate the potential health benefits and resulting changes in healthcare costs should it become feasible to base personalized warfarin dosing decisions on appropriate genetic testing. Using different assumptions regarding the costs and effectiveness of genetic testing, we estimate that formally integrating genetic testing into routine warfarin therapy could allow American warfarin users to avoid 4500-22,000 serious bleeding events annually. Genetic-based therapy could also reduce the incidence of strokes among patients taking warfarin. We estimate that the additional cost per patient from integrating genetic testing into warfarin therapy could range from US$300 in our pessimistic case, to substantial healthcare cost savings in the optimistic case.

Moraxella catarrhalis stimulates the release of proinflammatory cytokines and prostaglandin E from human respiratory epithelial cells and monocyte-derived macrophages.

The outer membrane proteins of Moraxella catarrhalis, a bacterial pathogen which causes disease in both children and adults, play an important role in its phenotypic properties. However, their proinflammatory potential with regard to respiratory epithelium and macrophages is unclear. To this end, we examined the cytokine- and mediator-inducing capacity of a heat-killed wild-type M. catarrhalis strain and a nonautoagglutinating mutant as well as their outer membrane proteins and secretory/excretory products using the A549 respiratory epithelial cell line. The outer membrane proteins and secretory/excretory products from both isolates as well as the heat-killed bacteria all induced interleukin (IL)-6, IL-8 and prostaglandin E2, but not IL-1beta, from the A549 cell line in a dose- and time-dependent manner. Heat-killed bacteria and secretory/excretory products stimulated the release of IL-1beta, IL-6, IL-8 and prostaglandin E2 from human monocyte-derived macrophages. Both heat-killed isolates also stimulated nuclear translocation and transactivation of nuclear factor-kappaB. The heat-killed wild-type autoagglutinating isolate induced significantly greater amounts of IL-6 and IL-8 from A549 cells than the nonautoagglutinating mutant compared with the monocyte-derived macrophages but no significant differences in the amounts induced by the two strains were observed. These differences were also evident when the respiratory cell line was stimulated with outer membrane proteins as well as in the degree of nuclear factor-kappaB transactivation. There was little difference in the stimulatory activity of the secretory/excretory products. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analyses revealed some differences in the outer membrane proteins and secretory excretory products between the two isolates. Combined, these data show that M. catarrhalis secretory excretory products and outer membrane proteins are associated with the induction of inflammatory responses in both respiratory epithelium and macrophages.

Pro-inflammatory effects of Burkholderia cepacia on cystic fibrosis respiratory epithelium.

Burkholderia cepacia causes pulmonary infection with high mortality in cystic fibrosis (CF) patients which is likely to involve interaction with respiratory epithelium. In this study the pro-inflammatory properties of B. cepacia were examined using a range of respiratory epithelial cell lines. B. cepacia and cell-free culture supernatants were used to stimulate cell lines with (SigmaCFTE29o- and IB3) and without (A549) the CF transmembrane conductance regulator mutation (CFTR), together with corrected cell lines (C38 and S9). Interleukin (IL)-6 and IL-8, but not GM-CSF or IL-1beta, were released from all the cell lines whereas PGE(2) (prostaglandin E(2)) was released from the A549, IB3 and S9 cell lines only. Nuclear factor (NF)-kappaB activation preceded cytokine release and suppression of NF-kappaB activity diminished cytokine release. These studies indicated that B. cepacia secretory products are potent pro-inflammatory agents for respiratory epithelium and suggest functional CFTR is not required for cytokine or prostanoid responses.

Nitric oxide production by alveolar macrophages in response to house dust mite fecal pellets and the mite allergens, Der p 1 and Der p 2.

BACKGROUND: Allergens are frequently found within or attached to particulate material. For example, house dust mite fecal pellets (HDMFP) contain the major mite allergens, exposure to which have been implicated in the development of asthma. Although several studies have examined the ability of purified allergens to generate inflammatory responses, few studies have investigated whether HDMFP per se, are biologically active. OBJECTIVE: Our objective was to examine the ability of whole HDMFP to stimulate nitric oxide (NO) release from alveolar macrophages. METHODS: The rat alveolar macrophage cell line, NR8383, was exposed to HDMFP, Der p 1, or Der p 2, and nitrite levels in the culture supernatants were measured with the Griess reagent. NO synthase mRNA expression was determined by RT-PCR. RESULTS: HDMFP stimulated the production of NO in a dose-dependent and time-dependent manner, with maximum NO levels measured after 48 hours of exposure. Inclusion of polymyxin B did not influence NO production, suggesting that LPS was not responsible for NO production. HDMFP-mediated NO release was down-modulated after treatment with N(G)-nitro-l-arginine methyl ester (L-NAME), dexamethasone, EDTA, and cysteine, but not heat treatment. Inducible nitric oxide synthase mRNA was observed 3 hours after HDMFP exposure, with maximum levels after 48 hours. Both purified Der p 1 and Der p 2 induced NO production, and inhibition of the cysteine protease activity of Der p 1 had little effect on NO production. CONCLUSIONS: HDMFP, Der p 1 and Der p 2 are potent inducers of NO. Neither LPS nor the enzymatic activity of Der p 1 was responsible for NO production observed.

Dendritic cell influx differs between the subglottic and glottic mucosae during acute laryngotracheitis induced by a broad spectrum of stimuli.

Clinically, the subglottic and glottic mucosae may react differently, eg, during acute laryngotracheitis. In healthy rats, we showed previously that the composition of the mucosal immune system of the larynx also differs between these areas. Neutrophils, lymphocytes, and dendritic cells (DCs) are part of this mucosal immune system. In particular, DCs occupy a key function. They migrate into inflamed mucosae during the early phase of the immune response, which is normally characterized by an influx of neutrophils. Thus, they help to overcome the time lag between the innate and the adaptive immune responses. In the present study, the influx of DCs, neutrophils, and T lymphocytes into the subglottic and glottic mucosae of rats was examined at different time points after challenge with a broad spectrum of stimuli such as dead Moraxella catarrhalis, viable Bordetella pertussis, viable Sendai virus, and the soluble protein ovalbumin. The number of DCs increased rapidly after the application of the antigens. This increase was as rapid as the increase in neutrophils. Depending on the kind of antigen, their number in the mucosa increased up to 1,000 cells per 0.1 mm2 (Sendai virus). The comparison of different mucosal areas shows that an overwhelming number of immunocompetent cells entered the subglottic mucosa, whereas only a few cells migrated into the adjacent glottic mucosa. In conclusion, after inhalation of different kinds of antigens, the subset of immunocompetent cells investigated in this study entered the laryngeal mucosa in high numbers. The number of DCs entering the laryngeal mucosa was higher than the numbers of the other immune cells investigated. This finding underlines their function as first-line sentinels of the mucosal immune system of the larynx. The observation that the number of cells entering the laryngeal mucosa is location-dependent indicates the ability of adjacent laryngeal regions to react differently. This is similar to the clinical observation of a selective subglottic reaction during acute laryngotracheitis.

Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells.

Epithelia from many tissues express protease-activated receptors (PARs) that play a major role in several different physiological processes. In this study, we examined their capacity to modulate IL-6, IL-8, and PGE(2) production in both the A459 and BEAS-2B cell lines and primary human bronchial epithelial cells (HBECs). All three cell types expressed PAR-1, PAR-2, PAR-3, and PAR-4, as judged by RT-PCR and immunocytochemistry. Agonist peptides corresponding to the nascent N termini of PAR-1, PAR-2, and PAR-4 induced the release of cytokines from A549, BEAS-2B, and HBECs with a rank order of potency of PAR-2 > PAR-4 > PAR-1 at 400 microM. PAR-1, PAR-2, and PAR-4 also caused the release of PGE(2) from A549 and HBECs. The PAR-3 agonist peptide was inactive in all systems tested. PAR-1, PAR-2, or PAR-4, in combination, caused additive IL-6 release, but only the PAR-1 and PAR-2 combination resulted in an additive IL-8 response. PAR peptide-induced responses were accompanied by changes in intracellular calcium ion concentrations. However, Ca(2+) ion shutoff was approximately 2-fold slower with PAR-4 than with PAR-1 or PAR-2, suggesting differential G protein coupling. Combined, these data suggest an important role for PAR in the modulation of inflammation in the lung.