Fungal peptide Destruxin A plays a specific role in suppressing the innate immune response in Drosophila melanogaster

Destruxins are a class of insecticidal, anti-viral, and phytotoxic cyclic depsipeptides that are also studied for their toxicity to cancer cells. They are produced by various fungi, and a direct relationship has been established between Destruxin production and the virulence of the entomopathogen Metarhizium anisopliae. Aside from opening calcium channels, their in vivo mode of action during pathogenesis remains largely uncharacterized. To better understand the effects of a Destruxin, we looked at changes in gene expression following injection of Destruxin A into the fruit fly Drosophila melanogaster. Microarray results revealed reduced expression of various antimicrobial peptides that play a major role in the humoral immune response of the fly. Flies co-injected with a non-lethal dose of Destruxin A and the normally innocuous Gram-negative bacteria Escherichia coli, showed increased mortality and an accompanying increase in bacterial titers. Mortality due to sepsis was rescued through ectopic activation of components in the IMD pathway, one of two signal transduction pathways that are responsible for antimicrobial peptide induction. These results demonstrate a novel role for Destruxin A in specific suppression of the humoral immune response in insects.     

Differences in rheotactic responses contribute to divergent habitat use between parapatric lake and stream threespine stickleback

Migration among populations is widely thought to undermine adaptive divergence, assuming gene flow arises from random movement of individuals. If individuals instead differ in dispersal behavior, phenotype‐dependent dispersal can reduce the effective rate of gene flow or even facilitate divergence. For example, parapatric populations of lake and stream stickleback tend to actively avoid dispersing into the adjoining habitat. However, the behavioral basis of this nonrandom dispersal was previously unknown. Here, we show that lake and stream stickleback exhibit divergent rheotactic responses (behavioral response to currents). During the breeding season, wild‐caught inlet stream stickleback were better than lake fish at maintaining position in currents, faced upstream more, and spent more time in low‐current areas. As a result, stream fish expended significantly less energy in currents than did lake fish. These divergent rheotactic responses likely contribute to divergent habitat use by lake and stream stickleback. Although rheotactic differences were absent in nonbreeding fish, divergent behavior of breeding‐season fish may suffice for assortative mating by breeding location. The resulting reproductive isolation between lake and stream fish may explain the fine‐scale evolutionary differentiation in parapatric stickleback populations.     

The Role of Palmitoylation for Protein Recruitment to the Inner Membrane Complex of the Malaria Parasite

To survive and persist within its human host, the malaria parasite Plasmodium falciparum utilizes a battery of lineage-specific innovations to invade and multiply in human erythrocytes. With central roles in invasion and cytokinesis, the inner membrane complex, a Golgi-derived double membrane structure underlying the plasma membrane of the parasite, represents a unique and unifying structure characteristic to all organisms belonging to a large phylogenetic group called Alveolata. More than 30 structurally and phylogenetically distinct proteins are embedded in the IMC, where a portion of these proteins displays N-terminal acylation motifs. Although N-terminal myristoylation is catalyzed co-translationally within the cytoplasm of the parasite, palmitoylation takes place at membranes and is mediated by palmitoyl acyltransferases (PATs). Here, we identify a PAT (PfDHHC1) that is exclusively localized to the IMC. Systematic phylogenetic analysis of the alveolate PAT family reveals PfDHHC1 to be a member of a highly conserved, apicomplexan-specific clade of PATs. We show that during schizogony this enzyme has an identical distribution like two dual-acylated, IMC-localized proteins (PfISP1 and PfISP3). We used these proteins to probe into specific sequence requirements for IMC-specific membrane recruitment and their interaction with differentially localized PATs of the parasite.     

Infrared Spectroscopic Biosignatures from Hidden Cave,New Mexico: Possible Applications for Remote Life Detection

Subsurface environments are known to support and preserve diverse microbial communities. Giant pool fingers from Hidden Cave, New Mexico consist of mm-scale dark micritic calcite layers alternating with clear dogtooth spar crystals and contain morphological and geochemical evidence of past microbial communities. We used Fourier Transform infrared spectroscopy to identify fatty acids, proteins, PO₂-carrying compounds, and polysaccharides spatially related to morphological fossil filaments throughout the surface micritic laminations and central pool finger regions. These biomolecular signatures are important components that contribute to the biosignature suite under development that identify microbial involvement in carbonate precipitation on Earth and remotely.     

Penumbra Pattern Assessment in Acute Stroke Patients: Comparison of Quantitative and Non-Quantitative Methods in Whole Brain CT Perfusion

Background And Purpose

While penumbra assessment has become an important part of the clinical decision making for acute stroke patients, there is a lack of studies measuring the reliability and reproducibility of defined assessment techniques in the clinical setting. Our aim was to determine reliability and reproducibility of different types of three-dimensional penumbra assessment methods in stroke patients who underwent whole brain CT perfusion imaging (WB-CTP).

Materials And Methods

We included 29 patients with a confirmed MCA infarction who underwent initial WB-CTP with a scan coverage of 100 mm in the z-axis. Two blinded and experienced readers assessed the flow-volume-mismatch twice and in two quantitative ways: Performing a volumetric mismatch analysis using OsiriX imaging software (MM_VOL) and visual estimation of mismatch (MM_EST). Complementarily, the semiquantitative Alberta Stroke Programme Early CT Score for CT perfusion was used to define mismatch (MM_ASPECTS). A favorable penumbral pattern was defined by a mismatch of ≥30% in combination with a cerebral blood flow deficit of ≤90 ml and an MM_ASPECTS score of ≥1, respectively. Inter- and intrareader agreement was determined by Kappa-values and ICCs.

Results

Overall, MM_VOL showed considerably higher inter-/intrareader agreement (ICCs: 0.751/0.843) compared to MM_EST (0.292/0.749). In the subgroup of large (≥50 mL) perfusion deficits, inter- and intrareader agreement of MM_VOL was excellent (ICCs: 0.961/0.942), while MM_EST interreader agreement was poor (0.415) and intrareader agreement was good (0.919). With respect to penumbra classification, MM_VOL showed the highest agreement (interreader agreement: 25 agreements/4 non-agreements/κ: 0.595; intrareader agreement 27/2/0.833), followed by MM_EST (22/7/0.471; 23/6/0.577), and MM_ASPECTS (18/11/0.133; 21/8/0.340).

Conclusion

The evaluated approach of volumetric mismatch assessment is superior to pure visual and ASPECTS penumbra pattern assessment in WB-CTP and helps to precisely judge the extent of 3-dimensional mismatch in acute stroke patients.     

Mental and Substance Use Disorders in Sub-Saharan Africa: Predictions of Epidemiological Changes and Mental Health Workforce Requirements for the Next 40 Years

The world is undergoing a rapid health transition, with an ageing population and disease burden increasingly defined by disability. In Sub-Saharan Africa the next 40 years are predicted to see reduced mortality, signalling a surge in the impact of chronic diseases. We modelled these epidemiological changes and associated mental health workforce requirements. Years lived with a disability (YLD) predictions for mental and substance use disorders for each decade from 2010 to 2050 for four Sub-Saharan African regions were calculated using Global Burden of Disease 2010 study (GBD 2010) data and UN population forecasts. Predicted mental health workforce requirements for 2010 and 2050, by region and for selected countries, were modelled using GBD 2010 prevalence estimates and recommended packages of care and staffing ratios for low- and middle-income countries, and compared to current staffing from the WHO Mental Health Atlas. Significant population growth and ageing will result in an estimated 130% increase in the burden of mental and substance use disorders in Sub-Saharan Africa by 2050, to 45 million YLDs. As a result, the required mental health workforce will increase by 216,600 full time equivalent staff from 2010 to 2050, and far more compared to the existing workforce. The growth in mental and substance use disorders by 2050 is likely to significantly affect health and productivity in Sub-Saharan Africa. To reduce this burden, packages of care for key mental disorders should be provided through increasing the mental health workforce towards targets outlined in this paper. This requires a shift from current practice in most African countries, involving substantial investment in the training of primary care practitioners, supported by district based mental health specialist teams using a task sharing model that mobilises local community resources, with the expansion of inpatient psychiatric units based in district and regional general hospitals.     

Shape Up or Ship Out: Can We Enhance Productivity in Coastal Aquaculture to Compete with Other Uses?

Coastal resources are coming under increasing pressure from competition between recreational, commercial and conservation uses. This is particularly so in coastal areas adjacent to major population centres. Given high recreational and conservation values in such areas, economic activities need to be highly efficient in order to persist. Management of these industries must therefore also encourage efficient production and full utilisation of the areas available. In order to achieve this, managers must first understand the level and drivers of productivity, and how these can be influenced. In this study, by way of illustration, the focus was on the Sydney rock oyster industry within Queensland''s Moreton Bay, a multiple use marine park with high recreational and conservation value adjacent to Australia’s third largest city. Productivity of the oyster industry in Moreton Bay is currently low compared to historic levels, and management has an objective of reversing this trend. It is unclear whether this difference is due to oyster farmers’ business choices and personal characteristics or whether varying environmental conditions in the Moreton Bay limit the capacity of the oyster industry. These require different management responses in order to enhance productivity. The study examined different productivity measures of the oyster industry using data envelopment analysis (DEA) to determine where productivity gains can be made and by how much. The findings suggest that the industry is operating at a high level of capacity utilisation, but a low level of efficiency. The results also suggest that both demographic and environmental conditions affect technical efficiency in the Bay, with water characteristics improvements and appropriate training potentially providing the greatest benefits to the industry. Methods used in this study are transferable to other industries and provide a means by which coastal aquaculture may be managed to ensure it remains competitive with other uses of coastal resources.     

Predicting the impact of the 2011 conflict in Libya on population mental health: PTSD and depression prevalence and mental health service requirements

Background

Mental disorders are likely to be elevated in the Libyan population during the post-conflict period. We estimated cases of severe PTSD and depression and related health service requirements using modelling from existing epidemiological data and current recommended mental health service targets in low and middle income countries (LMIC’s).

Methods

Post-conflict prevalence estimates were derived from models based on a previously conducted systematic review and meta-regression analysis of mental health among populations living in conflict. Political terror ratings and intensity of exposure to traumatic events were used in predictive models. Prevalence of severe cases was applied to chosen populations along with uncertainty ranges. Six populations deemed to be affected by the conflict were chosen for modelling: Misrata (population of 444,812), Benghazi (pop. 674,094), Zintan (pop. 40,000), displaced people within Tripoli/Zlitan (pop. 49,000), displaced people within Misrata (pop. 25,000) and Ras Jdir camps (pop. 3,700). Proposed targets for service coverage, resource utilisation and full-time equivalent staffing for management of severe cases of major depression and post-traumatic stress disorder (PTSD) are based on a published model for LMIC’s.

Findings

Severe PTSD prevalence in populations exposed to a high level of political terror and traumatic events was estimated at 12.4% (95%CI 8.5–16.7) and was 19.8% (95%CI 14.0–26.3) for severe depression. Across all six populations (total population 1,236,600), the conflict could be associated with 123,200 (71,600–182,400) cases of severe PTSD and 228,100 (134,000–344,200) cases of severe depression; 50% of PTSD cases were estimated to co-occur with severe depression. Based upon service coverage targets, approximately 154 full-time equivalent staff would be required to respond to these cases sufficiently which is substantially below the current level of resource estimates for these regions.

Discussion

This is the first attempt to predict the mental health burden and consequent service response needs of such a conflict, and is crucially timed for Libya.     

Quantifying small‐scale deforestation and forest degradation in African woodlands using radar imagery

Carbon emissions from tropical land‐use change are a major uncertainty in the global carbon cycle. In African woodlands, small‐scale farming and the need for fuel are thought to be reducing vegetation carbon stocks, but quantification of these processes is hindered by the limitations of optical remote sensing and a lack of ground data. Here, we present a method for mapping vegetation carbon stocks and their changes over a 3‐year period in a > 1000 km² region in central Mozambique at 0.06 ha resolution. L‐band synthetic aperture radar imagery and an inventory of 96 plots are combined using regression and bootstrapping to generate biomass maps with known uncertainties. The resultant maps have sufficient accuracy to be capable of detecting changes in forest carbon stocks of as little as 12 MgC ha^?1 over 3 years with 95% confidence. This allows characterization of biomass loss from deforestation and forest degradation at a new level of detail. Total aboveground biomass in the study area was reduced by 6.9 ± 4.6% over 3 years: from 2.13 ± 0.12 TgC in 2007 to 1.98 ± 0.11 TgC in 2010, a loss of 0.15 ± 0.10 TgC. Degradation probably contributed 67% (96.9 ± 91.0 GgC) of the net loss of biomass, but is associated with high uncertainty. The detailed mapping of carbon stock changes quantifies the nature of small‐scale farming. New clearances were on average small (median 0.2 ha) and were often additions to already cleared land. Deforestation events reduced biomass from 33.5 to 11.9 MgC ha^?1 on average_. Contrary to expectations, we did not find evidence that clearances were targeted towards areas of high biomass. Our method is scalable and suitable for monitoring land cover change and vegetation carbon stocks in woodland ecosystems, and can support policy approaches towards reducing emissions from deforestation and degradation (REDD).