Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Reared Microgastrine Wasps (Hymenoptera: Braconidae) from Yanayacu Biological Station and Environs (Napo Province, Ecuador): Diversity and Host Specialization

The microgastrine braconid wasps recovered up through 2007 by the NSF-sponsored rearing project “Caterpillars and Parasitoids of the Eastern Andes in Ecuador” are summarized in terms of their host specialization and faunistic uniqueness. Two hundred fifty eight rearings of caterpillars resulted in records of Microgastrinae, distributed among 14 genera (Apanteles Förster, Choeras Mason, Cotesia Cameron, Diolcogaster Ashmead, Distatrix Mason, Dolichogenidea Viereck, Exix Mason, Glyptapanteles Ashmead, Hypomicrogaster Ashmead, Papanteles Mason, Parapanteles Ashmead, Protapanteles Ashmead, Sathon Mason and Venanus Mason). Eleven records of hyperparasitoids of Microgastrinae are also summarized; Mesochorus Gravenhorst (Ichneumonidae) and Perilampidae are both recorded. The results are compared to those recovered by surveys in other parts of the world, especially by the Janzen-Hallwachs survey of the Area de Conservación Guanacaste (ACG) in Costa Rica. An annotated list of microgastrine genera not yet recorded at Yanayacu, but which we expect to eventually find there based on extrapolation from their known geographic distributions, is provided

Building Civic Capacity: The History & Landscape of NYC Integration Activism 2012–2021 [post-print]

Background: New York City is one of the most segregated school districts in the country, but in the last nine years, school integration has moved from being marginal to a central education policy. Existing narratives have emphasized parents, school and political leaders, downplaying the significance of citywide coalitions of activists, especially youth activists. Purpose: We examine how grassroots activists contributed to transform school integration policy, and the opportunities and challenges as a result through urban regime theory and specifically civic capacity, which highlights how various constituencies build a shared agenda for policy change. Research Design: Working in partnership with four youth interviewers at two integration activist organizations, we conducted 72 semi-structured interviews with New York City student, parent and community activists. We also observed 36 hours of public meeting observations and collected publicly available documents, including 360 newspaper articles and policy documents in order to triangulate our findings. Conclusions: We find that activist coalitions made progress in developing integration civic capacity through increased collaboration among diverse stakeholders, notably youth, toward a shared definition of integration. However, growing tensions with rival coalitions and the fragmented political landscape of NYC limited the strength and durability of civic capacity

Characterization of Material Micro & Nano Structures Using Machine Learning Algorithms

In order to understand how changes to a material at the atomic and nano-scales impact the way a material behaves, it is necessary to measure the material at that scale. Scanning transmission Electron Microscopy (STEM) is one such approach. Over the last 5 years, computer vision has been completely revolutionized by the advent of deep neural networks (DNN). One challenge of using DNNs for image processing is that they require often large amounts of labelled data in order to build a usable algorithm (model). Researchers at Pacific Northwest National Laboratory (PNNL) have developed a few-shot algorithm which allows the model to be operated using limited data. Using data from a sample micrograph, a new neural network is implemented with the objective of aptly segmenting the micrograph and obtaining classifications for the microstructures. This model investigates the use of existing image segmentation techniques, particularly region-based techniques. The success of this approach can provide a rapid and reconfigurable tool for identifying these microstructures. This research conducted in collaboration with Pacific Northwest National Laboratory

Fanning the flames: How the European Union is fuelling a new arms race - Executive Summary

At the time of writing in March 2022, a war has broken out in eastern Europe following the illegal invasion of Ukraine by Russian troops. Towards the end of 2021 unrest in the Balkans came close to boiling point. Tensions in the South China Sea continue to simmer and threaten regional and global stability. Wars and violence continue in Afghanistan, in Central Africa, Iraq, several countries across the Sahel, Syria, and Yemen among other countries and regions experiencing constant violence and consequent displacement. Some of the world's most powerful nations are sabre-rattling, drafting and deploying troops, stockpiling military materiel, and actively preparing for war – including the European Union (EU) and some of its member states. Contrary to the EU's founding principle of promoting peace, it too has been charting a course to establish itself as a global military power. History has shown, however, that far from contributing to stability and peace, militarism fuels tension, instability, destruction and devastation.In a 'watershed moment', in response to the war in Ukraine, the EU announced that it would, for the first time, fund and supply lethal weapons to a country under attack through the European Peace Facility (EPF). While this move is unprecedented, it is not unexpected. The EU has been pursuing a military path since the entry in to force of the Lisbon Treaty in 2009, which provides the legal underpinning to create a common security and defence policy. Less than a decade later, in a new point of departure, the EU created specific budget lines to allocate funding to military-related projects. This decision firmly set the EU on a new and deeply worrying trajectory, where international political and social problems were to be addressed not only through dialogue and diplomacy, but also through the threat of military solutions

KCC2 is required for the survival of mature neurons but not for their development

The K+/Cl- co-transporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly contribute to the subsequent changes in neuronal structure and viability that lead to epileptogenesis, remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons was sufficient to rapidly induce apoptosis, an effect that was not abrogated via blockade of neuronal depolarization using Tetrodotoxin (TTX). In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization or dendritic structure. However, removing KCC2 in immature neurons was sufficient to ablate the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to the loss of KCC2 function. In contrast, KCC2 appears to play a minimal role in mediating neuronal development or architecture

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Clinical outcomes in ovarian cancer patients receiving three versus more cycles of chemotherapy after neoadjuvant treatment and interval cytoreductive surgery

ObjectivesTo compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy.MethodsWe conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively.ResultsA total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities.ConclusionsExtending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment

Stepwise pathogenic evolution of Mycobacterium abscessus.

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones