The African mosquito-borne diseasosome: Geographical patterns and range expansion

Mosquito-borne diseases (MBDs) such as malaria, dengue, and Rift Valley fever threaten public health and food security globally. Despite their cohesive nature, they are typically treated as distinct entities. Applying biological system analysis to the African MBDs from a One Health perspective, we provide the first biogeographic description of the African mosquito fauna corresponding with the pathogens they transmit. After compiling records accumulated over a century, we find that there are 677 mosquito species in Africa, representing 16 genera, and 151 mosquito-borne pathogens (MBPs) circulating primarily among wild tetrapods, dominated by viruses (95) and protozoans (47). We estimate that reported MBPs represent ~1% of the actual number. Unlike mosquitoes, African arboviruses and mammalian plasmodia represent a higher share of the World's total based on the area- species richness relationship (P<0.0001), explaining the disproportional large share of global MBPs that originated from Africa. Species richness of African mosquitoes and MBPs are similarly concentrated along the equator, peaking in central Africa, with a secondary ridge along eastern Africa. Moderate diversity and low endemicity in mosquitoes across the Sahel reveals a fauna with high propensity for long-range migration. Regional differences in species richness, endemicity, and composition agreed with country-based results. The composition of mosquitoes and MBPs separates sub-Saharan Africa from north Africa, in accordance with the Palearctic and Afrotropical faunal realms, and west and central Africa are clustered together distinctly from the cluster of eastern and southern Africa. With ~25% of the species occupying a single country, ~50% in 1-3 countries and <5% found in >25 countries, the typical ranges of both mosquitoes and MBPs are surprisingly small. The striking similarity in diversity and especially in range distributions of mosquitoes and MBPs suggest that most MBPs are transmitted by one or few narrow-range mosquito vectors. Exceptionally widespread mosquito species (e.g., Ae. aegypti, Cx. quinquefasciatus, and 10 Anopheles species) feed preferentially on people and domestic animals, and nearly half are windborne migrants. Likewise, exceptionally widespread MBPs are transmitted between people or domestic animals and are vectored by one or more of the aforementioned widespread mosquitoes. Our results suggest that few MBPs have undergone a dramatic range expansion, after adapting to people or domestic animals as well as to exceptionally-widespread mosquitoes. During the intermediate phase of range expansion, MBPs extend their vector and vertebrate host ranges with a concomitant gradual increase in geographical range. Because range size may serve as a marker of the phase of range expansion, ranking the African MBPs according to range, we identified several MBPs that pose elevated risk for disease emergence (e.g., Wesselsbron virus). Taken together, our database, approach, and results can help improve MBD surveillance and lead to a better understanding of disease emergence. This knowledge has the potential to improve capacity to prevent and mitigate new and emerging MBD threats.

Synthesis of N-Glycans Implicated in Asthma and Allergy

<p><b>Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response.</b></p> <p>This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.</p>

Synthesis of N-Glycans Implicated in Asthma and Allergy

<p><b>Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response.</b></p> <p>This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.</p>

Synthesis of N-glycans implicated in asthma and allergy

<p>Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response. This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.</p>

Synthesis of N-glycans implicated in asthma and allergy

<p>Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response. This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.</p>

Museum Leadership in Practice: A New Zealand Case Study

<p>Museum leadership is an under investigated area of museum studies. This dissertation contributes to museum leadership research by applying leadership theory to a case study of the career of Jim Geddes, a museum director who works in the town of Gore in Southland, New Zealand. In 2008 Geddes won Museums Aotearoa's inaugural Individual Achievement Award for putting Gore on the national cultural map by establishing the Eastern Southland Gallery, the Hokonui Heritage Centre, the Croydon Aviation Museum and for expanding Gore's Historical Museum. How did Geddes achieve this successful cultural entrepreneurship in such an unlikely small rural town? The central research question asks how leadership has manifested itself in Gore's museums during Geddes' tenure from 1983 to the present. The theoretical framework draws on leadership theory, particularly the work of Suchy and others, who theorise leadership as a social practice rather than a set of management techniques. Several qualitative research methods are employed including interviews with Geddes and key museum stakeholders coupled with a review of how the media have presented Geddes' work. This research data is then compared against leadership theory, noting the convergences and divergences. The dissertation is the first in-depth New Zealand study to test the application of contemporary leadership theory to one museum leader's practice. The findings reveal that, while Geddes is not a conscious leader, his practice has a striking similarity to the engaging transformational leadership model in terms of stakeholder engagement and the inter-personal and emotional elements of leadership. This research provides a deeper understanding of the career of a successful local museum director, suggesting that a sense of place can function as a mechanism for museum leaders to profitably engage with stakeholders. It also presents the argument that successful leadership is a practice, a mode of operating and interacting with others that if consistently applied can spark a series of positive events for museums and their leaders. After considering the implications of this case study for museum practice, training and professional development, the dissertation concludes with five recommendations to improve museum leadership development in New Zealand.</p>

Museum Leadership in Practice: A New Zealand Case Study

<p>Museum leadership is an under investigated area of museum studies. This dissertation contributes to museum leadership research by applying leadership theory to a case study of the career of Jim Geddes, a museum director who works in the town of Gore in Southland, New Zealand. In 2008 Geddes won Museums Aotearoa's inaugural Individual Achievement Award for putting Gore on the national cultural map by establishing the Eastern Southland Gallery, the Hokonui Heritage Centre, the Croydon Aviation Museum and for expanding Gore's Historical Museum. How did Geddes achieve this successful cultural entrepreneurship in such an unlikely small rural town? The central research question asks how leadership has manifested itself in Gore's museums during Geddes' tenure from 1983 to the present. The theoretical framework draws on leadership theory, particularly the work of Suchy and others, who theorise leadership as a social practice rather than a set of management techniques. Several qualitative research methods are employed including interviews with Geddes and key museum stakeholders coupled with a review of how the media have presented Geddes' work. This research data is then compared against leadership theory, noting the convergences and divergences. The dissertation is the first in-depth New Zealand study to test the application of contemporary leadership theory to one museum leader's practice. The findings reveal that, while Geddes is not a conscious leader, his practice has a striking similarity to the engaging transformational leadership model in terms of stakeholder engagement and the inter-personal and emotional elements of leadership. This research provides a deeper understanding of the career of a successful local museum director, suggesting that a sense of place can function as a mechanism for museum leaders to profitably engage with stakeholders. It also presents the argument that successful leadership is a practice, a mode of operating and interacting with others that if consistently applied can spark a series of positive events for museums and their leaders. After considering the implications of this case study for museum practice, training and professional development, the dissertation concludes with five recommendations to improve museum leadership development in New Zealand.</p>

Computational simulations reveal that Abl activity controls cohesiveness of actin networks in growth cones

Extensive studies of growing axons have revealed many individual components and protein interactions that guide neuronal morphogenesis. Despite this, however, we lack any clear picture of the emergent mechanism by which this nanometer-scale biochemistry generates the multi-micron scale morphology and cell biology of axon growth and guidance in vivo. To address this, we studied the downstream effects of the Abl signaling pathway using a computer simulation software (MEDYAN) that accounts for mechanochemical dynamics of active polymers. Previous studies implicate two Abl effectors, Arp2/3 and Enabled, in Abl-dependent axon guidance decisions. We now find that Abl alters actin architecture primarily by activating Arp2/3, while Enabled plays a more limited role. Our simulations show that simulations mimicking modest levels of Abl activity bear striking similarity to actin profiles obtained experimentally from live-imaging of actin in wild type axons in vivo. Using a graph-theoretical filament-filament contact analysis, moreover, we find that networks mimicking hyperactivity of Abl (enhanced Arp2/3) are fragmented into smaller domains of actin that interact weakly with each other, consistent with the pattern of actin fragmentation observed upon Abl overexpression in vivo. Two perturbative simulations further confirm that high Arp2/3 actin networks are mechanically disconnected and fail to mount a cohesive response to perturbation. Taken together, these data provide a molecular-level picture of how the large-scale organization of the axonal cytoskeleton arises from the biophysics of actin networks.

First report of Gentian Kobu-sho-associated virus infecting peony in the United States and the Netherlands

Lemoine’s disease of peonies (LDP) is associated with root galls that could lead to stunted growth and reduced flowering. In the quest to identify the causal agent(s) of LDP, two symptomatic plants (cv. Alice Crousse [AC] and Alice Harding [AH]) were sampled in Arkansas in 2019 and sequenced as described (Shaffer et al., 2019). Gentian Kobu-sho-associated virus (GKaV) was present in both plants. The contigs from AH were mapped to the reference sequence of GKaV (AB698918; Kobayashi et al. 2013) yielding 87% of the ~23kb genome, which was completed by Sanger sequencing (Genbank accession no. MW646307) as per Thekke-Veetil et al. (2013). Sample AC was co-infected with cycas necrotic stunt virus (CNSV) and AH with CNSV, citrus leaf blotch virus and lychnis mottle virus. Gentiana triflora -Pall. and G. scabra Bunge plants with Kobu-sho disease symptoms that include galls/tumors on all parts of gentian were also positive for GKaV (Iwadate et al. 2006; Kodama et al. 2004). The striking similarity between symptoms of the two diseases led to the development of a GKaV screening protocol to determine its presence in LPD-affected material. Primers GKaVF 5’-TTAGTGATGAGTGCCTTTTCC-3’ and GKaVR 5’-CTGCCAGTCTTCTTGTGAACC-3’ which amplify a 574 nt region of the virus were used to screen 144 peony leaf samples from the University of Michigan’s Nichols Arboretum collection. Thirty-two (32) plants were stunted whereas 112 displayed normal growth. Nineteen (59%) of the stunted plants tested positive for GKaV compared to eight (6.5%) of the symptomless plants. Partial GKaV genome sequences of three isolates from stunted Michigan plants were deposited in GenBank (MW646310-12) along with three GKaV isolates from Arkansas collected at the same location and time as AC and AH (MW646308-9, MW646313); two had LDP symptoms and the status of the third was unknown. In 2020 four peony root samples from the Netherlands were sequenced as described in Hammond et al. (2021) to identify the causal agent of root galls in three samples. GKaV was present in two: cv. Paul M. Wild and #40391499 and the nearly complete genome sequences were deposited in GenBank (MW916234-5). ‘Paul M. Wild’ was co-infected with cucumber mosaic virus and tobacco rattle virus and #40391499 with a novel amalgavirid. The third symptomatic cv. Many Happy Returns was infected with CNSV while the fourth symptomless cv. Itoh was infected with CNSV and amazon lily mild mottle virus (Shaffer et al., 2021). Percent pairwise identities between sequences were calculated using the SDT Version 1.2 (Muhire et al. 2014). The six partial GKaV sequences from Michigan and Arkansas share 92-100% nt (98-100% aa) identity. Analysis of the three near full length GKaV genomes presented in this communication and the type isolate (NC020252) showed 87-91% nt (93-97% aa) identity. This report provides evidence that GKaV infects peony and is present in Europe and North America. The association of GKaV with LDP is not established, but the virus has been detected in 59% of the plants showing disease symptoms and in ˂7% of asymptomatic plants. We hypothesize that as in the case of Gentian, GKaV has an extended incubation period in peony (Kobayashi et al., 2013) and its titer may fluctuate between seasons as it has been well established for other crops (Villamor et al., 202x). The industry does not perform virus clean-up routinely; propagation material should be tested for GKaV to minimize its spread since the virus may be associated with LDP in at least some cultivars.