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The implementation of molecular techniques has been widely adopted throughout the life sciences except in the marine sciences. The latter trend is quickly being reversed as even more cutting-edge molecular platforms, referred to collectively as 'omics-related technologies, are being used in a number of laboratories that study various aspects of life in the marine environment. This review provides a brief overview of just a few representative studies that have used genomics, transcriptomics, or proteomics approaches to deepen our understanding, specifically, about the underlying molecular biology of harmful algae. The examples of the studies described here are particularly relevant in showing how the information gleaned from these technologies can uncover the genetic capacity of harmful algal bloom-forming species, can generate new hypotheses about mechanistic relationships that bridge gene—environment interactions, and can impinge on our understanding surrounding the ecology of these organisms.

Achieving global area-based conservation targets requires whole-of-government and whole-of-society approaches, particularly from biodiverse regions of the Global South. We present a practitioner-led examination of opportunities to expand the conservation network in Durban, South Africa, a biodiverse city, using local government mechanisms. We used local government spatial biodiversity and land-use planning data to identify conservation opportunities across tenure types, and an analytical framework to determine, at a high level, feasibility, effectiveness, policy/practice requirements, and climate resilience co-benefits. Traditional authority areas and private landholdings harbour most biodiversity outside conservation areas. Complementary land-use zones and unrealised conservation servitudes represent short-term interventions to increase conservation areas. Alignment of critical biodiversity with biophysical constraints offers significant potential conservation and sustainable development co-benefits. Priorities include developing mechanisms for area-based conservation in traditional authority areas and rezoning threatened vegetation. We provide mechanisms to increase Durban’s conservation estate, bridging the planning-implementation gap, with actionable learnings for Global South cities.

ObjectivesTo present our case series and management of Scedosporium apiospermum infections of the middle ear and mastoid, and review the current literature on this rare yet potentially life-threatening condition.MethodsMedical records of patients treated at the Royal Victorian Eye and Ear Hospital for S apiospermum middle ear and mastoid infections between 2009 and 2019 were reviewed. A literature search was conducted using PubMed, Medline and Cochrane Library databases.ResultsTwo patients were identified in our institution: a 62-year-old diabetic woman with otogenic skull base osteomyelitis, and a 12-year-old boy with unilateral chronic suppurative otitis media which developed after tympanostomy tube insertion. The persistence of otalgia and otorrhoea despite prolonged antibiotic treatment characterised these cases. Both patients received voriconazole, and achieved disease resolution without complications. Ten relevant cases were identified after review of the literature. Despite treatment, there were three patient deaths, and four patients with otological or neurological complications.ConclusionThe presence of a middle ear or mastoid infection refractory to appropriate topical and systemic antibiotics should prompt clinicians to consider a fungal infection. The role of surgical debridement in the treatment of S apiospermum infection of the middle ear and mastoid is equivocal.

Antimicrobial resistance is an emerging global health crisis. Consequently, we have a critical need to prolong our current arsenal of antibiotics, in addition to the development of novel treatment options. Acinetobacter baumannii is one of the world’s most problematic nosocomial pathogens. The combination of its intrinsic resistance and ability to acquire resistance markers allow this organism to adjust to antibiotic treatment. Despite being the primary barrier against antibiotic stress, our understanding of the A. baumannii membrane composition and its impact on resistance remains limited. In this study, we explored how the incorporation of host-derived polyunsaturated fatty acids (PUFAs) is associated with increased antibiotic susceptibility. Functional analyses of primary A. baumannii efflux systems indicated that AdeB-mediated antibiotic resistance was impacted by PUFA treatment. Molecular dynamics simulations of AdeB identified a specific morphological disruption of AdeB when positioned in the PUFA-enriched membrane. Collectively, we have shown that PUFAs can impact antibiotic efficacy via a vital relationship with antibiotic efflux pumps. Furthermore, this work has revealed that A. baumannii ’s unconditional desire for fatty acids may present a possible weakness in its multidrug resistance capacity. IMPORTANCE Antimicrobial resistance is an emerging global health crisis. Consequently, we have a critical need to prolong our current arsenal of antibiotics, in addition to the development of novel treatment options. Due to their relatively high abundance at the host-pathogen interface, PUFAs and other fatty acid species not commonly synthesized by A. baumannii may be actively acquired by A. baumannii during infection and change the biophysical properties of the membrane beyond that studied in standard laboratory culturing media. Our work illustrates how the membrane phospholipid composition impacts membrane protein function, which includes an important multidrug efflux system in extensively-drug-resistant A. baumannii . This work emphasizes the need to consider including host-derived fatty acids in in vitro analyses of A. baumannii . On a broader scope, this study presents new findings on the potential health benefits of PUFA in individuals at risk of contracting A. baumannii infections or those undergoing antibiotic treatment.

Objectives: To determine the effect of unknown exercise duration and an unexpected increase in exercise duration on rating of perceived exertion (RPE), affect, and running economy during treadmill running. Methods: Sixteen well trained male and female runners completed three bouts of treadmill running at 75% of their peak treadmill running speed. In the first trial, they were told to run for 20 minutes and were stopped at 20 minutes (20 MIN). In another trial, they were told to run for 10 minutes, but at 10 minutes were told to run for a further 10 minutes (10 MIN). In the final trial, they were not told for how long they would be running but were stopped after 20 minutes (unknown, UN). During each of the running bouts, RPE, oxygen consumption (ml/kg/min), heart rate (beats/min), stride frequency (min−1), affect scores (arbitrary units), and attentional focus (percentage associative thought scores) were recorded. Results: RPE increased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN and UN trials (p<0.05). The affect score decreased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN trial (p<0.05). Running economy, as measured by oxygen consumption, was significantly lower in the UN compared with the 20 MIN trial from 10 to 19 minutes (p<0.05). Conclusions: The change in RPE between 10 and 11 minutes in the 10 MIN trial suggests that RPE is not purely a measure of physical exertion, as treadmill speed was maintained at a constant pace both before and after the unexpected increase in exercise duration. The associated changes in affect score at similar times in the 10 MIN trial supports the hypothesis that RPE has an affective component.

The target pathogen of this study, Streptococcus pneumoniae , kills over 300,000 children <5 years of age every single year, and is the leading cause of pneumonia-associated mortality globally. While the capsular polysaccharide (CPS)-based vaccine Prevnar13 prevents serious illness caused by 13 serotypes, ongoing Prevnar13 use has driven the emergence of nonincluded serotypes as major causes of infection and disease. Streptococcus pneumoniae (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infections by vaccine-included serotypes but has led to increased infections by nonincluded serotypes. To date, high cost of PCVs has also limited their usefulness in low-income regions where disease burdens are highest. To overcome these limitations, serotype-independent vaccines are being actively researched. We have developed a whole-cell gamma-irradiated Spn vaccine (termed Gamma-PN) providing serotype-independent protection. We demonstrate that Gamma-PN immunization of mice or rabbits via the clinically relevant intramuscular route induces protein-specific antibodies able to bind numerous nonvaccine encapsulated serotypes, which mediate opsonophagocytic killing and protection against lethal challenges. Gamma-PN induced comparable or superior opsonophagocytic killing assay (OPKA) responses in rabbits to the licensed Prevnar 13 vaccine (PCV13) for vaccine-included serotypes, and a superior response to nonincluded serotypes, including emergent 22F and 35B. Additionally, despite a lower observed reactogenicity, administration of Gamma-PN without adjuvant resulted in higher OPKA responses and improved protection compared to adjuvanted Gamma-PN. To our knowledge, this has not been demonstrated previously for a whole-inactivated Spn vaccine. Eliminating the requirement for adjuvant comes with numerous benefits for clinical applications of this vaccine and poses interesting questions for the inclusion of adjuvant in similar vaccines in development. IMPORTANCE The target pathogen of this study, Streptococcus pneumoniae , kills over 300,000 children <5 years of age every single year, and is the leading cause of pneumonia-associated mortality globally. While the capsular polysaccharide (CPS)-based vaccine Prevnar13 prevents serious illness caused by 13 serotypes, ongoing Prevnar13 use has driven the emergence of nonincluded serotypes as major causes of infection and disease. To overcome this issue, we have developed a next-generation pneumococcal vaccine conferring serotype-independent protection. This vaccine shows equivalent or superior efficacy to Prevnar13, and performance was heightened when our vaccine was administered with no adjuvant. These findings should be considered for similar vaccines in development, as the benefit of adjuvant is often assumed and its automatic inclusion may be limiting product efficacy, resulting in potential abandonment of viable vaccine candidates, or prolonging their time to clinic.

Background Combined impacts from anthropogenic pressures and climate change threaten coastal ecosystems and their capacity to protect communities from hazards. One approach towards improving coastal protection is to implement “nature-based solutions” (NBS), which are actions working with nature to benefit nature and humans. Despite recent increases in global implementation of NBS projects for coastal protection, substantial gaps exist in our understanding of NBS performance. To help fill this gap, we systematically mapped the global evidence base on the ecological, physical, economic, and social performance of NBS interventions related to coastal protection. We focused on active NBS interventions, such as restoring or creating habitat, adding structure, or modifying sediment in six shallow biogenic ecosystems: salt marsh, seagrass, kelp forest, mangrove, coral reef, and shellfish reef. Methods We identified potentially relevant articles on the performance of NBS for coastal protection using predefined and tested search strategies across two indexing platforms, one bibliographic database, two open discovery citation indexes, one web-based search engine, and a novel literature discovery tool. We also searched 45 organizational websites for literature and solicited literature from 66 subject matter experts. Potentially relevant articles were deduplicated and then screened by title and abstract with assistance from a machine learning algorithm. Following title and abstract screening, we conducted full text screening, extracted relevant metadata into a predefined codebook, and analyzed the evidence base to determine the distribution and abundance of evidence and answer our research questions on NBS performance. Results Our search captured > 37,000 articles, of which 252 met our eligibility criteria for relevance to NBS performance for coastal protection and were included in the systematic map. Evidence stemmed from 31 countries and increased from the 1980s through the 2020s. Active NBS interventions for coastal protection were most often implemented in salt marshes (45%), mangrove forests (26%), and shellfish reefs (20%), whereas there were fewer NBS studies in seagrass meadows (4%), coral reefs (4%), or kelp beds (< 1%). Performance evaluations of NBS were typically conducted using observational or experimental methods at local spatial scales and over short temporal scales (< 1 year to 5 years). Evidence clusters existed for several types of NBS interventions, including restoration and addition of structures (e.g., those consisting of artificial, hybrid, or natural materials), yet evidence gaps existed for NBS interventions like alteration of invasive species. Evaluations of NBS performance commonly focused on ecological (e.g., species and population, habitat, community) and physical (e.g., waves, sediment and morphology) outcomes, whereas pronounced evidence gaps existed for economic (e.g., living standards, capital) and social (e.g., basic infrastructure, health) outcomes. Conclusions This systematic map highlights evidence clusters and evidence gaps related to the performance of active NBS interventions for coastal protection in shallow, biogenic ecosystems. The synthesized evidence base will help guide future research and management of NBS for coastal protection so that active interventions can be designed, sited, constructed, monitored, and adaptively managed to maximize co-benefits. Promising avenues for future research and management initiatives include implementing broad-scale spatial and temporal monitoring of NBS in multidisciplinary teams to examine not only ecological and physical outcomes but also economic and social outcomes, as well as conducting further synthesis on evidence clusters that may reveal measures of effect for specific NBS interventions. Since NBS can deliver multiple benefits, measuring a diverse suite of response variables, especially those related to ecosystem function, as well as social and economic responses, may help justify and improve societal benefits of NBS. Such an approach can help ensure that NBS can be strategically harnessed and managed to meet coastal protection goals and provide co-benefits for nature and people.

The spread of artemisinin resistant parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites two mechanisms: 'delayed death' by inhibiting the bacterium-like ribosomes of the apicoplast, and 'quick-killing' that kills rapidly across the entire blood stage development. Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against (the most virulent human malaria) and (a monkey parasite that frequently infects humans). Seventeen analogues showed improved quick-killing against both species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for and , respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of parasites (<12 hrs treatment) and were >5-fold more selective against than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite and the gram-positive bacterium did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment. The azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quick-killing antimalarial activity.

Streptococcus pneumoniae is the leading cause of bacterial paediatric meningitis after the neonatal period worldwide, but the bacterial factors and pathophysiology that drive pneumococcal meningitis are not fully understood. In this work, we have identified differences in raffinose utilization by S. pneumoniae isolates of identical serotype and sequence type from the blood and cerebrospinal fluid (CSF) of a single pediatric patient with meningitis. The blood isolate displayed defective raffinose metabolism, reduced transcription of the raffinose utilization pathway genes, and an inability to grow in vitro when raffinose was the sole carbon source. The fitness of these strains was then assessed using a murine intranasal infection model. Compared with the CSF isolate, mice infected with the blood isolate displayed higher bacterial numbers in the nose, but this strain was unable to invade the ears of infected mice. A premature stop codon was identified in the aga gene in the raffinose locus, suggesting that this protein likely displays impaired alpha-galactosidase activity. These closely related strains were assessed by Illumina sequencing, which did not identify any single nucleotide polymorphisms (SNPs) between the two strains. However, these wider genomic analyses identified the presence of an alternative alpha-galactosidase gene that appeared to display altered sequence coverage between the strains, which may account for the observed differences in raffinose metabolic capacity. Together, these studies support previous findings that raffinose utilization capacity contributes to disease progression, and provide insight into a possible alternative means by which perturbation of this pathway may influence the behavior of pneumococci in the host environment, particularly in meningitis.