Initial Public Health Laboratory Response After Hurricane Maria - Puerto Rico, 2017.

Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.

Spider-venom peptides: structure, pharmacology, and potential for control of insect pests.

Spider venoms are an incredibly rich source of disulfide-rich insecticidal peptides that have been tuned over millions of years to target a wide range of receptors and ion channels in the insect nervous system. These peptides can act individually, or as part of larger toxin cabals, to rapidly immobilize envenomated prey owing to their debilitating effects on nervous system function. Most of these peptides contain a unique arrangement of disulfide bonds that provides them with extreme resistance to proteases. As a result, these peptides are highly stable in the insect gut and hemolymph and many of them are orally active. Thus, spider-venom peptides can be used as stand-alone bioinsecticides, or transgenes encoding these peptides can be used to engineer insect-resistant crops or enhanced entomopathogens. We critically review the potential of spider-venom peptides to control insect pests and highlight their advantages and disadvantages compared with conventional chemical insecticides.

Onsite investigation at a mail-order hatchery following a multistate Salmonella illness outbreak linked to live poultry-United States, 2018.

Centers for Disease Control and Prevention (CDC), health departments, and other state and federal partners have linked contact with live poultry to 70 human Salmonella outbreaks in the United States from 2000 to 2017, which resulted in a total of 4,794 illnesses, 894 hospitalizations, and 7 deaths. During human salmonellosis outbreaks environmental sampling is rarely conducted as part of the outbreak investigation. CDC was contacted by state health officials on June 12, 2018, to provide support during an investigation of risk factors for Salmonella infections linked to live poultry originating at a mail-order hatchery. From January 1, 2018, to June 15, 2018, 13 human Salmonella infections in multiple states were attributed to exposure to live poultry from a single hatchery. Two serotypes of Salmonella were associated with these infections, Salmonella Enteritidis and Salmonella Litchfield. Molecular subtyping of the S. Enteritidis clinical isolates revealed they were closely related genetically (within 0 to 9 alleles) by core genome multi-locus sequence typing (cgMLST) to isolates obtained from environmental samples taken from hatchery shipping containers received at retail outlets. Environmental sampling and onsite investigation of practices was conducted at the mail-order hatchery during an investigation on June 19, 2018. A total of 45 environmental samples were collected, and 4 (9%) grew Salmonella. A chick box liner from a box in the pre-shipping area yielded an isolate closely related to the S. Enteritidis outbreak strain (within 1 to 9 alleles by cgMLST). The onsite investigation revealed lapses in biosecurity, sanitation, quality assurance, and education of consumers. Review of Salmonella serotype testing performed by the hatchery revealed that the number of samples and type of samples collected monthly varied. Also, S. Enteritidis was identified at the hatchery every year since testing began in 2016. Recommendations to the hatchery for biosecurity, testing, and sanitation measures were made to help reduce burden of Salmonella in the hatchery and breeding flocks, thereby reducing the occurrence of human illness.

Lessons from the reestablishment of Public Health Laboratory activities in Puerto Rico after Hurricane Maria.

Public Health Laboratories (PHLs) in Puerto Rico did not escape the devastation caused by Hurricane Maria. We implemented a quality management system (QMS) approach to systematically reestablish laboratory testing, after evaluating structural and functional damage. PHLs were inoperable immediately after the storm. Our QMS-based approach began in October 2017, ended in May 2018, and resulted in the reestablishment of 92% of baseline laboratory testing capacity. Here, we share lessons learned from the historic recovery of the largest United States' jurisdiction to lose its PHL capacity, and provide broadly applicable tools for other jurisdictions to enhance preparedness for public health emergencies.

Engaging rural Australian communities in National Science Week helps increase visibility for women researchers.

During a week-long celebration of science, run under the federally supported National Science Week umbrella, the Catch a Rising Star: women in Queensland research (CaRS) programme flew scientists who identify as women to nine regional and remote communities in the Australian State of Queensland. The aim of the project was twofold: first, to bring science to remote and regional communities in a large, economically diverse state; and second, to determine whether media and public engagement provides career advancement opportunities for women scientists. This paper focuses on the latter goal. The data show: (i) a substantial majority (greater than 80%) of researchers thought the training and experience provided by the programme would help develop her career as a research scientist in the future, (ii) the majority (65%) thought the programme would help relate her research to end users, industry partners or stakeholders in the future, and (iii) analytics can help create a compelling narrative around engagement metrics and help to quantify influence. During the week-long project, scientists reached 600 000 impressions on one social media platform (Twitter) using a program hashtag. The breadth and depth of the project outcomes indicate funding bodies and employers could use similar data as an informative source of metrics to support hiring and promotion decisions. Although this project focused on researchers who identify as women, the lessons learned are applicable to researchers representing a diverse range of backgrounds. Future surveys will help determine whether the CaRS programme provided long-term career advantages to participating scientists and communities.

A Transdisciplinary Approach to Managing Emerging and Resurging Mosquito-Borne Diseases in the Western Pacific Region.

Mosquitoes transmit a number of harmful diseases that have an impact on local communities and visitors, and many pose a threat to neighboring countries. As federal monitoring budgets shrink across the world, the increasing importance of citizen scientists in monitoring and identifying invasive species, as well as acting to prevent these diseases, are discussed. Examples of past mosquito management programs are provided, and future directions are discussed with an emphasis on the Western Pacific Region.

Resistance is not Futile: It Shapes Insecticide Discovery.

Conventional chemical control compounds used for the management of insect pests have been much maligned, but still serve a critical role in protecting people and agricultural products from insect pests, as well as conserving biodiversity by eradicating invasive species. Although biological control can be an effective option for area-wide management of established pests, chemical control methods are important for use in integrated pest management (IPM) programs, as well as in export treatments, eradicating recently arrived invasive species, and minimizing population explosions of vectors of human disease. Cogitated research and development programs have continued the innovation of insecticides, with a particular focus on combating insecticide resistance. Recent developments in the fields of human health, protecting the global food supply, and biosecurity will be highlighted.

Venomous and poisonous Australian animals of veterinary importance: a rich source of novel therapeutics.

Envenomation and poisoning by terrestrial animals (both vertebrate and invertebrate) are a significant economic problem and health risk for domestic animals in Australia. Australian snakes are some of the most venomous animals in the world and bees, wasps, ants, paralysis ticks, and cane toads are also present as part of the venomous and poisonous fauna. The diagnosis and treatment of envenomation or poisoning in animals is a challenge and can be a traumatic and expensive process for owners. Despite the potency of Australian venoms, there is potential for novel veterinary therapeutics to be modeled on venom toxins, as has been the case with human pharmaceuticals. A comprehensive overview of envenomation and poisoning signs in livestock and companion animals is provided and related to the potential for venom toxins to act as therapeutics.

Site-specific Labeling of a Protein Lysine Residue By Novel Kinetic Labeling Combinatorial Libraries.

The first example of a kinetic labeling library designed to enable the discovery of affinity labels is presented. Each library component (1) consists of a variable peptidyl component linked to a biotinyl moiety by a 4-mercaptobenzoyl linker in thioester format. We demonstrate that an affinity label can be uncovered by measuring reaction rates between library pools and the protein target, human serum albumin (HSA) and identifying significant outliers. By choosing peptide functionality compatible with a potentially reactive thioester labeling entity, libraries can be screened in pools. It is noteworthy that a limited subset of amino acids (R, S, E, F, Y, l, M, W, and Q) that compose the affinity moiety is sufficient to produce rate variances that guide the discovery process. After two rounds of deconvolution, J-FLYEE-NH2 (7-E) emerges as a bona fide affinity label of HSA. Unlike known affinity labels, the affinity moiety is not retained in the protein product, but is extruded upon acylation of the protein. This feature affords a method of introducing various payloads, without extraneous elements, onto protein frameworks.

Isolation of an orally active insecticidal toxin from the venom of an Australian tarantula.

Many insect pests have developed resistance to existing chemical insecticides and consequently there is much interest in the development of new insecticidal compounds with novel modes of action. Although spiders have deployed insecticidal toxins in their venoms for over 250 million years, there is no evolutionary selection pressure on these toxins to possess oral activity since they are injected into prey and predators via a hypodermic needle-like fang. Thus, it has been assumed that spider-venom peptides are not orally active and are therefore unlikely to be useful insecticides. Contrary to this dogma, we show that it is possible to isolate spider-venom peptides with high levels of oral insecticidal activity by directly screening for per os toxicity. Using this approach, we isolated a 34-residue orally active insecticidal peptide (OAIP-1) from venom of the Australian tarantula Selenotypus plumipes. The oral LD50 for OAIP-1 in the agronomically important cotton bollworm Helicoverpa armigera was 104.2±0.6 pmol/g, which is the highest per os activity reported to date for an insecticidal venom peptide. OAIP-1 is equipotent with synthetic pyrethroids and it acts synergistically with neonicotinoid insecticides. The three-dimensional structure of OAIP-1 determined using NMR spectroscopy revealed that the three disulfide bonds form an inhibitor cystine knot motif; this structural motif provides the peptide with a high level of biological stability that probably contributes to its oral activity. OAIP-1 is likely to be synergized by the gut-lytic activity of the Bacillus thuringiensis Cry toxin (Bt) expressed in insect-resistant transgenic crops, and consequently it might be a good candidate for trait stacking with Bt.

SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the SpiderP website.

Effects of vegetation, corridor width and regional land use on early successional birds on powerline corridors.

Powerline rights-of-way (ROWs) often provide habitat for early successional bird species that have suffered long-term population declines in eastern North America. To determine how the abundance of shrubland birds varies with habitat within ROW corridors and with land use patterns surrounding corridors, we ran Poisson regression models on data from 93 plots on ROWs and compared regression coefficients. We also determined nest success rates on a 1-km stretch of ROW. Seven species of shrubland birds were common in powerline corridors. However, the nest success rates for prairie warbler (Dendroica discolor) and field sparrow (Spizella pusilla) were <21%, which is too low to compensate for estimated annual mortality. Some shrubland bird species were more abundant on narrower ROWs or at sites with lower vegetation or particular types of vegetation, indicating that vegetation management could be refined to favor species of high conservation priority. Also, several species were more abundant in ROWs traversing unfragmented forest than those near residential areas or farmland, indicating that corridors in heavily forested regions may provide better habitat for these species. In the area where we monitored nests, brood parasitism by brown-headed cowbirds (Molothrus ater) occurred more frequently close to a residential area. Although ROWs support dense populations of shrubland birds, those in more heavily developed landscapes may constitute sink habitat. ROWs in extensive forests may contribute more to sustaining populations of early successional birds, and thus may be the best targets for habitat management.

Spider-venom peptides as bioinsecticides.

Over 10,000 arthropod species are currently considered to be pest organisms. They are estimated to contribute to the destruction of ~14% of the world's annual crop production and transmit many pathogens. Presently, arthropod pests of agricultural and health significance are controlled predominantly through the use of chemical insecticides. Unfortunately, the widespread use of these agrochemicals has resulted in genetic selection pressure that has led to the development of insecticide-resistant arthropods, as well as concerns over human health and the environment. Bioinsecticides represent a new generation of insecticides that utilise organisms or their derivatives (e.g., transgenic plants, recombinant baculoviruses, toxin-fusion proteins and peptidomimetics) and show promise as environmentally-friendly alternatives to conventional agrochemicals. Spider-venom peptides are now being investigated as potential sources of bioinsecticides. With an estimated 100,000 species, spiders are one of the most successful arthropod predators. Their venom has proven to be a rich source of hyperstable insecticidal mini-proteins that cause insect paralysis or lethality through the modulation of ion channels, receptors and enzymes. Many newly characterized insecticidal spider toxins target novel sites in insects. Here we review the structure and pharmacology of these toxins and discuss the potential of this vast peptide library for the discovery of novel bioinsecticides.

Aurora-A over-expression in high-grade PIN lesions and prostate cancer.

BACKGROUND: Over-expression of Aurora-A (Aurora 2 kinase, STK-15), a protein found in centrosomes thought to be associated with genetic instability, has been previously documented in prostate cancer [Pihan et al.: Cancer Res 61(5):2212-2219, 2001]. It is unknown if this protein is also over-expressed in high-grade prostatic intraepithelial neoplasia (PIN) lesions. METHODS: PIN lesions were examined for increased Aurora-A using immunohistochemical staining on archival paraffin embedded prostatectomy tissue. Aurora-A expression was scored using size, number, and staining intensity. Protein expression was examined and compared between stromal cells, normal glands, high-grade PIN lesions, and invasive cancer. RESULTS: Immunohistochemistry shows an increased expression of Aurora-A in 96% of high-grade PIN cases, and 98% in cancer lesions. Twenty-nine percent of cases of normal glands from cancerous prostates also showed increased Aurora-A expression. CONCLUSIONS: Over-expression of Aurora-A is present in some normal and the majority of high-grade PIN lesions indicating that this may be an early event that leads to the genetic instability seen in prostate carcinogenesis.