Publication date: February 2017 Source:Accident Analysis & Prevention, Volume 99, Part A Author(s): David A. Lombardi, William J. Horrey, Theodore K. Courtney Objective Given the aging U.S. population and resulting number of older drivers in the coming years, it is important to understand the factors leading to their involvement in vehicle crashes and develop counter-measures to reduce their frequency and severity. This is also useful for helping older adults “age in place” in terms of accessibility, mobility, quality of life and safety. Thus, the objective of this study was to provide up-to-date data on differences in age-related risks and rates for involvement in fatal intersection motor-vehicle crashes in the US. Methods Pooled data for the years 2011–2014 from the FARS, a census of fatal traffic crashes within the 50 States, the District of Columbia, and Puerto Rico, created by the US National Highway Traffic Safety Administration (NHTSA) were used to calculate summary statistics including annualized crash rates. Multivariate logistic regression models were used to evaluate age and gender-related differences in fatal intersection crash risk, controlling for covariates. An induced exposure analysis was conducted to calculate crash involvement ratios (CIRs) for all two-vehicle fatal intersection crashes. Older and younger drivers were compared with respect to the presence of factors related to intersection crashes using a multivariate Poisson regression model. Results During the period of 2011–2014, among the reported 120,809 fatal accidents in the US involving 178,489 drivers of vehicles, 48,733 (28%) were drivers involved in fatal intersection crashes. Age-adjusted annualized fatal intersection crash rates per 100,000 licensed drivers were highest for drivers aged 85 or older (9.89/100,000), followed by 20 years of age (8.93/100,000). Teen and older drivers (55+ years of age) were over-involved in fatal intersection crashes, drivers from 20 to 54 years old were under-involved. Male and female drivers, 70–74 years of age, were 20% and 21%, respectively, more likely to be involved in a fatal intersection crash than 20–24year olds (of same gender). By age 85, fatal intersection crash risk for all drivers was almost doubled. Significant differences in factors related to crashes involving younger (<65) and older (65+ years) drivers were time of day, lighting and weather conditions, day of week, roadway type and number of lanes, presence of visible traffic controls, speed limit and estimated driving speed, and whether the driver was deemed at fault for the crash Conclusion The results provide the most up-to-date analysis of aging and fatal intersection crash risk in the US, and underscore several trends worthy of further investigation. Older adults face a number of challenges associated with natural aging, including sensory, perceptual, cognitive and motor declines that may impact their driving. As with younger drivers, expanded or renewed approaches to driver training at licensing renewals, as well as safety-based technological advances are viable avenues toward improving the safety outlook for older adults.
Publication date: December 2016 Source:Animal Behaviour, Volume 122 Author(s): Christoph von Borell, Lars Kulik, Anja Widdig Although personality has been widely studied among animal species, only a few studies have investigated the long-term development of personality during early ontogeny. In fact, no study of nonhuman primates has consistently mapped personality development from birth to adulthood. Our study aimed at closing this gap by examining the development of personality among free-ranging rhesus macaques, Macaca mulatta, using longitudinal behavioural data of 24 subjects (3758h) collected from birth to 7 years of age on the island of Cayo Santiago, Puerto Rico, U.S.A. In our analyses we combined different frameworks of animal personality research to discuss behavioural differences in terms of latent personality models, behavioural syndromes and behavioural characters. The results showed that a core model of rhesus macaque personality, comprising three latent factors (Fearfulness, Aggression, Sociability), can already be established over the course of the first 7 years of life. However, only Fearfulness emerged consistently throughout development. While the factor of Sociability diffused during maturation, Aggression stabilized towards adulthood after having inconsistent loadings during infancy. When assessing correlations among behaviours separately on the within- and between-individual level, again only Fearfulness showed significant results averaged over the entire study period and can therefore be classified as behavioural syndrome or behavioural character. We discuss differences in correlations, interactions between sex and age and the effect of maternal rank as potential source of differences in stability of latent traits. Furthermore, we assessed plasticity of behaviour with regard to first maternity in females and natal dispersal of males. While the latter was accompanied by an increase of fearful behaviour and decrease of physical aggression, first maternity was marked by a mixed pattern of changes. Overall, our results suggest that rhesus macaques are not born into their personality, but grow into it.
Publication date: Available online 2 November 2016 Source:Vaccine Author(s): Michael M. Pieler, Sarah Frentzel, Dunja Bruder, Michael W. Wolff, Udo Reichl Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening studies requiring fast purification protocols. Graphical abstract
Publication date: December 2016 Source:Leukemia Research, Volume 51 Author(s): David P. Steensma The term “refractory anemia” was used in 1937 by Cornelius Parker Rhoads to describe patients whose anemia did not improve after treatment with liver extract or iron salts, and this term has been used to denote patients with certain subtypes of myelodysplastic syndromes (MDS) since the 1976 and 1982 French-American-British (FAB) classifications of acute leukemias and MDS. In 2016, the World Health Organization (WHO) proposed elimination of “refractory anemia” in a more general proposal for reclassification of myeloid neoplasia. A scandal relating to Dr. Rhoads’ possibly unethical medical experiments on anemic patients in Puerto Rico in 1931 and a racially offensive letter he wrote during that period prompted an international incident and Congressional-level inquiry. This dark history, as well as continued terminological problems with refractory anemia, suggest that this hoary term has indeed worn out its usefulness. This article reviews the history of “refractory anemia” and evolution in its use over the past 80 years. Rhoads' personal history, the potentially confusing nature of “refractory anemia”, and the fact that it is possible none of the 100 patients Rhoads described in 1937 actually had MDS all support the new WHO reclassification proposal to eliminate this term.
Publication date: Available online 19 October 2016 Source:European Journal of Medicinal Chemistry Author(s): Anastasiya S. Sokolova, Оlga I. Yarovaya, Dmitry S. Baev, Аndrey V. Shernyukov, Anna A. Shtro, Vladimir V. Zarubaev, Nariman F. Salakhutdinov A series of camphor derived imines was synthesised and evaluated in vitro for antiviral activity. Theoretical evaluations of ADME properties were also carried out. Most of these compounds exhibited significant activity against the drug-resistant strains of influenza A virus. Especially, compounds 2 (SI = 632) and 3 (SI = 417) presented high inhibition against influenza subtypes A/Puerto Rico/8/34 and A/California/07/09 of H1N1pdm09. Analysis of the structure-activity relationship showed that the activity was strongly dependent on the length of the aliphatic chain: derivatives with a shorter chain possessed higher activity, while the suppressing action of compounds with long aliphatic chains was lower. Graphical abstract
Publication date: October 2016 Source:Journal of the American Academy of Child & Adolescent Psychiatry, Volume 55, Issue 10, Supplement Author(s): Joalex L. Antongiorgi, Gustavo Fors, JeanMarie Acevedo, Gloria Gonzalez Tejera, Gloria M. Suau Sanchidrian
Publication date: Available online 15 October 2016 Source:World Neurosurgery Author(s): Yarelis Alvarado Reyes, Alexandra Perez, Gloria Rodriguez-Vega Objective Vitamin D deficiency has been associated with increased risk and adverse outcomes in many clinical settings including cardiovascular disease, stroke, and critically ill patients. Therefore we aimed to determine whether vitamin D deficiency had any effect in aneurysmal subarachnoid hemorrhage (aSAH) clinical outcomes. Methods A retrospective record review was conducted in a tertiary community hospital in Puerto Rico. Adult patients admitted to the neurosurgical intensive care unit (NICU) with a diagnosis of aSAH from January 2013 to July 2014, who had a 25-hydroxyvitamin-D level drawn, were included. Results A total of 40 patients were admitted with a diagnosis of aSAH and 33 met the inclusion criteria. Overall, 81% of patients were vitamin D deficient or insufficient. Subjects were grouped into those with vitamin D deficiency (n=13) and those without (n=20). Except for a larger prevalence of coronary artery disease, all other baseline parameters were similar. No significant difference in hospital mortality was observed (p=0.676). The percentage of vasospasms, vasopressor use, hydrocephalus, and infections was also similar. An increase in length of NICU stay and respiratory failure was observed in the vitamin D deficient group but it was not statistically significant. Conclusion A high prevalence of vitamin D deficiency and insufficiency was found among patients admitted with a diagnosis of aSAH in this cohort. Despite this no difference in clinical outcomes was observed in patients when compared by vitamin D group. Further studies are needed to assess potential effects of vitamin D deficiency in this patient population including long term follow-up after discharge.
Publication date: Available online 1 October 2016 Source:Geochimica et Cosmochimica Acta Author(s): Heather L. Buss, María Chapela Lara, Oliver W. Moore, Andrew C. Kurtz, Marjorie S. Schulz, Art F. White Lithologic differences give rise to the differential weatherability of the Earth’s surface and globally variable silicate weathering fluxes, which provide an important negative feedback on climate over geologic timescales. To isolate the influence of lithology on weathering rates and mechanisms, we compare two nearby catchments in the Luquillo Critical Zone Observatory in Puerto Rico, which have similar climate history, relief and vegetation, but differ in bedrock lithology. Regolith and pore water samples with depth were collected from two ridgetops and at three sites along a slope transect in the volcaniclastic Bisley catchment and compared to existing data from the granitic Río Icacos catchment. The depth variations of solid-state and pore water chemistry and quantitative mineralogy were used to calculate mass transfer (tau) and weathering solute profiles, which in turn were used to determine weathering mechanisms and to estimate weathering rates. Regolith formed on both lithologies is highly leached of most labile elements, although Mg and K are less depleted in the granitic than in the volcaniclastic profiles, reflecting residual biotite in the granitic regolith not present in the volcaniclastics. Profiles of both lithologies that terminate at bedrock corestones are less weathered at depth, near the rock-regolith interfaces. Mg fluxes in the volcaniclastics derive primarily from dissolution of chlorite near the rock-regolith interface and from dissolution of illite and secondary phases in the upper regolith, whereas in the granitic profile, Mg and K fluxes derive from biotite dissolution. Long-term mineral dissolution rates and weathering fluxes were determined by integrating mass losses over the thickness of solid-state weathering fronts, and are therefore averages over the timescale of regolith development. Resulting long-term dissolution rates for minerals in the volcaniclastic regolith include chlorite: 8.9 x 10-14 mol m-2 s-1, illite: 2.1 x 10-14 mol m-2 s-1 and kaolinite: 4.0 x 10-14 mol m-2 s-1. Long-term weathering fluxes are several orders of magnitude lower in the granitic regolith than in the volcaniclastic, despite higher abundances of several elements in the granitic regolith. Contemporary weathering fluxes were determined from net (rain-corrected) solute profiles and thus represent rates over the residence time of water in the regolith. Contemporary weathering fluxes within the granitic regolith are similar to the long-term fluxes. In contrast, the long-term fluxes are faster than the contemporary fluxes in the volcaniclastic regolith. Contemporary fluxes in the granitic regolith are generally also slightly faster than in the volcaniclastic. The differences in weathering fluxes over space and time between these two watersheds indicate significant lithologic control of chemical weathering mechanisms and rates.
Publication date: Available online 29 September 2016 Source:Continental Shelf Research Author(s): C. Sherman, W. Schmidt, R. Appeldoorn, Y. Hutchinson, H. Ruiz, M. Nemeth, I. Bejarano, J.J. Cruz Motta, H. Xu Although sediment dynamics exert a fundamental control on the character and distribution of reefs, data on sediment dynamics in mesophotic systems are scarce. In this study, sediment traps and benthic photo-transects were used to document spatial and temporal patterns of suspended-sediment and bed-load dynamics at two geomorphically distinct mesophotic coral ecosystems (MCEs) on the upper insular slope of southwest Puerto Rico. Trap accumulation rates of suspended sediment were relatively low and spatiotemporally uniform, averaging <1mgcm−2 d−1 and never exceeding 3mgcm−2 d−1 over the sampled period. In contrast, trap accumulation rates of downslope bed-load movement were orders of magnitude higher than suspended-sediment accumulation rates and highly variable, by orders of magnitude, both spatially and temporally. Percent sand cover within photo-transects varied over time from ~10% to more than 40% providing further evidence of downslope sediment movement. In general, the more exposed, lower gradient site had higher rates of downslope sediment movement, higher sand cover and lower coral cover than the more sheltered and steep site that exhibited lower rates of downslope sediment movement, lower sand cover and higher coral cover. In most cases, trap accumulation rates of suspended sediment and bed load varied together and peaks in trap accumulation rates correspond to peaks in SWAN-modeled wave-orbital velocities, suggesting that surface waves may influence sediment dynamics even in mesophotic settings. Though variable, off-shelf transport of sediment is a continuous process occurring even during non-storm conditions. Continuous downslope sediment movement in conjunction with degree of exposure to prevailing seas and slope geomorphology are proposed to exert an important influence on the character and distribution of insular-slope MCEs.
Publication date: Available online 28 September 2016 Source:Perspectives in Plant Ecology, Evolution and Systematics Author(s): Robert Muscarella, María Uriarte, David L. Erickson, Nathan G. Swenson, W. John Kress, Jess K. Zimmerman Determining how the relative strength of community assembly processes varies along resource gradients is critical for understanding community responses to environmental change. A key challenge for addressing this issue at regional scales is that environmental gradients typically encompass multiple coupled resource gradients (e.g. water, light, soils), which can complicate hypotheses about the drivers of community variation. We used data on functional traits and phylogenetic relatedness to infer assembly processes of tree communities across regional environmental gradients in Puerto Rico. We censused trees in 24, 0.25-ha mature plots located along a precipitation gradient and on soils derived from two parent materials (limestone and volcanic). In each plot, we quantified abiotic conditions in terms of mean annual precipitation, canopy openness, and soil nutrients. We used three functional traits with relevance for drought tolerance and resource acquisition strategies (wood density [WD], leaf mass per area [LMA], and maximum height [H max]), and a molecular phylogeny, to characterize tree community composition in terms of (i) community-weighted mean trait values (i.e., plot average trait values, weighted by relative basal area), (ii) functional diversity, and (iii) phylogenetic diversity. Mean annual precipitation was negatively correlated with understory light availability (for plots on both soil types), and soil fertility (among plots on limestone soils). Soil fertility varied substantially between plots on each parent material, and was generally higher among plots on limestone-derived soils. Among the limestone soil plots, which occur on the drier half of the precipitation gradient, increasing mean annual precipitation was associated with lower community-weighted mean WD and LMA, and taller H max. Additionally, functional diversity (of WD and H max) and phylogenetic diversity increased with precipitation among limestone soil plots, suggesting an important role for abiotic filtering in driving functional and phylogenetic convergence in arid conditions. In contrast, we did not find significant relationships between environmental conditions and community-weighted mean traits or diversity metrics among plots on volcanic-derived soils, which occur along the wetter half of the precipitation gradient. Together, our results suggest that drought tolerance is the dominant assembly mechanism controlling tree composition in dry forests. In wetter forests, functional diversity appears to be maintained by a combination of hierarchical competition for light and niche partitioning. Overall, our results exhibit geographic variation in the mechanisms governing composition of tropical forests across regional environmental gradients, and highlight the importance of considering complex environmental gradients at large spatial scales.
Publication date: Available online 28 September 2016 Source:Bioorganic & Medicinal Chemistry Author(s): Ekaterina A. Burakova, Irina V. Saranina, Nina V. Tikunova, Zhanna K. Nazarkina, Pavel P. Laktionov, Lubov’ A. Karpinskaya, Vadim B. Anikin, Vladimir V. Zarubaev, Vladimir N. Silnikov A series of 1,4-diazabicyclo[2.2.2]octane derivatives differing by linker moiety was evaluated for activity against several strains of both Gram-positive and Gram-negative bacteria including drug-resistant strains, one strain of fungus and influenza virus A/Puerto Rico/8/34 (H1N1). All compounds exhibited high antibacterial activity against all bacteria except Proteus vulgaris. The minimum inhibitory concentrations (MICs) of compound 1c with an o-phenylenebismethyl linker and compound 1e with a propylene aliphatic linker were found to be low and were comparable or better to the reference drug ciprofloxacin for Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, a time-kill assay was performed to examine the bactericidal kinetics. Compounds 1c and 1e displayed rapid killing effects against St. aureus and Ps. aeruginosa after 2 h. Furthermore, compounds 1a–c with aromatic linkers and compound 1e showed the highest antiviral activity. Graphical abstract
Publication date: December 2016 Source:Journal of Experimental Marine Biology and Ecology, Volume 485 Author(s): Michelle Cazabon-Mannette, Darren Browne, Nigel Austin, Adrian Hailey, Julia Horrocks Mitochondrial DNA control region haplotypes of immature hawksbills feeding in Tobago waters and adult females nesting on the beaches of Tobago were characterized. Eleven haplotypes were documented among foraging aggregations and six haplotypes among nesting females, including two which were previously of unknown natal origin. The Tobago rookery is genetically distinct from all other rookeries in the region characterized to date. Significant genetic differentiation was found between the foraging aggregations on the windward and leeward sides of Tobago. Within the rookery, greater diversity was detected among samples from the North-East coast compared to samples from the South-West coast, however no significant difference was detected based on pairwise F ST. Mixed stock analysis was conducted to estimate the natal origins of immature hawksbills foraging in Tobago waters and the contribution of the Tobago rookery to regional foraging aggregations using rookery size as a constraint. The analysis estimated that the Tobago foraging aggregation is mostly composed of animals originating from Cuba, Barbados (Leeward Coast) and Puerto Rico, though this represents only a small fraction of the production from these rookeries. The impact of harvest of juveniles in Tobago is likely to be distributed across the region and not concentrated on any particular rookery. A significant proportion of individuals from the Tobago rookery contributes to the foraging aggregation of the Cayman Islands, and a large proportion of both the Cayman Islands and Puerto Rico foraging aggregations are derived from the Tobago rookery.
Publication date: Available online 15 September 2016 Source:Journal of Invertebrate Pathology Author(s): Paola A. Barriga, Eleanore D. Sternberg, Thierry Lefèvre, Jacobus C. de Roode, Sonia Altizer Throughout their global range, wild monarch butterflies (Danaus plexippus) are infected with the protozoan Ophryocystis elektroscirrha (OE). In monarchs, OE infection reduces pupal eclosion, adult lifespan, adult body size and flight ability. Infection of other butterfly hosts with OE is rare or unknown, and the only previously published records of OE infection were on monarch and queen butterflies (D. gilippus). Here we explored the occurrence and specificity of OE and OE-like parasites in four Danaus butterfly species. We surveyed wild D. eresimus (soldier), D. gilippus (queen), D. petilia (lesser wanderer), and D. plexippus (monarch) from five countries to determine the presence of infection. We conducted five cross-infection experiments, on monarchs and queen butterflies and their OE and OE-like parasites, to determine infection probability and the impact of infection on their hosts. Our field survey showed that OE-like parasites were present in D. gilippus, D. petilia, and D. plexippus, but were absent in D. eresimus. Infection probability varied geographically such that D. gilippus and D. plexippus populations in Puerto Rico and Trinidad were not infected or had low prevalence of infection, whereas D. plexippus from S. Florida and Australia had high prevalence. Cross-infection experiments showed evidence for host specificity, in that OE strains from monarchs were more effective at infecting monarchs than queens, and monarchs were less likely to be infected by OE-like strains from queens and lesser wanderers relative to their own natal strains. Our study showed that queens are less susceptible to OE and OE-like infection than monarchs, and that the reduction in adult lifespan following infection is more severe in monarchs than in queens. Graphical abstract
Publication date: Available online 14 September 2016 Source:Estudios Gerenciales Author(s): William Suárez-Gómez, Jorge Ayala-Cruz El presente estudio examina el efecto multidimensional del cabotaje marítimo que regula el transporte marítimo entre los mercados de Estados Unidos de Norteamérica y Puerto Rico. El objetivo del estudio fue analizar los efectos que esta medida no tarifaria tiene sobre el sector agroindustrial en Puerto Rico. La metodología de investigación consistió de entrevistas semiestructuradas y análisis de datos secundarios de los rubros agrícolas de mayor importación. Los resultados obtenidos concluyen que es la interacción de medidas no tarifarias inherentes a la relación comercial entre ambos países que incide en la eficiencia y competitividad del sector agroindustrial en Puerto Rico. The present study examines the multidimensional effect of the maritime cabotage that regulates the maritime transport between United States of North America and Puerto Rico's markets. The objective of the study was to analyze the effects that this non-tariff measure has on the agro-industrial sector in Puerto Rico. The research methodology consisted of semi-structured interviews and secondary data analysis from the agricultural category of greater import. The results conclude that it is the interaction of non-tariff measures inherent to the business relationship between the two countries that has an impact on the efficiency and competitiveness of the agro-industrial sector in Puerto Rico.
Publication date: 15 December 2016 Source:Science of The Total Environment, Volume 573 Author(s): Henry Alegria, Michael Martinez-Colon, Askin Birgul, Gregg Brooks, Lindsey Hanson, Perihan Kurt-Karakus Polychlorinated biphenyls (PCBs) were quantified in 18 surface sediment samples, 1 sediment core, and several mangrove tissue samples collected in Jobos Bay, Puerto Rico in September 2013. Total PCBs in surface sediments ranged from 0.42 to 1232ngg−1 dw. Generally, higher levels were observed near-shore close to urban and industrial areas. The levels suggest significant pollution in Jobos Bay with respect to PCBs. Two-thirds of the sites were dominated by lighter PCB congeners (tri- to penta-chlorinated PCBs) while one-third had heavy PCB congeners (hexa- to octa-chlorinated PCBs) dominant. Total PCBs in a sediment core indicated levels fluctuating according to historical usage patterns. Total PCBs were measured in mangal leaves (14–747ngg−1 dw), roots (0.26–120ngg−1 dw), and seeds (16–93ngg−1 dw), suggesting bioaccumulation from sediments. This is the first report of a historical profile of PCBs in the study area and of PCB bioaccumulation in mangroves. This article provides new and useful information on PCBs in the Caribbean area of the GRULAC region. Graphical abstract
Publication date: Available online 3 September 2016 Source:Vaccine Author(s): Laurent Coudeville, Nicolas Baurin, Maïna L’Azou, Bruno Guy Background A tetravalent dengue vaccine demonstrated its protective efficacy in two phase III efficacy studies. Results from these studies were used to derive vaccination impact in the five Asian (Indonesia, Malaysia, Philippines, Thailand, Vietnam) and the five Latin American countries (Brazil, Colombia, Honduras, Mexico and Puerto Rico) participating in these trials. Methods Vaccination impact was investigated with an age-structured, host-vector, serotype-specific compartmental model. Parameters related to vaccine efficacy and levels of dengue transmission were estimated using data collected during the phase III efficacy studies. Several vaccination programs, including routine vaccination at different ages with and without large catch-up campaigns, were investigated. Results All vaccination programs explored translated into significant reductions in dengue cases at the population level over the first 10years following vaccine introduction and beyond. The most efficient age for vaccination varied according to transmission intensity and 9years was close to the most efficient age across all settings. The combination of routine vaccination and large catch-up campaigns was found to enable a rapid reduction of dengue burden after vaccine introduction. Conclusion Our analysis suggests that dengue vaccination can significantly reduce the public health impact of dengue in countries where the disease is endemic.
Publication date: Available online 3 September 2016 Source:Vaccine Author(s): Sally Sarawar, Yasuko Hatta, Shinji Watanabe, Peter Dias, Gabriele Neumann, Yoshihiro Kawaoka, Pamuk Bilsel Despite the annual public health burden of seasonal influenza and the continuing threat of a global pandemic posed by the emergence of highly pathogenic/pandemic strains, conventional influenza vaccines do not provide universal protection, and exhibit suboptimal efficacy rates, even when they are well matched to circulating strains. To address the need for a highly effective universal influenza vaccine, we have developed a novel M2-deficient single replication vaccine virus (M2SR) that induces strong cross-protective immunity against multiple influenza strains in mice. M2SR is able to infect cells and expresses all viral proteins except M2, but is unable to generate progeny virus. M2SR generated from influenza A/Puerto Rico/8/34 (H1N1) protected mice against lethal challenge with influenza A/Puerto Rico/8/34 (H1N1, homosubtypic) and influenza A/Aichi/2/1968 (H3N2, heterosubtypic). The vaccine induced strong systemic and mucosal antibody responses of both IgA and IgG classes. Strong virus-specific T cell responses were also induced. Following heterologous challenge, significant numbers of IFN-γ-producing CD8 T cells, with effector or effector/memory phenotypes and specific for conserved viral epitopes, were observed in the lungs of vaccinated mice. A substantial proportion of the CD8 T cells expressed Granzyme B, suggesting that they were capable of killing virus-infected cells. Thus, our data suggest that M2-deficient influenza viruses represent a promising new approach for developing a universal influenza vaccine.
Publication date: Available online 2 September 2016 Source:Acta Tropica Author(s): Ryan R. Hemme, B. Katherine Poole-Smith, Elizabeth A. Hunsperger, Gilberto E. Felix, Kalanthe Horiuchi, Brad J. Biggerstaff, Ricardo Lopez-Ortiz, Roberto Barrera An important step to incriminate a mosquito as a vector of a disease pathogen is finding evidence of direct contact between the mosquito and humans. Typically, this is accomplished through landing/biting catches, or host blood meal analysis in engorged mosquitoes via immunologic assays. An alternate approach is to identify the presence of specific mosquito anti-saliva protein antibodies in the blood of exposed hosts. Following the discovery of dengue infected, free roaming non-human primates in Puerto Rico, we investigated which mosquito species had bitten these primates using a serologic assay. Serum samples from 20 patas monkeys (Erythrocebus patas) and two rhesus macaques (Macaca mulatta) were used to evaluate mosquito bite exposure to Aedes aegypti, Aedes mediovittatus, Aedes taeniorhynchus, and Culex quinquefasciatus mosquitoes. Of 22 non-human primates examined 20 (90%), 17 (77%), 13 (59%), and 7 (31%) were positive for exposure to Ae. mediovittatus, Cx. quinquefasciatus, Ae. taeniorhynchus, and Ae. aegypti, respectively. Our findings indicated that free-roaming primates in Puerto Rico were exposed to the bites of one proven dengue vector, Ae. aegypti and one potential dengue vector, Ae. mediovittatus.
Publication date: Available online 2 September 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Christopher P. Karch, Jianping Li, Caroline Kulangara, Sara M. Paulillo, Senthil K. Raman, Sharareh Emadi, Anmin Tan, Zeinab H. Helal, Qing Fan, Mazhar I. Khan, Peter Burkhard Current influenza vaccines should be improved by the addition of universal influenza vaccine antigens in order protect against multiple virus strains. We used our self-assembling protein nanoparticles (SAPNs) to display the two conserved influenza antigens M2e and Helix C in their native oligomerization states. To further improve the immunogenicity of the SAPNs we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. We demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble and that they are able to stimulate TLR5 in a dose dependent manner. Chickens vaccinated with the self-adjuvanted-SAPNs induce significantly higher levels of antibodies than unadjuvanted-SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Upon immunization with self-adjuvanted-SAPNs mice were completely protected against a lethal challenge. Thus, we have generated a self-adjuvanted-SAPN with a great potential as a universal influenza vaccine. Graphical abstract
Publication date: October 2016 Source:Brain, Behavior, and Immunity, Volume 57, Supplement Author(s): S. Blackmore, M. Juda, J. Hernandez, R.W. Johnson, A.J. Steelman Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we utilized an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS and trigger disease. Specifically, we inoculated C57BL/6 mice with the H1N1 strain of influenza A virus (Puerto Rico/8/34; PR8) then measured: Transcriptomic alterations occurring in the cerebellum and spinal cord, immune cell surveillance of the CNS by flow cytometry and chemokine production from primary glial cultures by ELISA. Infected 2D2 mice were monitored for symptoms of inflammatory demyelination. Infection caused temporal alterations in the transcriptome of both the cerebellum and spinal cord that were consistent with glial activation. Infection of C57BL/6 mice increased CD3+CD4+ T-cell trafficking to the brain at day 8 p.i. Cytokine stimulation of primary glial cultures implicated astrocytes as a major source of chemokine production. Finally, clinical and histological EAE was observed in ∼ 27% of infected 2D2 mice. These data identify a new model with which to study how viral infection progresses disease in MS patients and suggests that peripheral infection induced glial activation precedes relapse.
