Reducing the risk of human immunodeficiency virus type 1 (HIV-1) transmission is still a public health priority. The development of effective control strategies relies on the quantification of the ...effects of prophylactic and therapeutic measures in disease incidence. Although several assays can be used to estimate HIV incidence, these estimates are limited by the poor performance of these assays in distinguishing recent from long-standing infections. To address such limitation, we have developed an assay to titrate p24-specific IgG3 antibodies as a marker of recent infection. The assay is based on a recombinant p24 protein capable to detect total IgG antibodies in sera using a liquid micro array and enzyme-linked immunosorbent assay. Subsequently, the assay was optimised to detect and titrate anti-p24 IgG3 responses in a panel of sequential specimens from seroconverters over 24 months. The kinetics of p24-specific IgG3 titres revealed a transient peak in the 4 to 5-month period after seroconversion. It was followed by a sharp decline, allowing infections with less than 6 months to be distinguished from older ones. The developed assay exhibited a mean duration of recent infection of 144 days and a false-recent rate of ca. 14%. Our findings show that HIV-1 p24-specific IgG3 titres can be used as a tool to evaluate HIV incidence in serosurveys and to monitor the efficacy of vaccines and other transmission control strategies.
Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in ...developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load.
We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4
and T CD8
) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen.
T CD4
and T CD8
lymphocytes cells stimulated by HBZ-peptides (HBZ
and HBZ
) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8
cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44
/CD62L
), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8
T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA.
Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
Inter-individual differences in size, maturity status, function, and behavior among youth of the same chronological age (CA) have long been a concern in grouping for sport. Bio-banding is a recent ...attempt to accommodate maturity-associated variation among youth in sport. The historical basis of the concept of maturity-matching and its relevance to youth sport, and bio-banding as currently applied are reviewed. Maturity matching in sport has often been noted but has not been systematically applied. Bio-banding is a recent iteration of maturity matching for grouping youth athletes into 'bands' or groups based on characteristic(s) other than CA. The percentage of predicted young adult height at the time of observation is the estimate of maturity status of choice. Several applications of bio-banding in youth soccer have indicated positive responses from players and coaches. Bio-banding reduces, but does not eliminate, maturity-associated variation. The potential utility of bio-banding for appropriate training loads, injury prevention, and fitness assessment merits closer attention, specifically during the interval of pubertal growth. The currently used height prediction equation requires further evaluation.
The purpose of the current study was to assess the developmental changes in change of direction and dribbling speed in youth soccer players taking into account skeletal age (SA), maturity status, ...body size, estimated fat mass, aerobic endurance, lower limb explosive strength and annual volume of training.
Eighty-three male soccer players aged 10-15 years (SA) at baseline were annually followed over 5 years, resulting in an average 4.4 observations per player. After testing for multicollinearity, multi-level regression modeling was used to examine the longitudinal developmental changes on change of direction and dribbling speed.
Maturity-associated variability was significant in change of direction and also dribbling speed among young soccer players aged 12-14 years with better scores being performed by late maturers. Moreover, the predicted longitudinal scores for change of direction and dribbling speed improved with SA (P<0.01), SA2 (P<0.01) and skeletal maturity status entered as an additional developmental predictor (P<0.05). Estimated fat-free mass (P<0.01), aerobic endurance (P<0.01) and lower limb strength (P<0.01) were additional predictors in both models. The soccer-specific skill, dibbling speed, was also explained by annual volume of training (P<0.05).
Skeletal maturity status explains inter-individual variability on maximal short-term run performances with and without the ball possession at early ages of participation in competitive soccer. The effects tend to persist across ages combined with longitudinal changes in body composition and functional fitness. In the particular case of the ball test, annual volume of training was also a longitudinal performance predictor.
The purpose of the study was to evaluate predicted maturity offset (time before age at PHV) and age at PHV (chronological age CA minus maturity offset) in a longitudinal sample of 58 under-13 club ...level soccer players in central Portugal for whom ages at PHV were estimated with the SITAR model. Two maturity offset prediction equations were applied: the original equation which requires CA sitting height, estimated leg length, height and weight, and a modified equation which requires CA and height. Predicted maturity offset increased, on average, with CA at prediction throughout the age range considered, while variation in predicted maturity offset and ages at PHV within CA groups was considerably reduced compared to variation in observed ages at offset and at PHV. Predicted maturity offset and ages at PHV were consistently later than observed maturity offset and age at PHV among early maturing players, and earlier than observed in late maturing players. Both predicted offset and ages at PHV with the two equations were, on average, later than observed among players maturing on time. Intra-individual variation in predicted ages at PHV with each equation was considerable. The results for soccer players were consistent with similar studies in the general population and two recent longitudinal studies of soccer players. The results question the utility of predicted maturity offset and age at PHV as valid indicators of maturity timing and status.
Species occurrence records provide the basis for many biodiversity studies. They derive from georeferenced specimens deposited in natural history collections and visual observations, such as those ...obtained through various mobile applications. Given the rapid increase in availability of such data, the control of quality and accuracy constitutes a particular concern. Automatic filtering is a scalable and reproducible means to identify potentially problematic records and tailor datasets from public databases such as the Global Biodiversity Information Facility (GBIF;
http://www.gbif.org
), for biodiversity analyses. However, it is unclear how much data may be lost by filtering, whether the same filters should be applied across all taxonomic groups, and what the effect of filtering is on common downstream analyses. Here, we evaluate the effect of 13 recently proposed filters on the inference of species richness patterns and automated conservation assessments for 18 Neotropical taxa, including terrestrial and marine animals, fungi, and plants downloaded from GBIF. We find that a total of 44.3% of the records are potentially problematic, with large variation across taxonomic groups (25–90%). A small fraction of records was identified as erroneous in the strict sense (4.2%), and a much larger proportion as unfit for most downstream analyses (41.7%). Filters of duplicated information, collection year, and basis of record, as well as coordinates in urban areas, or for terrestrial taxa in the sea or marine taxa on land, have the greatest effect. Automated filtering can help in identifying problematic records, but requires customization of which tests and thresholds should be applied to the taxonomic group and geographic area under focus. Our results stress the importance of thorough recording and exploration of the meta-data associated with species records for biodiversity research.
Control of canine visceral leishmaniasis (VL) remains a difficult and serious problem mostly because there is no reliable and effective vaccine available to prevent this disease. A mixture of three ...recombinant leishmanial antigens (TSA, LeIF and LmSTI1) encoded by three genes highly conserved in the Leishmania genus have been shown to induce excellent protection against infection in both murine and simian models of cutaneous leishmaniasis. A human clinical trial with these antigens is currently underway. Because of the high degree of conservation, these antigens might be useful vaccine candidates for VL as well. In the present study, using the dog model of the visceral disease, we evaluated the immunogenicity of these three antigens formulated with two different adjuvants, MPL-SE and AdjuPrime. The results were compared with a whole parasite vaccine formulated with BCG as the adjuvant. In order to investigate if sensitization with the recombinant antigens would result in recognition of the corresponding native parasite antigens upon infection, the animals were exposed for four weeks after the termination of the immunization protocol with the recombinant antigens to a low number of L. chagasi promastigotes, an etiological agent of VL. Immune response was evaluated by quantitative ELISA in the animal sera before and after exposure to the viable parasites. Both antigen specific IgG1 and IgG2 antibody levels were measured. Immunization of dogs with the recombinant antigens formulated in either MPL-SE or AdjuPrime resulted in high antibody levels particularly to LmSTI1. In addition, this immunization although to low levels, resulted in the development of antibody response to the whole parasite lysate. Importantly, experimental exposure with low numbers of culture forms of L. chagasi promastigotes caused a clear boost in the immune response to both the recombinant antigens and the corresponding native molecules. The boost response was predominantly of the IgG2 isotype in animals primed with the recombinant antigens plus MPL-SE. In contrast, animals primed with the recombinant antigens formulated in AdjuPrime as well as animals vaccinated with crude antigen preparation responded with mixed IgG1/IgG2 isotypes. These results point to the possible use of this antigen cocktail formulated with the adjuvant MPL-SE in efficacy field trials against canine VL.
In the past years, there has been a particular focus on the application of bacteriocins produced by lactic acid bacteria (LAB) in controlling the growth of pathogenic bacteria in foods. The aim of ...this study was to select LAB strains with antimicrobial activity, previously isolated from a traditional Azorean artisanal cheese (Pico cheese), in order to identify those with the greatest potential in reducing Listeria monocytogenes in fresh cheese. Eight bacteriocin producer strains identified as Lactococcus lactis (1) and Enterococcus faecalis (7) were tested. In general, the bacteriocin-producing strains presented a moderate growth in fresh cheese at refrigeration temperatures (4°C), increasing one log count in three days. They exhibited slow acidification capacity, despite the increased production of lactic acid displayed by some strains after 24h. Bacteriocin activity was only detected in the whey of fresh cheese inoculated with two Enterococcus strains, but all cheeses made with bacteriocin-producing strains inhibited L. monocytogenes growth in the agar diffusion bioassay. No significant differences were found in overall sensory evaluation made by a non-trained panel of 50–52 tasters using the isolates as adjunct culture in fresh cheese, with the exception of one Enterococcus strain. To test the effect of in situ bacteriocin production against L. monocytogenes, fresh cheese was made from pasteurized cows' milk inoculated with bacteriocin-producing LAB and artificially contaminated with approximately 106CFU/mL of L. monocytogenes. The numbers of L. monocytogenes were monitored during storage of fresh cheese at refrigeration temperature (4°C) for up to 15days. All strains controlled the growth of L. monocytogenes, although some Enterococcus were more effective in reducing the pathogen counts. After 7days, this reduction was of approximately 4 log units compared to the positive control. In comparison, an increase of 4logCFU/mL in pathogen numbers was detected over the same period, in the absence of bacteriocin-producing LAB. The combination of two bacteriocin producing Enterococcus sp. optimized the reduction of L. monocytogenes counts in fresh cheese, reducing by approximately 5logunits after 7days. The present work demonstrates that using bacteriocin-producing strains in the manufacture of fresh cheese might contribute to preventing the growth of undesirable pathogenic bacteria such as L. monocytogenes. A blend of two strains demonstrated great potential as a protective culture for the cheese making process.
•Application of bacteriocin-producing lactic acid bacteria to control listeria in fresh cheese•Bacteriocin-producing strains grow in fresh cheese at refrigeration temperatures.•Sensory profiles of fresh cheeses produced with bacteriocinogenic strains were similar.•All enterococci strains were effective in reducing listeria counts in fresh cheese.•A combination of two strains reduced listeria in cheese by 5logunits.
Abstract
The recent deuterium–tritium campaign in JET-ILW (DTE2) has provided a unique opportunity to study the isotope dependence of the L-H power threshold in an ITER-like wall environment (Be wall ...and W divertor). Here we present results from dedicated L-H transition experiments at JET-ILW, documenting the power threshold in tritium and deuterium–tritium plasmas, comparing them with the matching deuterium and hydrogen datasets. From earlier experiments in JET-ILW it is known that as plasma isotopic composition changes from deuterium, through varying deuterium/hydrogen concentrations, to pure hydrogen, the value of the line averaged density at which the threshold is minimum,
n
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e
,
min
, increases, leading us to expect that
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,
min
(T) <
n
ˉ
e
,
min
(DT) <
n
ˉ
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,
min
(D) <
n
ˉ
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,
min
(H). The new power threshold data confirms these expectations in most cases, with the corresponding ordering of the minimum power thresholds. We present a comparison of this data to power threshold scalings, used for extrapolation to future devices such as ITER and DEMO.