Longitudinal changes in response to a cycle-run field test of young male national "talent identification" and senior elite triathlon squads

This study investigated the changes in cardiorespiratory response and running performance of 9 male "Talent Identification" (TID) and 6 male Senior Elite (SE) Spanish National Squad triathletes during a specific cycle-run (C-R) test. The TID and SE triathletes (initial age 15.2 ± 0.7 vs. 23.8 ± 5.6 years, p = 0.03; V(O2)max 77.0 ± 5.6 vs. 77.8 ± 3.6 ml · kg(-1) · min(-1), nonsignificant) underwent 3 tests through the competitive period and the preparatory period, respectively, of 2 consecutive seasons: test 1 was an incremental cycle test to determine the ventilatory threshold (Th(vent)); test 2 (C-R) was 30-minute constant load cycling at the Th(vent) power output followed by a 3-km time-trial run; and test 3 (isolated control run [R]) was an isolated 3-km time-trial control run, in randomized counterbalanced order. In both seasons, the time required to complete the C-R 3-km run was greater than for R in TID (11:09 ± 00:24 vs. 10:45 ± 00:16 min:ss, p < 0.01 and 10:24 ± 00:22 vs. 10:04 ± 00:14, p = 0.006, for season 2005-2006 and 2006-2007, respectively) and SE (10:15 ± 00:19 vs. 09:45 ± 00:30, p < 0.001 and 09:51 ± 00:26 vs. 09:46 ± 00:06, p = 0.02 for season 2005-2006 and 2006-2007, respectively). Compared with the first season, the completion of the time-trial run was faster in the second season (6.6%, p < 0.01 and 6.4%, p < 0.01, for C-R and R tests, respectively) only in TID. Changes in post cycling run performance were accompanied by changes in pacing strategy, but there were only slight or nonsignificant changes in the cardiorespiratory response. Thus, the negative effect of cycling on performance may persist, independently of the period, over 2 consecutive seasons in TID and SE triathletes; however, improvements over time suggests that monitoring running pacing strategy after cycling may be a useful tool to control performance and training adaptations in TID.     

Functional anatomy of the female reproductive systems of two spider crabs (Decapoda,Majoidea)

To better understand the mating systems of majoid crabs, we studied the functional anatomy of the female reproductive systems of the spider crabs Leurocyclus tuberculosus and Libinia spinosa, comparing them with those of other Majoidea. Adult females were measured and dissected, and their reproductive systems described macroscopically and histologically. In females of both species, the seminal receptacles are paired globular structures of ecto‐mesodermal origin. The mesoderm‐derived region is lined by a stratified epithelium. The anchoring, proliferative, and secretory strata are clearly recognizable . The ectoderm‐derived region is lined by a simple cylindrical epithelium underlying a cuticle that increases in thickness toward the vagina. The transition between the ectoderm and mesoderm‐derived regions is abrupt, with differences between the studied species: Li. spinosa has a “velum,” whereas Le. tuberculosus presents prominent “folds.” In both species, the position in which the oviduct is connected to the seminal receptacles is intermediate between the dorsal and ventral types previously described in other eubrachyurans. The seminal receptacles of the studied species show four different conditions, which can be distinguished macroscopically based on their shape and amount of sperm stored. We compare our data with those from other Majoidea in an attempt to determine whether the morphology of the seminal receptacles is related to different mating strategies or behaviors.     

A New Species of Coronilla (Loteae, Fabaceae) from Southeastern Spain: Evidence from Morphological and Molecular Data

Currently, there are nine species classified within the genus Coronilla (Loteae, Fabaceae); however, some populations discovered in the province of Almería, SE Spain, have features that are not present, as a whole, in the other known species. These plants are related to Coronilla juncea and C. minima, although several features of branches, leaves, flowers and seeds (zigzag branches; fleshy, deciduous leaves without hyaline margin; connate reddish stipules; very narrow seeds with fluted foveolae) are usually recognized as belonging to distinct species. To clarify the taxonomic status of these populations, morphological and genetic studies have been performed. The results obtained suggest that their separate classification is appropriate. Accordingly, a new species, Coronilla talaverae, whose currently recorded range is restricted to three populations in southeastern Spain is described here. Regarding its risk of extinction, the IUCN red list criteria have been followed to assess its category, proposing the status EN B1ab(i,ii,iii,v)+2ab(i,ii,iii,v). In addition, an identification key is provided for the species of the genus Coronilla.     

Caloric restriction modifies both innate and adaptive immunity in the mouse small intestine

Although caloric restriction (CR) apparently has beneficial effects on the immune system, its effects on the immunological function of the intestinal mucosa are little known. The present study explored the effect of CR on the innate and adaptive intestinal immunity of mice. Balb/c mice were either fed ad libitum (control) or on alternate days fed ad libitum and fasted (caloric restriction). After 4 months, an evaluation was made of IgA levels in the ileum, the gene expression for IgA and its receptor (pIgR), as well as the expression of two antimicrobial enzymes (lysozyme and phospholipase A2) and several cytokines of the intestinal mucosa. CR increased the gene expression of lysozyme and phospholipase A2. The levels of IgA were diminished in the ileum, which apparently was a consequence of the reduced transport of IgA by pIgR. In ileum, CR increased the gene expression for most cytokines, both pro- and anti-inflammatory. Hence, CR differentially modified the expression of innate and adaptive immunity mediators in the intestine.     

Adipocytokines,Hepatic and Inflammatory Biomarkers and Incidence of Type 2 Diabetes. The CoLaus Study

Context

There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein – CRP; interleukin-1beta – IL-1β; interleukin-6– IL-6; tumour necrosis factor-α – TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes.

Methods

Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003–2008). The endpoint was the occurrence of type 2 diabetes.

Results

208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64–1.47), 0.84 (0.55–1.30) and 0.64 (0.40–1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used.

Conclusion

Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.     

VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

Background

A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4⁺ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects.

Methods

Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests.

Results

VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4⁺ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log₁₀ copies/mL; CD4⁺ T cell count: +135 cells/mm³) and fewest adverse events.

Conclusions

VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system activation associated with HIV-1 disease. Rapid reductions in markers of immune system hyperactivation and cellular proliferation were obtained despite the fact that VS411 did not attain maximal suppression of HIV RNA, suggesting this effect was due to the HALT component.

Trial Registration

ITEudraCT 2007-002460-98     

Oxidative Stress Induced in Sunflower Seedling Roots by Aqueous Dry Olive-Mill Residues

The contamination of soils with dry olive-mill residue can represent a serious problem as being an environmental stressor in plants. It has been demonstrated that inoculation of aqueous extract of olive oil-mill residue (ADOR) with saprobe fungi removes some phenolic compounds. In this paper we studied the effect of ADOR uninoculated or inoculated with saprobe fungi in sunflower seedling roots. The germination and root growth, O₂·^- generation, superoxide dismutase (SOD) and extracellular peroxidases (EC-POXs) activities, and the content of some metabolites involved in the tolerance of stress were tested. The roots germinated in ADOR uninoculated show a decrease in meristem size, resulting in a reduction of the root length and fresh weight, and in the number of layers forming the cortex, but did not alter the dry weight, protein and soluble amino acid content. ADOR caused the decreases in O₂·^- generation and EC-POX′s activities and protein oxidation, but enhanced SOD activity, lipid peroxidation and proline content. Fluorescence imaging showed that ADOR induced O₂·^- and H₂O₂ accumulation in the roots. The increase in SOD and the decrease in EC-POX′s activities might be involved in the enhancement of H₂O₂ content and lipid peroxidation. Control roots treated with ADOR for 10 min show an oxidative burst. Roots germinated in ADOR inoculated with saprobe fungi partially recovered normal levels of ROS, morphological characteristics and antioxidant activities. These results suggested that treatment with ADOR caused a phytotoxic effect during germination inducing an oxidative stress. The inoculation of ADOR with saprobe fungi limited the stress.     

Ageing increases vulnerability to aβ42 toxicity in Drosophila

Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's Disease (AD), for reasons that are not clear. The association could indicate that the duration or degree of exposure to toxic proteins is important for pathology, or that age itself increases susceptibility to protein toxicity. Using an inducible Drosophila model of AD, we investigated these possibilities by varying the expression of an Aβ42 transgene in neurons at different adult ages and measuring the effects on Aβ42 levels and associated pathological phenotypes. Acute induction of Arctic Aβ42 in young adult flies resulted in rapid expression and clearance of mRNA and soluble Arctic Aβ42 protein, but in irreversible expression of insoluble Arctic Aβ42 peptide. Arctic Aβ42 peptide levels accumulated with longer durations of induction, and this led to a dose-dependent reduction in negative geotaxis and lifespan. For a standardised level of mRNA expression, older flies had higher levels of Arctic Aβ42 peptide and associated toxicity, and this correlated with an age-dependent reduction in proteasome activity. Equalising Aβ42 protein at different ages shortened lifespan in correlation with the duration of exposure to the peptide, suggesting that Aβ42 expression accumulates damage over time. However, the relative reduction in lifespan compared to controls was greater in flies first exposed to the peptide at older ages, suggesting that ageing itself also increases susceptibility to Aβ42 toxicity. Indeed older flies were more vulnerable to chronic Aβ42 toxicity even with a much lower lifetime exposure to the peptide. Finally, the persistence of insoluble Aβ42 in both young and old induced flies suggests that aggregated forms of the peptide cause toxicity in later life. Our results suggest that reduced protein turnover, increased duration of exposure and increased vulnerability to protein toxicity at later ages in combination could explain the late age-of-onset of neurodegenerative phenotypes.     

Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation

In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21⁺) and both CD4⁺ and CD8⁺ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4⁺ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.