Floristic evidence for alternative biome states in tropical Africa.

The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited, however, and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleoecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs. savanna specialists, with some generalist species that span both biomes. In conjunction with georeferenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states but also provide empirical evidence for broad-scale bistability.

A 3D approach to model the taper of irregular tree stems: making plots biomass estimates comparable in tropical forests.

In tropical forests, the high proportion of trees showing irregularities at the stem base complicates forest monitoring. For example, in the presence of buttresses, the height of the point of measurement (HPOM ) of the stem diameter (DPOM ) is raised from 1.3 m, the standard breast height, up to a regular part of the stem. While DPOM is the most important predictor for tree aboveground biomass (AGB) estimates, the lack of harmonized HPOM for irregular trees in forest inventory increases the uncertainty in plot-level AGB stock and stock change estimates. In this study, we gathered an original non-destructive three-dimensional (3D) data set collected with terrestrial laser scanning and close range terrestrial photogrammetry tools in three sites in central Africa. For the 228 irregularly shaped stems sampled, we developed a set of taper models to harmonize HPOM by predicting the equivalent diameter at breast height (DBH') from a DPOM measured at any height. We analyzed the effect of using DBH' on tree-level and plot-level AGB estimates. To do so, we used destructive AGB data for 140 trees and forest inventory data from eight 1-ha plots in the Republic of Congo. Our results showed that our best simple taper model predicts DBH' with a relative mean absolute error of 3.7% (R2 = 0.98) over a wide DPOM range of 17-249 cm. Based on destructive AGB data, we found that the AGB allometric model calibrated with harmonized HPOM data was more accurate than the conventional local and pantropical models. At the plot level, the comparison of AGB stock estimates with and without HPOM harmonization showed an increasing divergence with the increasing share of irregular stems (up to -15%). The harmonization procedure developed in this study could be implemented as a standard practice for AGB monitoring in tropical forests as no additional forest inventory measurements is required. This would probably lead to important revisions of the AGB stock estimates in regions having a large number of irregular tree stems and increase their carbon sink estimates. The growing use of three-dimensional (3D) data offers new opportunities to extend our approach and further develop general taper models in other tropical regions.

Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo.

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.

Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy.

We show that the fraction of proliferating CD4+ lymphocytes is similar in HIV-infected subjects in the early stage of disease and in HIV-negative subjects, whereas the fraction of proliferating CD8+ lymphocytes is increased 6.8-fold in HIV-infected subjects. After initiation of antiviral therapy, there is a late increase in proliferating CD4+ T cells associated with the restoration of CD4+ T-cell counts. These results provide strong support for the idea of limited CD4+ T-cell renewal in the early stage of HIV infection and indicate that after effective suppression of virus replication, the mechanisms of CD4+ T-cell production are still functional in early HIV infection.

HLA-DR polymorphism affects the interaction with CD4.

Major histocompatibility complex (MHC) class II molecules are highly polymorphic and bind peptides for presentation to CD4+ T cells. Functional and adhesion assays have shown that CD4 interacts with MHC class II molecules, leading to enhanced responses of CD4+ T cells after the activation of the CD4-associated tyrosine kinase p56lck. We have addressed the possible contribution of allelic polymorphism in the interaction between CD4 and MHC class II molecules. Using mouse DAP-3-transfected cells expressing different isotypes and allelic forms of the HLA-DR molecule, we have shown in a functional assay that a hierarchy exists in the ability of class II molecules to interact with CD4. Also, the study of DR4 subtypes minimized the potential contribution of polymorphic residues of the peptide-binding groove in the interaction with CD4. Chimeras between the DR4 or DR1 molecules, which interact efficiently with CD4, and DRw53, which interacts poorly, allowed the mapping of polymorphic residues between positions beta 180 and 189 that can exert a dramatic influence on the interaction with CD4.

International institutions, global health initiatives and the challenge of sustainability: lessons from the Brazilian AIDS programme.

The sustainability of successful public health programmes remains a challenge in low and middle income settings. These programmes are often subjected to mobilization-demobilization cycle. Indeed, political and organizational factors are of major importance to ensure this sustainability. The cooperation between the World Bank and the Brazilian AIDS programme highlights the role of international institutions and global health initiatives (GHI), not only to scale up programmes but also to guarantee their stability and sustainability, at a time when advocacy is diminishing and vertical programmes are integrated within health systems. This role is critical at the local level, particularly when economic crisis may hamper the future of public health programmes. Political and organizational evolution should be monitored and warnings should trigger interventions of GHI before the decline of these programmes.

Relevance and Feasibility of a Personalized Dietary Intervention in Older People with Meals-On-Wheels: A Randomized Controlled Pilot Trial.

Objective: The present study aimed at assessing the feasibility and the effectiveness of a personalized dietary intervention in a meals-on-wheels service through a randomized controlled pilot trial. Design: Sixty recipients of home-delivered meals (75% of women; 70-97 years old) were recruited and randomly assigned to a control and an experimental group and followed over a period of 4 months. In the experimental group, the nutritional status (Mini-Nutritional Assessment - MNA questionnaire), the food intake and the food preferences were measured for each participant. Based on this screening, participants were provided with dietary guidance and follow-up. Those at risk of malnutrition were proposed enriched home-delivered meals. Enrichment was set up considering food preferences of the participants. Results: Looking at the whole sample at baseline, 80% (n=48/60) were at risk of malnutrition. Furthermore, 55% (n=33/60) ate less than 2/3 of their calorie and/or protein recommended allowances. In the experimental group, the intervention led to an increase of protein intakes and to a lower extent of calorie intake. In the control group, no significant changes were observed. Conclusion: To conclude, this study suggests that providing dietary guidance and adding nutrient-dense food to meals while considering food preferences is feasible and may help older beneficiaries of meals-on-wheels to increase calorie and protein intake and improve their nutritional status. However, there is a need to develop products or recipes to enrich the meals of the elderly more efficiently to achieve the recommended allowance.

The MHC-binding and gp120-binding functions of CD4 are separable.

CD4 is a cell surface glycoprotein that is thought to interact with nonpolymorphic determinants of class II major histocompatibility (MHC) molecules. CD4 is also the receptor for the human immunodeficiency virus (HIV), binding with high affinity to the HIV-1 envelope glycoprotein, gp120. Homolog-scanning mutagenesis was used to identify CD4 regions that are important in class II MHC binding and to determine whether the gp120 and class II MHC binding sites of CD4 are related. Class II MHC binding was abolished by mutations in each of the first three immunoglobulin-like domains of CD4. The gp120 binding could be abolished without affecting class II MHC binding and vice versa, although at least one mutation examined reduced both functions significantly. These findings indicate that, while there may be overlap between the gp120 and class II MHC binding sites of CD4, these sites are distinct and can be separated. Thus it should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules.

[Erythrocyte removal from bone marrow by density gradient separation using the COBE 2991 cell processor with the triple-bag processing set]. / Désérythrocytation de moelle osseuse par gradient de densité sur COBE 2991 avec le kit triple "bérets".

ABO-incompatible bone marrow transplantation requires red blood cell depletion. Lots of laboratory adopted the technique of density gradient centrifugation (Ficoll-hypaque) using the COBE 2991 cell processor with simple-bag processing set. However, tubing of this set is not adapted to the currently available peristaltic pumps. Moreover, two other sets are required: one for the buffy-coat and one for postgradient cell washing. We developed a method using triple-bag processing set to conduct whole-step procedure (concentration, Ficoll and washing). Peristaltic PVC tubing is provided in one line of the set allowing a safe processing without several connections thus reducing risks of microbial contamination. First, we used buffy-coat of total blood for training, then, we carried out red cell depletion of healthy bone marrow donors. The red blood cell depletion was 97.9+/-1.1% and CD34+ recovery was 89.6+/-8.7%. These results are very close to those obtained with the simple-bag set (red cell depletion.=94.0+/-6.8% and CD34+ recovery=95.9+/-20.3%). We conclude that the triple-bag system, very little used in France, is practical, simplified the manipulation and is more safety than the simple-bag set.

Exposure to contaminants and nutritional intakes in a French vegetarian population.

The NutriNet Santé study collected, on a voluntary basis, the dietary consumption of French vegetarian populations (N = 1766, including 188 vegan individuals) from 18 to 81 years (18-77 years for the vegan). Taking advantage of the availability of contamination data generated in the context of the second French total diet study, dietary exposures of French vegetarian populations to several contaminants were estimated. Results showed that exposures to persistent organic pollutants (PCBs, PCDD/Fs for instance) was dramatically lower than those of the general French population due to the non consumption of food of animal origins. On the other hand, exposures to phytoestrogens, some mycotoxins (T2 and HT2 toxins) and some trace elements (Cd, Al, Sn, Ni) were higher in the vegetarian population compared to those of the general population. Despite some limitations of this approach (both the consumption study and the total diet study were not aimed to estimate dietary exposure of the vegetarian populations), this study showed that dietary habits can dramatically influence the exposure of some contaminants.

Bystander immunotherapy as a strategy to control allergen-driven airway inflammation.

Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to induce regulatory CD4(+) T cells (Treg) specific to an exogenous antigen that could be later activated as needed in vivo to control allergic responses. We have established an experimental approach in which mice tolerized to ovalbumin (OVA) were sensitized to the Leishmania homolog of receptors for activated c kinase (LACK) antigen, and subsequently challenged with aerosols of LACK alone or LACK and OVA together. Upon OVA administration, AHR and allergic airway responses were strongly reduced. OVA-induced suppression was mediated by CD25(+) Treg, required CTLA-4 and ICOS signaling and resulted in decreased numbers of migrating airway dendritic cells leading to a strong impairment in the proliferation of allergen-specific Th2 cells. Therefore, inducing Treg specific to a therapeutic antigen that could be further activated in vivo may represent a safe and novel curative approach for allergic asthma.

Seeing Central African forests through their largest trees.

Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies.

Sampling lymphoid tissue cells by ultrasound-guided fine needle aspiration of lymph nodes in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To establish the feasibility of using ultrasound-guided lymph node needle aspiration as a means to obtain lymphoid tissue cells for the determination of a series of immunologic and virologic measures in HIV-infected patients. DESIGN: First, a comparison of the characteristics of cell populations obtained by simultaneous needle aspiration and standard excisional biopsy in six patients. Second, use of lymph node needle aspiration to assess longitudinally T-cell subset changes in patients initiating highly effective antiretroviral treatment. METHODS: T-cell subsets (CD4 and CD8) and percentage Ki67+ cycling T cells were measured in lymph node cell populations harvested by ultrasound-guided aspiration or standard biopsy by flow cytometry. Cellular RNA content was assessed by a modification of the Roche Amplicor HIV-1 Monitor test. RESULTS: CD4 and CD8 T-cell percentage and HIV RNA cell content of lymph node cell suspensions obtained from the simultaneous performance of ultrasound-guided needle aspiration and excisional biopsy in the same patients were correlated (n = 6). Among the 87 aspiration sessions reported here, mononuclear cell suspensions were obtained in 100% of the sessions, in numbers ranging between 4x10(4) to 6.7x10(6) cells (median: 7x10(5)). This limited number of cells did not allow to perform all type of analyses in all patients. By prioritizing the cells for the determination of T-cell subsets and proliferation rate, this approach was instrumental for demonstrating the normalization of the T-cell subset ratio and the kinetic of normalization of proliferating rates of CD4 and CD8 T cells, as well as the decrease in HIV-1 viral load in the lymph node following HAART initiation. CONCLUSION: Ultrasound-guided aspiration appears to be a non-invasive and ad libitum, safe and repeatable procedure for the longitudinal monitoring of changes in lymph nodes.

Virological and immunological characteristics of HIV treatment failure.

BACKGROUND: Resistance to antiretroviral treatment is prevalent. There is limited knowledge of the determinants of disease evolution in subjects infected with multidrug-resistant HIV (MDR-HIV). METHODS: Infectivity, replication, chemokine receptor usage, and env, gag, protease and reverse transcriptase sequence analysis was performed for MDR-HIV isolates from 14 HIV-infected individuals and compared to wild-type HIV isolates from individuals naive to antiretroviral treatment. Expression of CD45RO/RA, Ki67 and interferon-gamma and CD4 proliferative response to various antigens was determined for individuals infected with MDR-HIV and compared to that in individuals with optimal suppression of viral replication. RESULTS: Infectivity and replication are diminished for various MDR-HIV isolates, usually in the context of an increase in CD4 and CD4+CD45RA+ T-cell counts. However, a number of MDR-HIV isolates are associated with high in vivo viraemia and pronounced immunosuppression, and display in vitro levels of infectivity and replication comparable to those of wild-type strains. No specific genetic sequence or chemokine receptor usage predicted the fitness of an MDR isolate. CONCLUSIONS: Despite the biological diversity of resistant viruses and the range of host responses observed, our descriptive analysis indicates that viral factors play a role in determining the degree of immune damage observed in the context of MDR-HIV infection.

T cell regeneration in HIV-infected subjects under highly active antiretroviral therapy (review).

The initial idea that high amounts of cytopathic virus produced everyday can drive high CD4+ T cell production seemed logical and explained the progressive CD4+ T cell depletion observed in HIV-infected subjects. It was hypothesized that the CD4+ T lymphocyte production was increased up to 70-fold in HIV-infected subjects. Determination of the CD4+ T cell production was based on the kinetics of CD4+ T cell recovery following initiation of highly active antiretroviral therapy (HAART). However, this analysis is limited by: i) the assumption that blood CD4+ T cells are representative of the lymph node T cells; and ii) the lack of estimates of CD4+ T lymphocyte turnover in healthy HIV-negative subjects. Several immunologists have expressed caution regarding the assumptions used in modeling CD4+ T cell dynamics. Recent findings clearly show that blood is not representative of lymphoid tissues and invalidate the conclusion of high CD4 turnover drawn from blood studies on HIV-infected subjects. Indeed, when blood and lymph node compartments are considered together, we find that HIV-infected subjects naive to antiretroviral have similar or lower CD4+ T cell production, as compared to healthy subjects. This observation suggests an impaired T cell renewal capacity in HIV-1 infected patients.

[Inequities in health policies: the Latin American case]. / Iniqüidades nas políticas de saúdes: o caso da América Latina.

Four points relating to the iniquities of the health services are brought out. In the first, the economic crisis the region has been going through during recent decades, is discussed and the contention that the tendency to an overall improvement of the living conditions has not been deeply affected by this crisis is questioned. In the second the characteristics of the Latin-American process of development, marked by the deepening of the iniquities is examined. In the third an analysis of the pattern of social protection in the region is presented and in the last two polar models for the reformation of this pattern are discussed.

Comprehensive longitudinal characterization of canine muscular dystrophy by serial NMR imaging of GRMD dogs.

The Golden Retriever Muscular Dystrophy (GRMD) dog is the closest animal counterpart of Duchenne muscular dystrophy in humans and has, for this reason, increasingly been used in preclinical therapeutic trials for this disease. The aim of this study was to describe the abnormalities in canine dystrophic muscle non-invasively, quantitatively, thoroughly and serially by means of NMR imaging. Thoracic and pelvic limbs of five healthy and five GRMD dogs were imaged in a 3T NMR scanner at 2, 4, 6 and 9months of age. Standard and fat-saturated T(1)-, T(2)- and proton-density-weighted images were acquired. A measurement of T(1) and a two-hour kinetic study of muscle enhancement after gadolinium-chelate injection were also performed. Ten out of the 15 indices evaluated differed between healthy and GRMD dogs. The maximal relative enhancement after gadolinium injection and the proton-density-weighted/T(2)-weighted signal ratio were the most discriminating indices. Inter-muscle heterogeneity was found to vary significantly for most of the indices. The body of data that has been acquired here will help in designing and interpreting preclinical trials using dystrophin-deficient dogs.

Langerin+ dendritic cells are responsible for LPS-induced reactivation of allergen-specific Th2 responses in postasthmatic mice.

Allergic asthma is a T cell-dependent inflammatory lung disease that results from complex interactions between genetic predisposition and environmental factors, including exposure to lipopolysaccharide (LPS). In this study, we have shown that airway LPS exposure was sufficient to induce airway hyperreactivity (AHR) and eosinophil recruitment in mice that had previously experienced an acute episode of allergic asthma. LPS-induced disease reactivation depended on the activation of allergen-specific CD4(+) T cells by a subset of lung langerin(+) dendritic cells (DCs) that retained the allergen. Upon LPS exposure, migration of langerin(+) DCs from lungs to draining lymph nodes increased and LPS-exposed langerin(+) DCs instructed CD4(+) T cells toward a T helper (Th) 2 response. Selective depletion of langerin(+) DCs prevented LPS-induced eosinophil recruitment and T-cell activation, further demonstrating a critical role for langerin(+) DCs in disease reactivation. This finding provides a possible explanation for the subclinical worsening of asthmatics following exposure to low-dose LPS.

The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways.

The prevalence of asthma has steadily increased during the last decade, probably as the result of changes in the environment, including reduced microbial exposure during infancy. Accordingly, experimental studies have shown that deliberate infections with live pathogens prevent the development of allergic airway diseases in mice. Bacterial extracts are currently used in children suffering from repeated upper respiratory tract infections. In the present study, we have investigated whether bacterial extracts, commercially available as Broncho-Vaxom (BV), could prevent allergic airway disease in mice. Oral treatment with BV suppressed airway inflammation through interleukin-10 (IL-10)-dependent and MyD88 (myeloid differentiation primary response gene (88))-dependent mechanisms and induced the conversion of FoxP3 (forkhead box P3)(-) T cells into FoxP3(+) regulatory T cells. Furthermore, CD4(+) T cells purified from the trachea of BV-treated mice conferred protection against airway inflammation when adoptively transferred into sensitized mice. Therefore, treatment with BV could possibly be a safe and efficient strategy to prevent the development of allergic diseases in children.