Mechanical Instabilities of Biological Tubes

We study theoretically the shapes of biological tubes affected by various pathologies. When epithelial cells grow at an uncontrolled rate, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all of which are found in pathologies of tracheal, renal tubes or arteries. The final shape depends crucially on the mechanical parameters of the tissues : Young modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence

Influence of Amazonian deforestation on the future evolution of regional surface fluxes, circulation, surface temperature and precipitation

The extent of the Amazon rainforest is projected to drastically decrease in future decades because of land-use changes. Previous climate modelling studies have found that the biogeophysical effects of future Amazonian deforestation will likely increase surface temperatures and reduce precipitation locally. However, the magnitude of these changes and the potential existence of tipping points in the underlying relationships is still highly uncertain. Using a regional climate model at a resolution of about 50 km over the South American continent, we perform four ERA-interim-driven simulations with prescribed land cover maps corresponding to present-day vegetation, two deforestation scenarios for the twenty-first century, and a totally-deforested Amazon case. In response to projected land cover changes for 2100, we find an annual mean surface temperature increase of 0.5∘C over the Amazonian region and an annual mean decrease in rainfall of 0.17 mm/day compared to present-day conditions. These estimates reach 0.8∘C and 0.22 mm/day in the total-deforestation case. We also compare our results to those from 28 previous (regional and global) climate modelling experiments. We show that the historical development of climate models did not modify the median estimate of the Amazonian climate sensitivity to deforestation, but led to a reduction of its uncertainty. Our results suggest that the biogeophysical effects of deforestation alone are unlikely to lead to a tipping point in the evolution of the regional climate under present-day climate conditions. However, the conducted synthesis of the literature reveals that this behaviour may be model-dependent, and the greenhouse gas-induced climate forcing and biogeochemical feedbacks should also be taken into account to fully assess the future climate of this region

E-Learning and North-South collaboration: the experience of two public health schools in France and Benin

Introduction: Distance learning (e-learning) can facilitate access to training. Yet few public health E-learning experiments have been reported; institutes in developing countries experience difficulties in establishing on-line curricula, while developed countries struggle with adapting existing curricula to realities on the ground. In 2005, two schools of public health, one in France and one in Benin, began collaborating through contact sessions organised for Nancy University distance-learning students. This experience gave rise to a partnership aimed at developing training materials for e-Learning for African students. The distance-learning public health course at Nancy teaches public health professionals through a module entitled "Health and Development." The module is specifically tailored for professionals from developing countries. To promote student-teacher exchanges, clarify content and supervise dissertations, contact sessions are organized in centres proximate and accessible to African students. The Benin Institute's main feature is residential team learning; distance-learning courses are currently being prepared. Outcome: The two collaborating institutions have developed a joint distance-learning module geared toward developing countries. The collaboration provides for the development, diffusion, and joint delivery of teaching modules featuring issues that are familiar to African staff, gives the French Institute credibility in assessing research work produced, and enables modules on specific African issues and approaches to be put online. learned: While E-learning is a viable educational option for public health professionals, periodic contact can be advantageous. Our analysis showed that the benefit of the collaboration between the two institutions is mutual; the French Institute extends its geographical, cultural and contextual reach and expands its pool of teaching staff. The Benin Institute benefits from the technical partnership and expertise, which allow it to offer distance learning for Africa-specific contexts and applications

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases

Impact of soil map specifications for European climate simulations

Soil physical characteristics can influence terrestrial hydrology and the energy balance and may thus affect land–atmosphere exchanges. However, only few studies have investigated the importance of soil textures for climate. In this study, we examine the impact of soil texture specification in a regional climate model. We perform climate simulations over Europe using soil maps derived from two different sources: the soil map of the world from the Food and Agricultural Organization and the European Soil Database from the European Commission Joint Research Center. These simulations highlight the importance of the specified soil texture in summer, with differences of up to 2 °C in mean 2-m temperature and 20 % in precipitation resulting from changes in the partitioning of energy at the land surface into sensible and latent heat flux. Furthermore, we perform additional simulations where individual soil parameters are perturbed in order to understand their role for summer climate. These simulations highlight the importance of the vertical profile of soil moisture for evapotranspiration. Parameters affecting the latter are hydraulic diffusivity parameters, field capacity and plant wilting point. Our study highlights the importance of soil properties for climate simulations. Given the uncertainty associated with the geographical distribution of soil texture and the resulting differences between maps from different sources, efforts to improve existing databases are needed. In addition, climate models would benefit from tackling unresolved issues in land-surface modeling related to the high spatial variability in soil parameters, both horizontally and vertically, and to limitations of the concept of soil textural class

Autotransporters and Their Role in the Virulence of Burkholderia pseudomallei and Burkholderia mallei

Burkholderia pseudomallei and Burkholderia mallei are closely related Gram-negative bacteria responsible for the infectious diseases melioidosis and glanders, respectively. Autotransporters (ATs) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors. The B. pseudomallei K96243 genome contains 11 predicted ATs, eight of which share homologs in the B. mallei ATCC 23344 genome. This review distils key findings from in silico, in vitro, and in vivo studies on the ATs of B. pseudomallei and B. mallei. To date, the best characterized of the predicted ATs of B. pseudomallei and B. mallei is BimA, a predicted trimeric AT mediating actin-based motility which varies in sequence and mode of action between Burkholderia species. Of the remaining eight predicted B. pseudomallei trimeric autotransporters, five of which are also present in B. mallei, two (BoaA and BoaB), have been implicated in bacterial adhesion to epithelial cells. Several predicted Burkholderia ATs are recognized by human humoral and cell-mediated immunity, indicating that they are expressed during infection and may be useful for diagnosis and vaccine-mediated protection. Further studies on the mode of secretion and functions of Burkholderia ATs will facilitate the rational design of control strategies