Altered expression of calreticulin during the development of fibrosis

Tissue damage following injury leads to inflammation and fibrosis. To understand the molecular mechanisms and the proteins involved in the fibrotic process, we used the well-established unilateral ureteric obstruction rat model and we analyzed the alterations at early and late time intervals using a classical proteomic approach. Data analysis demonstrates a correlation between calreticulin up-regulation and progression of fibrosis. Calreticulin is involved in Ca++ homeostasis but has not been previously implicated in animal models of fibrosis. Proteomic analysis consistently revealed up-regulation of calreticulin in both early and late time intervals. These findings were further confirmed by biochemical and morphological approaches. Next, animal models of lung fibrosis (bleomycin-induced) and heart fibrosis (desmin-null) were examined. In the lung model, calreticulin expression was up-regulated from early time intervals, whereas in the heart model no change in the expression of calreticulin was observed. In addition, TGF-beta, a well known major contributing factor in several fibrotic processes, was found to up-regulate calreticulin in cultured human proximal tubule epithelial cells. The above observations suggest that calreticulin might be involved in fibrotic processes; however the mechanism(s) underlying its possible involvement are yet unresolved.     

Estimation of hand forces and propelling efficiency during front crawl swimming with hand paddles

The aim of the study was to investigate possible modifications caused by hand paddles in the relative contribution of the lift and drag forces of the hand and in the propelling efficiency, during front crawl swimming. Eight female swimmers swam 25 m with maximal intensity without paddles, with small (116 cm(2)) and with large paddles (268 cm(2)). Four cameras operating at 60 Hz were used to record the images and the Ariel Performance Analysis System was used for the digitisation. The results showed that, although during swimming with hand paddles the hand's velocity decreased, the greater propulsive area of the hand paddle caused an increase in the drag, lift, resultant and effective forces of the hand. However, the relative contribution of lift and drag forces on swimming propulsion was not modified, nor was the direction of the resultant force. Hand paddles also increased the propelling efficiency, the stroke length and the swimming velocity, mainly because of the larger propulsive areas of the hand in comparison with free swimming. However, the significant decrease of the stroke rate, might argue the effectiveness of hand paddle training, particularly when large paddles are used in front crawl swimming.     

Inelastic behavior in repeated shearing of bovine white matter

Understanding the brain's response to multiple loadings requires knowledge of how straining changes the mechanical response of brain tissue. We studied the inelastic behavior of bovine white matter and found that when this tissue is stretched beyond a critical strain threshold, its reloading stiffness drops. An upper bound for this strain threshold was characterized, and was found to be strain rate dependent at low strain rates and strain rate independent at higher strain rates. Results suggest that permanent changes to tissue mechanics can occur at strains below those believed to cause physiological disruption or rupture of axons. Such behavior is characteristic of disentanglement in fibrous-networked solids, in which strain-induced mechanical changes may result from fiber realignment rather than fiber breakage.     

Monoclonal antibodies in the treatment of lymphoid malignancies

Rituximab (Rit) was the first monoclonal antibody approved for therapeutic use in cancer patients. Rit is a chimeric mouse/human monoclonal antibody, consisting of the human IgG1 and k constant Fc region, and a mouse variable Fab region specific against the B-cell antigen CD20. Rit exerts its antilymphoma activity through many different mechanisms. Binding of antibody to CD20 antigen, provokes apoptosis through downstream signals that lead to caspase-3 activation. Complement activation by the Fc portion of the antibody results in complement-dependent cytotoxicity. However, the most effective mechanism of action seems to be antigen-dependent cellular cytotoxicity. Effector cytotoxic cells such as natural killer cells (NK) are activated after binding to the Fc portion of the anti-CD20 molecule. Activated NK cells kill the coated lymphoma cells with the use of granzyme-perforin system. More recently, pre-clinical data support the concept that Rituximab can provoke a vaccination-like effect. Finally in-vitro experiments and clinical trials have shown that co-administration of the antibody with cytotoxics confers a strong synergistic effect. The relative contribution of these mechanisms in vivo and in different lymphoma subtypes is not well known and remains to be further evaluated.

Among the different histological groups, follicular lymphoma (FL) has been proven to be the most sensitive to Rit when used as a single agent, with overall response rates of 80% and 50% in untreated and previously treated patients, respectively. Moreover, Rit in combination with chemotherapy is superior to chemotherapy alone in terms of response rate and event-free survival, while early data indicate a significant prolongation in overall survival as well. Similarly, the addition of Rit to standard chemotherapy improves the disease-free and overall survival of patients with diffuse large B-cell lymphoma. There is no doubt that Rit represents one of the greatest achievements of biotechnology engineering. However, we need to understand better the mechanisms of its action as well as the mechanisms of resistance to Rit, in order to design more effective treatment modalities.     

Surfactant gene polymorphisms and interstitial lung diseases

Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs). Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.     

Temperature responses of carbon mineralization in conifer forest soils from different regional climates incubated under standard laboratory conditions

¹⁴C‐labelled straw was mixed with soils collected from seven coniferous forests located on a climatic gradient in Western Europe ranging from boreal to Mediterranean conditions. The soils were incubated in the laboratory at 4°, 10°, 16°, 23° and 30 °C with constant moisture over 550 days. The temperature coefficient (Q₁₀) for straw carbon mineralization decreased with increasing incubation temperatures. This was a characteristic of all the soils with a difference of two Q₁₀ units between the 4–10° and the 23? 30 °C temperature ranges. It was also found that the magnitude of the temperature response function was related to the period of soil incubation. Initial temperature responses of microbial communities were different to those shown after a long period of laboratory incubation and may have reflected shifts in microbial species composition in response to changes in the temperature regime. The rapid exhaustion of the labile fractions of the decomposing material at higher temperatures could also lead to underestimation of the temperature sensitivity of soils unless estimated for carbon pools of similar qualities. Finally, the thermal optima for the organic soil horizons (Of and Oh) were lower than 30 °C even after 550 days of incubation. It was concluded that these responses could not be attributed to microbial physiological adaptations, but rather to the rates at which recalcitrant microbial secondary products were formed at higher temperatures. The implication of these variable temperature responses of soil materials is discussed in relation to modelling potential effects of global warming.     

Highly Invasive Listeria monocytogenes Strains Have Growth and Invasion Advantages in Strain Competition

Multiple Listeria monocytogenes strains can be present in the same food sample; moreover, infection with more than one L. monocytogenes strain can also occur. In this study we investigated the impact of strain competition on the growth and in vitro virulence potential of L. monocytogenes. We identified two strong competitor strains, whose growth was not (or only slightly) influenced by the presence of other strains and two weak competitor strains, which were outcompeted by other strains. Cell contact was essential for growth inhibition. In vitro virulence assays using human intestinal epithelial Caco2 cells showed a correlation between the invasion efficiency and growth inhibition: the strong growth competitor strains showed high invasiveness. Moreover, invasion efficiency of the highly invasive strain was further increased in certain combinations by the presence of a low invasive strain. In all tested combinations, the less invasive strain was outcompeted by the higher invasive strain. Studying the effect of cell contact on in vitro virulence competition revealed a complex pattern in which the observed effects depended only partially on cell-contact suggesting that competition occurs at two different levels: i) during co-cultivation prior to infection, which might influence the expression of virulence factors, and ii) during infection, when bacterial cells compete for the host cell. In conclusion, we show that growth of L. monocytogenes can be inhibited by strains of the same species leading potentially to biased recovery during enrichment procedures. Furthermore, the presence of more than one L. monocytogenes strain in food can lead to increased infection rates due to synergistic effects on the virulence potential.