Expression of Hoxa2 in cells entering chondrogenesis impairs overall cartilage development

Vertebrate Hox genes act as developmental architects by patterning embryonic structures like axial skeletal elements, limbs, brainstem territories, or neural crest derivatives. While active during the patterning steps of development, these genes turn out to be down-regulated in specific differentiation programs like that leading to chondrogenesis. To investigate why chondrocyte differentiation is correlated to the silencing of a Hox gene, we generated transgenic mice allowing Cre-mediated conditional misexpression of Hoxa2 and induced this gene in Collagen 2 alpha 1-expressing cells committed to enter chondrogenesis. Persistent Hoxa2 expression in chondrogenic cells resulted in overall chondrodysplasia with delayed cartilage hypertrophy, mineralization, and ossification but without proliferation defects. The absence of skeletal patterning anomaly and the regular migration of precursor cells indicated that the condensation step of chondrogenesis was normal. In contrast, closer examination at the differentiation step showed severely impaired chondrocyte differentiation. In addition, this inhibition affected structures independently of their embryonic origin. In conclusion, for the first time here, by a cell-type specific misexpression, we precisely uncoupled the patterning function of Hoxa2 from its involvement in regulating differentiation programs per se and demonstrate that Hoxa2 displays an anti-chondrogenic activity that is distinct from its patterning function.     

Future Impact of Various Interventions on the Burden of COPD in Canada: A Dynamic Population Model

Background

Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide. Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD. The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied.

Objectives

We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden.

Methods

Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study. The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage. The cost and quality adjusted life years (QALYs) associated with each intervention were estimated.

Results

The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach $3.61B ($7.33B undiscounted) per year in 2035. Over the next 25 years, COPD will be responsible for approximately $101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted). Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations. Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada.

Conclusion

Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates.     

Ergonomical valorization of working spaces in multipurpose ships

In this work it is shown how anthropological data are among the most needed factors in ergonomical valorization of crew working spaces. Ship's working or living environment involves many unique human factors, which should be specially considered in our case as limitation of crew space. In this work we have chosen ships of different years of construction to prove this tendency. As a micro study, the work posture analysis using the pulling force experiment is performed in order to determine lumbar moment, intra-abdominal pressure as a measure of evaluating and comparing different crew work positions. As a macro-study, the "crew work posture analysis" was carried out by the use of the data collected from real cases. The most probable work postures in different spaces of a ship are classified and after some corrections of the work place the profile and its grade were determined. The "statistical analysis for real ship's spaces" is also performed, as well as another macro study, in order to show some real designed ship spaces from the point of view of the allocated volume.     

Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function

Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety-four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty-four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre- and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.     

Physical and Biological Treatment of Oil-Contaminated Soil in a Baffled Roller Bioreactor

Physical and biological removal of diesel oil from contaminated soil was studied in a baffled roller bioreactor. Initially, the effects of four factors (soil loading, temperature, pH, and surfactant) on physical removal of diesel oil were investigated. Only the presence of a surfactant (sodium dodecyl sulfate [SDS]) demonstrated a significant effect on diesel oil removal. Diesel oil removal efficiency was increased from 32.0% to 63.9% in the presence of 100 mg/L SDS. Using a microbial culture enriched from contaminated soil, biological treatment of diesel oil polluted soil under different soil loadings (15% to 50%), different diesel oil concentrations (1 to 50 g/L), and different types of soil (sand, silt, and clay) was then investigated in the baffled roller bioreactor. Biodegradation consisted of both fast and slow stages for degradation of light and heavy compounds, respectively. All biodegradation experiments demonstrated significant decreases in diesel oil concentrations (88.3% in 14 days for initial diesel oil concentrations of 1000 mg/L and a wide range of soil loadings). The presence of silty or sandy soils enhanced the biodegradation rate compared to the control bioreactor (without soil). The sandy soil loading had no effect on the biodegradation results. Using the enriched culture, the baffled roller bioreactor was able to biodegrade high diesel concentrations (up to 50 g/L) with biodegradation rates of 112.2 and 39.3 mg/L· h during fast and slow stages, respectively.     

The Walking Behaviour of Pedestrian Social Groups and Its Impact on Crowd Dynamics

Human crowd motion is mainly driven by self-organized processes based on local interactions among pedestrians. While most studies of crowd behaviour consider only interactions among isolated individuals, it turns out that up to 70% of people in a crowd are actually moving in groups, such as friends, couples, or families walking together. These groups constitute medium-scale aggregated structures and their impact on crowd dynamics is still largely unknown. In this work, we analyze the motion of approximately 1500 pedestrian groups under natural condition, and show that social interactions among group members generate typical group walking patterns that influence crowd dynamics. At low density, group members tend to walk side by side, forming a line perpendicular to the walking direction. As the density increases, however, the linear walking formation is bent forward, turning it into a V-like pattern. These spatial patterns can be well described by a model based on social communication between group members. We show that the V-like walking pattern facilitates social interactions within the group, but reduces the flow because of its “non-aerodynamic” shape. Therefore, when crowd density increases, the group organization results from a trade-off between walking faster and facilitating social exchange. These insights demonstrate that crowd dynamics is not only determined by physical constraints induced by other pedestrians and the environment, but also significantly by communicative, social interactions among individuals.     

Optimisation of a microwave-assisted method for extracting withaferin A from Withania somnifera Dunal. using central composite design

Introduction – Recently, there have been growing attention on the modification and optimisation of new extraction and quantification methods, caused by the lack of environmentally friendly methodologies for the extraction of phytochemicals from complex matrices. In the case of pharmaceutical compounds, not only the extraction procedure but also the analysis method should be efficient, precise, fast and easy. Objectives – The essential pharmaceutical characteristics and trace concentration of withanolides led us to modify and optimise the previously reported extraction and quantification procedure for withaferin A (WA) as a candidate for withanolides. Matrial and methods – The WA from the air‐dried aerial part of Withania somnifera Dunal. was extracted using a microwave‐assisted extraction (MAE) technique. Four variables affecting the extraction procedure were optimised using the central composite design approach. The method of high‐performance thin‐layer chromatography assay was validated and applied for the quantification of each experiment. Results – The optimum values of factors were: extraction time (150 s), extraction temperature (68°C) and 17 mL of methanol : water in the ratio 25 : 75 as extracting solvent. The solvent system consisted of ethyl acetate : toluene : formic acid : 2‐propanol (7.0 : 2.0 : 0.5 : 0.5, v/v/v/v), and densitometric scanning at 220 nm was applied for the analysis. The dynamic linear range, LOD, LOQ and recovery with the inter‐day, and intra‐day RSDs of the developed method indicated the validity of the method. Conclusion – A pressurised MAE method for extracting WA from the plant's aerial part was optimised using factorial‐based design. The net effect of time, temperature, solvent volume and its ratio suggests that the yield of WA increases until each factor reaches its optimum value, and decreases with further increase in temperature or solvent ratio. Copyright © 2010 John Wiley & Sons, Ltd.     

HPV16-E7 Protein T Cell Epitope Prediction and Global Therapeutic Peptide Vaccine Design Based on Human Leukocyte Antigen Frequency: An In-Silico Study

International Journal of Peptide Research and Therapeutics - Cervical cancer is the second most common leading cause of women's death due to cancer worldwide, about 528,000 patients’...