Clostridial spores as live 'Trojan horse' vectors for cancer gene therapy: comparison with viral delivery systems

Solid tumours account for 90% of all cancers. Gene therapy represents a potential new modality for their treatment. Up to now, several approaches have been developed, but the most efficient ones are the viral vector based gene therapy systems. However, viral vectors suffer from several deficiencies: firstly most vectors currently in use require intratumoural injection to elicit an effect. This is far from ideal as many tumours are inaccessible and many may have already spread to other parts of the body, making them difficult to locate and inject gene therapy vectors into. Second, because of cell heterogeneity within a given cancer, the vectors do not efficiently enter and kill every cancer cell. Third, hypoxia, a prevalent characteristic feature of most solid tumours, reduces the ability of the viral vectors to function and decreases viral gene expression and production. Consequently, a proportion of the tumour is left unaffected, from which tumour regrowth occurs. Thus, cancer gene therapy has yet to realise its full potential. The facultative or obligate anaerobic bacteria have been shown to selectively colonise and regerminate in solid tumours when delivered systemically. Among them, the clostridial spores were easy to produce, stable to store and safe to use as well as having extensive oncolytic ability. However, research in animals and humans has shown that oncolysis was almost always interrupted sharply at the outer rim of the viable tumour tissue where the blood supply was sufficient. These clostridial spores, though, could serve as "Trojan horse" for cancer gene therapy. Indeed, various spores harbouring genes for cancerstatic factors, prodrug enzymes, or proteins or cytokines had endowed with additional tumour-killing capability. Furthermore, combination of these "Trojan horses" with conventional chemotherapy or radiation therapies often significantly perform better, resulting in the "cure" of solid tumours in a high percentage of animals. It is, thus, not too difficult to predict the potential outcomes for the use of clostridial spores as "Trojan horse" vectors for oncolytic therapy when compared with viral vector-mediated cancer therapy for it be replication-deficient or competent. However, to move the "Trojan horse" to a clinic, though, additional requirements need to be satisfied (i) target tumours only and not anywhere else, and (ii) be able to completely kill primary tumours as well as metastases. Current technologies are in place to achieve these goals.     

Effects of radiation quality on the opening of stomata in intact Phaseolus vulgaris L. leaves

In intact French bean (Phaseolus vulgaris L.) leaves blue radiation enhanced opening of stomata both when it was used individually and when it was used as preirradiation before "white light" irradiation. Effects of red radiation were just the contrary. This revised version was published online in June 2006 with corrections to the Cover Date.     

Comparative effectiveness research: Challenges for medical journals

Just like you would not buy a car without key information such as service history, you would not "buy" a clinical trial report without key information such as concealment of allocation. Implementation of the updated CONSORT 2010 statement enables the reader to see exactly what was done in a trial, to whom and when. A fully "CONSORTed" trial report does not necessarily mean the trial is a good one, but at least the reader can make a judgement. Clear reporting is a pre-requisite for judgement of study quality. The CONSORT statement evolves as empirical research moves on. CONSORT 2010 is even clearer than before and includes some new items with a particular emphasis on selective reporting of outcomes. The challenge is for everyone to use it.     

Arginine, scurvy and Cartier's "tree of life"

Hunting for wild animals is stimulated by the many different human uses of faunal resources, and these animals constitute important subsistence items in local communities in the Caatinga region. In order to gain access to these resources, hunters have developed a series of techniques and strategies that are described in the present work. The principal hunting techniques encountered were: waiting, especially directed towards hunting diurnal birds; calling ("arremedo"), a technique in which the hunters imitate the animal's call to attract it to close range; hunting with dogs, a technique mostly used for capturing mammals; tracking, a technique used by only a few hunters who can recognize and follow animal tracks; and "facheado", in which the hunters go out at night with lanterns to catch birds in their nests. Additionally, many animal species are captured using mechanical traps. The types of traps used by the interviewees were: dead-fall traps ("quixó"), iron-jaw snap traps ("arataca"), wooden cages with bait ("arapuca"), iron-cage traps ("gaiola'), "visgo", multi-compartment bird cages ("alçapão"), buried ground traps with pivoted tops ("fojo"), and nooses and cages for carnivorous. The choice of which technique to use depends on the habits of the species being hunted, indicating that the hunters possess a wide knowledge of the biology of these animals. From a conservation perspective, active hunting techniques (waiting, imitation, hunting with dogs, and "facheado") have the greatest impact on the local fauna. The use of firearm and dogs brought greater efficiency to hunting activities. Additional studies concerning these hunting activities will be useful to contribute to proposals for management plans regulating hunting in the region – with the objective of attaining sustainable use of faunal resources of great importance to the local human communities.     

γ射线与咖啡因复合处理对大麦的诱变效应

用五种不同剂量的γ射线和５ｍｍｏｌ／Ｌ咖啡因对大麦种子进行单独处理和γ射线与咖啡因间的复合处理,结果表明,辐照Ｍ１代的细胞学损伤及植株损指标均与辐照剂量呈直线相关,且相关系数达显著或极显著水平;Ｍ２代苗期的叶绿素突变率和性状弯异率均与辐照剂量呈指数函数关系,相关系数也均达显著或极显著水平。咖啡因本身对大麦不具诱变性,但以它作辐射后处理,不仅能加剧Ｍ１代细胞学损伤及植株损伤,而且能提高Ｍ２代叶绿素突     

A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion

Background

Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network.

Methods

We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a "bulls-eye" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL"B") and calcium chloride (XL "C").

Results

Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 ± 0.6 to 50.9 ± 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 μL to 150 μL of XL "B". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern.

Conclusion

The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased "expectoration".     

From novice to expert: agroecological competences of children orphaned by AIDS compared to non-orphans in Benin

In the Amazonian basin, the human populations that traditionally inhabit the forest use its natural resources in various ways. One example is the local fauna which, among several other uses, is an important source of protein. The general aim of our study was to investigate the importance of hunting to the lives of the Amazonian riverine communities and to identify the multiple uses and knowledge about the hunted animals. In this article we focused the study on the razor-billed curassow Pauxi tuberosa, a Cracidae of significant value to the studied community. The investigation was conducted in the "Riozinho do Anfrísio Extractive Reserve", a Brazilian Conservation Unit located at the Altamira municipality, in the state of Pará. We used an ethnoecological approach, which included participant observation and semi-structured interviews. Our results show that the razor-billed curassow is used by the "Riozinho do Anfrísio" local population mainly as food, but it also fulfils secondary functions, with the feathers being used as a domestic tool and as magic-religious symbol, some organs as traditional medicine, and some chicks even being raised as pets. Our study also revealed that the traditional ecological knowledge of the riverines about their environment is considerably large, and that the local biodiversity provides various ecosystem services.     

Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.     

An Affinity–Effect Relationship for Microbial Communities in Plant–Soil Feedback Loops

Feedback loops involving soil microorganisms can regulate plant populations. Here, we hypothesize that microorganisms are most likely to play a role in plant–soil feedback loops when they possess an affinity for a particular plant and the capacity to consistently affect the growth of that plant for good or ill. We characterized microbial communities using whole-community DNA fingerprinting from multiple "home-and-away" experiments involving giant ragweed (Ambrosia trifida L.) and common sunflower (Helianthus annuus L.), and we looked for affinity–effect relationships in these microbial communities. Using canonical ordination and partial least squares regression, we developed indices expressing each microorganism's affinity for ragweed or sunflower and its putative effect on plant biomass, and we used linear regression to analyze the relationship between microbial affinity and effect. Significant linear affinity–effect relationships were found in 75 % of cases. Affinity–effect relationships were stronger for ragweed than for sunflower, and ragweed affinity–effect relationships showed consistent potential for negative feedback loops. The ragweed feedback relationships indicated the potential involvement of multiple microbial taxa, resulting in strong, consistent affinity–effect relationships in spite of large-scale microbial variability between trials. In contrast, sunflower plant–soil feedback may involve just a few key players, making it more sensitive to underlying microbial variation. We propose that affinity–effect relationship can be used to determine key microbial players in plant–soil feedback against a low "signal-to-noise" background of complex microbial datasets.