Microbial-based therapy of cancer: a new twist to age old practice

The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumor-harboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential.

Conservation genetics of the New Holland mouse Pseudomys novaehollandiae, Waterhouse, 1843 (Rodentia: Muridae) : an analysis of mitochondrial DNA control region variation

An investigation of the genetic diversity of New Holland mouse populations using DNA. Ten distinct restriction enzyme fragment patterns or haplotypes were detected. From the fragment patterns, estimates of genetic divergence between the haplotypes revealed a degree of genetic structuring within New Holland mouse with four population assemblages apparent.

Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites

Techniques for targeted genetic disruption in Plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. The ability to use RNA interference (RNAi) to silence gene expression
would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in Plasmodium remains controversial. Here we have used various RNA-based gene silencing approaches to test the utility of RNAi in malaria
parasites and have undertaken an extensive comparative genomics search using profile hidden Markov models to clarify whether RNAi machinery
exists in malaria. These investigative approaches revealed that Plasmodium lacks the enzymology required for RNAi-based ablation of gene expression
and indeed no experimental evidence for RNAi was observed. In its absence, the most likely explanations for previously reported RNAi-mediated knockdown are either the general toxicity of introduced RNA (with global down-regulation of gene expression) or a specific antisense effect mechanistically distinct from RNAi, which will need systematic
analysis if it is to be of use as a molecular genetic tool for malaria parasites.

Population genetics of the spotted seahorse (Hippocampus kuda) in Thai waters : implications for conservation

A population genetics approach was used to investigate the genetic diversity of the spotted seahorse (Hippocampus kuda) in Thai waters; specifically, the degree of genetic differentiation and species evolution was inferred from sequence analysis of 353 bp of the mitochondrial (mt)DNA control region. The data were then used to identify discrete populations in Thai waters for effective conservation and management. Spotted seahorses were collected from 4 regions on the east and west coasts of the Gulf of Thailand and a geographically separated region in the Andaman Sea. Of the 101 mtDNA sequences analyzed, 7 haplotypes were identified, 5 of which were shared among individuals from the east and west coasts of the Gulf of Thailand. The remaining haplotypes were restricted to individuals from the Andaman Sea. Nucleotide and haplotype diversities were similar within the Gulf of Thailand samples, whereas diversity was lower in the Andaman Sea sample. Genetic differentiation appeared between pairs of samples from the Gulf of Thailand and Andaman Sea (FST, p < 0.0001). A large genetic variance appeared among the 2 population groups (94.46%, ΦCT = 0.94464, p < 0.01). A Neighbor-joining tree indicated that individuals from the Gulf of Thailand and Andaman Sea formed 2 phylogenetically distinct groups, which were segregated into different population-based clades. While results reported here indicate that populations from the Gulf of Thailand and Andaman Sea should be treated as separate conservation units, a larger sample size from the Andaman Sea is required to confirm this genetic partitioning and low level of diversity observed in the present study.

Drug release rate and anti-microbial effect of controlled-diffusion biopolymer membranes

In this study, a series of fibrous membranes made from cellulose acetate (CA) and polyester urethane (PEU) by co-electrospining or blend-electrospining were evaluated for drug release kinetics, in vitro anti-microbial activity and in vivo would healing performance when used as wound dressings. To stop common clinical infections, an antibacterial agent, Polyhexamethylene Biguanide (PHMB) was incorporated into e-spun fibres. The presence of CA in the wound healing membrane was found to improve hydrophilicity and permeability to air and moisture. The in vivo tests indicated that the addition of PHMB and CA considerably improved the wound healing efficiency. CA fibres became slightly swollen upon contacting with the wound exudates. It can not only speed up the liquid evaporation but also create a moisture environment for wound recovery. The drug release dynamics of membranes was controlled by the structure of membranes and component rations within membranes. The lower ration of CA:PEU retained the sound mechanical properties of membranes, and also reduced the boost release effectively and slowed down diffusion of antibacterial agent during in vitro tests. The controlled-diffusion membranes exert long-term anti-infective effect.

Genetics and public health - evolution, or revolution?

During the 19th and early 20th century, public health and genetics shared common ground through similar approaches to health promotion in the population. By the mid-20th century there was a division between public health and genetics, with eugenicists estranged and clinical genetics focused on single gene disorders, usually only relevant to small numbers of people. Now through a common interest in the aetiology of complex diseases such as heart disease and cancer, there is a need for people working in public health and genetics to collaborate. This is not a comfortable convergence for many, particularly those in public health. Nine main concerns are reviewed: fear of eugenics; genetic reductionism; predictive power of genes; non-modifiable risk factors; rights of individuals compared with populations; resource allocation; commercial imperative; discrimination; and understanding and education. This paper aims to contribute to the thinking and discussion about an evolutionary, multidisciplinary approach to understanding, preventing, and treating complex diseases.

Microbial lipases : at the interface of aqueous and non-aqueous media: a review

In recent times, biotechnological applications of microbial lipases in synthesis of many organic molecules have rapidly increased in non-aqueous media. Microbial lipases are the working horses' in biocatalysis and have been extensively studied when their exceptionally high stability in non-aqueous media has been discovered. Stability of lipases in organic solvents makes them commercially feasibile in the enzymatic esterification reactions. Their stability is affected by temperature, reaction medium, water concentration and by the biocatalyst's preparation. An optimization process for ester synthesis from pilot scale to industrial scale in the reaction medium is discussed. The water released during the esterification process can be controlled over a wide range and has a profound effect on the activity of the lipases. Approaches to lipase catalysis like protein engineering, directed evolution and metagenome approach were studied. This review reports the recent development in the field of non-aqueous microbial lipase catalysis and factors controlling the esterification/transesterification processes in organic media.

Microbial biosynthesis of biopolymers and applications in the biopharmaceutical, biomedical and food industries

Biopolymers can be produced through a variety of mechanisms. They can be derived from microbial systems, extracted from higher organisms such as plants, or synthesized chemically from basic biological building blocks. A wide range of emerging applications rely on all three of these production techniques. In recent years, considerable attention has been given to biopolymers produced by microbes. It is on the microbial level where the tools of genetic engineering can be most readily applied. A number of novel materials are now being developed or introduced into the market. Biopolymers are being developed for use as medical materials, packaging, cosmetics, food additives, clothing fabrics, water treatment chemicals, industrial plastics, absorbents, biosensors, and even data storage elements. This review identifies the possible commercial applications and describes the various methods of production of microbial biopolymers.