A theoretical and experimental investigation of the electronic spectra and tautomerization of nucleobases

The electronic structures of all possible tautomers of uracil, thymine, cytosine, adenine and guanine have been carefully examined within the MNDO-MO frame-work. Equilibrium geometries are determined and the relative stabilities are discussed. Allowance for solvent effect on the stabilities is made by assuming a tetrahedral solvent cage with the DNA base occupying its centre. The electronic absorption spectra of the studied DNA bases, in solvents of different polarities are recorded and discussed. Assignments of the observed bands are facilitated using MNDO-CI computations. It is suggested that in solution the DNA bases are in some statistical mixtures of the most stable tautomers, and the Watson-Crick (WC) structure cannot account for the observed spectra alone.     

Effective Non-Viral Delivery of siRNA to Acute Myeloid Leukemia Cells with Lipid-Substituted Polyethylenimines

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ～0.5 and led to siRNA/polymer complexes of ～100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia.     

Nutritional factors influence polyhydroxybutyrate in microalgae growing on palm oil mill effluent

Journal of Applied Phycology - Bioplastic made of microalgae is attractive since it does not consume high amounts of substrate compared to bacteria. However, to make the production more feasible,...     

The expected changes in the frequency of alleles affecting the sex ratio

An equation is derived giving the changes per generation in the frequency of alleles affecting the sex ratio. The alleles considered are assumed to be those of an autosomal locus and to act only in one sex. The results indicate that alleles determining the production of more males should always be more common in males than in females.     

In-vitro diagnosis of single and poly microbial species targeted for diabetic foot infection using e-nose technology

Background

Effective management of patients with diabetic foot infection is a crucial concern. A delay in prescribing appropriate antimicrobial agent can lead to amputation or life threatening complications. Thus, this electronic nose (e-nose) technique will provide a diagnostic tool that will allow for rapid and accurate identification of a pathogen.

Results

This study investigates the performance of e-nose technique performing direct measurement of static headspace with algorithm and data interpretations which was validated by Headspace SPME-GC-MS, to determine the causative bacteria responsible for diabetic foot infection. The study was proposed to complement the wound swabbing method for bacterial culture and to serve as a rapid screening tool for bacteria species identification. The investigation focused on both single and poly microbial subjected to different agar media cultures. A multi-class technique was applied including statistical approaches such as Support Vector Machine (SVM), K Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA) as well as neural networks called Probability Neural Network (PNN). Most of classifiers successfully identified poly and single microbial species with up to 90% accuracy.

Conclusions

The results obtained from this study showed that the e-nose was able to identify and differentiate between poly and single microbial species comparable to the conventional clinical technique. It also indicates that even though poly and single bacterial species in different agar solution emit different headspace volatiles, they can still be discriminated and identified using multivariate techniques.     

Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.     

Database and tools for metabolic network analysis

Metabolic network analysis has attracted much attention in the area of systems biology. It has a profound role in understanding the key features of organism metabolic networks and has been successfully applied in several fields of systems biology, including in silico gene knockouts, production yield improvement using engineered microbial strains, drug target identification, and phenotype prediction. A variety of metabolic network databases and tools have been developed in order to assist research in these fields. Databases that comprise biochemical data are normally integrated with the use of metabolic network analysis tools in order to give a more comprehensive result. This paper reviews and compares eight databases as well as twenty one recent tools. The aim of this review is to study the different types of tools in terms of the features and usability, as well as the databases in terms of the scope and data provided. These tools can be categorised into three main types: standalone tools; toolbox-based tools; and web-based tools. Furthermore, comparisons of the databases as well as the tools are also provided to help software developers and users gain a clearer insight and a better understanding of metabolic network analysis. Additionally, this review also helps to provide useful information that can be used as guidance in choosing tools and databases for a particular research interest.