Proteins: form and function

An overwhelming array of structural variants has evolved from a comparatively small number of protein structural domains; which has in turn facilitated an expanse of functional derivatives. Herein, I review the primary mechanisms which have contributed to the vastness of our existing, and expanding, protein repertoires. Protein function prediction strategies, both sequence and structure based, are also discussed and their associated strengths and weaknesses assessed

Probiotic therapy - recruiting old friends to fight new foes

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative

Maximum st-flow in directed planar graphs via shortest paths

Minimum cuts have been closely related to shortest paths in planar graphs via planar duality - so long as the graphs are undirected. Even maximum flows are closely related to shortest paths for the same reason - so long as the source and the sink are on a common face. In this paper, we give a correspondence between maximum flows and shortest paths via duality in directed planar graphs with no constraints on the source and sink. We believe this a promising avenue for developing algorithms that are more practical than the current asymptotically best algorithms for maximum st-flow.Comment: 20 pages, 4 figures. Short version to be published in proceedings of IWOCA'1

Functional Screening of the Cronobacter sakazakii BAA-894 Genome reveals a role for ProP (ESA_02131) in carnitine uptake

Cronobacter sakazakii is a neonatal pathogen responsible for up to 80% of fatalities in infected infants. Low birth weight infants and neonates infected with C. sakazakii suffer necrotizing enterocolitis, bacteraemia and meningitis. The mode of transmission most often associated with infection is powdered infant formula (PIF) which, with an aw of ∼0.2, is too low to allow most microorganisms to persist. Survival of C. sakazakii in environments subject to extreme hyperosmotic stress has previously been attributed to the uptake of compatible solutes including proline and betaine. Herein, we report the construction and screening of a C. sakazakii genome bank and the identification of ProP (ESA_02131) as a carnitine uptake system

Functional Environmental Screening of a Metagenomic Library Identifies stlA; A Unique Salt Tolerance Locus from the Human Gut Microbiome

Functional environmental screening of metagenomic libraries is a powerful means to identify and assign function to novel genes and their encoded proteins without any prior sequence knowledge. In the current study we describe the identification and subsequent analysis of a salt-tolerant clone from a human gut metagenomic library. Following transposon mutagenesis we identified an unknown gene (stlA, for “salt tolerance locus A”) with no current known homologues in the databases. Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed in silico analysis was also conducted to gain additional information on the properties of the encoded StlA protein. The stlA gene is rare when searched against human metagenome datasets such as MetaHit and the Human Microbiome Project and represents a novel and unique salt tolerance determinant which appears to be found exclusively in the human gut environment

Metagenomic Identification of a Novel Salt Tolerance Gene from the Human Gut Microbiome Which Encodes a Membrane Protein with Homology to a brp/blh-Family beta-Carotene 15,15\u27-Monooxygenase

The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane

Rational Design of Improved Pharmabiotics

Herein we review the most recent advances in probiotic research and applications with particular emphasis on the novel concept of patho-biotechnology: the application of pathogen-derived (ex vivo and in vivo) stress survival strategies for the design of more technologically robust and effective probiotic cultures with improved biotechnological and clinical applications

The K-Server Dual and Loose Competitiveness for Paging

This paper has two results. The first is based on the surprising observation that the well-known ``least-recently-used'' paging algorithm and the ``balance'' algorithm for weighted caching are linear-programming primal-dual algorithms. This observation leads to a strategy (called ``Greedy-Dual'') that generalizes them both and has an optimal performance guarantee for weighted caching. For the second result, the paper presents empirical studies of paging algorithms, documenting that in practice, on ``typical'' cache sizes and sequences, the performance of paging strategies are much better than their worst-case analyses in the standard model suggest. The paper then presents theoretical results that support and explain this. For example: on any input sequence, with almost all cache sizes, either the performance guarantee of least-recently-used is O(log k) or the fault rate (in an absolute sense) is insignificant. Both of these results are strengthened and generalized in``On-line File Caching'' (1998).Comment: conference version: "On-Line Caching as Cache Size Varies", SODA (1991