Showing papers in "Science Progress in 2008"

Preserving accuracy in GenBank

Abstract: GenBank, the public repository for nucleotide and protein sequences, is a critical resource for molecular biology, evolutionary biology, and ecology. While some attention has been drawn to sequence errors ([1][1]), common annotation errors also reduce the value of this database. In fact, for

Climate change impacts on seals and whales in the North Atlantic Arctic and adjacent shelf seas.

Abstract: In a warmer Arctic, endemic marine mammal species will face extreme levels of habitat change, most notably a dramatic reduction in sea ice. Additionally, the physical environmental changes, including less ice and increased water (and air) temperatures will result in alterations to the forage base of arctic marine mammals, including density and distributional shifts in their prey, as well as potential losses of some of their traditionally favoured fat-rich prey species. In addition they are likely to face increased competition from invasive temperate species, increased predation from species formerly unable to access them in areas of extensive sea ice or simply because the water temperature was restrictive, increased disease risk and perhaps also increased risks from contaminants. Over the coming decades it is also likely that arctic marine mammals will face increased impacts from human traffic and development in previously inaccessible, ice-covered areas. Impacts on ice-associated cetaceans are difficult to predict because the reasons for their affiliation with sea ice are not clearly understood. But, it is certain that ice-breeding seals will have marked, or total, breeding-habitat loss in their traditional breeding areas and will certainly undergo distributional changes and in all probability abundance reductions. If species are fixed in traditional spatial and temporal cycles, and are unable to shift them within decadal time scales, some populations will go extinct. In somewhat longer time frames, species extinctions can also be envisaged.

The epidemiological transition: the current status of infectious diseases in the developed world versus the developing world.

Abstract: Wealthy, industrialized countries of the developed world successfully underwent the "epidemiologic transition" from infectious diseases to degenerative diseases, but developing countries have not yet achieved that transition. This article reviews the current status of Omran's Theory of Epidemiologic Transition, comparing the burden of infectious diseases in the developed world versus the developing world. The advent of modern sanitation and hygiene practices, effective vaccines, and antibiotics have significantly diminished the burden in the developed world, but infectious diseases remain the most common cause of death worldwide. The persistence of this disease burden has been due to a failure to employee effective strategies and to unforeseen developments, such as the emergence of HIV and the re-emergence of malaria and tuberculosis driven by newly developed drug resistance. The challenge in accurately assessing infectious disease burden and developing effective interventions is reviewed along with the most common diseases and current intervention strategies.

Effects of climate change on polar bears.

Abstract: In this article, we review the effects on polar bears of global warming that have already been observed, and try to evaluate what may happen to the polar bears in the future. Many researchers have predicted a wide range of impacts of climate change on polar bear demography and conditions. A predicted major reduction in sea ice habitat will reduce the availability of ice associated seals, the main prey of polar bears, and a loss and fragmentation of polar bear habitat will ultimately lead to large future reductions in most subpopulations. It is likely that polar bears will be lost from many areas where they are common today and also that the total population will change into a few more distinctly isolated populations.

Global warming and effects on the Arctic fox.

Abstract: We predict the effect of global warming on the arctic fox, the only endemic terrestrial predatory mammals in the arctic region. We emphasize the difference between coastal and inland arctic fox pop...

Climate change and the microbiology of the Antarctic Peninsula region.

Abstract: Antarctic terrestrial ecosystems are cold, dry, low nutrient environments, with large temperature fluctuations and paradoxically low levels of water availability. These extreme environments are dominated by microorganisms (viruses, archaea, eubacteria, fungi and microsporidia, alveolata, stmramenopila, rhodophyta, green algae and protists), which can either tolerate or are adapted to exploit unfavourable growth conditions. However, climate change is altering the growth environment in Antarctica, and so selection pressures on these microorganisms are changing which, in turn, might affect microbial activity in key processes such as biogeochemical cycling. Although the direct effect of a change in, for example, temperature, is known for very few Antarctic microorganisms, molecular techniques (to monitor population structure) and genomic techniques (to identify specific gene function) are starting to give us an insight into what the potential effects of climate change might be at the cellular level. The key to how microorganisms respond to such change depends upon the rate and magnitude of the change along with the physiological capability of microorganisms to adapt or tolerate those changes. Here we will examine a number of case studies in which the effects of factors such as temperature, nutrient availability, grazing, salinity, seasonal cycle and carbon dioxide concentration have each been demonstrated to affect bacterial community structure in polar and alpine ecosystems. The results suggest that the spatial distribution of genetic variation and, hence, comparative rates of evolution, colonization and extinction are particularly important when considering the response of microbial communities to climate change.

The myth of the boiling point.

Abstract: Around 1800, many reputable scientists reported significant variations in the temperature of pure water boiling under normal atmospheric pressure. The reported variations included a difference of over 1 degree C between boiling in metallic and glass vessels (Gay-Lussac), and "superheating" up to 112 degrees C on extracting dissolved air out of water (De Luc). I have confirmed most of these observations in my own experiments, many of which are described in this paper. Water boils at the "boiling point" only under very particular circumstances. Our common-sense intuition about the fixedness of the boiling point is only sustained by our limited experience.

Transfer RNA and the origins of diversified life.

Abstract: The evolution of the transfer RNA (tRNA) molecule is controversial but embeds the history of protein biosynthesis, the genetic code, and the origins of diversified life. A new phylogenetic method based on RNA structure that we developed provides new lines of evidence to support the genome tag hypothesis and confirms that the 'top half' of tRNA is more ancient than the 'bottom half' Timelines of amino acid charging function generated from constraint analyses showed that selenocysteine, tyrosine, serine, and leucine specificities were ancient, while those related to asparagine, methionine, and arginine were more recent. The timelines also uncovered an early role of the second and then first codon bases, identified codons for alanine and proline as the most ancient, and revealed important evolutionary take-overs related to the loss of the long variable arm of tRNA. Furthermore, organismal timelines showed Archaea was the oldest superkingdom, followed by viruses, and superkingdoms Eukarya and Bacteria in that order, supporting conclusions from recent phylogenomic studies of protein architecture. Strikingly, results showed that the origin of viruses was not only ancient but was linked to Archaea, supporting the notion that the arehaeal lineage is the most ancient on earth and its origin predated diversification of tRNA function and specificity. Keywords: tRNA, secondary structure, Archaea, Bacteria, Eukarya, viruses, genetic code, amino acids charging, selenocysteine, phylogenetics Introduction The origins and evolution of the genetic code and proteins and the emergence of the diversified world embody fundamental biological questions that are of great importance to our understanding of life. Unfortunately, concrete answers to these questions are lacking, are incomplete, or are highly controversial. This is partially due to our inability to uncover significant evolutionary signal in the molecules of life that have been examined to date. For example, ribosomal RNA (rRNA) molecules have been used to reconstruct a tree of life but the rooting of the tree that defines Bacteria as the most ancient lineage contrasts with evidence derived from genomics and remains controversial. Transfer RNAs (tRNAs) are very ancient nucleic acid molecules and promising molecular fossil candidates. They are central to one of the most fundamental biological functions, the ability to synthesize proteins (translation). Translation is a property shared by all cellular organisms (generally missing in viruses) and its conservation suggests it is ancient and embeds the history of the living world. tRNA molecules are generally short and are composed of runs of ~73-95 nucleotides that generally adopt a typical cloverleaf-shaped secondary structure and fold into a L-like conformation in three dimensional (3D) space (Figure 1A). This cloverleaf structure is made up of two structural and functional domains. The acceptor (Acc) and the pseudouridine (T[PSI]C) arms comprise the "top half" domain, while the "bottom half" domain is composed of the dihydrouridine (DHU) and the anticodon (AC) arms. A variable (extra) arm spans the T[PSI]C and AC arms. tRNA plays vital roles in protein synthesis by: (i) transporting (charging) an amino acid onto its Acc arm thanks to the activity of specific aminoacyl-tRNA synthetases (aaRSs), and (ii) using a triplet (anticodon) nucleotide sequence located in the AC loop to translate information in a complementary (codon) sequence of messenger RNA (mRNA) that encodes amino acid charging and defines a "genetic code" (Figure 1B). When nested into the rRNA subunits of the ribosomal ensemble, the codons are deciphered along the mRNA and charged amino acids are enzymatically transformed into growing polypeptide chains, ultimately generating functional proteins. Because of their central role in protein synthesis, tRNA and several other macromolecules (e.g., aaRSs and rRNAs) have been considered critical references for evolutionary analysis. …

The oil question: nature and prognosis.

Abstract: A review is given of the nature and origins of crude oil (petroleum) along with factors relating to its production and demand for it. The modern globalised world economy and its population has grow...

Tidal Energy Extraction: Renewable, Sustainable and Predictable:

Abstract: The tidal flow of sea water induced by planetary motion is a potential source of energy if suitable systems can be designed and operated in a cost-effective manner This paper examines the physical origins of the tides and how the local currents are influenced by the depth of the seabed and presence of land mass and associated coastal features. The available methods of extracting energy from tidal movement are classified into devices that store and release potential energy and those that capture kinetic energy directly. A survey is made of candidate designs and, for the most promising, the likely efficiency of energy conversion and methods of installing them are considered. Overall, the need to reduce CO2 emissions, a likely continued rise in fossil fuel cost will result in a significantly increased use of tidal energy. What is still required, especially for kinetic energy devices, is a much greater understanding of how they can be designed to withstand long-term immersion in the marine environment.

Butterflies as indicators of climate change.

Abstract: In Britain, most butterfly species reach the limit of their range due to climate. Such species are the ones most likely to show rapid adaptations to climate change. There are indications that sever...

Towards recombinant antibody-fragment targeted photodynamic therapy.

Abstract: For the treatment of tumours and other proliferative conditions, widespread uptake of photodynamic therapy (PDT) has to some extent been hindered by its inability to target specifically photosensitisers (PSs) to localised lesions in the body PSs may be deposited in the skin, leading to painful and disfiguring photosensitivity, sometimes for weeks after initial treatment Targeting PSs specifically could not only avoid such side-effects, it could greatly improve PDT's therapeutic margin This review describes photoimmunoconjugates (PICs) produced via successful combination of PSs with recombinant monoclonal antibody fragments (sc-Fvs) PICs can not only target specifically and destroy tumour cells in vitro and in vivo, but counter-intuitively, it is possible to conjugate many more PSs to an sc-Fv than to the much larger parent monoclonal antibody The general utility of PICs is demonstrated by significant improvements to the potency and selectivity of already existing PSs Furthermore, critical features of sc-Fvs are discussed that enable them to make effective PICs This has implications for the future engineering of scFv carriers for PDT, in order to control the number and function of the PSs that can be coupled

Towards a Cure for Dementia: The Role of Axonal Transport in Alzheimer's Disease:

Abstract: Alzheimer's disease is an incurable, fatal illness characterised by years of progressive mental decline. It afflicts half a million people in the UK–more than any other dementia. The primary risk f...

The development of insulin resistance in Type 2 diabetes : insights from knockout studies

Abstract: Diabetes is a common endocrine disorder, primarily characterised by elevated plasma glucose levels. The disease affects all age groups worldwide. Most patients suffer from Type 2 diabetes, which is mainly due to insulin resistance. It is thought that changes in insulin signalling pathways underlie the development of insulin resistance. This article aims to review recent studies that have elucidated the role of individual proteins in these insulin signalling pathways. These studies have been undertaken using two strategies, one employing mice carrying a global null mutation of particular gene-encoding proteins by the homologous recombination method and another strategy using mice with tissue-specific insulin receptor and/or GLUT4 knockout by the Cre-loxP system. The various phenotypes of these knockout mice, and the light they shed on the etiology of insulin resistance, are discussed. By advancing our understanding of the complex molecular mechanisms underlying insulin resistance, these knock-out models may help us to develop more effective treatments for Type 2 diabetes.

How to study DNA and proteins by linear dichroism spectroscopy.

Abstract: The technique of linear dichroism (LD) is a simple absorbance technique that uses two polarised light beams Since only oriented molecules show different absorbances for different polarisations, LD detects only oriented molecules In aqueous solutions, flow orientation is an attractive orientation methodology as it selects long molecules or molecular assemblies LD thus is selective for molecules that are particularly challenging to study by more standard biophysical techniques In this article, a brief review of the application of LD to DNA, DNA-drug systems, DNA-protein enzymatic complexes, fibrous proteins and membrane peptides and proteins is given

A tribute to Howard Dalton and methane monooxygenase.

Abstract: This is a brief account of the scientific contribution of Professor Sir Howard Dalton FRS, who died in January 2008. It starts with his important study of the physiology of nitrogen-fixing bacteria, but concentrates on his work on methane oxidation. This started with the development of reliable assays for the methane monooxvgenase, leading in the discovery of two types of enzyme, soluble and membrane-bound and their regulation by copper levels in the growth medium. His contribution to our understanding of the structure and function of these enzymes is then discussed and the review closes with a brief summary o four present knowledge of these important enzymes. Keywords: Dalton, methane, methane oxidation, methylotrophs, methanotrophs Introduction Howard Dalton was one of the most distinguished and influential microbiologists of his generation. This review is based on my contribution to A Tribute to Celebrate the Life of Professor Sir Howard Dalton FRS, held at the University of Warwick in May 2008. His research career started when he undertook a DPhil with Professor John Postgate FRS at the ARC Unit of Nitrogen Fixation, Sussex University, where he worked on nitrogen fixation in the soil bacterium Azotobacter. He then worked for two years with Professor Len Mortensen at Purdue University, Indiana, on the biochemistry of nitrogenase in the anaerobic bacterium Clostridium. Recognising that physico-chemical spectroscopy techniques were going to be of great importance in studying metal-containing enzymes, he returned to Sussex University in 1970 to work with Professor Bob Bray on molybdenum enzymes. Professor Roger Whittenbury persuaded Dalton to take up a lectureship in Microbiology at the Department of Biological Sciences in the University of Warwick in 1973 where was awarded a Personal Chair in 1983. He was elected as a Fellow of the Royal Society in 1993, was appointed President of the Society for General Microbiology, 1997-2000, and awarded the Leeuwenhoek Medal in 2000. In 2002, Dalton was seconded to become Chief Scientific Adviser to Defra. He was Knighted in the New Year's Honours list in 2007. This review starts with a brief description of Dalton's contribution to the physiology of bacterial nitrogen fixation, but most of it describes his work on methane oxidation. The earlier 'historical' part concentrates on his direct contributions, and the later part provides a brief summary of our present knowledge about the methane monooxygenases, much of which was directly contributed, or was inspired, by Dalton's group at Warwick. Nitrogen fixation During bacterial nitrogen fixation, atmospheric nitrogen gas is reduced to ammonia in a reaction catalysed by the nitrogenase complex, consisting of two proteins containing the metals iron and molybdenum. This enzyme is famously extremely sensitive to oxygen but many nitrogen fixing bacteria require oxygen for growth, and sometimes the efficiency of fixation is higher when oxygen is present. This raises the question that formed the basis of Dalton's PhD work: How does the oxygen-sensitive nitrogenase function in bacteria in a highly aerobic environment? The chosen microbe for study was Azotobacter, which fixes nitrogen in aerobic conditions, during which the rate of oxygen consumption is extremely high, while its nitrogenase remains very sensitive to molecular oxygen. His approach provides an excellent example of the use of continuous culture to sort out a puzzling problem of bacterial physiology (1,2). Dalton's extensive imaginative study showed convincingly that this is due to a process of Respiratory Protection: "Nitrogenase is inactivated by oxygen but the organism's respiration normally scavenges oxygen and keeps it away from the enzyme." Appreciating that a better understanding of nitrogenase would be based on a physico-chemical approach, Dalton spent the next five years with Mortenson in Purdue and with Bray in Sussex studying nitrogenase and related metal-containing enzymes. …

Professor Sir Howard Dalton FRS: (8Th February 1944-12th January 2008)

Abstract: [ILLUSTRATION OMITTED] The untimely death of one of the UK's leading microbiologists was marked by a Memorial Event at the University of Warwick on 19th May 2008 attended by his wife and family and a very large number of his former colleagues and students. A number of lectures were given which were focused on those areas for which Howard Dalton had become renowned. One of these, given by Professor Christopher Anthony, is published here. Also we reproduce the obituary for Howard Dalton, prepared by his former colleague, Professor J. Colin Murrell of the same Department of Biological Sciences, University of Warwick. This is reproduced by kind permission of the Society for General Microbiology., it having first appeared in the May 2008 number of the Society journal 'Microbiology Today'. Terence Kemp Howard was born in New Malden, Surrey, the son of a lorry driver. He was highly intelligent with an inquiring mind and his early interest in science was evident from his many exploits with cocktails of chemicals, which often had explosive consequences, Having survived many escapades with these early 'laboratory' experiments, Howard was eager to learn more and his mother was extremely proud of him passing the 11+ examination and attending Raynes Park Grammar School. Howard was awarded a place at Queen Elizabeth College, University of London, graduating in 1965 with a BSc in Microbiology. His research career started when he undertook a DPhil with Professor John Postgate FRS at the ARC Unit of Nitrogen Fixation, University of Sussex, where he worked on nitrogen fixation in the soil bacterium Azotobacter and helped to elucidate how this aerobic soil bacterium protects its nitrogenase from oxygen damage by augmentation of respiration and conformational protection mechanisms. Howard then worked for 2 years as a postdoctoral fellow with Professor Len Mortensen at Purdue University, Indiana, on the biochemistry of nitrogenase in the anaerobic bacterium Clostridium. Ever resourceful, while in the USA he avoided the possibility of being drafted to Vietnam by his ordination into the Universal Life Church, ironically on 1 April 1969! Recognizing that electron spin resonance spectroscopic techniques were going to be of great importance in the study of metaloproteins, Howard returned to the University of Sussex in 1970 to work with Dr Bob Bray in the Department of Chemistry on two molybdenum-containing enzymes, nitrate reductase from Aspergillus nidulans and xanthine dehydrogenase from Veillonella alcalescens. The following year, Howard married Kira Rozdestvensky, whom he had met while living in the USA, and when Professor Roger Whittenbury persuaded Howard to take up a lectureship in Microbiology at the Department of Biological Sciences, University of Warwick in 1973, they settled in the village of Radford Semele near Leamington Spa. Roger recalls that Warwick in those days was hardly a magnet for microbiologists, offering only an abandoned chemistry laboratory containing just two pieces of equipment, a broken piano and a dartboard! A brief chat about his background and a promise that he would work on Roger's beloved methane-oxidizing bacteria and that was sufficient to initiate Howard's long and illustrious tenure at Warwick. Howard built up a large research group at Warwick and pioneered work on two enzymes involved in bacterial oxidation of methane, a soluble, cytoplasmic methane mono-oxygenase (MMO) and a completely distinct membrane-bound particulate MMO. These remarkable enzymes can convert methane, a rather inert compound, into methanol. Howard and colleagues were able to purify and characterize them at the biochemical and molecular level, work which led to much of our current understanding of the structure and catalytic mechanisms of these MMOs. Howard also quickly realized that the soluble MMO had remarkable co-oxidation properties, which stimulated a longstanding interest in biocatalysis and biotransformations using MMO and other oxygenases. …

Empirical tests of a theory of language, mathematics, and matter.

Abstract: In an earlier paper (Abler, 2006), I proposed a theory of language, especially sentences, based on the symmetrical structure of the equation. Here, I use the structure of equations to deduce neural...