bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold standard: Mass spectrometry and chromatography
Authors: Loftus Neil
Published: October 2019

Mass spectrometry (MS) interfaced with liquid chromatography (LC) was once considered a technology that was reserved for rather specific applications that appeared to work in sequence with the phases of the moon. Early adventures with thermospray and particle beam interfaces proved to be of limited use, and it was not until atmospheric pressure ionization established itself that we could regard LC–MS as the analytical tool of choice for a considerable range of challenges. Indeed, advances in source design and increased ion transmission have presented a new generation of instruments that use hybrid technology such as quadrupole-time of flight (QToF), ToF–ToF and quadrupole ion-trap ToF, which provide even higher levels of confidence as a consequence of higher mass accuracy and enhanced structural information.
Supporting Excellence in the Science Base: A future for research assessment -- but not as we know it?
Authors: Withnall Mike
Published: October 2019

Richard Reece says in his Editorial (see page 3) that the Research Assessment Exercise (RAE) has fulfilled its purpose of driving up research quality, and that there is no need for future exercises. The Director of the Science Policy Research Unit at Sussex University has reached a similar conclusion: after three rounds of the RAE there is little scope for further gains in efficiency within university departments and the cost of the exercise exceeds the benefits. But there will continue to be a need for some form of assessment of research. The Funding Councils are accountable for the quality of the work that they support. A lack of periodic assessment could lead to complacency and ossification, and universities established since 1992 may feel that they have not yet had sufficient time to develop top-ranking departments.
Teaching the scientists of tomorrow
Authors: Dallimore Liz
Published: October 2019

Since arriving in the UK as a young scientist from Australia, I have discovered that many of the attitudes and problems associated with science education are common to both countries. Government teachers and academic staff of both countries campaign to entice more young people, particularly women, to choose a career within science. Science appears to be a more prominent part of the curriculum in Australia at the equivalent of GCSE and AS/A2 levels. However, my perception is that students tend to see it as a stepping stone to university courses in other disciplines (e.g. medicine, dentistry and physiotherapy) and have little perception of the career opportunities open to graduate scientists.
Adding function to characterization: Combining mass spectrometry with surface plasmon resonance
Authors: Zhukov Andrei , Buijs Jos , Suckau Detlev
Published: October 2019

Since Sir J.J. Thomson of the Cavendish Laboratory at the University of Cambridge constructed the first mass spectrometer (then called a parabola spectrograph) at the turn of the last century, mass spectrometry (MS) has become the most ubiquitous analytical technique in use today. It represents a powerful tool in the study of all substances, because it provides more information about the composition and structure of a substance from a smaller amount of sample than any other analytical technique. It is also a powerful quantitative tool. Femtograms (10 15 g) of carcinogenic pesticide residues can be quantitated and identified in foodstuffs, whereas a genetic abnormality can be characterized from mere femtomole (10 15 mol) quantities of a protein.
Structural Biology in Drug Discovery and Drug Metabolism: Loughborough, 24–25 February 2003
Authors: Sansom Clare
Published: October 2019

Researchers from industry and academia mingled at AstraZeneca's impressive research and development facilities at Charnwood, near Loughborough, in February for a Biochemical Society Focused Meeting that was concerned with the place of metabolism and metabolic pathways in structure-based drug design.
Monitoring biomolecular interactions: Observing real-time molecular binding with surface plasmon resonance
Authors: Löfås Stefan
Published: October 2019

An understanding of the dynamics of biomolecular binding provides scientists with crucial information on the role of molecules in both health and disease. Whether it is antibodies recognizing antigens, cell-surface receptors binding to ligands, or if and how a potential drug candidate binds to its target, the ability to gather quality functional data on interactions is key. This is by no means a simple process. On top of the seemingly endless complexity of biomolecular interactions in the human body, many molecules need to be studied in a near-native environment. This places great demands on the technology used to study these systems. One technology that is capable of providing unique functional data on biomolecular interactions is surface plasmon resonance (SPR). SPR is currently being used for a wide variety of applications within drug development and life-science research, from proteomics to neurobiology and cancer, and even within the food industry. This article looks at the science behind the technique and how SPR has provided new data for neurobiology research into Alzheimer's disease.
Recruiting, funding and communicating: Supporting Excellence in the Science Base
Authors: Withnall Mike
Published: October 2019

A report of the Biochemical Society's annual meeting for Heads of Department, held at the Institute of Physics on 5 May 2004.
Death without stress: The stiletto approach against disease
Authors: Milner Jo
Published: October 2019

Gene silencing by RNA interference (RNAi) allows, for the first time, investigation of the balance between the life and death of a cell under stress-free conditions. Thus it is now possible to (i) identify key antiapoptotic genes that constitutively enable, for example, cancer cell survival, and (ii) map the pathways such genes control (using RNAi co-silencing). New gene targets for anticancer therapy are identified and, full circle, RNAi provides the means for their selective therapeutic silencing.
Cures from the ends of the earth: Novel thermostable enzymes and the pharmaceutical industry
Authors: Littlechild Jenny
Published: October 2019

Enzymes that are found naturally in thermophilic and hyperthermophilic organisms are being used as robust biocatalysts in the fine-chemical and pharmaceutical industries. Knowledge of their biochemical properties and three-dimeasional structures has proved invaluable in understanding their mechanism and in optimizing their commercial use.
Models and reality: The role of computational biology
Authors: Noble Denis
Published: October 2019

The last half of the 20th century saw the phenomenal success of the reductionist approach to biology. The structures of numerous macromolecules were unravelled, the chemical nature of DNA was discovered, and the genome sequences of a number of organisms were largely or completely determined. Readers of The Biochemist need no reminding -- the Biochemical Society played a major role in these monumental achievements. But this very success has created a difficult challenge for the 21st century: what does all this data mean? Could we imagine that with this information and limitless computing power we could simulate the complete functioning of an organism in an exhaustive bottom-up fashion?
The challenge of science in the media
Authors: Bithell Claire
Published: October 2019

Science and the media do not always mix in the way that scientists may want. Where scientists want the media to educate and inform, the media want scientists to entertain and amaze. At best the relationship between these two different disciplines is fraught.
Embryonic stem cells: Past, present, future
Authors: Welham Melanie J.
Published: October 2019

The derivation of embryonic stem (ES) cells from pre-implantation mouse embryos was first reported in 19811,2, although it was not until some 17 years later that human ES cells were successfully isolated3. Few could have predicted that nearly a quarter of a century later, murine ES cells, and their human counterparts, would be under such intense investigation and have sparked so much political, media and public debate. This article gives an overview of our current understanding of how the behaviour of mouse and human ES cells is regulated, focusing in particular on the extrinsic and intrinsic signals involved.
Transcription factors: Analysing regulation in stem cells
Authors: Lee Tony , Volkert Tom
Published: October 2019

The field of systems biology is in an early state of explosive growth as a rare influx of new advances, methods and technologies are combining to enable insights on some of the most compelling problems in human health and disease. One of the most exciting areas of research involves the recent derivation of human ES (embryonic stem) cells, which have the unique ability to grow and divide in an undifferentiated state in culture while maintaining the potential to generate any cell type in the body. These cells represent a rare opportunity for understanding human development and differentiation and hold great promise for regenerative therapeutics. A key to understanding the unique properties of ES cells rests in understanding how the underlying gene expression programmes are brought about by a combination of transcription factors and chromatin modifiers acting on the genome.
Overcoming the tyranny of biology
Authors: Sargent Michael G.
Published: October 2019

Education, Education, Education! I remember the Prime Minister's exhortation but recall no specific proposals or objectives except the paramount need for more tests and targets. Most academics, however, are quite clear; the objective is to introduce children to the seminal ideas that drive human society.
Gripping stuff: Allosteric ribozymes
Authors: Rentmeister Andrea , Famulok Michael
Published: October 2019

Allosteric ribozymes combine the features of ligand-binding aptamers with the catalytic activity of ribozymes and can be generated by rational design or diverse selection strategies. Their activity can be controlled by different types of effectors, ranging from small molecules to oligonucleotides and proteins. This direct coupling of molecular recognition to signal generation in real time allows the generation of versatile reporters that can be applied to report molecular interactions.
special feature: from in vitro curiosity to contributor to cell pathology
Authors: Ross Meredith F. , Murphy Michael P.
Published: October 2019

The MPT (mitochondrial permeability transition) occurs when a protein pore opens in the mitochondrial inner membrane in response to calcium overloading, adenine nucleotide depletion and oxidative stress, causing the disruption of mitochondrial function. For a number of years, this intriguing phenomenon was thought to be an in vitro curiosity of uncertain relevance to mitochondrial function within cells and tissues. However, this view was fundamentally altered with the help of three papers published in the Biochemical Journal in the 1980s and 1990s. Together, these studies demonstrated that CsA (cyclosporin A) selectively blocked induction of the MPT, that the mitochondrial matrix protein cyclophilin D was required for induction of the MPT, and that the MPT contributed to tissue damage during IR (ischaemia–reperfusion) injury.
Reaction painting: Finding art in science
Authors: Burns Lizzie
Published: October 2019

Which do you prefer, art or science? I am often asked this question and always struggle to give an adequate answer. In fact, why do we have to make a choice between the two? Clearly, they are different subjects, but they do have many things in common. Science is such a visual subject and much of its fascination comes from comprehending what we are made of and, inevitably, what that looks like. Observation is central to science and art, as well as the ability to question and formulate new ideas. The best science often has come about through a breakthrough in the imagination rather than a logical, incremental advance in knowledge. As children, we combined both art and science without questioning them as different subjects, but as adults we are encouraged to be either scientifically minded or artistically inclined.
Tissue regeneration: Formation and repair of the extracellular matrix
Authors: Hardingham Tim , Tew Simon , Murdoch Alan
Published: October 2019

All tissues in the body contain an extracellular matrix (ECM) that provides tissue shape and form. We would indeed be the proverbial blob of jelly on the floor if this extracellular structure were not there. So the ECM is an implicit part of being multicellular and having specialized tissues and organs to carry out different functions. As something labelled as ‘structural’, the ECM tends to be taken for granted when tissue functions are being thought about. However, this belies the fact that the ECM structure is essential to support most tissue functions.
Biochemists in the Blogosphere
Authors: Sansom Clare
Published: October 2019

Do you blog? If so, you are certainly not alone. Analysts estimate that there are currently over 57 million weblogs, or blogs, in existence; that's almost one for every inhabitant of Great Britain.
Powder trail: Coaine
Authors: Henry John
Published: October 2019

Although cocaine is thought of as a modern drug, use of the South American coca plant (Erythroxylon coca) as a stimulant dates back to the Incas of Peru, and it was during the 19th Century that the major discoveries were made concerning the drug. Albert Niemann first synthesized pure cocaine in 1860, and Karl Koller, an ophthalmologist, discovered its local anaesthetic effect in 1884, which led to its medicinal use, mainly in ear, nose and throat surgery, where it still has a place1. Cocaine was added to drinks, being a constituent of the popular Vin Mariani and also of Coca Cola until it was realized this might not be a good thing. Cocaine was strongly endorsed by Sigmund Freud2 and used by many others over the years for its stimulant and euphoriant effects; Arthur Conan Doyle even had Sherlock Holmes taking a 7% solution of cocaine hydrochloride in The Sign of Four. Nevertheless, cocaine retained a reputation as a relatively safe, non-addictive agent until the early 1980s3.
What the Society is doing: Strategies for a fairer future
Authors: Kirk Chris , DeFriend Lily
Published: October 2019

History tells us that there have been many famous women biochemists over the years, from those that have won the Nobel Prize to those who have been written out of the history books altogether. Nevertheless, a cursory glance at the faculty lists of most UK universities is enough to show that women are usually not well represented amongst their senior staff. Why should this be? This article looks at the current situation through the eyes of the Biochemical Society and outlines some of the actions that the Society is taking in an attempt to address this important issue.
Playing tag: Histone acetylation
Authors: CraneRobinson Colyn
Published: October 2019

Acetylation of the e-amino group of specific lysine residues of core histones – principally but not exclusively in their unstructured N-terminal tails – is a key biochemical modification for establishing the transcriptional competence of genes bound by such histones. High resolution mapping of acetylated core histones by chromatin IPs (ChIPs) has shown them to be preferentially located at the promoters and enhancers of active genes rather than throughout the transcribed regions. Particular distributions of acetylated lysines are part of the nucleosomal ‘histone code’ that defines and to a considerable extent determines the functional status of the local chromatin. HHe istone acetylation is deposited and removed by numerous histone acetyltransferases (HATs) and deacetylases (HDACs) and acetyl-lysines are recognised (i.e. the histone code is ‘read’) by bromodomain-containing proteins.
Chains of command: Ubiquitin in proinflammatory signalling
Authors: Evans Karine Enesa and Paul C.
Published: October 2019

The 2004 Nobel Prize in Chemistry was awarded to Aaron Chiechanover, Avram Hershko and Irwin Rose for their pioneering studies of ubiquitination and its role in regulating protein stability. Now, 30 years after their discovery, we are beginning to understand the pleiotropic nature of ubiquitin and its roles in diverse physiological processes. Here we review an emerging concept that the signal ling pathways that control inflammation are tightly regulated by a multitude of ubiquitination and deubiquitination reactions.
Sequencing the Neanderthalgenome: Mummy? Daddy?
Authors: De Subhajyoti
Published: October 2019

The Neanderthals were a hominoid species that became extinct in Europe soon after the anatomically modern humans had migrated there from Africa around 28000–40000 years ago. The sequencing of the Neanderthal genome has begun, and it is hoped to find out whether any gene was transferred from the Neanderthals to modern humans and to identify very recent changes in the human genome that have functional consequences. The results will have great significance for the biological understanding of human evolution and for technological progress in genomics.
Putting on a new face: Face transplantation
Authors: Pushpakumar Sathnur B. , Jr Joseph C. Banis , Knopf David , Barker John H.
Published: October 2019

Human face transplantation is now a clinical reality. This new treatment has long captured the interest and imagination of scientists, the media and the public. This is not surprising since, like no other part of our anatomy, we associate our face with so many qualities that make us uniquely human. It is this great importance we attach to our face that makes facial disfigurement such a devastating condition. Of all the physical handicaps, none is more socially devastating than facial disfigurement, which often leads to depression, social isolation, and even suicide1.
Oxford University's first spin-off company: Oxford GlycoSystems
Authors: Dwek Raymond A.
Published: October 2019

One of the greatest changes in recent decades has been the way in which Government demands to see palpable and financially quantifiable results from science. Recent exchanges before the House of Commons Committee of Public Accounts show this well1.
Intervention in utero: Fetal gene therapy
Authors: Waddington Simon N. , Buckley Suzanne M.K. , Coutelle Charles
Published: October 2019

Postnatal gene therapy is a reactive approach to disease treatment. The disease in question will have been diagnosed, usually after symptoms have appeared. Children with lethal immune deficiency diseases have been treated by gene therapy with a high success rate in Paris and London, and many other clinical gene therapy trials for various genetic diseases, acquired conditions and different forms of cancer are presently underway or planned in adult patients.
A summer school for research?
Authors: Sargent Michael G.
Published: October 2019

“You should treasure your time as a Nuffield Student; you will be at university almost 2 years before you do practical or written work like this” -- the startling unsolicited comment made by a Nuffield Bursary student of the 2004 vintage to last year's summer school at the National Institute for Medical Research. She was looking back to what she remembered as a fabulous summer, when she discovered the fascination of research in neuroendocrinology.
Too old, too soon: Hutchinson–Gilford progeria syndrome
Authors: He Xiaoning , Bridger Joanna M. , Kill Ian R.
Published: October 2019

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease that is characterized by precocious aging in infants and always leads to early death from heart attacks or strokes at a mean age of around 13–14 years. The premature aging is manifest through cutaneous changes resembling normal aged skin, alopecia (hair loss), lipodystrophy, skeletal changes (coxa valga and low bone mineral density, although this may not be due to osteoporosis as in normal aging, but rather a failure to properly develop bone throughout infancy) and intense atherosclerosis. Other changes commonly associated with aging are absent, such as cataracts and diabetes mellitus, and there are no reported problems with cognition or CNS neurology1. Thus HGPS belongs to the small group of genetic disorders called the segmental progeroid syndromes (Figure 1).
Summer in Derby
Authors: Oczypok Elizabeth
Published: October 2019

This summer I had the opportunity to carry out a Biochemical Society Studentship at the University of Nottingham Graduate Entry Medical School in Derby, under the supervision of Dr Nathaniel Szewczyk.
Sex in the brain: How the brain regulates reproductive function
Authors: Tena-Sempere Manuel , Huhtaniemi Ilpo
Published: October 2019

Reproductive functions are maintained by a complex hormonal regulatory network called the hypothalamic–pituitary–gonadal (HPG) axis, which is under the hierarchical control of a network of neurohormones that ultimately modulate the synthesis and pulsatile release of the decapeptide gonadotropin-releasing hormone (GnRH) by specialized neural cells distributed along the mediobasal hypothalamus. This neuropeptide drives the production of the two gonadotropic hormones of the anterior pituitary gland, luteinizing hormone (LH) and folliclestimulating hormone (FSH), which are released into the circulation and regulate specific functions of the ovary and testis. In turn, hormones produced by the gonads feed back to the hypothalamic– pituitary level to maintain functional balance of the HPG axis, through negative and positive (only in females) regulatory loops. In this article, we review the main hormonal regulatory systems that are operative in the HPG axis with special emphasis on recent developments in our knowledge of the neuroendocrine pathways governing GnRH secretion, including the identification of kisspeptins and G-protein-coupled receptor 54 (GPR54) as major gatekeepers of puberty onset and fertility.
Eve's curse: and the birth of the contraceptive pill
Authors: McEwan Iain J.
Published: October 2019

2010 sees the 50th anniversary of the introduction of the oral contraceptive pill in 1960. This development was made possible by the synthesis of the first orally active progestin some 9 years earlier. The contraceptive pill is the most popular means of family planning in developed countries, and arguably the most effective. It is the most common method of contraception in the USA (18%), Canada (14%), Australia (27%), New Zealand (20%) and most European countries, including the UK (26%)1. Reproductive health and success have in the past and continue today to be important contributors to our survival as a species. However, even from ancient times, there have been attempts to limit the effect of Eve's curse by reducing the number of children and spacing of successive pregnancies. However, it was only with advances in both scientific knowledge and understanding, together with social reforms, that information about birth control and the means to control fertility became widely available in the last century.
Scents and sex: Insect pheromones
Authors: Pickett John A. , Birkett Michael A. , Woodcock Christine M. , Zhou Jing-Jiang
Published: October 2019

Pheromones are chemical signals (semiochemicals) that act between members of the same species, sex pheromones being the signals that facilitate sexual reproduction. Many organisms use such semiochemicals, but it is insects to which the main research attention has been directed. This article will therefore concentrate on the insect sex pheromones.
Mathematical modelling of metabolism: Summing up
Authors: McDonald Andrew G. , Tipton Keith F. , Davey Gavin P.
Published: October 2019

Biochemistry is as much a quantitative subject as qualitative. Initial observations of single- or multicellular organisms have given rise to our discipline, which is the discovery and characterization of the chemistry of all living things. We have moved from Lavoisier's seminal observation of respiration as a form of combustion, to a much more detailed knowledge of the associated biochemistry.
Phosphoinositides: Navigation through the endosomal maze
Authors: Rutherford Anna C. , Cullen Peter J.
Published: October 2019

For many years, the phosphoinositide (PI) family of membrane lipids was studied because of its importance as intermediates in signal transduction pathways. Over the last decade, it has become increasingly clear that, in addition to these signalling functions, PIs are one of the key regulators governing the identity of intracellular membranes and the flux of membrane through the cell.
More light and colour: Science and the new media
Authors: Curry Stephen
Published: October 2019

Last summer, the galley proofs of my review article on the structural analysis of human serum albumin landed on my desk. The article, which included a summary of over 10 years of work by my group, was scrawled with comments from the subeditor. Some I agreed with, some I didn't, but one remark in particular creased my brow with irritation: “Author should avoid use of the personal pronoun.” No, I thought, I damn well shouldn't. The impulse that sparked this reaction was the probably same one that propelled me into the world of science blogging.
Context is everything: Electron cryotomography
Authors: Moores Carolyn
Published: October 2019

Jostling macromolecules coordinate the essential processes of life as components of complex networks, both inside and outside cells. Visualization of the mechanisms of communication within and between these networks provides information about normal function in healthy cells and tissues and how their disruption causes disease. Molecular structural biology tech niques – Xray crystallography, NMR and cryoelectron microscopy (cryoEM) – reveal details of individual components or minimally reconstituted complexes. In contrast, light microscopy provides a dynamic but still relatively lowresolution view of living cells. Electron tomography (ET) harnesses the theoretical resolving power of the transmission electron microscope [<1 Å (0.1 nm)] to provide insight into the unique structures of macromolecular machines operating in a cellular context1,2.
The Maillard reaction in food processing and cooking: A classic case of risk and benefit
Authors: Halford Nigel G. , Curtis Tanya Y. , Muttucumaru Nira
Published: October 2019

The Maillard reaction is one of the most important in the food industry and home cooking, being largely responsible for the colour, flavour, aroma and texture of some of our favourite foods. However, it also results in the formation of undesirable products, including the neurotoxin and probable carcinogen, acrylamide. The food industry is grappling with the task of reducing acrylamide levels in its products while retaining the characteristics that consumers want and expect.
How far has it come?: Systems Biology
Authors: Cornish-Bowden Athel
Published: October 2019

As a phrase, ‘systems biology’ was probably invented in 1968 by Mesarovć1, but for the first three decades it had essentially no impact: PubMed lists just 19 publications that mention it in all the years before 2000. However, the first output from the human genome project stimulated an explosive growth, and the number of publications referring to ‘systems biology’ reached about 500 in 2005 alone, the year when the Biochemical Society organized a Focused Meeting entitled ‘Systems Biology: will it work?’. After that it became too much effort to continue counting, and the number is certainly much higher now.
Solvent production – not to be sniffed at!: Biobutanol: 21st Century biofuel
Authors: Minton Nigel , Winzer Klaus
Published: October 2019

For much of the latter half of the 20th Century, those researchers who chose to work on solven togenic clostridia, such as Clostridium acetobutylicum, were viewed by many as somewhat eccentric. Why would anyone wish to focus on such a backwater area of science? As we entered the 21st Cen tury, the clamour for a reduction in our reliance on dwindling supplies of fossil fuels intensified, principally driven by concerns over greenhouse gas (GHG) emissions and fossil fuel security. One solution is to commercialize industrial processes based on the microbial conversion of renewable biomass into transportation fuels and other useful chemical commodities. In this regard, there has been a resurgence of interest in C. acetobutylicum, no longer the old warhorse of 20th Century solvent production, but a modernday saviour of the planet through the production of the 21st Century biofuel biobutanol.
A new emphasis on influence
Authors: Garrett Gemma
Published: October 2019

Over the last 18 months, the Biochemical Society's Education Department has made a conscious effort to become more involved with education policy work. During this time, we have responded to consultations, advised the awarding organizations on the content of their new science GCSEs, established a series of education policy events and contributed to the National Curriculum review. Wherever possible, we have worked in close partnership with the Society of Biology (SB) and other sister societies. Read on to find out more…
A fishy tale: A missing part of the inorganic ocean carbon cycle
Authors: Wilson Rod W. , Reardon Erin E. , Perry Christopher T.
Published: October 2019

Human activities, such as burning fossil fuels, are playing an important role in the rising levels of carbon dioxide (CO2) in the Earth's atmosphere1. The oceans may store a large portion of CO2 that we are releasing into the atmosphere, with up to 40% already taken up by the oceans. Although this absorption helps to offset some of the greenhouse effect of atmospheric CO2, it also contributes to ocean acidification, or a fall in the pH of sea water. The historical global mean pH of oceanic sea water is about 8.2, and this has already declined by 0.1 pH units (a 30% increase in H+ concentration) and is predicted to reach pH ~7.7 by the end of the century if current rates of fossil fuel use continue, leading to an atmospheric CO2 level of 800 p.p.m.1,2. Even this extreme potential fall in pH would still leave seawater above the neutral point (pH 7.0), so technically it is more accurate to say that the ocean is becoming less alkaline, rather than truly acidic (i.e. below pH 7.0). However, the magnitude is perhaps less important than the speed of pH change which is occurring faster than at any time during the previous 20 million years. Over this time, the average ocean pH has probably never fallen below pH 8.02,3. It is only during the last decade that the importance of ocean acidification has come to the forefront of concerns for scientists1,2. Consequences of these changes in global CO2 production are predicted to include elevated global temperatures, rising sea levels, more unpredictable and extreme weather patterns, and shifts in ecosystems1. In order to more fully understand the implications of ocean acidification, teams of researchers, including fisheries scientists, physiologists, geologists, oceanographers, chemists and climate modellers, are working to refine current understanding of the ocean carbon cycle.
Bacteria, good and bad: Host–microbiota interactions in inflammatory bowel disease
Authors: Flanagan Paul , Campbell Barry J. , Rhodes Jonathan M.
Published: October 2019

Inflammatory bowel disease (IBD), a term encompassing the conditions ulcerative colitis (UC) and Crohn's disease, affects around 1 in 300 people in the UK and causes significant morbidity, although, thankfully, little mortality1. Although UC is limited to the colon and causes mucosal ulceration, Crohn's disease can affect any part of the intestine and causes ulceration, transmural inflammation, stricturing, fistula and abscess formation. Both are relapsing and remitting diseases and, despite advances in medical treatments, including immunosuppressants and drugs which specifically block pro-inflammatory molecules (tissue necrosis factor; TNF), about 25% with UC and 50–80% with Crohn's disease will require major surgery at least once in their lives.
Eureka Moments: the Golden Age of Genetics: Alec Jeffreys in conversation with John Armour
Authors: Cox Amy
Published: October 2019

As part of our Centenary celebrations, a number of the Society's Honorary Members have been asked to talk about the important moments in their careers and the future of the discipline. These interviews will be made available throughout the year on the Society's website as a series of podcasts.
More than an enzyme: The biochemical basis of bacterial disease revealed
Authors: Titball Richard W.
Published: October 2019

The work of MacFarlane and Knight which was published in the Biochemical Journal in 1941 changed the way in which bacterial disease was viewed. They found that the ability of Clostridium perfringens to cause disease was almost entirely attributable to the production of -toxin, which had enzymatic activity – it was a phospholipase C. This was the first time that a bacterial toxin was shown to have an enzymatic activity and founded many of the principles which were subsequently applied to the study of other bacterial toxins. This BJ Classics article considers the historical context of this work and how this work has allowed subsequent studies which have changed our understanding of disease caused by C. perfringens.
Natural synthesis: Biologics, biosimilars and biobetters in protein hormone therapy
Authors: Pradhananga Sarbendra , Sayers Jon R.
Published: October 2019

Hormone therapies have been used since the early 20th Century and belong to a group of drugs that has recently become known as ‘biologics’. Biologics are medicinal products that have been produced by biological processes as opposed to chemically synthesized drugs. The term biologics spans a wide range of products that include therapeutics such as organs, tissue, cells, blood or blood components, vaccines and proteins. This ‘proteins’ subgroup can be further subdivided into therapeutics such as antibodies, enzymes and hormones. The first hormone therapeutics were extracted from human or animal sources; however, with the advent and development of cloning and protein production technologies from the late-20th Century onwards, protein hormone therapeutics are now produced by recombinant DNA technology.
The molecular basis of selective autophagy
Authors: Popovic Doris , Dikic Ivan
Published: October 2019

Autophagy is an evolutionarily conserved intracellular degradation process, through which large cellular cargos are sequestered into double-membrane vesicles (autophagosomes) and delivered to the lysosome. Starvation-induced autophagy represents a general non-selective degradation pathway that breaks down cellular components for energy replenishment. Alternatively, selective autophagy targets specific organelles, protein aggregates or invading pathogens that need to be precisely removed from the cell during development or pathogenic infection. Selective autophagy receptors noncovalently bind to the family of ATG8 modifiers and can be controlled by post-translational protein modifications, including ubiquitination and phosphorylation. In this article, we review recent advances in our understanding of the molecular basis of cargo selection in autophagy.
Health consequences of exercise and inactivity: The endurance athlete: high aerobic capacity and improved longevity
Authors: Shaw Christopher , Wagenmakers Anton
Published: October 2019

Adaptations to the cardiovascular, pulmonary and skeletal muscle systems allow endurance athletes to perform exercise for prolonged periods and delay the onset of fatigue. These adaptations explain why the current men's marathon world record holder can run 42.195 km (26.2 miles) in a little over 2 hours at an average speed of over 20 km/h. The adaptations which enable sustained endurance performance also offer protection against many chronic diseases and increase average lifespan. For example, former cyclists who competed in the Tour de France before 1964 demonstrated a 17% increase in average longevity compared with the general population1. Therefore studying the elite endurance athlete can give us clues as to how partaking in regular physical activity, or failure to do so, alters disease risk and life expectancy.
Run, swim, throw, cheat: The future of drugs in sport
Authors: Cooper Chris
Published: October 2019

Modern sport as we know it originated in 19th Century England, codifying competition while emphasizing fair play within a strong moral creed, at least as defined by 19th Century upperand upper-middle-class Englishmen1. Its bible is the semi-mythical description of sport at Rugby School described in Tom Brown's Schooldays. This book so inspired the Frenchman Baron Pierre de Coubertin that he founded the modern Olympic Games in 1896. We await the London version in 2012 with anticipation.
Gopher Science Lab launched with a bang!
Authors: Thomson Jane
Published: October 2019

As usual, I promise myself ‘never again!’ as I finally collapse on the sofa having hosted yet another traditional ‘at home’ style birthday party for six small boys! Musical bumps, pass the parcel, treasure hunts, they were into everything. Having annihilated the piñata, the inquisitive little tribe finally settled down with a box of old toys, pulling them apart, seeing how they worked and pushing buttons just to find out what would happen (a spell on the naughty step if they're not careful!). The indoor firework finale led to lively debate about what would happen if we …ate them? …breathed in the fumes? …ground them all up and set fire to the dust? These 8-year-olds were riddled with curiosity.
Legume root nodule symbiosis: An evolving story in biology and biotechnology
Authors: Brewin Nicholas J.
Published: October 2019

The evolution of biological nitrogen fixation is central to the evolution of life on earth. Nitrogen is an essential component of proteins and nucleic acids and its restricted availability to living organisms has often been a major factor limiting growth. Despite the overwhelming abundance of N2 gas in the atmosphere, di-nitrogen is chemically inaccessible to most forms of life. For their growth and metabolism, most organisms use the ‘fixed’ forms of nitrogen, either as ammonium (NH4+) or as nitrate (NO3-), or derivatives thereof. However, the major input into the global nitrogen cycle is through the reductive process of biological nitrogen fixation which converts atmospheric N2 into ammonia (NH3). This process evolved in bacteria and/or archaea over 2.5 billion years ago while the planet still had a reducing atmosphere. Today, biological nitrogen fixation is still restricted to the bacteria and archaea. The legume root nodule symbiosis allows the host plant to benefit directly by association with soil bacteria, collectively termed rhizobia, which fix nitrogen as endosymbionts.
Seeing the unseen: How plants sense UV-B
Authors: Baxter Katherine J. , Jenkins Gareth I.
Published: October 2019

Sunlight not only drives photosynthesis, but also provides cues to regulate plant growth and development. Termed photomorphogenesis, this ability to modulate development in response to changes in light is key to plant survival. Plants have evolved several photoreceptors to perceive and respond to different wavelengths of light found in the daylight spectrum. The majority of plant photoreceptors are proteins with a bound chromophore, a non-protein component that captures photon energy from a particular wavelength of light and converts it into a signal by inducing conformational changes in the protein itself. The resulting changes in the protein activate a signal cascade, which in turn produces alterations in gene expression, allowing the plant to adapt to the light environment. This article discusses what is known about a novel plant photoreceptor, UVR8, and the signalling pathway it activates.
The Seven Deadly Sins of Twitter
Authors: Sansom Clare
Published: October 2019

When I last covered Twitter for the Cyberbiochemist in 2010, I was something of a newbie: my own account was less than 3 months old. Now 3 years later in this ‘Seven Deadly Sins’ themed issue I am following it up by looking at pitfalls for Twitter users to avoid.
Small-angle scattering and the protein crystallographer: A relationship of ever-increasing interest
Authors: Scott David J.
Published: October 2019

Protein crystallography is one of the great intellectual achievements of the 20th Century, and it continues to open up new vistas of research as scientists are able to visualize in exquisite detail the molecules of Life. It has become increasingly apparent, however, that not all proteins are amenable to crystallographic analysis. These include (but are not confined to) proteins with functional flexible segments, glycoproteins and intrinsically disordered proteins. There are also proteins that, although rigid and folded, refuse to crystallize as an entire full-length construct, and hence high-resolution information has to be pieced together domain by domain. It is into this space that small-angle scattering is increasingly being used as the technique of choice with regard to attainable structural information.
William Dobinson Halliburton (1860–1931): The first Honorary Member
Authors: Lagnado John
Published: October 2019

In 1924, in a rarely quoted but remarkably sharp address on the status of biochemistry in Britain, F. Gowland Hopkins deplored how painfully little, “as compared to any other country of importance”, British work had contributed to advancing the subject [of biochemistry] until the beginning of the 20th Century1. However, as we shall see, W.D. Halliburton appears to be a notable exception to Hopkins' generalization. And indeed, in a retrospective assessment, Hopkins came to regard Halliburton as a pioneer in his own discipline: “He was the first in this country, by his works and his writing, to secure for it [biochemistry] general recognition and respect”2. That, in essence, explains why the Biochemical Society which he was instrumental in founding (see Plimmer's history3 elected him as its first Honorary Member in 1923.
Knockout tissue models: Targeted gene disruption in three dimensions
Authors: Carstairs Alice , Marshall Julia , Genever Paul
Published: October 2019

The use of animal studies in scientific research is increasing, mostly attributed to the rising requirement for genetically modified animals. In 2012, 4.11 million animal procedures were conducted within the UK, the majority of which involved genetically modified animals; a first since records began. Although animal models bring clear scientific insight, they have their limitations and alternative research methods are actively sought. The development of new targeted gene disruption technologies, such as transcription activatorlike effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR), combined with innovative 3D human cell culture methods can provide an attractive in vitro alternative.
Looking for life elsewhere: Photosynthesis and astrobiology
Authors: Kiang Nancy Y.
Published: October 2019

Photosynthesis produces signs of life we can see from space: the absorbance spectrum of surface photosynthetic pigments and, with oxygenic photosynthesis, atmospheric oxygen. Since the first discovery of a planet in another solar system in 1989, there has been an explosion in the detection of exoplanets (over 1849 as of 7 November 2014) and we are getting ever closer to finding that Goldilocks planet that might harbour life. With telescope observations of these planets, oxygenic photosynthesis has been considered our most robust target ‘biosignature’ that would not appear on a lifeless planet. Since anoxygenic photosynthetic organisms do not produce unambiguously biogenic gases, there is interest in their pigments serving as spectral indicators of life. But will they look the same as on Earth, can we distinguish them from the abiotic, and what will dominate on another planet? Examples from Earth provide us with the potential to extrapolate some rules for photosynthesis to predict its signature on another planet, but there are yet things we must answer about life here to improve our confidence. In particular, given the combination of the available stellar spectrum and molecular constraints on photon energy use, can we predict the pigment spectral features that will dominate, which reductant will match, and what biogenic gases would result? We take clues from the diversity of anoxygenic photosynthetic metabolisms and three very recent examples of oxygenic photosynthesis utilizing other reaction centre (RC) chlorophylls in addition to chlorophyll a (Chl a).
CoA regulation and metabolic control
Authors: Jackowski Suzanne , Rock Charles O.
Published: October 2019

All organisms require coenzyme A (CoA) for intermediary metabolism. CoA ushers organic acid substrates, particularly fatty acids, through multiple reactions that supply energy, building blocks for membrane structure, protein modifications that alter subcellular interactions or activities and secondary metabolite production. Acetyl-CoA is an allosteric regulator of key metabolic activities that direct carbon flux. CoA synthesis from pantothenate is dynamic and responsive to nutritional and environmental conditions, with the goal of cell homoeostasis during proliferation and in support of specialized tissue functions. Pantothenate is the unique precursor of CoA, and the pantothenate kinase (PanK) family of enzymes exerts control over the amount of CoA produced. The PanKs are regulated co-ordinately by several mechanisms, and the complexity of CoA regulation is currently unfolding. Little is known about the mechanisms of CoA degradation that work together with biosynthesis to maintain a threshold level of cellular CoA.
Dynamic mRNA modifications: An emerging layer of gene regulation
Authors: Whitehouse Adrian
Published: October 2019

More than 100 different types of chemical modifications are found in cellular RNAs, including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA) and small nuclear RNA (snRNA). Internal modifications of mRNA were first observed in the 1970s, but, until recently, the role of these mRNA modifications has been a largely neglected field. A long-standing view was that mRNA modifications were static and unalterable, having a minor role in fine-tuning the structure and function of mRNAs. However, recent exciting discoveries now suggest that certain mRNA modifications are dynamic and, in some cases, reversible. Therefore they may have critical regulatory roles in gene expression, analogous to those which dynamically regulate DNA and protein modifications. As such, understanding the scope and mechanisms of these dynamic mRNA modifications represents an emerging layer of gene regulation at the RNA level, termed epitranscriptomics or RNA epigenetics.
AUGmenting the proteome: Novel initiation codons and their role in protein isoform generation
Authors: Coldwell Mark J. , Cowan Joanne L.
Published: October 2019

As the field of molecular biology developed, and the understanding of how inherited genetic material results in the expression of proteins was established, the initial hypothesis was that one gene gave rise to one protein1. As researchers delved deeper into the organization of the genetic code and advances in messenger RNA (mRNA) and protein sequencing were subsequently made, it has become abundantly clear that multiple mechanisms exist meaning that many mRNAs encode more than one version of a protein. Although alternative promoters and alternative splicing play a considerable role in the generation of protein isoforms, in this article we discuss how usage of alternative translation initiation codons in eukaryotes can also lead to an expanded proteome.