bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum attenuates learning and memory impairments in scopolamine-treated mice
Authors: Zhang Mengmeng , Xie Mingguo , Wei Daneng , Wang Li , Hu Meibian , Zhang Qing , He Zuxin , Peng Wei , Wu Chunjie
Published: October 2019

Learning and memory impairments are common symptoms of dementia in neurodegenerative disorders.
Remote-controlled multi-enzyme system for enhanced tumor therapy via dark/light relay catalysis
Authors: Chen Ying , Li Zi-Hao , Hu Jing-Jing , Peng Si-Yuan , Rong Lei , Sun Yunxia , Zhang Xian-Zheng
Published: October 2019

A dark/light relay strategy based on a remote-controllable multi-enzyme system was proposed to kill tumor cells upon light irradiation.
Selective ion sieving through arrays of sub-nanometer nanopores in chemically tunable 2D carbon membranes
Authors: van Deursen Pauline M. G. , Tang Zian , Winter Andreas , Mohn Michael J. , Kaiser Ute , Turchanin Andrey A. , Schneider Grégory F.
Published: October 2019

Two-dimensional carbon nanomembranes synthesized from molecular precursors act as ion sieving membranes. The pore density and efficiency of ion selectivity are probed using a combination of HR-TEM and ion transport measurements.
Versatility of bilayer metal oxide coatings on silver nanowire networks for enhanced stability with minimal transparency loss
Authors: Aghazadehchors Sara , Nguyen Viet Huong , Muñoz-Rojas David , Jiménez Carmen , Rapenne Laetitia , Nguyen Ngoc Duy , Bellet Daniel
Published: October 2019

Silver nanowire (AgNW) networks have been lately much investigated thanks to their physical properties and are therefore foreseen to play a key role in many industrial devices as transparent electrodes, but their stability can be an issue.
A novel AIE-active dye for fluorescent nanoparticles by one-pot combination of Hantzsch reaction and RAFT polymerization: synthesis, molecular structure and application in cell imaging
Authors: Chen Yali , Huang Zengfang , Liu Xiaobo , Mao Liucheng , Yuan Jinying , Zhang Xiaoyong , Tao Lei , Wei Yen
Published: October 2019

This work reported the fabrication of a novel AIE-active dye and its amphiphilic PEG-TPD fluorescent polymers via one-pot combination of RAFT polymerization and Hantzsch reaction, which showed potential applications in bioimaging.
Gamma radiation as a green method to enhance the dielectric behaviour, magnetization, antibacterial activity and dye removal capacity of Co–Fe LDH nanosheets
Authors: Amin Rafat M. , Taha Mohamed , Abdel Moaty S. A. , Abo El-Ela Fatma I. , Nassar Hossam F. , GadelHak Yasser , Mahmoud Rehab K.
Published: October 2019

Nowadays, improving the physico-chemical properties of nanomaterials to enhance their performance towards various applications is urgent.
Cyanobacterial promoted enrichment of rare earth elements europium, samarium and neodymium and intracellular europium particle formation
Authors: Fischer Christian B. , Körsten Susanne , Rösken Liz M. , Cappel Felix , Beresko Christian , Ankerhold Georg , Schönleber Andreas , Geimer Stefan , Ecker Dennis , Wehner Stefan
Published: October 2019

Efficient biosorption and intracellular accumulation of selected rare earth elements from aqueous solutions by cyanobacteria type Anabaena.
Retracted Article: Knockdown of long non-coding RNA OIP5-AS1 suppresses cell proliferation and migration in ox-LDL-induced human vascular smooth muscle cells (hVMSCs) through targeting miR-152-3p/PAPPA axis
Authors: Yang Xiangya , Li Zhongrui , Zhang Lei , Wu Xiaoshan , Kang Qixin , Li Li
Published: October 2019

Knockdown of OIP5-AS1 suppressed ox-LDL-treated hVMSCs proliferation and migration; overexpression of miR-152 played the similar role of OIP5-AS1 knockdown; OIP5-AS1 functioned as ceRNA to regulate PAPPA expression through sponging miR-152.
High-yielding Pd2(dba)3·C6H6-based four-fold Sonogashira coupling with selenophene-conjugated magnesium tetraethynylporphyrin for organic solar cells
Authors: Wang Huan , Nakagawa Takafumi , Zhang Meng-Meng , Ogumi Keisuke , Yang Shangfeng , Matsuo Yutaka
Published: October 2019

A catalytic system using Pd2(dba)3·(C6H6)/PPh3/CuI for Sonogashira coupling was demonstrated to synthesize a selenophene-conjugated magnesium tetraethynylporphyrin Mg-TEP-(Se-DPP)4 (2a).
A mathematical model of a slurry reactor for the direct synthesis of hydrogen peroxide
Authors: Pizzetti Fabio , Granata Vittoria M. A. , Riva Umberto , Rossi Filippo , Masi Maurizio
Published: October 2019

The direct synthesis of H2O2 is a green alternative to the conventional large-scale anthraquinone process and offers a significantly economic advantageous way of producing a compound for which the global demand is ever increasing.
A rare earth hydride supported ruthenium catalyst for the hydrogenation ofN-heterocycles: boosting the activityviaa new hydrogen transfer path and controlling the stereoselectivity
Authors: Wu Yong , Yu Hongen , Guo Yanru , Jiang Xiaojing , Qi Yue , Sun Bingxue , Li Haiwen , Zheng Jie , Li Xingguo
Published: October 2019

A novel Ru/YH3catalyst with excellent performance in terms of activity and stereoselectivity for hydrogenation ofN-heterocycles is developed.
Layer-by-layer assembly for immobilizing enzymes in enzymatic biofuel cells
Authors: Zhang Jiru , Huang Xingcan , Zhang Lili , Si Yawei , Guo Shuai , Su Hang , Liu Jian
Published: October 2019

Various methods of immobilizing enzymes on electrodes have been developed for the research of enzymatic biofuel cells (EBFCs).
Supporting Excellence in the Science Base: Reaching the inner ear of the EC: how scientists lobby for their interests at the European Commission
Authors: Moore Andrew
Published: October 2019

In 1999, one American university alone spent US$760,000 on lobbying politicians for funding to improve its science facilities. Boston University was criticized when it contracted a professional lobbying agency, Cassidy & Associates, to do the ‘dirty’ work. That is how it would be considered in the medieval world of European science politics. Welcome to the arcane, unintuitive and dimly lit labyrinth of the European Commission (EC). While some wander the narrow passageways with no more than a tallow torch to light their way, eventually joining the dusty skeletons, others seem to be friends with its keepers, and know the passwords to the secret rooms.
Teaching the scientists of tomorrow
Authors: Loosley Rachel
Published: October 2019

All three of the Society's Biochemical Basis of Biology videos are now available to view on the Internet, thanks to the Lifesign project. The project's website hosts the digital video programmes, which are fed live to the user's computer screen. Unlike downloading files (which can take absolutely ages!) the video stream is not saved onto the computer; it is sent out from the central server in real time and decoded directly at the user's computer. To view the videos you will need version 6.4 of Microsoft Windows Media Player, which can be downloaded free from the Lifesign website.
Proteins: from Chemical to Physiological Mechanism: 26 October 2001
Authors: Trentham David , Greeves Michael
Published: October 2019

The Molecular Enzymology Group of the Biochemical Society held a special 1-day meeting at the Royal Society on ‘Proteins: from Chemical to Physiological Mechanism’. The aim of the meeting was to inform and stimulate discussion on kinetic approaches to the life sciences by bringing together work on dynamic aspects of protein function. The meeting also honoured Professor H. (Freddie) Gutfreund, FRS, on his 80th birthday. Professor Gutfreund persuaded the Executive Committee of the Society to found the Molecular Enzymology Group, the first sub-group of the Society. His view of the strategic value in encouraging like-minded biochemists to interact has done much to provide the critical mass necessary for sustaining excellence in the various sub-disciplines of biochemistry.
Adrenaline junkies: Addicted to the rush?
Authors: García-Sáinz J. Adolfo
Published: October 2019

In 1895, Oliver and Schäfer reported the marked effects that crude extracts of the adrenal gland induced on cardiac function and blood pressure. This was the birth of medical research on adrenaline1,2. Adrenaline is a key player in the maintenance of homoeostasis and it is difficult to mention a major physiological function in which the natural adrenergic amines, adrenaline and noradrenaline, are not involved; they also have their ‘dark side’, participating as they do in the pathogenesis of different diseases2,3.
Glycomics: A complex challenge
Authors: Hansson Gunnar
Published: October 2019

At a time when the sequencing of genomes is becoming trivial, defining the proteome by proteomics is causing more difficulties; however, the real challenge will be the study of the co- and posttranslational modifications of these proteins. Among these, the study of glycosylation will be the most challenging owing to the chemical nature of glycans. These are built on several monosaccharide types that can be linked together at different linkage positions with two linkage configurations ( and ), and finally, more than one sugar can be attached to one monosaccharide unit, which give rise to branching. Over the years, the various ways that two monosaccharides can be linked together have been discussed, although this is a theoretical exercise that has limited practical meaning as the number of actual linkage positions and configurations used is much less and is limited by the specificities of the glycosyltransferases, the enzymes that are responsible for the biosynthesis of glycans.
Teaching the scientists of tomorrow
Authors: Dallimore Elizabeth
Published: October 2019

Who can name the ten top male scientists who have ever lived? Answers will vary depending on your interests, but the majority of scientists shouldn't have a problem in naming ten, or perhaps even 20. Now what about the top ten female scientists? Much more difficult perhaps! Names such as Marie Curie and Rosalind Franklin are no doubt in the list, but what about in the last 10 years? How many men have won the Nobel prize for medicine in the last 5 years, compared with the number of women? (The answer is that no women have won the Nobel prize in the last 5 years. Indeed, in the last 20 years only three women have been awarded this prestigious prize, compared with 40 men.)
Integral membrane enzymes: What are the problems?
Authors: Lee Anthony G.
Published: October 2019

Integral membrane enzymes have to function in the environment provided by the lipid bilayer component of a membrane. This raises interesting problems of design; not only must these enzymes contain hydrophobic -helices or -barrels to span the lipid bilayer, they must also have a design compatible with the translocation machinery used to insert proteins into membranes. One solution is to separate functions in the enzyme as far as is possible, so that the enzymology is carried out in domains located outside the lipid bilayer. When active sites are located within the lipid bilayer, they are often located at protein-protein interfaces in dimeric structures. Because these enzymes are designed to operate in a lipid bilayer, they are best studied after reconstitution into lipid bilayers.
Past times: A biochemical correspondent
Authors: Campbell Peter
Published: October 2019

I have recently written a book, A Biochemical Foreign Correspondent: Stories and Impressions from Around the World*, which describes my experiences in many countries when working for IUBMB, FEBS and other international organizations. Apart from the pleasure of writing, my object has been to emphasize how privileged we academics are in being members of a benevolent club. I feel sure that I can land in almost any large city in the world and find a biochemist with whom I can share common values. My hope is that we scientists may, thereby, be able to make a broad contribution to World understanding. Here, I would like to take the opportunity to reflect more generally on my impressions.
Improving the lot of contract-research staff: Supporting Excellence in the Science Base
Authors: Withnall Mike
Published: October 2019

The Roberts review of the supply of scientists and engineers in 2002 identified a range of concerns about the recruitment, retention and development of university contractresearch staff, notably the lack of a clear career structure, together with uncertain job prospects. The review anticipated that the implementation of the European Directive on Fixed Term Work would remove some of this uncertainty. The Directive requires that the use of successive fixed-term contracts with the same employer is limited to 4 years unless an extension can be justified on objective grounds.
Let there be light!: Clock photoreceptors and the need for rhythm
Authors: Heintzen Christian , Elvin Mark , Price-Lloyd Nathan
Published: October 2019

Light is one of the major signals that keep biological clocks in harmony with the outside world. Consequently, if we want to understand how circadian clocks function at the molecular level, a study of the lightinput pathways to the clock is of fundamental importance.
Multiplication and division: Archaic modes of DNA replication initiation
Authors: Robinson Nicholas P. , Bell Stephen D.
Published: October 2019

Proliferating cells must produce a complete and accurate copy of their genetic material by DNA replication prior to cell division, and in all organisms this duplication begins at discrete sites known as replication origins. In eukaryotic cells, DNA synthesis is initiated from a large number of these regions, whereas bacterial cells replicate less complex genomes from a single origin. It is only in recent years that the process of replication initiation has become elucidated in the third domain of life, the Archaea.
The way forward: the Executive Committee's views on the proposed European Research Council: Supporting Excellence in the Science Base
Authors: Coggins John
Published: October 2019

The Biochemical Society has been asked by FEBS for its views on the structure, organization and role of the proposed European Research Council (ERC). This was discussed at the January Strategy Meeting of the Executive Committee and there was a clear consensus among the members present. These views, which are summarized below, were communicated to FEBS in February.
The European Bioinformatics Institute: Leading the bioinformatics revolution
Authors: Thornton Janet , Cameron Graham , Brooksbank Cath
Published: October 2019

Life without databases is almost inconceivable to today's researchers in the biomolecular sciences -- the world of biomolecules is freely available on the Internet, along with a powerful set of tools for analysing the data. Many of the world's most widely used data resources are hosted and developed at the European Molecular Biology Laboratory (EMBL)'s European Bioinformatics Institute (EBI), often in collaboration with partners throughout the world. The EBI is also a thriving research centre.
Whither biochemistry and chemistry?: Supporting Excellence in the Science Base
Authors: Stockley Peter , Townsend Rodney
Published: October 2019

At the start of the 21st Century both biochemistry and chemistry appeared well-placed to capitalize on the ‘century of biology’ and the exciting possibilities promised by ‘nanotechnology’. In addition, both appeared to be essential elements in understanding and monitoring environmental quality and its impact on human health, with major sectors within the UK economy critically dependent on the flow of highly trained personnel in these fields. The future, surely, looked rosy. However, in the last 6 months, three major UK university chemistry departments have been closed down, and over the last 5 years or so, the numbers of biochemistry departments returning separately under the National Research Assessment Exercise (RAE) has fallen dramatically. Here, we explore the background to these apparently incongruous developments and what they could portend for the future.
Life in frozen veins: Coping with the cold
Authors: Thomas David N. , Mock Thomas
Published: October 2019

Every autumn a fundamental transition occurs in the surface waters of polar oceans. Millions of square kilometres of surface waters freeze to form an ice layer that varies from a few centimetres through to several metres thick, and which effectively separates the ocean from the atmosphere above. Ice made from seawater is a porous, semi-solid matrix permeated by a labyrinth of brine channels and pores, and within these a diverse microbial assemblage, including viruses, Archaea, bacteria, flagellates and unicellular algae can thrive. These assemblages can reach such high abundances that the ice becomes a rich coffee colour. The microbial assemblages are in turn a rich food source for grazing protoplankton and zooplankton, especially in winter when food in the water column is scarce.
A matter of taste: Nutrient Sensing Through the Plasma Membrane of Eukaryotic Cells, a Biochemical Society Focused Meeting, held at the Royal Agricultural College, Cirencester, 25–29 September 2004
Authors: Shirazi-Beechey Soraya
Published: October 2019

Sensing nutrients is a fundamental property of all living cells. Indeed, it is an absolute requirement for their ability to adapt to changes in their nutritional environment.There are an increasing number of published reports describing examples of nutrient-sensing molecules in the plasma membrane of fungi, plant and animal cells.These nutrientsensing molecules include nutrient carriers, molecules analogous with nutrient transporters, but without demonstrable transport function, and members of a large superfamily of GPCRs (G-protein-coupled receptors).These reports have added a fascinating new function to the plasma membrane as a nutrient-sensing device.
Mitochondrial DNA and disease: What happens when things go wrong
Authors: Schapira Anthony
Published: October 2019

Mitochondria are ubiquitous in eukaryotic cells and one of their important functions is to provide ATP via oxidative phosphorylation (OXPHOS). The mitochondria also host other biochemical pathways, including -oxidation, Krebs' citric acid cycle and parts of the urea cycle. Thus, the mitochondria play a pivotal role in cellular biochemistry. The relationship of mitochondria to human disease has been identified only recently, but has now become one of the most rapidly expanding areas of human pathology. Mitochondrial disorders may be a consequence of inherited defects of either the nuclear or mitochondrial genomes or, alternatively, may be due to endogenous or exogenous environmental toxins. This article will focus upon abnormalities of mitochondrial DNA (mtDNA) and human disease.
Studying live embryos in 4D: Selective plane illumination microscopy: a new technique for high-resolution four-dimensional imaging
Authors: Huisken Jan
Published: October 2019

Selective plane illumination microscopy (SPIM) offers an alternative way of optically sectioning the sample in fluorescence microscopy. By illuminating the sample with a sheet of light, a sectioning effect can be obtained that is similar to that in confocal microscopy. However, in combination with widefield detection, such an approach has several advantages over confocal scanning microscopy. SPIM offers reduced fluorophore1 bleaching, fast, highly efficient image recording, and high depth penetration, especially when multiple views are combined. SPIM performs especially well in large samples such as fish or fly embryos, which can be observed live for several days. The principle is universal and can also be applied to micrometre-sized samples.
Digital images in science: Fair or fraud?
Authors: Entwistle Alan
Published: October 2019

Almost all scientific images are now collected and saved as digital data rather than physical photographs, pen recordings etc., making it far easier to alter their contents. This has led researchers to question what is valid practice and what is inappropriate manipulation of image data1. Some have even proposed that there should be rigid rules, but I argue that this is excessively restrictive and will do nothing to curb fraudulent practices.
Tetrahymena – the advanced eukaryote model: Complexity that can be exploited
Authors: Gaertig Jacek
Published: October 2019

The recent completion of sequencing the genome of the ciliate Tetrahymena thermophila by The Institute for Genomic Research (TIGR)1 is an opportunity to re-evaluate this fascinating organism as an experimental eukaryotic model.
Stem cells in liver repair
Authors: Kallis Yiannis N. , Forbes Stuart J.
Published: October 2019

The liver can be subjected to many damaging insults, usually from toxins, viral infections, immune or metabolic diseases, during its lifetime. Normal restoration of liver tissue occurs via division of mature functional hepatocytes. In addition, a liver-stem-cell compartment, lying deep within the intrahepatic biliary tree, can be activated during severe or iterative stress. Recent studies have suggested that the bone marrow (BM) may also contribute to liver regeneration, although these observations remain controversial.
Signalling: the remarkable dynasties
Authors: Irvine Robin
Published: October 2019

The list of Biochemical Journal papers selected by the Editorial Board1–12 for the ‘classic’ status in signalling (plus a couple of directly relevant classics from the metabolism/enzymes section that I have included) consists almost entirely of papers with inositol or inositide in the title. This reflects a truly remarkable relationship between inositides, UK scientists and the Biochemical Journal.
Flexing their muscles: the discovery of myosin phosphorylation
Authors: Walsh Michael P.
Published: October 2019

The classic Biochemical Journal paper by Perrie, Smillie and Perry1, A phosphorylated light-chain component of myosin from skeletal muscle (1973), is a beautiful example of the long-term impact of rigorous biochemical detective work. In essence, the authors had previously observed that one of the three light-chain subunits of skeletal muscle myosin II detected by SDS/PAGE could be separated into two protein bands by charge gel electrophoresis in the presence of urea2. The key advance reported in this paper1 was the characterization of the difference between the two proteins: the species migrating more rapidly towards the anode was shown to be a phosphorylated form of the slower-migrating polypeptide. This discovery turned out to have profound biological implications.
The Biochemical Society: Supporting Excellence in the Science Base: A single health research fund: have your say
Authors: Burgess Mark
Published: October 2019

In his budget speech, Chancellor Gordon Brown promised to strengthen excellence in medical research by establishing a single budget for the Medical Research Council (MRC) and the Department of Health Research and Development. The Government is now seeking comments on its proposal to form this single ‘Health Research Fund’, jointly owned by the National Health Service (NHS) and MRC. The fund will have a budget of ‘at least’ £1 billion: the NHS and MRC at present have a combined budget of £1.3 billion.
Shedding light on the dark reactions: Hatch and Slack and C4 photosynthesis
Authors: Gutteridge Steven
Published: October 2019

Some 40 years ago almost to the month, Hatch and Slack1 reported in the Biochemical Journal that the initial reactions of CO2 fixation in some plants were significantly different from those recently accepted to describe the general process of photosynthetic carbon assimilation. Their observations that C4 dicarboxylic acids were the initial products of assimilation rather than 3-phosphoglycerate confounded established assertions. This work, and subsequent papers that emerged, made a huge impact, both biochemical and physiological, on the field of photosynthesis.
Teaching the scientists of tomorrow: Introduce someone to research with a Summer Vacation Studentship
Authors: Baker Hannah
Published: October 2019

The next application deadline for Summer Vacation Studentships is 28 February 2007. Forms, rules and guidelines can be found at http://www.biochemistry.org/education/vacation.htm

The Learning Curve feature in the August 2006 issue of The Biochemist provided a snapshot of the Society's Summer Vacation Studentship Awards and the expectations of the ten students about to embark upon 8-week research projects at institutions across the globe. In this followup article, I catch up with the undergraduates and their supervisors to find out how they each benefited from a summer in the laboratory.
Tissueengineered skin and the treatment of burns: Skin doctor
Authors: Berthod François
Published: October 2019

The increasing survival rates of extensively burnt patients due to the progress in intensive care has amplified the need to find alternative strategies to cover these deep burns. Tissueengineered skin models have been developed; culturing keratinocytes over a collagen gel or sponge populated with fibroblasts. Some of these models have been commercialized as biomaterials or highly sophisticated wound dressings, demonstrating the feasibility of tissueengineered skin development from bench to bedside. Investigations now aim to optimize these models to overcome some limitations encoun tered in their clinical applications, such as their vascularization and innervation.
New vessels: Vascular tissue engineering
Authors: Kannan Ruben Y. , Sarkar Sandip , Mirzay-Razaz Jalaledin , Seifalian Alexander M.
Published: October 2019

The use of vascular bypass grafts in patients is not new. The high prevalence of atherosclerosis has seen them being used in the treatment of some of the 800 000 cases of myocardial infarction in the UK. So, is there a need for tissue-engineered blood vessels if there is a functional prosthetic alternative? While this may hold true for vessels with high-blood-flow rates1, the patency rates of poly(ethylene terephthalate) (Dacron®) and expanded polytetrafluoroethylene (ePTFE) grafts are less satisfactory at lower flow rates. Given the limitations with synthetic materials alone, a biological or bio-hybrid vascular prosthesis could provide us with the ideal blood-vessel substitute.
Design by chip: Computer-aided tissue engineering
Authors: Sun Jae Nam, Binil Starly and Wei
Published: October 2019

Computer-aided tissue engineering (CATE) is an evolving, multi-disciplinary field that utilizes the tools of medical image processing, computer-aided design (CAD), computational analysis, multiscale modelling and biomanufacturing for the purposes of tissue engineering. The merging of computation and automation with tissue engineering could have the potential for profound advances in developing tissue replacements and also in better understanding of physiology and pathology at a cellular, tissue, and organ level.
The cloning revolution: DNA cloning and biochemistry
Authors: Hartley James L.
Published: October 2019

According to the online reference source Wikipedia (www.wikipedia.org), biochemistry is “the study of the chemical processes and transformations in living organisms. It deals with the structure and function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules.” It seems appropriate to start with a definition from the World Wide Web, which has changed information retrieval as much as DNA cloning has changed biochemistry. Here I attempt to provide some perspectives on that transformation.
The use of fibroblasts: Smoothing away wrinkles
Authors: Ueda Minoru
Published: October 2019

Following tooth loss, alveolar bone has a tendency to be absorbed1–3. The loss of supporting bone often results in shrinkage of soft tissue and creates aesthetic problems in the perioral skin. This is especially true when anterior teeth have been missing for a relatively long period. A prosthesis, including dentures or implants, can partially compensate for the lost tissue and collapsed facial profile. However, once wrinkles have formed in lip skin, the correction of this aesthetic problem may not be fully achieved by prosthesis alone.
Fighting sleeping sickness: Krebs Memorial Scholarship
Authors: Vasileva Nadina
Published: October 2019

My name is Nadina Vasileva and I am Bulgarian. I was born in Odessa, Ukraine, where my parents were studying to obtain their PhDs in science. We remained in Odessa until I was 10 years old, but, due to lack of sufficient income, my family returned to Bulgaria, where the work opportunities were better for my parents at the time. I completed my secondary education at the 1st English High School in the city of Varna, where I was inspired for the first time to pursue a career in the biological sciences.
Zinc-finger exercisesThe ‘cutting edge’ of gene therapy … literally
Authors: Segal David J.
Published: October 2019

The traditional gene-therapy approach relies on the delivery of a therapeutic transgene into a cell, typically to compensate for a gene that is not functional owing to a genetic defect. But why not just correct the genetic defects directly? The answer used to be that there was no methodology for making precise genetic modifications in a highly efficient manner. That is changing now. Over the last decade, researchers have devised a way to stimulate the natural DNA-repair mechanisms of the cell to occur at any desired site in the genome. The enabling technological advance has been the development of programmable nucleases, which use re-engineered ZF (zinc-finger) DNA-binding domains to cut the DNA in a living cell at a precise user-defined location. These methods have been shown to produce genetic modifications at frequencies of >1 correct event per ten treated cells, representing a 100 000-fold stimulation of targeted gene repair. The first Phase I clinical trial of a therapeutic ZFN (zinc-finger nuclease) is scheduled for 2008.
Success and risk: Gene therapy for severe combined immunodeficiency
Authors: Thornhill Susannah I. , Thrasher Adrian J.
Published: October 2019

SCIDs are a group of inherited disorders characterized by profound defects in both cellmediated and humoral immunity (Figure 1). These diseases represent the most severe forms of primary immunodeficiencies, affecting approximately 1 child in every 75000 livebirths. The molecular pathology of these disorders has been deter mined for the majority of cases (Table 1), which typi cally present in the first few months of life with failure to thrive, chronic diarrhoea and recurrent infections. Conventional treatment for SCID is HSCT (haemo poietic stem cell transplantation) with high longterm survival rates for transplants from genotypically matched family donors. For the majority of patients for whom a matched family donor is unavailable, how ever, mismatched procedures offer a poorer prognosis and may be associated with incomplete recovery of immunity. Gene therapy therefore presents an attractive therapeutic alternative, and several features of SCIDs make these disorders particularly amenable to correc tion by this technology. First, as stated above, the molecular basis of the majority of SCID phenotypes has been defined and at tributed to defects in single genes (Table 1). Secondly, treatment by HSCT is curative, supporting the notion that correction of a patient's own bone marrow stem cells will lead to restoration of immunity. The target stem cells are easily accessible (allowing gene therapy to be performed ex vivo) and, furthermore, correction of the gene defect in these cells should confer a strong growth and survival advantage in the SCID setting. The gene therapy procedure can therefore be performed without or with minimal chemotherapeutic conditioning. This concept is supported by the partial immunological re constitution observed in two patients following spon taneous mutationreversion events and demonstrates that the correction of even a small number of lymphoid precursors may confer significant therapeutic benefit1,2.
Enzyme action: lock up your waters?: Water and active sites
Authors: Lapthorn Adrian J. , Price Nicholas C.
Published: October 2019

Water is thought of as the universal solvent for biological macromolecules, and its interaction with the different amino acid side chains of proteins determines their folding. Only a small proportion of the water associated with enzymes is tightly bound, but this can play crucial roles in determining the rates and specificities of reactions. Water itself is a relatively poor nucleophile, and enzymes can employ different strategies to facilitate hydrolytic reactions.
Ethics and plagiarism: Helping undergraduates write right
Authors: Willmott Chris , Badge Joanne
Published: October 2019

In June 2008, celebrity psychiatrist Raj Persaud was disciplined by the General Medical Council for the unattributed republication of work by other scholars as though it was his own1. This high-profile case is only one example of a growing anxiety about plagiarism, both in academic works and, particularly, in undergraduate courses. Indeed, concern about plagiarism now starts before students even get to Higher Education. For example, the discovery that 233 university applicants all cited as their inspiration to study medicine2 the same childhood incident – in which they set fire to their pyjamas – has led to the routine screening of all UCAS (Universities and Colleges Admissions Service) applications.
What makes a man?: The effect of androgen receptors on male fertility
Authors: Smith Lee B. , Saunders Philippa T.K.
Published: October 2019

Androgens are the major drivers of masculinization and male fertility, and disruption of androgen signalling has been implicated in the most common male congenital abnormalities, such as hypo spadias (opening of the urethra in a position not at the tip of the penis) and cryptorchidism (testes in the abdomen not the scrotum), as well as with an increased risk of developing testicular cancer or having a low sperm count in adulthood1.
Pollution and fertility: Potential effects for environmental xeno-oestrogens
Authors: Deroo Bonnie J. , Burns Katherine A. , Winuthayanon Wipawee , Korach Kenneth S.
Published: October 2019

Xeno-oestrogens are man-made compounds that have oestrogenic-like activity, and exposure to xeno-oestrogens in critical periods of development and during adulthood may adversely affect both the male and female reproductive systems and fertility. For example, some studies suggest semen quality is declining globally due to xeno-oestrogen exposure, although this remains a controversial issue1.
Mapping life's reactions: A brief history of metabolic pathways and their regulation
Authors: Newsholme Philip
Published: October 2019

It is now recognized that almost all chemical reactions that take place in a living cell require an enzyme to catalyse the reaction. An enzyme catalyses one (or, in rare cases, more than one closely related) chemical reaction. The complete synthesis or degradation of complex biological substances such as glycogen, nucleic acids, proteins and lipids requires a series of linked sequences of reactions. A chain of such reactions is referred to as a ‘metabolic pathway’.
Under the lash: Demodex mites in human diseases
Authors: Lacey Noreen , Kavanagh Kevin , Tseng Scheffer C.G.
Published: October 2019

Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mites, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3–0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2–0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.
Science for the public: Beyond the wow factor
Authors: Brown Tracey
Published: October 2019

We seem to be in a second golden age when it comes to sharing science. If this article has caught your eye, the chances are that you are involved in some kind of public outreach activity. Compared with just 7 short years ago, when we battled against an absence of scientific voices in civil society, Sense About Science now works in a much more ‘can do’ environment, where researchers embark on their careers with some expectation of a public interface, where research grants regularly stipulate it, colleagues often support it and institutions run science programmes and festivals. Yet, if we look at all of the sharing and engaging activity according to its purpose, we find that, as a society, we have barely begun to explore popularizing science as a tool for empowering the public.
The bright future: Imaging dynamic cellular events with quantum dots
Authors: Smith Andrew M. , Wen Mary M. , Nie Shuming
Published: October 2019

Semiconductor quantum dots (QDs) are tiny light-emitting particles that have emerged as a new class of fluorescent labels for biology and medicine. Compared with traditional fluorescent probes, QDs have unique optical and electronic properties such as size-tuneable light emission, narrow and symmetric emission spectra, and broad absorption spectra that enable the simultaneous excitation of multiple fluorescence colours.
From the Philosopher's Stone to the Researcher's Dream: Bringing ease-of-use to fluorescence and confocal microscopy
Authors: Barghaan Jan
Published: October 2019

Although naturally occurring luminescence has been observed for many centuries, the first study on it was not completed until the golden age of alchemy by Vincenzo Casciarolo, who discovered ‘Bolognian Phosphorus’ often referred to as ‘Bolgnian Stone’ or ‘Litheophosphorus’1. Much was debated and written on this supposed philosopher's stone, but the physicochemical basis of its absorption and emission of light remained poorly illuminated. Through seminal work by many researchers, including Sir George Stokes2, our knowledge of such properties has clearly increased, and we now have a deeper understanding of the specific excitation and emission wavelengths of an enormous number of different fluorescent molecules. As a result, fluorescence (and to a lesser extent luminescence) is used across many life science research protocols to track and ana lyse molecules within many different paradigms. Although a number of molecules possess intrinsic fluorescence (or even luminescence), the majority of applications involve the use of exogenous fluorescence dyes or recombinant proteins to tag a molecule of interest. Arguably, the investiga tive tool that has benefitted the most from the application of this fluorescence knowledge, and in turn contributed greatly to the advancement of science, is microscopy3. But fluorescence micro scopy and its derivations are far from simple and involve a large amount of user knowledge. A new concept, however, is set to provide advanced microscopy that bypasses the need for indepth optical knowhow – a researcher's dream.
Storming the light limit: How far can you go?
Authors: Drent Peter
Published: October 2019

Optical light microscopy is set to enter a new era of superresolution with the development of technolo gies that overcome the resolution limit of traditional light microscopes. Ideal for a variety of disciplines within the biological sciences, these new technologies enable the study of cell structure at the nanoscale, revealing cellular features previously impossible to see. Whereas nanoscale imaging has been possible for many years using electron microscopy methods, the new superresolution optical technologies en able twodimensional and threedimensional imaging of fixed and/or living specimens. In this article, we provide a brief overview of the development of superresolution microscopy and Nikon's offering for superresolution fluorescence imaging, NSIM, with lateral resolution twice that of conventional light microscopes and suitable for fixed and live cell imaging, and NSTORM, which achieves a remarkable lateral resolution of approximately 20 nm and axial resolution of approximately 50 nm in fixed specimens.
Putting equality on the agenda
Authors: Smith Rebecca
Published: October 2019

At a recent Policy Lunchbox event, Jane Butcher the Deputy Director of the UK Resource Centre for Women in Science, Engineering and Technology (UKRC SET) gave a presentation on ‘Women in science: a policy perspective’. The following is a report from this meeting.
The most poisonous substances known: What makes some bacterial toxins so dangerous?
Authors: Moss David , Basak Ajit , Naylor Claire
Published: October 2019

We are used to thinking of proteins as beneficial, so it is surprising to realize that the most toxic substances known to man are also protein molecules. These are the bacterial exotoxins, proteins secreted by pathogenic bacteria. Toxicity is measured by the median lethal dose (LD50). An LD50 value is defined as the mass of toxin per kg of body weight required to wipe out half of an animal population. Whereas classic poisons, such as potassium cyanide or arsenic trioxide, have LD50 values in the range 5–15 mg/ kg, the causative agent of botulism, botulinum toxin, has an LD50 in the range 1–3 ng/kg, a million times more toxic!
Killing me softly: Alcohol is the poison of choice
Authors: Davies Nathan
Published: October 2019

Alcohol is toxic. Even though it is consumed regularly by a large proportion of the population, it is indisputable that alcohol is poisonous to the body. Fortunately, the body is equipped with detoxification mechanisms to ameliorate the extent of the damage caused by alcohol, primarily in the liver. However, these defences are limited, and repeated exposure to excessive alcohol levels will result in significant long-term damage.
Epigenetics and aging
Authors: Mellor Jane
Published: October 2019

Aging is the accumulation of changes in an organism over time that leads to reduced viability. Studies in model organisms indicate that aging is genetically determined and that alterations to specific genes can extend or shorten lifespan. Some organisms exhibit negligible aging with no loss of metabolic functions or fertility over time, despite a high metabolic rate, raising the question as to why and how some organisms age and die. A number of theories of aging have been proposed, including telomere shortening, wear and tear (somatic mutations, error accumulation, loss of protein function, etc.), autoimmune disease and reduced mitochondrial function leading to oxidative stress and damage to DNA and proteins1.
The wiring of protein networks: Computational approaches for predicting protein interaction networks
Authors: Ta Hung Xuan , Holm Liisa
Published: October 2019

A great number of cellular behaviours are mediated by proteins which always carry out their functions by interacting with each other. Unravelling protein–protein interactions (PPIs) is one of the central goals in proteomics, which will decipher the molecular mechanisms underlying the biological functions and thereby help to understand human diseases on a system-wide level. A number of experimental techniques, especially high-throughput approaches, have resulted in a large amount of PPI data that still suffer from incompleteness and contradiction. Moreover, these experimental techniques are expensive, time-consuming and labour-intensive. Computational methods have emerged as complementary tools to experimental approaches to discover PPIs. Promisingly, computational methods can guide, assess and validate experimental data and finally predict novel PPIs.
Silicomics: Silicon enters the 'omics arena
Authors: Lopez Pascal Jean
Published: October 2019

Silicon is the second most abundant element in the Earth's crust, making up about onequarter of the crust by mass. In the modern surface waters of recent oceans, silicon is undersaturated, but it is estimated that its concentration was much higher before the rise of the diatoms during the Jurassic–Cretaceous periods. Since silicon is everywhere, it is not surpris ing that, over time, a large number of marine and terrestrial organisms have acquired or developed the ability to use or to transform silicon. It is generally known that many organisms accumulate and/or use silicon to construct inter nal or external skeletons. One such organism is diatoms, a class of photosynthetic microalgae capable of creating beautiful threedimensional silica structures, called frustules. The importance of silicon has also been demonstrated by numerous studies in plants showing that silicon improves the resistance to diseases and mitigates other biotic or abiotic stresses. In this article, I highlight selected studies that aimed to understand the meta bolism of silicon, with a particular emphasis on the diatoms.
Expanding the oceanic carbon cycle: Jellyfish biomass in the biological pump
Authors: Lebrato Mario , Jones Daniel O.B.
Published: October 2019

With atmospheric CO2 concentrations increasing, it is vital to improve our understanding of the processes that sequester carbon, the most important being the biological pump of the world's oceans. Jellyfish might not spring to mind as major players in the global carbon cycle but the evidence of large jelly-falls on the world's deep seabeds suggests that gelatinous zooplankton have a greater role in the biological pump than we thought previously. Jellyfish blooms may be increasing and dead jellyfish may offer a rapidly accessible food source as they sink. We have developed a model to explore the remineralization of gelatinous carcasses as they sink, which is allowing us to predict the effects of jelly-falls on carbon transfer around the world.
The History of the Biochemical Society: Why write another one?
Authors: Kirk Chris
Published: October 2019

Well, the Biochemical Society is 100 years old this year. This event is being celebrated in a variety of ways, as outlined by the Chair, Colin Kleanthous, in his article in the December 2010 issue of The Biochemist1. A significant birthday like 100 certainly invites members, or at least those of us old enough to remember to our 75th Jubilee year in 1986, to reflect on how the Society has changed over the years.
Autophagy: Dance of the yeast ATGs and worm EPGs
Authors: Wu Fan , Zhang Hong
Published: October 2019

Macroautophagy (hereinafter referred to simply as autophagy) is a lysosome-mediated intracellular degradation process that involves the bulk segregation and digestion of portions of the cytoplasm in membrane-enclosed vacuoles1. The dynamic process of autophagy starts with the formation of a cup-shaped membrane sac (known as the isolation membrane or phagophore) which engulfs a portion of cytoplasm, and then elongates and seals off to form a double-membraned autophagosome. The autophagosome fuses with lysosomes to form the autolysosome, where the cargo together with the inner membrane of the autophagosome is degraded. Finally, the digested material is released back into the cytosol through lysosomal permeases for recycling1. Autophagy plays an important role in a wide variety of physiological processes in higher eukaryotes, including adaptation to various metabolic stress conditions, removal of aggregate-prone proteins and damaged organelles, and elimination of invading pathogens. Dysregulated autophagy activity has been linked to various pathological diseases such as neurodegeneration, cardiomyopathy and tumorigenesis2.