bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery, metabolism and functions of NAD and NADP
Authors: VanLinden Magali R. , Skoge Renate Hvidsten , Ziegler Mathias
Published: October 2019

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are two major players in metabolism as they participate as electron carriers in a multitude of redox reactions. Moreover, they act in life and death decisions on a cellular level in all known life forms. NAD and NADP both exist in two states; the oxidized forms are characterized by a positive charge on the nicotinamide (Nam) moiety, denoted NAD+ and NADP+ respectively. The reduced forms are denoted NADH and NADPH (Figure 1).
Vitamin imposters: Hijacking the biosynthesis of coenzyme A for antimicrobial drug development
Authors: Villiers Marianne de , Strauss Erick
Published: October 2019

Humankind's struggle to find cures for infectious diseases is as old as humanity itself. During the last century, we have probably made the greatest advance in our battle against these diseases: the discovery of antibiotics. Importantly, the first antimicrobial agents introduced for clinical use in 1937, the sulfonamide drugs, act by hijacking the disease-causing organism's biosynthetic pathway for making folic acid, a vitamin that is required in the synthesis of DNA and RNA. Since then, many other antibiotics with diverse mechanisms of action have been discovered, and, by the early 1960s, it seemed as if any infection could be treated successfully with a course of antibiotics. However, since the first introduction of these drugs, we have also started to suffer our greatest defeat: bacterial strains that show resistance against nearly every antibiotic were often isolated within a few years of their first clinical use. We have been forced back to the drawing board to come up with new antimicrobials, and this has led us to revisit the antimetabolite inhibition strategy used by the sulfonamide drugs. This article discusses the recent advances that have made in discovering compounds that interfere with the biosynthesis of the essential metabolic cofactor coenzyme A (CoA) from pantothenate (vitamin B5).
Mitochondrial RNA and its eccentricities
Authors: ChrzanowskaLightowlers Zofia M.
Published: October 2019

For those who do not work on mitochondria, their knowledge is often restricted to eubacterial origins, production of ATP and perhaps an appreciation of the non-Mendelian maternal inheritance patterns. These features are true enough, but things then start to get more complicated. Although the origins of mitochondria are accepted as a eubacterial endosymbiont of evolving eukaryotic cells1, there were organisms that were described as having jettisoned these ‘organelles’, referred to as amitochondriate eukaryotes. This concept has been challenged, and rudimentary mitochondria, or mitosomes, have now been found in those eukaryotes, which are apparently reluctant to lose this organelle2. The consequences of mitochondrial evolution can be seen in the divergence from the standard repertoire of RNA elements. These eccentricities pose challenges to our understanding of molecular mechanisms underlying mitochondrial gene expression.
Tailored liposomes against bacterial toxins: A novel approach at anti-infective therapy
Authors: Babiychuk Eduard B. , Draeger Annette
Published: October 2019

Almost one century after the first systemic administration of antibacterial compounds, bacterial pathogens continue to threaten human health as medications are increasingly made ineffective by the development of bacterial resistance. Ironically, it is precisely the great success of antibiotic therapy that has delayed the pursuit of alternative strategies to combat bacterial infections. However, the fear of untreatable antibiotic-resistant infections has recently rekindled research interest in alternative approaches.
A timeline of human evolution: What has made us human?
Authors: McIntosh Rebecca L.L. , Stevenson Danielle C. , Varela Tristan
Published: October 2019

What makes us human? That we walk upright, on two legs? That we have complex language? That we use tools? Or is it our ability to ask this question? For centuries, philosophers and scientists have all grappled with this fundamental question.
Unravelling why some people have drug side effects
Authors: Bordbar Aarash , Palsson Bernhard O.
Published: October 2019

Pharmaceuticals have had an immense positive impact on modern medicine. However, they often trigger unintended and injurious side effects, or adverse drug reactions (ADRs). Traditionally, many ADRs were thought to be rare and difficult to predict. However, recent advances in both experimental and computational biology are revolutionizing how we understand both individual patient physiology and pharmaceutical compounds, providing an opportunity to unravel the mysteries of why drug side effects occur and why some people have drug side effects and others do not.
Biomarkers in personalized medicine: discovery and delivery
Authors: Chaffey Ben , Silmon Angela
Published: October 2019

The rapidly developing field of personalized or precision medicine is moving clinical practice towards a new paradigm centred on ‘right patient – right medication – right time'. Such information is obtained through analysis of biomarkers, usually specific proteins or DNA sequences. To expand the range of conditions in which a precision approach can be used, it is vital that new biomarkers continue to be discovered and qualified as having clinical utility. Once this is achieved, it is just as important that clinically validated assays to measure these biomarkers are made available to clinical groups to guide prescribing practice.
Frontiers in RNA biology: advances from a small fly Drosophila melanogaster
Authors: Brown James B. , Celniker Susan E.
Published: October 2019

In this article, we discuss emerging frontiers in RNA biology from a historical perspective. The field is currently undergoing yet another transformative expansion. RNA-seq has revealed that splicing, and, more generally, RNA processing is far more complex than expected, and the mechanisms of regulation are correspondingly sophisticated. Our understanding of the molecular machines involved in RNA metabolism is incomplete and derives from small sample sizes. Even if we manage to complete a catalogue of molecular species, RNA isoforms and the ribonucleoprotein complexes that drive their genesis, the horizons of molecular dynamics and cell-type-specific processing mechanisms await. This is an exciting time to enter into the study of RNA biology; analytical tools, wet and dry, are advancing rapidly, and each new measurement modality brings into view another new function or activity of versatile RNA. Since the dawn of sequence-based RNA biology, we have come a long way.
Patents in the time of CRISPR: Who owns gene editing?
Authors: Sherkow Jacob S.
Published: October 2019

New gene-editing technologies, like CRISPR, promise revolutionary advances in biology and medicine. However, several patent disputes in the USA and UK may have complicated who can use CRISPR. What does this mean for the future of gene editing?
Hydrogen sulfide: stench from the past as a mediator of the future
Authors: Zivanovic Jasmina , Filipovic Milos R.
Published: October 2019

The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between these roles and the actual mechanism(s) behind these processes is getting larger. We propose a way that protein cysteine residues can be modified to form protein persulfides (P-SSH) and explain how this process is controlled in a physiologically relevant fashion. This article provides an overview of H2S signalling in the human body with particular emphasis on the latest discoveries regarding the mechanisms of protein persulfidation and depersulfidation, as well as about the biological reactivity of persulfides and their role in health and disease.
Is AMR the new climate change?
Authors: Stefanidou Anastasia
Published: October 2019

Antimicrobial resistance (AMR) has the potential to affect everyone and it cannot be taken lightly. Drug resistant infections must be addressed as a priority, particularly in light of projections that 10 million people a year will die by 2050 if the problem isn't tackled now.
As precision medicine becomes more important, is it finally time for increased emphasis on gender medicine?
Authors: Reckelhoff Jane F. , Cordozo Licy L. Yanes
Published: October 2019

Gender medicine is the topic of this issue of The Biochemist. In 2014, Francis Collins, Director of the National Institutes of Health (NIH), and Janine Clayton, Director of the Office of Research on Women's Health (ORWH) at NIH, announced that NIH would begin requiring all preclinical grant proposals to address sex as a biological variable1. The ORWH was set up in 1990 with the specific mandate to promote the inclusion of women and minority individuals in all clinical trials going forward2. Similar guidelines are imposed by the European Commission and the Canadian Institutes of Health Research.
Biochemical Society announces Diversity in Science Grant winners
Authors: Butkute Gabriele
Published: October 2019

The Biochemical Society is committed to fostering diversity and equal opportunity for entry and progression in our discipline. In addition to funding a Daphne Jackson Fellowship, Stay-Connected bursaries and supporting In2Science placements for young people from disadvantaged backgrounds, the Society offers a Diversity in Science grants scheme to support our community in their activities to deliver a more inclusive environment for all.
Searching for new therapy options – the microbiome in the spotlight of stroke research
Authors: Meisel Andreas , Winek Katarzyna
Published: October 2019

Commensal microorganisms are indispensable for the proper function of the central nervous system, and alterations in the composition and function of the microbiome are linked to different disease states. In this feature, we provide insight into microbiome research from a neuroscientific perspective and trace back basic ideas concerning the contribution of the microbiome to the pathophysiological processes in stroke – one of the most important neurological disorders.
Rift Valley fever virus: future emergence and the impact on One Health
Authors: Grossi-Soyster Elysse N. , LaBeaud A. Desiree
Published: October 2019

Rift Valley fever virus (RVFV) is a mosquito-borne Bunyavirus that currently affects livestock and humans, causing a wide spectrum of symptoms. RVFV was confined to the African continent for many decades and spread to the Arabian Peninsula in recent history. The potential for widespread emergence into new regions and populations is possible and likely, as many outbreaks are driven by human behaviour and livestock trade. While many imported human cases have been detected, establishment of the virus in new geographic areas will depend on amplification in dense animal populations. Western and European countries have identified a substantial risk for the emergence of RVFV, as agricultural industries constitute a large percentage of the global economy.
Inflammation at the inception of cancer: using fish and fly to tell the story
Authors: Feng Yi , Kelly Lisa
Published: October 2019

The use of fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio) as models in cancer biology has recently led to the discovery that the earliest pre-cancerous cell induces an inflammatory response, which was later found to be important for pre-neoplastic cell (PNC) early progression by providing trophic support for PNC growth. Therefore, an understanding of the mechanisms that regulate the trophic inflammatory response toward PNCs might help us develop cancer prevention strategies. The use of fly and fish models for live imaging studies of the initiation of cancer and what we know so far about the signalling mechanisms involved during the earliest interactions between PNC and its host is discussed here, as well as some future perspectives.
From the inside out: the gut microbiome and inflammatory bowel disease
Authors: Viladomiu Monica , Longman Randy S.
Published: October 2019

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal (GI) tract with two main clinical types: Crohn's disease, which can affect any part of the GI tract, and ulcerative colitis (UC), which is limited to the colon. While early research focused primarily on the immune dysregulation and genetic susceptibilities associated with IBD, recent groundbreaking technological advances have allowed the investigation of additional factors, including diet and microbial exposures, in the onset and severity of disease. Advances in high-throughput microbial sequencing, anaerobic bacterial culturing techniques and generating germ-free mouse models have revolutionized our understanding of the microbial species associated with inflammation. While the long-standing clinical efficacy of antibiotics or surgery for Crohn's disease highlights the potential contribution of the socalled ‘IBD microbiome’ to inflammation, recent seminal studies revealed the impact of IBD-derived gut microbiota on host mucosal and systemic inflammation. This mechanistic understanding of how our ‘microbial organ’ functionally impacts both mucosal and systemic inflammatory pathways will help drive novel diagnostic and therapeutic approaches for IBD.
The role of epigenetics in maintaining genome stability
Authors: Riddle Nicole C.
Published: October 2019

Epigenetic mechanisms play important roles in maintaining our genomes, helping to ensure that after every cell division each daughter cell contains an intact copy of the genome without the structural integrity of the chromosomes being compromised. They are also important for the segregation of chromosomes during cell division and help protect the genome from transposable elements – DNA sequences that are able to move around the genome, generating new copies of themselves and potentially interfering with important genes. As we age, the frequency of errors during cell division increases, partly due to less effective epigenetic mechanisms tasked with maintaining genome stability. Whether the lower efficiency of epigenetic mechanisms is a by-product of ageing or if the increased genome instability drives ageing is currently the topic of on-going research.
From stars to cells – harnessing the power of the crowd for research
Authors: Spiers Helen
Published: October 2019

Modern research techniques allow more data to be generated than can be easily analyzed by the scientists who produce it. An original solution to this problem is to recruit volunteers to help with data analysis through online citizen science projects such as the Zooniverse.
I know what you did last summer
Authors: Brown James
Published: October 2019

The Biochemical Society Summer Vacation Studentships offer stipends of £200 per week for 6–8 weeks, and up to £1,600 in total, to support an undergraduate student to carry out a summer lab placement. This scheme not only benefits the student as they get valuable research experience, but the supervisor also gains an extra pair of hands in the lab. Here, a selection of students share their experiences of summer 2017.
Understanding Animal Research one step at a time
Authors: Jarrett Wendy
Published: October 2019

Understanding Animal Research (UAR) is the UK's only organization devoted solely to helping the public understand why and how animals are used in scientific research and to maintaining a supportive operating environment for such research in this country. Formed in January 2009, following a merger between the Research Defence Society and the Coalition for Medical Progress, UAR has a small staff of around 10 people and a Council of 12, chaired by Professor Jeremy Pearson, which oversees our governance. We also have an Expert Network of individuals from across the bioscience sector and related stakeholder organizations that help to inform our work.
Engineering the immune system
Authors: Sadtler Kaitlyn
Published: October 2019

From ancient Greece via 19th century France, through to the present day, the development of our knowledge of the immune system has grown exponentially. This complex network of cells and secreted proteins is present in almost every organ of the human body. Our immune systems play intricate roles in both homeostasis and disease, regulating processes from bacterial infection to tissue development. The idea of engineering the immune system has been around for over 100 years. In 1880, Louis Pasteur first presented his findings on vaccination to the public, and by 1885 he had immunized the first child against the rabies virus. In the 1890s, William Coley described the deliberate infection of cancer patients with streptococcus bacteria, which led to a reduction in tumour burden, and has been described as the first cancer immunotherapy. Jumping forward to the present day, we have begun modulating immune responses through the use of nanoparticles, biomaterial scaffolds and small molecule drugs. These approaches to engineer immune responses can be used in a variety of applications from disease prevention to tissue regeneration.
Bacteria are out of this world! Could they help us clean up our act?
Authors: Baker Catherine
Published: October 2019

Bacteria are everywhere, in your hair, your clothes, your body, your food, your pets, your house, your garden and even in the air surrounding you! They can survive almost anywhere on the planet. Some even survived a trip into space on the International Space Station. So how is it that something so small can live a happy life in conditions where humans don't stand a chance?
Getting in2science
Authors: Aston Joy
Published: October 2019

We live in a society where your socio-economic background can predict what career path you take. Almost 60% of academics and life science professionals, and over 50% of scientists, come from professional or managerial families. For clinical doctors the figure sits at 73%. For context, only 33% of the entire population comes from these backgrounds. The contrasting figures for those from workingclass backgrounds are less than 15% of academics, less than 10% life science professionals, around 15% of scientists and 6% of doctors. These figures come from a January 2017 report ‘Insights from The Labour Force Survey’ published by The Social Mobility Commission.
Not just a pretty cargo carrier: the other face of kinesins
Authors: Friel Claire
Published: October 2019

If you've only ever heard of one kinesin, it's likely to be one that walks along microtubules and carries cargo around in the cell. However, this type of kinesin is only part of the kinesin story. The ‘kinesin superfamily’ is a large family of microtubule motors and members of the superfamily are critical to a variety of cellular functions. This article focuses on a class of kinesins that regulate the growth and shrinkage dynamics of microtubules. These kinesins orchestrate the construction and maintenance of microtubule structures required temporarily by cells, such as the apparatus that separates replicate chromosomes during cell division.
Out of the classroom and into the workplace
Authors: Brown James
Published: October 2019

According to the Wellcome Trust Monitor in 2013, most young people (63%) said they knew little or nothing about careers in science and very few (4%) knew a great deal. High quality continuing professional development (CPD) for teachers is one way to address these concerns, inspiring and informing teachers so that they may in turn do the same for their students. Since teachers will typically work with hundreds of young people over their career, the impact of effective CPD can potentially be huge. While CPD may often take place in school or through external conferences and workshops, other experiences are also key. The Royal Society's Vision report published in 2014 highlights the importance of teacher CPD being experienced through “peer-to-peer networking and sharing; technical visits to STEM-related sites; and mentoring provided at school and by business and industry”.
Food production in an age of global warming and weirding
Authors: Thompson Stuart
Published: October 2019

Some estimates suggest that we will need to double food production by 2050, and do so despite the effects of climate change on crop yields. The competing demands of agriculture and human populations upon water supplies can only become more extreme with time and are likely to be exacerbated by the impact of increased evaporation due to global warming and changes to rainfall patterns. Therefore, this article will examine some of the ways that we can produce food using less water.
Sequencing DNA, RNA and related molecules as a tool to advance space exploration
Authors: Burton Aaron S.
Published: October 2019

As humans seek to return to the Moon, and eventually to Mars and beyond, new challenges must be overcome to keep astronauts safe and healthy. This includes protecting crew members from harmful organisms in their environment, treating infections that may arise, monitoring nutrition and understanding how the human body adapts to spaceflight during missions that could last multiple years. Since the International Space Station (ISS) was first occupied in 2000, crew health has been monitored with thorough check-ups before and after flight, and the collection of many samples during flight that are brought back to Earth for analysis. During longer missions to more distant solar system locales, where returning samples to Earth is no longer practical, being able to analyse samples aboard the spacecraft could be very important.
The setting for the origin of life: a geological– geochemical perspective
Authors: Kranendonk Martin J. Van
Published: October 2019

There are many different scientific aspects involved in the challenge of understanding the origin of life (OoL). These include organic geochemistry – how to make RNA and DNA molecules from the simple organic building blocks delivered from space in the form of amino acids and some other compounds. Other aspects involve the study of inorganic geochemistry – how elements are made available to promote organic molecule complexification, under what conditions will lipid membranes form and how to bring together the different components that make a functioning cell.
Neo-antigen peptide vaccines as emerging cancer therapeutics
Authors: Urionabarrenetxea Ainhoa Gonzalez , Fahraeus Robin , Hupp Ted , Ball Kathryn
Published: October 2019

Aging-related diseases, including cancer, will form the major socio-economic health burdens of Western societies this coming century. Enormous expenditure on innovative technologies including combinatorial chemistry, whole genome sequencing, crystallography, high-throughput drug screening and computational science have generated significant advances in understanding the molecular basis of cancer. These advances have rapidly generated hundreds of promising drug leads to key oncogenic targets. However, despite this increased expenditure and research and development (R&D), the number of effective drugs reaching the clinic is in steady decline. There are many possible explanations for this, including political and infrastructure drag. A technical problem is the lack of robust age-dependent, sporadic immune-competent models of human cancer that predict toxicity and response in patients. An ideological hurdle is that, until recently, we have had to use ‘models’ of cancer, such as yeast, worms and flies to identify druggable targets. These models reflect features of a cancer cell but do not mimic tumour tissue in vivo. It is difficult to experimentally model an actual tumour. A tumour could be considered a tissue that includes cancer cells themselves, normal supporting tissue including nutrient conduits, a complex local environment that could be very low in oxygen and many types of immune cells that carry out diverse functions.
Introducing the New Chair of the Education, Training and Public Engagement Committee
Authors: Watson Helen
Published: October 2019

Dr Helen Watson became Chair of the Biochemical Society's Education, Training and Public Engagement Committee in January 2019. Here she provides an overview of the work of this Committee and key priorities for the future.
Growing the future: UK Plant Sciences Federation releases its latest report
Authors: Carruthers Jonathan
Published: October 2019

The UK Plant Sciences Federation (UKPSF) launched its latest report on 29 January 2019 with a meeting in parliament. Growing the future sets out opportunities and priorities for plant sciences in the UK, and how plant sciences are crucial to address some of today's global challenges. UKPSF is a special advisory committee of the Royal Society of Biology, with a wide range of member organisations, including the Biochemical Society. The full report can be found at www.rsb.co.uk/growingthefuture.
Living computers powered by biochemistry
Authors: Greco F. Veronica , Tarnowski Matthew J. , Gorochowski Thomas E.
Published: October 2019

Electronic computers have revolutionized virtually all aspects of our lives. However, long before these existed, cells have relied on computations implemented using biochemistry to make decisions about how to improve their chance of survival. The emerging field of synthetic biology offers a new perspective on life, attempting to apply engineering principles to modify and repurpose biological systems or even create new ones from scratch. This is opening up exciting opportunities to reprogram cellular functions, enabling us to better understand how biological computations are implemented, as well as providing a window into the inner workings of the living computers that surround us.
Using synthetic biology to unleash the potential of plants
Authors: Kallam Kalyani , Cai Yao-Min , Bickerton Peter
Published: October 2019

Synthetic biology applies the principles of engineering to biology, helping us to design, redesign and build novel biological systems. First applied to microorganisms it has enabled the industrialscale production of beneficial, bio-based products such as pharmaceuticals, flavourings and textiles. It is now advancing to multicellular organisms. In plants, the field is still in its infancy, yet the potential for plants as light-powered, sustainable biomanufacturing platforms is tremendous.
Probing the dark matter of the human genome with big DNA
Authors: Laurent Jon M. , Pinglay Sudarshan , Mitchell Leslie , Brosh Ran
Published: October 2019

Less than 2% of our genome is protein-coding DNA. The vast expanses of non-coding DNA make up the genome's “dark matter”, where introns, repetitive and regulatory elements reside. Variation between individuals in non-coding regulatory DNA is emerging as a major factor in the genetics of numerous diseases and traits, yet very little is known about how such variations contribute to disease risk. Studying the genetics of regulatory variation is technically challenging as regulatory elements can affect genes located tens of thousands of base pairs away, and often, multiple distal regulatory variations, each with a very small effect, combine in an unknown way to significantly modulate the expression of genes. At the Center for Synthetic Regulatory Genomics (SyRGe) we directly tackle these problems in order to systematically elucidate the mechanisms of regulatory variation underlying human disease.
The secret life of calcium in cell signaling
Authors: Patel Sandip
Published: October 2019

Calcium is an abundant alkaline earth metal. In the body, it is found as calcium ions (Ca2+), and most of it is deposited in hard tissues such as bones and teeth. But less well known is the role of Ca2+ as a messenger within cells. Here, I provide an overview of this hidden but critical function of Ca2+.
Expect the unexpected: presenting research leads to unforeseen gains
Authors: Lane Dan
Published: October 2019

Dan Lane is a first year PhD student at the University of Leicester, developing biochemical methods in non-adherence testing alongside Leicester Diabetes Centre. A pilot study he helped to conduct prior to the start of his postgraduate degree was accepted by Diabetes UK and so, with the help of a travel grant from the Biochemical Society, he travelled to Liverpool to present his work. The Biochemical Society provides General Travel Grants to support attendance at scientific meetings, training events or any other event relevant to your career. Postgraduate, Early Career, Full and Emeritus Members are encouraged to apply to further their lifelong learning.
AI: More than human: A Barbican Exhibition
Authors: Borthwick Ben
Published: October 2019

Artificial intelligence (AI) is on the brink of breaching our collective consciousness. While already deeply interwoven into our way of life, many of us remain relatively unaware of its degree of influence, with even less of an idea of where its influence is likely to take us. The AI exhibition at the Barbican Centre, therefore, arrives at a pivotal moment to distil an immensely complex subject into a series of creative and engaging exhibits which will undoubtedly stimulate us to consider further its place in our own lives.
Identification of novel non-synonymous variants associated with type 2 diabetes-related metabolites in Korean population
Authors: Park Tae-Joon , Lee Heun-Sik , Kim Young Jin , Kim Bong-Jo
Published: October 2019

Metabolome-genome wide association studies (mGWASs) are useful for understanding the genetic regulation of metabolites in complex diseases, including type 2 diabetes (T2D). Numerous genetic variants associated with T2D-related metabolites have been identified in previous mGWASs; however, these analyses seem to have difficulty in detecting the genetic variants with functional effects. An exome array focussed on potentially functional variants is an alternative platform to obtain insight into the genetics of biochemical conversion processes. In the present study, we performed an mGWAS using 27,140 non-synonymous variants included in the Illumina HumanExome BeadChip and nine T2D-related metabolites identified by a targetted metabolomics approach to evaluate 2,338 Korean individuals from the Korea Association REsource (KARE) cohort. A linear regression analysis controlling for age, sex, BMI, and T2D status as covariates was performed to identify novel non-synonymous variants associated with T2D-related metabolites. We found significant associations between glycine and CPS1 (rs1047883) and PC ae C36:0 and CYP4F2 (rs2108622) variants (P<2.05 × 10−7, after the Bonferroni correction for multiple testing). One of the two significantly associated variants, rs1047883 was newly identified whereas rs2108622 had been previously reported to be associated with T2D-related traits. These findings expand our understanding of the genetic determinants of T2D-related metabolites and provide a basis for further functional validation.
Engineering anti-cancer nanovaccine based on antigen cross-presentation
Authors: Warrier Vaishnavi U. , Makandar Amina I. , Garg Manoj , Sethi Gautam , Kant Ravi , Pal Jayanta K. , Yuba Eiji , Gupta Rajesh Kumar
Published: October 2019

Dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules, thereby activating CD8+ T cells, contributing to tumor elimination through a mechanism known as antigen cross-presentation. A variety of factors such as maturation state of DCs, co-stimulatory signals, T-cell microenvironment, antigen internalization routes and adjuvants regulate the process of DC-mediated antigen cross-presentation. Recently, the development of successful cancer immunotherapies may be attributed to the ability of DCs to cross-present tumor antigens. In this review article, we focus on the underlying mechanism of antigen cross-presentation and ways to improve antigen cross-presentation in different DC subsets. We have critically summarized the recent developments in the generation of novel nanovaccines for robust CD8+ T-cell response in cancer. In this context, we have reviewed nanocarriers that have been used for cancer immunotherapeutics based on antigen cross-presentation mechanism. Additionally, we have also expressed our views on the future applications of this mechanism in curing cancer.
Structural dynamics of P-type ATPase ion pumps
Authors: Dyla Mateusz , Basse Hansen Sara , Nissen Poul , Kjaergaard Magnus
Published: October 2019

P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.
Endoplasmic reticulum stress and mitochondrial biogenesis are potential therapeutic targets for abdominal aortic aneurysm
Authors: Miyao Masashi , Cicalese Stephanie , Cooper Hannah A. , Eguchi Satoru
Published: October 2019

Endoplasmic reticulum (ER) and mitochondria are crucial organelles for cell homeostasis and alterations of these organelles have been implicated in cardiovascular disease. However, their roles in abdominal aortic aneurysm (AAA) pathogenesis remain largely unknown. In a recent issue of Clinical Science, Navas-Madronal et al. ((2019), 133(13), 1421–1438) reported that enhanced ER stress and dysregulation of mitochondrial biogenesis are associated with AAA pathogenesis in humans. The authors also proposed that disruption in oxysterols network such as an elevated concentration of 7-ketocholestyerol in plasma is a causative factor for AAA progression. Their findings highlight new insights into the underlying mechanism of AAA progression through ER stress and dysregulation of mitochondrial biogenesis. Here, we will discuss the background, significance of the study, and future directions.
Mathematical modelling of cell migration
Authors: Butler George , Rudge Jonathan , Dash Philip R.
Published: October 2019

The complexity of biological systems creates challenges for fully understanding their behaviour. This is particularly true for cell migration which requires the co-ordinated activity of hundreds of individual components within cells. Mathematical modelling can help understand these complex systems by breaking the system into discrete steps which can then be interrogated in silico. In this review, we highlight scenarios in cell migration where mathematical modelling can be applied and discuss what types of modelling are most suited. Almost any aspect of cell migration is amenable to mathematical modelling from the modelling of intracellular processes such as chemokine receptor signalling and actin filament branching to larger scale processes such as the movement of individual cells or populations of cells through their environment. Two common ways of approaching this modelling are the use of models based on differential equations or agent-based modelling. The application of both these approaches to cell migration are discussed with specific examples along with common software tools to facilitate the process for non-mathematicians. We also highlight the challenges of modelling cell migration and the need for rigorous experimental work to effectively parameterise a model.
DNA methylation dynamics at transposable elements in mammals
Authors: Jansz Natasha
Published: October 2019

Transposable elements dominate the mammalian genome, but their contribution to genetic and epigenetic regulation has been largely overlooked. This was in part due to technical limitations, which made the study of repetitive sequences at single copy resolution difficult. The advancement of next-generation sequencing assays in the last decade has greatly enhanced our understanding of transposable element function. In some instances, specific transposable elements are thought to have been co-opted into regulatory roles during both mouse and human development, while in disease such regulatory potential can contribute to malignancy. DNA methylation is arguably the best characterised regulator of transposable element activity. DNA methylation is associated with transposable element repression, and acts to limit their genotoxic potential. In specific developmental contexts, erasure of DNA methylation is associated with a burst of transposable element expression. Developmental regulation of DNA methylation enables transposon activation, ensuring their survival and propagation throughout the host genome, and also allows the host access to regulatory sequences encoded within the elements. Here I discuss DNA methylation at transposable elements, describing its function and dynamic regulation throughout murine and human development.
Synthetic biology industry: data-driven design is creating new opportunities in biotechnology
Authors: Freemont Paul S.
Published: October 2019

Synthetic biology is a rapidly emerging interdisciplinary research field that is primarily built upon foundational advances in molecular biology combined with engineering design. The field considers living systems as programmable at the genetic level and has been defined by the development of new platform technologies. This has spurned a rapid growth in start-up companies and the new synthetic biology industry is growing rapidly, with start-up companies receiving ∼$6.1B investment since 2015 and a global synthetic biology market value estimated to be $14B by 2026. Many of the new start-ups can be grouped within a multi-layer ‘technology stack’. The ‘stack’ comprises a number of technology layers which together can be applied to a diversity of new biotechnology applications like consumer biotechnology products and living therapies. The ‘stack’ also enables new commercial opportunities and value chains similar to the software design and manufacturing revolution of the 20th century. However, the synthetic biology industry is at a crucial point, as it now requires recognisable commercial successes in order for the industry to expand and scale, in terms of investment and companies. However, such expansion may directly challenge the ethos of synthetic biology, in terms of open technology sharing and democratisation, which could unintentionally lead to multi-national corporations and technology monopolies similar to the existing biotechnology/biopharma industry.
Creating proxies of extinct species: the bioethics of de-extinction
Authors: Seddon Philip J. , King Mike
Published: October 2019

In April 2013 the National Geographic magazine carried the cover title ‘Reviving extinct species, we can, but should we?’ suggesting that the technical challenges had been met, but some ethical concerns remained unresolved. Seven years later it is clear that this is not the case. Here we consider the technical scope, the uncertainties, and some of the bioethical issues raised by the future prospect of de-extinction. Biodiversity and welfare will not always align, and when a clash is unavoidable, a trade-off will be necessary, seeking the greatest overall value. De-extinction challenges our current conservation mind-set that seeks to preserve the species and population diversity that currently exists. But if we want to sustain and enhance a biodiverse natural world we might have to be forward looking and embrace the notion of bio-novelty by focussing more on ecosystem stability and resilience, rather than backward looking and seeking to try and recreate lost worlds.
HoloInjection: augmented reality support for CT‐guided spinal needle injections
Authors: Heinrich Florian , Schwenderling Luisa , Becker Mathias , Skalej Martin , Hansen Christian
Published: October 2019

The correct placement of needles is decisive for the success of many minimally‐invasive interventions and therapies. These needle insertions are usually only guided by radiological imaging and can benefit from additional navigation support. Augmented reality (AR) is a promising tool to conveniently provide needed information and may thus overcome the limitations of existing approaches. To this end, a prototypical AR application was developed to guide the insertion of needles to spinal targets using the mixed reality glasses Microsoft HoloLens. The system's registration accuracy was attempted to measure and three guidance visualisation concepts were evaluated concerning achievable in‐plane and out‐of‐plane needle orientation errors in a comparison study. Results suggested high registration accuracy and showed that the AR prototype is suitable for reducing out‐of‐plane orientation errors. Limitations, like comparatively high in‐plane orientation errors, effects of the viewing position and missing image slices indicate potential for improvement that needs to be addressed before transferring the application to clinical trials.
Details preserved unsupervised depth estimation by fusing traditional stereo knowledge from laparoscopic images
Authors: Luo Huoling , Hu Qingmao , Jia Fucang
Published: October 2019

Depth estimation plays an important role in vision‐based laparoscope surgical navigation systems. Most learning‐based depth estimation methods require ground truth depth or disparity images for training; however, these data are difficult to obtain in laparoscopy. The authors present an unsupervised learning depth estimation approach by fusing traditional stereo knowledge. The traditional stereo method is used to generate proxy disparity labels, in which unreliable depth measurements are removed via a confidence measure to improve stereo accuracy. The disparity images are generated by training a dual encoder–decoder convolutional neural network from rectified stereo images coupled with proxy labels generated by the traditional stereo method. A principled mask is computed to exclude the pixels, which are not seen in one of views due to parallax effects from the calculation of loss function. Moreover, the neighbourhood smoothness term is employed to constrain neighbouring pixels with similar appearances to generate a smooth depth surface. This approach can make the depth of the projected point cloud closer to the real surgical site and preserve realistic details. The authors demonstrate the performance of the method by training and evaluation with a partial nephrectomy da Vinci surgery dataset and heart phantom data from the Hamlyn Centre.
Marker‐less real‐time intra‐operative camera and hand‐eye calibration procedure for surgical augmented reality
Authors: Kalia Megha , Mathur Prateek , Navab Nassir , Salcudean Septimiu E.
Published: October 2019

Accurate medical Augmented Reality (AR) rendering requires two calibrations, a camera intrinsic matrix estimation and a hand‐eye transformation. We present a unified, practical, marker‐less, real‐time system to estimate both these transformations during surgery. For camera calibration we perform calibrations at multiple distances from the endoscope, pre‐operatively, to parametrize the camera intrinsic matrix as a function of distance from the endoscope. Then, we retrieve the camera parameters intra‐operatively by estimating the distance of the surgical site from the endoscope in less than 1 s. Unlike in prior work, our method does not require the endoscope to be taken out of the patient; for the hand‐eye calibration, as opposed to conventional methods that require the identification of a marker, we make use of a rendered tool‐tip in 3D. As the surgeon moves the instrument and observes the offset between the actual and the rendered tool‐tip, they can select points of high visual error and manually bring the instrument tip to match the virtual rendered tool tip. To evaluate the hand‐eye calibration, 5 subjects carried out the hand‐eye calibration procedure on a da Vinci robot. Average Target Registration Error of approximately 7mm was achieved with just three data points.
Experiences with transformer diagnosis by DGA: case studies
Authors: Mahmoudi Nami , Samimi Mohammad Hamed , Mohseni Hossein
Published: October 2019

Power transformers are key apparatuses in power delivery, and due to this fact, several diagnostic methods have been established for it. Dissolved gas analysis (DGA) is a chemical diagnostic tool, which plays an important role in the industry since it can detect a transformer fault in the early stages and save the transformer from consecutive major failures. In this study, after reviewing the significant points in the DGA procedure, five real cases are reported which explain the transformer diagnosis by DGA. In all these cases, DGA plays a key role while other diagnostic tools such as measuring the winding DC resistance, tan δ, dielectric resistance etc. are also employed to discover the problem. In the final part, a fuzzy softening method combined with evidential reasoning is proposed to ease the DGA interpretation for the less expert technicians. This method amends and combines standard methods and does not need a training phase. In summary, the experiences shared in this study can help the industry personnel dealing with transformers to diagnose a transformer problem with more expertise.
Eco‐driving control for hybrid electric trams on a signalised route
Authors: Xiao Zhuang , Feng Xiaoyun , Wang Qingyuan , Sun Pengfei
Published: October 2019

This study proposes an integrated eco‐driving controller, in which speed profile and power split optimisation are simultaneously treated. A speed profile controller is designed based on a multi‐phase dynamic programming (DP) algorithm, which is utilised to optimise speed trajectories with the detailed model of the traction power system, vehicle dynamics system, and signal constraints at intersections. The optimised speed and demand power profiles are designed as the reference of the power split optimal controller. A DP algorithm is presented to determine voltage trajectories of supercapacitors with power plant voltage limitations and dynamic power losses. The performance of the proposed integrated method is evaluated by numerical simulation based on an actual route of Chengdu Tramway Line 2. The energy reduction can be achieved by the speed profiles controller, compared to the eco‐cruising benchmark strategies. Energy efficiency can be further improved by the integrated eco‐driving controller. Moreover, the influences of green signal time windows and trip time on the shape of the optimised solution are investigated. For a given journey, the trip time with minimum energy consumption can be obtained. The integrated eco‐driving control method can be implemented by driver assistant systems or automatic train operation systems.