bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate immunity in plants and animals: Differences and similarities
Authors: Haney Cara H. , Ausubel Frederick M. , Urbach Jonathan M.
Published: October 2019

Plants and animals must avoid becoming a free meal to microbes, which vastly outnumber eukaryotic life in both quantity and diversity. Adaptive immunity in the strict sense, whereby the host creates an immunological memory after exposure to a pathogen, is limited to vertebrates. Both plants and animals (including insects and mammals) have an innate immune system, which helps protect hosts from the majority of microbes they encounter during their lifetime. Plant and animal innate immune systems recognize an overlapping set of conserved microbe-associated molecular patterns (MAMPs). This observation suggests that the innate immune system in plants and animals may have been derived from a common ancestor. However, the majority of data indicate that innate immunity has arisen independently in plants and animals and that functional overlap is the result of convergent evolution: confronted with the same problem, and given the same molecular tools, plants and animals have independently derived similar solutions. This review discusses the functional and mechanistic details of the innate immune system in plants and animals including receptor-mediated immunity, endolysosomal immunity, and the interplay of the innate immune system and host-associated microbial communities.
Spliceosome: the unravelling complexity: The evolution of cellular machines
Authors: Makarova Olga V.
Published: October 2019

The genome of eukaryotes is interspersed with sequences, known as introns, which are removed from the primary gene transcripts. The sequences that remain are known as exons, and they are spliced together as the introns are removed, forming the mRNA. The machinery responsible for splicing reactions is called the spliceosome. It is so intricate and dynamic that it is deservedly known as the most complex molecular machine in the cell.
Science Communication Competition
Authors: Alfaradhi Maria
Published: October 2019

The Science Communication Competition, launched in the Society's Centenary year, is now an annual event. It aims to find young talented science writers and give them the opportunity to have their work published, both online and in The Biochemist. The competition attracted lots of entries, and these are the second and third prize winners.
Engaging with young people from disadvantaged backgrounds
Authors: Hime Alexa
Published: October 2019

Young people who are at a relative socioeconomic disadvantage can find it hard to connect with certain educational and cultural experiences, meaning that a wealth of inspiring and enjoyable science activities may be inaccessible to such young people, with their main connection with science being mediated through formal schooling.
Plasmids and the spread of antibiotic resistance
Authors: Lazdins Alessandro , Miller Claire , Thomas Christopher M.
Published: October 2019

The term plasmid was first coined in 1952 by Joshua Lederberg to encompass all extra-chromosomal hereditary determinants1. One of the first plasmids discovered allowed the movement of genes from one bacterial strain to another, creating a sort of ‘bacterial sex’ or ‘fertility’ so that the entity responsible was called the ‘fertility factor’ or F-factor2. Plasmids carrying antibiotic resistance were soon discovered and became a topic of intense research which contributed to the development of cloning vectors that underpinned the gene cloning revolution in the 1970s. Although the problems created by plasmids were clear to many from the beginning, we do not yet have ways to control their acquisition and spread of resistance.
New Delhi metallo-β-lactamase (NDM)
Authors: Yang Hao , Crowder Michael W.
Published: October 2019

Metallo-β-lactamases (MBLs) are a class of Zn(II)-containing enzymes that hydrolyse the β-lactam bond in β-lactam-containing antibiotics, resulting in products that no longer exhibit antibacterial activity. Currently, there are 29 known MBLs (not including variants), and these enzymes have been classified on the basis of primary amino acid sequence and functionality into three or four classes (see www.mbled.uni-stuttgart.de for an updated MBL database)1. MBLs in classes B1 and B3 are known for their ability to hydrolyse all β-lactam antibiotics, except monobactams, including penicillins, carbapenems and cephalosporins. The class B2 enzymes exhibit a narrower substrate preference and preferentially hydrolyse carbapenems2. The most clinically important MBLs belong to class B1, which contains VIM (Verona integrinencoded MBLs), IMP (imipenemase) and NDM (New Delhi MBL), and all of these enzymes have multiple clinical variants (VIM-1—VIM-46, IMP-1—IMP-51, and NDM-1—NDM-16) (www.lahey.org/Studies/). The presence of multiple variants poses a challenge to identify clinical inhibitors because the variants often exhibit different substrate specificities and are affected differently by known non-clinical inhibitors3.
Aging: designed to die?
Authors: Kirkwood Thomas B.L.
Published: October 2019

Aging is a normal biological process that occurs in every human being who manages to escape the fate of a premature death. On the whole, there is a consistency about aging's hallmarks such that we can judge a person's age pretty accurately at just a glance. What is more natural, then, than to suppose that aging has been fashioned by natural selection as an adaptation in its own right, perhaps to clear the older generations out of the way and make room for the new ones? Longevity runs in families, which means that genes are involved1. Doesn't this imply that aging itself follows a genetic programme, perhaps merely a continuation of the same programming that gave shape to our bodies' growth and development?
James and the Giant Gene
Authors: Yhnell Emma
Published: October 2019

The Science Communication Competition is now in its fifth year. As in previous years, it aims to find young talented science writers and give them the opportunity to have their work published in The Biochemist. In 2015, a new branch of the competition was launched to include video entries. Overall this year's competition attracted 47 entries and these were reviewed by our external panel of expert judges. The first prize in the written category was awarded to Emma Yhnell from Cardiff University, whose article is presented here; the winner of the video category was Chris Morgan from the University of Birmingham. Chris Morgan's winning video can be viewed on the Society's website: http://bit.ly/1kxt8eH
From DNA to a human: What the ENCODE and Roadmap Epigenome Projects can teach us about how we are who we are
Authors: Lowdon Rebecca F. , Swain-Lenz Devjanee
Published: October 2019

The assembly of the human genome sequence revealed that there are 3.2 billion bases in our genome, but what was less clear at the time was how this vast amount of information was organised and expressed to ensure that a single-celled zygote was able to develop into a fully functioning human body. The ENCODE project began the quest to identify and assign function to different elements within the genome and the Roadmap Epigenome Project has continued this journey by mapping chemical modifications such as DNA methylation, which are known to affect gene expression. Understanding these elements and processes in greater depth will allow us to learn more about how we became who we are and what differentiates humans from other animals.
Is artificial blood safe for vampires to eat?
Authors: Cooper Chris
Published: October 2019

What are the daily recommended nutritional requirements for a vampire? What does artificial blood taste like? Would you rather be a vampire or a zombie? These are not questions I ever thought I would be asked as a young scientist, but both have featured when I have been communicating my science to the general public. When I was growing up, vampires were evil and to be feared. Yet in recent years it appears that they were, in fact, much maligned and misunderstood; they really just want to live their lives in peace with their mortal compatriots. It is not reported what the late – and recently much lamented – Sir Christopher Lee thought of this transformation, although I strongly suspect that, like myself, he prefers his vampires raw in tooth and claw (or rather fang).
Children of the Night in The Others
Authors: Hernandez H. David Urquiza
Published: October 2019

Children of the Night, Children of the Moon or Children of the Dark are names used for referring to children suffering from xeroderma pigmentosum, a rare genetic disease in which the affected children cannot be exposed to sunlight, which can be fatal for them. This disease have been explored in a few films: Children of the Dark (a made-for-TV film), Dark Side of the Sun, a direct-to-DVD film and, finally, a mainstream film depicting children with this disease, The Others, an acclaimed and award-winning film directed by Alejandro Amenábar, starring Nicole Kidman as Grace, Fionnula Flanagan as Bertha and Alakina Mann and James Bentley as the children1. In The Others, Grace, the mother, and her two children Anna and Nicholas live in a big, dark, almost empty house. Later, we find out that the children cannot be exposed to the sun, so they only play inside the house, which has been emptied of superfluous furniture for the children to have more space in which to run around. The mother employs a new maid (Bertha) and two other new servants, and a series of events occur in such a way that the family, and the audience, begins to believe that the house is haunted. This article focuses on the depiction of children with xeroderma pigmentosum as represented in this film and how the film's approach and description of the disease match with the reality that families with affected children find every day.
Jurassic World: just how impossible is it?
Authors: Parry Geraint
Published: October 2019

In the movie business, bigger is usually better, bigger spaceships, bigger disasters, bigger dinosaurs and the latter was especially true in the latest installment of the Jurassic Park franchise, Jurassic World. Although the Indominus rex knocked the Tyrannosaurus rex into a cocked hat when it came to size, strength, speed and special abilities, the ‘scientific’ details of its creation are perhaps not so far-fetched if you accept the original premise of Jurassic Park. However, that is a big IF! Twenty years ago many of us enjoyed the scientific ideas suggested by Jurassic Park, either in the Michael Crichton book or in the Spielberg film. For those younger readers who haven't seen the original film; the idea was that scientists had managed to extract dinoDNA from a mosquito that had been trapped in prehistoric amber. This DNA was attached to a nucleic acid scaffold from a frog and ‘voila!’ there were more Stegosauri, Brontosauri and T. rex's than you could shake a pipette at! Inevitably as we left the cinema, we asked if this would ever be ‘possible’? Indeed there are current efforts to recreate long-extinct creatures, although on a slightly less ambitious scale. Whatever the source of your dinosaur DNA; be it from fossilized bones or from an amber-trapped mosquito, the chances of it being intact are essentially nil making the idea of the creation of new dinosaurs from preserved DNA more fiction than fact.
Rewriting the book of life
Authors: Taylor Güne
Published: October 2019

The recent advent of CRISPR-Cas9--an unparalleled and precise DNA-editing technology--has changed the way in which molecular biology research is performed. From basic blue skies research to the study of human congenital disorders, the application of this technology is revolutionizing how scientists are conducting their research. This article introduces the basics of genome biology, the neural crest and the potential for CRISPR-Cas9 in a specific human congenital disorder.
The extracellular matrix: a new dimension in disease diagnosis and treatment
Authors: Aungier Susan , Midwood Kim
Published: October 2019

The extracellular matrix (ECM) forms the complex and dynamic 3D environment that defines tissue structure and function. Matrix molecules provide much of the microenvironmental plasticity that dictates cell behaviour, and their dysregulated expression is associated with a wide range of diseases including cancers, and inflammatory and fibrotic conditions. Here, we describe how these matrix molecules are beginning to be used for disease diagnosis and treatment.
The quest to 3D print body parts
Authors: Atala Anthony , Richardson Karen
Published: October 2019

From engineering and manufacturing to art and education, 3D printing is helping to drive innovation in many different fields. Medicine is no exception. The technology is being used to print prosthetic limbs and to fabricate patient-specific models of body parts for surgeons to use as guides during reconstructive surgery. A 3D printed titanium jawbone has been implanted in a patient, as has a tailormade, bioresorbable tracheal splint that saved a baby's life.
How bacteria breathe in hydrogen sulfide-rich environments
Authors: Forte Elena , Giuffrè Alessandro
Published: October 2019

Hydrogen sulfide (H2S) is now universally recognized as an endogenous signalling molecule playing a central role in human physiology. This gas, although it controls a number of physiological processes at low (submicromolar) concentrations, is toxic at high concentrations as it blocks cell respiration by potently inhibiting cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain. In a recent study on the model micro-organism Escherichia coli, it was shown that the bacterial respiratory oxidase cytochrome bd is resistant to H2S inhibition, thus enabling bacterial O2 respiration and growth in the presence of sulfide. This may be relevant because many microbes are H2S producers and some of them live in sulfide-rich environments, such as the human gut and other natural habitats. The potential impact of this finding in different areas (environment, life evolution and human health) is discussed.
How decreasing oxygenase activity helps cells cope with hypoxia
Authors: Flashman Emily
Published: October 2019

The ability of our bodies to adapt to reduced oxygen availability (hypoxia) by increasing red blood cell formation was recognized in the 19th century, but almost 200 years passed before the molecular mechanism underlying this hypoxic response was revealed. In animals, hypoxia tolerance is enabled by turning on a plethora of genes, all under the control of the hypoxia inducible transcription factor protein, HIF. Crucially, levels of HIF are controlled by a set of enzymes, whose activity is exquisitely sensitive to oxygen availability. A low-oxygen response system is arguably more important for plants which, as sessile organisms, cannot employ behavioural responses to hypoxia, and recent findings reveal a distinct yet analogous mechanism. It seems that in plants as well as in animals, oxygen-dependent enzymes are the linchpins connecting oxygen availability with the cellular response to hypoxia.
Fatty acids and feminism: Ida Smedley MacLean, the first woman to Chair the Biochemical Society
Authors: Freedman Robert
Published: October 2019

In 2017, Professor Anne Dell will take over as Chair of the Biochemical Society. She is only the fourth woman to hold that office in more than 100 years, with the first of her predecessors taking up the office 90 years ago in 1927! Fostering diversity and equal opportunity is one of the Society's strategic objectives. Having inclusivity as a norm – and an expectation on the part of our members and community – would not have been possible without the pioneering role of women such as Ida Smedley MacLean.
The disease of theories: unravelling the mechanisms of pre-eclampsia
Authors: George Eric M.
Published: October 2019

Perhaps no disease of pregnancy has been more thoroughly studied than pre-eclampsia (PE), and yet despite all of our efforts we are only beginning to understand the molecular mechanisms which underpin the disease. Many people are surprised by the frequency of PE in the population, as it is believed to occur in approximately one pregnancy out of 20 in the United States, with similar rates throughout the developed world. In severe cases the disorder can progress to eclampsia, which is characterized by maternal seizures and can lead to death. PE can only be treated by ending the pregnancy, often by inducing labour prior to term, making PE a leading cause of premature birth and all of the associated health complications which accompany it. All in all, PE is one of the leading causes of maternal and fetal morbidity and mortality. It is now also becoming apparent that PE disposes both the mother and the baby to increased risk of cardiovascular disease throughout life, meaning that we still don't fully understand the long-term implications of the disease.
Brain food for babies
Authors: Freeman Dilys J. , Meyer Barbara J.
Published: October 2019

How does a mother supply a key building block of the brain required for neurodevelopment to her fetus in pregnancy? The critical requirement of docosahexaenoic acid (DHA) for fetal brain development, and the poor efficiency of its synthesis in humans, is a tricky metabolic problem to be overcome in pregnant women. Supplying this unique fatty acid to the fetus requires exquisite specificity and timing, processes that can unravel in disease conditions such as pre-eclampsia.
The future of public engagement: Biochemical Society and beyond
Authors: Brown James
Published: October 2019

Last November, the British Science Association held its inaugural Huxley Summit, titled Trust in the 21st Century. Named for Thomas Huxley (Darwin's Bulldog), who was instrumental in bringing Darwin's theory of evolution to the general public, the event aimed to capture the spirit of public debate, engagement, and interest in a high profile arena – and, crucially, involve people from beyond the boundaries of science. In a period of time when, apparently, “people in this country have had enough of experts” how do we as scientists rebuild this trust?
Untreatable gonorrhoea, are we there yet?
Authors: Bromhead Collette , Hendrickson Heather
Published: October 2019

Gonorrhoea is a relatively common and easily spread bacterial sexually transmitted disease that can cause a wide spectrum of symptoms from none to severe outcomes. Through its penchant for modifying its own genetics, Neisseria gonorrhoeae has gradually evolved to become one of modern medicine's greatest adversaries. In most countries we have only one antibiotic left to treat it with, and even that option is rapidly running out. So how do we stop this train wreck? What do we do when the treatments run out altogether?
Resolution in an ‘over-inflamed’ era
Authors: Perretti Mauro , MonteroMelendez Trinidad
Published: October 2019

Unlike other pathologies, inflammation is a condition that all individuals experience in their lives. Toothache, sunburn, a twisted ankle or cutting your hand while slicing bread, they all evoke what we call an acute inflammatory response. This type of response normally displays the cardinal signs of inflammation originally described by Aulus Cornelius Celsus: redness, swelling, heat and pain. Acute inflammation does not normally require any therapeutic intervention other than perhaps a painkiller, as it resolves, with the damage being naturally repaired. Inflammation is also at the root of many other diseases in a more ‘silent’ way as the cardinal signs of inflammation are not so evident. It is now appreciated that inflammatory mechanisms and processes contribute to the pathogenesis of a number of conditions including obesity, cancer, rheumatoid arthritis, atherosclerosis and diabetes. These are examples of chronic inflammation, arising either by the persistence of the injurious element causing it, or by a defect in our endogenous natural protective mechanisms grouped under the terminology of pro-resolving mechanisms. A common perception, likely to have been enhanced by the large variety of nonprescription antiinflammatory drugs available to anyone experiencing mild-to-moderate pain, is that inflammation is something harmful that must be stopped. In the next sections we will discuss on the protective life-saving role of the inflammatory response, the existence of our own body's resolutive mechanisms that regulate it and on when and why we need a pharmacological intervention to treat inflammation.
The microbiome and food that fuels the fire of inflammation
Authors: Melgar Silvia
Published: October 2019

Inflammatory bowel diseases (IBD), encompassing two main conditions – Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic intestinal inflammatory diseases with increasing incidence worldwide, especially in countries adopting a westernized lifestyle. Recent findings point towards a major impact of diet on human health since it can affect both the gut microbiota and the host response. Epidemiological studies have identified that the consumption of processed food, red meat, saturated fat and low fibre/vegetables are high-risk factors for IBD, while the consumption of fatty fish, fermentable fibres and vegetables lowers risk for IBD. Experimental studies have supported these findings. Animals fed certain specific diets demonstrate alterations in host immune responses and microbiota composition including the blooming of pathobionts as a result of diet treatment. Recent seminal studies have also provided evidence on the role of food additives such as emulsifiers in IBD and metabolic diseases. In the future, controlled trials and mechanistic studies will identify diet-induced beneficial or triggering mechanisms which will lead to the development of new treatment strategies for these debilitating diseases.
From womb to tomb: stress across a lifetime
Authors: Potter Harry
Published: October 2019

Stress. What does it mean to you? We probably all refer to it after a long or strenuous day at work, during a particularly heated family argument, or when thinking about our finances. But what does the word really mean, and why is it so important in our everyday lives? Can it increase our risk of developing serious health conditions such as obesity, heart disease, and lung cancer? Is it something that can affect our children as they develop in the womb? Is it even something that can affect our children's children? It may seem surprising, but the answer to all of these questions is yes.
If you want something doing, do it yourself
Authors: Brown James
Published: October 2019

The Biochemical Society's panel discussion event, DIY Biology, explored the possibilities for citizen science and collaborative research projects.
Iron microbe: outfitting organisms for extreme environments
Authors: Sakimoto Kelsey K.
Published: October 2019

As NASA and other space agencies across the world prepare their astronauts to withstand the hazards of space travel and habitation on Mars, tinier adventurers have begun to receive a similar outfitting. For humans to live in extreme environments such as the darkest, coldest, radiation bombarded reaches of space, we must equip useful microorganisms to thrive and survive under similar conditions. This insight has expanded microbial sciences to the materials sciences: blending soft, squishy cells with hard, rocky crystals. And just as billionaire-playboy-philanthropist Tony Stark donned an array of gadgetry to become Iron Man, so too must bacteria and yeast receive the cyborg treatment to augment their functionality for the future of biotechnology.
Crystal clear: protein found in tears can generate electricity
Authors: Stapleton Aimee , Soulimane Tewfik , Syed Tofail
Published: October 2019

Sometimes crying over spilled milk isn't such a bad thing – especially if you're trying to produce electricity. Both tears and milk contain a protein called lysozyme that produces an electrical charge when squeezed. This new discovery begs the question: what could this be used for? In the future, this protein may serve as an energy-harvesting material to power medical devices.
The bacterial flagellar motor and the evolution of molecular machines
Authors: Beeby Morgan
Published: October 2019

Understanding how life on earth evolved is an enduringly fascinating and profound question. Relative to our understanding of eukaryotic evolution, however, our understanding of how the molecular machines underpinning life have evolved is poor. The bacterial flagellar motor, which drives a rotary propeller for motility, offers a fascinating case study to explore this further, and is now revealing recurring themes in molecular evolution. This article describes recent discoveries about how flagellar motors have diversified since the first flagellar motor evolved, and what this diversity tells us about molecular evolution.
Meiosis and fertility: an old wives' tale
Authors: Hartshorne Geraldine
Published: October 2019

For a variety of different reasons, women are delaying attempts to get pregnant until later in their lives. However, age-related decline in egg quality is a major factor in otherwise-unexplained infertility. What are the underlying biochemical processes contributing to this loss of fertility?
PGS: a four-letter word?
Authors: Griffin Darren , Oğur Çağri
Published: October 2019

Preimplantation genetic screening (PGS) involves the identification of chromosome abnormalities in IVF embryos (rather than targeting diagnosis to a specified gene). Chiefly employed for couples with advanced maternal age, recurrent miscarriage or recurrent IVF failure, it aims to improve IVF success, and reduce miscarriage and affected live birth rates. The process involves the sampling of cells by embryo biopsy, cytogenetic diagnosis, then selective transfer of an apparently chromosomally normal embryo in the hope of establishing a pregnancy. Although PGS is the most common variant of PGD (preimplantation genetic diagnosis), accounting for 80% of cases it has, from the outset, been one of the most controversial areas of reproductive medicine. The subject of intense debate, it attracts opinions ranging from recommendations that it should be applied in all IVF cases, through to the suggestion it should be discontinued completely. What do you think? Should it continue or not?
Santiago Ramón y Cajal, the ultimate scientist?
Authors: Macip Salvador
Published: October 2019

The Nobel Prize in Physiology or Medicine for 1906 was shared by two scientists that set the basis for understanding how the brain works: Camillo Golgi and Santiago Ramón y Cajal were awarded the honour “in recognition of their work on the structure of the nervous system”. Yet, contrary to what usually happens in these situations, one of them was wrong and tried to sabotage the theories of the other one, refusing to admit his mistakes even when he gave his acceptance speech. How did Santiago Ramón y Cajal, a humble Spanish doctor, manage to upstage the legendary Italian pathologist and change forever the way we see the brain?
Looking back at 2018 and ahead to 2019: Royal Society of Biology News
Authors: FRSB Mark Downs, CSci
Published: October 2019

The year ahead will bring big changes; we will be leaving the EU, there will be a UK spending review with implications for research and education budgets, and there will be further visibility of UKRI's strategy for public research funding in action. Despite all these changes, it will be the people and the science, as always, that will power our community and give us focus.
A commentary on the Nobel Prize award for Physiology or Medicine – for the discovery of cancer therapy by inhibition of negative immune regulation
Authors: Hill Samuel L. , Elliott Tim J. , Johnson Peter W.M.
Published: October 2019

The promise of harnessing the immune system to fight cancer has long been dreamt of. In the late 19th century William Coley, a New York cancer surgeon, found that inflammation caused by purposely injecting streptococcal bacteria into sarcoma lesions could control the spread of the disease, at least temporarily. Over time, his ideas were left by the wayside as techniques in cancer surgery and radiotherapy were honed and the new science of chemotherapy was developed.
Does the immune system grow old gracefully?
Authors: Palmer Donald B. , Freiberger Tamar
Published: October 2019

‘You don’t stop laughing when you grow old, you grow old when you stop laughing'. George Bernard Shaw
Minimizing side effects, maximizing returns: what makes a smart therapeutic design?
Authors: Lee Jungmin , Redfield Katherine , Way Jeffrey , Silver Pamela
Published: October 2019

Symptoms of cancer can be devastating. However, the side effects of cancer treatments aimed at leaving the patient tumour-free, often inflict their own brutal attack on the body. The same treatments that kill rapidly dividing tumour cells will just as easily kill any other rapidly dividing cells in the body, wreaking havoc on the lining of our intestines, our replenishing blood cells and our usually industrious hair follicles. This is an extreme example of a common problem: drugs have frequent, unintended and largely unpleasant side effects as a result of indiscriminate binding to both their desired targets and a multitude of other sites. How can synthetic biologists help?
The prospect of N2-fixing crops galore!
Authors: Cocking Edward , Dent David
Published: October 2019

The impact of carbon on our climate has been of major concern for a number of years. However, we are now learning to be equally concerned about the next element in the periodic table, nitrogen, and the consequences of using synthetic nitrogen fertilizers in agriculture that pollute our planet and its atmosphere.
Wild-type menin is rapidly degraded via the ubiquitin-proteasome pathway in a rat insulinoma cell line
Authors: Jiang Zongzhe , Wan Shengrong , Xing Bowen
Published: October 2019

Menin is encoded by multiple endocrine neoplasia type 1 (MEN1) gene, the germ line mutations of which are the main cause of pancreatic neuroendocrine tumors (PNETs). To date, a large number of frameshift, nonsense and missense mutations of MEN1 have been identified to be responsible for part of MEN1-defficient PNETs patients due to truncation or rapid degradation of menin protein. However, the stability of the wild-type (WT) menin in PNETs is totally unknown. In the present study, we observed ubiquitination of WT menin in 293T cells by transfection of ectopic WT menin and HA-ubiquitin. As expected, either endogenous or ectopic WT menin is stable in 293T cells, whereas in INS-1 cells, a rat insulinoma cell line derived from PNETs, either endogenous or ectopic WT menin is rapidly degraded through ubiquitin-proteasome pathway. Furthermore, the degradation of WT menin is more rapid in the presence of serum. Our findings suggest that in part of PNETs patients with WT MEN1, a ubiquitin-proteasome system targeting menin is untimely activated.
A novel mass assay to measure phosphatidylinositol-5-phosphate from cells and tissues
Authors: Ghosh Avishek , Sharma Sanjeev , Shinde Dhananjay , Ramya Visvanathan , Raghu Padinjat
Published: October 2019

Phosphatidylinositol-5-phosphate (PI5P) is a low abundance lipid proposed to have functions in cell migration, DNA damage responses, receptor trafficking and insulin signalling in metazoans. However, studies of PI5P function are limited by the lack of scalable techniques to quantify its level from cells and tissues in multicellular organisms. Currently, PI5P measurement requires the use of radionuclide labelling approaches that are not easily applicable in tissues or in vivo samples. In the present study, we describe a simple and reliable, non-radioactive mass assay to measure total PI5P levels from cells and tissues of Drosophila, a genetically tractable multicellular model. We use heavy oxygen-labelled ATP (18O-ATP) to label PI5P from tissue extracts while converting it into PI(4,5)P2 using an in vitro kinase reaction. The product of this reaction can be selectively detected and quantified with high sensitivity using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform. Further, using this method, we capture and quantify the unique acyl chain composition of PI5P from Drosophila cells and tissues. Finally, we demonstrate the use of this technique to quantify elevations in PI5P levels, from Drosophila larval tissues and cultured cells depleted of phosphatidylinositol 5 phosphate 4-kinase (PIP4K), that metabolizes PI5P into PI(4,5)P2 thus regulating its levels. Thus, we demonstrate the potential of our method to quantify PI5P levels with high sensitivity from cells and tissues of multicellular organisms thus accelerating understanding of PI5P functions in vivo.
Association between methylenetetrahydrofolate reductase tagging polymorphisms and susceptibility of hepatocellular carcinoma: a case–control study
Authors: Zhang Sheng , Lin Jing , Jiang Jiakai , Chen Yu , Tang Weifeng , Liu Longgen
Published: October 2019

Polymorphisms in one-carbon metabolism genes may influence the susceptibility to hepatocellular carcinoma (HCC). In the present study, we studied methylenetetrahydrofolate reductase (MTHFR) tagging polymorphisms in 584 HCC cases and 923 controls. Polymerase chain reaction was harnessed to detect MTHFR genotype. Overall, our results showed that genotype distribution of MTHFR rs4846048 and rs4845882 polymorphisms was not different between HCC patients and controls. MTHFR rs9651118 and rs1801133 loci were protective factors for HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.49–0.90, P=0.008 and TC/CC vs. TT: adjusted OR = 0.70, 95% CI: 0.53–0.93, P=0.015; rs1801133: GA vs. GG: adjusted OR = 0.72, 95% CI: 0.54–0.97, P=0.031, AA/GA vs. GG: adjusted OR = 0.76, 95% CI: 0.57–0.99, P=0.045). However, MTHFR rs3753584 locus was a candidate for susceptibility to HCC (CT vs. TT: adjusted OR = 1.67, 95% CI: 1.20–2.32, P=0.003 and TC/CC vs. TT: adjusted OR = 1.59, 95% CI: 1.15–2.20, P=0.005). Results of haplotype analysis suggested that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Trs9651118 was associated with the risk of HCC (OR = 1.55, 95% CI: 1.16–2.07, P=0.003). The power of our study also confirmed these associations (the value of power >0.80). In summary, our findings suggested that MTHFR rs3753584, rs9651118 and rs1801133 polymorphisms may affect the risk of HCC in Chinese Han population. In future, our findings should be further validated in additional case–control studies.
Inhibition of human lung adenocarcinoma growth and metastasis by JC polyomavirus-like particles packaged with an SP-B promoter-driven CD59-specific shRNA
Authors: Lin Mien-Chun , Shen Cheng-Huang , Chang Deching , Wang Meilin
Published: October 2019

Lung cancer ranks first in both incidence and mortality and is a major health concern worldwide. Upon recognition of specific antigens on tumor cells, complement-dependent cytotoxicity (CDC) is activated, arresting cell growth or inducing apoptosis. However, by overexpressing CD59, a membrane complement regulatory protein (mCRP), lung cancer cells develop resistance to CDC. We previously showed that virus-like particles (VLPs) of human JC polyomavirus (JCPyV) could be used as a gene therapy vector to carry a suicide gene expression plasmid with a lung-specific promoter (SP-B (surfactant protein B)) for lung adenocarcinomas. Herein, we designed a CD59-specific short hairpin RNA (shRNA) expression plasmid driven by SP-B (pSPB-shCD59) to effectively and specifically inhibit CD59 overexpression in lung cancer cells. Treatment of lung cancer cells in vitro with JCPyV VLPs containing pSPB-shCD59 (pSPB-shCD59/VLPs) induces CDC and death of cancer cells. Mice that were subcutaneously injected with human lung cancer cells showed an 87% inhibition in tumor growth after tail vein injection of pSPB-shCD59/VLPs. Moreover, in a mouse model of lung cancer metastasis, a reduction in the lung weight by 39%, compared with the control group, was observed in mice treated with pSPB-shCD59/VLPs after tail vein injection of human lung cancer cells. Furthermore, tissue sectioning showed that the number and size of tumors produced was significantly reduced in the lungs of mice in the treatment group than those of the untreated group, indicating inhibition of metastasis by pSPB-shCD59/VLPs. Together, these results demonstrate the potential of pSPB-shCD59/VLPs as a therapeutic agent for CD59 overexpressed lung cancer.
Recombinant DNA technology and DNA sequencing
Authors: Roberts Mark A. J.
Published: October 2019

DNA present in all our cells acts as a template by which cells are built. The human genome project, reading the code of the DNA within our cells, completed in 2003, is undoubtedly one of the great achievements of modern bioscience. Our ability to achieve this and to further understand and manipulate DNA has been tightly linked to our understanding of the bacterial and viral world. Outside of the science, the ability to understand and manipulate this code has far-reaching implications for society. In this article, we explore some of the basic techniques that enable us to read, copy and manipulate DNA sequences alongside a brief consideration of some of the implications for society.
Differential Long-Term Outcomes for Individuals With Histories of Preschool Speech Sound Disorders
Authors: Lewis Barbara A. , Freebairn Lisa , Tag Jessica , Igo Robert P. , Ciesla Allison , Iyengar Sudha K. , Stein Catherine M. , Taylor H. Gerry
Published: October 2019

Purpose

The goal of this study was to determine whether adolescent outcomes for individuals with histories of early speech sound disorders (SSD) could be differentiated by speech and language skills at earlier ages (preschool, 4–6 years, and school age, 7–10 years).

Method

The study used a retrospective longitudinal design. Participants with and without histories of early SSD were classified in adolescence as having no SSD, resolved SSD, low multisyllabic word (MSW; difficulty with MSW repetition but no errors in conversational speech), or persistent speech disorders (errors in both conversational speech and MSW repetition). Analysis of variance was employed to determine whether early speech, language, and literacy skills distinguished these adolescent outcome groups.

Results

Preschool and school-age skills differed for adolescents whose SSD had resolved from those who had persistent speech errors. Adolescents with errors solely in production of MSWs (Low MSW) did not differ in early speech and language skills from adolescents who had difficulty with both MSWs and persistent errors in conversation.

Conclusions

Speech and language assessments earlier in childhood can help establish risks for persistent SSD and other language and literacy difficulties in adolescence. Early identification of these clinically relevant subgroups of SSD may allow for early targeted interventions.

Supplemental Material

https://doi.org/10.23641/asha.9932279
Optimal operation and cost–benefit allocation for multi‐participant cooperation of integrated energy system
Authors: Luo Yan‐Hong , Zhang Xin‐Wen , Yang Dong‐Sheng , Sun Qiu‐Ye , Zhang Hua‐Guang
Published: October 2019

In the trend of multi‐energy integration development and the intellectualisation for demand‐side, the application of integrated energy system (IES) contained demand response is of great significance to the economic operation of energy systems. The energy hubs are widely studied as effective tools for integrating regional energy in the IES. With the expansion of schedulable devices, the mode of multiple energy hubs (MEHs) cooperative operation is proposed in this study. Moreover, in order to adjust the periodic loads, the authors further study the responsiveness of electric vehicles, air‐conditioning and energy storages according to time‐of‐use price incentive mechanisms, and the total operation cost is minimised. Meanwhile, the eco‐friendly target is achieved by the pollutant trading market. Furthermore, due to the complementary characteristic of MEHs, the economics allocation issues are also carefully considered where the cost and benefit of each participant are allocated by cooperative game theory to make them satisfied with the profit brought by cooperation. The simulation takes three hubs cooperation as an example to verify the effectiveness of the proposed methods. The results show that the total profit increased by 53.54% and the peak load is reduced by 27.06% after optimal operation, and the modified propensity to disrupt verifies the fairness of allocation.
Moving target detection with polarimetric distributed MIMO radar in heterogeneous clutter
Authors: Xiang Yan , Liu Zhiwen , Huang Yulin , Xu Yougen
Published: October 2019

In this study, the authors consider the problem of moving target detection in the presence of heterogeneous clutter. The knowledge‐aided method has been extended to derive the polarimetric multiple‐input multiple‐output (MIMO) radar detector. And the polarimetric clutter covariance matrix was modelled as a complex inverse Wishart distribution. More precisely, the clutter covariance matrices between different transmitter–receiver (Tx–Rx) pairs are assumed to follow the distribution which shares a prior clutter covariance matrix structure while with different values of the power levels. Under this assumption, the generalised likelihood ratio test (GLRT) approach has been adopted to develop the polarimetric knowledge‐aided detector without secondary data. Numerical results are shown to illustrate the effectiveness of the polarimetric knowledge‐aided GLRT detector in heterogeneous clutter.
Long-period comet C/1963 A1 (Ikeya), the probable parent body of π-Hydrids, δ-Corvids, November α-Sextantids, and ϑ-Leonids
Authors: Neslušan L. , Hajduková M.
Published: October 2019

Aims. We study the meteoroid stream of the long-period comet C/1963 A1 (Ikeya) to predict the meteor showers originating in this comet. We also aim to identify the predicted showers with their real counterparts.

Methods. We modeled 23 parts of a theoretical meteoroid stream of the parent comet considered. Each of our models is characterized by a single value of the evolutionary time and a single value of the strength of the Poynting–Robertson effect. The evolutionary time is defined as the time before the present when the stream is modeled and when we start to follow its dynamical evolution. This period ranges from 10 000 to 80 000 yr. In each model, we considered a stream consisting of 10 000 test particles that dynamically evolve, and their dynamics is followed via a numerical integration up to the present. At the end of the integration, we analyzed the mean orbital characteristics of particles in the orbits approaching Earth’s orbit, which thus enabled us to predict a shower related to the parent comet. We attempted to identify each predicted shower with a shower recorded in the International Astronomical Union Meteor Data Center list of all showers. In addition, we tried to separate, often successfully, a real counterpart of each predicted shower from the databases of real meteors.

Results. Many modeled parts of the stream of comet C/1963 A1 are identified with the corresponding real showers in three video-meteor databases. No real counterpart is found in the IAU MDC photographic or radio-meteor data. Specifically, we predict five showers related to C/1963 A1. Two predicted showers are identified with π-Hydrids #101 and δ-Corvids #729. The third predicted shower is only vaguely similar to November α-Sextantids #483, when its mean orbit is compared with the mean orbit of the November α-Sextantids in the IAU MDC list of all showers. However, the prediction is very consistent with the corresponding showers newly separated from three video databases. Another predicted shower has no counterpart in the IAU MDC list, but there is a good match of the prediction and a shower that we separated from the Cameras for Allsky Meteor Surveillance video data. We name this new shower ϑ-Leonids. The last of the predicted showers should be relatively low in number and, hence, no real counterparts were either found in the IAU MDC list or separated from any considered database.
Stellar population astrophysics (SPA) with the TNG
Authors: Ryde N. , Hartman H. , Oliva E. , Origlia L. , Sanna N. , Rainer M. , Thorsbro B. , Dalessandro E. , Bono G.
Published: October 2019

Context. In the advent of new infrared high-resolution spectrometers, accurate and precise atomic data in the infrared are urgently needed. Identifications, wavelengths, strengths, broadening, and hyper-fine splitting parameters of stellar lines in the near-infrared are in many cases not accurate enough to model observed spectra, and in other cases, these parameters do not even exist. Some stellar features are unidentified.

Aims. The aim with this work is to identify a spectral feature at λvac = 1063.891 nm or λair = 1063.600 nm that is visible in spectra of stars of different spectral types that are observed with the GIANO-B spectrometer.

Methods. The search for spectral lines to match the unidentified feature in line lists from standard atomic databases was not successful. However, by investigating the original published laboratory data, we were able to identify the feature and solve the problem. To confirm its identification, we modelled the presumed stellar line in the solar intensity spectrum and found an excellent match.

Results. We find that the observed spectral feature is a stellar line originating from the 4s′–4p′ transition in S I, and that the reason for its absence in atomic line databases is a neglected air-to-vacuum correction in the original laboratory measurements from 1967 for this line only. From interpolation we determine the laboratory wavelength of the S I line to be λvac = 1063.8908 nm or λair = 1063.5993 nm, and the excitation energy of the upper level to be 9.74978 eV.
The impact of introduced Ponto-Caspian mysids (Paramysis lacustris) on the trophic position of perch (Perca fluviatilis) in European mesotrophic lakes
Authors: Rakauskas Vytautas
Published: October 2019

Paramysis lacustris was introduced into Lithuanian lakes in the middle of the 20th century. It was assumed that P. lacustris will enhance efficiency of primary production utilization and channelling of primary production towards higher trophic levels, i.e. commercially important fish species. However, at the time of P. lacustris introduction, there were no reliable data about its trophic position in lakes. Thus, P. lacustris was considered to have no or little impact on native ecosystems. Until now, there is a gap in the knowledge of the trophic role and potential impacts of P. lacustris on local food webs in lakes. Here we investigated the impact of P. lacustris on the food chain length of its potential predator Perca fluviatilis in temperate lakes. In this study, gut contents and stable isotope analyses were performed to assess the diet and trophic position of P. lacustris and P. fluviatilis in lakes with and without invasive mysids. The results obtained revealed that P. lacustris consumes a significant amount of animal prey and occupies the third trophic level in lake littoral zones. Furthermore, our results showed that P. lacustris might enhance the food chain length for at least some zooplanktivorous fishes. Overall, the assumption that P. lacustris invasion has no whole-ecosystem consequences, as it was thought before its introduction, is not correct.