Genetics

Podcast: Bird poop, pus, and the Manhattan projectthe surprising origins of the genetic alphabet – Genetic Literacy Project

On the latest episode of Genetics Unzipped, biologist Kat Arney explores the origins of the genetic alphabet: A, C, T and Gthe four letters that spell out all the genetic recipes encoded in DNA.

These letters are the initials of the four nucleotide chemicals that make up DNA: adenine, cytosine, thymine and guanine. They are ingrained in the scientific lexicon and burned into the brain of anyone whos ever worked with or even just learned about genes, genomes and DNA. Its a code thats as inseparable from genetics as the double helix itself.

But while many people know that the structure of DNA was figured out in the 1950s, far fewer people realize that the identities of these molecular letters were uncovered far earlier. In search of the origins of nucleotide names, Arney takes us from the bird poop boom of the 1840s through the heyday of atomic weapons research in the 1940s and beyond.

First we explore the guano mountains of Peru giant hills of solidified seabird excrement which were mined for fertilizer to feed a fast-developing world. Intrigued by the nourishing properties of guano, 19th-century scientists started to investigate its chemical components. This led to German chemist Julius Ungers discovery of guanine in 1846 the first nucleotide molecule to be identified.

DNA itself wasnt discovered until nearly twenty years later, when Johannes Friedrich Miescher isolated a strange sludgy substance from pus-soaked bandages obtained from a nearby clinic. He called it nuclein a name that still lingers in the formal chemical name for DNA, deoxyribonucleic acid. However, his discovery almost went ignored as his supervisor, Felix Hoppe-Seyler, did not believe that such an inexperienced researcher could make such an important finding.

Following up on Mieschers work, his colleague Albrecht Kossel identified cytosine, thymine and adenine as the other components of this mysterious nuclein, after purifying the chemicals from huge amounts of cow organs obtained from a nearby slaughterhouse.

The story of nucleotides doesnt end with the discovery of A, C, T and G. Although these four letters make up the genetic code of DNA, theres another base Uracil, or U that replaces thymine in RNA, a kind of molecular photocopy thats made when genes are read. And we also now know that DNA and RNA bases can be chemically altered to extend the genetic code in some very interesting ways. Finally, we hear how the discovery of the first modified RNA base, pesudouridine, came from a surprising source: the US atomic weapons program at Oak Ridge laboratory in Tennessee.

Full transcript, links and references available online atGeneticsUnzipped.com

Genetics Unzippedis the podcast from the UKGenetics Society,presented by award-winning science communicator and biologistKat Arneyand produced byFirst Create the Media.Follow Kat on Twitter@Kat_Arney,Genetics Unzipped@geneticsunzip,and the Genetics Society at@GenSocUK

Listen to Genetics Unzipped onApple Podcasts(iTunes)Google Play,Spotify,orwherever you get your podcasts

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Podcast: Bird poop, pus, and the Manhattan projectthe surprising origins of the genetic alphabet - Genetic Literacy Project

Genetics

From Iceland COVID-19 In Iceland: deCODE Genetics Will Screen General Population For Virus – Reykjavk Grapevine

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Magns Andersen

CEO of deCODE Genetics Kri Stefnsson (shown above) intends to screen the entire Icelandic population for COVID-19, of which there have been 60 confirmed cases at the time of this writing.

While almost all of these cases come from three flights returning from Italy and Austria, with the arrivals put in quarantine while testing is underway, the virus has unfortunately found its way into the general population.

Kris desire to screen the general population was not without controversy, as both the Data Protection Authority and the Scientific Ethics Committee initially believed Kri required a special permit in order to conduct the screening. However, Frttablai now reports that both bodies have reversed their position on the matter, as the screening is considered clinical work; not a scientific study.

In fact, a statement from deCODE emphasises that peoples personal data will not be permanently recorded nor put in the companys general knowledge bank. Rather, the purpose of the screening is meant to inform those who have symptoms whether or not they have COVID-19, in conjunction with the Directorate of Health, in order to assist already ongoing efforts.

This screening is expected to go forward within the next week.

Symptoms of COVID-19 include dry cough, fever, and aches in the bones. If you are worried you may have COVID-19, have been to any of the high-risk areas or in contact with anyone who has within the last 14 days, you are urged to call 1700 from an Icelandic phone number or +354 544 4113 from any other phone, where a health care professional will give you further information and guidance.

To prevent transmission or contact with the virus, the cardinal rule is to wash your hands frequently before eating and after touching common surfaces, and avoid touching your face. If you must sneeze or cough, do so into the crook of your elbow or into a tissue. It also naturally follows that you should avoid contact with sick people.

The Directorate of Health in fact has extensive information in English on COVID-19, including a handy FAQ.

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From Iceland COVID-19 In Iceland: deCODE Genetics Will Screen General Population For Virus - Reykjavk Grapevine

Cell Biology

New discovery could lead to better strategies for preventing breast cancer metastasis – The Medical News

New discovery in breast cancer could lead to better strategies for preventing the spread of cancer cells to other organs in the body, effectively reducing mortality in breast cancer patients.

According to a study, published today in Nature Cell Biology, breast cancer cells shift their metabolic strategy in order to metastasize. Instead of cycling sugar (glucose) for energy, they preferentially use mitochondrial metabolism.

This has important potential clinical implications because it suggests that drugs targeting mitochondrial metabolism may have efficacy for preventing metastatic spread in patients. Historically, tumors were thought to contain dysfunctional mitochondria and be principally sustained by anaerobic glycolysis, or Warburg metabolism. Our work challenges that dogma and shows that breast cancer cells use mitochondrial metabolism during metastatic spread."

Devon A. Lawson, PhD, assistant professor in the UCI Department of Physiology and Biophysics and a member of the Chao Family Comprehensive Cancer Center at the UCI School of Medicine

Despite major advances in the detection and treatment of early stage disease, metastasis - when cancer cells in the breast spread to other organs in the body - accounts for approximately 40,000 deaths among women in the U.S. each year. It is the number one cause of nearly all mortality associated with breast cancer.

Previous work suggests that metastasis is seeded by rare primary tumor cells with unique biological properties that enable them to spread, causing the cancer to take hold in other locations in the body. While properties promoting cell motility and migration are well studied, mechanisms governing the seeding and establishment of small collections of cancer cells in distal tissues are not. This is in part because metastatic seeding cannot be studied in humans, and because it is technically challenging to detect and analyze rare cells at this transient stage in animal models.

"Through our research, we established a robust new method for identifying global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA-sequencing and patient-derived xenograft (PDX) models of breast cancer," said Ryan Davis, first author on the study and a doctoral student in the Lawson laboratory. "We found that metastatic cells harbor distinct RNA molecules that are highly predictive of poor survival in patients and alter metabolism in a way that can be targeted therapeutically."

Source:

Journal reference:

Davis, R.T., et al. (2020) Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nature Cell Biology. doi.org/10.1038/s41556-020-0477-0.

Posted in: Cell Biology | Biochemistry

Tags: Anatomy, Breast Cancer, Cancer, Cell, Cell Biology, Cycling, Drugs, Education, Efficacy, Epidemiology, Genetic, Glucose, Glycolysis, Laboratory, Medicine, Metabolism, Metastasis, Mitochondria, Mortality, Pathology, Pharmacology, Physiology, Public Health, Research, RNA, Tumor, Xenograft

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Physiology

Introduction to physiology: History, biological systems, and …

Physiology is the study of normal function within living creatures. It is a sub-section of biology, covering a range of topics that include organs, anatomy, cells, biological compounds, and how they all interact to make life possible.

From ancient theories to molecular laboratory techniques, physiological research has shaped our understanding of the components of our body, how they communicate, and how they keep us alive.

Merrian-Webster defines physiology as:

[A] branch of biology that deals with the functions and activities of life or of living matter (such as organs, tissues, or cells) and of the physical and chemical phenomena involved.

Here are some key points about physiology. More detail and supporting information is in the main article.

The study of physiology is, in a sense, the study of life. It asks questions about the internal workings of organisms and how they interact with the world around them.

Physiology tests how organs and systems within the body work, how they communicate, and how they combine their efforts to make conditions favorable for survival.

Human physiology, specifically, is often separated into subcategories; these topics cover a vast amount of information.

Researchers in the field can focus on anything from microscopic organelles in cell physiology up to more wide-ranging topics, such as ecophysiology, which looks at whole organisms and how they adapt to environments.

The most relevant arm of physiological research to Medical News Today is applied human physiology; this field investigates biological systems at the level of the cell, organ, system, anatomy, organism, and everywhere in between.

In this article, we will visit some of the subsections of physiology, developing a brief overview of this huge subject. Firstly, we will run through a short history of physiology.

The study of physiology traces its roots back to ancient India and Egypt.

As a medical discipline, it goes back at least as far as the time of Hippocrates, the famous father of medicine around 420 BC.

Hippocrates coined the theory of the four humors, stating that the body contains four distinct bodily fluids: black bile, phlegm, blood, and yellow bile. Any disturbance in their ratios, as the theory goes, causes ill health.

Claudius Galenus (c.130-200 AD), also known as Galen, modified Hippocrates theory and was the first to use experimentation to derive information about the systems of the body. He is widely referred to as the founder of experimental physiology.

It was Jean Fernel (1497-1558), a French physician, who first introduced the term physiology, from Ancient Greek, meaning study of nature, origins.

Fernel was also the first to describe the spinal canal (the space in the spine where the spinal cord passes through). He has a crater on the moon named after him for his efforts it is called Fernelius.

Another leap forward in physiological knowledge came with the publication of William Harveys book titled An Anatomical Dissertation Upon the Movement of the Heart and Blood in Animals in 1628.

Harvey was the first to describe systemic circulation and bloods journey through the brain and body, propelled by the heart.

Perhaps surprisingly, much medical practice was based on the four humors until well into the 1800s (bloodletting, for instance). In 1838, a shift in thought occurred when the cell theory of Matthias Schleiden and Theodor Schwann arrived on the scene, theorizing that the body was made up of tiny individual cells.

From here on in, the field of physiology opened up, and progress was made quickly:

The major systems covered in the study of human physiology are as follows:

There are a great number of disciplines that use the word physiology in their title. Below are some examples:

The topics mentioned above are just a small selection of the available physiologies. The field of physiology is as essential as it is vast.

Anatomy is closely related to physiology. Anatomy refers to the study of the structure of body parts, but physiology focuses on how these parts work and relate to each other.

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Physiology

Anatomage Introduces Physiology Functions to Digital Cadavers with Table 7 – BioSpace

SAN JOSE, Calif., March 5, 2020 /PRNewswire/ -- Anatomage Inc, a leader in 3D medical technology, today announces the launch of Table 7, bringing physiology elements to real human cadavers.

Anatomage is the first company to successfully integrate physiology functions into a real human cadaver. Through the Table 7 software release for the Anatomage Table, users can restore a portion of a cadaver back to life using four physiology tools - Heart Motion, Nerve Connection, Pathways, and Catheterization.

The Heart Motion tool restores the cardiac physiological functions of the cadaver's heart. By simulating the entire cardiac cycle and synchronizing heart rhythms with the integrated digital electrocardiography, the tool can be used to elevate cardiovascular physiology learning.

The Nerve Connection tool interactively displays the cadaver's nerve innervation from the brain to a dermatome, muscle or organ. The tool provides students with the physiological context of the human nervous system, allowing them to locate the nerve root responsible for any stimulus, thereby supporting neuroanatomy education.

The Pathways tool illustrates drug delivery and different physiological pathways on the cadaver. Depicting the physiological mechanism occurring during the transport of chemical compounds, this tool offers visual references of physiology for toxicology, pharmacology, and any applicable studies in medicine.

The Catheterization tool enables users to practice catheter insertion on a digital cadaver. With the Anatomage Table, students can learn how real-life cardiac catheterization procedures are carried out on a living human body, preparing them for medical careers.

Introducing physiology elements to deceased bodies is the first step toward building a digital body that functions as an alive human body for medical simulation and educational applications. Aside from the physiology elements, Table 7 features medical-school level educational materials, including 60 3D real-cadaver prosections with annotations, 400 fully-prepared medical illustration presets, and 3D radiology reports reviewed by real radiologists. The update also comes with additional high-resolution regional anatomy scans, improved quizzing options, annotated bony landmarks, and refinements in the Table's histology-viewing feature such as the ability to compare 4 different histology tissues. Altogether, these technologies bring values that a physical cadaver couldn't deliver to various medical disciplines.

Containing 4 life-size real human cadavers and over 1,000 real-life pathology cases, the Anatomage Table has been trusted and adopted by thousands of educational and clinical institutes worldwide. Now with the launch of Table 7, the Anatomage Table has become an unrivaled healthcare education platform that marks a beginning of an era where learning with a living cadaver is possible.

For more information about Table 7, please visit here.

About Anatomage

A market leader in medical imaging technology, Anatomage enables an ecosystem of 3D anatomy hardware and software, allowing users to visualize anatomy at the highest level of accuracy. Through its highly innovative products, Anatomage is transforming standard anatomy learning, medical diagnosis and treatment planning.

Contact:Jack ChoiCEOAnatomage Inc.Phone: 1-408-885-1474Email: info@anatomage.comwww.anatomage.com

View original content to download multimedia:http://www.prnewswire.com/news-releases/anatomage-introduces-physiology-functions-to-digital-cadavers-with-table-7-301016802.html

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Physiology

Teaching about coronavirus: Science teacher on why her students are not panicking – The Morning Call

Still, I knew this alone wouldnt be enough to make students feel as if they were real-world health professionals in training. So I explored another innovation available to online learners: simulators. Simulators can mimic what goes on outside the classroom, or in the case of an anatomy and physiology class, what goes on inside the body.

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Teaching about coronavirus: Science teacher on why her students are not panicking - The Morning Call

Physiology

Red and blue nets impact on physiological and morphological traits of tomato – hortidaily.com

Plants can detect the quality, quantity and direction of light and use it as a signal to adapt their morphogenesis and growth. Thus according to their light transmission, coloured nets used to protect plants from pests and limit irradiance can also affect plant growth and production.

Scientists at Yezin Agricultural University (Myanmar), Kasetsart University (Thailand), INRA and CIRAD (France) have determined the importance of the light spectrum on plant growth, reproductive characteristics and fruit chemical composition in tomato plants, grown under blue or red nets transmitting similar photosynthetic yield from transplanting to the end of harvest.

Results showed that the morphological traits, organ physiology and fruit composition were strongly influenced by net colour. Plants under the red net were taller with a greater leaf area and a shoot to root ratio. An increased blue to red ratio slightly enhanced the reproductive development (visible bud development and 1st flowering) of tomato plants. An increased red to blue ratio enhanced the tomato glucose (17%) and fructose (6%) contents, while the citric (5%) and malic acids (4%) contents decreased, triggering a higher sugar/acid ratio. A high blue to red light limited organ growth and plant light interception was reduced despite a higher photosynthetic yield and a slight enhancement of the organ appearance rate.

"A low blue to red light increased fruit weight at harvest and even if it did not significantly improve fruit yield, it favoured fruit quality as it enhanced the tomato sugar/acid ratio," explain the scientists.

Source: Aye Aye Thwe, Poonpipope Kasemsap, Gilles Vercambre, Frdric Gay, Jessada Phattaralerphong, Hlne Gautier, 'Impact of red and blue nets on physiological and morphological traits, fruit yield and quality of tomato (Solanum lycopersicum Mill.)', 2020, Scientia Horticulturae, Volume 264, 109185.

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Physiology

Meet the Lebanese Scientist Who Was Awarded a Nobel Prize – The961

The Lebanese scientist awarded a Nobel Prize is Peter Brian Medawar who was born in 1915 in Rio De Janeiro, Brazil, to a Lebanese father with British nationality.

He studied zoology in Oxford, then pathology anatomy after graduation, and continued his work in scientific research related to medicine.

He began working in Oxford and then in London. He was then appointed director of the National Institute for Medical Scientific Research in the year 1962.

The Lebanese scientists research began in the study of tissue transplantation and in the regeneration of peripheral nerves. During World War II, he was asked to investigate the cause of the bodys rejection of any skin taste taken from another donor.

Medawar was the Chairmen of Zoology at the University of Birmingham (1947-1951) and then at the University of London (1951-1962), and held other prestigious scientific positions.

Some of his published researches are The Uniqueness of the Individual (1959), The Future of Man (1959), Platos Republic (1982), and Memoirs of a Thinking Radish (1986).

The prevailing theories up to that time were that vertebrates inherit the ability to distinguish their tissues from the tissues of any other vertebrates during pregnancy.

Medawar conducted studies on cattle twins by vaccinating one of the twins skins with skin taken from the other twin.

The immunologist noted that the graft was not rejected by the body in the real (monozygotic) twins, while it was rejected in some dizygotic twins and accepted in others.

It was clear to Medawar and his colleagues that the reason for this acceptance is that the dizygotic twins exchange considerable amounts of erythrocytes during pregnancy. This made the twins count the erythrocytes as their own.

According to the scientist, the transplantation of skin from a third team leads immediately to its rejection and excretion, as it includes all tissues of the twins and is not limited to one particular fabric.

Australian Frank M. Burnet was the first to say that there was acquired immunological tolerance. Mudawer adopted the Burnet theory and added his own research into it.

He demonstrated that newborn mice can acquire immune tolerance by injecting other donor mouse cells, thereby gaining tolerance to their cells and tissues as well as to cells of true twinning and tissue.

As a result of this study, Medawar developed his theory of organ immunity, which was the basis for his subsequent studies on tissue transplantation and organ transplantation.

Medawar and his colleagues thus came to present his theory of acquired immunological tolerance for homografts. This discovery earned him many awards, including the Nobel Prize.

He was awarded the Knighthood in 1965 and the Order of Merit in the year 1981. Earlier in 1951, he was elected a Fellow of the Royal Academy in recognition of his scientific contributions.

The Lebanese scientist was also awarded the Gold Medal Medal in 1959, and the Nobel Prize for Medicine and Physiology in 1960 in partnership with Frank Macfarlane Burnet.

Peter Medawar is the first scientist of Lebanese origin to be awarded the Nobel Prize in Physiology (Medicine).

Medawar confirmed in part of his Nobel prize acceptance speech that he used this discovery and demonstrated with [his] colleagues that this natural manifestation of immunological tolerance can be achieved experimentally in fetuses or in newborns.

He explained in his time many aspects of immune and autoimmune diseases, as well as in the advancement of human transplantation technologies. The scientist died at 75 years old in London.

According to the Nobel Prize official website, Medawar won the Nobel Prize for the discovery of acquired immunological tolerance in The Nobel Prize in Physiology or Medicine 1960.

The website explains: He could perform new transplants on the mice when they became adults, something that did not work when the transplants were not performed during the fetus stage. The results had significance for organ transplants.

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Meet the Lebanese Scientist Who Was Awarded a Nobel Prize - The961

Physiology

Understanding the mother-breastmilk-infant triad – Science Magazine

A Rohingya Muslim refugee holds her malnourished child in Bangladesh. Better understanding of breastmilk could improve therapeutic foods to treat undernutrition.

Breastfeeding and breastmilk exert remarkable influence on infant survival and health (1, 2), including reduced risk from infections and promoting various aspects of postnatal development. The many maternal benefits include protection from breast and ovarian cancer and cardiometabolic disorders. Although the mechanisms underlying some of these benefits have been elucidated, the origins of others that have been reported, such as influence on adult IQ and later protection against obesity and diabetes, remain more obscure. Hence, timely investments in research designed to clarify the operations and biological effects of the mother-breastmilk-infant triad, and their translation into public health, are needed.

Breastmilk does not stand alone; maternal physiology, breastmilk composition, and infant physiology are parts of a coadapting system, with variations in each influencing the trajectory of infant development and maternal health. In addition to macronutrients and micronutrients essential for child survival, breastmilk contains other myriad bioactive components, including cells and microbes (3, 4). Breastmilk can be considered a live tissue whose composition varies between women and changes over the course of lactation. Structurally diverse human milk oligosaccharides (HMOs) represent the third most abundant nonaqueous component of breastmilk (after lactose and lipids). One prominent example illustrating how maternal genotype affects breastmilk composition is a single-nucleotide polymorphism that introduces a premature stop codon in the fucosyltransferase-2 (FUT2) gene. This mutation abolishes the ability to synthesize (1-2)-fucosylated HMOs. The presence or absence of these HMOs creates specific maternal lactotypes, known as secretors and nonsecretors, respectively, with the breastmilk of secretors conveying reduced risk of common forms of infectious diarrhea (5).

Comprehensive characterization of the components of each axis of the triad through longitudinal and cross-sectional studies of maternal-infant cohorts has expanded markedly. Increasingly, high-throughput analytical methods have been used to characterize more than 150 different HMO structures, and intra- and interpersonal variations in their representation within and across different populations (6). Other components of breastmilk, including compounds associated with the membrane that surrounds milk fat globules, microRNAs, and bacterial constituents, as well as antibodies and immune cells, are being actively cataloged and characterized. In addition to quantifying the products of metabolism in infants and their mothers by mass spectrometry, platforms are now available for simultaneously measuring the concentration of thousands of proteins circulating in blood that are biomarkers and regulators of numerous physiologic, metabolic, and immune processes, as well as other facets of growth and homeostasis (7). Furthermore, recent studies have highlighted how, with the use of culture-independent methods, features of gut microbial community development in infants and young children can be used as a readout for their nutritional status (8, 9).

Mechanistic insights hold the promise of providing more informative definitions of health status, better predictions of health outcomes, improved recommendations for preventing disease, and new therapeutic targets.

Although datasets pertaining to each axis are available, considerably more work is needed to quantitatively relate how environmental influences affect the triad and in turn, how variations in each of its axes influence the other (see the figure). For example, it will be interesting to discover what other maternal genetic factors affect biosynthesis of HMOs and other milk constituents. The mechanisms that link maternal nutritional status and other aspects of their physiology to breastmilk features and infant growth phenotypes are also an important issue. Additionally, which signaling pathways allow infant health status to regulate maternal biology, including breastmilk composition, should be investigated. How varied sociocultural, behavioral, and environmental factors shape and perturb the development of the triad is important to understand so that a normal range can be defined. Two disorders, childhood malnutrition and necrotizing enterocolitis (NEC), illustrate how a deeper understanding of the mother-breastmilk-infant triad could improve child health with potential lifelong benefits, and how some of the analytic challenges might be surmounted.

Childhood malnutrition contributes to 45% of deaths worldwide in those under the age of five; it manifests early in life and involves disruption of multiple biological systems fundamental to healthy growth, including host pathways influenced by the developing gut microbiota, which are key consumers of breastmilk constituents (8, 9). One approach for obtaining new insights about disease pathogenesis is to conduct longitudinal studies of healthy and malnourished children living in areas where disease burden is high, and to comprehensively characterize the plasma proteomes, metabolomes, and developing microbial communities of malnourished infants and their healthy counterparts, their mothers' breastmilk composition, and the products of microbial HMO utilization.

A strategy for defining functionally important interactions between triad components is to borrow from studies conducted in disparate fields where statistical covariation is used for feature reduction. Components that covary with each other are deemed important for defining the behaviors or functions of dynamic complex systems. Applying this approach to the developing gut microbiota of healthy members of a Bangladeshi birth cohort sampled monthly from 1 to 60 months of age disclosed a network composed of 15 covarying bacterial taxa (9). The abundances of these taxa describe normal gut microbial community assembly in healthy members of birth cohorts residing in diverse geographic locales and are useful for quantifying the degree of impaired microbial community development in children with moderate and severe acute malnutrition.

From the limited evidence available, microbiota immaturity associated with these conditions is not repaired with standard therapeutic foods. Affordable, culturally acceptable complementary foods have been identified that in combination repair the gut microbiota of Bangladeshi children with moderate acute malnutrition toward a state resembling that of age-matched, healthy growing children. This is accompanied by increases in numerous blood plasma protein biomarkers and mediators of growth, bone formation, neurodevelopment, metabolism, and immune function (8, 9).

These findings support the idea that healthy growth is linked in part to healthy development of the gut microbiota. They also raise the question of what factors shape microbial community development during the period of exclusive breastmilk feeding, and as children transition to complementary foods during the weaning period. Members of the bacterial genus Bifidobacterium, notably B. longum subsp. infantis, have suites of genes involved in the import and metabolism of HMOs. It is important that efforts be directed to defining the representation of B. infantis and other HMO-consuming bacteria in healthy versus malnourished infants and their mothers. This information, together with characterizing the representation of genes involved in HMO acquisition and degradation in different bacterial strains cultured from these children, would allow an assessment of (i) whether and how the presence of these different organisms and their genome features correlate with maternal breastmilk composition and (ii) the degree to which products of breastmilk metabolism correlate with host features. The answers, from analyses of human biospecimens as well as animal models colonized with consortia of human gut microbes representing different stages of community assembly (10, 11), could have important therapeutic implications. These include the development of new probiotic, HMO-based prebiotic and/or synbiotic (prebiotic combined with probiotic) therapies (12).

NEC provides a different type of opportunity to characterize the mother-breastmilk-infant triad. One of the most common and fatal gastrointestinal disorders in preterm infants, NEC develops within the first few weeks of delivery. It is characterized by destruction of the integrity of the intestinal wall, invasion of luminal bacteria, marked inflammation, and sepsis. Maternal and infant physiology are immature after preterm delivery in terms of producing and digesting breastmilk. Moreover, the use of antibiotics and other medications and interventions, when both mother and infant face serious and often life-threatening crises, further disrupts the mother-breastmilk-infant triad, including initial colonization of the infant intestine. Although breastmilk composition is not fully adapted to the physiological needs of the premature infant, breastmilk feeding, compared to enteral feeding with specialized breastmilk substitutes, reduces NEC incidence by 6- to 10-fold (13). The mechanisms underlying these protective effects remain largely uncharacterized.

HMOs significantly improve survival and reduce pathology in a neonatal rat model of NEC, leading to the identification of the HMO, disialyllacto-N-tetraose (DSLNT), as a protective factor (14), likely through its direct interactions with gut epithelial and immune cells. A multicenter study of mothers and their very-low-birthweight infants found that infants who developed NEC received breastmilk containing less DSLNT than infants who did not develop NEC (15). Proof of a causal relationship requires a randomized controlled clinical trial, which raises several challenges, including the availability of DSLNT and ethical considerations if control groups of high-risk infants were to be treated with formula alone. More generally, NEC illustrates the need to comprehensively define states of triad immaturity. This would entail longitudinal studies of the set of features that define breastmilk given to prematurely born neonates who do and do not develop this devastating disease. It would also require a simultaneous effort to obtain comprehensive definitions of the biological characteristics of chronologically age-matched preterm infants with and without NEC, as well as of their mothers.

Mothers face a balancing-act between various socioeconomic, cultural, and even marketing pressures to maintain or forego breastfeeding and their motivation to provide their infants with what is best for their health and development. This balancing act is perpetuated in part by confusion surrounding the respective attributes of breastmilk versus breastmilk substitutes, with consumer understanding being heavily influenced by commercial interests. Aspirational goals include new parameters for defining health status and deeper understanding of how health outcomes are related to breastfeeding and breastmilk components. Within a risk-stratified continuum of care, knowledge of the latter has potential therapeutic implications and opportunities, personalized to the circumstances of an individual mother and her infant (1). Such efforts will not only provide new appreciation of the remarkable properties of nature's first food, but also serve to further develop analytic approaches that yield insights into the dynamic systems that direct infant development.

Acknowledgments: We thank M. Barratt and S. Moukarzel for helpful input during writing. L.B. and A.S.R. contributed equally to this work. L.B. is a coinventor on patent applications related to the use of HMOs in preventing NEC and other inflammatory diseases. J.I.G. is a cofounder of Matatu, Inc., which characterizes the role of diet-by-microbiota interactions in animal health.

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Physiology

Top U of A subjects rise in new ranking of world’s best – Folio – University of Alberta

The University of Alberta landed in the top 10 of sport-related subjects for the fourth year in a row and inched closer to the top 10 in the categories of mining and minerals engineering and nursing, according to the latest QS World University Rankings by Subject.

The 2020 version of the subject rankings saw sports-related subjects jump to seventh from ninth, while mining and minerals engineering moved from 12th to 11th and nursing fought its way back into the top 20 to land at 18th.

Other U of A subjects that ranked in the top 50 included earth and marine sciences, which rose from 44th to tie for 41st; education, which rebounded from 47th to stick at 44th; and anatomy and physiology, which ranked 44th.

James Young, professor and chair of the U of As Department of Physiology, said he pins the U of As excellence in physiology to strategic recruitment pushes over the past four decades.

We've had really sustained recruitment of really excellent young faculty members who want to be part of an excellent environment, and we offer that, said Young. They're not just joining the Department of Physiology, they're joining the faculty and becoming part of a number of research institutes and facilities that really are world class.

Clayton Deutsch, director of the U of As School of Mining and Petroleum Engineering, said part of the programs success is the impact alumni are having on the mining industry.

You go around to different mining schools around the world, there will be U of A alumni there, said Deutsch. In mining companies all over the world, there are always U of A alumni around there.

He also said the programs approach of being committed academically while remaining practical is what places the U of As mining education among the worlds best.

Even despite some economic woes in the province, we have essentially 100 per cent employment of our students graduating within six months of finishing, said Deutsch. We do that by remaining current and steadfast in our focus on solving real-world mining problems.

One of the enduring legacies of Kerry Mummery, outgoing dean of the Faculty of Kinesiology, Sport, and Recreation, will be the university finishing in the top 10 in the category of sport-related fields for four years in a row.

"During my tenure as dean, I've had the pleasure of working with and bringing in some of the top professors in their field," said Mummery. "I've always been impressed with the quality of their work and how that work makes its way into the classroom to provide our students with a solid foundation of knowledge they wouldn't have found anywhere else."

Overall, the U of A ranked in the top 100 in 14 subjects and 35 in the top 250. No ranked subject had the U of A lower than ninth nationally, and the U of A was ranked top five in Canada in 18 categories.

As for the five broad subject ranks, the U of A moved up seven spots to 90th in life sciences and medicine, while dipping slightly in engineering and technology (down to 112 from 107), natural sciences (111 to 116) and arts and humanities (137 to 143). Social sciences and management surged 12 spots to finish at 160.

The methodology for compiling each subject ranking can vary greatly and depends on the publishing rates in each area. Academic reputation, which accounts for anywhere from 30 to 90 per cent of the weight given in determining the rank in a subject area, draws on responses from thousands of academics worldwide.

Other measures include employer reputation, which makes up between 10 and 30 per cent of the measure; citations per paper, which also accounts for between 10 and 30 per cent; and h-indexa way of measuring both the productivity and impact of an academic's published workwhich is valued anywhere from 10 to 30 per cent.

The success in this latest QS ranking follows news in October that the U of A moved back into the top five in Maclean's 2020 Canadian University Rankings, thanks in part to strong showings by the faculties of nursing, business and science.

In August, the ShanghaiRanking Consultancys 2019 Academic Ranking of World Universities by Subject saw the U of A jump into an eighth-place tie with Princeton in the category of environmental science and engineering. Overall, the U of A finished among the top 100 in 21 of the 54 subjects assessed for the ranking, one more than the previous year, with eight subjects ranking in the top 50.

Earlier, the 2019 NTU Ranking of research output placed the U of A 81st in the world, up seven spots over the prior year. The advancement was bolstered by the university's 43rd-place performance in the subject of agricultural science, 47th in environment/ecology and 48th in electrical engineering.

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Top U of A subjects rise in new ranking of world's best - Folio - University of Alberta