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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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Understanding the mother-breastmilk-infant triad - Science Magazine

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

How to lose visceral fat: Best type of exercise to do to reduce the harmful belly fat – Express

Visceral fat increases a persons risk of developing various health conditions, such as hypertension and heart disease. Which exercise is the best at reducing levels of this harmful belly fat?

Researchers from the Duke University Medical Centre have discovered the best type of exercise to cut levels of visceral fat.

Their eight-month study compared how much visceral fat was lost due to aerobic exercise, resistance training or both.

Documenting 196 people, they found aerobic exercise to be the most efficient and effective way to lose the harmful belly fat.

Published in the American Journal of Physiology, lead author physiologist Cris Slentz, Ph.D. said: Our study sought to identify the most effective form of exercise to get rid of that unhealthy fat.

[If] you want to lose belly fat, aerobic exercise is the better choice because it burns more calories."

The study revealed aerobic exercise burned 67 percent more calories than resistance training.

The aerobic group performed an equivalent of 12 miles of jogging per week at 80 percent maximum heart rate.

READ MORE: Vitamin D deficiency symptoms: The sign on your head you need to watch out for

The resistance group, on the other hand, performed three sets of eight, 12 repetitions, three times per week.

What really counts is how much exercise you do, how many miles you walk and how many calories you burn," Slentz said.

If you choose to work at a lower aerobic intensity, it will simply take longer to burn the same amount of unhealthy fat."

Examples of aerobic exercise include anything that gets your heart pumping.

There are free aerobic workout videos to follow on the NHS website, which include dancing.

And aerobic exercises, also known as cardio, include spinning, running, swimming and hiking.

By repeatedly moving large muscles in the arms, legs and hips, breathing will get become rapid.

This maximises the amount of oxygen in your blood, according to the Mayo Clinic.

Additionally, the body will release endorphins natural painkillers which will promote an increased sense of wellbeing.

If youre new to moderate-intensity exercise, its best to start off slowly.

Also, if you have any current health conditions, do discuss your plans to exercise more with your doctor who can advise you further.

The NHS state: Aim to be physically active every day. Any activity is better than none, and more is better still.

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How to lose visceral fat: Best type of exercise to do to reduce the harmful belly fat - Express

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

Physiology

Stoners Bake Snacks with Scientific Hacks – The LumberJack

Edibles or cannabis-infused foods are a common way to consume marijuana. The process of making edibles, just like baking brownies, is a science. The primary psychoactive compound in marijuana is called cannabinoids. When making edibles, you infuse a fat with cannabinoids to activate the chemical.

Mark Wilson, a Humboldt State University professor with a Ph.D. in microbiology, genetics and toxicology explained that cannabinoids are fat soluble and dont break down in water.

Some substances are water soluble and some substances are fat soluble, Wilson said. THC is primarily composed of carbon-carbon bonds and carbon-hydrogen bonds, so it cant interact well with water, but it can interact well with fats and oils.

This characteristic of THC, tetrahydrocannabinol, limits what can be turned into an edible. THC cant steep in hot water for weed tea. Marijuana would need to be steeped in hot milk instead, where the THC would break down and bond with the milk fats.

Things that dissolve into our fat tend to remain in our system much longer. That is, they slowly diffuse into fat, and slowly diffuse out. The fat acts as a sort of absorption compartment. That makes it detectable in drug tests for weeks.

Many people use butter as the main fatty ingredient in edibles. Dairy-based fats are a good option for infusing cannabinoids, but lactose-free alternatives are also solid options, including coconut and olive oil. Bacon fat can absorb cannabinoid infusions too, if youre looking for a savory option.

Joseph Szewczak, an HSU professor who studies and teaches comparative physiology and physiological ecology explained the physical changes to the body when people eat cannabis-infused fats rather than smoking cannabis plants.

Things that dissolve into our fat tend to remain in our system much longer, Szewcxak said. That is, they slowly diffuse into fat, and slowly diffuse out. The fat acts as a sort of absorption compartment. That makes it detectable in drug tests for weeks.

Whether inhaled or eaten, the THC enters the blood stream and messes with brain-cell functions in a unique way. Since THC is shaped like a chemical in the brain, the brain recognizes the chemical and allows to alter normal brain function. That chemical usually tells brain neurons to rest, but THC forces the brain to keep firing, which leads to deep thoughts, increased creativity and anxiety.

In light of these effects, its important to understand whats going to happen after eating an edible. First, since the body takes some time to digest edibles and since their THC is stored in fat, the high lasts longer. Second, the nature of THC and marijuana may lead to discomfort or anxiety, or may lead to creativity and fun, but thats dependent on many factors.

Co-Director of the Humboldt Institute for Interdisciplinary Marijuana Research Josh Meisel is researching the significance of set and setting, or who youre with and where you are, and how those things impact a high.

Peoples negative experiences may be influenced by edible use, Meisel said. But set and setting may be as influential or more influential than the psychoactive properties of the substance itself.

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Stoners Bake Snacks with Scientific Hacks - The LumberJack

Physiology

An atlas of the protein-coding genes in the human, pig, and mouse brain – Science Magazine

Mapping the mammalian brain

The diverse physiology of the brain is reflected in its complex organization at regional, cellular, and subcellular levels. Sjstedt et al. combined databoth newly acquired and from other large-scale brain mapping projectsfrom transcriptomics, single-cell genomics, in situ hybridization, and antibody-based protein profiling to map the molecular profiles in human, pig, and mouse brain. The analysis is consistent with a conserved basic brain architecture during mammalian evolution, but it does show differences in regional gene expression profiles.

Science, this issue p. eaay5947

The brain is the most complex organ of the mammalian body, boasting a diverse physiology combined with intricate cellular organization. In an effort to expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of the main regions of the human, pig, and mouse brain using transcriptomics and antibody-based mapping. With this approach, we have identified regional expression profiles and observed similarities and differences in expression levels between these three mammalian species.

There is a need for a comprehensive overview of genes expressed in the mammalian brain categorized by organ, brain region, and species specificity. To address this need, a brain-centered knowledge resource of RNA and protein expression in the brain of three mammalian species has been created and used for cell topological analysis, systems modeling, and data integration. The regional expression of all protein-coding genes is reported, and this classification is integrated with results from the analysis of tissues and organs of the whole human body. All generated data, including high-resolution images and metadata, have been made publicly available in an open-access Human Protein Atlas (HPA) Brain Atlas.

The global analysis suggests similar regional organization and expression patterns in the three mammalian species, consistent with the view that basic brain architecture is preserved during mammalian evolution. However, there is considerable variability between species for many neurotransmitter receptors, in particular between human and mouse. This calls for caution when using the mouse as a model system for the human brain, for example, in attempts to develop therapeutic strategies. For some of the brain regions, such as the cerebellum and hypothalamus, the human global expression profile is closer to that of the pig than it is to that of the mouse, suggesting that the pig might be considered a preferred animal model to study many brain processes. We show that many signature genes identified previously for specific brain cell types (such as astrocytes, microglia, oligodendrocytes, and neurons) are expressed at even higher levels in peripheral organs. In fact, our results support a view of shared functions between many genes in microglia and immune cells, and a large number of genes previously identified as signature genes for astrocytes are shown to be shared with liver or skeletal muscle. The cerebellum stands out as having a distinct molecular signature with many regionally enriched genes. Several genes suggested to be involved in neuropsychiatric diseases are selectively expressed in the cerebellum.

The integration of data from several sources has allowed us to combine data from transcriptomics, single-cell genomics, in situ hybridization, and antibody-based protein profiling. This integrative approach for mapping the molecular profiles in the human, pig, and mouse brain has generated a detailed multilevel genome-wide view on the protein-coding genes of the mammalian brain, where we compared tissue specificity across the whole body, as classified in the HPA (www.proteinatlas.org). The open-access HPA Brain Atlas resource offers the opportunity to explore individual genes and classes of genes and their expression profiles in the various parts of the mammalian brain.

Multiple regions of the human, pig, and mouse brain were dissected and analyzed. A uniform manifold approximation and projection (UMAP) analysis (middle) shows the global expression patterns of 1710 samples in the human brain, with the cerebellum as the outlier. The HPA Brain Atlas (right) shows the expression of individual genes, for example, synaptosomal-associated protein 25 (SNAP25), in the different brain regions in the three mammalian species.

The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.

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An atlas of the protein-coding genes in the human, pig, and mouse brain - Science Magazine

Immunology

How to boost your immune system to avoid colds and coronavirus – The Guardian

Its been a long, wet winter. Everybody has got colds, and now we are braced for a coronavirus epidemic. Boosting our immune system has rarely felt more urgent, but, beyond eating more tangerines and hoping for the best, what else can we do?

Sheena Cruickshank, a professor of immunology at the University of Manchester, has a shocking cold when we speak at a safe distance, over the phone. To know how to take care of your immune system, she says, first you need to understand the weapons in your armoury a cheeringly impressive collection, it turns out.

When you come into contact with a germ youve never met before, she says, youve got various barriers to try to stop it getting into your body. As well as skin, we have mucus snot is a really important barrier and a microbiome, the collective noun for the estimated 100tn microbes that live throughout our bodies, internally and externally. Some of these helpful bugs make antimicrobial chemicals and compete with pathogens for food and space.

Beneath these writhing swamps of mucus and microbes, our bodies are lined with epithelial cells which, says Cruickshank, are really hard to get through. They make antimicrobial products including, most relevant to coronavirus, antiviral compounds that are quite hostile.

If a pathogen breaches these defences, it has to deal with our white blood cells, or immune cells. One type, called macrophages, inhabit all our body tissue and, says Cruickshank, have all these weapons ready to go, but theyre not terribly precise. They report to the cleverer, adaptive white blood cells known as lymphocytes. They are the ones that remember germs, so if you meet that germ again, says Cruickshank, theyll just deal with it probably without you even knowing. Thats when youve got immunity and is the basis of vaccination. Its trying to bypass all the early stuff and create the memory, so you dont have to be sick.

Our immune systems may have blind spots. This might mean that our immune response doesnt recognise certain bugs, she says, or the bugs have sneaky evasion strategies. Personally, my immune system is not necessarily very good at seeing colds. But a healthy lifestyle will ensure your defences are as good as they get.

Seeing as our bodies contain more cells belonging to microbes, such as bacteria and yeasts, than human ones, lets start with the microbiome. We live in a symbiotic relationship with our gut bacteria, says Prof Arne Akbar, the president of the British Society for Immunology and a professor at University College, London. Having the right ones around, that we evolved with, is best for our health. Anything we do that alters that can be detrimental.

Not only do our microbes form protective barriers, they also programme our immune systems. Animals bred with no microbiome have less well developed immune responses. Older people, and those with diseases that are characterised by inflammation, such as allergies, asthma, rheumatoid arthritis and diabetes, tend to have less varied gut microbiomes.

To feed your gut flora, Cruickshank recommends eating a more varied diet with lots of high-fibre foods. Being vegetarian isnt a prerequisite for microbiome health, but the more plant foods you consume, the better. The microbiome really likes fibre, pulses and fermented foods, she adds.

Kefir yoghurt and pickles such as sauerkraut and kimchi are among the fermented delicacies now fashionable thanks to our increasing knowledge of the microbiome. But the evidence for taking probiotic supplements, she says, is mixed. Its not a dead cert that they will survive the journey through your digestive tract, or that they will hang around long enough if they do. Its more effective to change your diet, says Cruickshank.

The skin microbiome is important, too, but we know less about it. High doses of ultraviolet light (usually from the sun) can affect it negatively, weakening any protective functions (as well as triggering immune suppression in the skin itself). Overwashing with strong soaps and using antibacterial products is not friendly to our skin microbiomes. Combinations of perfumes and moisturisers might well also have an effect, says Cruickshank.

To be immunologically fit, you need to be physically fit. White blood cells can be quite sedentary, says Akbar. Exercise mobilises them by increasing your blood flow, so they can do their surveillance jobs and seek and destroy in other parts of the body. The NHS says adults should be physically active in some way every day, and do at least 150 minutes a week of moderate aerobic activity (hiking, gardening, cycling) or 75 minutes of vigorous activity (running, swimming fast, an aerobics class).

The advice for older people, who are more vulnerable to infection, is to do whatever exercise is possible. Anythings better than nothing, says Akbar. But a lifetimes exercise could significantly slow your immune system declining with age. In 2018, a study by University of Birmingham and Kings College London found that 125 non-smoking amateur cyclists aged 55 to 79 still had the immune systems of young people.

The other side of the coin, says Akbar, is elite athletes who become very susceptible to infections because you can exercise to a point where it has a negative impact on your immune system. This problem is unlikely to affect most of us unless, says Cruickshank, youre a couch potato and suddenly try and run a marathon, this could introduce stress hormones and be quite bad for your immune system.

One of the many happy side-effects of exercise is that it reduces stress, which is next on our list of immune-boosting priorities. Stress hormones such as cortisol can compromise immune function, a common example of which, says Akbar, is when chickenpox strikes twice. If you have had it, the virus never completely goes away. During periods of stress, he says, it can reactivate again and we get shingles.

Forget boozing through the coronavirus crisis, because heavy drinking also depletes our immune cells. Some studies have suggested that the first-line-of-defence macrophages are not as effective in people who have had a lot of alcohol, says Cruickshank. And theres been suggestions that high alcohol consumption can lead to a reduction of the lymphocytes as well. So if the bug gets into you, youre not going to be as good at containing and fighting it off.

Cruickshank says that vitamin D has become a hot topic in immunology. It is used by our macrophages, and is something that people in Britain can get quite low on in the winter. Necking extra vitamin C, however, is probably a waste of time for well-fed westerners. Its not that vitamin C isnt crucial to immune function (and other things, such as bone structure). All the vitamins are important, says Cruickshank, but vitamin C is water soluble, its not one that your body stores. Eating your five a day of fruits and vegetables is the best way to maintain necessary levels.

Exercising and eating well will have the likely knock-on effect of helping you sleep better, which is a bonus because a tired body is more susceptible to bugs. One study last year found that lack of sleep impaired the disease-fighting ability of a type of lymphocyte called T cells, and research is demonstrating the importance of our natural biorhythms overall.

Janet Lord, a professor at the University of Birmingham, recently showed that vaccinating people in the morning is more effective than doing so in the afternoon. Your natural biorhythms are, to some extent, dictated by sleep, says Akbar. If youve got a regular sleep pattern, you have natural body rhythms and everythings fine. If they go out of kilter, then youve got problems.

The seriousness of an infection largely depends on the dose you are hit with, which could in turn depend on how contagious the carrier is when they cough near you. Were constantly exposed to germs, and we only get sick from a handful of those, says Cruickshank.

If youre reasonably young and healthy, says Akbar, the mild benefits you may achieve from being extra good probably wont fend off a severe dose of coronavirus or flu. The likely scenario if you catch the infection is, he says, youll be sick for a while and you will recover.

From a public-health perspective, when nasty viruses such as coronavirus are doing the rounds, Akbars priority is not boosting already healthy peoples immune systems, but protecting the vulnerable people. Older people dont respond that well to the flu jab, though its better for them to have it than not. Its a general problem of immune decline with ageing.

When we get older, he says, the barrier function in the gut doesnt work that well, so you have something called leaky gut syndrome, where bugs creep into our bodies causing mild infections. This causes inflammation around the body, as does the natural accumulation of old zombie cells, called senescent cells, and inflammation compromises the immune response.

Akbar is working on developing drug treatments to reduce inflammation in older people but they are a way off yet. Age 65 is when, medically, one is considered older, but thats arbitrary, says Akbar. Some old people might get problems much earlier. And there are older people who are totally healthy.

In terms of coronavirus, says Cruickshank, its mostly spread by droplet transmission, as far as we can tell, so the biggest thing is hygiene. So wash your hands, and sneeze and cough into tissues, she suggests, between sniffles. No one can completely avoid getting sick, not even top immunologists.

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Immunology

Hinojosa: Working Together to Beat Cancer – Rio Grande Guardian

Cancer is the second most common cause of death in Texas adults, and the same is true inthe Rio Grande Valley.

According to the Texas Cancer Registry Annual Report 2019, anestimated 124,383 new cases of cancer will be diagnosed in Texas and an estimated45,524 Texans will die from cancer.

In 2017, Hidalgo County had2,411 cancer cases of which 814 resulted in death.

Last year, Dr. John Krouse, dean of the University of Texas Rio Grande Valley School ofMedicine, stated that cervical cancer in women occurs more frequently in the Valley andwhen it occurs the mortality rate is much higher in the Valley. That is just unacceptable.That is something we need to address, and we need to fix.I completely agreeand we have been taking the necessary steps to tackle these challenges.

The first step in this process was passing a bill in 2013 that created the University of TexasRio Grande Valley (UTRGV) and the accompanying School of Medicine (SOM).Thistransformational institution has brought millions of dollars in state and federalfunding to our region, increased our health care infrastructure and personnel, and hasallowed us to begin addressing many of our health care needs.

It has also opened the doors to public-private partnerships that benefit us all, such as theopening of the UTRGV Biomedical Research Building. This opening was made possible due to thecollaboration between the SOM, the City of McAllen, and DHR Health (DHR). This building,located in McAllen, is home to the South Texas Center of Excellence in CancerResearch and a new cancer immunology team that will focus on womens cancerstarting with cervical cancer and transitioning to breast cancer. I appreciate the City ofMcAllens financial contribution and commitment to fund this research program.Thiscooperative effort will lead to new treatment opportunities for patients with cancer.

To continue making progress to address the challenge with Breast and Cervical Cancer, I secured $2.7 million in State funds to support the Cervical Dysplasia and Cancer Immunology Center.We have been working to transfer the Center from the University of Texas Medical Branch to UTRGV School of Medicine. This will improve cooperation and coordination of diagnoses, treatment and research to fight Breast and Cervical Cancer.

Another program that could help improve cancer diagnosis and prognosis for those in theValley is a biorepository for cancer research. DHR is currently working to obtain a Cancer Prevention and Research Institute of Texas (CPRIT) grant that will allow them to expand the current BorderBioRepository at DHR to establish a cancer biorepository.

These efforts will be of great benefit to the women in the Valley and South Texas, but there is still more to bedone. Cancer has no boundaries and can impact anyone regardless of age, gender, or race.For this reason, we are working with community leaders in both the public and privatesector on establishing a world-class cancer treatment clinic that will provide care toValley patients here at home. We are pursuing partnerships with the best entities in thefield, to make this vision a reality.

In the past six months, we have met with CPRIT leadership to advocate not only for additional funding to help prevent cancer, but also for financial support to recruit oncologists and expand our cancer treatment infrastructure in South Texas. CPRIT is a key funding source for cancer research and treatment provided to our universities, medical schools, and other entities committed to fighting cancer. For this reason, I advocated for and supported the appointment of Dr. Ambrosio Hernandez to the CPRIT Board. He is a physician with extensive experience in public health, is a dedicated public servant, and understands the needs of our communities.

We have also pushed for additional partnerships with the best entities in the field, such as M.D. Anderson. UTRGV is currently in the process of developing an oncology program that will assist in actively recruiting clinical oncologists to increase our clinical workforce in this field and provide guidance and expertise in developing best practices and treatments for patient care.

We must give our South Texas patients all the help they can get from modern medicine in the fight against cancer here at home. We will keep working to secure the partnerships and investments necessary so that in the future our patients in South Texas will have access to top notch facilities and world-class doctors. By working together, we can ensure that Valley residents have all of these resourcesavailable to them during their battle. Working together, we can beat cancer.

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Immunology

Coronavirus Market Correction: Where to Invest $1,000 Right Now – Motley Fool

What should I do?

That's the question that's on the mind of many investors right now. Fears about the global coronavirus outbreak have caused a market correction. A natural instinct is to flee -- run as fast as you can away from the stock market. But I suspect most investors know that this natural instinct isn't the best choice. The smarter approach is to take advantage of the buying opportunity that the market correction presents.

And that leads to another question: What stocks should I buy? There are actually plenty of good answers to that question because there are plenty of great stocks.

My view is that there are three kinds of stocks that you should consider buying during the market downturn. First, look at stocks that have held up well despite the overall market downturn -- the exceptions to the rule. Second, check out stocks that are dirt cheap because of the correction. And third, invest in stocks that are simply great businesses to own no matter what happens with the overall market.

If you have some available cash, I think that investing $1,000 in each of the following three stocks that represent each of those categories is a great place to start.

Image source: Getty Images.

Few stocks have been able to defy the gravity of the overall stock market decline in recent days. But Gilead Sciences (NASDAQ:GILD) is one of them. It helped a lot that a World Health Organization (WHO) official stated recently that Gilead's experimental drug remdesivir appears to have the most potential in being effective at treating COVID-19, the disease caused by the novel coronavirus.

While Gilead's promising antiviral drug remdesivir is the reason why the stock has risen by a double-digit percentage this year, it's not the main reason I like the biotech stock. There are actually four other things that I like even more about Gilead than its coronavirus program. The first three relate to the company's current drugs and pipeline candidates.

Gilead continues to be a juggernaut in HIV. Biktarvy appears destined to become the most successful HIV drug in history. Thanks to the company's 2017 acquisition of Kite Pharma, Gilead is a leader in cancer cell therapy -- an area that I think will gain momentum in the future. The biotech is also poised to enter the immunology market if filgotinib wins FDA approval later this year in treating rheumatoid arthritis. Some analysts project that filgotinib could generate peak annual sales of close to $6 billion if approved for multiple indications.

That leaves the fourth reason I like Gilead: Its dividend. Most biotechs don't pay dividends, but Gilead is yet again an exception to the rule. Its dividend yield currently stands at close to 3.6%. Gilead has increased its dividend payout by 58% since initiating its dividend program in 2015. With more dividend increases probably on the way and growth drivers in HIV, oncology, and immunology (plus potentially with its coronavirus drug), Gilead should provide market-beating returns over the long run.

TD Ameritrade Holding (NASDAQ:AMTD) has fallen hard during the market downturn. Shares of the online brokerage are down nearly 30%, a significantly worse performance than its peers. TD Ameritrade stock now trades at less than 14 times expected earnings.

Granted, it's not just worries about the coronavirus outbreak that have caused TD Ameritrade's stock to drop. The antitrust division of the Department of Justice is investigating the pending acquisition of TD Ameritrade by Charles Schwab (NYSE:SCHW). There's a possibility that the deal could be blocked.

But those fears could be overblown. Schwab and TD Ameritrade say they're cooperating fully with the DOJ and expect the transaction to close in the second half of this year.

What if the DOJ prevents the acquisition? I still think the future for TD Ameritrade looks bright. Investors continue to flock to online brokerages. The greatest generational transfer of wealth is on the way. Research firm Cerulli Associates estimates that over the next 25 years $68 trillion will shift from older parents to their children. A lot of that money will be invested in stocks, creating a major opportunity for TD Ameritrade whether it remains an independent entity or not.

Last -- and certainly not least -- Brookfield Infrastructure Partners (NYSE:BIP) is just a great business to own. I'd make that claim even if the stock hasn't performed pretty well this year (which it has).

If you can think of a type of infrastructure asset, Brookfield Infrastructure probably owns it. Cell towers, data centers, electricity transmission systems, natural gas pipelines, ports, railroads, toll roads, and more are all in the company's portfolio.

I personally bought shares of Brookfield Infrastructure earlier this year, mainly because I think the company's business model is rock-solid. Brookfield doesn't have to worry about a viral epidemic impacting its financial strength. Close to 95% of its adjusted EBITDA comes from regulated or contracted revenue that won't change with twists and turns in the overall economy.

Brookfield Infrastructure also pays a dividend that yields more than 4%. The company has boosted its dividend payout by 52% over the last five years. With Brookfield's strategy of selling lower-performing assets to reinvest in more promising assets, I look for solid earnings growth plus more dividend increases in the future.

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Coronavirus Market Correction: Where to Invest $1,000 Right Now - Motley Fool

Immunology

New ‘Immuno-Engineering to Improve Immunotherapy’ Center formed to advance cancer therapy – The Medical News

Harvard University's Wyss Institute of Biologically Inspired Engineering and its collaborating institutions, the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), Dana-Farber Cancer Institute (Dana-Farber), and Harvard's Department of Stem Cell and Regenerative Biology, announce the formation of a new NIH-funded Immuno-Engineering to Improve Immunotherapy (i3) Center. The cross-institutional and cross-disciplinary i3 Center includes world-leading researchers in the cancer immunology and bioengineering fields and will create biomaterials-based approaches to enable anti-cancer immuno-therapy in settings where it currently is limited, such as in myeloid malignancies and solid tumors.

The Harvard i3 Center is part of NIH's Cancer MoonshotSM initiative that was formed to accelerate cancer research to make more therapies available to more patients, while also improving the ability to prevent cancer and detect it at an early stage.

We aim to develop new technologies that induce robust anti-cancer T cell immunity, and we also hope that the i3 Center's highly cross-disciplinary and cross-fertilizing mechanisms will provide a center of gravity for many future efforts in the immuno-therapy space across and beyond our collaborating institutions."

David Mooney, Ph.D., Wyss Institute Founding Core Faculty member, one of the two principal investigators (PIs) of the i3 Center

Mooney also is the Robert P. Pinkas Family Professor of Bioengineering at SEAS and leads the Wyss Institute's broader Immuno-Materials Initiative. His team has developed a number of strategies that use immune-modulating biomaterials to trigger and enhance T cell-mediated immune responses against tumors. Most notably, together with clinical collaborators, they succeeded in creating the first implantable vaccine ever to eliminate melanoma tumors in mice, which the Wyss Institute and Dana-Farber are investigating in an ongoing Phase I clinical trial at the Dana-Farber.

F. Steven Hodi, Jr., M.D., Director of Melanoma Center and The Center for Immuno-Oncology at Dana-Farber, and Professor of Medicine at Harvard Medical School (HMS), is leading the clinical cancer vaccine trial, and is the i3 Center's other PI. Hodi has been at the forefront of developing cancer immunotherapies using "immune checkpoint inhibitors," a class of drugs able to re-activate tumor-destroying T cells that are muted in the tumor microenvironment. "The funding for this center provides a unique opportunity to unite key investigators for translating fundamental advancements in immunology and biomedical engineering into highly synergistic approaches to improve the treatments for cancer patients," said Hodi.

Using both in vivo and ex vivo biomaterials-based approaches, the i3 Center aims to boost tumor-specific activities of cytotoxic T cells, by boosting different stages of the normal process by which T cells develop, and acquire anti-cancer activity. T cells' normal development starts in the bone marrow where hematopoietic stem cells generate T cell progenitor cells. These migrate to the thymus to differentiate into nave T cells, which then travel further to lymph nodes. There, they encounter cancer-derived antigens presented to them by specialized antigen-presenting cells (APCs) that can activate T cells to recognize and eliminate cancer cells.

In relation to "adoptive T cell" therapies in which T cells are given to patients to fight their cancers, one team at the i3 Center will be led by Dana-Farber researchers Catherine J. Wu, M.D., and Jerome Ritz, M.D., who along with Mooney, will develop and test biomaterials that can better mimic normal APCs in activating and directing the function of patient-derived T cells outside the human body, prior to their transplantation. Wu is Chief of the Division of Stem Cell Transplantation and Cellular Therapies, and Ritz is Executive Director of the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber.

"We need to make efforts to enhance the ability of the immune system to recognize tumor cells. One direction my laboratory is taking makes use of innovative biomaterials to help us to efficiently expand polyclonal tumor-specific functionally-effective T cells ex vivo in a way that can be readily translated to the clinical setting. In our studies, we are currently focusing on melanoma and acute myeloid leukemia," said Wu, whose research interests include understanding the basis of effective human anti-tumor responses, including the identification and targeting of the tumor-specific antigens.

A second project explores the use of DNA origami, biocompatible nanostructures composed of DNA, to create cancer vaccines. DNA origami could provide significant advantages in presenting tumor-specific antigens and immune-enhancing adjuvants to APCs because the concentrations, ratios, and geometries of all components can be modulated with nano-scale precision to determine configurations that are more effective than other vaccination strategies. The project will be run by Wyss Institute Core Faculty member William Shih, Ph.D., Derin Keskin, Ph.D., lead immunologist at Dana-Farber's Translational Immunogenomics Lab, and Mooney.

In a third project, David Scadden, M.D., the Gerald and Darlene Jordan Professor of Medicine at Harvard University, and Professor at Harvard's Department of Stem Cell and Regenerative Biology, and Mooney, based on their previous work, will engineer biomaterials that recreate key features of the normal hematopoietic stem cell niche in the bone marrow. Such implantable biomaterials could help rapidly amplify T cell progenitor cells, and enhance T cell-mediated anti-cancer immunity.

The i3 Center's investigators anticipate that it will stimulate additional cross-disciplinary concepts and research, due to the culture of continuous interactions, sharing of findings, data and samples between all investigators, as well strong biostatistical expertise provided by Donna Neuberg, Sc.D., a senior biostatistician broadly involved with exploring immune-modulating cancer interventions at the Dana-Farber.

"This new i3 Center for cancer immunotherapy innovation really embodies how the Wyss Institute with its unparalleled capabilities in bioengineering and serving as a site for multidisciplinary collaboration, and can liaise with clinicians and researchers at our collaborating institutions to confront major medical problems and bring about transformative change," said Wyss Founding Director Donald Ingber, M.D., Ph.D. He is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at SEAS.

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New 'Immuno-Engineering to Improve Immunotherapy' Center formed to advance cancer therapy - The Medical News