Geologic evidence supports a coastal theory of early settlement

Date:
May 30, 2018

Source:
University at Buffalo

Summary:
A geological study provides compelling evidence to support the hypothesis that ancient humans migrated into the Americas via a coastal route. By analyzing boulders and bedrock, a team shows that part of a coastal migration route became accessible to humans 17,000 years ago. During this period, ancient glaciers receded, exposing islands of southern Alaska’s Alexander Archipelago to air and sun — and, possibly, to human migration.

 

University at Buffalo Ph.D. candidate Alia Lesnek works at Suemez Island.
Credit: Jason Briner

 

 

When and how did the first people come to the Americas?

The conventional story says that the earliest settlers came via Siberia, crossing the now-defunct Bering land bridge on foot and trekking through Canada when an ice-free corridor opened up between massive ice sheets toward the end of the last ice age.

But with recent archaeological evidence casting doubt on this thinking, scientists are seeking new explanations. One dominant, new theory: The first Americans took a coastal route along Alaska’s Pacific border to enter the continent.

A new geological study provides compelling evidence to support this hypothesis.

By analyzing boulders and bedrock, a research team led by the University at Buffalo shows that part of a coastal migration route became accessible to humans 17,000 years ago. During this period, ancient glaciers receded, exposing islands of southern Alaska’s Alexander Archipelago to air and sun — and, possibly, to human migration.

The timing of these events is key: Recent genetic and archaeological estimates suggest that settlers may have begun traveling deeper into the Americas some 16,000 years ago, soon after the coastal gateway opened up.

The research will be published online on May 30 in the journal Science Advances.

“People are fascinated by these questions of where they come from and how they got there,” says lead scientist Jason Briner, PhD, professor of geology in UB’s College of Arts and Sciences. “Our research contributes to the debate about how humans came to the Americas. It’s potentially adding to what we know about our ancestry and how we colonized our planet.”

“Our study provides some of the first geologic evidence that a coastal migration route was available for early humans as they colonized the New World,” says UB geology PhD candidate Alia Lesnek, the study’s first author. “There was a coastal route available, and the appearance of this newly ice-free terrain may have spurred early humans to migrate southward.”

The findings do not mean that early settlers definitely traversed Alaska’s southern coast to spread into the Americas: The project examined just one section of the coast, and scientists would need to study multiple locations up and down the coastline to draw firmer conclusions.

Still, the work is exciting because it hints that the seafaring theory of migration is viable.

The bones of an ancient ringed seal — previously discovered in a nearby cave by other researchers — provide further, tantalizing clues. They hint that the area was capable of supporting human life at the time that early settlers may have been passing through, Briner says. The new study calculates that the seal bones are about 17,000 years old. This indicates that the region was ecologically vibrant soon after the ice retreated, with resources including food becoming available.

Co-authors on the research included Briner; Lesnek; Charlotte Lindqvist, PhD, an associate professor of biological sciences at UB and a visiting associate professor at Nanyang Technological University; James Baichtal of Tongass National Forest; and Timothy Heaton, PhD, of the University of South Dakota.

A landscape, touched by ice, that tells a story

To conduct their study, the scientists journeyed to four islands within the Alexander Archipelago that lie about 200 miles south/southeast of Juneau.

The team traveled by helicopter to reach these remote destinations. As soon as the researchers arrived, Briner knew that the islands had once been covered by ice.

“The landscape is glacial,” he says. “The rock surfaces are smooth and scratched from when the ice moved over it, and there are erratic boulders everywhere. When you are a geologist, it hits you in the face. You know it immediately: The glacier was here.”

To pinpoint when the ice receded from the region, the team collected bits of rock from the surfaces of boulders and bedrock. Later, the scientists ran tests to figure out how long the samples — and thus the islands as a whole — had been free of ice.

The researchers used a method called surface exposure dating. As Lesnek explains, “When land is covered by a glacier, the bedrock in the area is hidden under ice. As soon as the ice disappears, however, the bedrock is exposed to cosmic radiation from space, which causes it to accumulate certain chemicals on their surface. The longer the surface has been exposed, the more of these chemicals you get. By testing for these chemicals, we were able to determine when our rock surfaces were exposed, which tells us when the ice retreated.

“We use the same dating method for huge boulders called erratics. These are big rocks that are plucked from the Earth and carried to new locations by glaciers, which actually consist of moving ice. When glaciers melt and disappear from a specific region, they leave these erratics behind, and surface exposure dating can tell us when the ice retreated.”

For the region that was studied, this happened roughly 17,000 years ago.

The case for a coastal migration route

In recent years, evidence has mounted against the conventional thinking that humans populated North America by taking an inland route through Canada. To do so, they would have needed to walk through a narrow, ice-free ribbon of terrain that appeared when two major ice sheets started to separate. But recent research suggests that while this path may have opened up more than 14,000 years ago, it did not develop enough biological diversity to support human life until about 13,000 years ago, Briner says.

That clashes with archaeological findings that suggest humans were already living in Chile about 15,000 years ago or more and in Florida 14,500 years ago.

The coastal migration theory provides an alternative narrative, and the new study may mark a step toward solving the mystery of how humans came to the Americas.

“Where we looked at it, the coastal route was not only open — it opened at just the right time,” Lindqvist says. “The timing coincides almost exactly with the time in human history that the migration into the Americas is thought to have occurred.”

The research was funded by a UB IMPACT award, and Lesnek’s work on the project, which will contribute to her dissertation, was supported by the National Science Foundation.

Story Source:

Materials provided by University at Buffalo. Original written by Charlotte Hsu. Note: Content may be edited for style and length.


Journal Reference:

  1. Alia J. Lesnek, Jason P. Briner, Charlotte Lindqvist, James F. Baichtal, Timothy H. Heaton. Deglaciation of the Pacific coastal corridor directly preceded the human colonization of the AmericasScience Advances, 2018; 4 (5): eaar5040 DOI: 10.1126/sciadv.aar5040

 

Source: University at Buffalo. “In ancient boulders, new clues about the story of human migration to the Americas: Geologic evidence supports a coastal theory of early settlement.” ScienceDaily. ScienceDaily, 30 May 2018. <www.sciencedaily.com/releases/2018/05/180530144144.htm>.

Date:
May 29, 2018

Source:
Newcastle University

Summary:
The first human corneas have been 3D printed by scientists.

 

Dr. Steve Swioklo and Professor Che Connon with a dyed cornea.
Credit: Newcastle University, UK

 

 

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture — or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel — a combination of alginate and collagen — keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

Reference:

3D Bioprinting of a Corneal Stroma Equivalent. Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research.

Story Source:

Materials provided by Newcastle UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Isaacson A, Swioklo S, Connon C. 3D bioprinting of a corneal stroma equivalentExperimental Eye Research, 2018 DOI: 10.1016/j.exer.2018.05.010

 

Source: Newcastle University. “First 3D-printed human corneas.” ScienceDaily. ScienceDaily, 29 May 2018. <www.sciencedaily.com/releases/2018/05/180529223312.htm>.

Memorial Day Weekend

 

On this Memorial Day weekend, we salute the brave men and women who respond to the call and join the military, dedicating their lives to the protection of this great country. Nothing is more precious than life; therefore, nothing is a greater gift, or more heroic, than offering one’s life to defend one of mankind’s great social experiments, America, the beautiful.

 

Springtime in NYC

 

This past Friday was a beautiful day, so we decided to stroll through Central Park. The rhododendrons were flowering and if you look closely, you will see 5th Avenue in the background

 

Springtime in NYC – ©Target Health Inc.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

QUIZ

Filed Under News | Leave a Comment

SNPs

 

Each person has the same set of genes – about 20,000 in all. The differences between people come from slight variations in these 1) ___. For example, a person with red hair doesn’t have the “red hair gene“ while a person with brown hair has the “brown hair gene.“ Instead, all people have genes for hair color, and different versions of these genes dictate whether someone will be a redhead or a brunette. The human 2) ___ contains 50 trillion cells, and almost every one of them contains the complete set of instructions for making an individual human. These instructions are encoded in your DNA, which is a long, ladder-shaped molecule. Each rung on the ladder is made up of a pair of interlocking units, called bases, that are designated by the four letters in the DNA alphabet – A, T, G and C. ‘A’ always pairs with ‘T’, and ‘G’ always pairs with ‘C’.

 

The long molecules of DNA in each cell is organized into pieces called chromosomes. Humans have 23 pairs of 3) ___. Other organisms have different numbers of pairs – for example, chimpanzees have 24 pairs. The number of chromosomes doesn’t determine how complex an organism is – bananas have 11 pairs of chromosomes, while fruit flies have only 4. Chromosomes are further organized into short segments of DNA called genes. Each gene has a list of instructions, written in the DNA alphabet: – A, T, C, and G. Each gene’s instructions tell each cell how to function and what traits to express. For example, curly hair results, because the genes inherited from parents are instructing hair follicle 4) ___ to make curly strands. Cells follow the instructions, written in genes, to make proteins. Proteins do much of the work in the cells and in the body. Some proteins give cells their shape and structure. Others help cells carry out biological processes like digesting food or carrying oxygen in the blood. Using different combinations of the As, Cs, Ts and Gs, DNA creates the different 5) ___.

 

Cells come in a array of types; there are brain cells and blood cells, skin cells and liver cells and bone cells. But every cell contains the same instructions in the form of DNA. Cells know whether to make an eye or a foot because of intricate systems of genetic switches. Master genes turn other genes on and 6) ___, making sure that the right proteins are made at the right time in the right cells. To make new cells, an existing cell divides in two. But first it copies its DNA so the new cells will each have a complete set of genetic instructions. Cells sometimes make mistakes during the copying process – kind of like typos. These typos lead to variations in the 7) ___ sequence at particular locations, called single nucleotide polymorphisms, or SNPs (pronounced “snips“). SNPs are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. Millions of SNP’s have been cataloged in the human genome. Some SNPs cause disease, like sickle cell anemia. Other SNPs are normal variations in the genome. SNPs can generate biological variation between people by causing differences in the 8) ___ for proteins that are written in genes. Those differences can in turn influence a variety of traits such as appearance, disease susceptibility or response to drugs. While some SNPs lead to differences in health or physical appearance, most SNPs seem to lead to no observable differences between people at all.

 

DNA is passed from parent to 9) ___. SNPs are inherited versions from parents. An individual will be a match with siblings, grandparents, aunts, uncles, and cousins because of these SNPs. Each person will have far fewer matches with distantly related people. The number of SNPs that match another person can therefore be used to tell how closely related you are. The next generation of SNP annotation webservers can take advantage of the growing amount of data in core bioinformatics resources and use intelligent agents to fetch data from different sources as needed. From a user’s point of view, it is more efficient to submit a set of SNPs and receive results in a single step, which makes meta-servers the most attractive choice. However, if SNP annotation tools deliver heterogeneous data covering sequence, structure, regulation, pathways, etc., they must also provide frameworks for integrating data into a decision algorithm(s), and quantitative confidence measures so users can assess which data are relevant and which are not.

 

An associated freeware computer program called Promethease, developed by the SNPedia team, allows users to compare personal genetics results against the SNPedia database, generating a report with information about a person’s attributes, such as propensity to diseases, based on the presence of specific SNPs within their genome. In May 2008 Cariaso, using Promethease, won an online contest sponsored by 23andMe to determine as much information as possible about an anonymous woman based only on her genome. Cariaso won in all three categories of “accuracy, creativity and cleverness“. In 2009, the anonymous woman (“Lilly Mendel“) was revealed to be 23andMe co-founder Linda Avey, allowing a direct comparison between her actual traits and those predicted by Promethease a year earlier.

 

A single 10) ___ polymorphism (SNP) is a change to a single nucleotide in a DNA sequence. The relative mutation rate for an SNP is extremely low. This makes them ideal for marking the history of the human genetic tree. SNPs are named with a letter code and a number. The letter indicates the lab or research team that discovered the SNP. The number indicates the order in which it was discovered. For example, M173 is the 173rd SNP documented by the Human Population Genetics Laboratory at Stanford University, which uses the letter M.

https://ghr.nlm.nih.gov/primer/genomicresearch/snp; 23andMe.com; Wikipedia

 

ANSWERS: 1) genes; 2) body; 3) chromosomes; 4) cells; 5) proteins; 6) off; 7) DNA; 8) instructions; 9) child; 10) nucleotide

 

Professor Thomas Hunt Morgan, Geneticist

Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that the chromosome plays in heredity. Photo credit: Unknown – http://wwwihm.nlm.nih.gov/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=549067; This image is one of several created for the 1891 Johns Hopkins yearbook of 1891.

 

Thomas Hunt Morgan received his Ph.D. from Johns Hopkins University in zoology in 1890. Following the rediscovery of Mendelian inheritance in 1900, Morgan began to study the genetic characteristics of the fruit fly Drosophila melanogaster. In his famous Fly Room at Columbia University, Morgan demonstrated that genes are carried on chromosomes and are the mechanical basis of heredity. These discoveries formed the basis of the modern science of genetics. As a result of his work, Drosophila became a major model organism in contemporary genetics. The Division of Biology which he established at the California Institute of Technology has produced seven Nobel Prize winners.

 

Morgan was born in Lexington, Kentucky, to Charlton Hunt Morgan and Ellen Key Howard Morgan. Part of a line of Southern planter elite on his father’s side, Morgan was a nephew of Confederate General John Hunt Morgan and his great-grandfather John Wesley Hunt had been the first millionaire west of the Allegheny Mountains. Through his mother, he was the great-grandson of Francis Scott Key, the author of the “Star Spangled Banner“, and John Eager Howard, governor and senator from Maryland. Beginning at age 16, Morgan attended the State College of Kentucky (now the University of Kentucky). He focused on science and particularly enjoyed natural history. He worked with the U.S. Geological Survey in his summers and graduated as valedictorian in 1886 with a BS degree. Following a summer at the Marine Biology School in Annisquam, Massachusetts, Morgan began graduate studies in zoology at Johns Hopkins University. After two years of experimental work with morphologist William Keith Brooks, Morgan received a master of science degree from the State College of Kentucky in 1888. The college offered Morgan a full professorship; however, he chose to stay at Johns Hopkins and was awarded a relatively large fellowship to help him fund his studies. Under Brooks, Morgan completed his thesis work on the embryology of sea spiders, to determine their phylogenetic relationship with other arthropods. He concluded that with respect to embryology, they were more closely related to spiders than crustaceans. Based on the publication of this work, Morgan was awarded his Ph.D. from Johns Hopkins in 1890, and was also awarded the Bruce Fellowship in Research. He used the fellowship to travel to Jamaica, the Bahamas and to Europe to conduct further research. Nearly every summer from 1890 to 1942, Morgan returned to the Marine Biological Laboratory to conduct research. He became very involved in governance of the institution, including serving as an MBL trustee from 1897 to 1945.

 

In 1890, Morgan was appointed associate professor (and head of the biology department) at Johns Hopkins’ sister school Bryn Mawr College. During the first few years at Bryn Mawr, he produced descriptive studies of sea acorns, ascidian worms and frogs. In 1894 Morgan was granted a year’s absence to conduct research in the laboratories of Stazione Zoologica in Naples, where Wilson had worked two years earlier. There he worked with German biologist Hans Driesch, whose research in the experimental study of development piqued Morgan’s interest. Among other projects that year, Morgan completed an experimental study of ctenophore (commonly known as comb jellies, that live in marine waters worldwide. At the time, there was considerable scientific debate over the question of how an embryo developed. Following Wilhelm Roux’s mosaic theory of development, some believed that hereditary material was divided among embryonic cells, which were predestined to form particular parts of a mature organism. Driesch and others thought that development was due to epigenetic factors, where interactions between the protoplasm and the nucleus of the egg and the environment could affect development. Morgan was in the latter camp and his work with Driesch demonstrated that blastomeres isolated from sea urchin and ctenophore eggs could develop into complete larvae, contrary to the predictions (and experimental evidence) of Roux’s supporters.

 

When Morgan returned to Bryn Mawr in 1895, he was promoted to full professor. Morgan’s main lines of experimental work involved regeneration and larval development; in each case, his goal was to distinguish internal and external causes to shed light on the Roux-Driesch debate. He wrote his first book, The Development of the Frog’s Egg (1897). He began a series of studies on different organisms’ ability to regenerate. He looked at grafting and regeneration in tadpoles, fish and earthworms; in 1901 he published his research as Regeneration. Beginning in 1900, Morgan started working on the problem of sex determination, which he had previously dismissed when Nettie Stevens discovered the impact of the Y chromosome on gender. He also continued to study the evolutionary problems that had been the focus of his earliest work. In 1904, E. B. Wilson invited Morgan to join him at Columbia University. This move freed him to focus fully on experimental work. When Morgan took the professorship in experimental zoology, he became increasingly focused on the mechanisms of heredity and evolution. He had published Evolution and Adaptation (1903); like many biologists at the time, he saw evidence for biological evolution (as in the common descent of similar species) but rejected Darwin’s proposed mechanism of natural selection acting on small, constantly produced variations. Embryological development posed an additional problem in Morgan’s view, as selection could not act on the early, incomplete stages of highly complex organs such as the eye. The common solution of the Lamarckian mechanism of inheritance of acquired characters, which featured prominently in Darwin’s theory, was increasingly rejected by biologists. Around 1908 Morgan started working on the fruit fly Drosophila melanogaster, and encouraging students to do so as well. In a typical Drosophila genetics experiment, male and female flies with known phenotypes are put in a jar to mate; females must be virgins. Eggs are laid in porridge which the larva feed on; when the life cycle is complete, the progeny are scored for inheritance of the trait of interest. With Fernandus Payne, he mutated Drosophila through physical, chemical, and radiational means. Morgan began cross-breeding experiments to find heritable mutations, but they had no significant success for two years. Castle had also had difficulty identifying mutations in Drosophila, which were tiny. Finally, in 1909, a series of heritable mutants appeared, some of which displayed Mendelian inheritance patterns; in 1910 Morgan noticed a white-eyed mutant male among the red-eyed wild types. When white-eyed flies were bred with a red-eyed female, their progeny were all red-eyed. A second generation cross produced white-eyed males – a gender-linked recessive trait, the gene for which Morgan named white. Morgan also discovered a pink-eyed mutant that showed a different pattern of inheritance. In a paper published in Science in 1911, he concluded that (1) some traits were gender-linked, the trait was probably carried on one of the Y or X chromosomes, and (3) other genes were probably carried on specific chromosomes as well. Morgan proposed that the amount of crossing over between linked genes differs and that crossover frequency might indicate the distance separating genes on the chromosome. The later English geneticist J. B. S. Haldane suggested that the unit of measurement for linkage be called the morgan. Morgan’s student Alfred Sturtevant developed the first genetic map in 1913.

 

Morgan’s fly-room at Columbia became world-famous, and he found it easy to attract funding and visiting academics. In 1927 after 25 years at Columbia, and nearing the age of retirement, he received an offer from George Ellery Hale to establish a school of biology in California. Morgan moved to California to head the Division of Biology at the California Institute of Technology in 1928. In 1933 Morgan was awarded the Nobel Prize in Physiology or Medicine. As an acknowledgement of the group nature of his discovery he gave his prize money to Bridges’, Sturtevant’s and his own children. Morgan declined to attend the awards ceremony in 1933, instead attending in 1934. The 1933 rediscovery of the giant polytene chromosomes in the salivary gland of Drosophila may have influenced his choice. Until that point, the lab’s results had been inferred from phenotypic results, the visible polytene chromosome enabled them to confirm their results on a physical basis. Morgan’s Nobel acceptance speech entitled “The Contribution of Genetics to Physiology and Medicine“ downplayed the contribution genetics could make to medicine beyond genetic counselling. In 1939 he was awarded the Copley Medal by the Royal Society.

 

Morgan eventually retired in 1942, becoming professor and chairman emeritus. George Beadle returned to Caltech to replace Morgan as chairman of the department in 1946. Although he had retired, Morgan kept offices across the road from the Division and continued laboratory work. In his retirement, he returned to the questions of sexual differentiation, regeneration, and embryology. Morgan had throughout his life suffered with a chronic duodenal ulcer. In 1945, at age 79, he experienced a severe heart attack and died from a ruptured artery.

 

Below is Thomas Hunt Morgan’s Drosophila melanogaster genetic linkage map. This was the first successful gene mapping work and provides important evidence for the chromosome theory of inheritance. The map shows the relative positions of allelic characteristics on the second Drosophila chromosome. The distance between the genes (map units) are equal to the percentage of crossing-over events that occurs between different alleles.

 

Thomas Hunt Morgan’s Drosophila melanogaster genetic linkage map. This was the first successful gene mapping work and provides important evidence for the Boveri-Sutton chromosome theory of inheritance. The map shows the relative positions of allelic characteristics on the second Drosophila chromosome. The distance between the genes (map units) are equal to the percentage of crossing-over events that occurs between different alleles. This gene linkage map shows the relative positions of allelic characteristics on the second Drosophila chromosome. The alleles on the chromosome form a linkage group due to their tendency to form together into gametes. The distance between the genes (map units) are equal to the percentage of crossing-over events that occurs between different alleles. This diagram is also based on the findings of Thomas Hunt Morgan in his Drosophila cross. Graphic credit: Twaanders17 – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40694655

 

Source: https://www.ncbi.nlm.nih.gov; Wikipedia

 

Severe Atopic Eczema and Long Term Risk of Cardiovascular Disease

 

According to an article published online in the British Medical Journal (23 May 2018), a population-based matched cohort study was performed to investigate whether adults with atopic eczema are at an increased risk of cardiovascular disease and whether the risk varies by atopic eczema severity and condition activity over time. For the study, data were obtained from 1) UK electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics, and 2) data from the Office for National Statistics, 1998-2015.

 

Study participants included adults with a diagnosis of atopic eczema, matched (on age, gender, general practice, and calendar time), and patients without atopic eczema. The main outcome measures were cardiovascular outcomes as measured by myocardial infarction, unstable angina, heart failure, atrial fibrillation, stroke, and cardiovascular death).

 

The study obtained data from a total of 387,439 patients with atopic eczema were matched to 1,528,477 patients without atopic eczema. The median age was 43 at cohort entry and 66% were female. Median follow-up was 5.1 years. Evidence of a 10% to 20% increased hazard for the non-fatal primary outcomes for patients with atopic eczema was found by using Cox regression stratified by matched set. Results showed a strong dose-response relation with severity of atopic eczema. Patients with severe atopic eczema had a 20% increase in the risk of stroke (hazard ratio 1.22, 99% confidence interval 1.01 to 1.48), 40% to 50% increase in the risk of myocardial infarction, unstable angina, atrial fibrillation, and cardiovascular death, and 70% increase in the risk of heart failure (hazard ratio 1.69, 99% confidence interval 1.38 to 2.06). Patients with the most active atopic eczema (active >50% of follow-up) were also at a greater risk of cardiovascular outcomes. Additional adjustment for cardiovascular risk factors as potential mediators partially attenuated the point estimates, though associations persisted for severe atopic eczema.

 

According to the authors, severe and predominantly active atopic eczema are associated with an increased risk of cardiovascular outcomes and that targeting cardiovascular disease prevention strategies among these patients should be considered.

 

Gut Microbiome Controls Antitumor Immune Function in the Liver

 

The microbiome is the collection of bacteria and other microorganisms that live in or on the body. In humans, the greatest proportion of the body’s total microbiome is in the gut. Despite extensive research into the relationship between the gut microbiome and cancer, the role of gut bacteria in the formation of liver cancer has remained poorly understood. According to an article published online in Science (24 May 2018), a connection has been found between bacteria in the gut and antitumor immune responses in the liver. The study showed that bacteria found in the gut of mice affect the liver’s antitumor immune function. The findings have implications for understanding the mechanisms that lead to liver cancer and for therapeutic approaches to treat them.

 

To investigate whether gut bacteria affect the development of tumors in the liver, the authors used three mouse models of liver cancer. Results showed that when the gut bacteria were depleted using an antibiotic “cocktail,“ the mice that had the antibiotics developed fewer and smaller liver tumors and had reduced metastasis to the liver. The authors then studied the immune cells in the liver to understand how the depletion of gut bacteria suppressed tumor growth in the liver of the antibiotic-treated mice. Results showed that antibiotic treatment increased the numbers of a type of immune cell called NKT cells in the livers of the mice. Further experiments showed that, in all three mouse models, the reduction in liver tumor growth that resulted from antibiotic treatment was dependent on these NKT cells. Next, it was found that the accumulation of the NKT cells in the liver resulted from an increase in the expression of a protein called CXCL16 on cells that line the inside of capillaries in the liver. The authors than asked why do mice treated with antibiotics have more CXCL16 production in these endothelial cells? The authors added that ended up being the critical point, when they found that bile acids can control the expression of CXCL16. They then did further studies, and found that if the mice were treated with bile acids, it can change the number of NKT cells in the liver, and thereby the number of tumors in the liver.

 

Finally, the investigators found that one bacterial species, Clostridium scindens, controls metabolism of bile acids in the mouse gut  — and ultimately CXCL16 expression, NKT cell accumulation, and tumor growth in the liver. The authors explained that while many studies have shown an association between gut bacteria and immune response, this study is significant in that it identifies not just a correlation, but a complete mechanism of how bacteria affect the immune response in liver. In the same study, the authors found that bile acids also control the expression of the CXCL16 protein in the liver of humans and wrote that, although these results are preliminary, the novel mechanism described in this study could potentially apply to cancer patients.

 

FDA Approves a New Treatment for PKU

 

Phenylketonuria (PKU) is rare and serious genetic disease that affects about 1 in 10,000 to 15,000 people in the United States. Patients with PKU are born with an inability to break down phenylalanine (Phe), an amino acid present in protein-containing foods and high-intensity sweeteners used in a variety of foods and beverages. If untreated, PKU can cause chronic intellectual, neurodevelopmental and psychiatric disabilities. Lifelong restriction of phenylalanine intake through the diet is needed to prevent buildup of Phe in the body, which can cause long-term damage to the central nervous system.

 

The FDA has approved Palynziq (pegvaliase-pqpz) for adults with PKU. Palynziq is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment. The safety and efficacy of Palynziq were studied in two clinical trials in adult patients with PKU with blood phenylalanine concentrations greater than 600 ?mol/L on existing management. Most PKU patients in the Palynziq trials were on an unrestricted diet prior to and during the trials. The first trial was a randomized, open-label trial in patients treated with increasing doses of Palynziq administered as a subcutaneous injection up to a target dose of either 20 mg once daily or 40 mg once daily. The second trial was an 8-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with Palynziq. Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations.

 

The most common adverse events reported in the Palynziq trials included injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea. Hypersensitivity reactions occurred in most patients, likely due to formation of antibodies to the product. The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment. Because of this serious risk, the labeling for Palynziq includes a Boxed Warning and the product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS Program. Notable requirements of the Palynziq REMS Program include the following:

 

1. Prescribers must be certified by enrolling in the REMS program and completing training

2. Prescribers must prescribe auto-injectable epinephrine with Palynziq

3. Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive Palynziq

4. Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment with Palynziq

5. Patients must have auto-injectable epinephrine available at all times while taking Palynziq

 

The FDA granted approval of Palynziq to BioMarin Pharmaceutical Inc.

 

Spring Asparagus Cheese Pie

Experimented with many times, this version of the asparagus pie has the onion/garlic mixture on the bottom. ©Joyce Hays, Target Health Inc.

 

This entree size slice of the asparagus cheese pie, has no onions in the bottom layer. ©Joyce Hays, Target Health Inc.

 

This entree slice does have a bottom layer of onions, garlic and mushrooms. ©Joyce Hays, Target Health Inc.

 

Here is a brunch slice of the asparagus cheese pie, with a smoked salmon layer. You can’t see the hot home brewed coffee made with freshly ground (French roasted) coffee beans. ©Joyce Hays, Target Health Inc.

 

Another brunch scene at our house. ©Joyce Hays, Target Health Inc.

 

Appetizer size: a delicious way to start any dinner. The garnish on this version, is crunshed Nori. ©Joyce Hays, Target Health Inc.

 

Ingredients

9 or 10 asparagus, washed, dried, stalks trimmed

1 cup ricotta

4 eggs

1/4 cup sour cream

1/4 cup plain Greek yogurt

1 onion, chopped

1 scallion, chopped (white part in recipe, green for garnish)

10 cloves garlic, sliced

1 anchovy fillet, well chopped (instead of salt)

1 jalapeno, seeds removed, chopped well

1 pinch black pepper

1 Tablespoon black mustard seeds

Zest of 1 fresh lemon

Juice of 1 fresh lemon

1 cup sharp cheddar, grate it at home

1 cup gruyere, grate it at home

1 cup buffalo mozzarella, shred or grate it at home

 

 

Directions

1. Do all cutting, slicing, chopping, grating

It’s a little extra work, but try to do all of your grated cheese at home. Although, it’s not found on each label, most store-bought cheese has a little something extra added to keep it fresher longer. ©Joyce Hays, Target Health Inc.

 

2. Preheat oven to 350 degrees.

3. Oil a pie baking dish

4. In a skillet, cook the onion, garlic, scallions, jalapeno, mustard seeds, anchovy mashed.

Just starting to cook the onions, garlic, scallions, mustard seeds, jalapeno. ©Joyce Hays, Target Health Inc.

 

5. In a small bowl, add the ricotta and beat eggs, one egg at a time, into the ricotta. Stir to combine well.

Beat in the eggs to the ricotta, one egg at a time. ©Joyce Hays, Target Health Inc.

 

6. In a skillet, cook the onion, garlic, scallions, jalapeno, mustard seeds, anchovy mixture, seasoning, lemon zest, lemon juice. Cook until garlic is golden.

7. In a large bowl, mix all cheeses, including the ricotta/eggs, yogurt and sour cream

Mixing all the cheeses with the ricotta & egg. ©Joyce Hays, Target Health Inc .

 

8. In the oiled baking dish, with a spatula, scrape everything out of the skillet and into the baking dish. Smooth this out.

9. Pour all of the cheese mixture, over the onion mixture.

Pouring the cheeses & eggs mixture over the onions & garlic. ©Joyce Hays, Target Health Inc.

 

10. Place all of the asparagus, in a circle, on top of the cheese mixture.

The final touch: Adding 10 fresh asparagus on top and in a circle. ©Joyce Hays, Target Health Inc.

 

11. Bake until cheese is golden and asparagus tender, 20 to 30 minutes.

Just out of the oven. You should allow this pie to cool down for about 15 to 30 minutes or the cheesy custard will not have time to set. ©Joyce Hays, Target Health Inc.

 

12. Remove from oven and let the pie cool down for15 to 30 minutes. When we tried to cut slices, too soon, the cheese mixture did not hold its shape. You need to wait for the cheese/egg mixture to solidify as it cools down.

One of many options: Serve with a garden salad and maybe fish, like salmon, or not. Maybe, fillet of sole sauteed with garlic butter and green grapes

 

We had the asparagus cheese pie as the centerpiece of dinner and also served fresh broccoli sauteed with extra virgin olive oil and garlic slices. ©Joyce Hays, Target Health Inc.

 

In addition to the broccoli we had a new recipe I’m experimenting with, stuffed mushrooms. Will share when ready. ©Joyce Hays, Target Health Inc.

 

This is a light and luscious entree. Not sure which is better, with or without the more savory bottom layer. ©Joyce Hays, Target Health Inc.

 

Simply delicious and so pretty for Springtime! ©Joyce Hays, Target Health Inc.

 

Louis Jadot produces a consistently delicious Pouilly-Fuisse, which we serve over and over again. If you’ve never tried it, go ahead. Perfect for Spring and Summer. ©Joyce Hays, Target Health Inc.

 

This weekend, we saw a beautifully acted, highly stimulating play, Dan Cody’s Yacht. It’s playing at the Manhattan Theater Club on West 55th Street, one of the theater clubs where Target Health is a Patron. We recommend this play because it is fine theater.

 

Have a great week everyone!

From Our Table to Yours

Bon Appetit!

 

Ultra-low-power sensors carrying genetically engineered bacteria can detect gastric bleeding

Date:
May 24, 2018

Source:
Massachusetts Institute of Technology

Summary:
Researchers have built an ingestible sensor equipped with genetically engineered bacteria that can diagnose bleeding in the stomach or other gastrointestinal problems.

 

MIT engineers have designed an ingestible sensor equipped with bacteria programmed to sense environmental conditions and relay the information to an electronic circuit.
Credit: Lillie Paquette/MIT

 

 

MIT researchers have built an ingestible sensor equipped with genetically engineered bacteria that can diagnose bleeding in the stomach or other gastrointestinal problems.

This “bacteria-on-a-chip” approach combines sensors made from living cells with ultra-low-power electronics that convert the bacterial response into a wireless signal that can be read by a smartphone.

“By combining engineered biological sensors together with low-power wireless electronics, we can detect biological signals in the body and in near real-time, enabling new diagnostic capabilities for human health applications,” says Timothy Lu, an MIT associate professor of electrical engineering and computer science and of biological engineering.

In the new study, appearing in the May 24 online edition of Science, the researchers created sensors that respond to heme, a component of blood, and showed that they work in pigs. They also designed sensors that can respond to a molecule that is a marker of inflammation.

Lu and Anantha Chandrakasan, dean of MIT’s School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science, are the senior authors of the study. The lead authors are graduate student Mark Mimee and former MIT postdoc Phillip Nadeau.

Wireless communication

In the past decade, synthetic biologists have made great strides in engineering bacteria to respond to stimuli such as environmental pollutants or markers of disease. These bacteria can be designed to produce outputs such as light when they detect the target stimulus, but specialized lab equipment is usually required to measure this response.

To make these bacteria more useful for real-world applications, the MIT team decided to combine them with an electronic chip that could translate the bacterial response into a wireless signal.

“Our idea was to package bacterial cells inside a device,” Nadeau says. “The cells would be trapped and go along for the ride as the device passes through the stomach.”

For their initial demonstration, the researchers focused on bleeding in the GI tract. They engineered a probiotic strain of E. coli to express a genetic circuit that causes the bacteria to emit light when they encounter heme.

They placed the bacteria into four wells on their custom-designed sensor, covered by a semipermeable membrane that allows small molecules from the surrounding environment to diffuse through. Underneath each well is a phototransistor that can measure the amount of light produced by the bacterial cells and relay the information to a microprocessor that sends a wireless signal to a nearby computer or smartphone. The researchers also built an Android app that can be used to analyze the data.

The sensor, which is a cylinder about 1.5 inches long, requires about 13 microwatts of power. The researchers equipped the sensor with a 2.7-volt battery, which they estimate could power the device for about 1.5 months of continuous use. They say it could also be powered by a voltaic cell sustained by acidic fluids in the stomach, using technology that Nadeau and Chandrakasan have previously developed.

“The focus of this work is on system design and integration to combine the power of bacterial sensing with ultra-low-power circuits to realize important health sensing applications,” Chandrakasan says.

Diagnosing disease

The researchers tested the ingestible sensor in pigs and showed that it could correctly determine whether any blood was present in the stomach. They anticipate that this type of sensor could be either deployed for one-time use or designed to remain the digestive tract for several days or weeks, sending continuous signals.

Currently, if patients are suspected to be bleeding from a gastric ulcer, they have to undergo an endoscopy to diagnose the problem, which often requires the patient to be sedated.

“The goal with this sensor is that you would be able to circumvent an unnecessary procedure by just ingesting the capsule, and within a relatively short period of time you would know whether or not there was a bleeding event,” Mimee says.

To help move the technology toward patient use, the researchers plan to reduce the size of the sensor and to study how long the bacteria cells can survive in the digestive tract. They also hope to develop sensors for gastrointestinal conditions other than bleeding.

In the Science paper, the researchers adapted previously described sensors for two other molecules, which they have not yet tested in animals. One of the sensors detects a sulfur-containing ion called thiosulfate, which is linked to inflammation and could be used to monitor patients with Crohn’s disease or other inflammatory conditions. The other detects a bacterial signaling molecule called AHL, which can serve as a marker for gastrointestinal infections because different types of bacteria produce slightly different versions of the molecule.

“Most of the work we did in the paper was related to blood, but conceivably you could engineer bacteria to sense anything and produce light in response to that,” Mimee says. “Anyone who is trying to engineer bacteria to sense a molecule related to disease could slot it into one of those wells, and it would be ready to go.”

The researchers say the sensors could also be designed to carry multiple strains of bacteria, allowing them to diagnose a variety of conditions.

“Right now, we have four detection sites, but if you could extend it to 16 or 256, then you could have multiple different types of cells and be able to read them all out in parallel, enabling more high-throughput screening,” Nadeau says.

Story Source:

Materials provided by Massachusetts Institute of TechnologyNote: Content may be edited for style and length.


Journal Reference:

  1. Mark Mimee, Phillip Nadeau, Alison Hayward, Sean Carim, Sarah Flanagan, Logan Jerger, Joy Collins, Shane McDonnell, Richard Swartwout, Robert J. Citorik, Vladimir Bulović, Robert Langer, Giovanni Traverso, Anantha P. Chandrakasan, Timothy K. Lu. An ingestible bacterial-electronic system to monitor gastrointestinal healthScience, 2018; 360 (6391): 915 DOI: 10.1126/science.aas9315

 

Source: Massachusetts Institute of Technology. “Ingestible ‘bacteria on a chip’ could help diagnose disease: Ultra-low-power sensors carrying genetically engineered bacteria can detect gastric bleeding.” ScienceDaily. ScienceDaily, 24 May 2018. <www.sciencedaily.com/releases/2018/05/180524141712.htm>.

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