Perfect Summer Slaw: Carrots, Cilantro, Dill, Honey, Lime, Toasted Mustard Seeds, Raisins, Peanuts

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Tossed with raisins. ©Joyce Hays, Target Health Inc.

 

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Tossed without raisins. ©Joyce Hays, Target Health Inc.

 

 

Ingredients

 

Zest of 1/2 a fresh lime

Juice of 1/2 fresh lime

2.5 cups unsalted pre-roasted peanuts

1/2 to 1 cup raisins (optional)

4 cloves garlic, minced

2 Tablespoons white vinegar, more later, to your taste

3 Tablespoons rice wine vinegar, more later, to your taste

1 Tablespoon honey

2 Tablespoon toasted sesame oil

1/2 cup black mustard seeds, toasted

Pinch chili flakes

Pinch Kosher salt

Pinch black pepper

1 ? to 2 pounds carrots, scrubbed, then peeled julienne,

lengthwise into long thin strands.

1 cup tightly packed cilantro leaves, very finely chopped

1 cup fresh dill, very finely chopped

 

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These ingredients will hold up in warmer weather. Besides, this is a very tasty summer slaw. ©Joyce Hays, Target Health Inc.

 

 

Directions

 

Toast the black mustard seeds, then set aside.

 

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Here, I’m toasting black mustard seeds with enough sesame seeds for this salad and another recipe I’m working on at the same time. ©Joyce Hays, Target Health Inc.

 

 

Make the carrot strands: Scrub, then julienne all the carrots. Swipe the julienne peeler from the thick end of carrot, to tip of carrots, to make long thin strips. Make the strips as thin as you can. If you don’t have one, a julienne peeler, is a good investment for your kitchen, to make the thin strands of any veggie.

 

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Scrub, then julienne all the carrots. ©Joyce Hays, Target Health Inc.

 

 

In a wooden salad serving bowl, mash the garlic with a fork, until it looks like a paste. Add the two types of vinegar, honey, sesame oil, sesame (optional) & black mustard seeds, chili flakes, pinch black pepper and pinch salt. Combine all of these dressing ingredients together, well.

 

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Chop everything that needs chopping at the same time, on the same board. This is the cilantro & dill. ©Joyce Hays, Target Health Inc.

 

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Mashing the garlic with a fork. ©Joyce Hays, Target Health Inc.

 

 

Add the finely chopped cilantro & finely chopped dill, to the dressing in the wooden salad bowl and toss again to distribute the herbs well.

 

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Everything except the carrots has been added to salad bowl. ©Joyce Hays, Target Health Inc.

 

Finally, add all of the carrot strips and toss once again, until each carrot strand is completely coated with dressing.

Add the unsalted, pre-roasted peanuts, half and whole pieces. I’ve experimented with different sizes of peanut in this recipe. Leaving them in halves and whole, works the best for this particular salad. No need to chop them at all.

Finally, add the raisins and toss. Add 1/2 cup, 1 cup or more. It’s your taste that counts.

Serve.

 

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This is such a delicious salad and perfect for summer weather. It’s easy to make and left-overs store well. This slaw is packed with vitamins and minerals, so on a warm evening, you might just want to have it for the whole meal, along with an icy drink and rolls warmed up in a toaster oven or microwave.

 

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We have been experimenting with lighter cooler drinks this summer and one of these is the effervescent Sofia Blanc de Blanc, tasting of fresh juicy pears, melon and honeysuckle. Zesty, cool and fun, as you see above. This light fizzy wine comes from the vineyards of director Francis Ford Coppola.

 

Next week the heat wave continues so try to stay cool. Walk, don’t run, drink lots of icy water all day, and do your best to avoid stressful situations.

 

From Our Table to Yours !

 

Bon Appetit!

Date:
July 21, 2016

Source:
University of Pennsylvania

Summary:
Scientists have mathematically modeled the coevolutionary processes that describe how antibodies and viruses interact and adapt to one another over the course of a chronic infection, such as HIV/AIDS.

 

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HIV + blood sample.
Credit: © jarun011 / Fotolia

 

 

It has remained frustratingly difficult to develop a vaccine for HIV/AIDS, in part because the virus, once in our bodies, rapidly reproduces and evolves to escape being killed by the immune system.

“The viruses are constantly producing mutants that evade detection,” said Joshua Plotkin, a professor in the University of Pennsylvania’s Department of Biology in the School of Arts & Sciences. “A single person with HIV may have millions of strains of the virus circulating in the body.”

Yet the body’s immune system can also evolve. Antibody-secreting B-cells compete among themselves to survive and proliferate depending on how well they bind to foreign invaders. They dynamically produce diverse types of antibodies during the course of an infection.

In a new paper in PLOS Genetics, Plotkin, along with postdoctoral researcher Jakub Otwinowski and Princeton University research scholar Armita Nourmohammad, mathematically modeled these dueling evolutionary processes to understand the conditions that influence how antibodies and viruses interact and adapt to one another over the course of a chronic infection.

Notably, the researchers considered the conditions under which the immune system gives rise to broadly neutralizing antibodies, which can defeat broad swaths of viral strains by targeting the most vital and immutable parts of the viral genome. Their findings, which suggest that presenting the immune system with a large diversity of viral antigens may be the best way to encourage the emergence of such potent antibodies, have implications for designing vaccines against HIV and other chronic infections.

“This isn’t a prescription for how to design an HIV vaccine,” Plotkin said, “but our work provides some quantitative guidance for how to prompt the immune system to elicit broadly neutralizing antibodies.”

The biggest challenge in attempting to model the co-evolution of antibodies and viruses is keeping track of the vast quantity of different genomic sequences that arise in each population during the course of an infection. So the researchers focused on the statistics of the binding interactions between the virus and antibodies.

“This is the key analytical trick to simplify the problem,” said Otwinowski. “It would otherwise be impossible to track and write equations for all the interactions.”

The researchers constructed a model to examine how mutations would affect the binding affinity between antibodies and viruses. Their model calculated the average binding affinities between the entire population of viral strains and the repertoire of antibodies over time to understand how they co-evolve.

“It’s one of the things that is unique about our work,” said Nourmohammad. “We’re not only looking at one virus binding to one antibody but the whole diversity of interactions that occur over the course of a chronic infection.”

What they saw was an S-shaped curve, in which sometimes the immune system appeared to control the infection with high levels of binding, but subsequently a viral mutation would arise that could evade neutralization, and then binding affinities would go down.

“The immune system does well if there is active binding between antibodies and virus,” Plotkin said, “and the virus does well if there is not strong binding.”

Such a signature is indicative of a system that is out of equilibrium where the viruses are responding to the antibodies and vice versa. The researchers note that this signature is likely common to many antagonistically co-evolving populations.

To see how well their model matched with data from an actual infection, the researchers looked at time-shifted experimental data from two HIV patients, in which their antibodies were collected at different time points and then “competed” against the viruses that had been in their bodies at different times during their infections.

They saw that these patient data are consistent with their model: Viruses from earlier time points would be largely neutralized by antibodies collected at later time points but could outcompete antibodies collected earlier in infection.

Finally, the researchers used the model to try to understand the conditions under which broadly neutralizing antibodies, which could defeat most strains of virus, would emerge and rise to prominence.

“Despite the effectiveness of broadly neutralizing antibodies, none of the patients with these antibodies has been cured of HIV,” Plotkin said. “It’s just that by the time they develop them, it’s too late and their T-cell repertoire is depleted. This raises the intriguing idea that, if only they could develop these antibodies earlier in infection, they might be prepared to combat an evolving target.”

“The model that we built,” Nourmohammad said, “was able to show that, if viral diversity is very large, the chance that these broadly neutralizing antibodies outcompete more specifically targeted antibodies and proliferate goes up.”

The finding suggests that, in order for a vaccine to elicit these antibodies, it should present a diverse set of viral antigens to the host. That way no one specialist antibody would have a significant fitness advantage, leaving room for the generalist, broadly neutralizing antibodies to succeed.

The researchers said that there has been little theoretical modeling of co-evolutionary systems such as this one. As such, their work could have implications for other co-evolution scenarios.

“Our theory can also apply to other systems, such as bacteria-phage co-evolution,” said Otwinowski, in which viruses infect bacteria, a process that drives bacterial evolution and ecology.

“It could also shed light on the co-evolution of the influenza virus in the context of evolving global immune systems,” Nourmohammad said.

The work was supported by funding from the U.S. National Science Foundation, James S. McDonnell Foundation, David and Lucile Packard Foundation, U.S. Army Research Office and U.S. Department of the Interior.


Story Source:

The above post is reprinted from materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. Armita Nourmohammad, Jakub Otwinowski, Joshua B. Plotkin. Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections. PLOS Genetics, 2016; 12 (7): e1006171 DOI: 10.1371/journal.pgen.1006171

 

Source: University of Pennsylvania. “How the immune system might evolve to conquer HIV.” ScienceDaily. ScienceDaily, 21 July 2016. <www.sciencedaily.com/releases/2016/07/160721180333.htm>.

Nature-inspired synthetic membranes could aid water purification, energy, and healthcare needs

Date:
July 19, 2016

Source:
DOE/Pacific Northwest National Laboratory

Summary:
Materials scientists have created a new material that performs like a cell membrane found in nature. Such a material has long been sought for applications as varied as water purification and drug delivery. The material can assemble itself into a sheet thinner but stabler than a soap bubble, the researchers report.

 

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This simulated cross-section shows how the lipid-like peptoids interact to form a membrane. Each peptoid has two sections: a fatty-like region that interacts via benzene rings (shown in pink) with its neighbors to form a sheet. And a water-loving region that juts above or below the flat sheet. Each region can be designed to have specific functions.
Credit: Chun-Long Chen/PNNL

 

 

Materials scientists have created a new material that performs like a cell membrane found in nature. Such a material has long been sought for applications as varied as water purification and drug delivery.

Referred to as a lipid-like peptoid (we’ll unpack that in a second), the material can assemble itself into a sheet thinner, but more stable, than a soap bubble, the researchers report July 12 in Nature Communications. The assembled sheet can withstand being submerged in a variety of liquids and can even repair itself after damage.

“Nature is very smart. Researchers are trying to make biomimetic membranes that are stable and have certain desired properties of cell membranes,” said chemist Chun-Long Chen at the Department of Energy’s Pacific Northwest National Laboratory. “We believe these materials have potential in water filters, sensors, drug delivery and especially fuel cells or other energy applications.”

The amazing membrane

Cell membranes are amazing materials. Made from thin sheets of fatty molecules called lipids, they are at least ten times thinner than an iridescent soap bubble and yet allow cells to collectively form organisms as diverse at bacteria, trees and people.

Cell membranes are very selective about what they let pass through, using tiny embedded proteins as gatekeepers. Membranes repair dings to their structure automatically and change thickness to pass signals from the outside environment to the cell’s interior, where most of the action is.

Scientists would like to take advantage of membrane properties such as gatekeeping to make filters or signaling to make sensors. A cell-membrane-like material would have advantages over other thin materials such as graphene. For example, mimicking a cell membrane’s efficient gatekeeping could result in water purifying membranes that don’t require a lot of pressure or energy to push the water through.

Synthetic molecules called peptoids have caught the interest of researchers because they are cheap, versatile and customizable. They are like natural proteins, including those that embed themselves in cell membranes, and can be designed to have very specific forms and functions. So Chen and colleagues decided to see if they could design peptoids to make them more lipid-like.

Designing membranes

Lipid molecules are long and mostly straight: They have a fatty end that prefers to hang out with other fats, and a water-like end that prefers the comfort of water. Because of this chemistry, lipid molecules arrange themselves with the fatty ends pointed toward each other, sandwiched between the water-loving ends pointed out. Scientists call this a lipid bilayer, essentially a sheet that envelops the contents of a cell. Proteins or carbohydrate molecules embed themselves in the membranous sheet.

Inspired by this, Chen and colleagues designed peptoids in which each base peptoid was a long molecule with one end water-loving and the other end fat-loving. They chose chemical features that they hoped would encourage the individual molecules to pack together. They examined the resulting structures using a variety of analysis methods, including some at the Advanced Light Source and the Molecular Foundry, two DOE Office of Science User Facilities at Lawrence Berkeley National Laboratory.

The team found that after putting the lipid-like peptoids into a liquid solution, the molecules spontaneously crystallized and formed what the scientists call nanomembranes — straight-edged sheets as thin as cell membranes — floating in the beaker. These nanomembranes maintained their structure in water or alcohol, at different temperatures, in solutions with high or low pH, or high concentrations of salts, a feat that few cell membranes could accomplish.

A view from the middle

To better understand the nanomembranes, the team simulated how single peptoid molecules interacted with each other using molecular dynamics software. The simulated peptoids formed a membrane reminiscent of a lipid bilayer: The fat-loving ends lined up in the middle, and their water-loving ends pointed outward either above or below.

To test whether their synthetic membranes had the signaling ability of cell membranes, the researchers added a touch of sodium chloride salt. Salt is involved in the last step in many signaling sequences and causes real cell membranes to thicken up. And thicken up the peptoids did. The more salt the researchers added, the thicker the nanomembranes became, reaching about 125 percent of their original thickness in the range of salt concentrations they tested.

Real membranes also hold proteins that have specific functions, such as ones that let water, and only water, through. Chen’s group tested the ability of peptoids to do so by introducing a variety of side chains. Side chains are essentially small molecules of different shapes, sizes and chemical natures attached to the longer lipid-like peptoids. They tried 10 different designs. In each case, the peptoids assembled into the nanomembranes with the core structure remaining intact. The team could also build a carbohydrate into nanomembranes, showing the material can be designed to have versatile functions.

The team then tested the nanomembranes to see if they could repair themselves, a useful feature for membranes that could get scratched during use. After cutting slits in a membrane, they added more of the lipid-like peptoid. Viewed under a microscope over the course of a few hours, the scratches filled up with more peptoid and the nanomembrane became complete again. (Compare this to cuts in paper, which don’t spontaneously repair themselves even after being taped up.)

Taken together, the results showed the researchers that they are on the right path to making synthetic cell membrane-like materials. However, there are still some challenges to be addressed for applications. For example, the researchers would like to better understand how the membranes form so they can make many desirable sizes.

The next step, Chen said, is to build biomimetic membranes by incorporating natural membrane proteins or other synthetic water channels such as carbon nanotubes into these sheet matrices. The team is also looking into ways to make the peptoid membranes conductive for energy uses.

This work was supported by the Department of Energy Office of Science and PNNL.


Story Source:

The above post is reprinted from materials provided by DOE/Pacific Northwest National Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haibao Jin, Fang Jiao, Michael D. Daily, Yulin Chen, Feng Yan, Yan-Huai Ding, Xin Zhang, Ellen J. Robertson, Marcel D. Baer, Chun-Long Chen.Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids. Nature Communications, 2016; 7: 12252 DOI: 10.1038/ncomms12252

 

Source: DOE/Pacific Northwest National Laboratory. “Scientists create new thin material that mimics cell membranes: Nature-inspired synthetic membranes could aid water purification, energy, and healthcare needs.” ScienceDaily. ScienceDaily, 19 July 2016. <www.sciencedaily.com/releases/2016/07/160719144728.htm>.

New research on HIV worldwide raises ‘significant challenges’ to ending the AIDS pandemic, despite progress in lowering AIDS mortality

Date:
July 19, 2016

Source:
Institute for Health Metrics and Evaluation

Summary:
A new study found that 74 countries saw increases in age-standardized rates of new infections between 2005 and 2015.

 

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A major new analysis reveals that although deaths from HIV/AIDS have been steadily declining from a peak in 2005, 2.5 million people worldwide became newly infected with HIV in 2015, a number that hasn’t changed substantially in the past 10 years.
Credit: © designer491 / Fotolia

 

 

AIDS deaths are falling in most countries worldwide, but the rate of new infections increased in several countries over the past decade, threatening to undermine efforts to end the AIDS epidemic by 2030, a new scientific paper shows.

The study from the Global Burden of Disease collaborative network, published today in The Lancet HIV, found that 74 countries saw increases in age-standardized rates of new infections between 2005 and 2015, including Egypt, Pakistan, Kenya, the Philippines, Cambodia, Mexico, and Russia.

The new research, released at the International AIDS Conference in Durban, South Africa, also found that while the global number of new cases continues to decline, the pace has greatly slowed. New infections of HIV fell by an average of only 0.7% per year between 2005 and 2015, compared to the 2.7% drop per year between 1997 and 2005.

The study is based on findings from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) coordinated by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle. With more than 1,700 collaborators in 124 countries, the GBD is the largest and most comprehensive effort measuring epidemiological levels and trends worldwide.

“If this trend of stubbornly high new infections continues, there will be significant challenges in meeting the UN’s Sustainable Development Goal for the world to witness the end of AIDS in less than 15 years,” said IHME Director Dr. Christopher Murray. “Everyone in population health — researchers, policymakers, practitioners, pharmaceutical companies, advocates, and others — needs to understand that even if more people are living with HIV, we cannot end AIDS without stopping new infections.”

Professor Peter Piot, who is the director of the London School of Hygiene and Tropical Medicine and was the founding executive director of UNAIDS, also remarked on the paper’s findings.

“This study shows that the AIDS epidemic is not over by any means and that HIV/AIDS remains one of the biggest public health threats of our time,” Professor Piot said. “The continuing high rate of over 2 million new HIV infections represents a collective failure which must be addressed through intensified prevention efforts and continued investment in HIV vaccine research.”

The study examines HIV mortality, prevalence, and incidence between 1980 and 2015, and is part of the Global Burden of Disease Study 2015, which provides comprehensive population health estimates on disease, injuries, and related risk factors.

In contrast to the overall slow decline in new infections, the number of people living with HIV has significantly increased globally, largely due to the expansion of antiretroviral therapy (ART). IHME estimates there were about 39 million people globally living with HIV in 2015, as compared to 28 million in 2000.

In 2015, 41% of the people living with HIV were using ART, as compared to less than 2% in 2000.

“We’re keeping people alive longer, and these numbers should give those using antiretroviral therapies considerable hope,” said IHME Associate Professor Dr. Haidong Wang, the lead author on the study. Such improvement, however, is still far away from the ambitious 90-90-90 goals set by the global community for the year 2020. Those goals aim for 90% of people living with HIV knowing their HIV status, 90% of people diagnosed with HIV receiving antiretroviral therapy, and 90% of people receiving antiretroviral therapy experiencing viral suppression.

Interestingly, use of ART is different between men and women. On average, global ART use is 10% higher among women living with HIV, and in some sub-Saharan nations in 2015, it is 50% higher. However, in some Eastern European and South Asian nations, the percentage of men using ART is as much as 50% higher than women.

“The Global Burden of Disease HIV study provides critical health information to help shape and support national and global decision-making,” said Peter Hayward, editor of The Lancet HIV. “The estimates are also key to strengthening accountability to ensure that promises made by politicians and policymakers with regard to specific HIV targets are being delivered.”

In regard to mortality, women tend to die at younger ages from HIV than men, likely due to age-disparate relationships in which men have sex with younger women. In total, approximately 1.2 million people died from HIV in 2015, down from a peak of 1.8 million in 2005.

The results of IHME’s study underscore the need for more effective efforts to prevent new infections, as well as additional funding for these efforts. This analysis shows that development assistance for health (DAH) dedicated to HIV/AIDS grew fastest between 2000 and 2009, yet such funding has stagnated since 2010. According to Financing Global Health 2015, a report published in April by IHME, annual funding globally for HIV/AIDS peaked at US$11.2 billion in 2013, but dropped to US$10.8 billion in 2015. With slowdown in the decline of new infections and in funding for HIV/AIDS, it will be challenging to achieve the goal set by the global community to end AIDS by 2030.


Story Source:

The above post is reprinted from materials provided by Institute for Health Metrics and Evaluation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haidong Wang et al. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. The Lancet HIV, 2016; DOI:10.1016/S2352-3018(16)30087-X

 

Source: Institute for Health Metrics and Evaluation. “Rate of new HIV infections increased in 74 countries over past decade: New research on HIV worldwide raises ‘significant challenges’ to ending the AIDS pandemic, despite progress in lowering AIDS mortality.” ScienceDaily. ScienceDaily, 19 July 2016. <www.sciencedaily.com/releases/2016/07/160719091639.htm>.

Date:
July 18, 2016

Source:
Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research

Summary:
Scientists have overcome a seeming weakness of global climate models. They had previously not been able to simulate the extreme warm period of the Eocene.

 

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Ocean. Researchers decipher the temperature indicator TEX86 and overcome a seeming weakness of global climate models.
Credit: Copyright Michele Hogan

 

 

Scientists from the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI) have overcome a seeming weakness of global climate models. They had previously not been able to simulate the extreme warm period of the Eocene. One aspect of this era that particularly draws interests to climatologists: It was the only phase in recent history when greenhouse gas concentration was as high as researchers predict it to be for the future. The AWI scientists have now found that the apparent model weakness is due to a misinterpretation of the temperature indicator TEX86. These molecules, which are produced by archaea do not record the surface temperature of the ancient ocean as expected, but rather the temperature of water depths up to 500 metres. In the current issue of the journal Nature Geoscience, the scientists report on this new finding which has now made it possible to correctly simulate the temperature distribution of the Eocene in climate models.

Climate scientists often hear the same complaint: How can climate models accurately predict the future of our planet if it is not even possible to correctly reproduce the climate of the past? One of the unsolved problems was that all previous attempts to simulate the extreme temperatures of the Eocene with climate models failed.

At that time, 49 to 55 million years ago, the carbon dioxide content of the air was likely more than 1000 ppm (parts per million) — i.e. at least two times the current greenhouse gas concentration. The earth warmed up so strongly that the icesheets on Greenland and Antarctica disappeared. Instead of ice crystals, palm trees grew there. “Until recently, we believed that the sea surface temperature near the North Pole at the time was 23 degrees Celsius; in Antarctica, it was believed to have been more than 30 degrees Celsius,” says Dr Thomas Laepple, climate researcher at the AWI Potsdam.

These temperature estimates were based on data from the climate indicator TEX86. This abbreviation stands for a ratio of specific organic compounds produced by archaea, depending on the water temperature in which they lived. “Archaea are unicellular organisms that can in part withstand surprisingly high ambient temperatures. The molecules of the organisms that were living at that time are still preserved in the sedimentary layers of the seafloor. They are one of our most important archives for warm climate conditions, but as we have seen, we decoded them wrongly in the past,” says Thomas Laepple.

He and his AWI colleague at the time, Sze Ling Ho, first had doubts about the interpretation of the TEX86 temperature indicator during a comparison of climate data from the most recent ice age. The scientists noticed that the TEX86 temperatures were far too cold compared to other geological evidence. “The discrepancy was so obvious that we started to review the TEX86 values of around 3,000 sediment samples from different ocean basins and from different epochs of the Earth. It soon became apparent that the average temperature change inferred from TEX86 was exaggerated, always and on all time scales, by one and a half to two times. The temperature it showed for cold periods was much too cold and the one for warm periods was much too warm,” explains geochemist Sze Ling Ho.

The cause of this pattern had to be of a fundamental nature, a suspicion that was confirmed upon closer analysis. “TEX86 had previously been interpreted as an indicator of sea surface temperature, in spite the fact that the archaea that produce TEX86 rarely directly live at the sea surface. Through the comparison with other climate archives, we have been able to constrain the depth in which the TEX86 signal is produced. We now assume that TEX86 represents the water temperature at a depth of up to 500 metres,” Sze Ling Ho explains.

At this water depth, the temperature difference between the tropical oceans and the polar seas is smaller than at the surface. This has direct consequences for climate reconstruction, since the information generated from the indicator is differently translated into temperature values. “In practice, the TEX86 extreme values need to be roughly halved in the climate reconstructions. Comparing the corrected temperatures with the models shows that they now reflect the climate of the Eocene in a realistic and physically consistent way,” explains Thomas Laepple.

However, we also have to correct our temperature-conception of the Eocene. Thomas Laepple: “The era remains the warmest period of the past 65 million years. The water temperatures that we assumed for the Arctic and Antarctica, though, were overstated by at least ten degrees Celsius. Now, we know that the water in the Southern Ocean had a temperature of about 20 to 25 degrees Celsius at that time. The region was therefore still warm enough for there to be palm trees sprouting on the beach.”


Story Source:

The above post is reprinted from materials provided by Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sze Ling Ho, Thomas Laepple. Flat meridional temperature gradient in the early Eocene in the subsurface rather than surface ocean.Nature Geoscience, 2016; DOI: 10.1038/NGEO2763

 

Source: Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research. “Long-awaited breakthrough in the reconstruction of warm climate phases.” ScienceDaily. ScienceDaily, 18 July 2016. <www.sciencedaily.com/releases/2016/07/160718133009.htm>.

We Measure Our Success by the Success of Our Clients

 

Target Health was established as a full-service eCRO in 1993 with a culture of Our Clients First. Two of our mottos are ““ and “Better to be Smart than Sorry“ and “The Harder We Work, the Luckier We Get.“

 

There are 3 main stakeholders in a business, 1) customers; 2) employees and 3) shareholders. It is the opinion of Target Health and many others, that without customers there is no need for employees and without customers and employees, there is no need for shareholders. Thus are the priorities of our company. With this approach we now represent 46 companies at FDA, have over 40 products on the market and currently have 2 NDA’s under review.

 

Giant Thunderstorm Hits NYC on 14 July 2016

 

A sporadic thunderstorm quickly blew through New York City this past Thursday. As quickly as the storm arrived, it left and then the sun came out. Here is the view from the 24th floor at 261 Madison. The Empire Stet Building is on the left. The brighter buildings are the result of a lightening flash.

 

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View From the 24th Floor During a Massive Thunderstorm. ©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 or Ms. Joyce Hays. 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

 

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The Endocannabinoid System

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NIH Coference

 

The ECS or Endocannabinoid system, is a unique and ubiquitous cell-signaling system that is just beginning to be understood. The biochemistry of EC synthesis, metabolism, and bioactivity has been difficult to study in the past. Newer techniques such as genetically modified animals, pharmacologic probes, and molecular biology promise to reveal some of these mysteries in the future. The greater promise is that with this understanding, the ECS will yield an important therapeutic target for future pharmacologic therapy.

 

Pharmacologic 1) ___ is approved and available today world-wide. THC and cannabidiol (which together make up the drug Sativex) are active components of Cannabis sativa that bind to CB1-R and CB2-R receptors. A buccal spray is approved for use for neuropathic pain associated with multiple sclerosis in Canada only. Dronabinol (Marinol), a synthetic THC, is a CB1-R and CB2-R receptor agonist that has been approved by the FDA for use as an antiemetic for chemotherapy and an appetite stimulant for persons with acquired immunodeficiency syndrome (AIDS). Its bioavailability is 10%. Nabilone (Cesamet) is a synthetic analogue of THC; it is a CB1-R and CB2-R receptor agonist that has been FDA approved as an antiemetic in chemotherapy patients in whom all other therapy has failed. Unapproved use is employed in patients with upper motor neuron syndrome who have spasticity-related pain not controlled by conventional treatment.

 

CB1-R receptor antagonists:

CB1-R receptors activate the dopaminergic reward 2) ___. Commonly abused drugs, such as nicotine, opiates, THC, and alcohol, share a common pathway, the dopaminergic surge in the nucleus accumbens. Independent studies involving humans and mice, respectively, reported an increase in smoking cessation rates, decreased alcohol intake, and a reduction in cocaine-seeking behavior with CB1-R antagonism. Rimonabant (Acomplia or Zimulti) is a selective CB1-R receptor antagonist, SR141716, with an affinity to centrally acting CB1-R receptors. Rimonabant was sold in Europe for the treatment of obesity. It was not approved in the United States and later withdrawn because of psychiatric effects, especially depression. Nevertheless, the ECS is a ubiquitous regulator of cellular function in both health and diseases, which offers many potential therapeutic targets. Below is a list of ECS agonist and antagonist intervention with therapeutic potential. Potential therapeutic targets for cannabinoid pharmacologic intervention are as follows:

 

Pain

Anti-nausea

Cough

Glaucoma

Cachexia

Neurologic diseases: Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, alcohol-induced neuroinflammation/neurodegeneration, traumatic brain injury, stroke, seizures

Autoimmune diseases: Autoimmune uveitis, systemic sclerosis, inflammatory bowel disease

Infection: HIV-1 brain infection

Psychiatric disorders: Anxiety-related disorders, impulsivity, bipolar disorder, personality disorders, attention-deficit/hyperactivity disorder, substance abuse and addictive disorders, anorexia nervosa

Cardiovascular: Atherosclerosis

Gastrointestinal: Gut motility disorders, inflammatory bowel syndrome, chronic liver diseases, alcoholic liver disease

Diabetic nephropathy

Osteoporosis

Cancer: Breast, prostate, skin, pancreatic, colon, and lymphatic, among others

 

Multiple human and animal studies support that endocannabinoids play a key role in memory, mood, brain reward systems, drug addiction, and metabolic processes, such as lipolysis, glucose 3) ___, and energy balance. Cannabidiol, or CBD, is a cannabinoid which has recently emerged from the looming shadow of its more famous cousin, tetrahydrocannabinol, or THC. The recent history of medical cannabis is one that is increasingly focused on CBD, as research is finding that it may have potential therapeutic use for several ailments. In addition, CBD, unlike THC, does not have psychotropic effects, meaning there is no “high“associated with its consumption.

 

The endocannabinoid system (ECS) is a group of endogenous cannabinoid receptors located in the mammalian 4) ___ and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors. Known as “the body’s own cannabinoid system”, the ECS is involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory, and in mediating the psychoactive effects of cannabis. Two primary endocannabinoid receptors have been identified: CB1, first cloned in 1990; and CB2, cloned in 1993. CB1 receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), Anandamide, as well as its mimetic phytocannabinoid, THC. One other main endocannabinoid is 2-Arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD. 2-AG and CBD are involved in the regulation of appetite, immune system functions and 5) ___ management.

 

The endocannabinoid system, broadly speaking, includes:

The endogenous arachidonate-based lipids, anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG); these are known as “endocannabinoids“and are physiological ligands for the cannabinoid receptors. Endocannabinoids are all eicosanoids.

The enzymes that synthesize and degrade the endocannabinoids, such as fatty acid amide hydrolase or monoacylglycerol lipase.

The cannabinoid receptors CB1 and CB2, two G protein-coupled receptors that are located in the central and peripheral nervous systems.

The neurons, neural pathways, and other cells where these molecules, enzymes, and one or both cannabinoid receptor types are all colocalized form the endocannabinoid system.

 

The endocannabinoid system has been studied using genetic and pharmacological methods. These studies have revealed that cannabinoids act as neuromodulators for a variety of processes, including motor learning, appetite, and pain sensation, among other cognitive and physical processes. The localization of the CB1 receptor in the endocannabinoid system has a very large degree of overlap with the orexinergic projection system, which mediates many of the same functions, both physical and 6) ___. Moreover, CB1 is colocalized on orexin projection neurons in the lateral hypothalamus and many output structures of the orexin system, where the CB1 and orexin receptor 1 (OX1) receptors physically and functionally join together to form the CB1-OX1 receptor heterodimer. For more details on receptor localization, see Cannabinoid receptor type 1 (CB1) and Cannabinoid receptor type 2 (CB2).

 

Cannabinoid binding sites exist throughout the 7) ___ central and peripheral nervous systems. The two most relevant receptors for cannabinoids are the CB1 and CB2receptors, which are expressed predominantly in the brain and immune system respectively. Density of expression varies based on species and correlates with the efficacy that cannabinoids will have in modulating specific aspects of behavior related to the site of expression. For example, in rodents, the highest concentration of cannabinoid binding sites are in the basal ganglia and cerebellum, regions of the brain involved in the initiation and coordination of movement. In humans, cannabinoid receptors exist in much lower concentration in these regions, which helps explain why cannabinoids possess a greater efficacy in altering rodent motor movements than they do in humans. A recent analysis of cannabinoid binding in CB1 and CB2 receptor knockout mice found cannabinoid responsiveness even when these receptors were not being expressed, indicating that an additional binding receptor may be present in the brain. Binding has been demonstrated by 2-arachidonoylglycerol (2-AG) on theTRPV1 receptor suggesting that this receptor may be a candidate for the established response. During neurotransmission, the pre-synaptic neuron releases neurotransmitters into the synaptic cleft which bind to cognate receptors expressed on the post-synaptic neuron. Based upon the interaction between the transmitter and receptor, neurotransmitters may trigger a variety of effects in the post-synaptic cell, such as excitation, inhibition, or the initiation of second messenger cascades. Based on the cell, these effects may result in the on-site synthesis of endogenous cannabinoids anandamide or 2-AG by a process that is not entirely clear, but results from an elevation in intracellular calcium. Evidence suggests that the depolarization-induced influx of 8) ___ calcium into the post-synaptic neuron causes the activation of an enzyme called transacylase. This enzyme is suggested to catalyze the first step of endocannabinoid biosynthesis by converting phosphatidylethanolamine, a membrane-resident phospholipid, into N-acyl-phosphatidylethanolamine (NAPE). The synthesis of 2-AG is less established and warrants further research.

 

Once released into the extracellular space by a putative endocannabinoid transporter, messengers are vulnerable to glial cell inactivation. Endocannabinoids are taken up by a transporter on the glial cell and degraded by fatty acid amide hydrolase (FAAH), which cleaves anandamide into arachidonic acid and ethanolamine or monoacylglycerol lipase (MAGL), and 2-AG into arachidonic acid and glycerol. While arachidonic acid is a substrate for leukotriene and prostaglandinsynthesis, it is unclear whether this degradative byproduct has unique functions in the central nervous system. Emerging data in the field also points to FAAH being expressed in postsynaptic neurons complementary to presynaptic neurons expressing cannabinoid receptors, supporting the conclusion that it is major contributor to the clearance and inactivation of anandamide and 2-AG after endocannabinoid reuptake. A neuropharmacological study demonstrated that an inhibitor of FAAH (URB597) selectively increases anandamide levels in the brain of rodents and primates. Such approaches could lead to the development of new drugs with analgesic, anxiolytic-like and antidepressant-like effects, which are not accompanied by overt signs of abuse liability.

 

Evidence suggests that endocannabinoids may function as both neuromodulators and immunomodulators in the immune system. Here, they seem to serve an autoprotective role to ameliorate muscle spasms, inflammation, and other symptoms of multiple sclerosis and skeletal muscle spasms. Interestingly, some disorders seem to trigger an upregulation of cannabinoid receptors selectively in cells or tissues related to symptom relief and inhibition of disease progression, such as in that rodent neuropathic pain model, where receptors are increased in the spinal 9) ___ cord microglia, dorsal root ganglion, and thalamic neurons.

 

Historical records from ancient China and Greece suggest that preparations of Cannabis indica were commonly prescribed to ameliorate multiple sclerosis-like symptoms such as tremors and muscle pain. Modern research has confirmed these effects in a study on diseased mice, wherein both endogenous and exogenous agonists showed ameliorating effects on tremor and spasticity. It remains to be seen whether pharmaceutical preparations such as dronabinol have the same effects in humans. Due to increasing use of medical Cannabis and rising incidence of multiple sclerosis patients who self-medicate with the drug, there has been much interest in exploiting the endocannabinoid system in the cerebellum to provide a legal and effective relief. In mouse models of multiple sclerosis, there is a profound reduction and reorganization of CB1 receptors in the cerebellum. Serial sections of cerebellar tissue subjected to immunohistochemistry revealed that this aberrant expression occurred during the relapse phase but returned to normal during the remitting phase of the disease. These studies point to the exciting possibility that cannabinoid treatment may not only be able to attenuate the symptoms of multiple sclerosis but also improve oligodendrocyte function.

 

The developing embryo expresses cannabinoid receptors early in development that are responsive to anandamide secreted in the uterus. This signaling is important in regulating the timing of embryonic implantation and uterine receptivity. Peripheral expression of cannabinoid receptors led researchers to investigate the role of cannabinoids in the autonomic nervous system. Research found that the CB1 receptor is expressed presynaptically by motor neurons that innervate visceral organs. The endocannabinoid most researched in pain is palmitoylethanolamide. Endocannabinoids are involved in placebo induced analgesia responses. Increased endocannabinoid signaling within the central nervous system promotes sleep-inducing effects. Intercerebroventricular administration of anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep. Administration of anandamide into the basal forebrain of rats has also been shown to increase levels of adenosine, which plays a role in promoting 10) ___sleep and suppressing arousal. REM sleep deprivation in rats has been demonstrated to increase CB1 receptor expression in the central nervous system. Furthermore, anandamide levels possess a circadian rhythm in the rat, with levels being higher in the light phase of the day, which is when rats are usually asleep or less active, since they are nocturnal.

 

Below are links to original research currently being carried out around the world into CBD’s medical potential.

 

Medical Research

Cancer: Cannabidiol as potential anticancer drug
Cancer: Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol
Epilepsy: Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders
Schizophrenia: Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Stress: The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system

New research at Harvard Medical School, etc.

 

ANSWERS: 1) therapy; 2) system; 3) metabolism; 4) brain; 5) pain; 6) cognitive; 7) central; 8) calcium; 9) cord; 10) sleep

 

Dr. Raphael Mechoulam (1930 to Present)

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Professor Raphael Mechoulam – Source: commons.wikimedia.org/w/index.php?curid=976850

 

Raphael Mechoulam is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of delta 9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs

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Raphael Mechoulam was born in Sofia, Bulgaria on November 5, 1930 to a Sephardic Jewish family. His father was a physician and head of a local hospital, while his mother who had studied in Berlin, enjoyed the life of a well-to-do Jewish family. He attended an “American Grade School“ until his parents were forced to leave their hometown because of anti-semitic laws. His father was subsequently sent to a concentration camp, from which he survived. After the communist takeover of then pro-German Bulgaria in 1944, he studied chemical engineering, which he “disliked.“ In 1949 his family immigrated to Israel where he later studied chemistry. He gained his first research experience in the Israeli Army working on insecticides. Mechoulam received his M.Sc. in biochemistry from the Hebrew University of Jerusalem (1952), and his Ph.D. at the Weizmann Institute, Re?ovot (1958), with a thesis on the chemistry of steroids. After postdoctoral studies at the Rockefeller Institute, New York (1959-60), he was on the scientific staff of the Weizmann Institute (1960-65), before moving to the Hebrew University of Jerusalem, where he became professor (1972) and Lionel Jacobson Professor of Medicinal Chemistry from 1975. He was rector (1979-82) and pro-rector (1983-85). In 1994 he was elected a member of the Israel Academy of Sciences. Some of his honors and awards include:

 

Member of the Israel Academy of Sciences and Humanities (1994)

Israel Prize in Exact Sciences – Chemistry (2000)

Honorary doctorate from Ohio State University (2001)

Honorary Member of the Israeli Society of Physiology and Pharmacology (2002)

Honorary doctorate from Complutense University (2006)

NIDA Discovery Award (2011)

EMET Prize in Exact Sciences – Chemistry (2012)

President of the International Cannabinoid Research Society (1999-2000)

 

Another research project initiated by him led to the isolation of the first described endocannabinoid anandamide which was isolated and characterized by two of his postdoctoral researchers, Lum?r Ondrej Hanus and William Devane. Another endogenous cannabinoid, 2-AG, was soon discovered by Shimon Ben-Shabat, one of his PhD students. He has published more than 350 scientific articles.

 

History of endocannabinoid research

When Mechoulam and colleagues isolated THC in 1964, they made it possible to further understand the complex nature of the human endocannabinoid system. Other important events in endocannabinoid research are as follows:

 

2000-650 BCE: Cannabis (azaluu or gurgurru) mentioned in Assyrian pharmacopoeia at the library of Assurbanipal

1964: THC isolation and structure elucidation

1988: Cannabinoid-binding sites in rat brains identified

1991: Human CB1-R receptor successfully cloned

1992: Endogenous CB1-R ligand (EC), anandamide (based on Sanskrit for “supreme joy“), discovered in the brain

1993: CB2-R receptor found in the immune system successfully cloned

1995: Second EC, 2-AG discovered and more abundant in the brain than AEA

 

In the 21st century, new discoveries of other endocannabinoids, their site distributions, and roles are deepening our understanding of the endocannabinoid system.

 

Click for an interesting PBS news report about Dr. Raphael Mechoulam, his valuable research, CBD and THC for epilepsy, cancer, anxiety disorder and many other diseases.

 

Report of a Parent Survey of Cannabidiol-enriched Cannabis Use in Pediatric Treatment-resistant Epilepsy

 

Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments.

 

A study published in Epilepsy and Behavior (2013; 29:574-577), a parent survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child’s seizures. Nineteen responses met the following inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy.

 

Results of the survey showed that the average number of antiepileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child’s seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction. Other beneficial effects included increased alertness, better mood, and improved sleep. Side effects included drowsiness and fatigue.

 

The survey showed that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy, and because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children are not available. The authors concluded that objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated, and efficacious at controlling seizures in this pediatric population with difficult-to-treat seizures

 

DIABETES

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Genetics of Type 2 Diabetes Revealed in Unprecedented Detail

 

Type 2 diabetes is a global health concern, with approximately 10% of the world’s population diagnosed with the disease or likely to develop it in their lifetime. Previous studies into the genetics of diabetes risk have identified over 80 areas in the human genome associated with type 2 diabetes. However, it remains unknown exactly how these genetic changes, known as variants, are distributed among populations and how they lead to increased risk. Functional explanations for these risk variants have been particularly elusive because most of them fall outside the coding region of genes, and are presumably involved in gene regulation.

 

A comprehensive investigation of the underlying genetic architecture of type 2 diabetes has unveiled the most detailed look at the genetic differences that heighten a person’s risk for disease development. The findings, published in the journal Nature (11 July 2016), reveal the complexity of the disease in more detail than previously appreciated, but also identify several promising targets for new treatments.

 

Using DNA sequencing in more than 120,000 people with ancestral origins in Europe, South and East Asia, the Americas and Africa, the authors evaluated the genome at a greater level of detail than had been previously attempted for type 2 diabetes. Some individuals had their entire genome sequenced while for others the authors focused on the part of the genome that codes directly for proteins, known as the exome. The authors then compared the genetic changes between affected and healthy participants.

 

The findings suggest that most of the genetic risk of type 2 diabetes can be attributed to common, shared genetic variants — each contributing a small amount to an individual’s risk of the disease — rather than many rare variants unique to individuals. This resolves a question about the genetics of type 2 diabetes that has puzzled researchers for decades. The authors also identified over a dozen genes in affected participants where changes in the DNA sequence altered the structure or composition of the proteins they encode, suggesting that those genes and proteins are directly involved in the development of the disease and providing important clues to the mechanism by which they confer risk. That, in turn, provides possible clues to new drug targets. Results from this study suggest that any personalized approach to treatment and prevention of type 2 diabetes will need to be tailored on the basis of an individual’s broader genetic profile, as well as environmental factors.

 

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