Date:
May 30, 2017

Source:
University of Texas at Austin

Summary:
Astronomers have put a basic principle of black holes to the test, showing that matter completely vanishes when pulled in. Their results constitute another successful test for Albert Einstein’s General Theory of Relativity.

 

This artist’s impression shows a star crossing the event horizon of a supermassive black hole located in the center of a galaxy. The black hole is so large and massive that tidal effects on the star are negligible, and the star is swallowed whole. The effects of gravitational lensing distorting the light of the star are not shown here.
Credit: Mark A. Garlick/CfA

 

 

Astronomers at The University of Texas at Austin and Harvard University have put a basic principle of black holes to the test, showing that matter completely vanishes when pulled in. Their results constitute another successful test for Albert Einstein’s General Theory of Relativity.

Most scientists agree that black holes, cosmic entities of such great gravity that nothing can escape their grip, are surrounded by a so-called event horizon. Once matter or energy gets close enough to the black hole, it cannot escape — it will be pulled in. Though widely believed, the existence of event horizons has not been proved.

“Our whole point here is to turn this idea of an event horizon into an experimental science, and find out if event horizons really do exist or not,” said Pawan Kumar, a professor of astrophysics at The University of Texas at Austin.

Supermassive black holes are thought to lie at the heart of almost all galaxies. But some theorists suggest that there’s something else there instead — not a black hole, but an even stranger supermassive object that has somehow managed to avoid gravitational collapse to a singularity surrounded by an event horizon. The idea is based on modified theories of General Relativity, Einstein’s theory of gravity.

While a singularity has no surface area, the noncollapsed object would have a hard surface. So material being pulled closer — a star, for instance — would not actually fall into a black hole, but hit this hard surface and be destroyed.

Kumar, his graduate student Wenbin Lu, and Ramesh Narayan, a theorist from the Harvard-Smithsonian Center for Astrophysics, have come up with a test to determine which idea is correct.

“Our motive is not so much to establish that there is a hard surface,” Kumar said, “but to push the boundary of knowledge and find concrete evidence that really, there is an event horizon around black holes.”

The team figured out what a telescope would see when a star hit the hard surface of a supermassive object at the center of a nearby galaxy: The star’s gas would envelope the object, shining for months, perhaps even years.

Once they knew what to look for, the team figured out how often this should be seen in the nearby universe, if the hard-surface theory is true.

“We estimated the rate of stars falling onto supermassive black holes,” Lu said. “Nearly every galaxy has one. We only considered the most massive ones, which weigh about 100 million solar masses or more. There are about a million of them within a few billion light-years of Earth.”

They then searched a recent archive of telescope observations. Pan-STARRS, a 1.8-meter telescope in Hawaii, recently completed a project to survey half of the northern hemisphere sky. The telescope scanned the area repeatedly during a period of 3.5 years, looking for “transients” — things that glow for a while and then fade. Their goal was to find transients with the expected light signature of a star falling toward a supermassive object and hitting a hard surface.

“Given the rate of stars falling onto black holes and the number density of black holes in the nearby universe, we calculated how many such transients Pan-STARRS should have detected over a period of operation of 3.5 years. It turns out it should have detected more than 10 of them, if the hard-surface theory is true,” Lu said.

They did not find any.

“Our work implies that some, and perhaps all, black holes have event horizons and that material really does disappear from the observable universe when pulled into these exotic objects, as we’ve expected for decades,” Narayan said. “General Relativity has passed another critical test.”

Now the team is proposing to improve the test with an even larger telescope: the 8.4-meter Large Synoptic Survey Telescope (LSST, now under construction in Chile). Like Pan-STARRS, LSST will make repeated surveys of the sky over time, revealing transients — but with much greater sensitivity.


Story Source:

Materials provided by University of Texas at Austin. Note: Content may be edited for style and length.


Journal Reference:

  1. Wenbin Lu, Pawan Kumar, Ramesh Narayan. Stellar disruption events support the existence of the black hole event horizon. Monthly Notices of the Royal Astronomical Society, 2017

 

Source: University of Texas at Austin. “Do stars fall quietly into black holes, or crash into something utterly unknown?.” ScienceDaily. ScienceDaily, 30 May 2017. <www.sciencedaily.com/releases/2017/05/170530115127.htm>.

CTTI Registry Trials Recommendations Now Publicly Available

 

This is a must for those interested in clinical trials of the future.

 

Recommendations from the Clinical Trials Transformation Initiative (CTTI) Registry Trials Project were publicly announced last week in a CTTI-hosted webinar. The recommendations describe how to design new registries or evaluate and modify existing registries to conduct clinical trials suitable for regulatory purposes.  By applying these recommendations, stakeholders can make registries into reusable platforms for clinical trials.  CTTI has invited interested parties to consider the application of these recommendations in their clinical trials, and encourages sharing the recommendations and webinar recording with colleagues.

 

The Team Leaders on the project included:  Dawn Flick (Celgene), John Laschinger (FDA), Ted Lystig (Medtronic), and Jimmy Tcheng (Duke)

 

Team Members included:  Chunrong Cheng (FDA), Christopher Dowd (Cystic Fibrosis Foundation), Nicolle Gatto (Pfizer), Lauren Mclaughin (Michael J Fox Foundation for Parkinson’s Research), Stephen Mikita (Patient Representative), Kristen Miller (FDA), Daniel Mines (Merck), Jules Mitchel (Target Health), Magnus Petterson (AstraZeneca), Sunil Rao (Duke), Arlene Swern (Celgene), and Emily Zeitler (Duke)

 

Project ManagersSara Calvert and previously Steve Mikita

 

Webinar Presenters:

John Laschinger, MD, Medical Officer, Center for Devices and Radiological Health, US Food and Drug Administration

Jules Mitchel, MBA, PhD, President, 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

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Blood Brain Barrier (BBB)

An astrocyte cell grown in tissue culture stained with antibodies to GFAP and vimentin. The GFAP is coupled to a red fluorescent dye and the vimentin is coupled to a green fluorescent dye. Both proteins are present in large amounts in the intermediate filaments of this cell, so the cell appears yellow, the result of combining strong red and green signals. The blue signal is DNA revealed with DAPI, and shows the nucleus of the astrocyte and of other cells in this image. Image was captured on a confocal microscope in the EnCor Biotechnology laboratory. Image credit: GerryShaw – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=29369565

 

 

Every thought and action requires precise communication between the nerve cells of the brain and the cells involved in the action. For these messages to be successfully transmitted and received, the surrounding environment needs to be stable. The brain separates itself from the natural chemical fluctuations that occur in the body by elaborate means called the blood brain barrier. The brain is the only organ known to have its own security system, a network of blood vessels that allows the entry of essential nutrients while blocking other substances. Unfortunately, this barrier is so effective at protecting against the passage of foreign substances that it often prevents life-saving drugs from being able to repair the injured or diseased brain. New studies are guiding researchers toward creative ways to open this barrier and “trick“ it into allowing medicines to enter.

 

The brain’s blood vessels are lined with endothelial cells that are wedged tightly together creating a nearly impermeable boundary between the brain and bloodstream. The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds from blood to brain. Three cellular elements of the brain microvasculature compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight junctions (TJs), present between the cerebral endothelial cells, form a diffusion barrier, which selectively excludes most blood-borne substances from entering the brain. Astrocytic end-feet tightly ensheath the vessel wall and appear to be critical for the induction and maintenance of the TJ barrier, but astrocytes are not believed to have a barrier function in the mammalian brain. Dysfunction of the BBB, for example, impairment of the TJ seal, complicates a number of neurologic diseases including stroke and neuroinflammatory disorders. A paucity of TJs or PCs, coupled with incomplete coverage of blood vessels by astrocyte end-feet, may account for the fragility of blood vessels in the GM of premature infants.

 

Many researchers are concerned with the pathogenesis of increased BBB permeability in hypoxia-ischemia and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced dementia, multiple sclerosis, and Alzheimer disease. Already recognized for their health benefits as a food compound, omega-3 fatty acids now appear to also play a critical role in preserving the integrity of the blood-brain barrier, which protects the central nervous system from blood-borne bacteria, toxins and other pathogens, according to new research from Harvard Medical School. Reporting in the May 3 issue of Neuron, a team led by Chenghua Gu, associate professor of neurobiology at Harvard Medical School, describes the first molecular explanation for how the barrier remains closed by suppressing transcytosis — a process for transporting molecules across cells in vesicles, or small bubbles. They found that the formation of these vesicles is inhibited by the lipid composition of blood vessel cells in the central nervous system, which involves a balance between omega-3 fatty acids and other lipids maintained by the lipid transport protein Mfsd2a.

 

While the blood-brain barrier is a critical evolutionary mechanism that protects the central nervous system from harm, it also represents a major hurdle for delivering therapeutic compounds into the brain. Blocking the activity of Mfsd2a may be a strategy for getting drugs across the barrier and into the brain to treat a range of disorders such as brain cancer, stroke and Alzheimer’s. The blood-brain barrier is composed of a network of endothelial cells that line blood vessels in the central nervous system. These cells are connected by tight junctions that prevent most molecules from passing between them, including many drugs that target brain diseases. In a 2014 study published in Nature, Gu and colleagues discovered that a gene and the protein it encodes, Mfsd2a, inhibits transcytosis and is critical for maintaining the blood-brain barrier. Mice that lacked Mfsd2a, which is found only in endothelial cells in the central nervous system, had higher rates of vesicle formation and leaky barriers, despite having normal tight junctions.

 

In the current study, Gu, Benjamin Andreone, a neurology student at Harvard Medical School, and their colleagues examined how Mfsd2a maintains the blood-brain barrier. Mfsd2a is a transporter protein that moves lipids containing DHA, an omega-3 fatty acid found in fish oil and nuts, into the cell membrane. To test the importance of this function to the barrier, the team created mice with a mutated form of Mfsd2a, in which a single amino acid substitution shut down its ability to transport DHA. They injected these mice with a fluorescent dye and observed leaky blood-brain barriers and higher rates of vesicle formation and transcytosis — mirroring mice that completely lacked Mfsd2a. A comparison of the lipid composition of endothelial cells in brain capillaries against those in lung capillaries — which do not have barrier properties and do not express Mfsd2a — revealed that brain endothelial cells had around two- to five-fold higher levels of DHA-containing lipids. Additional experiments revealed that Mfsd2a suppresses transcytosis by inhibiting the formation of caveolae — a type of vesicle that forms when a small segment of the cell membrane pinches in on itself. As expected, mice with normal Cav-1, a protein required for caveolae formation, and that lacked Mfsd2a exhibited higher transcytosis and leaky barriers. Mice that lacked both Mfsd2a and Cav-1, however, had low transcytosis and impermeable blood-brain barriers.

 

By revealing the role of Mfsd2a and how it controls transcytosis in the central nervous system, Gu and her colleagues hope to shed light on new strategies to open the barrier and allow drugs to enter and remain in the brain. They are currently testing the efficacy of an antibody that potentially can temporarily block the function of Msfd2a, and whether caveolae-mediated transcytosis can be leveraged to shuttle therapeutics across the barrier. According to Gu, “Many of the drugs that could be effective against diseases of the brain have a hard time crossing the blood-brain barrier, and that suppressing Mfsd2a may be an additional strategy that allows us to increase transcytosis, and deliver cargo such as antibodies against beta-amyloid or compounds that selectively attack tumor cells. If we can find a way across the barrier, the impact would be enormous.“

 

This work was supported by The National Institutes of Health (grants F31NS090669, NS092473), the Mahoney postdoctoral fellowship, the Howard Hughes Medical Institute, the Kaneb Fellowship, Fidelity Biosciences Research Initiative and the Harvard Blavatnik Biomedical Accelerator. Sources: Harvard Medical School: Benjamin J. Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A. Deik, David D. Ginty, Clary B. Clish, Chenghua Gu. Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis. Neuron, 2017; 94 (3): 581 DOI: 10.1016/j.neuron.2017.03.043

 

BBB Quiz Questions

 

1. What is blood brain barrier?

2. The BBB is both what? And what?

3. The BBB is a Barrier between what fluid?

4. Brain capillaries create what barrier?

5. The BBB is not truly a what?

6. What role does a membrane play re: the BBB?

7. What is the roll of the endothelial cells in the BBB?

8. Astrocytes hold various roles, mostly supporting neurons. What type of cell are astrocytes.

9. What types of substances are isolated from the brain by the BBB?

10. The brain uses information from the multiple receptors to determine properties of a what?

 

Quiz ANSWERS

 

1. A physiological mechanism that alters the permeability of brain capillaries so that some substances, such as certain drugs, are prevented from entering brain tissue, while other substances are allowed to enter freely.

2. Physical barrier and a system of cellular transport mechanisms.

3. Interstital fluid and the blood around the blood

4. A functional barrier

5. It’s not truly a barrier, but actually selective permeability caused by tight junction between endothelial cells

6. A membrane carries and channels select nutrients and molecules across the BBB -Bood brain barrier

7. The endothelial cells control vascular function.

8. Astrocytes are one of six types of star shaped glial cells in the brain and spinal cord. Glial cells are the most abundant cell of the human brain.

9. Toxins and other dangerous substances are kept out of the brain by the BBB.

10. Stimulus

 

First Contributors to an Understanding of the Blood Brain Barrier

 

Paul Ehrlich

 

Paul Ehrlich MD (1854-1915): Photo credit: Harris & Ewing – This image is available from the United States Library of Congress’ s Prints and Photographs division under the digital ID hec.04709. Public Domain, Wikipedia Commons

 

Paul Ehrlich’ s work illuminated the existence of the blood-brain barrier, and in1908, he was awarded The Nobel Prize in Physiology or Medicine for his work on immunity.

 

Paul Ehrlich, a German Jewish physician, was a bacteriologist studying staining, a procedure that is used in many microscopic studies to make fine biological structures visible using chemical dyes. As Ehrlich injected some of these dyes (notably the aniline dyes that were then widely used), the dye stained all of the organs of some kinds of animals except for their brains. At that time, Ehrlich attributed this lack of staining to the brain simply not picking up as much of the dye. However, in a later experiment in 1913, Edwin Goldman (one of Ehrlich’ s students) injected the dye into the cerebro-spinal fluids of animals’ brains directly. He found that in this case the brains did become dyed, but the rest of the body did not. This clearly demonstrated the existence of some sort of compartmentalization between the two. At that time, it was thought that the blood vessels themselves were responsible for the barrier, since no obvious membrane could be found. The concept of the blood-brain barrier (then termed hematoencephalic barrier) was proposed in 1900 by a Berlin physician, Lewandowsky. It was not until the introduction of the scanning electron microscope to the medical research fields in the 1960s that the actual membrane could be observed and proved to exist.

 

Edwin Goldmann

 

Edwin Goldmann MD (1862-1913)  Credit: Von unbekannt – [1] M?nchen. med. Wchnschr. lx, 2735, 1913, PD-alt-100, https://de.wikipedia.org/w/index.php?curid=5721774

 

Edwin Ellen Goldmann (born November 12, 1862 in Burgherdorp, South Africa), was a German Jewish surgeon. He studied medicine in London, and in 1888 he received the Doctor of Medicine and PhD degrees. He got his first job at Karl Weigert in Frankfurt. He stayed there for six months and then went to Freiburg to join Eugen Baumann, where he devoted himself to physiological-chemical studies. In his work he dealt with the cystine, sulfur-containing compounds of urine and iodothyrine. His Habilitationsschrift from the year 1895 dealt with the doctrine of the neurons. In 1898 he became an extraordinary professor and later a full honorary professor. He headed the surgical department of the Diakonissenkrankenhaus in Freiburg and worked mainly in the field of cancer research.

 

Goldmann made a significant contribution to the discovery of the blood-brain barrier. In 1913, he injected Trypan blue, a water-soluble azo dye stuff first synthesized by Paul Ehrlich in 1904, directly into the cerebrospinal fluid of dogs. The result showed staining of the entire central nervous system (brain and spinal cord) but no other organ.

In 1913 Goldmann died of cancer in Freiburg.

 

Rudolph Virchow

 

Rudolph Virchow (1821-1902); Photo credit: Unknown – http://ihm.nlm.nih.gov; Public Domain, Wikipedia Commons

 

The appearance of perivascular spaces was first noted in 1843 by Durant-Fardel. In 1851, Rudolph Virchow was the first to provide a detailed description of these microscopic spaces between the outer and inner/middle lamina of the brain vessels. Charles-Philippe Robin confirmed these findings in 1859 and was the first to describe the perivascular spaces as channels that existed in normal anatomy. The spaces were called Virchow-Robin spaces and are still also known as such. The immunological significance was discovered by Wilhelm His, Sr. in 1865 based on his observations of the flow of interstitial fluid over the spaces to the lymphatic system. For many years after Virchow-Robin spaces were first described, it was thought that they were in free communication with the cerebrospinal fluid in the subarachnoid space. It was later shown with the use of electron microscopy that the pia mater serves as separation between the two. Upon the application of MRI, measurements of the differences of signal intensity between the perivascular spaces and cerebrospinal fluid supported these findings. As research technologies continued to expand, so too did information regarding their function, anatomy and clinical significance.

 

A perivascular space, also known as a Virchow-Robin space, is an immunological space between an artery and a vein (not capillaries) and the pia mater that can be expanded by leukocytes. The spaces are formed when large vessels take the pia mater with them when they dive deep into the brain. The pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. Perivascular cuffs are regions of leukocyte aggregation in the spaces, usually found in patients with viral encephalitis. Perivascular spaces are extremely small and can usually only be seen on MRI images when dilated. While many normal brains will show a few dilated spaces, an increase in these has been shown to correlate with the incidence of several neurodegenerative diseases, making the spaces a popular topic of research. One of the most basic roles of the perivascular space is the regulation of fluid movement in the central nervous system and its drainage. The spaces ultimately drain fluid from neuronal cell bodies to the cervical lymph nodes. In particular, the “tide hypothesis“ suggests that the cardiac contraction creates and maintains pressure waves to modulate the flow to and from the subarachnoid space and the perivascular space. By acting as a sort of sponge, they are essential for signal transmission and the maintenance of extracellular fluid. Another function is as an integral part of the blood-brain barrier (BBB). While the BBB is often described as the tight junctions between the endothelial cells, this is an oversimplification that neglects the intricate role that perivascular spaces take in separating the venous blood from the parenchyma of the brain. Often, cell debris and foreign particles, which are impermeable to the BBB will get through the endothelial cells, only to be phagocytosed in the perivascular spaces. This holds true for many T and B cells, as well as monocytes, giving this small fluid filled space an important immunological role. Perivascular spaces also play an important role in immunoregulation; they not only contain interstitial and cerebrospinal fluid, but they also have a constant flux of macrophages, which is regulated by blood-borne mononuclear cells, but do not pass the basement membrane of the glia limitans. Similarly, as part of its role in signal transmission, perivascular spaces contain vasoactive neuropeptides (VNs), which, aside from regulating blood pressure and heart rate, have an integral role in controlling microglia. VNs serve to prevent inflammation by activating the enzyme adenylate cyclase which then produces cAMP.

 

Modified Experimental Vaccine Protects Monkeys From Plasmodium falciparum Malaria

 

Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the Plasmodium type. Malaria causes symptoms that typically include fever, feeling tired, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito’s saliva into a person’s blood. The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread by humans. Most deaths are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of disease.

 

Malaria symptoms occur when the plamodium parasite replicates inside red blood cells and cause them to burst. To enter blood cells, the parasite first secretes its own receptor protein, RON2, onto the cell’s surface. Another parasite surface protein, AMA1, then binds to a specific portion of RON2, called RON2L, and the resulting complex initiates attachment to the outer membrane of the red blood cell. Several experimental malaria vaccines previously tested in people were designed to elicit antibodies against AMA1 and thus prevent parasites from entering blood cells. Although AMA1 vaccines did generate high levels of antibodies in humans, they have shown limited efficacy in field trials in malaria-endemic settings.

 

According to an article published on line in the journal npj Vaccines (22 May 2017), a modified experimental malaria vaccine showed that it that it was able to completely protect four of eight monkeys who received it against challenge with the virulent Plasmodium falciparum malaria parasite. In three of the remaining four monkeys, the vaccine delayed the time when parasites first appeared in the blood, by more than 25 days. To improve vaccine efficacy, the authors modified an AMA1 vaccine to include RON2L so that it more closely mimics the protein complex used by the parasite. Monkeys were vaccinated with either AMA1 alone or with the AMA1-RON2L complex vaccine. Although the overall levels of antibodies generated did not differ between the two groups, animals vaccinated with the complex vaccine produced much more neutralizing antibody, indicating a better quality antibody response with AMA1-RON2L vaccination. Moreover, antibodies taken from AMA1-RON2L-vaccinated monkeys neutralized parasite strains that differed from those used to create the vaccine. This suggests, the authors noted, that an AMA1-RON2L complex vaccine could protect against multiple parasite strains. The authors then concluded that taken together, the data from this study justify progression of this next-generation AMA1 vaccine toward possible human trials.

 

Brain Blood Vessel Lesions Connected to Intestinal Bacteria

 

Cerebral cavernous malformations (CCMs) are clusters of dilated, thin-walled blood vessels that can lead to seizures or stroke when blood leaks into the surrounding brain tissue. According to an article published online in Nature (10 May 2017), a research team at the University of Pennsylvania investigated the mechanisms that cause CCM lesions to form in genetically engineered mice and discovered an unexpected link to bacteria in the gut. When bacteria were eliminated, the number of lesions was greatly diminished. This study in mice and humans suggests that bacteria in the gut can influence the structure of the brain’s blood vessels, and may be responsible for producing malformations that can lead to stroke or epilepsy. The study adds to an emerging picture that connects intestinal microbes and disorders of the nervous system.

 

The authors had been studying a well-established mouse model that forms a significant number of CCMs following the injection of a drug to induce gene deletion. However, when the animals were relocated to a new facility, the frequency of lesion formation decreased to almost zero. While investigating the cause of this sudden variability, one of the authors noticed that the few mice that continued to form lesions had developed bacterial abscesses in their abdomens — infections that most likely arose due to the abdominal drug injections. The abscesses contained Gram-negative bacteria, and when similar bacterial infections were deliberately induced in the CCM model animals, about half of them developed significant CCMs. The mice that formed CCMs also had abscesses in their spleens, which meant that the bacteria had entered the bloodstream from the initial abscess site. According to the authors, this suggested a connection between the spread of a specific type of bacteria through the bloodstream and the formation of these blood vascular lesions in the brain.

 

The question remained as to how bacteria in the blood could influence blood vessel behavior in the brain. Gram-negative bacteria produce molecules called lipopolysaccharides (LPS) that are potent activators of innate immune signaling. When the mice received injections of LPS alone, they formed numerous large CCMs, similar to those produced by bacterial infection. Conversely, when the LPS receptor, TLR4, was genetically removed from these mice they no longer formed CCM lesions. The authors also found that, in humans, genetic mutations causing an increase in TLR4 expression were associated with a greater risk of forming CCMs.

 

The authors then explored changes to the body’s bacteria (microbiome) in two ways. First, newborn CCM mice were raised in either normal housing or under germ-free conditions. Second, these mice were given a course of antibiotics to “reset“ their microbiome. In both the germ-free conditions and following the course of antibiotics, the number of lesions was significantly reduced, indicating that both the quantity and quality of the gut microbiome could affect CCM formation. Finally, a drug that specifically blocks TLR4 also produced a significant decrease in lesion formation. This drug has been tested in clinical trials for the treatment of sepsis, and these findings suggest a therapeutic potential for the drug in the treatment of CCMs, although considerable research remains to be done.

 

“These results are especially exciting because they show that we can take findings in the mouse and possibly apply them at the human patient population,“ said Koenig. “The drug used to block TLR4 has already been tested in patients for other conditions, and it may show therapeutic potential in the treatment of CCMs, although considerable research still remains to be done.“

 

The authors plan to continue to study the relationship between the microbiome and CCM formation, particularly as it relates to human disease. Although specific gene mutations have been identified in humans that can cause CCMs to form, the size and number varies widely among patients with the same mutations. The group next aims to test the hypothesis that differences in the patients’ microbiomes could explain this variability in lesion number.

 

HUGE: FDA Approves First Cancer Treatment for Any Solid Tumor With a Specific Genetic Biomarker

 

EDITOR’S NOTE: THIS APPROVAL IS BEYOND HUGE AS WE CAN NOW START TREATING THE ROOT CAUSE OF DISEASES RATHER THAN THEIR ORGAN (e.g. Colon Cancer)

 

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

 

The FDA has granted accelerated approval to a treatment for patients whose cancers have a specific genetic biomarker. This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

 

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.

 

According to Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “This is an important first for the cancer community, since until now, the FDA has approved cancer treatments based on where in the body the cancer started – for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.“

 

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells. The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

 

Keytruda was approved for this new indication using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Keytruda, and the sponsor is currently conducting these studies in additional patients with MSI-H or dMMR tumors.

 

The safety and efficacy of Keytruda for this indication were studied in patients with MSI-H or dMMR solid tumors enrolled in one of five uncontrolled, single-arm clinical trials. In some trials, patients were required to have MSI-H or dMMR cancers, while in other trials, a subgroup of patients were identified as having MSI-H or dMMR cancers by testing tumor samples after treatment began. A total of 15 cancer types were identified among 149 patients enrolled across these five clinical trials. The most common cancers were colorectal, endometrial and other gastrointestinal cancers.

 

The review of Keytruda for this indication was based on the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and for how long (durability of response). Of the 149 patients who received Keytruda in the trials, 39.6% had a complete or partial response, and for 78% of those patients, the response lasted for six months or more. Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea. Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Complications or death related to allogeneic hematopoietic stem cell transplantation after using Keytruda has occurred. Patients who experience severe or life-threatening infusion-related reactions should stop taking Keytruda. Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby. The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.

 

Asparagus Baked with Goat Cheese, Dill, Flax, Sherry & Gruyere

This asparagus dish is delicious on its own or with fish and/or seafood. Take note that I’m not including a recipe for crust, because I wanted to keep the calories down.  However, feel free to use your favorite crust recipe and/or buy a frozen crust from your local market. ©Joyce Hays, Target Health Inc.

 

 

Ingredients

 

1 red onion, sliced. Use 2 if you want to bake onion circles on top

2 scallion stalks, well chopped

8 fresh garlic cloves, sliced

2 Tablespoons cream sherry

1 Tablespoon chickpea flour

Pinch salt

Pinch black pepper

Pinch chili flakes

1 teaspoon curry powder

1 teaspoon flax seeds

3 Tablespoons, fresh dill, chopped very fine

1 pound asparagus, trimmed, cut into 2-inch pieces, stalks and tips kept separate

2 teaspoons extra-virgin olive oil

4 large eggs, room temperature

1 cup coconut cream or coconut milk

4 ounces Gruyere cheese, grated

4 ounces creamy fresh goat cheese, crumbled into large pieces

 

Use the thick asparagus, rather than the pencil thin variety. Use fresh dill rather than dried dill in a bottle. ©Joyce Hays, Target Health Inc.

 

Directions

1. Be sure to clean the asparagus well, under cold running water, so that you get all of the sand and/or grit off each stalk. The first time I bought Spring asparagus, this year, I was not careful to do this. Nothing ruins a recipe more than having your teeth grind down on sand.

2. Do all your cleaning, cutting, slicing, chopping, etc. If using the 2nd red onion, slice it into medium thick rings and set aside in coconut or extra virgin olive oil

 

Chopping onion, scallion, garlic. ©Joyce Hays, Target Health Inc.

 

 

3. Use a frying pan with coconut oil. Add asparagus stalks (not tips), onion, scallion, garlic, all herbs & all seasoning and cook until the asparagus is crisp-tender, about 2 minutes. Just before you transfer the contents of this pan, add the white wine and stir in, so everything is well combined. Now, put in a bowl or a plate and let everything cool. Set aside.

 

Be sure to remove tips from each asparagus stalk. You want to decorate the top of the dish with slices of red onion and the tips. ©Joyce Hays, Target Health Inc.

 

 

4. Add asparagus tips to the pan with coconut oil and cook 30 seconds. Put the asparagus tips into a bowl and toss with extra virgin olive oil. Set aside.

 

Use the tips for decoration. ©Joyce Hays, Target Health Inc.

 

 

5. Transfer asparagus stalks and everything, (not tips) to a food processor or blender. If food processor is small, do this slowly, removing each batch, to a deep baking dish, then add another batch to be pulsed. Add eggs, cream, flour, goat cheese, salt to food processor or blender and puree until very smooth. Pulse each batch until it’s pureed and very smooth. Pour each batch of puree into the oiled deep baking dish.

 

If you have a small food processor, pulse until smooth, in batches. Wait to use food processor, until the cooked ingredients have cooled down. ©Joyce Hays, Target Health Inc.

 

Scrape all of the blended ingredients, out of the food processor and into an oiled baking dish. ©Joyce Hays, Target Health Inc.

 

 

6. Preheat oven to 350 degrees

7. Sprinkle the top with the grated Gruyere and top the cheese with red onion rings and asparagus tips. Bake about 40 minutes, until edges of custard are puffed, the top is golden brown, and the center is set. If the top is golden brown but the center is not set, make a tent of foil, to prevent browning too much, but still baking until the center is set. Let cool on a wire rack 15 minutes before serving.

 

About to go into oven. ©Joyce Hays, Target Health Inc.

 

With a nice baking dish, your whole (or part) meal can go from oven to table. ©Joyce Hays, Target Health Inc.

 

Everyone wants second helpings. ©Joyce Hays, Target Health Inc.

 

Once again, Louis Jadot, well chilled, Pouilly-Fuisse worked well with the asparagus recipe. ©Joyce Hays, Target Health Inc.

 

 

We had a quiet weekend, with Jules overcoming jet lag. I don’t know how he does it. First back and forth to meetings in Iceland; followed by a week at our NY headquarters, then week long meetings in Israel.

 

We did go to the theater once, at Signature Theater on 42nd Street, where we are patrons. The play by Suzan-Lori Parks, is: Venus, based on the true story of Sarah Baartman, born in South Africa in the 1700s and brought to Europe when she was around 20 years old. Jules liked this play, I did not. I’m sharing the below information because I preferred learning about this well known African woman, by reading and viewing a documentary. I do understand why an African American playwright, would want to present the story of Sarah Baartman. Suzan-Lori Parks won a Pulitzer Prize for Drama in 2002. Her list of other awards and honors is long. She received Phi Beta Kappa at Mount Holyoke College. This is the second play by Parks, that we’ve seen.

 

click here to read more

 

click here for a documentary about Sarah Baartman

 

Suzan-Lori Parks

Photo credit: By I, DerSchwabel, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2523613

 

 

From Our Table to Yours

Bon Appetit!

 

Date:
May 29, 2017

Source:
Korea Advanced Institute of Science and Technology

Summary:
Semi-transparent perovskite solar cells have been developed that could be great candidates for solar windows, say researchers.

 

Prototype of a semi-transparent perovskite solar cell with thermal-mirror functionality.
Credit: Copyright: Korea Advanced Institute of Science and Technology (KAIST)

 

A Korean research team has developed semi-transparent perovskite solar cells that could be great candidates for solar windows.

Scientists are exploring ways to develop transparent or semi-transparent solar cells as a substitute for glass walls in modern buildings with the aim of harnessing solar energy. But this has proven challenging, because transparency in solar cells reduces their efficiency in absorbing the sunlight they need to generate electricity.

Typical solar cells today are made of crystalline silicon, which is difficult to make translucent. By contrast, semi-transparent solar cells use, for example, organic or dye-sensitized materials. But compared to crystalline silicon-based cells, their power-conversion efficiencies are relatively low. Perovskites are hybrid organic-inorganic photovoltaic materials, which are cheap to produce and easy to manufacture. They have recently received much attention, as the efficiency of perovskite solar cells has rapidly increased to the level of silicon technologies in the past few years.

Using perovskites, a Korean research team, led by Professor Seunghyup Yoo of the Korea Advanced Institute of Science and Technology and Professor Nam-Gyu Park of Sungkyunkwan University, has developed a semi-transparent solar cell that is highly efficient and functions very effectively as a thermal mirror.

One key to achieving efficient semitransparent solar cells is to develop a transparent electrode for the cell’s uppermost layer that is compatible with the photoactive material. The Korean team developed a ‘top transparent electrode’ (TTE) that works well with perovskite solar cells. The TTE is based on a multilayer stack consisting of a metal film sandwiched between a high refractive index layer and an interfacial buffer layer. This TTE, placed as a solar cell’s top-most layer, can be prepared without damaging ingredients used in the development f perovskite solar cells. Unlike conventional transparent electrodes that only transmit visible light, the team’s TTE plays the dual role of allowing visible light to pass through while at the same time reflecting infrared rays.

The semi-transparent solar cells made with the TTEs exhibited an average power conversion efficiency as high as 13.3%, reflecting 85.5% of incoming infrared light. Currently available crystalline silicon solar cells have up to 25% efficiency but are opaque.

The team believes that if the semi-transparent perovskite solar cells are scaled up for practical applications, they can be used in solar windows for buildings and automobiles, which not only generate electrical energy but also allow smart heat management in indoor environments, thereby utilizing solar energy more efficiently and effectively.


Story Source:

Materials provided by Korea Advanced Institute of Science and Technology. Note: Content may be edited for style and length.

 

Source: Korea Advanced Institute of Science and Technology. “Harnessing energy from glass walls.” ScienceDaily. ScienceDaily, 29 May 2017. <www.sciencedaily.com/releases/2017/05/170529142441.htm>.

Date:
May 25, 2017

Source:
Cornell University

Summary:
How water relates to and interacts with biological systems — like DNA, the building block of all living things — is of critical importance, and a research group has used a relatively new form of spectroscopy to observe a previously unknown characteristic of water.

 

Water is Earth’s most abundant natural resource, but it’s also something of a mystery due to its unique solvation characteristics — that is, how things dissolve in it.

 

“It’s uniquely adapted to biology, and vice versa,” said Poul Petersen, assistant professor of chemistry and chemical biology at Cornell University. “It’s super-flexible. It dissipates energy and mediates interactions, and that’s becoming more recognized in biological systems.”

How water relates to and interacts with those systems — like DNA, the building block of all living things — is of critical importance, and Petersen’s group has used a relatively new form of spectroscopy to observe a previously unknown characteristic of water.

“DNA’s chiral spine of hydration,” published May 24 in the American Chemical Society journal Central Science, reports the first observation of a chiral water superstructure surrounding a biomolecule. In this case, the water structure follows the iconic helical structure of DNA, which itself is chiral, meaning it is not superimposable on its mirror image. Chirality is a key factor in biology, because most biomolecules and pharmaceuticals are chiral.

“If you want to understand reactivity and biology, then it’s not just water on its own,” Petersen said. “You want to understand water around stuff, and how it interacts with the stuff. And particularly with biology, you want to understand how it behaves around biological material — like protein and DNA.”

Water plays a major role in DNA’s structure and function, and its hydration shell has been the subject of much study. Molecular dynamics simulations have shown a broad range of behaviors of the water structure in DNA’s minor groove, the area where the backbones of the helical strand are close together.

The group’s work employed chiral sum frequency generation spectroscopy (SFG), a technique Petersen detailed in a 2015 paper in the Journal of Physical Chemistry. SFG is a nonlinear optical method in which two photon beams — one infrared and one visible — interact with the sample, producing an SFG beam containing the sum of the two beams’ frequencies, or energies. In this case, the sample was a strand of DNA linked to a silicon-coated prism.

More manipulation of the beams and calculation proved the existence of a chiral water superstructure surrounding DNA.

In addition to the novelty of observing a chiral water structure template by a biomolecule, chiral SFG provides a direct way to examine water in biology.

“The techniques we have developed provide a new avenue to study DNA hydration, as well as other supramolecular chiral structures,” Petersen said.

The group admits that their finding’s biological relevance is unclear, but Petersen thinks the ability to directly examine water and its behavior within biological systems is important.

“Certainly, chemical engineers who are designing biomimetic systems and looking at biology and trying to find applications such as water filtration would care about this,” he said.

Another application, Petersen said, could be in creating better anti-biofouling materials, which are resistant to the accumulation of microorganisms, algae and the like on wetted surfaces.


Story Source:

Materials provided by Cornell University. Original written by Tom Fleischman. Note: Content may be edited for style and length.


Journal Reference:

  1. M. Luke McDermott, Heather Vanselous, Steven A. Corcelli, Poul B. Petersen. DNA’s Chiral Spine of Hydration. ACS Central Science, 2017; DOI: 10.1021/acscentsci.7b00100

 

Source: Cornell University. “Water forms ‘spine of hydration’ around DNA, group finds.” ScienceDaily. ScienceDaily, 25 May 2017. <www.sciencedaily.com/releases/2017/05/170525141530.htm>.

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