Photosynthetic bacteria give biologists a cool new tool: Synthetic biologists turn protein pathway into reversible photoreceptor -- ScienceDaily

Photosynthetic bacteria that have lived on Earth for 2.7 billion years are the source of a new and valuable biological regulatory tool being developed by Rice University bioengineers.

Synechocystis bacteria produce a protein pathway that senses the presence of UV-violet light and activates a motor protein that moves the single-cell organism into safer surroundings.

The pathway responds quickly to UV-violet light, a narrow band in the spectrum that includes long ultraviolet and short violet wavelengths, and is blind to all others. That makes it a perfect addition to the growing optogenetic suite of reversible photoreceptors being developed by researchers in the lab of Rice synthetic biologist Jeffrey Tabor. Tabor and graduate student Prabha Ramakrishnan co-authored a new paper about this research in the American Chemical Society journal ACS Synthetic Biology.

"The human eye can see colors that go all the way from violet to red," Ramakrishnan said. "It turns out that marine algae -- especially the bacteria these sensors come from -- have evolved to see these and other colors as well."

Optogenetics is a fairly new discipline in which light-activated, genetically encoded photoreceptors are used to sense or control molecular biological processes like the expression of desired proteins. Because light is easy to direct and control, photoreceptors are simpler to use than tools that respond to chemical prompts.

The Rice researchers turned the photosynthetic bacterial proteins into photoreversible, transcriptional regulators and installed them in Escherichia coli bacterial for lab testing. They reported exploiting them to program gene-expression signals "with high predictability."

The protein pathway known as UirS-UirR is the only optogenetic tool that responds exclusively to UV-violet light and gives biologists the ability to program circuits with light-activated proteins that won't interfere with each other, Tabor said. "Biological systems are regulated by numerous interacting genes, and multiple optogenetic tools that don't optically cross-react are needed to study these networks," he said.

The photoreversible pathway can be turned on by exposure to ultraviolet light and turned off by exposure to green light, or vice versa, depending on how the circuit is designed. Tabor expects they will be useful tools for scientists who design metabolic pathways for drug manufacture and biological sensors.

The new sensors offer speed and versatility in circuit design. "We found that light sensors developed by others take more than two hours to switch on or off, and respond to a broad range of wavelengths," Tabor said. "These aspects are not ideal for studying and controlling bacterial processes."

By contrast, the UV-violet sensor can be switched on or off in 10 minutes, Ramakrishnan said. "That's good because producing proteins or controlling a biological process can be expensive for cells. Producing something that's neither necessary for the cell nor to the product you're trying to synthesize is wasteful."

"Our photoreversible tools allow gene expression to be tuned to different levels more precisely, like a good dimmer switch," Tabor added. "They allow gene expression to be changed to a new level more quickly than a nonphotoreversible tool. All of these features are beneficial for using the tool to study native bacterial gene networks or for industrial applications."

Because the UV-violet sensor responds to such a narrow wavelength of light -- from 380 to 420 nanometers -- there's no crosstalk with the red and green photoreversible tools already developed by the lab. "When these are put together in a single system, the fact that they don't interact with each other at all and turn on and off rapidly is going to be very useful," Ramakrishnan said.

Long-term Warfarin use may increase dementia rates in AF patients

In continuation of  Warfarin

A new study of more than 10,000 patients treated long term with the blood thinner, Warfarin, reveals higher rates of dementia for patients with atrial fibrillation versus non-AF patients.

The study by researchers at the Intermountain Medical Center Heart Institute in Salt Lake City found that atrial fibrillation patients treated long term with Warfarin had higher rates of dementia, Alzheimer's disease and vascular dementia compared to anticoagulated non-atrial fibrillation patients.

Results of the research were presented today at Heart Rhythm 2016, the Heart Rhythm Society's 37th Annual Scientific Sessions in San Francisco.

Atrial fibrillation is is the most common type of arrhythmia, which is a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm. Incidence rates of atrial fibrillation are growing dramatically as the population ages.

Dementia is a neurological disorder that impairs memory and other cognitive abilities, and it is now listed among the leading causes of morbidity and mortality in developed countries.

Atrial fibrillation can increase the risk of dementia because it exposes patients to both large and small clots that can affect brain function. Blood thinners used to prevent all forms of clots and strokes can increase the risk of both large and small brain bleeds that can also negatively impact brain function over time.

The study was conducted through the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service, which is part of the Intermountain Healthcare system based in Salt Lake City.

Researchers enrolled a total of 10,537 patients with no history of dementia prior to the study. They were treated with a blood thinner for atrial fibrillation and non-AF conditions like valvular heart disease and thromboembolism on a long-term basis.

Other variables in the patients studied included age, hypertension, diabetes, hyperlipidemia, renal failure, smoking history, prior myocardial infarction or cerebral vascular accident, and heart failure. Participants were aged 18 years and older.

Studies show mango consumption may contribute to protective health effects

Four new studies surrounding the effects of mango consumption suggest this superfruit has the potential to help combat adverse effects associated with high fat diets and obesity (animal study), as well inhibit growth of fat cells (anti-lipogenic properties in an in-vivo study), slow advancement of breast cancer tumors (animal study), as well as improve regularity and decrease inflammation associated with constipation (human subject study). The research was presented at the 2016 Experimental Biology conference in San Diego.

"While more research is needed, especially in humans, there is a growing body of studies that suggest mango consumption may contribute to some protective effects in relation to obesity, certain cancers, gut health, and inflammation," said Leonardo Ortega, Director of Research at the National Mango Board.

OBESITY

* Nutrition science researcher, Babajide Ojo at Oklahoma State University, was selected by the American Society for Nutrition (ASN) as one of five finalists to present his research at the 2016 ASN Young Minority Investigator Oral Competition. Ojo's study investigated the effects of supplementing mangos (in the form of freeze-dried mango pulp) in mice fed a high fat diet on body composition, glucose homeostasis and gut inflammatory markers.

* Ojo, B., et. al., Mango Supplementation Prevents Gut Microbial Dysbiosis and Modulates Short Chain Fatty Acid Production Independent of Body Weight Reduction in C57BL/6 Mice Fed a High Fat Diet. The FASEB Journal, April 2016, vol. 30 no. 1 Supplement 1166.6 http://tinyurl.com/zyz6dpc

* Chuo Fang, PhD, of the department of Nutrition and Food Science at Texas A&M University investigated the potential role of mango and its microbial metabolites in regulating lipid metabolism and adipogenesis via the activation of AMPK in differentiated 3T3-L1 adipocytes.

* Fang, C., et. al, Mango polyphenols (Mangifera Indica L.) and their microbial metabolites suppress adipogenesis and fat accumulation by mediating AMPK signaling pathways in 3T3L-1 adipocytes. The FASEB Journalvol. 30 no. 1 Supplement 691.10 http://tinyurl.com/zwe78kq

BREAST CANCER

* Researcher Matt Nemec, of the Interdisciplinary Program of Toxicology at Texas A&M University, studied the anti-proliferative activities of pyrogallol, an intestinal microbial metabolite of gallotannin, a mango polyphenol, on mice with ductal carcinoma in situ breast cancer (DCIS).

* Nemec, M., et. al., Pyrogallol, a microbial metabolites from mango tannins (Mangifera Indica L.) suppresses breast cancer ductal carcinoma in situ proliferation in both in vitro and in vivo. The FASEB Journal, April 2016, vol. 30 no. 1 Supplement 688.7 http://tinyurl.com/ze3y5kx

CONSTIPATION

* Vinicius Paula Venancio, of the Department of Nutrition and Food Science at Texas A&M University, studied the consumption of 300 grams of mango compared to an equivalent amount of fiber (1 teaspoon of a fiber supplement) and its effect on abdominal distention and constipation in otherwise healthy human volunteers.

* Venancio, V.P., et. al., Mango (Mangifera Indica L.) in the promotion of intestinal regularity and decreases inflammation in human subjects with constipation. The FASEB Journal, April 2016, vol. 30 no. 1 Supplement 420.7 http://tinyurl.com/h6pvwnn

Studies show mango consumption may contribute to protective health effects: Four new studies surrounding the effects of mango consumption suggest this superfruit has the potential to help combat adverse effects associated with high fat diets and obesity (animal study), as well inhibit growth of fat cells (anti-lipogenic properties in an in-vivo study), slow advancement of breast cancer tumors (animal study), as well as improve regularity and decrease inflammation associated with constipation (human subject study).

Experimental drug ozanimod moderately effective in treatment of ulcerative colitis

Researchers at University of California San Diego School of Medicine have shown that ozanimod (RPC1063), a novel drug molecule, is moderately effective in the treatment of ulcerative colitis. Results of the Phase II clinical trial will appear in the May 5 issue of theNew England Journal of Medicine.

"This new class of immunotherapy drug traps white blood cells in the lymph nodes to prevent their escape into the gut where they cause inflammation," said William J. Sandborn, MD, professor of medicine at UC San Diego School of Medicine and director of the Inflammatory Bowel Disease Center at UC San Diego Health. "In addition to inducing remission in patients, the experimental drug reduced rectal bleeding and healed the mucosal lining of the intestine."

Ulcerative colits is a debilitating autoimmune disease that causes chronic diarrhea. One of the disease's defining characteristics is an abnormal accumulation of lymphocytes or T-cells in the lining of the gut. This activation of immune cells causes inflammation resulting in chronic, painful bowel movements. To counter this activity, ozanimod, a sphingosime 1-phospahte receptor modulator, halts the body's ability to recruit cells for an immune response.

"A one milligram pill of the drug induced clinical remission at week eight," said Sandborn. "Unlike other currently available drugs for inflammatory bowel disease, ozanimod can be orally administered and does not suppress the immune system to the point of increasing likelihood of infection or cancer."

Patients in the study were randomized to ozanimod 0.5 mg, 1.0 mg, or placebo. The most common side effects were anemia and headache.

Other symptoms of ulcerative colitis include intestinal bleeding and weight loss. Bowel obstruction, colon cancer, and malnutrition can also occur, resulting in hospitalization and the possible need for surgical removal of portions of the bowel and colon.

Ref : https://health.ucsd.edu/news/releases/Pages/2016-05-04-ozanimod-effective-for-treating-ulcerative-colitis.aspx

Drinking tart Montmorency cherry juice can reduce early signs of hypertension

 

The Montmorency cherry is a variety of sour cherry (Prunus cerasus) grown in the United States, Canadaand France, particularly in Michigan and in Door County, Wisconsin. Montmorency cherries are part of the lighter-red Amarelle cultivar of sour cherries, rather than the darker-red Morello cultivar. Michigan produces over 90,000 tons of Montmorency cherries each year.

Drinking tart Montmorency cherry juice significantly reduces high blood pressure at a level comparable to that achieved by medication, according to new research from Northumbria University, Newcastle.

The findings, which are published in The American Journal of Clinical Nutrition today (Wednesday 4 May), found that men with early signs of hypertension - more commonly known as high blood pressure - saw a 7% reduction in blood pressure after drinking Montmorency cherry concentrate when compared to drinking a fruit-flavoured cordial.

This reduction is comparable to the level achieved by anti-hypertensive medication.

High blood pressure affects over five million people in England and, if left untreated, increases risk of heart attack, heart failure, kidney disease, stroke or dementia. Normal blood pressure is around 120/80 mmHg.

Researchers from Northumbria University's Department of Sport, Exercise and Rehabilitation worked with fifteen participants who were displaying early hypertension with blood pressure readings of at least 130/90 mmHg, meaning they were at higher risk of experiencing cardiovascular related problems.

They were told that the study was to investigate the effect of a fruit juice on vascular function and were given either 60ml of a Montmorency cherry concentrate or the same amount of a commercially available fruit-flavoured cordial.

Blood pressure and blood samples were taken before the cherry concentrate was consumed and blood pressure was measured on an hourly basis thereafter. Blood samples and a series of other cardiovascular screening tests were taken again on a regular basis over the following eight hours.

The researchers found that the participants who were given the cherry concentrate saw a peak reduction in their blood pressure of 7 mmHg in the three hours after consuming the drink.

Past studies have shown that a reduction of between 5-6 mmHg over a sustained period has been associated with a 38% reduced risk of stroke and 23% reduced risk of coronary heart disease.

Interestingly, those participants with blood pressure levels at the higher end of the scale saw the most benefit.

The greatest improvement in systolic blood pressure occurred when the phenolic acids, protocatechuic and vanillic, within the cherry concentrate reached their peak levels in the plasma. The researchers believe that these particular compounds are, at least in part, responsible for the reduction.

Lead author and Lecturer in Sport and Exercise Nutrition, Karen Keane, explained: "The majority of cardiovascular disease is caused by risk factors that can be controlled, treated or modified, such as high blood pressure, cholesterol, obesity, tobacco use, lack of physical activity and diabetes. Raised blood pressure is the leading cause of deaths from cardiovascular disease, yet relatively small reductions in blood pressure can have a large impact on mortality rates.

"The magnitude of the blood pressure lowering effects we observed was comparable to those achieved by a single anti-hypertensive drug and highlights the potential importance that Montmorency cherries could have in the effective management of high blood pressure."

Drinking tart Montmorency cherry juice can reduce early signs of hypertension: Drinking tart Montmorency cherry juice significantly reduces high blood pressure at a level comparable to that achieved by medication, according to new research from Northumbria University, Newcastle.

The 2016 Nobel Prize in Chemistry.......

A tiny lift, artificial muscles and miniscule motors. The Nobel Prize in Chemistry 2016 is awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. They have developed molecules with controllable movements, which can perform a task when energy is added.

The development of computing demonstrates how the miniaturisation of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturised machines and taken chemistry to a new dimension.

The first step towards a molecular machine was taken by Jean-Pierre Sauvage in 1983, when he succeeded in linking two ring-shaped molecules together to form a chain, called a catenane. Normally, molecules are joined by strong covalent bonds in which the atoms share electrons, but in the chain they were instead linked by a freer mechanical bond. For a machine to be able to perform a task it must consist of parts that can move relative to each other. The two interlocked rings fulfilled exactly this requirement.

The second step was taken by Fraser Stoddart in 1991, when he developed arotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip.

Bernard Feringa was the first person to develop a molecular motor; in 1999 he got a molecular rotor blade to spin continually in the same direction. Using molecular motors, he has rotated a glass cylinder that is 10,000 times bigger than the motor and also designed a nanocar.

2016's Nobel Laureates in Chemistry have taken molecular systems out of equilibrium's stalemate and into energy-filled states in which their movements can be controlled. In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. Molecular machines will most likely be used in the development of things such as new materials, sensors and energy storage systems.

Details : https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2016/advanced-chemistryprize2016.pdf

  

Blueberry component PS may protect against dry eye disease

  

Pterostilbene (PS), a component of blueberries, have been found to protect against dry eye disease according to a new study. The research is being presented at the 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Seattle, Wash.

When introduced to human corneal epithelial cells, PS significantly reduced the levels of oxidative damage, which in turn reduced inflammation. Inflammation can contribute to dry eye disease, a condition that becomes increasing common with age. PS is a molecule chemically related to resveratrol.

Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

Omega-3 fish oil supplements may improve the effectiveness of antidepressants, new research suggests.

Researchers reviewed the findings of eight clinical trials worldwide, as well as other evidence, and concluded that the supplements appear to help battle depression in people already on medication.

"Omega-3 fish oil -- in combination with antidepressants -- had a statistically significant effect over a placebo," said study leader Jerome Sarris. He is head of the ARCADIA Mental Health Research Group at the University of Melbourne in Australia.

The study looked at the result of trials where patients battling depression took either a standard antidepressant plus a form of omega-3 fish oil, versus the antidepressant plus an inactive placebo.

"The difference for patients taking both antidepressants and omega-3, compared to a placebo, was highly significant," Sarris said in a university news release. "This is an exciting finding because here we have a safe, evidence-based approach that could be considered a mainstream treatment," he explained.

"Many studies have shown omega-3s are very good for general brain health and improving mood, but this is the first analysis of studies that looks at using them in combination with antidepressant medication," Sarris said.

Doctors may be reluctant to prescribe dietary supplements in combination with antidepressants due to a lack of scientific evidence and concerns about safety. But, Sarris noted, the researchers found no major safety concerns in combining the two therapies.

However, the study authors stressed that patients should always talk with their health care provider before taking dietary supplements. In addition, people need to be aware that these supplements can differ in quality.

"We're not telling people to rush out and buy buckets of supplements. Always speak to your medical professional before changing or initiating a treatment," Sarris said.

One expert in the United States believes the findings might be of use to patients.

"The general population is often looking for natural remedies to treat health problems," said Dr. Victor Fornari.

"A large number of individuals with depression do not reach remission with one or two trials of medication," added Fornari. He directs child and adolescent psychiatry at Cohen Children's Medical Center in New Hyde Park, N.Y.

"This may enhance the recovery of individuals who do not respond to antidepressants alone," he said. However, Fornari agreed with the authors that "individuals are cautioned to consult with their medical professional before proceeding."

Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects  

Coffee, Wine Good for Healthy Gut, Sodas May Be Bad

The food you eat and the medicines you take can alter your gut bacteria in ways that either help or harm your health, two new studies suggest.

Foods like fruits, vegetables, coffee, tea, wine, yogurt and buttermilk can increase the diversity of bacteria in a person's intestines. And that diversity can help ward off illness, said Dr. Jingyuan Fu, senior author of one of the studies.

"It is believed that higher diversity and richness [in gut bacteria] is beneficial," explained Fu. She is an associate professor of genetics at the University of Groningen in the Netherlands.

On the other hand, foods containing loads of simple carbohydrates appear to reduce bacterial diversity in the gut, Fu and colleagues found. These include high-fat whole milk and sugar-sweetened soda.

In addition, medications can also play a part in the makeup of your gut bacteria. Antibiotics, the diabetes drug metformin and antacids can cut down on gut bacterial diversity, the researchers found. Smoking and heart attacks also can have a negative effect, the team said.

Each person's intestines contain trillions of microorganisms, which doctors refer to as the "gut microbiome," said Dr. David Johnson. He is chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology.

The gut microbiome plays an essential but little-understood role in human health, said Johnson, who was not involved with the new studies.

"It's the largest immune system in the body," Johnson explained. "These bacteria have a very dramatic and prominent role in determining health and disease."

To study the effect of lifestyle on the gut microbiome, Fu and her colleagues collected stool samples from more than 1,100 people living in the northern Netherlands.

The samples were used to analyze the DNA of the bacteria and other organisms that live in the gut. In addition to stools, the study collected information on the participants' diets, medicine use and health.

In the second study, researchers with the Flemish Gut Flora Project performed a similar analysis on stool samples taken from 5,000 volunteers in Belgium.

Both studies concluded that diet has a profound effect on the diversity of gut bacteria, although, Fu said, the "underlying theories of these dietary factors remain largely unknown."

Johnson added that medicines can have the same effect, and antibiotics actually can kill off some important strains of gut bacteria. "One dose of an antibiotic may disrupt your gut bacteria for a year," he said.

Both sets of researchers emphasized that their studies only help explain a fraction of gut bacteria variation -- roughly 18 percent for the Netherlands study, and about 7 percent for the Flemish study.

However, the findings from the two groups overlapped about 80 percent of the time, indicating that they are on the right track, the researchers said.

The Belgian researchers estimated that over 40,000 human samples will be needed to capture a complete picture of gut bacteria diversity.

Johnson noted that other research has shown that poor sleep, obesity, diabetes and the use of artificial sweeteners also can interfere with gut bacteria.

"The general rule is a balanced diet with high fiber and low carbs tends to drive a better gut health overall," he said.

According to Fu, once researchers have a clearer understanding of the gut microbiome and its effects on health, doctors could be able to help prevent or heal illness by reading or influencing the bacteria within people's bodies.

"The personalized microbiome may assist in personalized nutrition, personalized medicine, disease risk stratification and treatment decision-making," she said.

Both studies were published in the April 29 issue of the journal Science.

Coffee, Wine Good for Healthy Gut, Sodas May Be Bad  

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

In continuation of my updates on Erlotinib, gemcitabine and capecitabine

Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new French study reports.

Researchers looked at the effects of adding a second drug -- erlotinib (Tarceva) -- to the initial round of chemotherapy. They also tested whether adding radiation to a second round of chemotherapy (chemoradiotherapy) would offer any survival benefit.

 erlotinib (Tarceva)

Unfortunately, the addition of the second drug didn't help people live longer, and those on chemoradiotherapy didn't fare any better.

"Chemoradiotherapy was not superior to chemotherapy," said the study's senior author, Dr. Pascal Hammel. Hammel is from the department of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France.

The study was funded by the pharmaceutical company Roche, the maker of Tarceva, and the French National Institute of Cancer.

More than 53,000 Americans are diagnosed with pancreatic cancer annually, the U.S. National Cancer Institute (NCI) says. About 42,000 Americans die each year from the disease, the NCI reports.

The new study focused on 449 people with pancreatic cancer. Their average age was just over 63.

All received standard four-month chemotherapy with the drug gemcitabine (Gemzar). Gemzar is currently used to treat a range of cancers, including pancreatic, ovarian, breast, and non-small cell lung cancers, the drug's labeling information says. For the study, about half the patients (219) also took Tarceva along with Gemzar.

 gemcitabine (Gemzar).

After completing initial treatment, imaging tests revealed that 269 patients appeared to have tumors that were under control. That meant their cancer was stable and didn't appear to have spread, or metastasized.

But the tumors couldn't be surgically removed because they had developed around the arteries surrounding the pancreas, study authors said.

About half this group of stable patients (136) received two additional months of the same chemotherapy regimen. The other half (133) was treated with a combination of radiation and the chemotherapy drug capecitabine (Xeloda).

 capecitabine (Xeloda)

After three years of follow-up, the researchers found that patients given Gemzar chemotherapy alone survived an average of 13.6 months. Those given the combination of Gemzar and Tarceva had an average survival of 11.9 months, the study found.

Patients treated with chemoradiotherapy lived an average of 15.2 months. Those who got chemotherapy alone lived an average of 16.5 months, the study found.

Hammel said there's still work to be done to improve the results of both chemotherapy and radiotherapy treatments.

But for now, Dr. Deborah Schrag agreed that "the French trial demonstrates that routine addition of chemo-radiation following initial chemotherapy for patients with locally advanced pancreatic cancer does not improve survival compared to continued chemotherapy." Schrag, chief of the Division of Population Sciences, Medical Oncology, at the Dana-Farber Cancer Institute in Boston, wrote an accompanying editorial in the same issue of the journal.

"[And] given the burdens of daily radiation therapy, there is no routine role for the application of this treatment strategy," added Schrag.

Schrag said it's possible there might be a certain group of pancreatic cancer patients who could get some measurable benefit from radiation. "Further evaluation of the tumor samples from the study participants might help to more precisely determine who might benefit from radiation, and such data are eagerly awaited," she said.

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study