Live imaging captures how blood stem cells take root in the body


A see-through zebrafish and enhanced imaging provide the first direct glimpse of how blood stem cells take root in the body to generate blood. Reporting online in the journal Cell today, researchers in Boston Children’s Hospital’s Stem Cell Research Program describe a surprisingly dynamic system that offers several clues for improving bone marrow transplants in patients with cancer, severe immune deficiencies and blood disorders, and for helping those transplants “take.”

The steps are detailed in an animation narrated by senior investigator Leonard Zon, MD, director of the Stem Cell Research Program (see below).

“The same process occurs during a transplant as occurs in the body naturally,” says Zon. “Our direct visualization gives us a series of steps to target, and in theory we can look for drugs that affect every step of that process.”

“Stem cell and bone marrow transplants are still very much a black box—cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can’t be seen,” says Owen Tamplin, PhD, the paper’s co-first author. “Now we have a system where we can actually watch that middle step. ”

The blood system’s origins

It had already been known that blood stem cells bud off from cells in the aorta, then circulate in the body until they find a “niche” where they’re prepped for their future job creating blood for the body. For the first time, the researchers reveal how this niche forms, using time-lapse imaging of naturally transparent zebrafish embryos and a genetic trick that tagged the stem cells green.

On arrival in its niche (in the zebrafish, this is in the tail), the newborn blood stem cell attaches itself to the blood vessel wall. There, chemical signals prompt it to squeeze itself through the wall and into a space just outside the blood vessel.

“In that space, a lot of cells begin to interact with it,” says Zon. Nearby endothelial (blood-vessel) cells wrap themselves around it: “We think that is the beginning of making a stem cell happy in its niche, like a mother cuddling a baby.”

As the stem cell is being “cuddled,” it’s brought into contact with a nearby stromal or “nurse” cell that helps keep it attached. The stem cell hooks onto the nurse cell tightly, in a process Zon likens to early “attachment” of an infant to its mother.

The “cuddling” was reconstructed from confocal and electron microscopy images of the zebrafish taken during this stage. Through a series of image slices, the researchers were able to reassemble the whole 3D structure—stem cell, cuddling endothelial cells, and stromal cells.

“Nobody’s ever visualized live how a stem cell interacts with its niche,” says Zon. “This is the first time we get a very high-resolution view of the process.”

Eventually, the cuddled stem cell begins dividing. One daughter cell leaves the niche while the other stays. Eventually, all the stem cells leave and begin colonizing their future site of blood production (in fish, this is in the kidney).

Further imaging done in mice found evidence that blood stem cells go through much the same process in mammals, which makes it likely in humans too. In humans, set up permanent residence in the bone marrow.

These detailed observations are already informing the Zon Lab’s attempt to improve bone marrow transplantation. By doing a chemical screen in large numbers of zebrafish embryos, the researchers found that the compound lycorine promotes interaction between the blood stem cell and its niche, leading to greater numbers of blood in the adult fish.

This temporary tattoo can monitor diabetics’ glucose levels as accurately as a finger prick .


A flexible and easy-to-wear temporary tattoo could help diabetics manage their condition without daily finger pricks.

Engineers from the University of California, San Diego have developed an ultra-thin temporary tattoo that can painlessly and accurately monitor the glucose levels of diabetics.

The flexible device costs just a few cents and lasts for a day at a time, and early tests have shown that it’s just as sensitive as a finger-prick test.

But even cooler is the fact that the system works without blood, by extracting and measuring the glucose from the fluid in between skin cells, and could eventually be adapted to detect other important metabolites in the body, or deliver medicine.

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At the moment, people with diabetes need to monitor their glucose levels multiple times a day by pricking their finger and assessing their blood. But in the future the tattoo will allow their levels to be continuously measured throughout the day. This means they’ll be able to more sensitively maintain their glucose levels and better manage their condition.

Created by graduate student Amay Bandodkar, the device is made up of woven electrodes printed out on rub-on tattoo paper, and works by applying a very mild electrical current to the skin for 10 minutes. This forces sodium ions from the fluid between skin cells, which carry glucose, to flow towards the tattoo.

A sensor built into the tattoo then measures the strength of the electrical charge produced by this glucose. The levels of glucose in this fluid are, overall, around 100 times lower than the levels found in someone’s blood, so the device requires a more sensitive sensor. But an early trial on seven men and women aged aged between 20 and 40 without diabetes has revealed that it’s just as accurate as a finger-prick test. The users also couldn’t feel anything while wearing the device, other than a mild tingling in the first 10 seconds of use.

The results of the trial have been described in the journal Analytical Chemistry.

Right now, the tattoo can’t provide a numerical read-out that diabetics would need in order to regulate their blood sugar levels, but it’s an important proof-of-concept. The team is now working on adding that user-friendly capability.

“The readout instrument will also eventually have Bluetooth capabilities to send this information directly to the patient’s doctor in real-time or store data in the cloud,” said Bandodkar in a press release.

And the engineers are also working on ways to make the tattoo last longer.

“Presently the tattoo sensor can easily survive for a day. These are extremely inexpensive – a few cents – and hence can be replaced without much financial burden on the patient,” said Bandookar.

It’s not often you get a chance to take care of your health while looking good at the same time, and we can’t wait for these to hit the market.

How To Stop Negative Thoughts From Getting You Down .


Everyone has negative thoughts from time to time, and they certainly have their place in the world. You wouldn’t want to be so positive that you believe you can travel across a city from building to building, for example.

But what happens to many of us is that negative, defeatist thoughts run on repeat in our heads, preventing us from taking action and moving forward when we’re more than capable of doing so.

If it were easy to stop this negativity playlist, pretty much everyone would. Sadly, it’s not the simplest change to make. That’s why the folks at Happify have created an infographic that details some surprising statistics about negative mindsets, and offers some effective techniques to shift to a more positive outlook.

Check out the infographic and share some of your strategies for cutting out negative thoughts!

How To Increase Your Memory By Up To 75% From Sniffing This.


This is a wonderful herb with a tradition of use spanning back to ancient times. It has innumerable uses in both the kitchen and in herbal medicine.

Did you know that rosemary has been associated with memory enhancement since long ago? The truth is that it has even been referred to from the latter part of the Elizabethan Era to the Early Romantic period as the “herb of remembrance”.

In Shakespeare’s Hamlet, Ophelia says, “There’s rosemary, that’s for remembrance.”  It has also long been used as a symbol for remembrance during weddings, war commemorations and funerals in Europe and Australia.  Mourners in old times would wear it as a buttonhole, burn it as incense or throw it into graves as a symbol of remembrance for the dead.

Because of this seemingly esoteric association, rosemary has at times been made into a sort of herbal-amulet, where it was placed beneath pillowcases, or simply smelt as a bouquet, and it was believed that using rosemary in these ways could protect the sleeper from nightmares, as well as increase their memory.

What’s fascinating is that several scientific studies have now found remarkable results for rosemary’s effects on memory:

Rosemary essential oil’s role in aromatherapy as an agent that promotes mental clarity was validated by the study of Moss, Cook, Wesnes, and Duckett, in which the inhalation of rosemary essential oil significantly enhanced the performance for overall quality of memory and secondary memory factors of study participants.

More recently, in 2012 a study on 28 older people (average 75 years old) found statistically significant dose-dependent improvements in cognitive performance with doses of dried rosemary leaf powder.

Further studies by Mark Moss and team have found memory enhancements of up to an amazing 75% from diffusion of rosemary essential oil.

He said ‘We wanted to build on our previous research that indicated rosemary aroma improved long-term memory and mental arithmetic.

‘In this study we focused on prospective memory, which involves the ability to remember events that will occur in the future and to remember to complete tasks at particular times. This is critical for everyday functioning, for example when someone needs to remember to post a birthday card or to take medication at a particular time.’

Rosemary essential oil was diffused in to a testing room by placing four drops on an aroma stream fan diffuser and switching this on five minutes before people entered the room.

Altogether 66 people took part in the study and were randomly allocated to either the rosemary-scented room or another room with no scent.

In each room participants completed a test designed to assess their prospective memory functions.

Blood was taken from volunteers and analysed to see if performance levels and changes in mood following exposure to the rosemary aroma were related to concentrations of a compound known as 1,8-cineole present in the blood.

The compound is also found in the essential oil of rosemary and has previously been shown to act on the biochemical systems that underpin memory.

The results showed that participants in the rosemary-scented room performed better on the prospective memory tasks than the participants in the room with no scent.

This was the case for remembering events, remembering to complete tasks at particular times, and the speed of recall.

The results from the blood analysis found that significantly greater amounts of 1,8-cineole were present in the plasma of those in the rosemary scented room, suggesting that sniffing the aroma led to higher concentrations.

Researcher Jemma McCready said ‘The difference between the two groups was 60-75 per cent, for example one group would remember to do seven things compared with four tasks completed by those who did not smell the oil, and they were quicker.

‘We deliberately set them a lot of tasks, so it’s possible that people who multi-task could function better after sniffing rosemary oil.’ Miss McCready said ‘There was no link between the participants’ mood and memory. This suggests performance is not influenced as a consequence of changes in alertness or arousal.

‘These findings may have implications for treating individuals with memory impairments.

‘It supports our previous research indicating that the aroma of rosemary essential oil can enhance cognitive functioning in healthy adults, here extending to the ability to remember events and to complete tasks in the future.

‘Remembering when and where to go and for what reasons underpins everything we do, and we all suffer minor failings that can be frustrating and sometimes dangerous. ‘Further research is needed to investigate if this treatment is useful for older adults who have experienced memory decline’ she added.

Source: Complete Health and Happiness

SIZING UP GIANTS UNDER THE SEA: BIOLOGISTS CORRECT INACCURACIES FOR 25 MARINE SPECIES


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A team of scientists and undergraduate students have analyzed the body size for 25 marine species, including whales, sharks, squids, and other ocean giants. The project elucidates both the challenges of arriving at exact measurements and the human bias toward larger individuals.

“Several years ago I noticed that people kept staying that giant squids reached 60 feet in length, which is amazingly long,” says Craig McClain, the assistant director of the National Evolutionary Synthesis Center in Durham, N.C., and the primary author of the paper. “When I started actually looking at the data, I found that that estimate was actually quite unrealistic.”

McClain explained that the muscle fibers in squids loosen and stretch during decomposition, which could account for the measurement of specimens found ashore in the 1800s. This new research indicates that the longest scientifically verified length is estimated at 12 meters (nearly 40 feet).

“It’s one part a databasing effort and one part historical research: double-checking museum specimens; talking with other scientists and collectors; and even checking eBay for specimens for sale,” McClain says.

To cast a wider net, he invited graduate and undergraduate students to join the project and select the marine species that most fascinated them. The results of their collective research will be published Tuesday, January 13 to PeerJ.

The species range from well-known behemoths like the Great White Shark, Giant Octopus, and walrus to more obscure creatures such as the Giant Tubes Worm and the Colossal Squid.

Meghan Balk, a coauthor and Ph.D. candidate at the University of New Mexico, researched the Southern Elephant Seal, as well as several shark species. For her, the study illustrated the great variability of size within a single species.

“What people think of as the biggest representatives aren’t usually the most optimal,” Balk says. “It says a lot about what it means to be large. How beneficial is it to be the biggest in a big species?”

Bigger isn’t always better. The tallest man in recorded history, Robert Wadlow, stood at 2.72 meters (nearly 9 feet), which is far from the average human height. Individuals like Wadlow often had shortened lifespans because of health complications related to their size.

Marine megafauna can also fall into a wide range of sizes within the same species.

“It’s fascinating as to why there is size variation [and] why everything isn’t less skewed,” Balk says. “How many sizes does an organism go through from the time it’s born to the time it’s an adult?” She explains that while mammals eat the same diet throughout their lives, animals like fish, sharks, and turtles eat different foods as they grow. For these species, size has a cascading effect within marine food webs.

The authors also considered environmental factors that could give rise to bigger species, as well as situations in which a larger size would be beneficial. For example, the Giant Clam can reach lengths of 1.37 meters (4.5 feet) because it receives additional nourishment from symbiotic photosynthetic bacteria. Similarly, larger Whale Sharks and Blue Whales are less susceptible to starvation: If a habitat is depleted of food, these filter-feeders have the mass to support a migration and subsequent fasting to reach more plankton-rich waters.

“Metabolism is a function of size because it indicates how much oxygen and carbon an animal consumes,” McClain says. “Knowing whether a whale shark is 10 tons, 15 tons, or 20 tons lets us know how many light bulbs worth of energy it uses every day.”

In tackling a search that would become quite gigantic itself, the authors contacted fisheries, marine centers, and other scientists.

“This is one of my first experiences in doing research in such a collaborative setting,” says Catherine Chen, a coauthor and Duke University junior who investigated the Blue Whale, Sperm Whale, and Ocean Sunfish. “I got to work with the International Whaling Commission’s datasets, which allowed me to look and play with over 200 years of whale capture data.”

Social media also proved advantageous to the project. McClain created a website, The Story of Size, where the authors posted regularly. The students promoted their work by sharing updates and their own impressions. With posts like, “Why You Should Give a Damn about a Giant Clam,” the site added a playful tone to the scientific discourse and also made the project more accessible to the general public.

“Having them write everything as a report is probably a disservice. Those are different styles of writing that require different techniques,” McClain says. “The big question is: Can you do research and outreach at the same time and not have it become a burden?”

The students were also required to tweet about their research, which for some, including Chen, meant creating their first Twitter accounts.

“Twitter’s really good for reaching out to the general public but also for talk between scientists,” Chen says. Through Twitter she met Trevor Branch, a professor of aquatic and fishery science at the University of Washington. Branch was able to help Chen with data on Blue Whales and even became a coauthor of the paper.

While academics including Branch and institutions like the IWC welcomed the opportunity to share their data, some sources were reluctant. The team hopes their work will help shift the attitude toward open access in a more favorable direction.

“A lot of questions that we sought to answer are still not answered either because of lack of research or lack of access,” Balk says. “I think that this paper will open up discussions about collecting and sharing data to gain a broader understanding of a species.”

Despite challenges, McClain is pleased with his team’s results, which he thinks will slowly replace the erroneous measurements found in academic papers, fishery databases, textbooks, and more.

“Precise, accurate, and quantified measurements matter at both a philosophical and pragmatic level,” McClain says. “Saying something is approximately ‘this big,’ while holding your arms out won’t cut it, nor will inflating how large some of these animals are.”

POSSIBLE TREATMENTS IDENTIFIED FOR HIGHLY CONTAGIOUS STOMACH VIRUS


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Antibiotics aren’t supposed to be effective against viruses. But new evidence in mice suggests antibiotics may help fight norovirus, a highly contagious gastrointestinal virus, report scientists atWashington University School of Medicine in St. Louis.

The researchers found antibiotics could help prevent norovirus infections. The same team also showed that a recently identified immune system molecule can cure persistent norovirus infections even in mice with partially disabled immune systems. The surprising findings, available online in Science, will appear Jan. 16 in the journal’s print edition.

Outbreaks of norovirus are notoriously difficult to contain and can spread quickly on cruise ships and in schools, nursing homes and other closed spaces.

The researchers found that norovirus works its way into gut tissue in mice that have been pretreated with antibiotics but that the virus cannot establish a persistent infection. Follow-up studies showed that norovirus needs a bacterial collaborator to establish a persistent infection in the gut. Eradicating the bacterial partner with an antibiotic can prevent persistent norovirus infection in mice.

“The virus actually requires the bacteria to create a persistent infection,” said senior author Herbert W. Virgin IV, MD, PhD, the Edward Mallinckrodt Professor of Pathology and head of the Department of Pathology and Immunology. “The virus appears to have a symbiotic relationship with the bacteria — they share the job of establishing persistence.”

No studies have indicated that animals or insects carry and spread human norovirus. Therefore, scientists suspect that the sources of outbreaks may be people who have persistent norovirus infections but don’t have symptoms, such as stomach pain, nausea, diarrhea and vomiting. Virgin and his team decided to explore this possibility by studying a mouse model of chronic norovirus infection.

In additional tests, the scientists found they could restore the norovirus infections by transplanting fecal material from untreated mice into mice that earlier had been treated with the antibiotics. The transplants contained the bacteria eliminated by the antibiotics.

The scientists also looked for mouse proteins essential to preventing chronic norovirus infections. They found that a receptor protein for an immune inflammatory factor known as interferon lambda was required for antibiotics to prevent infection. Giving the mice interferon lambda also prevented norovirus infection, suggesting it also should be evaluated as a treatment for norovirus.

In the second study, the Washington University researchers reported that treatment with interferon lambda offers a significant advantage: It not only prevents the start of persistent norovirus infections but also eliminates established persistent infections. This was true even in mice lacking immune cells that scientists thought were essential to eradicating viral infections.

“I believe that’s a new concept in immunology,” said Virgin. “We thought that interferon lambda and other related molecules in the immune system could only contain viral infections until other parts of the immune system, including antibodies and T cells, finished the job.”

The researchers speculated that other viruses and bacteria may form similar symbiotic partnerships in humans.

“We need a much more detailed understanding of how antibiotic treatment affects the links among host, bacteria and virus,” Virgin said.

ELECTRICAL STIMULATION ‘TUNES’ VISUAL ATTENTION


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“Existing theories of visual attention propose that working memory representations, also known as short-term memory, typically control how attention is focused on targets in our visual field,” Geoffrey Woodman, assistant professor of psychology at Vanderbilt University and co-author of the study along with Ph.D. candidate Robert M.G. Reinhart, said. “These new findings provide evidence that long-term memory representations can also underlie our ability to rapidly configure attention to focus on certain objects, and that long-term memory performance can be sharply accelerated using electrical stimulation.”

Researchers have long known that attention could be tuned, like a radio dial, to hone in on specific features, but how and where in the brain this tuning occurs has remained an open question.

By passing very weak electrical current through the brains of healthy volunteers using a process called transcranial direct-current stimulation, researchers were able to cause the volunteers to much more quickly find target objects embedded in arrays of distracting objects. The study showed that after 20 minutes of passing safe levels of weak electrical current through electrodes placed on the head, the volunteers were able to more effectively focus attention on the searched-for targets, with dramatic increases in speed.

To determine the source of the attentional improvements, the researchers examined the recordings of the volunteers’ brain activity for the neurophysiological signatures of visual working memory and long-term memory. They found that the rapid improvement in attention was most closely related to increased activity in long-term, rather than working, memory. Their findings further indicate that long-term memory more immediately integrates information that is used to control attention than was previously thought, offering new insights into the relationship between working and long-term memory in controlling attention.

More Falls for Those Starting Newer Antipsychotics


Falls, fractures up 50% in patients with new prescriptions for atypical antipsychotics.

Receiving a new prescription for an atypical antipsychotic medicine was associated with more serious falls and more fractures in a new retrospective cohort study.

Adults ages 65 and older who received a new prescription had a 53% increased risk of falling and a 50% increased risk of nonvertebral osteoporotic fracture, found the study. It was published as a research letter in JAMA Internal Medicine on Jan. 13, 2015, and was led by Lisa-Ann Fraser, MD, from the University of Western Ontario in Canada.

“These findings call into question the widespread off-label use of atypical antipsychotic medications and support increasing evidence of safety concerns regarding their use in older adults,” Fraser and colleagues wrote.

In the retrospective study of 200,000 residents of Ontario, whose medical records are kept in a central database, those who received a new prescription for one of three atypical antipsychotics — quetiapine (Seroquel), risperidone (Risperdal), or olanzapine (Zyprexa) — from 2003 to 2011 were matched 1:1 with other Ontario residents who didn’t receive such a prescription. Controls were matched to cases for fracture risk factors. Medical encounters over the following 90 days were analyzed for fracture and fall outcomes.

Starting atypical antipsychotics was associated with increased rates of hip fracture (odds ratio 1.67, 95% CI 1.53-1.81), nonvertebral osteoporotic fracture (OR 1.51, 95% CI 1.41-1.60), and falls (OR 1.54 95% CI 1.47-1.61). The risk of fracture and falling wasn’t related to the type of atypical medication used, the dosage, or whether the individual lived in a long-term care facility.

The raw data indicated that 7.0% of those receiving antipsychotic prescriptions experienced fractures versus 5.5% of the controls. Similarly, falls occurred in 4.4% of the antipsychotic recipients compared with 2.9% of controls.

Antipsychotic medications have been found to be associated with fracture risk in some previous studies, although the strength and nature of the link has been debated.

“Atypical antipsychotic medications have been found previously to be associated with hypotension, sedation, and gait abnormalities; therefore, it is possible that falls are the mechanism by which these drugs increase fracture risk,” researchers wrote.

The authors noted limitations to the study. It was retrospective, observational, and based on administrative records; there may also have been unmeasured confounding factors. Also, the analysis did not examine use of first-generation antipsychotic drugs.

CDC: Most Nosocomial Infections Fall


Progress seen at national level, though more mixed in state-by-state analysis..

Rates of most major types of healthcare-associated infections have declined markedly in recent years, the CDC said Wednesday, although the trend did not extend to catheter-associated urinary tract infections.

In 2013, significant decreases in standardized infection rates were seen for central line-associated bloodstream infections (down 46% from 2008), surgical site infections (down 19% from 2008), hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) infections (down 8% from 2011), and hospital-onset Clostridium difficile infections (down 10% from 2011), according to the National and State Healthcare-Associated Infections Progress Report.

But catheter-associated urinary tract infections had a 6% uptick from 2009 to 2013, the report said. On the other hand, “initial data seem to indicate that these infections have started to decrease.”

Data for the report came from the CDC’s National Healthcare Safety Network, which collects information from some 14,500 hospitals and other facilities.

In addition to the national summary, the report also included state-by-state data (including the District of Columbia and Puerto Rico) on the major classes of healthcare-associated infection, for which the picture was more mixed.

Some states saw massive increases in certain types of infection — a 42% increase in rates of MRSA bacteremia in Alabama, for example — while others showed dramatic declines, such as Louisiana’s decrease of 37% in C. difficile.

Obesity Device Wins FDA OK


A vagus nerve stimulator seeks to combat obesity by controlling satiety.

The FDA has okayed an electrical stimulation device for treating obesity that targets the abdominal vagus nerve to control satiety, the agency announced.

The Maestro Rechargable System was approved for patients ages 18 and older who haven’t been able to shed pounds in a weight-loss program and who have a body mass index (BMI) of 35 to 45 with at least one other obesity-related condition, such as type 2 diabetes.

The system is the first obesity device approved by the FDA since 2007, the agency said. It consists of a rechargeable electrical pulse generator, wire leads, and electrodes that are surgically implanted into the abdomen.

The device sends intermittent electrical pulses to the trunks in the abdominal vagus nerve, which is involved in regulating stomach emptying and signaling to the brain whether the stomach is empty or full.

But the FDA noted in its press release that the exact mechanisms by which the device helps patients lose weight are unknown. The pivotal trial on which approval was baseddid not assess food intake or other factors that might have accounted for the weight loss.

That trial enrolled 233 patients with a BMI of 35 or higher. Patients received either the actual device or a sham device.

The primary endpoint of at least 10% greater excess weight loss than in controls was not met; they only lost 8.5% more. But an FDA advisory committee agreed that 18-month data were supportive of sustained weight loss and agreed that the benefits of the device outweighed its risks, the FDA said.

Also, about half of the patients in the device group lost at least 20% of their exess weight, and about 38% lost at least 25% of their excess weight.

Serious adverse events included nausea, pain at the neuroregulator site, vomiting, and surgical complications. Other adverse events included pain, heartburn, problems swallowing, belching, mild nausea, and chest pain, the FDA said.

Device maker EnteroMedics will have to conduct a 5-year postmarketing study of at least 100 patients for outcomes including weight loss, adverse events, surgical revisions, explants, and changes in obesity-related conditions.