WHAT CAUSES DEJA VU

Déjà vu (French for 'already seen') occurs in approximately 60 to 80 percent of people -- a phenomenon that's almost always fleeting and may manifest at any time.

You walk into a room and suddenly your brain goes fuzzy with an overwhelming wave of familiarity -- although this is a totally new experience. Like something out of a sci-fi plot, it almost seems as if you've walked into the future.

Chances are, you've experienced this situation, known as déjà vu, during your life. Déjà vu (French for 'already seen') occurs in approximately 60 to 80 percent of people -- a phenomenon that's almost always fleeting and may manifest at any time. Despite wide-spread coverage, bursts of déjà vu are still misunderstood by the scientific community.

"Because there is no clear, identifiable stimulus that elicits a déjà vu experience (it is a retrospective report from an individual), it is very difficult to study déjà vu in a laboratory," said Michelle Hook, Ph.D., assistant professor in the Department of Neuroscience and Experimental Therapeutics, at the Texas A&M Health Science Center College of Medicine.

A glitch in the brain?

"According to many studies, approximately two-thirds of individuals have experienced at least one episode of déjà vu in their life," Hook said. "Understanding how memory storage works may shed some light on why some experience it more than others."

Episodes of déjà vu may be closely related to how memory is stored in the brain. Retention of long-term memories, events and facts are stored in the temporal lobes, and, specific parts of the temporal lobe are also integral for the detection of familiarity, and the recognition of certain events. The takeaway: The temporal lobe is where you make and store your memories.

While déjà vu's connection to the temporal lobe and memory retention is still relatively unknown, clues about the condition were derived from people who suffer from temporal lobe epilepsy (a condition in which nerve cell activity in the brain is disturbed -- causing seizures). Findings suggest that déjà vu events may be caused by an electrical malfunction in the brain.

Epileptic seizures are characterized by dysfunctional neuron (nerve cell) activity across the brain which disrupts the electrical impulses that 'fire' neurons. These impulses can spread across the whole brain -- inducing seizures. "Clinical reports show that some patients who suffer from temporal lobe epilepsy report experiencing déjà vu, almost as a sort of warning, before an epileptic seizure event," Hook said.

But, what is the basis for déjà vu in healthy people without epilepsy? Some researchers describe it as a 'glitch' in the brain -- when the neurons for recognition and familiarity fire -- allowing the brain to mistake the present for the past. In fact, the same abnormal electrical impulses that contribute to epilepsy can present in healthy people. An example of this is a hyponogogic jerk (an involuntary muscle spasm that occurs as a person is falling asleep).

Shortcuts in neural pathways

Instances of déjà vu in healthy individuals may also be attributed to a 'mismatch' in the brain's neural pathways. This could be because the brain is constantly attempting to create whole perceptions of the world around us with limited input.

For example, it only takes a small amount of sensory information -- like a familiar smell -- for the brain to create a detailed recollection. Déjà vu could be linked to discrepancies in the memory systems of the brain, leading the sensory information to by-pass short-term memory and reach long-term memory instead. This may produce the unsettling feeling that we've experienced a new moment before.

In the visual system, sensory information travels through multiple pathways to the higher cortical centers of the brain (areas that play a key role in memory, attention, perception, awareness, thought, language and consciousness), with all information reaching those centers at or around the same time.

"Some suggest that when a difference in processing occurs along these pathways, the perception is disrupted and is experienced as two separate messages. The brain interprets the second version, through the slowed secondary pathway -- as a separate perceptual experience -- and thus the inappropriate feeling of familiarity (déjà vu) occurs," Hook said.

According to Hook, there is still much to learn about déjà vu and the mechanisms behind it. "There may not be a simple answer for the mechanisms behind déjà vu yet, but, with further research and studies, conclusive evidence for the phenomenon may be discovered in the future," she said. Wouldn't that be like experiencing déjà vu all over again?

ZIKA VIRUS AND ITS GENETICAL EVOLUTION

This is a phylogenetic tree constructed from nucleotide data from 41 viral complete ORF sequences of ZIKV strains by the maximum likelihood-method logarithm in MEGA7 based on the Tamura-Nei model. A bootstrap percentage for 1,000 replicates was shown on the left. Branches corresponding to partitions reproduced in less than 70% of bootstrap replicates are not shown. Strains isolated from human, mosquito, and monkey (NIH reference strain) were labeled with blue, orange, and black circles, respectively. The two subtypes were labeled on the right side of the tree. The new strains Rio-U1 and Rio-S1 were highlighted using (*).

Credit: Wang and Valderramos et al./Cell Host & Microbe 2016

An analysis comparing the individual differences between over 40 strains of Zika virus (30 isolated from humans, 10 from mosquitoes, and 1 from monkeys) has identified significant changes in both amino acid and nucleotide sequences during the past half-century. The data, published April 15 in Cell Host & Microbe, support a strong divergence between the Asian and African lineages as well as human and mosquito isolates of the virus, and will likely be helpful as researchers flush out how a relatively unknown pathogen led to the current outbreak.

The project--led by researchers at the University of California, Los Angeles, and the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing--builds on other viral sequence analyses conducted over the past two months, with new large-scale and structural comparisons. Highlights of the findings include:

• All contemporary human Zika virus strains share a more similar sequence to the Malaysian/1966 strain than the Nigerian/1968 strain, suggesting the strains in the recent human outbreak evolved from the Asian lineage.
• All human strains identified in the 2015-2016 epidemic appear to be more closely related to the French Polynesia/2013 strain than the Micronesia/2007 strain, suggesting that the two variants evolved from a common ancestor.
• The prM (pre-membrane precursor) protein of the Zika virus had the highest percentage variability between the Asian human and the African mosquito subtypes, and modeling suggests that some of this variability contributes to a significant structural change.

"We believe these changes may, at least partially, explain why the virus has demonstrated the capacity to spread exponentially in the human population in the Americas," says senior study author Genhong Cheng, a professor in UCLA's Department of Microbiology, Immunology & Molecular Genetics. "These changes could enable the virus to replicate more efficiently, invade new tissues that provide protective niches for viral propagation, or evade the immune system, leading to viral persistence. Of course, all of these hypotheses will need to be tested in experimental models."

Future sequencing work will likely focus on understanding the Zika strain causing the 2015-2016 epidemic, which has yet to be isolated from a mosquito. Cheng's group and others will also begin to elucidate the structure of the viral proteins, which can inform drug and vaccine design. "We hope that our work provides a strong basis that will help the larger scientific community in accelerating Zika virus research," he says.

MOTHERS MILK AND THE INFANT GUT MICROBIOTA: An ancient symbiosis

Mother's milk guides the development of neonates' gut microbiota, nourishing a very specific bacterial population that, in turn, provides nourishment and protects the child.

Nursing infants' gastrointestinal tracts are enriched with specific protective microbes. Mother's milk, itself, guides the development of neonates' gut microbiota, nourishing a very specific bacterial population that, in turn, provides nourishment and protects the child. Now a team from the University of California, Davis, has identified the compound in the milk that supplies this nourishment, and has shown that it can be obtained from cow's milk. This work could result in using cow's milk to provide that compound as a prebiotic for infants. The research is published ahead of print on April 15th in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

In earlier research, these investigators, led by David A. Mills, PhD, had shown that glycoproteins from milk, which contain both protein, and molecules containing multiple sugars, called oligosaccharides, were the source of that nourishment. They also had found that the infant-associated subspecies of the bacterium, Bifidobacterium longum subsp. infantis (B. infantis), produced an enzyme that could cleave the oligosaccharides from the milk glycoproteins, and they had identified that enzyme.

For the current study, Mills, who is Professor and Shields Endowed Chair in Dairy Food Science, and his collaborators posited that these oligosaccharides were the food source for B. infantis. They then showed that the enzyme could break down glycoproteins not only from mother's milk, but from cow's milk, releasing the oligosaccharides.

"The released oligosaccharides turned out to be an incredible substrate for B. infantis' growth," said Mills. At the same time, Mills et al. showed that the oligosaccharides did not nourish adult-associated bifidobacteria.

All that suggests that getting the bioactive oligosaccharides into infant formula could improve it, said Mills. But his emphasis is on the science, he said. "The amazing thing to me is how selective these released oligosaccharides are as a substrate for growth."

Mills noted that B. infantis has many genes involved in breaking down glycoproteins in mother's milk in order to release the oligosaccharides. Mother's milk coevolved over millions of years with mammals, and with their beneficial gut microbiota that it helped to thrive. "It is the only food that co-evolved with humans to make us healthy," said Mills.

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NEW ESOPHAGUS TISSUE RECONSTRUCTED

The esophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the esophagus (esophagectomy) to treat cancer or injury requires reconnecting the remaining part of the esophagus to the stomach to allow swallowing and the passage of food.

Credit: © 7activestudio / Fotolia

Writing in The Lancet, US doctors report the first case of a human patient whose severely damaged esophagus was reconstructed using commercially available FDA approved stents and skin tissue. Seven years after the reconstruction and 4 years after the stents were removed, the patient continues to eat a normal diet and maintain his weight with no swallowing problems.

Until now, this regeneration technique has only been tested in animals. The authors, reporting on the outcome of the procedure, say that research, including animal studies and clinical trials, are now needed to investigate whether the technique can be reproduced and used in other similar cases.

Professor Kulwinder Dua from the Medical College of Wisconsin, Milwaukee, USA, and colleagues report using metal stents as a non-biological scaffold and a regenerative tissue matrix from donated human skin to rebuild a full-thickness 5cm defect in the esophagus of a 24-year-old man. The patient was urgently admitted to hospital with a disrupted esophagus resulting in life-threatening infection and inability to swallow following complications from an earlier car accident which had left him partially paralysed. Despite several surgeries, the defect in the esophagus was too large to repair.

The esophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the esophagus (esophagectomy) to treat cancer or injury requires reconnecting the remaining part of the esophagus to the stomach to allow swallowing and the passage of food. Part of the stomach or colon is used to make this connection. However, the procedure was not possible in this case because the defect in the esophagus was too large, and the patient too ill to undergo the procedure.

The team hypothesized that if the three-dimensional shape of the esophagus could be maintained in its natural environment for an extended period of time while stimulating regeneration using techniques previously validated in animals, esophageal reconstruction may be possible.

They used commercially available, FDA-approved, materials to repair the defect. To maintain the shape of the esophagus and bridge the large defect, they used an endoscope to place self-expanding metal stents. The defect was then surgically covered with regenerative tissue matrix and sprayed with a platelet-rich plasma gel produced from the patient's own blood to deliver high concentrations of growth factors that not only stimulate growth but also attract stem cells to stimulate healing and regeneration. The sternocleidomastoid, a muscle running along the side of the neck, was placed over the matrix and the adhesive platelet-rich plasma gel.

The team planned on removing the stent 12 weeks after reconstruction, but the patient delayed the procedure for three and a half years because of fears of developing a narrowing or leakage in the esophagus. One year after the stents were removed, endoscopic ultrasound images showed areas of fibrosis (scarring) and regeneration of all five layers of the esophageal wall. Full recovery of functioning was also established by swallowing tests showing that esophageal muscles were able to propel water and liquid along the esophagus into the stomach in both upright and 45° sitting positions. But, how long the regeneration process took is unclear because the patient delayed stent removal for several years.

According to Professor Dua, "This is a first in human operation and one that we undertook as a life-saving measure once we had exhausted all other options available to us and the patient. The use of this procedure in routine clinical care is still a long way off as it requires rigorous assessment in large animal studies and phase 1 and 2 clinical trials. The approach we used is novel because we used commercially available products which are already approved for use in in the human body and hence didn't require complex tissue engineering."

Scientists discover how Chinese medicinal plant makes anti-cancer compound

New research from the John Innes Centre reveals how a plant used in traditional Chinese medicine produces compounds that may help to treat cancer and liver diseases.

Credit: Qing Zhao, Chinese Academy of Sciences

New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

The Chinese skullcap, Scutellaria baicalensis -- otherwise known in Chinese medicine as Huang-Qin -- is traditionally used as a treatment for fever, liver and lung complaints.

Previous research on cells cultured in the lab has shown that certain compounds called flavones, found in the roots of this plant, not only have beneficial anti-viral and anti-oxidant effects, but they can also kill human cancers while leaving healthy cells untouched. In live animal models, these flavones have also halted tumour growth, offering hope that they may one day lead to effective cancer treatments, or even cures.

As a group of compounds, the flavones are relatively well understood. But the beneficial flavones found in Huang-Qin roots, such as wogonin and baicalin, are different: a missing -- OH (hydroxyl) group in their chemical structure left scientists scratching their heads as to how they were made in the plant.

Professor Cathie Martin, lead author of the paper published in Science Advances, explains: "Many flavones are synthesised using a compound called naringenin as a building block. But naringenin has this -OH group attached to it, and there is no known enzyme that will remove it to produce the flavones we find in Huang-Qin roots."

Working in collaboration with Chinese scientists, Cathie and her team explored the possibility that Huang-Qin's root-specific flavones (RSFs) were made via a different biochemical pathway. Step-by-step, the scientists unravelled the mechanism involving new enzymes that make RSFs using a different building block called chrysin.

"We believe that this biosynthetic pathway has evolved relatively recently inScutellaria roots, diverging from the classical pathway that produces flavones in leaves and flowers, specifically to produce chrysin and its derived flavones," said Professor Martin.

"Understanding the pathway should help us to produce these special flavones in large quantities, which will enable further research into their potential medicinal uses. It is wonderful to have collaborated with Chinese scientists on these traditional medicinal plants. Interest in traditional remedies has increased dramatically in China since Tu Youyou was awarded the Nobel Prize for Medicine in 2015 for her work on artemisinin. It's exciting to consider that the plants which have been used as traditional Chinese remedies for thousands of years may lead to effective modern medicines".

The Magnificent Macaws

BRILLIANT colors burst from the forest canopy as a flock of birds take wing! This magnificent sight amazed the European explorers who arrived in Central and South America beginning in the late 15th century. What they saw were macaws, long-tailed parrots that can be found in the tropical regions of the Americas. Before long, pictures of these spectacular creatures appeared on maps of the region as a symbol of the newly found paradise.

Both male and female macaws are vividly colored, an oddity among brightly colored avians. Macaws are also intelligent, social birds with harsh squawks and piercing shrieks. In flocks of up to about 30 individuals, they leave their roosts early in the morning to forage for seeds, tropical fruits, and other foods. Typical of parrots, they often use their claws to grasp food, which they bite into with their big, curved bill. They can even crack open the tough shells of nuts! After feeding, they commonly flock to cliffs or riverbanks to nibble on clay, which may help to neutralize toxins in their food as well as to supply needed chemical elements.

Macaws normally mate for life, and they cooperate in caring for their young. The various species nest in tree hollows, in holes in riverbanks and termite mounds, or in the cavities and crevices of cliffs, where mates can be seen preening each other. Though fully grown at six months of age, the young stay with their parents for about three years. In the wild, macaws live between 30 and 40 years, but in captivity some have lived for more than 60. There are about 18 species, some of which are shown here.

Scarlet macaw. Length: 33 inches (85 cm)

Green-winged macaw, also called red-and-green macaw. Length: up to 37 inches (95 cm)

Hyacinth macaw. Length: up to 39 inches (100 cm). The largest of all parrots, it can weigh over three pounds (1.3 kg)

Scientists find surprise lurking in crocodilian jaw

Crocodilians, which include alligators, crocodiles and caimans, live in tropical and temperate regions worldwide and are top predators in watery environments. With a crushing force of more than 16,000 newtons, they have the strongest bite of any animal on Earth, a distinction scientists believe they have likely maintained going back to the Mesozoic era, when their giant ancestors co-existed with the T-rex and other impressive biters. By comparison, the typical human bite involves around 500 newtons of force.

Researchers recently discovered that alligators and related crocodilian species have a previously unknown second jaw joint that helps to distribute the extreme force of their bite, which is the most powerful of any living animal. The finding raises new questions about the evolution of our own meager-by-comparison jaws and could potentially lead to a better understanding of common jaw disorders.

"When we discovered that crocs had built this new jaw joint, it made us re-evaluate how mammals actually evolved our jaw joint and reinterpret what we thought we knew about where parts of our jaw joint came from," said Casey Holliday, Ph.D., assistant professor of anatomy at the University of Missouri, who led the research. "It's one of those awesome 'tapestry of life' stories that's given us a new way of looking at 250 million years of evolution for crocs and also 250 million years of independent evolution toward mammals."

Holliday will present the new findings and other highlights of recent research about crocodilian anatomy at the American Association of Anatomists Annual Meeting during Experimental Biology 2016. He is the recipient of the 2016 American Association of Anatomists Morphological Sciences Award.

Crocodilians, which include alligators, crocodiles and caimans, live in tropical and temperate regions worldwide and are top predators in watery environments. With a crushing force of more than 16,000 newtons, they have the strongest bite of any animal on Earth, a distinction scientists believe they have likely maintained going back to the Mesozoic era, when their giant ancestors co-existed with the T-rex and other impressive biters. By comparison, the typical human bite involves around 500 newtons of force.

"Though they have a reputation as 'living fossils' and indeed have patrolled Earth's waterways for millions of years, they aren't just some holdover or relic from the days of the dinosaurs," said Holliday. "In fact, they have continued to evolve and continue to reveal new features that are surprisingly similar in function to those we find in mammals, birds and other animals. Crocodilians are a treasure trove of adaptations that can help us understand the form, function and evolution of many animals."

The research team made the discovery by using a variety of imaging, computational and 3-D modeling tools to investigate the bones, cartilage, and tissues of the alligator head. It appears the second joint helps to distribute the bite force throughout the skull and stabilizes the jaw to prevent it from twisting during feeding. Mammals have only one jaw joint; birds, lizards, snakes and fishes have multiple flexible joints in their heads, though these joints are not all considered jaw joints.

Because the crocodilians' second jaw joint is similar in structure to the temporomandibular joint in people, Holliday said the findings could have relevance for understanding a group of painful jaw-related conditions known as temporomandibular joint dysfunction, TMD or TMJ. The causes of TMJ, which is estimated to affect up to 30 percent of adults, are not well understood.

Holliday also highlighted his team's other active areas in alligator research. One recent study yielded new insights on a pair of nerves that run down each side of the animal's long snout. A series of small holes along the snout allow the nerves to sense pressure and vibration in the environment, akin to invisible whiskers that help the animal locate prey when hunting at night.

Another promising area is the study of crocodilian cartilage. Holliday said a better understanding of how this cartilage develops and functions could help researchers find new ways to counteract one of the downsides of human anatomy -- our relatively thin layers of cartilage that become worn down over time, creating arthritis.

"Over on the other side of the animal tree, we have this whole stock of successful animals that don't have anything like arthritis -- they have these huge caps of cartilage that they maintain throughout life. Our hope is that there might be some way to bioengineer gator cartilage for research or even clinical applications to help us deal with human cartilage problems like arthritis," said Holliday.