Culture

Scientists discover that human cell function removes extracellular amyloid protein

image: Fluorescence-labelled clusterin-aberrant protein complex (arrow) on cell surface membrane.

Image: 
Eisuke Itakura

The accumulation of aberrant proteins in the body will cause various neurodegenerative diseases. Amyloid β, one of these aberrant proteins, is a known risk factor for Alzheimer's disease. Eisuke Itakura, an assistant professor at Chiba University, says, "Human cells have functions for maintaining homeostasis. Scientists are now actively studying the typical intracellular protein degradation systems by autophagy and proteasome, but our knowledge of how cells act on aberrant external substances is still limited."

The research team led by Itakura gained new knowledge of the functions that human cells have for maintaining homeostasis through experiments in petri dishes. The team discovered a system in which cells could capture, degrade and remove aberrant extracellular proteins. This study will be published February 18th in the Journal of Cell Biology.

In these experiments, the team focused on Clusterin, an extracellular molecular chaperone. By developing an original proprietary cell internalization assay in which cells fluoresce when extracellular Clusterin is taken up, they established a new method for visually observing the state of proteolysis in the body (Fig 1).

Itakura's team found that extracellular Clusterin selectively binds to aberrant proteins and forms a complex. They then observed how cells take up this complex using the fluorescence assay and genome-wide CRISPR screening. The team identified that cells lacking a gene related to the heparan sulfate receptor on the cell surface did not take up the aberrant protein-Clusterin complex. They also demonstrated that cells could take up Clusterin complex with amyloid β via the heparan sulfate receptor and that the complex was degraded in organelle lysosomes.

"Clusterin is a type of molecular chaperone that binds to immature proteins to protect them. If we can artificially develop Clusterin that easily binds to amyloid β and inject it into the body, it could be a treatment for Alzheimer's disease," says Itakura.

The heparan sulfate receptor was previously known to be a viral and growth factor receptor. This is the first time that scientists have demonstrated it to be an abnormal protein receptor. The research group has named this homeostasis system "the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway" and now they are planning to apply it in disease treatment through further research.

Credit: 
Chiba University

Early exposure to household cleaning products is associated with asthma and wheeze in young children

Early exposure of babies to household cleaning products is associated with the development of childhood asthma and wheeze by age 3 years, according to new research in CMAJ (Canadian Medical Association Journal).

"Most of the evidence linking asthma to the use of cleaning products comes from adults," says Professor Tim Takaro, the study's lead researcher and a clinician-scientist in Simon Fraser University's Faculty of Health Sciences (SFU). "Our study looked at infants, who typically spend 80%-90% of their time indoors and are especially vulnerable to chemical exposures through the lungs and skin due to their higher respiration rates and regular contact with household surfaces."

Researchers looked at data from questionnaires completed by parents of 2022 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study who were exposed to cleaning products from birth to age 3-4 months. Participants in the CHILD Cohort Study were recruited from mostly urban centres in 4 provinces: Vancouver, BC; Edmonton, Alberta; Winnipeg, Morden and Winkler, Manitoba; and Toronto, Ontario. The children were then assessed at age 3 years to determine whether they had asthma, recurrent wheeze or atopy (allergic sensitization).

Highlights:

While there appears to be an association between early exposure to cleaning products and risk of asthma and wheeze, there appears to be no association with atopy.

The most common cleaning products used were hand dishwashing soap, dishwasher detergent, multisurface cleaners, glass cleaners and laundry soap.

Scented and sprayed cleaning products were associated with the highest risk of respiratory issues.

The majority of children were white (65%), had not been exposed to tobacco smoke up to age 3-4 months (76%) and did not have a parental history of asthma (65%).

The researchers hypothesize that chemicals in cleaning products may damage the respiratory lining by triggering inflammatory pathways of the immune system, leading to asthma and wheeze. The modulation of the infant's microbiome may also play a role.

Data were collected between 2008 and 2015.

"These findings add to our understanding of how early life exposures are associated with the development of allergic airway disease, and identify household cleaning behaviours as a potential area for intervention," says Jaclyn Parks, lead author and a graduate student in SFU's Faculty of Health Sciences.

Reading labels on cleaning products and choosing those that are not sprayed or contain volatile organic compounds will help minimize a child's exposure and balance the risk associated with using cleaning products in an effort to achieve a mould-free, low-allergen home.

"[S]tudies that identify avoidable factors to inform asthma prevention efforts are of paramount importance," writes Dr. Elissa Abrams, Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, Manitoba and the University of British Columbia, Vancouver, BC, in a linked commentary. "The linked study points to small preventive changes that could be considered, especially among families of children at risk of asthma."

While the American Lung Association recommends against using cleaning products that contain volatile organic compounds, fragrance and other irritants, manufacturers in Canada and the United States are not required to list all ingredients in cleaning products. Some "green" products may contain harmful substances, as these products are not regulated.

Credit: 
Canadian Medical Association Journal

Discovery at 'flower burial' site could unravel mystery of Neanderthal death rites

image: The Neanderthal skull, flattened by thousands of years of sediment and rock fall, in situ in Shanidar Cave, Iraqi Kurdistan.

Image: 
Graeme Barker

 

 

 

The first articulated Neanderthal skeleton to come out of the ground for over 20 years has been unearthed at one of the most important sites of mid-20th century archaeology: Shanidar Cave, in the foothills of Iraqi Kurdistan.

Researchers say the new find offers an unparalleled opportunity to investigate the "mortuary practices" of this lost species using the latest technologies.

Shanidar Cave was excavated in the 1950s, when archaeologist Ralph Solecki uncovered partial remains of ten Neanderthal men, women and children.

Some were clustered together, with clumps of ancient pollen surrounding one of the skeletons. Solecki claimed this showed Neanderthals buried their dead and conducted funerary rites with flowers.

The 'flower burial' captured the public imagination, and prompted a reappraisal of a species that - prior to Shanidar Cave - was thought to have been dumb and animalistic.

It also sparked a decades-long controversy over whether evidence from this extraordinary site did actually point to death rituals, or burial of any kind, and if Neanderthals were really capable of such cultural sophistication.

More than 50 years later, a team of researchers have reopened the old Solecki trench to collect new sediment samples, and discovered the crushed skull and torso bones of another Shanidar Neanderthal.

The discovery has been named Shanidar Z by researchers from Cambridge, Birkbeck and Liverpool John Moores universities.

The work was conducted in conjunction with the Kurdistan General Directorate of Antiquities and the Directorate of Antiquities for Soran Province. The find is announced today in a paper published in the journal Antiquity.

"So much research on how Neanderthals treated their dead has to involve returning to finds from sixty or even a hundred years ago, when archaeological techniques were more limited, and that only ever gets you so far," said Dr Emma Pomeroy, from Cambridge's Department of Archaeology, lead author of the new paper.

"To have primary evidence of such quality from this famous Neanderthal site will allow us to use modern technologies to explore everything from ancient DNA to long-held questions about Neanderthal ways of death, and whether they were similar to our own."

Ralph Solecki died last year aged 101, having never managed to conduct further excavations at his most famous site, despite several attempts.

In 2011, the Kurdish Regional Government approached Professor Graeme Barker from Cambridge's McDonald Institute of Archaeology about revisiting Shanidar Cave. With Solecki's enthusiastic support, initial digging began in 2014, but stopped after two days when ISIS got too close. It resumed the following year.

"We thought with luck we'd be able to find the locations where they had found Neanderthals in the 1950s, to see if we could date the surrounding sediments," said Barker. "We didn't expect to find any Neanderthal bones."

In 2016, in one of the deepest parts of the trench, a rib emerged from the wall, followed by a lumbar vertebra, then the bones of a clenched right hand. However, metres of sediment needed carefully digging out before the team could excavate the skeleton.

During 2018-19 they went on to uncover a complete skull, flattened by thousands of years of sediment, and upper body bones almost to the waist - with the left hand curled under the head like a small cushion.

Early analysis suggests it is over 70,000 years old. While the sex is yet to be determined, the latest Neanderthal discovery has the teeth of a "middle- to older-aged adult".

Shanidar Z has now been brought on loan to the archaeological labs at Cambridge, where it is being conserved and scanned to help build a digital reconstruction, as more layers of silt are removed.

The team is also working on sediment samples from around the new find, looking for signs of climate change in fragments of shell and bone from ancient mice and snails, as well as traces of pollen and charcoal that could offer insight into activities such as cooking and the famous 'flower burial'.

Four of the Neanderthals, including the 'flower burial' and the latest find, formed what researchers describe as a "unique assemblage". It raises the question of whether Neanderthals were returning to the same spot within the cave to inter their dead.

A prominent rock next to the head of Shanidar Z may have been used as a marker for Neanderthals repeatedly depositing their dead, says Pomeroy, although whether time between deaths was weeks, decades or even centuries will be difficult to determine.

"The new excavation suggests that some of these bodies were laid in a channel in the cave floor created by water, which had then been intentionally dug to make it deeper," said Barker. "There is strong early evidence that Shanidar Z was deliberately buried."

CT-scans in Cambridge have revealed the petrous bone - one of the densest in the body; a wedge at the base of the skull - to be intact, offering hope of retrieving ancient Neanderthal DNA from the hot, dry region where "interbreeding" most likely took place as humans spilled out of Africa.

Added Pomeroy: "In recent years we have seen increasing evidence that Neanderthals were more sophisticated than previously thought, from cave markings to use of decorative shells and raptor talons.

"If Neanderthals were using Shanidar cave as a site of memory for the repeated ritual interment of their dead, it would suggest cultural complexity of a high order."

Credit: 
University of Cambridge

Scientists may have a way to let preemies breath easier

image: This image from a study in the journal Immunity shows fluoresced cells in the developing perinatal lung of baby mouse as it forms air sacs called alveolar. The areas highlighted by dotted circles show the molecular components that form Type 3 innate lymphoid cells, which help lungs development a durable immune defense against microbial infections. Not shown is a companion comparison image that shows dysfunctional development in the lung of a premature baby mouse. The illustrations at left diagram normal and premature development of air sacs.

Image: 
Cincinnati Children's

CINCINNATI - The continuing epidemic of pre-term births includes this stark reality: tiny, fragile babies are born with underdeveloped lungs and prone to lifelong respiratory infections and related chronic illnesses.

Cincinnati Children's researchers report in Immunity the discovery of a complex biological processes that in premature lungs stimulates production of Type 3 innate lymphoid cells in air sacs called alveolar. Born without these cells, premature infants' lungs cannot mount an effective immune defense against microbial lung infections. This opens the door to bacterial pneumonia and other severe respiratory illnesses, according study authors at the Cincinnati Children's Perinatal Institute.

"This study gives us important new information that helps us develop new and cost effective methods to boost innate lung immunity in preterm babies. This could help them develop lifelong pulmonary resistance to respiratory infections,'' said Hitesh Deshmukh, MD, PhD, senior study author and a Cincinnati Children's neonatologist.

Deshmukh and his colleagues now plan pre-clinical studies in pre-term laboratory mouse pups to find out if they can harness their newly discovered biogenetic processes to stimulate production of Type 3 innate lymphoid cells in developing lungs. Their theory is that this will promote durable immune defenses in the mouse lungs against infection and tissue damaging inflammation.

A Biological Ballet

The current study reveals a complex interplay between beneficial bacteria in the intestines, the maturation of lung tissues and the growth of immune cells in what the researchers call the gut-lung axis. It happens in neonates during an early and critical development window of the newborn lung, according to their report.

Commensal bacteria from the gut stimulate the production of Type 3 innate lymphoid cells. This occurs in early alveolar cells called fibroblasts when biological cues from the gut stimulate production of a hormone called insulin-like growth factor 1 (IGF1). IGF1 orchestrates expansion and maturation of early pulmonary innate lymphoid cells, the study shows.

When researchers deleted pulmonary IGF1 in the lungs of baby mice, it interrupted the biogenic development of Type 3 innate lymphoid cells and made the mice susceptible to lung infections and pneumonia. They confirmed this by analyzing the underdeveloped lungs of premature mouse pups and donated lung tissues from the families of premature human infants.

The findings have potential clinical implications because premature infants are depleted of helpful gut bacteria by the need for oxygen ventilation to help them breath. This is exacerbated by what Deshmukh called a "double whammy" when the babies have to be administered antibiotics to fight their vulnerability to infection.

The preclinical study on mice to test potential therapies will include administering helpful gut bacteria and pulmonary IGF1 to see if this stimulates to development of a robust immune defense. Deshmukh said therapeutic administration of commensal bacteria and the IGF1 hormone are both being tested clinical in humans for other medical conditions.

Never Ending Challenge

Although medical science and technology continue to advance, premature birth and its complications remain a major challenge as the largest contributors to global infant death, according to the March of Dimes. In 2018, the most recent year statistically available, the preterm birth rate in the United States worsened for the fourth straight year, from 9.63 percent in 2015 to 10.02 percent in 2018.

Bacterial pneumonia kills more than one million infants around the world each year, study authors note.

Prior to the new study in Science Immunity the researchers published previous papers in Nature Medicine and Science Translational Medicine establishing the critical of role of the Gut-Lung Axis molecular interplay and the potentially harmful impact of aggressive antibiotic regimens in premature infants.

Credit: 
Cincinnati Children's Hospital Medical Center

Highly sensitive sensors show promise in enhancing human touch

image: The visually aided tactile enhancement system, VATES, applied for precise motion control. The ultrathin highly sensitive crack-based sensor, signal acquisition circuit and real-time display system are used to realize the induction of tiny deformations. Ultrathin sensors exceed human skin sensitivity and do not disturb the human skin's tactile sensation. A real-time display can be used as a supplement to assist a person's tactile sensation.

Image: 
Rongrong Bao

WASHINGTON, February 18, 2020 -- People rely on a highly tuned sense of touch to manipulate objects, but injuries to the skin and the simple act of wearing gloves can impair this ability. Surgeons, for example, find that gloves decrease their ability to manipulate soft tissues. Astronauts are also hampered by heavy spacesuits and find it difficult to work with equipment while wearing heavy gloves.

In this week's issue of Applied Physics Reviews, by AIP Publishing, scientists report the development of a new tactile-enhancement system based on a highly sensitive sensor. The sensor has remarkable sensitivity, allowing the wearer to detect the light brush of a feather, the touch of a flower petal, water droplets falling on a finger and even a wire too small to be seen.

The crack-based sensor used in this device was inspired by a spider's slit organ, an idea first proposed by other researchers. This pattern of cracks in the exoskeleton allows the spider to detect small movements. In the same way, the ultrathin crack-based strain sensor, or UCSS, uses cracks formed in a thin layer of electrically conductive silver.

The UCSS is fabricated from several layers of flexible polymer film coated with silver. The entire system is draped and stretched over a curved surface, causing the silver to crack, and generating parallel channels that conduct electricity and are sensitive to movement.

The investigators found thinner layers of both the flexible film and the silver yielded sensors with higher sensitivity, while thicker ones exhibited a larger sensing range. To achieve a balance of these two effects, UCSSs with 15-micron thick polymer layers and 37-nanometer thick silver layers were the best choice.

The investigators also designed a visually aided tactile enhancement system, VATES, by connecting one or more UCSSs to a signal acquisition unit and visual readout device. They attached UCSSs to gloves, either on the fingertips or on the back of the hand, producing a type of electronic skin, or e-skin. Tiny movements, as small as a person's pulse moving the tip of a finger, could be monitored.

The investigators suggest UCSSs could be used in a variety of ways: as highly sensitive electronic whiskers, which can be used to map wind flow patterns; as wearable sensors for heartbeat and pulse detection; or as sensors on prosthetics to enhance the sense of touch.

They also demonstrated their use when applied to various parts of the body. UCSSs were able to detect movement due to smiling, frowning and eye blinking.

Co-author Caofeng Pan said, "These results demonstrate the wide applications of our ultrathin strain sensor in e-skin and human-machine interfaces."

Credit: 
American Institute of Physics

GI societies issue updated colorectal cancer screening recommendations

Bethesda, Maryland (Feb. 18, 2020) - Patients at average risk of colorectal cancer who have a normal colonoscopy do not need to repeat screening for 10 years. It is common for polyps to be removed and tested during a colonoscopy, but the amount and size of polyps removed will change the patient's follow-up screening schedule. In two new publications from the U.S. Multisociety Task Force (MSTF) on Colorectal Cancer, experts provide a timeline for patients to be rechecked for colorectal cancer based on their initial colonoscopy as well as recommendations for physicians to apply the safest and most effective techniques to completely remove polyps.

Colorectal cancer, the second leading cause of cancer death in the U.S., is preventable when precancerous polyps are found and removed before they turn into cancer. Screening for average-risk patients is recommended to begin at age 50. The recommendation documents from the U.S. Multisociety Task Force -- which is comprised of representatives of the American College of Gastroenterology, the American Gastroenterological Association and the American Society for Gastrointestinal Endoscopy -- aim to improve colorectal cancer prevention and early detection.

Recommendations for Follow-Up After Colonoscopy and Polypectomy1

For this publication, the U.S. MSTF reviewed their 2012 recommendations2 and provide an updated schedule for follow-up colonoscopy following a patient's initial high-quality exam:

Patient has no polyps: Next colonoscopy in 10 years

Patient has 1?2 polyps

Patient has 3-4 polyps

Patient has more than 10 polyps: Next colonoscopy in 1 year (instead of 3 years)

Patient has serrated polyps: Review the document for complete recommendations

Patient has advanced polyps: Next colonoscopy in 3 years

To review all MSTF recommendations for patient follow-up, review the full publication. https://www.gastrojournal.org/article/S0016-5085(19)41479-0/fulltext

Recommendations for Endoscopic Removal of Colorectal Lesions3

In this publication, the U.S. MSTF provides best practices for the endoscopic removal of precancerous colorectal polyps during colonoscopy, which is called a polypectomy.

Best practices for polyp assessment and description

MSTF recommends macroscopic characterization of a polyp, which provides information to facilitate the polyp's histologic prediction, and optimal removal strategy.

Best practices for polyp removal

The primary aim of polypectomy is complete removal of the colorectal lesion, and the subsequent prevention of colorectal cancer. Overall, the vast majority of benign colorectal lesions can be safely and effectively removed using endoscopic removal techniques. When an endoscopist encounters a suspected benign colorectal polyp that he/she is not confident to completely remove, MSTF recommends referral to an endoscopist experienced in advanced polypectomy for subsequent evaluation and management in lieu of referral for surgery.

Patient has diminutive (? 5mm) and small (6-9mm) polyp(s): Recommend cold snare polypectomy

Patient has non-pedunculated (? 20mm) polyp(s): Recommend endoscopic mucosal resection; Recommend snare resection of all grossly visible tissue of a polyp in a single colonoscopy session and in the safest minimum number of pieces; Recommend against the use of ablative techniques on endoscopically visible residual tissue of a polyp; Recommend the use of adjuvant thermal ablation of the post-EMR margin where no endoscopically visible adenoma remains despite meticulous inspection

Patient has pedunculated polyp(s): Recommend prophylactic mechanical ligation of the stalk with a detachable loop or clips on pedunculated polyps with head ?20mm or with stalk thickness ?5mm to reduce immediate and delayed post-polypectomy bleeding

Best practices for surveillance

MSTF recommends intensive follow-up schedule in patients following piecemeal endoscopic mucosal resection (lesions ? 20 mm) with the first surveillance colonoscopy at 6 months, and the intervals to the next colonoscopy at 1 year, and then 3 years.

Credit: 
American Gastroenterological Association

Cyber researchers at Ben-Gurion University fool autonomous vehicle systems with phantom images

image: In the Ben-Gurion University of the Negev Research Telsa considers the phantom image (left) as a real person and (right) Mobileye 630 PRO autonomous vehicle system considers the image projected on a tree as a real road sign.

Image: 
Cyber@bgu

BEER-SHEVA, ISRAEL...February 18, 2020 - Researchers from Ben-Gurion University of the Negev's (BGU) Cyber Security Research Center have found that they can cause the autopilot on an autonomous vehicle to erroneously apply its brakes in response to "phantom" images projected on a road or billboard.

In a new research paper, "Phantom of the ADAS," published on IACR.org, the researchers demonstrated that autopilots and advanced driving-assistance systems (ADASs) in semi-autonomous or fully autonomous cars register depthless projections of objects (phantoms) as real objects. They show how attackers can exploit this perceptual challenge to manipulate the vehicle and potentially harm the driver or passengers without any special expertise by using a commercial drone and inexpensive image projector.

While fully and semi-autonomous cars are already being deployed around the world, vehicular communication systems that connect the car with other cars, pedestrians and surrounding infrastructure are lagging. According to the researchers, the lack of such systems creates a "validation gap," which prevents the autonomous vehicles from validating their virtual perception with a third party, relying only on internal sensors.

In addition to causing the autopilot to apply brakes, the researchers demonstrated they can fool the ADAS into believing phantom traffic signs are real, when projected for 125 milliseconds in advertisements on digital billboards. Lastly, they showed how fake lane markers projected on a road by a projector-equipped drone will guide the autopilot into the opposite lane and potentially oncoming traffic. Click here for video

"This type of attack is currently not being taken into consideration by the automobile industry. These are not bugs or poor coding errors but fundamental flaws in object detectors that are not trained to distinguish between real and fake objects and use feature matching to detect visual objects," says Ben Nassi, lead author and a Ph.D. student of Prof. Yuval Elovici in BGU's Department of Software and Information Systems Engineering and Cyber Security Research Center.

In reality, depthless objects projected on a road are considered real even though the depth sensors can differentiate between 2D and 3D. The BGU researchers believe that this is the result of a "better safe than sorry" policy that causes the car to consider a visual 2D object real.

The researchers are developing a neural network model that analyzes a detected object's context, surface and reflected light, which is capable of detecting phantoms with high accuracy.

Credit: 
American Associates, Ben-Gurion University of the Negev

Exposure to cleaning products in first 3 months of life increases risk of childhood asthma

image: Jaclyn Parks a graduate student in the Faculty of Health Sciences at SFU and lead author.

Image: 
Simon Fraser University

New research from the CHILD Cohort Study shows that frequent exposure to common household cleaning products can increase a child's risk of developing asthma.

Asthma is the most common chronic childhood disease and is the primary reason why children miss school or end up in hospital.

The study was published today in the Canadian Medical Association Journal. It found that young infants (birth to three months) living in homes where household cleaning products were used frequently were more likely to develop childhood wheeze and asthma by three years of age.

"Most of the available evidence linking asthma to the use of cleaning products comes from research in adults," said the study's lead researcher, Dr. Tim Takaro, a professor and clinician- scientist in the Faculty of Health Sciences at Simon Fraser University (SFU). "Our study looked at infants, who typically spend 80-90% of their time indoors and are especially vulnerable to chemical exposures through the lungs and skin due to their higher respiration rates and regular contact with household surfaces."

In the study, at three years of age, children living in homes where cleaning products were used with high frequency during their infancy were more likely to have:

Recurrent wheeze (10.8 percent, compared to 7.7 percent of infants in homes with low use of these products)

Recurrent wheeze with atopy, a heightened immune response to common allergens (3.0 percent, compared to 1.5 percent of infants in homes with low use of these products)

Asthma (7.9 percent, compared to 4.8 percent of infants in homes with low use of these products)

Other factors known to affect the onset of asthma, such as family history and early life exposure to tobacco smoke, were accounted for in the analysis.

"Interestingly, we did not find an association between the use of cleaning products and a risk of atopy alone," noted Dr. Takaro. "Therefore, a proposed mechanism underlying these findings is that chemicals in cleaning products damage the cells that line the respiratory tract through innate inflammatory pathways rather than acquired allergic pathways."

"We also found that at age three, the relationship between product exposure and respiratory problems was much stronger in girls than boys," he added. "This is an interesting finding that requires more research to better understand male versus female biological responses to inflammatory exposures in early life."

The study used data from 2,022 children participating in the CHILD Cohort Study and examined their daily, weekly and monthly exposure to 26 types of household cleaners, including dishwashing and laundry detergents, cleaners, disinfectants, polishes, and air fresheners.

"The risks of recurrent wheeze and asthma were notably higher in homes with frequent use of certain products, such as liquid or solid air fresheners, plug-in deodorizers, dusting sprays, antimicrobial hand sanitizers and oven cleaners," commented the paper's lead author, Jaclyn Parks, a graduate student in the Faculty of Health Sciences at SFU. "It may be important for people to consider removing scented spray cleaning products from their cleaning routine. We believe that the smell of a healthy home is no smell at all."

"The big takeaway from this study is that the first few months of life are critical for the development of a baby's immune and respiratory systems," concluded Parks. "By identifying hazardous exposures during infancy, preventive measures can be taken to potentially reduce childhood asthma and subsequent allergy risk."

Credit: 
Simon Fraser University

USask study reveals origin of endangered Colombian poison frog hybrids

image: Andres Posso-Terranova and team are probing evolutionary secrets of Colombian poison frogs.

Image: 
Jose Andres

The origin of an understudied hybrid population of poisonous frogs--highly endangered colorful animals that live deep in the Colombian jungle--is the result of natural breeding and not caused by wildlife traffickers moving them, a University of Saskatchewan (USask) study shows.

"We found that these unique hybrid frogs appeared more than 20 years ago--before they became the target of illegal trafficking--and live only in a small patch of jungle," said USask biology researcher Andrés Posso-Terranova. "Our study will help the Colombian government understand what these frogs are and why they need to be saved and preserved."

The study, recently published in the journal Molecular Ecology, shows that the hybrid frogs are interbreeding between two known "pure" species--Oophaga anchicayensis and the critically endangered Oophaga lehmanni. The USask findings indicate that the hybrids do not pose a genetic threat to the other frog species but rather co-exist healthily with the "parent" populations.

"These hybrid frogs aren't a threat to the other two species, but benefit the ecosystem as a healthy addition to the genetic diversity of the tropical rainforest," said Posso-Terranova. "Genetic variation usually ensures stronger, more disease-resistant populations, both animals and plants. That's why it's important to preserve these frogs."

Poison frogs are highly sought on the international black market and collectors love them for their amazing variation in colors and patterns. Each frog is worth up to $2,000, which prompts local impoverished people to sell them to traffickers. But the Colombian government is campaigning with locals to offer alternative income sources that could stop the trafficking.

The bright colors of the frogs provide a warning cue to predators that they are poisonous, a feature that comes from a diet of toxic bugs. The frogs' color patterns also indicate where the species originate because they change depending upon the area of the Chocó jungle in which the frogs live. The hybrids of the USask study show distinct color patterns that mix those of both the "parent" species.

Noticing the uniqueness of these frogs, the researchers photographed and took tissue samples of more than 170 frogs to classify them. Back at USask, they used state-of-art genetic tools to study the frogs' genome--up to three times larger than the human one--showing that the gene flow between the hybrid and the other two groups of frogs is limited. This means they all keep living along with one another.

Posso-Terranova said that this is not a case where the hybrids start breeding with the "parent" species, eventually making them disappear. The hybrids are instead the outcome of a natural breeding process.

The researchers found that one species lived at a higher altitude than the other, and probably they eventually expanded and started mixing with each other.

"If traffickers had moved some of the frogs from a different part of the jungle, the genetic results would show that the breeding was recent, but our findings indicate that this has happened for longer than one or two generations," said Posso-Terranova.

Clarifying that the process has happened naturally is important for the conservation of these frogs, because policies tend to preserve pure species over the hybrids when humans are the cause of the hybridization.

"Our research confirms that all three frog groups need to be equally protected," said former USask post-doctoral fellow Jana Ebersbach, first author of the paper.

Credit: 
University of Saskatchewan

Creating custom light using 2D materials

image: Artistic view of a junction of different 2D light-emitting materials.

Image: 
© Xavier Ravinet

Finding new semi-conductor materials that emit light is essential for developing a wide range of electronic devices. But making artificial structures that emit light tailored to our specific needs is an even more attractive proposition. However, light emission in a semi-conductor only occurs when certain conditions are met. Today, researchers from the University of Geneva (UNIGE), Switzerland, in collaboration with the University of Manchester, have discovered an entire class of two-dimensional materials that are the thickness of one or a few atoms. When combined together, these atomically thin crystals are capable of forming structures that emit customisable light in the desired colour. This research, published in the journal Nature Materials, marks an important step towards the future industrialisation of two-dimensional materials.

Semi-conductor materials capable of emitting light are used in sectors as diverse as telecommunications, light emitting devices (LEDs) and medical diagnostics. Light emission occurs when an electron jumps inside the semi-conductor from a higher energy level to a lower level. It is the difference in energy that determines the colour of the emitted light. For light to be produced, the velocity of the electron before and after the jump must be exactly the same, a condition that depends on the specific semiconducting material considered. Only some semi-conductors can be used for light emission: for example, silicon - used to make our computers - cannot be employed for manufacturing LEDs.

"We asked ourselves whether two-dimensional materials could be used to make structures that emit light with the desired colour", explains Alberto Morpurgo, a professor in the Department of Quantum Matter Physics, at the UNIGE Faculty of Science. Two-dimensional materials are perfect crystals which, like graphene, are one or a few atoms thick. Thanks to recent technical advances, different two-dimensional materials can be stacked on top of each other to form artificial structures that behave like semi-conductors. The advantage of these "artificial semi-conductors" is that the energy levels can be controlled by selecting the chemical composition and thickness of the materials that make up the structure.

"Artificial semi-conductors of this kind were made for the first time only two or three years ago", explains Nicolas Ubrig, a researcher in the team led by professor Morpurgo. "When the two-dimensional materials have exactly the same structure and their crystals are perfectly aligned, this type of artificial semi-conductor can emit light. But it's very rare." These conditions are so strict that they leave little freedom to control the light emitted.

Custom light

"Our objective was to manage to combine different two-dimensional materials to emit light while being free from all constraints", continues professor Morpurgo. The physicists thought that, if they could find a class of materials where the velocity of the electrons before and after the change in energy level was zero, it would be an ideal scenario which would always meet the conditions for light emission, regardless of the details of the crystal lattices and their relative orientation.

A large number of known two-dimensional semi-conductors have a zero-electron velocity in the relevant energy levels. Thanks to this diversity of compounds, many different materials can be combined, and each combination is a new artificial semi-conductor emitting light of a specific colour. "Once we had the idea, it was easy to find the materials to use to implement it", adds professor Vladimir Fal'ko from the University of Manchester. Materials that were used in the research included various transition metal dichalcogenides (such as MoS2, MoSe2 and WS2) and InSe. Other possible materials have been identified and will be useful for widening the range of colours of the light emitted by these new artificial semi-conductors.

Tailor-made light for mass industrialisation

"The great advantage of these 2D materials, thanks to the fact that there are no more preconditions for the emission of light, is that they provide new strategies for manipulating the light as we see fit, with the energy and colour that we want to have", continues Ubrig. This means it is possible to devise future applications on an industrial level, since the emitted light is robust and there is no longer any need to worry about the alignment of atoms.

The collaboration between UNIGE and the University of Manchester took place within the framework of the EU Graphene Flagship Project.

Credit: 
Université de Genève

Getting a grip: An innovative mechanical controller design for robot-assisted surgery

image: A new controller design for robot-assisted surgery.

Image: 
Tokyo Institute of Technology

Scientists at Tokyo Institute of Technology designed a new type of controller for the robotic arm used in robotic surgery. Their controller combines the two distinct types of gripping used in commercially available robotic systems to leverage the advantages of both, reducing the efforts of the surgeon and providing good precision.

Robotics has weaved its way into many different fields, and medicine is no exception; robot-assisted surgery has advanced dramatically over the past decade in almost every surgical subspecialty. Robot-assisted surgery is usually performed using surgical robot systems that involve a master-slave configuration, in which the "master" is a controller device that the surgeon manipulates to control a robotic arm. Such systems improve the dexterity and precision of surgeons by filtering out hand tremors and scaling their hand motions into smaller movements. They also reduce the risk of common surgical complications such as surgical site infection.

However, robot-assisted surgery comes with its own disadvantages, especially for the person performing the surgery. Robotic surgeons sometimes feel physical discomfort during surgery, with finger fatigue being common. This discomfort is associated with the way in which they grip the master controller. Two types of grips are usually used to control surgical robots: the "pinch grip" and "power grip." The pinch grip has been used in conventional surgeries for centuries; it involves using the thumb, middle, and index fingers to achieve high-precision movements. On the other hand, the power grip involves grabbing a handle with the entire hand and is more suitable for forceful work and large movements.

Because the pinch grip puts tension on certain muscles of the hand and fingers, it is more likely to cause fatigue. And although the power grip does not seem to cause such discomfort, it offers less precise control. Therefore, there is a trade-off between the discomfort caused by the pinch grip and the lack of fine control of the power grip. Fortunately, Mr. Solmon Jeong and Dr. Kotaro Tadano, a pair of researchers from Tokyo Institute of Technology (Tokyo Tech), found a clever solution to this problem. In a study published in The International Journal of Medical Robotics and Computer Assisted Surgery , the researchers speculated that a master controller that combines both types of gripping can be designed. Dr. Tadano explains, "In robotic surgery, the limitations of the two conventional gripping methods are strongly related to the advantages and disadvantages of each gripping type. Thus, we wanted to investigate whether a combined gripping method can improve the manipulation performance during robotic surgery, as this can leverage the advantages of both gripping types while compensating for their disadvantages."

After a proof-of-concept experiment that yielded promising results, the researchers designed a robotic surgery system with a modular master controller that could be adjusted to employ either pinch, power, or combined gripping. The system was tested through a pointing experiment, in which 15 participants had to control a robotic arm to bring the tip of a needle into target holes in the least amount of time without touching obstacles. Various conditions were tested for each gripping type, such as the use of arm and palm rests, use of handle, gripping type, and pinch grip motion. The findings showed that the combined grip yielded better performance in the pointing experiment on various fronts, including number of failures (touching an obstacle), time required, and overall length of the movements performed to reach the targets. Many participants also reported to prefer the combined gripping method over the other two, owing to the ease and comfort in using this method.

This new master controller design could be a step in the right direction in robot-assisted surgery. "The manipulating method of master controllers for robotic surgery has a significant influence in terms of intuitiveness, comfort, precision, and stability. In addition to enabling precise operation, a comfortable manipulating method could potentially benefit both the patient and the surgeon," remarks Dr. Tadano. Although future work is needed to analyze other variables involved in robotic arm manipulation, this work surely paves the way for advanced surgical robot systems.

Credit: 
Tokyo Institute of Technology

How language proficiency correlates with cognitive skills

An international team of researchers carried out an experiment at HSE University demonstrating that knowledge of several languages can improve the performance of the human brain. In their study, they registered a correlation between participants' cognitive control and their proficiency in a second language.

It is widely believed that bilinguals and multilinguals are better equipped to deal with multiple tasks and that they have a better attention than those who speak only one language. This would seem reasonable: bilinguals and multilinguals have to constantly switch their attention between languages they speak, and alternate between words and grammar structures that are quite different from one another. As a result, their cognitive control function -- action-monitoring and decision-making systems -- works more efficiently than that of monolinguals.

Meanwhile, the scientific evidence regarding this phenomenon is rather controversial, as not all of the findings demonstrating this "bilingual advantage" effect have been replicated. According to Nikolay Novitskiy, the paper's first author, one study comparing bilingual children from the Basque Country with Spanish monolingual children found little evidence for the bilingual advantage effect. Similarly, this effect has not been observed in another study comparing the cognitive abilities of senior speakers in the region, while earlier studies had demonstrated the opposite.

Several researchers maintain that the bilingual advantage has only been seen in a subset of studies, which used limited participant samples and did not rigorously control for a variety of variables including the participants' socio-economic status (SES). In other words, the reported findings may reflect imbalances in the selection of participants rather than a genuine bilingual advantage effect as bilinguals are often recruited from immigrant or ethnic minority populations whose SES may often be quite different from that of the monolingual population. When group studies use participants widely varying in their education level, income, and other factors, the observed differences in their cognitive abilities may reflect these and other uncontrolled variables rather than their language skills.

'Imbalanced parameters in group experiments is a common problem in behavioral studies,' said Yury Shtyrov, Professor at Aarhus University and an invited leading scientist at the HSE Institute of Cognitive Neuroscience. He also notes: 'It is virtually impossible to control all potentially relevant parameters in a group design, and many factors including social ones may influence the results of individual studies.'

In order to avoid the problem of respondents' heterogeneity, the team's study analyzed the effect of bilingualism on executive control in a homogeneous group of participants. The authors selected 50 unbalanced bilinguals for their study, all HSE University students, who did not speak their second language (English) from early childhood (unlike balanced bilinguals), but started learning it later -- during their school years.

As a result, the participants' proficiency in English varied, and the researchers suggested that the relative level of proficiency in second language might correlate with an individual's cognitive control efficiency.

In order to test this hypothesis, they measured the students' English proficiency and also asked them to perform on a cognitive control task. 'Our working hypothesis was that a higher second language proficiency would correlate with how often participants have to use it,' said Andriy Myachykov, Associate Professor at Northumbria University and a leading research fellow at the HSE Centre for Cognition & Decision Making, adding: 'Therefore, the more often they must switch their attention between their mother tongue, Russian, and the second language, English, the stronger bilingual advantage effect on their cognitive control efficiency we should find.'

Cognitive control efficiency was tested with the help of the so-called Attention Network Test, which measures the efficiency of an individual's attention by comparing response times in conditions requiring different degree of focusing and switching attention from one stimulus to another. As such, the task measures the efficiency of main 'attention networks': alertness (readiness for the stimulus), orientation (directing attention to the stimulus), and executive control (switching attention from one stimulus to another).

The results of the study demonstrated a correlation between the performance on the attention network test and language proficiency: The better the students knew the second language, the better they could perform on the executive control task.

First, this study demonstrates that an approach taking into account relative levels of the respondents' second language skills rather than a group design may help researchers better understand a complex interplay between language and cognition at the level of individual speakers. Second, the study used an objective method (translation task) in order to evaluate second language proficiency while many other studies are based largely on subjective language proficiency self-evaluation and associated measures, such as the nominal length of learning a second language.

Credit: 
National Research University Higher School of Economics

Smart contact lens sensor developed for point-of-care eye health monitoring

image: This is a schematic illustration and images of the 'smart' contact lens for point-of-care eye health monitoring

Image: 
DU Xuemin

A research group led by Prof. DU Xuemin from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences has developed a "smart" contact lens that can show real-time changes in moisture and pressure by altering colors. The "smart" contact lens can potentially be used for point-of-care (POC) diagnosis of xerophthalmia and high intraocular pressure disease.

Early diagnosis is important for avoiding severe eye problems, such as exophthalmia - which causes relatively mild symptoms - or glaucoma - which may lead to loss of vision. Such diagnoses rely on facile and reliable monitoring of several features with significant pathologic relevance, such as the amount of tears and intraocular pressure.

However, current methods usually require complex procedures and instruments operated by professionals, causing difficulties for point-of-care (POC) ophthalmic health monitoring.

The "smart" contact lens features periodic nanostructures within the poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel matrix, resulting in bright, tunable structural colors ranging from red to green to blue.

This structurally colored contact lens sensor is made solely from a biocompatible hydrogel, without the addition of any chemical pigments, thus exhibiting superior biosafety and comfort for wearable applications.

Importantly, the spacing of periodic nanostructures within the pHEMA hydrogel are sensitive to changes in moisture and pressure, leading to real-time color changes in the "smart" contact lens.

"Based on these features, the 'smart' contact lens was explored as a means for monitoring xerophthalmia and high intraocular pressure disease. In normal eye-simulation conditions, its color will not change over time; while its color changes from red to blue in the xerophthalmia-simulation condition in about 25 minutes," said ZHAO Qilong, first author of the study.

Additionally, a linear decrease in the wavelength of the reflectance peak of the "smart" cosmetic contact lens is observed when human intraocular pressure changes in the pathological range.

"This study provides a novel and smart wearable device for timely and facile warning of the risks of xerophthalmia and high intraocular pressure disease. It will also inspire the design of a new generation of wearable devices with colorimetric sensing capabilities for real-time POC monitoring of various human body signs and diseases," said Prof. DU.

Credit: 
Chinese Academy of Sciences Headquarters

Trust your gut on plant-based diets for heart health

Reducing animal product intake and following a primarily plant-based diet can decrease your risk of heart disease by minimizing the adverse effects of a gut-microbiome associated with increased risk of coronary heart disease, according to research published today in the Journal of the American College of Cardiology.

The body's gut microbiota is comprised of a series of microbes that play an important role in our metabolism, nutrient absorption, energy levels and immune response. A gut-microbiota related metabolite known as trimethylamine N-oxide (TMAO) is produced when gut bacteria digests nutrients commonly found in animal products such as red meat. It has been connected to increased heart attack and coronary heart disease (CHD) risk. Maintaining a vegan or vegetarian diet has been found to reduce the amount of TMAO produced in the body.

The study authors examined 760 women in the Nurses' Health Study, a prospective cohort study of 121,701 female registered nurses aged 30 to 55 years old. Women were asked to report data on dietary patterns, smoking habit and physical activity, plus other demographic data and provide two blood samples taken at Cleveland Clinic, 10 years apart. The researchers measured plasma concentrations of TMAO from the first collection to the second blood collection. After adjusting for participants with available plasma TMAO levels at both collections, there were 380 cases of CHD and 380 demographically matched-control participants without CHD chosen by the researchers included in the analysis.

The risk of CHD was calculated by changes in TMAO levels in the body throughout the follow-up period. Assessing TMAO levels relies on diet and nutrient intake; the researchers investigated how diet quality modifies the association between TMAO and CHD. Women who developed CHD had higher concentrations of TMAO levels, higher BMI, family history of heart attack and did not follow a healthy diet including higher intake of vegetables and lower intake of animal products. Women with the largest increases in TMAO levels across the study had a 67% higher risk of CHD.

"Diet is one of the most important modifiable risk factors to control TMAO levels in the body," said Lu Qi, MD, director of the Tulane University Obesity Research Center and the study's senior author. "No previous prospective cohort study has addressed whether long-term changes in TMAO are associated with CHD, and whether dietary intakes can modify these associations. Our findings show that decreasing TMAO levels may contribute to reducing the risk of CHD, and suggest that gut-microbiomes may be new areas to explore in heart disease prevention."

The study authors found no differences in TMAO levels between the CHD and control participants at the first blood sample collection. TMAO levels examined in the second blood sample collection taken 10 years later were significantly higher the participants with CHD. Every increase in TMAO was associated with a 23% increase in CHD risk. This association remained after controlling for demographic, diet and lifestyle factors, confirming the link between higher TMAO levels and CHD risk.

"The findings of the study provide further evidence for the role of TMAO as a predictive biomarker for heart disease and strengthens the case for TMAO as a potential intervention target in heart disease prevention," said Paul A. Heidenreich, MD, MS, professor of medicine at the Stanford University School of Medicine, in an accompanying editorial comment. "The results should encourage us to continue to advocate for a more widespread adoption of healthy eating patterns."

Credit: 
American College of Cardiology

Atomic structures mapped in measles, mumps, flu and RSV

image: The atomic structure of a polymerase in human parainfluenza virus 5 reveals an irregular, round-shaped globule with a long tail made of four phosphoproteins. The structure contains more than 2,000 amino acids and five proteins.

Image: 
Northwestern University

First study to map atomic structure of a key enzyme complex in paramyxoviruses, a family of RNA viruses

Enzyme is responsible for assembling RNA molecules, providing a target for new antiviral drugs

Although from a different family, coronavirus functions similarly

Researchers used cryo-EM, a revolutionary technique that gives a clear view of proteins

EVANSTON, Ill. -- Northwestern University researchers have, for the first time, determined the 3D atomic structure of a key complex in paramyxoviruses, a family of viruses that includes measles, mumps, human parainfluenza and respiratory syncytial virus (RSV).

This information could help others design and develop antiviral drugs for these viruses as well as for coronavirus, which functions similarly to paramyxoviruses.

"This takes some of the guesswork out of designing drugs," said Northwestern's Robert Lamb, who co-led the study. "Traditionally, you have to develop drugs randomly and hope you hit a target, but it doesn't happen very often."

To find the unique structure, researchers used cryogenic electron microscopy (cryo-EM). The relatively new technique enables researchers to peer inside molecules to determine the 3D shape of proteins, which are often thousands of times smaller than the width of a human hair. Before cryo-EM, researchers mainly used X-ray crystallography, which is incapable of capturing high-resolution images of this enzyme. Called a polymerase, the enzyme assembles RNA molecules.

"Crystallography only works for very orderly and organized proteins," said Northwestern's Yuan He, who co-led the study. "Virus polymerase complexes are too big to be crystallized and don't have uniformity."

The study will be published on Feb. 17 in the Proceedings of the National Academy of Sciences.

Lamb is the Kenneth F. Burgess Professor of Molecular Biosciences in Northwestern's Weinberg College of Arts and Sciences and an investigator of the Howard Hughes Medical Institute. Yuan He is an assistant professor of molecular biosciences in Weinberg.

Although the first documented case of mumps occurred in the 5th century and measles in the 9th century, researchers did not have the equipment to characterize their atomic structures until relatively recently. A trio of biophysicists received the 2017 Nobel Prize in Chemistry for developing cryo-EM, which ultimately opened the door for Lamb and He.

Cryo-EM works by blasting a stream of electrons at a flash-frozen sample to take many 2D images. For this study, He and his team captured hundreds of thousands of images of one sample of human parainfluenza virus 5 polymerase. The team then used computational algorithms to reconstruct a 3D image.

The resulting image was an irregular, round-shaped globule with a long tail made of four phosphoproteins (or proteins containing phosphorous). The structure contains more than 2,000 amino acids and five proteins.

"Part of the image was expected," Lamb said. "But part of it was a surprise. Two of the proteins are completely new. They have never been seen before."

Another surprise: the team found that this virus uses the same protein to switch between genome replication and transcription.

"This machinery has a dual-function," He said. "It gets both jobs done with one enzyme. The virus's genome is so small, and this gives it economy of scale."

Lamb and He hope this work can help others design and develop new drugs for illnesses such as measles and mumps, which have experienced outbreaks in past years.

"A lot of people don't want to get vaccinated, and they're getting the disease," Lamb said. "And for people who are vaccinated, it still takes three to four weeks for that vaccine to take effect. We need more antiviral drugs so people who get infected can be treated immediately."

Credit: 
Northwestern University