At a time when the incidence and social costs of dementia and Alzheimer’s disease in particular continue to rise, this breakthrough is very timely as it could enable the detection of the disease much earlier than current approaches. The findings are also important for the testing of therapies against this devastating disease.

Alzheimer’s disease is characterized by two pathological changes in brain tissue. One is a protein called tau while the other involves the amyloid beta peptide. Both can form clumps of aggregates that progressively accumulate in specific areas of the brain. For tau, individual units of the protein can aggregate into finely-ordered fibrillar structures facilitated by a biochemical process called phosphorylation. Throughout the disease process, amyloid beta and phosphorylated tau (p-tau) are released from the brain into cerebrospinal fluid; the amount of the released proteins are used as reliable surrogate markers for clinical diagnoses of Alzheimer’s disease.

Normally, amyloid beta levels in cerebrospinal fluid become abnormal several years before p-tau. The current clinical tests for p-tau become abnormal when memory failings develop. This makes it difficult to identify people with the disease at the very early stages before it is too late. How can we, therefore, reliably detect these sub-threshold disease changes?

To address these challenges, the scientists discovered that there are specific forms of p-tau that undergo very minute increases in cerebrospinal fluid and blood in people with emerging Alzheimer pathology. Consequently, the researchers developed highly sensitive techniques to measure these biological markers that precede clinical signs by several years.

In the first study, conducted in the Alfa parent cohort study at the Barcelona Beta Research Centre (BBRC), with the support of “la Caixa” Foundation, about a third of the 381 people evaluated had brain evidence of Alzheimer pathology but without any cognitive problems, meaning that these changes could not be detected in the clinic by memory assessments. Remarkably, the new p-tau markers correctly identified these emerging abnormalities measured in cerebrospinal fluid and regular blood samples.

Subsequent studies performed in Gothenburg, Paris and Ljubljana revealed that these new markers continue to increase from the preclinical stage through the onset of cognitive problems to the late dementia stages. For this reason, progressive increases in p-tau could provide insights into the biological and clinical development of Alzheimer’s disease. The studies are now published in the leading journals EMBO Molecular Medicine and Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Kaj Blennow, professor of neurochemistry at the University of Gothenburg, who directed the work said “A possible way to improve the chances of future therapies is to test them on people in the very early stages of the disease with elusive biological changes but lacking clinical symptoms including memory failings. Candidate drug trials have not been too successful.” He added that: “The practical challenge, however, is that these very tiny initial changes are incredibly difficult to measure reliably. This compromises our chances to identify and recruit preclinical AD patients for clinical trials.”

Dr. Thomas Karikari, an assistant professor at the University of Gothenburg, who co-led the discovery commented: “The remarkable findings reported in these publications show that the new highly sensitive tools capture the earliest Alzheimer disease changes in the brain in clinically normal people. These tools therefore have the potential to advance population screening and clinical trials.”

According to Dr. Marc Suárez-Calvet, neurologist and ERC researcher at BBRC, “the biomarker detected in blood may change clinical practice in the coming years, since it will improve the diagnosis of patients with Alzheimer’s disease, both in its asymptomatic and symptomatic phases.”

Story Source:

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

A new study — published today [Wednesday 2 December 2020] in the international journal Pain from researchers at the universities of Bath (UK) and Calgary (Canada) — analysed how characters’ experiences of pain were depicted across different media aimed at 4 to 6-year olds.

The team behind the research were interested in assessing what painful incidents characters were subject to, as well as how they and others around them responded.

Their analysis looked at 10 family movies from 2009 onwards (Despicable Me 2, The Secret Life of Pets, Toy Story 3 & 4, Incredibles 2, Inside Out, Up, Zootopia, Frozen and Finding Dory), as well as popular kids’ TV programmes (Sofia the First, Shimmer and Shine, Paw Patrol, Octonauts, Peppa Pig, Daniel Tiger’s Neighbourhood).

These programmes were chosen to represent either girl-focused, boy-focused or gender-neutral TV series (dependent on the key characters).

Over the 10 movies and six TV series (which equated to over 52 hours of film / TV), the researchers identified:

• 454 painful incidents — a mean of 8.66 incidents of pain per hour.
• Violent pain or injury being the most common type of pain depicted (occurring in over two-thirds of instances — 79%).
• Boy characters much more likely to experience severe pain in comparison with girl characters (according to facial expressions).
• Examples of everyday pain (i.e. a character falling over or bumping their knee), being much less common, represented in only 20% of incidents.
• A general lack of empathy from other characters in responding to pain: 75% of painful instances were seen by others, yet in 41% of cases those witnessing it did not respond or where they did they were generally not empathetic.

Researchers say this work matters because what children watch on TV shapes and models their behaviours. They want producers to use their influence to re-think how pain is portrayed in order to better equip young people to cope with common, everyday pain which they are more likely to experience but is often forgotten and misunderstood. Indeed, how children’s pain is often sidelined was a topic highlighted in a recent and significant Lancet Commission report, also authored by pain researchers from the University of Bath.

Dr Abbie Jordan of the Department of Psychology and Centre for Pain Research at the University of Bath explained: “How children experience, model, understand and manage pain has real lasting consequences for them as individuals but also for all of us across wider society. Pain, in particular chronic pain, can have hugely debilitating effects on the lives of children and young people right through into adulthood.

“Part of the challenge in this is how we talk about pain. We know children spend increasing amounts of time watching these influential programmes and films and that what they depict feeds through to their understanding and awareness of an issue. When it comes to pain, as we see from this study, the picture presented by these media is not reflective of children’s common experiences, instead focusing much more on extreme and violent pain.

“Our assessment is that these programmes could do much more to help children understand pain by modelling it in different ways and crucially by showing more empathy when characters experience pain. That’s important for how children interact with others when one of them experiences pain, such as when a friend might fall over in the playground or when they go to the doctors for routine vaccinations.”

Lead researcher, Dr Melanie Noel, Associate Professor of Clinical Psychology from the University of Calgary said: “We examined shows and movies that millions of young children in North America and beyond are watching. The findings were, frankly, shocking.

“It is undoubtable that the media is a powerful force in how children learn about the world. The way pain is unrealistically portrayed is teaching young children that pain is not worthy of help or empathy from others, and that it will be experienced and responded to differently if you are a boy or a girl. We have a responsibility to change these societal narratives about pain.”

Story Source:

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

In a healthy person, the body absorbs calcium to maintain strong bones and perform other important functions like helping muscles move and nerves carry messages between the brain and body parts. Vitamin D is critical for this calcium absorption from the intestine and for the function of the intestine.

The study, published in the journal Molecular and Cellular Biology, highlights the importance of the distal segments of the intestine — including the colon — in vitamin D regulation of calcium and bone calcification. Previously, this regulation was thought to only occur in the proximal intestine, the first section of the intestine immediately beyond the stomach.

From the study, researchers also learned that a transporter of manganese — an essential element that plays a role in many cellular processes — was one of the genes most induced by vitamin D in both the proximal and distal intestine.

The study’s lead author, Sylvia Christakos, a professor in the Department of Microbiology, Biochemistry and Molecular Genetics at Rutgers New Jersey Medical School, says these findings suggest that vitamin D plays other roles as well. “The findings suggest that vitamin D may have a role not only in calcium absorption, but also in the cellular regulation of other essential ions and in the function of intestinal stem cells,” she said.

This research may lead to new strategies that can compensate for calcium malabsorption and increase the efficacy of intestinal calcium uptake to minimize bone loss due to bariatric surgery, small bowel resection or reduced calcium absorption after menopause or due to aging.

Co-authors include Michael Verzi, Department of Genetics, Rutgers University; Noah Shroyer, Baylor College of Medicine; and James Fleet, Purdue University.

Story Source:

Materials provided by Rutgers University. Original written by Patti Verbanas. Note: Content may be edited for style and length.

The researchers envision their hybrid optical-acoustic system one day being used to conduct drone-based biological marine surveys from the air, carry out large-scale aerial searches of sunken ships and planes, and map the ocean depths with a similar speed and level of detail as Earth’s landscapes. Their “Photoacoustic Airborne Sonar System” is detailed in a recent study published in the journal IEEE Access.

“Airborne and spaceborne radar and laser-based, or LIDAR, systems have been able to map Earth’s landscapes for decades. Radar signals are even able to penetrate cloud coverage and canopy coverage. However, seawater is much too absorptive for imaging into the water,” said study leader Amin Arbabian, an associate professor of electrical engineering in Stanford’s School of Engineering. “Our goal is to develop a more robust system which can image even through murky water.”

Subhead: Energy loss

Oceans cover about 70 percent of the Earth’s surface, yet only a small fraction of their depths have been subjected to high-resolution imaging and mapping.

The main barrier has to do with physics: Sound waves, for example, cannot pass from air into water or vice versa without losing most — more than 99.9 percent — of their energy through reflection against the other medium. A system that tries to see underwater using soundwaves traveling from air into water and back into air is subjected to this energy loss twice — resulting in a 99.9999 percent energy reduction.

Similarly, electromagnetic radiation — an umbrella term that includes light, microwave and radar signals — also loses energy when passing from one physical medium into another, although the mechanism is different than for sound. “Light also loses some energy from reflection, but the bulk of the energy loss is due to absorption by the water,” explained study first author Aidan Fitzpatrick, a Stanford graduate student in electrical engineering. Incidentally, this absorption is also the reason why sunlight can’t penetrate to the ocean depth and why your smartphone — which relies on cellular signals, a form of electromagnetic radiation — can’t receive calls underwater.

The upshot of all of this is that oceans can’t be mapped from the air and from space in the same way that the land can. To date, most underwater mapping has been achieved by attaching sonar systems to ships that trawl a given region of interest. But this technique is slow and costly, and inefficient for covering large areas.

Subhead: An invisible jigsaw puzzle

Enter the Photoacoustic Airborne Sonar System (PASS), which combines light and sound to break through the air-water interface. The idea for it stemmed from another project that used microwaves to perform “non-contact” imaging and characterization of underground plant roots. Some of PASS’s instruments were initially designed for that purpose in collaboration with the lab of Stanford electrical engineering professor Butrus Khuri-Yakub.

At its heart, PASS plays to the individual strengths of light and sound. “If we can use light in the air, where light travels well, and sound in the water, where sound travels well, we can get the best of both worlds,” Fitzpatrick said.

To do this, the system first fires a laser from the air that gets absorbed at the water surface. When the laser is absorbed, it generates ultrasound waves that propagate down through the water column and reflect off underwater objects before racing back toward the surface.

The returning sound waves are still sapped of most of their energy when they breach the water surface, but by generating the sound waves underwater with lasers, the researchers can prevent the energy loss from happening twice.

“We have developed a system that is sensitive enough to compensate for a loss of this magnitude and still allow for signal detection and imaging,” Arbabian said.

The reflected ultrasound waves are recorded by instruments called transducers. Software is then used to piece the acoustic signals back together like an invisible jigsaw puzzle and reconstruct a three-dimensional image of the submerged feature or object.

“Similar to how light refracts or ‘bends’ when it passes through water or any medium denser than air, ultrasound also refracts,” Arbabian explained. “Our image reconstruction algorithms correct for this bending that occurs when the ultrasound waves pass from the water into the air.”

Subhead: Drone ocean surveys

Conventional sonar systems can penetrate to depths of hundreds to thousands of meters, and the researchers expect their system will eventually be able to reach similar depths.

To date, PASS has only been tested in the lab in a container the size of a large fish tank. “Current experiments use static water but we are currently working toward dealing with water waves,” Fitzpatrick said. “This is a challenging but we think feasible problem.”

The next step, the researchers say, will be to conduct tests in a larger setting and, eventually, an open-water environment.

“Our vision for this technology is on-board a helicopter or drone,” Fitzpatrick said. “We expect the system to be able to fly at tens of meters above the water.”

See video: https://youtu.be/2YyAnxQkeuk

Researchers at Texas A&M University have invented a high-throughput cell separation method that can be used in conjunction with droplet microfluidics, a technique whereby tiny drops of fluid containing biological or other cargo can be moved precisely and at high speeds. Specifically, the researchers successfully isolated pathogens attached to host cells from those that were unattached within a single fluid droplet using an electric field.

“Other than cell separation, most biochemical assays have been successfully converted into droplet microfluidic systems that allow high-throughput testing,” said Arum Han, professor in the Department of Electrical and Computer Engineering and principal investigator of the project. “We have addressed that gap, and now cell separation can be done in a high-throughput manner within the droplet microfluidic platform. This new system certainly simplifies studying host-pathogen interactions, but it is also very useful for environmental microbiology or drug screening applications.”

The researchers reported their findings in the August issue of the journal Lab on a Chip.

Microfluidic devices consist of networks of micron-sized channels or tubes that allow for controlled movements of fluids. Recently, microfluidics using water-in-oil droplets have gained popularity for a wide range of biotechnological applications. These droplets, which are picoliters (or a million times less than a microliter) in volume, can be used as platforms for carrying out biological reactions or transporting biological materials. Millions of droplets within a single chip facilitate high-throughput experiments, saving not just laboratory space but the cost of chemical reagents and manual labor.

Biological assays can involve different cell types within a single droplet, which eventually need to be separated for subsequent analyses. This task is extremely challenging in a droplet microfluidic system, Han said.

“Getting cell separation within a tiny droplet is extremely difficult because, if you think about it, first, it’s a tiny 100-micron diameter droplet, and second, within this extremely tiny droplet, multiple cell types are all mixed together,” he said.

To develop the technology needed for cell separation, Han and his team chose a host-pathogen model system consisting of the salmonella bacteria and the human macrophage, a type of immune cell. When both these cell types are introduced within a droplet, some of the bacteria adhere to the macrophage cells. The goal of their experiments was to separate the salmonella that attached to the macrophage from the ones that did not.

For cell separation, Han and his team constructed two pairs of electrodes that generated an oscillating electric field in close proximity to the droplet containing the two cell types. Since the bacteria and the host cells have different shapes, sizes and electrical properties, they found that the electric field produced a different force on each cell type. This force resulted in the movement of one cell type at a time, separating the cells into two different locations within the droplet. To separate the mother droplet into two daughter droplets containing one type of cells, the researchers also made a downstream Y-shaped splitting junction.

Han said although these experiments were carried with a host and pathogen whose interaction is well-established, their new microfluidic system equipped with in-drop separation is most useful when the pathogenicity of bacterial species is unknown. He added that their technology enables quick, high-throughput screening in these situations and for other applications where cell separation is required.

“Liquid handling robotic hands can conduct millions of assays but are extremely costly. Droplet microfluidics can do the same in millions of droplets, much faster and much cheaper,” Han said. “We have now integrated cell separation technology into droplet microfluidic systems, allowing the precise manipulation of cells in droplets in a high-throughput manner, which was not possible before.”

Story Source:

Materials provided by Texas A&M University. Original written by Vandana Suresh. Note: Content may be edited for style and length.

Anthropology professor Paul “Jim” Roscoe led the development of Power Theory, a model emphasizing the role of demography in political centralization, and applied it to the shift in power dynamics in prehistoric northern coastal societies in Peru.

To test the theory, he, Daniel Sandweiss, professor of anthropology and Quaternary and climate studies, and Erick Robinson, a postdoctoral anthropology researcher at Utah State University, created a summed probability distribution (SPD) from 755 radiocarbon dates from 10,000-1,000 B.P., or before present.

The team found a correlation between the tenets of their Power Theory, or that population density and size influence political centralization, and the change in power dynamics in early Peruvian societies.

The team shared their findings in a report published in Philosophical Transactions of the Royal Society B.

“I’ve always been interested in how, in the space of just five to 10,000 years, humans went from biddy little hunter-gatherer groups in which nobody could really push anyone else around to vast industrial states governed by a few people with enormous power. From my fieldwork and other research in New Guinea, it became clear that leaders mainly emerged in large, high-density populations, and Power Theory explained why,” Roscoe says. “Unfortunately, it was difficult until recently for archaeologists to get a handle on the size and densities of populations in the past. SPD techniques are a major help in bringing these important variables into understanding how human social life underwent this dramatic transformation.”

Scientists have previously posited that population in northern coastal Peru rose during the Late Preceramic, Initial, Early Horizon and Early Intermediate periods, or between about 6,000-1,200 B.P. The SPD from Roscoe and his colleagues validates the notion.

The people who settled in the coastal plain first lived as mobile hunter-gatherers or incipient horticulturalists in low density groups, according to researchers. Millennia afterward in the Late Preceramic period, however, several developments brought increased interaction and shareable resources. People began farming, developed irrigation systems and became more settled as time passed. Eventually, some of the world’s first ‘pristine’ states formed in the plain.

The onset and growth of agriculture, irrigation and sedentism, propelled by upticks in population size and density, fostered the capacity of political agents to interact with and manipulate others. Political centralization and hierarchy formed as a result, according to researchers.

Roscoe and his colleagues demonstrated through their radio-carbon SPD that the rise in centralized authorities in early Peruvian communities that resulted from farming, irrigation and settlement coincided with an uptick in population size. The results of their work demonstrate “a broad, low-resolution congruence between the expectations of Power Theory and what is currently known about coastal Peruvian antiquity,” they wrote in their study.

The project also highlights the capability of SPDs for examining the influence of demography in the growth of prehistoric political centralization. Determining the extent of that influence, however, requires additional study.

“We’re hoping this work demonstrates the value of SPDs for understanding the role of demography in the emergence and development of power centers on Earth,” Roscoe says. “What we need now is to increase the size of our SPD databases and filter out some of the weaknesses we know they contain.”