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Immune genes are altered in Alzheimer’s patients’ blood

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Immune genes are altered in Alzheimer’s patients’ blood


A new Northwestern Medicine study has found the immune system in the blood of Alzheimer’s patients is epigenetically altered. That means the patients’ behavior or environment has caused changes that affect the way their genes work.

Many of these altered immune genes are the same ones that increase an individual’s risk for Alzheimer’s. Northwestern scientists theorize the cause could be a previous viral infection, environmental pollutants or other lifestyle factors and behaviors.

“It is possible that these findings implicate the peripheral immune response in Alzheimer’s disease risk,” said lead investigator David Gate, assistant professor of neurology at Northwestern University Feinberg School of Medicine. “We haven’t yet untangled whether these changes are reflective of brain pathology or whether they precipitate the disease.”

The study was published Feb. 9 in Neuron.

Previous research showed that many of the mutated genes putting a person at higher risk for Alzheimer’s are in the immune system. But scientists primarily studied the central immune system in the brain because Alzheimer’s is a brain disease. They have largely ignored the immune system in the blood, also known as the peripheral immune system.

Gate decided to study the blood. He and colleagues discovered every immune cell type in Alzheimer’s patients has epigenetic changes, indicated by open chromatin. Chromatin is the packaging of the DNA within cells. When chromatin is open — or exposed — the cells’ genome is vulnerable to alterations.

Then, Gate examined which genes are more open in these immune cells. He discovered that a receptor — CXCR3 — on the T cells was more exposed. Gate believes CXCR3 functions like an antenna on T cells that allows the cells to enter the brain. T cells do not normally enter the brain because they can cause inflammation.

“The brain is emitting a signal that it is damaged, and the T cells are homing to that signal by their antenna, CXCR3,” Gate said.

“T cells can be very toxic in the brain, but we also don’t know if these cells might be attempting to repair the damage in the brain,” Gate said.

Gate also discovered epigenetic changes in inflammatory proteins in white blood cells called monocytes.

“Altogether, these findings indicate that immune function in Alzheimer’s patients is significantly altered,” Gate said. “It could be that environmental factors, like pollutants, or infections that a person has in their lifetime cause these epigenetic changes.”

The findings revealed several genes that may be therapeutic targets for manipulating the peripheral immune system. Next steps in the research are preclinical studies using in vitro culture systems and animal models to test these targets.

Other Northwestern authors include Abhirami Ramakrishnan, Natalie Piehl, Brooke Simonton, Milan Parikh, Ziyang Zhang, Victoria Teregulova and Lynn van Olst.

The title of the article is “Epigenetic dysregulation in Alzheimer’s disease peripheral immunity.”

The research is supported by National Institute of Neurological Disorders and Stroke grant NS112458 and National Institute on Aging grant AG078713, both of the National Institutes of Health, Bright Focus Foundation, Alzheimer’s Association and Cure Alzheimer’s Fund.



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Warming of Antarctic deep-sea waters contribute to sea level rise in North Atlantic, study finds

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Warming of Antarctic deep-sea waters contribute to sea level rise in North Atlantic, study finds


Analysis of mooring observations and hydrographic data suggest the Atlantic Meridional Overturning Circulation deep water limb in the North Atlantic has weakened. Two decades of continual observations provide a greater understanding of the Earth’s climate regulating system.

A new study published in the journal Nature Geoscience led by scientists at University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, and the National Oceanic and Atmospheric Administration’s Atlantic Oceanographic and Meteorological Laboratory, found that human-induced environmental changes around Antarctica are contributing to sea level rise in the North Atlantic.

The research team analyzed two decades of deep sea oceanographic data collected by observational mooring programs to show that a critical piece of Earth’s global system of ocean currents in the North Atlantic has weakened by about 12 percent over the past two decades.

“Although these regions are tens of thousands of miles away from each other and abyssal areas are a few miles below the ocean surface, our results reinforce the notion that even the most remote areas of the world’s oceans are not untouched by human activity,” said the study’s lead author Tiago Biló, an assistant scientist at the Rosenstiel School’s NOAA Cooperative Institute for Marine and Atmospheric Studies.

As part of the NOAA-funded project DeepT (Innovative analysis of deep and abyssal temperatures from bottom-moored instrument), the scientists analyzed data from several observational programs to study changes over time in a cold, dense, and deep water mass located at depths greater than 4,000 meters (2.5 miles) below the ocean surface that flow from the Southern Ocean northward and eventually upwells to shallower depths in other parts of the global ocean such as the North Atlantic.

This shrinking deep-ocean branch — that scientists call the abyssal limb — is part of the Atlantic Meridional Overturning Circulation (AMOC), a three-dimensional system of ocean currents that act as a “conveyer belt” to distribute heat, nutrients, and carbon dioxide across the world’s oceans.

This near-bottom branch is comprised of Antarctic bottom water, which forms from the cooling of seawater in the Southern Ocean around Antarctica during winter months. Among the different formation mechanisms of this bottom water, perhaps the most important is the so-called brine rejection, a process that occurs when salty water freezes. As sea ice forms, it releases salt into the surrounding water, increasing its density. This dense water sinks to the ocean floor, creating a cold, dense water layer that spreads northward to fill all three ocean basins — the Indian, Pacific, and Atlantic oceans. During the 21st century, the researchers observed that the flow of this Antarctic layer across 16°N latitude in the Atlantic had slowed down, reducing the inflow of cold waters to higher latitudes, and leading to warming of waters in the deep ocean.

“The areas affected by this warming spans thousands of miles in the north-south and east-west directions between 4,000- and 6,000-meters of depth,” said William Johns, a co-author and professor of ocean sciences at the Rosenstiel School. “As a result, there is a significant increase in the abyssal ocean heat content, contributing to local sea level rise due to the thermal expansion of the water.”

“Our observational analysis matches what the numerical models have predicted — human activity could potentially impose circulation changes on the entire ocean,” said Biló. “This analysis was only possible because of the decades of collective planning and efforts by multiple oceanographic institutions worldwide.”



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Octopus inspires new suction mechanism for robots

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Octopus inspires new suction mechanism for robots


A new robotic suction cup which can grasp rough, curved and heavy stone, has been developed by scientists at the University of Bristol.

The team, based at Bristol Robotics Laboratory, studied the structures of octopus biological suckers, which have superb adaptive suction abilities enabling them to anchor to rock.

In their findings, published in the journal PNAS today, the researchers show how they were able create a multi-layer soft structure and an artificial fluidic system to mimic the musculature and mucus structures of biological suckers.

Suction is a highly evolved biological adhesion strategy for soft-body organisms to achieve strong grasping on various objects. Biological suckers can adaptively attach to dry complex surfaces such as rocks and shells, which are extremely challenging for current artificial suction cups. Although the adaptive suction of biological suckers is believed to be the result of their soft body’s mechanical deformation, some studies imply that in-sucker mucus secretion may be another critical factor in helping attach to complex surfaces, thanks to its high viscosity.

Lead author Tianqi Yue explained: “The most important development is that we successfully demonstrated the effectiveness of the combination of mechanical conformation — the use of soft materials to conform to surface shape, and liquid seal — the spread of water onto the contacting surface for improving the suction adaptability on complex surfaces. This may also be the secret behind biological organisms ability to achieve adaptive suction.”

Their multi-scale suction mechanism is an organic combination of mechanical conformation and regulated water seal. Multi-layer soft materials first generate a rough mechanical conformation to the substrate, reducing leaking apertures to just micrometres. The remaining micron-sized apertures are then sealed by regulated water secretion from an artificial fluidic system based on the physical model, thereby the suction cup achieves long suction longevity on diverse surfaces but with minimal overflow.

Tianqi added: “We believe the presented multi-scale adaptive suction mechanism is a powerful new adaptive suction strategy which may be instrumental in the development of versatile soft adhesion.

“Current industrial solutions use always-on air pumps to actively generate the suction however, these are noisy and waste energy.

“With no need for a pump, it is well known that many natural organisms with suckers, including octopuses, some fishes such as suckerfish and remoras, leeches, gastropods and echinoderms, can maintain their superb adaptive suction on complex surfaces by exploiting their soft body structures.”

The findings have great potential for industrial applications, such as providing a next-generation robotic gripper for grasping a variety of irregular objects.

The team now plan to build a more intelligent suction cup, by embedding sensors into the suction cup to regulate suction cup’s behaviour.



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One third of China’s urban population at risk of city sinking, new satellite data shows

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One third of China’s urban population at risk of city sinking, new satellite data shows


Land subsidence is overlooked as a hazard in cities, according to scientists from the University of East Anglia (UEA) and Virginia Tech.

Writing in the journal Science, Prof Robert Nicholls of the Tyndall Centre for Climate Change Research at UEA and Prof Manoochehr Shirzaei of Virginia Tech and United Nations University for Water, Environment and Health, Ontario, highlight the importance of a new research paper analysing satellite data that accurately and consistently maps land movement across China.

While they say in their comment article that consistently measuring subsidence is a great achievement, they argue it is only the start of finding solutions. Predicting future subsidence requires models that consider all drivers, including human activities and climate change, and how they might change with time.

The research paper, published in the same issue, considers 82 cities with a collective population of nearly 700 million people. The results show that 45% of the urban areas that were analysed are sinking, with 16% falling at a rate of 10mm a year or more.

Nationally, roughly 270 million urban residents are estimated to be affected, with nearly 70 million experiencing rapid subsidence of 10mm a year or more. Hotspots include Beijing and Tianjin.

Coastal cities such as Tianjin are especially affected as sinking land reinforces climate change and sea-level rise. The sinking of sea defences is one reason why Hurricane Katrina’s flooding brought such devastation and death-toll to New Orleans in 2005.

Shanghai — China’s biggest city — has subsided up to 3m over the past century and continues to subside today. When subsidence is combined with sea-level rise, the urban area in China below sea level could triple in size by 2120, affecting 55 to 128 million residents. This could be catastrophic without a strong societal response.

“Subsidence jeopardises the structural integrity of buildings and critical infrastructure and exacerbates the impacts of climate change in terms of flooding, particularly in coastal cities where it reinforces sea-level rise,” said Prof Nicholls, who was not involved in the study, but whose research focusses on sea-level rise, coastal erosion and flooding, and how communities can adapt to these changes.

The subsidence is mainly caused by human action in the cities. Groundwater withdrawal, that lowers the water table is considered the most important driver of subsidence, combined with geology and weight of buildings.

In Osaka and Tokyo, groundwater withdrawal was stopped in the 1970s and city subsidence has ceased or greatly reduced showing this is an effective mitigation strategy. Traffic vibration and tunnelling is potentially also a local contributing factor — Beijing has sinking of 45mm a year near subways and highways. Natural upward or downward land movement also occurs but is generally much smaller than human induced changes.

While human-induced subsidence was known in China before this study, Profs Nicholls and Shirzaei say these new results reinforce the need for a national response. This problem happens in susceptible cities outside China and is a widespread problem across the world.

They call for the research community to move from measurement to understanding implications and supporting responses. The new satellite measurements are delivering new detailed subsidence data but the methods to use this information to work with city planners to address these problems needs much more development. Affected coastal cities in China and more widely need particular attention.

“Many cities and areas worldwide are developing strategies for managing the risks of climate change and sea-level rise,” said Prof Nicholls. “We need to learn from this experience to also address the threat of subsidence which is more common than currently recognised.”



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