Scientists build ‘valves’ in DNA to shape biological information flows

DNA valve controlling molecular processes along DNA
Credit: Thomas Gorochowski

Scientists at the University of Bristol have developed new biological parts that are able to shape the flow of cellular processes along DNA.

The work, now published in the journal Nature Communications, offers a fresh perspective on how information is encoded in DNA and new tools for building sustainable biotechnologies.

Despite being invisible to the naked eye, microorganisms are integral for our survival. They operate using DNA, often referred to as the code of life. DNA encodes numerous tools that could be useful to us, but we currently lack a complete understanding of how to interpret DNA sequences.

Matthew Tarnowski, first author and a PhD student in Bristol’s School of Biological Sciences, said: “Understanding the microbial world is tricky. While reading a microbe’s DNA with a sequencer gives us a window into the underlying code, you still need to read a lot of different DNA sequences to understand how it actually works. It’s a bit like trying to learn a new language, but from only a few small fragments of text.”

To tackle this problem, the Bristol team focused on how the information encoded in DNA is read, and specifically, how the flow of cellular processes along DNA are controlled. These biological information flows orchestrate many of the core functions of a cell and an ability to shape them would offer a way to guide cellular behaviors.

Taking inspiration from nature, where it is known that flows on DNA are often complex and interwoven, the team focused on how these flows could be regulated by creating “valves” to tune the flow from one region of DNA to another.

Suicide Attempts on the Rise, But Help is Hard to Get

The rate of suicidal behavior among Americans increased from 2008 to 2019, but usage of mental health services didn’t budge, reports a team led by UConn Health. The results, reported in JAMA Psychiatry, show that people need help to overcome existing barriers to care.

Suicide overall is still rare, but the rate of people attempting it in the US increased from 2008 to 2019, despite an improving economy during that period. A team of researchers including UConn Health School of Medicine psychiatric epidemiologist Greg Rhee looked at data from a survey done by the National Institutes of Health and Substance Abuse and Mental Health Services Administration of 484,732 people across the US.

The survey found rates of attempted suicide rose by 1.8 times from 2008 to 2019 in young people aged 18-25. It also rose among people struggling with substance abuse. Suicide attempts are the single most important risk factor for suicide; the rate of suicide is 100 times greater among people who’ve already made the attempt in the past year compared to the general population. Getting people mental health services soon after a suicide attempt is one of the most effective ways to help them.

The survey also asked respondents if there was a time in the last 12 months when they needed mental health services but did not receive them, and if so, why.

Arthritis-related gene also regenerates cartilage in joints and growth plates

Spine from a healthy mouse (left) and a mouse with
genetically disrupted cartilage progenitor cells 
Image by Dawei Geng and Tea Jashashvili

The IL-6 family of proteins has a bad reputation: it can promote inflammation, arthritis, autoimmune disease and even cancer. However, a new USC-led study published in Communications Biology reveals the importance of IL-6 and associated genes for maintaining and regenerating cartilage in both the joints and in the growth plates that enable skeletal growth in children.

“We show, for the first time, that the IL-6 family, previously almost exclusively associated in the musculoskeletal field with arthritis, bone and muscle loss, and other chronic inflammatory diseases, is required for the maintenance of skeletal stem and progenitor cells, and for the healthy growth and function of the joints and spine,” said the study’s corresponding author Denis Evseenko, who is the J. Harold and Edna LaBriola Chair in Genetic Orthopedic Research, and an associate professor of orthopaedic surgery, and stem cell biology and regenerative medicine at USC. “Our study establishes a link between inflammation and regeneration, and may explain why stem and progenitors are exhausted in chronic inflammation.”

In the study, first author Nancy Q. Liu from USC and her colleagues took a close look at a key gene activated by IL-6: STAT3. In both lab-grown human cells and in mice, the scientists demonstrated that STAT3 is critical for the proliferation, survival, maturation and regeneration of cartilage-forming cells in the joints and growth plates. When the gene ceased to function, cartilage-forming cells became increasingly dysfunctional over time, resulting in smaller body size, prematurely fused growth plates, underdeveloped skeletons and mildly degenerated joint cartilage.

Mice experienced the same issues when they lacked a protein called glycoprotein 130 (gp130), which all IL-6 proteins use to activate Stat3. Deactivating another gene Lifr, which encodes a protein that works with gp130 to recognize one of the IL-6 proteins called Lif, produced similar but milder skeletal and cartilage changes.

Making the invisible visible: tracing the origins of plants in West African cuisine

Excavated Nok vessels are cleaned and photographed at the Janjala research station, shown in the picture: Dr Gabriele Franke, Goethe University
Credit: Peter Breunig

A team of scientists, led by the University of Bristol, in co-operation with colleagues from Goethe University, Frankfurt, has uncovered the first insights into the origins of West African plant-based cuisine, locked inside pottery fragments dating back some 3,500 years ago.

West African cuisine has long been known for its distinct ingredients and flavors, often enhanced by the addition of a large and diverse range of plant foods.

A traditional meal comprises a starchy staple cooked in a pot, served with a sauce prepared from vegetables, fish and/or meat, often accompanied by pulses.

These starchy staples include root crops such as yams, cassava, sorghum, pearl millet and maize. In the northern Sahel and savanna zones, pearl millet is mainly prepared as porridge, while in the southern forest zone, a pounded mash from tuber crops such as yam, called fufu, is the major starch-rich element.

Excavating Nok terracotta pottery vessel at Ifana 3 site
Credit: Peter Breunig

Indigenous vegetables, eaten at almost every West African meal, include eggplant, pumpkin and watermelon, okra (used as a thickener for soups and stews), as well as a staggering variety of both farmed and foraged green leafy vegetables, little known or used outside of the African continent.

These include leaves from the amaranth, roselle and baobab tree. However, investigating the origin of vegetables and leafy greens is difficult as they do not generally survive over archaeological timescales.

The Bristol team carried out chemical analysis of more than 450 prehistoric potsherds from the Central Nigerian Nok culture to investigate what foods they were cooking in their pots. The Nok people are known for their remarkable large-scale terracotta figurines and early iron production in West Africa, around the first millennium BC.

Powerful volcanic blast not the cause for 2018 Indonesian island collapse

The dramatic collapse of Indonesia’s Anak Krakatau volcano in December 2018 resulted from long-term destabilizing processes, and was not triggered by any distinct changes in the magmatic system that could have been detected by current monitoring techniques, new research has found.

The volcano had been erupting for around six months prior to the collapse, which saw more than two-thirds of its height slide into the sea as the island halved in area. The event triggered a devastating tsunami, which inundated the coastlines of Java and Sumatra and led to the deaths of more than 400 people.

A team led by the University of Birmingham examined volcanic material from nearby islands for clues to determine whether the powerful, explosive eruption observed after the collapse had itself triggered the landslide and tsunami. Their results are published in Earth and Planetary Science Letters.

Working with researchers at the Bandung Institute of Technology, the University of Oxford and the British Geological Survey, the team looked at the physical, chemical and microtextural characteristics of the erupted material. They concluded that the large explosive eruption associated with the collapse was probably caused by the underlying magmatic system becoming destabilized as the landslide got underway.

This means the disaster was less likely to have been caused by magma forcing its way to the surface and triggering the landslide. Current volcano monitoring methods record seismic activity and other signals caused by magma rising through the volcano, but since this event was not triggered from within, it would not have been detected using these techniques.

The Roman Space Telescope's Simulated Ultra-Deep Field Image

This video demonstrates how Roman could expand on Hubble’s iconic Ultra Deep Field image. While a similar Roman observation would be just as sharp as Hubble’s and see equally far back in time, it could reveal an area 300 times larger, offering a much broader view of cosmic ecosystems.

Also on our You Tube channel 

Source/Credit: 
Video: NASA / Goddard Space Flight Center
Music: "Subterranean Secret" and "Expectant Aspect" from Universal Production Music.
Final Editing and Conversion Scientific Frontline

sn011622_01

Researchers discover how deep-sea worms help keep natural gases on ice

Sabellidae, or feather duster worms, are a family
of marine polychaete tube worms

It is well known that natural gas hydrates, crystalline lattices of hydrogen-bonded water molecules that encapsulate small hydrocarbon molecules, on the ocean floors constitute both a potential accelerator of climate change and one of the greatest energy sources on Earth. But whether the huge amounts of natural gas that are so confined remain safely locked in crystalline hydrate cages, or are liberated into the ocean potentially to become atmospheric greenhouse gases, may depend in part on an unusual sea-floor symbiosis between worms and their microbial neighbors.

Researchers at the NYU Tandon School of Engineering discovered that this natural ecosystem involving feather duster worms (Sabellidae, Annelida) and both heat-generating and heat-absorbing bacteria (Archaea) that consume methane enclathrated — or locked into a crystalline structure — by hydrates in deep marine environments play a key role in maintaining equilibrium that keeps hydrates frozen.

Seeking to examine the influence that subtle temperature fluctuations may have on the dynamic stability of the hydrate deposits, the investigators, led by Ryan Hartman, professor of chemical and biomolecular engineering at NYU Tandon, found that feather duster worms, which thrive around crystalline hydrates, by selectively consuming heat-generating bacteria called methanotrophs that metabolize methane, put the brakes on the potential melting of these crystal structures (releasing trapped methane) due to the microbes’ exothermic metabolism.

In a newly published study, “Microbe-Worm Symbiosis Stabilizes Methane Hydrates in Deep Marine Environments,” in Energy & Fuels, researchers including lead author Tianyi Hua, Maisha Ahmad, and Tenzin Choezin, simulated the ecosystem by solving the associated energy balance and methane hydrate dissociation kinetics. They examined and analyzed the dissociation rate — the rate at which frozen hydrates disassembled into molecular components — and found that the symbiosis established among methanogens (methane-producing bacteria), methanotrophs, and feather duster worms indeed stabilizes methane hydrates at depths where the crystals are exposed to the ocean and its living organisms.

Citizen science helps nurture our health through nature

From lifting our moods, to boosting our immune systems, the intrinsic health benefits of being in nature are well known. But as urbanization continues to encroach on green spaces, finding ways to connect with natural environments is becoming more challenging.

Now, University of South Australia researchers are urging governments to consider nature-based citizen science as part of their public health policies in an effort improve the health and wellbeing of people living in urban areas.

By 2050, the United Nations estimates that 88 per cent of the population will be living in urban areas.

Given such mass urbanization, UniSA’s Professor Craig Williams says it’s more important than ever to maintain a connection with natural environments.

“Whether you’re watering the garden, taking a stroll around the block, or simply watching the world go by, getting out into nature is good for your health,” Prof Williams says.

“Natural environments can enhance human performance, improve success at work (or school) and are known to provide significant mental, emotional, and physical health benefits.

“Conversely, urbanization can negatively affect human health by increasing the prevalence of allergic, autoimmune, inflammatory, and infectious diseases, with some of these factors contributing to rise in cancers, depression and cardiovascular disease.

“As cities grow, fewer people have access to natural environments, which is part of the reason urban living can be bad for your health.

World's largest fish breeding area discovered in Antarctica

Fish nests in Weddell Sea 
Photo: PS124, AWI OFOBS team

Near the Filchner Ice Shelf in the south of the Antarctic Weddell Sea, a research team has found the world's largest fish breeding area known to date. A towed camera system photographed and filmed thousands of nests of icefish of the species Neopagetopsis ionah on the seabed. The density of the nests and the size of the entire breeding area suggest a total number of about 60 million icefish breeding at the time of observation. These findings provide support for the establishment of a Marine Protected Area in the Atlantic sector of the Southern Ocean. A team led by Autun Purser from the Alfred Wegener Institute publish their results in the current issue of the scientific journal Current Biology.

The joy was great when, in February 2021, researchers viewed numerous fish nests on the monitors aboard the German research vessel Polarstern, which their towed camera system transmitted live to the vessel from the seabed, 535 to 420 meters below the ship, from the seafloor of the Antarctic Weddell Sea. The longer the mission lasted, the more the excitement grew, finally ending in disbelief: nest followed nest, with later precise evaluation showing that there were on average one breeding site per three square meters, with the team even finding a maximum of one to two active nests per square meter.

The mapping of the area suggests a total extent of 240 square kilometers, which is roughly the size of the island of Malta. Extrapolated to this area size, the total number of fish nests was estimated to be about 60 million. "The idea that such a huge breeding area of icefish in the Weddell Sea was previously undiscovered is totally fascinating," says Autun Purser, deep-sea biologist at the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) and lead author of the current publication. After all, the Alfred Wegener Institute has been exploring the area with its icebreaker Polarstern since the early 1980s. So far, only individual Neopagetopsis ionah or small clusters of nests have been detected here.

Using Only 100 Atoms, Electric Fields Can Be Detected and Changed

A conceptual drawing of the new molecular device. for experiments outside the human body (in vitro), the device would nest on the cell’s membrane: A “reporter” molecule would detect the local electric field when activated by red light; An attached “modifier” molecule would alter that electric field when activated by blue light.
Illustration by katya kadyshevskaya

Bioelectricity, the current that flows between our cells, is fundamental to our ability to think and talk and walk.

In addition, there is a growing body of evidence that recording and altering the bioelectric fields of cells and tissue plays a vital role in wound healing and even potentially fighting diseases like cancer and heart disease.

Now, for the first time, researchers at the USC Viterbi School of Engineering have created a molecular device that can do both: record and manipulate its surrounding bioelectric field.

The triangle-shaped device is made of two small, connected molecules — much smaller than a virus and similar to the diameter of a DNA strand.

It’s a completely new material for “reading and writing” the electric field without damaging nearby cells and tissue. Each of the two molecules, linked by a short chain of carbon atoms, has its own separate function: one molecule acts as a “sensor” or detector that measures the local electric field when triggered by red light; a second molecule, “the modifier,” generates additional electrons when exposed to blue light. Notably, each function is independently controlled by different wavelengths of light.

Though not intended for use in humans, the organic device would sit partially inside and outside the cell’s membrane for in vitro experiments.

Researchers discover a new approach to breaking bacterial antibiotic resistance and rescue frontline drug treatments

Dr Erin Brazel from the University of Adelaide’s
Research Center for Infectious Diseases.

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), The University of Queensland, Griffith University, The University of Adelaide, and St Jude Children’s Research Hospital (USA), have unlocked a key to making existing frontline antibiotics work again against the deadly bacteria that cause pneumonia.

In a world first, this international team discovered how to repurpose a molecule called PBT2 – originally developed as a potential treatment for disorders such as Alzheimer's, Parkinson’s and Huntington’s diseases – to break bacterial resistance to commonly used frontline antibiotics.

Led by University of Melbourne’s Professor Christopher McDevitt, a laboratory head at the Doherty Institute, this discovery may soon see the comeback of readily available and cheap antibiotics, such as penicillin and ampicillin, as effective weapons in the fight against the rapidly rising threat of antibiotic resistance.

In a paper published today in Cell Reports Professor McDevitt and his collaborators described how they discovered a way to break bacterial drug resistance and then developed a therapeutic approach to rescue the use of the antibiotic ampicillin to treat drug-resistant bacterial pneumonia caused by Streptococcus pneumoniae in a mouse model of infection.

This may become a game-changer against the global health threat of antibiotic resistance. Last year the World Health Organization (WHO) described antibiotic resistance as one of the greatest threats to global health, food security, and development. Rising numbers of bacterial infections – such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis – are becoming harder to treat as the antibiotics used against them are becoming less effective. With few new drugs on the horizon, it is predicted that by 2050 antibiotic resistant infections will cause more deaths than cancers and cardiac disease, accounting for more than 10 million deaths per year.

Risky food-finding strategy could be the key to human success

A group of Hadza women share a meal of roasted tubers. Food sharing allows them to spend more energy to find food, knowing they won’t starve if they return to camp empty-handed. (
Credit: Herman Pontzer)

It’s a cold and rainy Sunday afternoon: would you rather be running after tasteless wild berries, or curled up on your couch with fuzzy socks and a good book?

You might not have had that choice if our ancestors had not taken a big gamble with their food.

A new study published in Science shows that early human foragers and farmers adopted an inefficient high-risk, high-reward strategy to find food. They spent more energy in pursuit of food than their great ape cousins, but brought home much more calorie-rich meals that could be shared with the rest of their group. This strategy allowed some to rest or tackle other tasks while food was being acquired.

“Hunting and gathering is risky and inefficient, but the rate of return is enormous,” said study co-leader, Herman Pontzer, an associate professor of Evolutionary Anthropology at Duke University. “We can share our food, and because we got so many calories before noon, we can hang out around each other in this new space, a free-time space.”

Humans spend a lot more energy than great apes. We have big brains that eat up a lot of calories, we live a long time, we can have long pregnancies that produce big babies, and these babies rely on adults for a long time.

A spray to protect against lung damage from Covid-19

Prof. Stefan Engelhardt and startup rnatics develop an RNA-based drug that can prevent inflammatory lung conditions associated with Covid-19.
Image Credit: Andreas Heddergott / TUM

rnatics, a startup at the Technical University of Munich (TUM), has created an RNA-based drug to prevent lung damage from infections as seen in serious Covid-19 cases. The Federal Ministry of Education and Research (BMBF) is providing 7 million euros in funding to support the development of the drug. The team is using a substance that inhibits the inflammation-promoting microRNA. The therapy is expected to be efficacious in current and future mutations of SARS-CoV2.

Covid-19 infections can lead to serious inflammations of the lung and the formation of scar tissue (fibrosis). This can have a long-term impact on lung function and is one of the causes of “long covid”. A team working with Stefan Engelhardt, Professor of Pharmacology and Toxicology at TUM has developed a new RNA-based drug that can prevent these inflammatory lung conditions. When administered via the respiratory passages, it quickly targets immune cells in the alveoli (tiny air sacs in the lungs) and inhibits a microRNA molecule found in these cells.

In Covid patients, misguided immune cells called macrophages play a substantial role in severe inflammatory infections and lung damage. However, when the new drug blocked the microRNA molecule in macrophages in mice, there was a significant reduction in inflammation and lung damage and a considerable improvement in lung function. Stefan Engelhardt is confident that serious infections and thus the kind of lung damage associated with long covid can be prevented in human patients receiving the drug through an inhaler.

Earth’s interior is cooling faster than expected

The Earth's core gives off heat to the mantle (or­ange to dark red),
which con­trib­utes to the slow cool­ing of the Earth
Source: ETH Zurich

Re­search­ers at ETH Zurich have demon­strated in the lab how well a min­eral com­mon at the bound­ary between the Earth’s core and mantle con­ducts heat. This leads them to sus­pect that the Earth’s heat may dis­sip­ate sooner than pre­vi­ously thought.

The evol­u­tion of our Earth is the story of its cool­ing: 4.5 bil­lion years ago, ex­treme tem­per­at­ures pre­vailed on the sur­face of the young Earth, and it was covered by a deep ocean of magma. Over mil­lions of years, the planet’s sur­face cooled to form a brittle crust. How­ever, the enorm­ous thermal en­ergy em­an­at­ing from the Earth’s in­terior set dy­namic pro­cesses in mo­tion, such as mantle con­vec­tion, plate tec­ton­ics and vol­can­ism.

Still un­answered, though, are the ques­tions of how fast the Earth cooled and how long it might take for this on­go­ing cool­ing to bring the afore­men­tioned heat-​driven pro­cesses to a halt.

One pos­sible an­swer may lie in the thermal con­duct­iv­ity of the min­er­als that form the bound­ary between the Earth’s core and mantle.

This bound­ary layer is rel­ev­ant be­cause it is here that the vis­cous rock of the Earth’s mantle is in dir­ect con­tact with the hot iron-​nickel melt of the planet’s outer core. The tem­per­at­ure gradi­ent between the two lay­ers is very steep, so there is po­ten­tially a lot of heat flow­ing here. The bound­ary layer is formed mainly of the min­eral bridg­man­ite. How­ever, re­search­ers have a hard time es­tim­at­ing how much heat this min­eral con­ducts from the Earth’s core to the mantle be­cause ex­per­i­mental veri­fic­a­tion is very dif­fi­cult.

New Study Sheds Light on Origins of Life on Earth

A Rutgers-led team has discovered the structures of proteins that may be responsible for the origins of life in the primordial soup of ancient Earth.

Addressing one of the most profoundly unanswered questions in biology, a Rutgers-led team has discovered the structures of proteins that may be responsible for the origins of life in the primordial soup of ancient Earth.

The study appears in the journal Science Advances.

The researchers explored how primitive life may have originated on our planet from simple, non-living materials. They asked what properties define life as we know it and concluded that anything alive would have needed to collect and use energy, from sources such as the Sun or hydrothermal vents.

In molecular terms, this would mean that the ability to shuffle electrons was paramount to life. Since the best elements for electron transfer are metals (think standard electrical wires) and most biological activities are carried out by proteins, the researchers decided to explore the combination of the two — that is, proteins that bind metals.

They compared all existing protein structures that bind metals to establish any common features, based on the premise that these shared features were present in ancestral proteins and were diversified and passed down to create the range of proteins we see today.