Earth

Rutgers researchers have discovered the origins of the protein structures responsible for metabolism: simple molecules that powered early life on Earth and serve as chemical signals that NASA could use to search for life on other planets.

Their study, which predicts what the earliest proteins looked like 3.5 billion to 2.5 billion years ago, is published in the journal Proceedings of the National Academy of Sciences.

The scientists retraced, like a many thousand piece puzzle, the evolution of enzymes (proteins) from the present to the deep past. The solution to the puzzle required two missing pieces, and life on Earth could not exist without them. By constructing a network connected by their roles in metabolism, this team discovered the missing pieces.

"We know very little about how life started on our planet. This work allowed us to glimpse deep in time and propose the earliest metabolic proteins," said co-author Vikas Nanda, a professor of Biochemistry and Molecular Biology at Rutgers Robert Wood Johnson Medical School and a resident faculty member at the Center for Advanced Biotechnology and Medicine. "Our predictions will be tested in the laboratory to better understand the origins of life on Earth and to inform how life may originate elsewhere. We are building models of proteins in the lab and testing whether they can trigger reactions critical for early metabolism."

A Rutgers-led team of scientists called ENIGMA (Evolution of Nanomachines in Geospheres and Microbial Ancestors) is conducting the research with a NASA grant and via membership in the NASA Astrobiology Program. The ENIGMA project seeks to reveal the role of the simplest proteins that catalyzed the earliest stages of life.

"We think life was built from very small building blocks and emerged like a Lego set to make cells and more complex organisms like us," said senior author Paul G. Falkowski, ENIGMA principal investigator and a distinguished professor at Rutgers University-New Brunswick who leads the Environmental Biophysics and Molecular Ecology Laboratory. "We think we have found the building blocks of life - the Lego set that led, ultimately, to the evolution of cells, animals and plants."

The Rutgers team focused on two protein "folds" that are likely the first structures in early metabolism. They are a ferredoxin fold that binds iron-sulfur compounds, and a "Rossmann" fold, which binds nucleotides (the building blocks of DNA and RNA). These are two pieces of the puzzle that must fit in the evolution of life.

Proteins are chains of amino acids and a chain's 3D path in space is called a fold. Ferredoxins are metals found in modern proteins and shuttle electrons around cells to promote metabolism. Electrons flow through solids, liquids and gases and power living systems, and the same electrical force must be present in any other planetary system with a chance to support life.

There is evidence the two folds may have shared a common ancestor and, if true, the ancestor may have been the first metabolic enzyme of life.

A drug candidate has been found in preclinical trials to stop tumor growth entirely, deliver more cancer-busting power than many commonly used chemotherapy drugs and do so with fewer toxic side effects and more ability to overcome resistance.

Researchers from The University of Texas at Austin, The University of Texas MD Anderson Cancer Center and Austin-based biotech firm OncoTEX report their results this week in the journal Proceedings of the National Academy of Sciences.

"As a cancer researcher and cancer survivor, I'm excited by the fact that our compound shows promise for platinum resistant ovarian cancer and platinum resistant colon cancer, both of which have poor prognoses," said Jonathan Sessler, professor and R.P. Doherty, Jr. - Welch Regents Chair in Chemistry at UT Austin and co-principal investigator on the project.

The drug candidate, called OxaliTEX, is made of two parts: a star-shaped molecule called texaphyrin that acts like a kind of delivery truck, and a modified version of a platinum drug that acts like a toxic package for cancer cells.

Some of the most commonly used chemotherapy drugs -- such as cisplatin, carboplatin and oxaliplatin -- can cause toxic side effects such as kidney damage. They also often lose effectiveness as cancerous cells develop resistance. But the texaphyrin molecule is designed to be more easily absorbed by cancerous cells than healthy human cells, reducing the drug's side effects. The new platinum drug has modifications that not only make it less toxic to healthy cells, further reducing side effects, but also that make it harder for cancerous cells to develop resistance.

The drug was developed by four inventors: Sessler; Jonathan Arambula, now vice president for research at OncoTEX; Grégory Thiabaud, a former UT Austin postdoctoral researcher, now a research associate at the Massachusetts Institute of Technology; and Zahid H. Siddik, a professor of pharmacology at MD Anderson.

The researchers compared the relative effectiveness of the new drug candidate OxaliTEX, and carboplatin, a platinum drug approved by the Food and Drug Administration commonly used to treat ovarian cancer, on mice that were carrying tumors. The mice that received carboplatin did not have a reduction in tumor growth.

Meanwhile, mice treated with OxaliTEX had 100% inhibition, meaning the tumors completely stopped growing. Two to three weeks after the drug treatment ended, tumors tended to begin growing again.

"We hope that with optimized dosing, we might be able to wipe out these tumors entirely," Arambula said.

The researchers also compared relative toxic side effects in mice between the new drug candidate OxaliTEX and oxaliplatin, an FDA-approved platinum drug used to treat colorectal and other cancers. They found OxaliTEX had much lower toxicity.

"We created something that's better tolerated than currently approved drugs," Arambula said. "That's the big message."

Next, the researchers plan to conduct more extensive toxicology studies and, assuming those go well, hope to start a Phase 1 human clinical trial within two years.

Since 2005, millions of bats have perished from white-nose syndrome, a disease caused by the fungus Pseudogymnoascus destructans. Although the disease has been found throughout much of the world, severe population declines have only occurred in North America -- and now researchers at Virginia Tech know why.

In a new PNAS study led by Joseph Hoyt, an assistant professor in the Department of Biological Sciences in the College of Science, researchers have found that the pathogen levels in the environment play a major role in whether bat populations are stable or experience severe declines from white-nose syndrome.

Hoyt and his international team of researchers published their findings in the Proceedings of the National Academy of Sciences on March 16.

"This study shows that more contaminated environments, or potential 'hot spots,' are going to result in higher disease impacts. By understanding the relationship between how much pathogen is present in the environment and the size of an outbreak, we can know exactly how much environmental sanitization is needed to reduce the epidemic potential," said Hoyt.

When infectious diseases first arise, it is crucial to understand how the disease is being transmitted. With a pathogen like Pseudogymnoascus destructans, which can exist outside of the host, researchers looked to the environmental pathogen reservoir -- or the habitat in which a pathogen persists or grows in the absence of hosts.

Pseudogymnoascus destructans is a cold-loving fungus, which resides on the walls of caves, mines, and other subterranean environments. Every year, as the cold and debilitating winter draws near, bats hibernate in these infected sites until they can return to the landscape in spring. And it is during this time that bats contract white-nose syndrome.

As Hoyt and his team journeyed out to find the historical origin of this disease, they were the first to find that the pathogen has already been present in Asia for thousands of years. In an even more astounding discovery, they found that European and Asian bat populations face little to no impacts from white-nose syndrome compared to bats in North America.

This unprecedented study revealed that the environmental pathogen reservoir in European and Asian sites decayed over the summer months, which left a smaller amount of pathogen in the environment for bats to come into contact with the following winter. In contrast, there was no decay of the pathogen in sites over the summer in North America, which resulted in widespread infection and mortality.

"The fact is that bats are experiencing much less severe infections at the beginning of the hibernation season across Europe and Asia. As a result, they are still getting infected but the process of infection is delayed relative to North American bats. So, they are experiencing far lower transmission from the environment than bats experience here in North America," said Kate Langwig, the second author of this paper and an assistant professor in the Department of Biological Sciences in the College of Science and an affiliated faculty member of the Global Change Center, housed under the Fralin Life Sciences Institute. "The differences in the environmental reservoir are really important for driving the dynamics of the disease across space."

With lower transmission of the pathogen and some time on their side, bats will be able to emerge from their infected roosts in just enough time to escape certain death.

"Because the pathogen decays in the environment over summer in Europe and Asia, most bats don't become infected until mid- to late- winter, which is too late for the infections to manifest into mortality. If you have delayed transmission, then bats are able to emerge in the spring and clear infection before it can ever result in death," said Hoyt.

This is one of the first papers to link the extent of the environmental reservoir to the size of an outbreak, the number of individuals that become infected, the severity of those infections, and population impacts.

Hoyt hopes that this paper will highlight the importance of environmental pathogen reservoirs in driving infectious disease outbreaks.

"The environmental pathogen reservoir has the potential to be really important. The idea that as you get a more contaminated environment, that scales with the degree of population impacts, is something that hasn't really been demonstrated before," said Hoyt.

Hoyt and his team are now trying to use findings from Eurasian bat populations to help North American bats. More specifically, they are trying to reduce the amount of pathogen in the environment in North America over summer when bats are absent from these sites.

"We are trying to replicate the pathogen decay that is happening in Europe and Asia, and delay transmission. If we can push bats to not get infected until later in the winter, then they might be able to survive until spring," said Hoyt.

Paleoclimate research offers an overview of Earth's climate change over the past 65 million years or longer and helps to improve our understanding of the Earth's climate system.

Unfortunately, our knowledge of weather-timescale extreme events (i.e., paleoweather occurring in days or even hours and minutes), such as tropical cyclones, cold/heat waves, and rainstorms under different climate conditions, is almost absent because current paleoclimatic reconstructions rarely provide information with temporal resolutions shorter than a month.

A new Chinese study may remedy this problem, though.

Recently, a research team led by Prof. YAN Hong, from the Institute of Earth Environment (IEE) of the Chinese Academy of Sciences, found that shells of the Giant Clam (Tridacna, the largest bivalve species in the ocean) from the western Pacific have clear and continuous daily growth bands.

Several daily to hourly biological and geochemical records, including daily growth rate, hourly element/Ca ratios and fluorescence intensity, were developed from the daily bands of Tridacna shells.

The researchers demonstrated that these ultra-high resolution records can clearly record, even quantitatively, the activities of past typical extreme weather events.

"This result indicated that Tridacna shells have the potential to be used as an unprecedented archive for Paleoweather reconstructions," said Prof. YAN.

As a result, fossils shells from different geological epochs have the potential to provide Paleoweather data from past warm and warming periods that can help improve the prediction of future extreme weather events under the expected global warming.

Topological insulators (TIs) are bulk insulating materials that nonetheless exhibit metallic conductivity on their surfaces. This conductivity is guaranteed by the bulk band structure's topology--the surface features these states as long as the symmetry defining the topological index remains the same.

In so-called strong TIs, these states are protected and so featured on all surfaces. In weak TIs however, these properties are only protected at surfaces with a certain orientation. Stacking two-dimensional TIs, that is QSHIs, to form a three-dimensional crystal, for example, generally produces a weak TI with no protected states on the top or bottom surfaces of the crystal: there are metallic surface states inherited from the edge states of the 2D TI, but also an insulating surface plane that lies normal to the stacking direction.

Recent theoretical work, also carried out by MARVEL researchers, suggested however that this might not be the case for stacked, or bulk, jacutingaite. The research suggested a more complicated scenario--the material may be a topological crystalline insulator (TCI) as well as a weak TI. In TCIs, the topology is defined by symmetry with respect to a mirror plane and metallic surface states can be found on surfaces perpendicular to it. This state might be expected in the material because of it threefold mirror symmetry. Jacutingaite also maintains translational symmetry in the stacking of the layers though, meaning that it might also feature the properties of a weak TI. Until now, however, there have been no experimental results on the bulk band structure.

Research initiated by EPFL's THEOS lab and carried out in collaboration with the Department of Quantum Matter Physics at the University of Geneva and other groups including the Diamond Light Source in the UK, has now however described the first ever synthesis of a single crystal of jacutingaite and used the sample to provide evidence for their dual-topological nature by comparing the bulk and surface electronic structure determined from synchrotron-based angle-resolved photoemission (ARPES) experiments with DFT calculations. The paper, Bulk and Surface Electronic Structure of the Dual-Topology Semimetal Pt2HgSe3, has recently been published in Physical Review Letters.

The work revealed topologically-protected surface states in the natural cleavage plane (001) of the material, unexpected as it should rather support a weak topological phase since it is a stack of 2D QSHIs. Calculations of certain topological invariants confirmed the weak topological insulator phase generally characterized by gapless modes on the lateral surfaces, but fully gapped states on the top and bottom surfaces. The surface states found on the 001 surface were therefore assumed to be the manifestation of a different topological phase.

The researchers hypothesized that it might be an indication of the TCI phase associated with the threefold mirror symmetry of the crystal. In such a case, topologically protected surface states are expected on crystal surfaces that preserve the mirror symmetry and this was the case for the cleaved (001) surface.

Using first principles calculations, the researchers were able to identify this surface state as the signature of a TCI phase that coexists with the generic WTI phase found in the same calculations. The results thus provide evidence for the predicted dual topology of Pt2HgSe3. What remained unclear however is the mechanism behind jacutingaite's status as a dual topological insulator.

This very topic was addressed in theoretical work developed at EPFL's THEOS, research that complemented the experimental and computational work carried out in the other paper. In the paper Emergent dual topology in the three-dimensional Kane-Mele Pt2HgSe3, researchers Antimo Marrazzo, Nicola Marzari, and colleague Marco Gibertini at the University of Geneva, formerly of THEOS, extended the two-dimensional Kane-Mele (KM) model used to describe topological materials to bulk jacutingaite. The paper was recently published in Physical Review Research.

They showed that the unexpected topology in bulk jacutingaite comes from a strong interlayer hybridization that leads to a 3D generalization of the KM model. While nearest layers are almost decoupled, there is a large, peculiar hopping term that indicates strong coupling between layers that are two layers apart. Even and odd layers are then more or less independent and can be separately described by a 3D KM model, dubbed J3KM in the paper, that includes a band inversion driven by this novel hopping term. This results in a nodal line that is gapped by spin-orbit coupling and a nonzero Chern number--that is, protected surface states consistent with TCIs. When coupling between even and odd layers is restored though, the material again acts as a WTI.

This insight provides a microscopic understanding of the emergent dual topology of the material. The J3KM model predicts the presence of surface states and nodal lines gapped by spin-orbit interactions, in agreement with the ARPES measurements and first-principles simulations carried out in the other paper. The model is relevant for all other layered materials made of stacked honeycomb lattices and provides an appealing strategy for breaking the standard paradigm of weak topological insulators.

Finally, the combination of the experimental evidence, first-principles simulations and theoretical models on 3D jacutingaite supports THEOS's earlier prediction that 2D jacutingaite is a Kane-Mele (graphene-like) quantum spin Hall insulator.

A new study from the University of Birmingham has shown that Faecal Microbiota Transplants (FMT) are highly successful in treating patients with Clostridioides difficile (C.diff) infection.

Published in EClinical Medicine, results from the first licenced English stool bank, which supplies FMT treatment to patients in the NHS, have shown that in 78% of cases the patient's diarrhoea had stopped and had not returned in the 90 days after treatment.

Antibiotics can be effective in treating the first episode of C.diff. However, 10-20% of patients don't respond and the infection then recurs. Success rates of antibiotics in relapsing infection can be as low as 30%.

C.diff infections result from the good gut bacteria being killed by antibiotics given for other infections and causes severe diarrhoea, abdominal pain and may be fatal in elderly patients.

During FMT, the good bacteria in the faeces of a healthy donor are transferred to the gut of a patient with the infection.

The Microbiome Treatment Centre at the University of Birmingham is the first in the UK to be licenced for FMT preparation by the Medicines and Healthcare products Regulatory Agency (MHRA), supplying NHS patients across the country.

Before the dedicated centre was set up, many patients across the UK were unable to access this treatment.

Scientific studies have demonstrated that FMT treatment is better than treatment with special expensive antibiotics for C.diff infections, particularly when the patient's infection has come back again.

The development of a licenced FMT service at the University of Birmingham will widen the supply and improve equality of access to FMT treatment across the NHS. It will provide critical support for researchers both here in Birmingham and in other centres working on how FMT produces a cure not only in C.diff infection but also conditions such as ulcerative colitis and other diseases which seem to be linked to the gut microbiome.

Lead author Dr Victoria McCune, Consultant Clinical Scientist in Microbiology at South Tees Hospital NHS Foundation Trust, said:

"Our research has successfully shown the benefits of treating recurrent C.diff patients with FMT. Our standardised approach to making FMT will improve the quality and safety of this treatment for many more patients."

Professor Peter Hawkey, Professor of Clinical and Public Health Bacteriology at the University of Birmingham's Institute of Microbiology and Infection, said:

"This work has turned an unregulated potentially dangerous method of faecal transplantation into a national service providing rapid, safe regulated, life-saving treatment for a serious disease affecting thousands of patients in the UK."

New research lends credence to an unorthodox retelling of the story of early Earth first proposed by a geophysicist at Scripps Institution of Oceanography at UC San Diego.

In a study appearing March 15 in the journal Earth and Planetary Science Letters, Scripps Oceanography researchers Dave Stegman, Leah Ziegler, and Nicolas Blanc provide new estimates for the thermodynamics of magnetic field generation within the liquid portion of the early Earth's mantle and show how long that field was available.

The paper provides a "door-opening opportunity" to resolve inconsistencies in the narrative of the planet's early days. Significantly, it coincides with two new studies from UCLA and Arizona State University geophysicists that expand on Stegman's concept and apply it in new ways.

"Currently we have no grand unifying theory for how Earth has evolved thermally," Stegman said. "We don't have this conceptual framework for understanding the planet's evolution. This is one viable hypothesis."

The trio of studies are the latest developments in a paradigm shift that could change how Earth history is understood.

It has been a bedrock tenet of geophysics that Earth's liquid outer core has always been the source of the dynamo that generates its magnetic field. Magnetic fields form on Earth and other planets that have liquid, metallic cores, rotate rapidly, and experience conditions that make the convection of heat possible.

In 2007, researchers in France proposed a radical departure from the long-held assumption that the Earth's mantle has remained entirely solid since the very beginnings of the planet. They argued that during the first half of the planet's 4.5-billion-year history, the bottom third of Earth's mantle would have had to have been molten, which they call "the basal magma ocean." Six years later, Stegman and Ziegler expanded upon that idea, publishing the first work showing how this once-liquid portion of the lower mantle, rather than the core, could have exceeded the thresholds needed to create Earth's magnetic field during that time.

The Earth's mantle is made of silicate material that is normally a very poor electrical conductor. Therefore, even if the lowermost mantle were liquid for billions of years, rapid fluid motions inside it wouldn't produce large electrical currents needed for magnetic field generation, similar to how Earth's dynamo currently works in the core. Stegman's team asserted the liquid silicate might actually be more electrically conductive than what was generally believed.

"Ziegler and Stegman first proposed the idea of a silicate dynamo for the early Earth," said UCLA geophysicist Lars Stixrude. The idea was met with skepticism because their early results "showed that a silicate dynamo was only possible if the electrical conductivity of silicate liquid was remarkably high, much higher than had been measured in silicate liquids at low pressure and temperature."

A team led by Stixrude used quantum-mechanical computations to predict the conductivity of silicate liquid at basal magma ocean conditions for the first time.

According to Stixrude, "we found very large values of the electrical conductivity, large enough to sustain a silicate dynamo." The UCLA study appeared in the Feb. 25 issue of Nature Communications.

In another paper, Arizona State geophysicist Joseph O'Rourke applied Stegman's concept to consider whether it's possible that Venus might have at one point generated a magnetic field within a molten mantle.

These new studies are signs that the premise is starting to take hold, but is still far from being widely accepted.

"No one is going to believe it until they do it themselves and now two other highly esteemed scientists have done it themselves," said Stegman.

"The pioneering studies of Dave Stegman and his collaborators directly inspired my work on Venus," said O'Rourke. "Their recent paper helps answer a question that vexed scientists for many years: How has Earth's magnetic field survived for billions of years?"

If Stegman's premise is correct, it would mean the mantle could have provided the young planet's first magnetic shield against cosmic radiation. It could also underpin studies of how tectonics evolved on the planet later in history.

"If the magnetic field was generated in the molten lower mantle above the core, then Earth had protection from the very beginning and that might have made life on Earth possible sooner," Stegman said.

"Ultimately, our papers are complementary because they demonstrate that basal magma oceans are important to the evolution of terrestrial planets," said O'Rourke. "Earth's basal magma ocean has solidified but was key to the longevity of our magnetic field."

WOODS HOLE, Mass. -- It's not spring in New England until the herring are running. From late February to early April, two species of herring --alewife and blueback herring--return from the ocean and swarm the region's ponds and streams, seeking the waters in which they were born.

"[Alewife] come back every year to find areas to reproduce, much like salmon [do] in freshwater ponds," says Ivan Valiela, Distinguished Scientist at the Ecosystems Center at the Marine Biological Laboratory (MBL). The species are "canaries in the coal mines" indicating shifts in the health of the Northeastern coastal environment, he said.

Populations of coastal alewife have been in decline since the 1960s, with a sharp drop in the 2000s, according to a new research paper by Valiela and colleagues. Commercial landings of river herring in 2005 were only about 1 percent of 1958's catch.

The study, led by Rita Monteiro Pierce, examined how urban development of New England coastal watersheds affects the size and health alewife stocks. They found that "the more developed the watershed, the less well off the alewives that were leaving them," says Valiela. "Growth and the condition of the fish [were] impaired by increased urbanization."

The researchers chose nine coastal ponds --six on Cape Cod, Mass., and three in Maine--and sampled alewife born in 2008 as they headed out to sea for the first time. The ponds, all known alewife breeding sites, were part of watersheds with a wide range of urbanization (from 3 to 60 percent urban land use cover).

Johns Pond in Sandwich, Mass., was the most-urbanized area studied. The young alewife sampled there were nearly half as long and up to 10 times lighter than alewife collected in streams coursing through the less urbanized areas.

Monteiro Pierce conducted research at the MBL Ecosystems Center for several years while a doctoral student at the State University of New York College of Environmental Science and Forestry in Syracuse, N.Y.

RIVERSIDE, Calif. -- How does the brain form "fear memory" that links a traumatic event to a particular situation? A pair of researchers at the University of California, Riverside, may have found an answer.

Using a mouse model, the researchers demonstrated the formation of fear memory involves the strengthening of neural pathways between two brain areas: the hippocampus, which responds to a particular context and encodes it, and the amygdala, which triggers defensive behavior, including fear responses.

Study results appear today in Nature Communications.

"It has been hypothesized that fear memory is formed by strengthening the connections between the hippocampus and amygdala," said Jun-Hyeong Cho, an assistant professor in the Department of Molecular, Cell and Systems Biology and the study's lead author. "Experimental evidence, however, has been weak. Our study now demonstrates for the first time that the formation of fear memory associated with a context indeed involves the strengthening of the connections between the hippocampus and amygdala."

According to Cho, weakening these connections could erase the fear memory.

"Our study, therefore, also provides insights into developing therapeutic strategies to suppress maladaptive fear memories in post-traumatic stress disorder patients," he said.

Post-traumatic stress disorder, or PTSD, affects 7% of the U.S. population. A psychiatric disorder that can occur in people who have experienced or witnessed a traumatic event, such as war, assault, or disaster, PTSD can cause problems in daily life for months, and even years, in affected persons.

Cho explained the capability of our brains to form a fear memory associated with a situation that predicts danger is highly adaptive since it enables us to learn from our past traumatic experiences and avoid those dangerous situations in the future. This process is dysregulated, however, in PTSD, where overgeneralized and exaggerated fear responses cause symptoms including nightmares or unwanted memories of the trauma, avoidance of situations that trigger memories of the trauma, heightened reactions, anxiety, and depressed mood.

"The neural mechanism of learned fear has an enormous survival value for animals, who must predict danger from seemingly neutral contexts," Cho said. "Suppose we had a car accident in a particular place and got severely injured. We would then feel afraid of that -- or similar -- place even long after we recover from the physical injury. This is because our brains form a memory that associates the car accident with the situation where we experienced the trauma. This associative memory makes us feel afraid of that, or similar, situation and we avoid such threatening situations."

According to Cho, during the car accident, the brain processes a set of multisensory circumstances around the traumatic event, such as visual information about the place, auditory information such as a crash sound, and smells of burning materials from damaged cars. The brain then integrates these sensory signals as a highly abstract form -- the context -- and forms a memory that associates the traumatic event with the context.

The researchers also plan to develop strategies to suppress pathological fear memories in PTSD.

For years Professor Kenneth Leung Mei Yee from the HKU School of Biological Sciences and the Swire Institute of Marine Science and his research team, have been dedicated to the monitoring of toxic substances tribuyltin (TBT) and triphenyltin (TPT) compounds in our marine environment.

Globally, organotin compounds such as tribuyltin (TBT) and triphenyltin (TPT) have been widely used as antifouling agents on ship hulls and submerged mariculture facilities over the past decades. Hence, they are often detected in seawater, sediment and biota samples collected from coastal marine environments of urbanised coastal cities worldwide. At very low concentrations, these compounds can cause endocrine disruption or even death in marine organisms. The International Maritime Organisation (IMO) of the United Nations has implemented a global ban on the use of organotin compounds on the hull of sea-going vessels since 2008.

Together with their collaborators, Professor Leung's research team discovered that despite a decline of TBT concentration in our marine environment in recent years, the levels of TPT contamination remained serious with an increasing trend. In addition to TPT contamination in seafood, the team's recent research has also confirmed the occurrence of biomagnification of TPT compounds along the marine food chain, resulting in very high concentrations of TPT in two top predators, the Chinese white dolphin and the finless porpoises.

This is the first study in the world to confirm the trophic magnification of TPT in food webs of cetacean species, and the findings were recently published in Environment International.

Background

TBT and TPT are highly toxic biocides which can cause growth inhibition to marine algae and mortality to many marine invertebrates and fishes at 1-50 μg/L*. At very low concentrations (1-10 ng/L**), these compounds can cause endocrine disruption in marine organisms such as growth retardation and shell thickening in oysters, and abnormal development of male sex organs on females of gastropods. TBT and TPT accumulate along the food chain in larger organisms such as fish, and may have an adverse effect on health when consumed by humans.

Professor Kenneth Leung and his research team have been monitoring organotin pollution in the marine environment of Hong Kong since 2004. They discovered that TPT contamination remained serious with an increasing trend. TPT had been found in our seafood and in some case, their concentrations (e.g. those in tonguefishes) exceeded the food safety limit for human consumption. In 2017, the Government of the Hong Kong Special Administrative Region finally established a new legislation (Cap. 413, section 3) to support the IMO's global ban of using organotin compounds on vessels, and enhance the control of their release.

Methodology

In order to fully understand the extent of the contamination, Professor Leung and his team have recently completed a follow-up research in collaboration with Xiamen University and the State Key Laboratory of Marine Pollution, to investigate the extent of TPT contamination in marine food webs in Hong Kong, and verify whether TPT and its degradation products (i.e., mono- and di-phenyltin; MPT and DPT) can be biomagnified through the food chain, leading to very high concentrations in local Chinese white dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides).

The Chinese white dolphins prefer the inner estuary of the Pearl River Delta, while the porpoises have a greater home range from the southwest to the southeast waters of Hong Kong. Between 2015 and 2017, the study team obtained samples of stranded dolphins and porpoises from the Ocean Park Conservation Fund Hong Kong and collected samples of marine molluscs, crustaceans and fishes from waters at the northwest (i.e., inner estuary) and southwest (i.e., outer estuary) of Lantau Island, respectively. Muscle tissues of all biota samples were analysed for MPT, DPT and TPT using gas chromatography-mass spectrometry, and used for determination of trophic levels using a stable isotope ratio mass spectrometer.

Research findings

Research findings showed that TPT was the predominant phenyltin compound in the marine mammals, indicating that contamination is an on-going issue. High concentrations of TPT were recorded in the muscle tissue of the Chinese white dolphins and the finless porpoises, with an average of 1,893.8 ng/g w. w. and 1,477.6 ng/g w. w. recorded respectively, even higher than the highest concentration of TPT ever reported in marine mammals the false killer whale worldwide (the false killer whale in Japan with 649 ng/g w. w.[1]). The highest concentration of TPT detected in an adult Chinese white dolphin in this study (3,476.6 ng/g w. w.) was five times higher than that of the false killer whale. At elevated concentrations, TPT can lead to sublethal adverse effects to the immune, nervous, cardiovascular and reproductive systems of mammals, resulting in a negative impact on the population fitness of these local dolphins and porpoises in the Pearl River Delta.

Alarmingly, this study also found that the highest TPT concentration in a juvenile finless porpoise (3,455.6 ng/g w. w.) was ten times higher than the highest value (310 ng/g w. w.) recorded in the same species collected from Hong Kong in 2003[2], indicating a worsening situation of TPT contamination.

Based on the results of stable isotope and chemical analyses, tissue concentrations of both DPT and TPT significantly increased with increasing trophic level of marine organisms in the food web of the Chinese white dolphins (i.e., inner estuary) while only TPT tissue concentration showed a positive relationship with the trophic level of the biota in the food web of the finless porpoises. For the Chinese white dolphins, trophic magnification factors (TMF) of DPT and TPT were found to be 6.03-11.48 and 2.45-3.39, respectively. For the finless porpoises, the TMF of TPT was found to be 2.51-3.47. When a TMF is greater than 1, it indicates that the chemical compound can be biomagnified through the marine food chain.

The results of the study suggest that high trophic organisms including humans are likely to be vulnerable to the exposure of DPT and TPT compounds via dietary intake due to the high trophic magnification potential of these chemicals. Therefore, environmental and human health risks of these compounds should be assessed with consideration of their biomagnification potentials along the food chain.

Regarding ways to reduce the health risk of TPT exposure, Professor Leung said, "The public should avoid and minimise the consumption of very large fishes such as sharks and Reeve's croakers, and also benthic fish species such as the flathead and tongue sole fishes, as they probably contain high concentrations of TPT and other persistent organic pollutants in their tissues. Instead, they can consume crustaceans (e.g. shrimps and crabs), shellfishes (e.g. mussels, clams and oysters), and small fishes as an effective way to reduce the intake of TPT and other chemical contaminants."

Dr James Lam Chung Wah, an environmental toxicologist and Assistant Professor at the Department of Science and Environmental Studies of the Education University of Hong Kong, who was not involved in the study, commented, "This interesting and impactful study led by HKU provided solid evidence of such a significant biomagnification of TPT along the marine food chain of marine mammals. Their results also highlight the greater impact of TPT on top predators in the sea and in humans through seafood consumption." He also added, "To improve the current situation of organotin contamination, we must reduce their use and release at the source. Around the world, every government needs to play a part in strengthening the regulation and control of the use of toxic chemicals (like TPT compounds) in order to minimise their release into the environment."

KAIST researchers developed a three-dimensional (3D) hierarchically porous nanostructured catalyst with carbon dioxide (CO2) to carbon monoxide (CO) conversion rate up to 3.96 times higher than that of conventional nanoporous gold catalysts. This new catalyst helps overcome the existing limitations of the mass transport that has been a major cause of decreases in the CO2 conversion rate, holding a strong promise for the large-scale and cost-effective electrochemical conversion of CO2 into useful chemicals.

As CO2 emissions increase and fossil fuels deplete globally, reducing and converting CO2 to clean energy electrochemically has attracted a great deal of attention as a promising technology. Especially due to the fact that the CO2 reduction reaction occurs competitively with hydrogen evolution reactions (HER) at similar redox potentials, the development of an efficient electrocatalyst for selective and robust CO2 reduction reactions has remained a key technological issue.

Gold (Au) is one of the most commonly used catalysts in CO2 reduction reactions, but the high cost and scarcity of Au pose obstacles for mass commercial applications. The development of nanostructures has been extensively studied as a potential approach to improving the selectivity for target products and maximizing the number of active stable sites, thus enhancing the energy efficiency.

However, the nanopores of the previously reported complex nanostructures were easily blocked by gaseous CO bubbles during aqueous reactions. The CO bubbles hindered mass transport of the reactants through the electrolyte, resulting in low CO2 conversion rates.

In the study published in the Proceedings of the National Academy of Sciences of the USA (PNAS) on March 4, a research group at KAIST led by Professor Seokwoo Jeon and Professor Jihun Oh from the Department of Materials Science and Engineering designed a 3D hierarchically porous Au nanostructure with two different sizes of macropores and nanopores. The team used proximity-field nanopatterning (PnP) and electroplating techniques that are effective for fabricating the 3D well-ordered nanostructures.

The proposed nanostructure, comprised of interconnected macroporous channels 200 to 300 nanometers (nm) wide and 10 nm nanopores, induces efficient mass transport through the interconnected macroporous channels as well as high selectivity by producing highly active stable sites from numerous nanopores.

As a result, its electrodes show a high CO selectivity of 85.8% at a low overpotential of 0.264 V and efficient mass activity that is up to 3.96 times higher than that of de-alloyed nanoporous Au electrodes.

"These results are expected to solve the problem of mass transfer in the field of similar electrochemical reactions and can be applied to a wide range of green energy applications for the efficient utilization of electrocatalysts," said the researchers.

he molecule NCAM2, a glycoprotein from the superfamily of immunoglobulins, is a vital factor in the formation of the cerebral cortex, neuronal morphogenesis and formation of neuronal circuits in the brain, as stated in the new study published in the journal Cerebral Cortex. The deficit of NCAM2 causes an incorrect migration of neurons and alters the morphology, cytoskeleton and functionality of these cells in the central nervous system.

This article studies for the first time the activity of NCAM2 in the cortex and the hippocampus, brain structures where the function of this factor was so far unknown. The study is led by the experts Eduardo Soriano and Lluís Pujades, from the Faculty of Biology and the Institute of Neurosciences of the University of Barcelona (UBNeuro), the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) and the Vall d'Hebron Research Institute (VHIR). The first author of the study is the researcher Antoni Parcerisas, member of the above-mentioned centers.

Other participants in this study are the experts from the Catalan Institution for Research and Advanced Studies (ICREA), Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology (BIST), the Spanish National Research Council (CSIC), the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the University of California in Davis (United States).

NCAM2: an unknown function in the cortex and hippocampus

The NCAM2 glycoprotein is a cell-adhesion molecule present in all vertebrates and which plays a decisive role in the organization of neuronal circuits in the central nervous system. This factor is largely expressed in the brain -from embryonic phases to adulthood- and specially in the olfactory bulb. Traditionally, all previous studies were focused on the olfactory bulb and proved a key role of the protein in neuronal synapses and neuronal compartmentalization between axons and dendrites. Recent studies described the involvement of NCAM2 in the formation and growth of neurites in cortical neurons, in the loss of synapsis in hippocampal neurons -caused by the amyloid peptide in Alzheimer's disease- and the proliferation of neuronal progenitors in the spinal cord.

The new study describes for the first time the function of NCAM2 and the observed phenotypes in the development of the cortex and the hippocampus, a highly complex process regulated by many proteins. "In the study we confirm that a loss of NCAM2 creates an incorrect migration and position of neurons -these do not join the corresponding layer- and it also alters the neuronal morphology and the features of the cytoskeleton of nervous cells", notes researcher Antoni Parcerisas.

"In the neuronal phenotype -adds Parcerisas- we see an altered dendritic tree -smaller and with many small and short dendrites- and an axon with more branches. In certain cases, some neurons show problems of neuronal polarization as well".

An essential factor in the neuronal cytoarchitecture

A new study on brain neurobiology applies several experimental approaches -in vitro and in vivo techniques and live-imaging experiments- to see how neurons evolve. According to the conclusions, the isoform NCAM2.1 interacts direct and indirectly with the cell cytoskeleton and it modulates the dynamics of its components -microtubules and proteins- which are essential for the migration and development process of the neuron.

The loss of NCAM2 would cause the retraction of the existing dendrites and would alter the cell cytoskeleton (lower stability and altered dynamics of microtubule formation). This hypothesis is supported by the fact that when Taxol -chemical agent that boosts microtubule stability- is added, it can reverse the phenotype generated by the loss of NCAM2.

Moreover, NCAM2.1 can also interact with several proteins that regulate the stability of the cytoskeleton, such as MAP2 and 14-3-3. In particular, NCAM2.1 would form a protein complex with MAP2 and 14-3-3 that would ease the stabilization processes of the microtubule cytoskeleton, essential for the development of the dendritic tree.

What role does NCAM2 play in neuronal polarization?

The dynamics and organization of cytoskeleton microtubules are essential to maintain the neuronal polarization, which defines the morphological and functional differences between axons and dendrites and enables the transmission of the nervous impulse.

Although the NCAM2 participation pathway is unknown in neuronal polarization processes, "we observed a deficit of NCAM2 leads to the apparition of multiple axonal structures (instead of one axon only, as expected) due to the changes that occur in the dynamics of the neuron cytoskeleton. Therefore, NCAM2 is a necessary factor during the process of neuronal polarization to provide structures with stability and enable the differentiation of a neurite in axon", notes Parcerisas.

Deficit of NCAM2 protein and cognitive developmental pathologies

NCAM2 presents an expression pattern which is typical from those proteins involved in neuronal morphogenesis and synaptogenesis. Moreover, the expression pattern of NCAM2 shows changes in cell location depending on the neuronal developmental phases.

"A deficit of this protein -at a genomic or protein scale- would cause neuronal alterations in several developmental phases. In this context, some genetics note that the loss of NCAM2 could be the origin of cognitive alterations in patients with autism spectrum disorders and neurodevelopmental problems", note the authors.

"It would be important to promote new genetic and proteomic studies in patients with neurodevelopmental pathologies to help determine the causes of these diseases. In case this hypothesis was confirmed -if there was a relation between these pathologies with the deficit of NCAM2- researchers could think about doing research on new molecular targets to help regulate the signaling pathways and the affected cell processes", conclude the authors of the new study.

In recent years, the development of quantum computers beyond the capability of classical computers has become a new frontier in science and technology and a key direction to realize quantum supremacy. However, conventional quantum computing has a serious challenge due to quantum decoherence effect and requires a significant amount of error correction in scaling quantum qubits. Therefore, the exploration of fault-tolerant quantum computation using quantum states topologically protected against local environmental perturbations is an important endeavor of both fundamental value and technological significance for realizing large-scale quantum computation.

Majorana zero-energy bound states (ZEBSs) in condensed matter systems such as superconductors are such rare quantum states with topological protection against local perturbations. These so called Majorana zero modes (MZMs) are charge neutral and obey non-abelian exchange statistics and serve as the building block of topological qubits. MZMs are theoretically predicted to exist in the vortex core of p-wave topological superconductors or at the ends of one-dimensional (1D) topological superconductors. Being a ZEBS, one of the main characteristics of the MZM is the differential conductance peaks for tunneling at zero bias voltage. Experimentally, the current Majorana platforms include the following. One is using a three-dimensional (3D) topological insulator proximity-coupling to an s-wave superconductor to realize the superconducting topological surface states and detect the vortex states by applying a magnetic field. The other one is using a 1D spin-orbit coupling nanowire proximity-coupling to an s-wave superconductor to detect zero-bias conductance peaks at the ends under an external magnetic field. However, the complicated fabrication of the hybrid structures, the extremely low temperature and the applied magnetic field required for observation present great challenges to the possible application of MZMs.

Recently, Professor Wang Jian's group at Peking University, in collaboration with Professor Wang Ziqiang's group at Boston College, discovered MZMs at both ends of 1D atomic line defects in two-dimensional (2D) iron-based high-temperature superconductors and provided a promising platform to detect topological zero-energy excitations at a higher operating temperature and under zero external magnetic field. Wang Jian's group successfully grew large-area and high-quality one-unit-cell-thick FeTe 0.5Se 0.5
films on SrTiO3(001) substrates by molecular beam epitaxy (MBE) technique, which show Tc (~62 K) much higher than that (~14.5 K) in bulk Fe(Te,Se). By in situ low-temperature (4.2 K) scanning tunneling microscopy/spectroscopy (STM/STS), the 1D atomic line defects formed by the missing topmost Te/Se atoms can be clearly identified on the monolayer FeTe 0.5
Se 0.5
films. The ZEBSs are detected at both ends of the 1D atomic line defect (Figure 1), while the tunneling spectra in the middle of the line defect recover to the fully gapped superconducting states. As the temperature increases, the ZEBS reduces in intensity, and finally vanishes at a temperature (around 20 K) far below Tc. The ZEBS does not split with increasing tunneling barrier conductance and becomes sharper and higher as the tip approaches the film, showing the robust property. Moreover, on the shorter defect chain, the coupling between the ZEBSs at both ends leads to reduced zero-bias conductance peaks even in the middle section of the atomic line defect chain (Figure 2). The positive correlation between the zero-bias conductance and line defect lengths can be deduced from the statistics. The spectroscopic properties of the ZEBSs, including the evolution of the peak height and width with temperature, the disappearing temperature of ZEBS, the tunneling spectra in tip-approaching-sample process, as well as unsplit property are found to be consistent with the MZMs interpretation. Other possibilities such as Kondo effect, conventional impurity states or the Andreev zero-energy bound states in nodal high-temperature superconductors can be excluded in general.

Professor Wang Ziqiang's group at Boston College proposed a possible theoretical explanation by extending the band theory of the Shockley surface state to the case of superconductors. Due to the large spin-orbit coupling, the 1D atomic line defect in monolayer FeTe 0.5
Se 0.5
film may become an emergent 1D topological superconductor and a Kramers pair of MZMs appearing at the ends of the line defect protected by time-reversal symmetry. Even without time-reversal symmetry along the line defect, the 1D topological superconductor can also be realized with a single MZM located at each end of the chain. This work, for the first time, reveals a class of topological zero-energy excitations at both ends of 1D atomic line defects in 2D high-temperature superconducting monolayer FeTe 0.5
Se 0.5
films, which show the advantages of being a single material, higher operating temperature and zero external magnetic field, and may offer a new platform for future realizations of applicable topological qubits.

These findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system. The results of this research are published in Cell Stem Cell on March 12, 2020.

Stem cells in our bodies act as reservoirs of cells that divide to produce new stem cells, as well as a myriad of different types of specialized cells, required to secure tissue renewal and function. Commonly called "blood stem cells", the hematopoietic stem cells (HSC) are nestled in the bone marrow, the soft tissue that is in the center of large bones such as the hips or thighs. Their role is to renew the repertoire of blood cells, including cells of the immune system which are crucial to fight infections and other diseases.

Until a decade ago, the dogma was that HSCs were unspecialized cells, blind to external signals such as infections. Only their specialized daughter cells would sense these signals and activate an immune response. But work from Prof. Michael Sieweke's laboratory and others over the past years has proven this dogma wrong and shown that HSCs can actually sense external factors to specifically produce subtypes of immune cells "on demand" to fight an infection. Beyond their role in an emergency immune response, the question remained as to the function of HSCs in responding to repeated infectious episodes. The immune system is known to have a memory that allows it to better respond to returning infectious agents. The present study now establishes a central role for blood stem cells in this memory.

"We discovered that HSCs could drive a more rapid and efficient immune response if they had previously been exposed to LPS, a bacterial molecule that mimics infection", said Dr. Sandrine Sarrazin, Inserm researcher and senior-author of the publication. Prof. Michael Sieweke, Humboldt Professor at TU Dresden, CNRS Research Director and last author of the publication, explained how they found the memory was stored within the cells: "The first exposure to LPS causes marks to be deposited on the DNA of the stem cells, right around genes that are important for an immune response. Much like bookmarks, the marks on the DNA ensure that these genes are easily found, accessible and activated for a rapid response if a second infection by a similar agent was to come."

The authors further explored how the memory was inscribed on the DNA, and found C/EBP? to be the major actor, describing a new function for this factor, which is also important for emergency immune responses. Together, these findings should lead to improvements in tuning the immune system or better vaccination strategies.

"The ability of the immune system to keep track of previous infections and respond more efficiently the second time they are encountered is the founding principle of vaccines. Now that we understand how blood stem cells book mark immune response circuits, we should be able to optimize immunization strategies to broaden the protection to infectious agents. It could also more generally lead to new ways to boost the immune response when it underperforms or turn it off when it overreacts", concluded Prof. Michael Sieweke.

The research group of Prof. Michael Sieweke works at the interface of immunology and stem cell research. The scientists focus on the study of hematopoietic stem cells and macrophages, long-lived mature cells of the immune system that fulfil an important role in tissue regeneration. In 2018, Prof. Michael Sieweke received the most valuable research award in Germany: the Alexander von Humboldt Professorship, which brings top international researchers to German universities. In addition to his position as Research Director at the Centre for Immunology at the University of Marseille Luminy, he now acts as Deputy Director at the Center for Regenerative Therapies at TU Dresden (CRTD). CRTD is academic home for scientists from more than 30 nations. Their mission is to discover the principles of cell and tissue regeneration and leveraging this for recognition, treatment and reversal of diseases. The CRTD links the bench to the clinic, scientists to clinicians to pool expertise in stem cells, developmental biology, gene-editing and regeneration towards innovative therapies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease, hematological diseases such as leukaemia, metabolic diseases such as diabetes, retina and bone diseases.

A protein that normally deposits mineralized calcium in tooth enamel may also be responsible for calcium deposits in the back of the eye in people with dry age-related macular degeneration (AMD), according to a study from researchers at the National Eye Institute (NEI). This protein, amelotin, may turn out to be a therapeutic target for the blinding disease. The findings were published in the journal Translational Research. NEI is part of the National Institutes of Health.

"Using a simple cell culture model of retinal pigment epithelial cells, we were able to show that amelotin gets turned on by a certain kind of stress and causes formation of a particular kind of calcium deposit also seen in bones and teeth. When we looked in human donor eyes with dry AMD, we saw the same thing," said Graeme Wistow, Ph.D., chief of the NEI Section on Molecular Structure and Functional Genomics, and senior author of the study.

There are two forms of AMD - wet and dry. While there are treatments that can slow the progression of wet AMD, there are currently no treatments for dry AMD, also called geographic atrophy. In dry AMD, deposits of cholesterol, lipids, proteins, and minerals accumulate at the back of the eye. Some of these deposits are called soft drusen and have a specific composition, different from deposits found in wet AMD. Drusen form under the retinal pigment epithelium (RPE), a layer of cells that transports nutrients from the blood vessels below to support the light-sensing photoreceptors of the retina above them. As the drusen develop, the RPE and eventually the photoreceptors die, leading to blindness. The photoreceptors cannot grow back, so the blindness is permanent.

Recently, researchers found a calcium-containing mineral compound called hydroxyapatite (HAP) in dry AMD deposits. HAP is a key component of tooth enamel and bone. Small balls of HAP filled with cholesterol, called spherules, were found only in drusen from people with dry AMD, and not in those with wet AMD or without AMD.

In this study, Wistow's team discovered that if they starved RPE cells grown in transwells, a type of cell culture system, for 9 days, the cells began to deposit HAP. They determined that the protein amelotin, encoded by the gene AMTN, is strongly upregulated after extended starvation and is responsible for the mineralization of HAP in their cell culture model. Blocking this pathway in their RPE cell line also blocked the production of these drusen-like deposits.

To verify that their cell culture model was accurately representing dry AMD, the researchers examined human cadaver eyes with dry AMD, wet AMD, or without AMD. They found HAP and amelotin only in the eyes with dry AMD, and not in the other eyes. While amelotin was found sometimes in areas of dry AMD without drusen, it was primarily present in soft drusen areas with large deposits of HAP.

"Prior to this study, nobody really knew how the hydroxyapatite was accumulating in the dry AMD drusen," said Dinusha Rajapakse, Ph.D., the first author of the study. "Finding this tooth-specific protein in the eye, this protein that's linked to hydroxyapatite deposition - that was really unexpected."

Why RPE cells in dry AMD begin depositing these HAP spherules is unclear, but Wistow thinks it may be a protective mechanism gone awry. It's possible, he says, that these protein, lipid and mineral deposits may help damaged RPE cells block blood vessels from growing into the retina, a problem that is one of the key features of wet AMD. But when the mineral deposits get too extensive, they may also block nutrient flow to the RPE and photoreceptors, leading to retinal cell death.

"Mechanistically, amelotin looks like a key player for the formation of these very specific hydroxyapatite spherules. That's what it does in the teeth, and here it is in the back of the eye. Conceptually, you could see coming up with drugs that specifically block the function of amelotin in eye, and this might delay the progression of the disease. But we won't know until we try it," said Wistow.

Good animal models for testing dry AMD therapeutics are urgently needed. Based on the findings from this study, Wistow and his team are creating a new mouse model for the disease. Additionally, Wistow believes his cell culture model, which mimics features of dry AMD, could potentially be useful for high throughput drug screening to find molecules that slow or prevent the development of soft drusen.