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New genetic analysis and years of painstaking research has revealed that one of the world's most endangered marine mammals is actually two species rather than one, as scientists had long assumed.

Scientists spent about two decades crossing Asia and Europe in pursuit of river dolphins skulls and reexamining tissue samples with modern genetic techniques. Their findings revealed that Indus and Ganges river dolphins are separate species, according to a new study published in Marine Mammal Science.

The two dolphins that live in the muddy waters of the Ganges and Indus rivers have lost their eyesight and rely on sophisticated sonar to hunt for prey. The new research recognized that the dolphins have clear genetic differences, as well as different numbers of teeth, coloration, growth patterns and skull shapes. Together, these differences distinguish them as separate species.

"The genetic tools we have today help us extract new information from samples collected years ago," said Eric Archer, leader of the Marine Mammal Genetics Program at NOAA Fisheries' Southwest Fisheries Science Center. The analysis of the river dolphin genetics included tissue samples from the Science Center's Marine Mammal and Sea Turtle Research Tissue Collection, the largest of its kind in the world. Archer added: "Without collections such as this and those at other museums around the world, it would be impossible to identify difficult to study species such as these dolphins."

An estimated several thousand Ganges river dolphins live in the rivers of Bangladesh, India, and Nepal, but their numbers and range are thought to be declining. Indus river dolphins have increased in number from about 1,200 in 2001 to almost 2,000 in 2017. This increase reflects dedicated conservation efforts by local communities and the provincial and national government authorities that oversee their management.

Some scientists suggested as early as the 1970s that the two dolphins were separate species. However, the findings were dismissed until the new analysis proved the original indications were accurate. The revelation is one of many recent genetic studies that have revealed new information about marine mammal populations around the world. Other recent discoveries include a new subspecies of fin whale in the Pacific Ocean and a new and critically endangered whale species in the Gulf of Mexico.

"Recognizing the species-level differences between Indus and Ganges river dolphins is extremely important, as only a few thousand individual dolphins of each species remain," said Gill Braulik of the Sea Mammal Research Unit at the University of St. Andrews, who led the study. "My hope is that our findings will bring much-needed attention to these remarkable animals, helping to prevent them sliding towards extinction."

"Serious challenges still face this incredible species and all other river dolphin populations, but we can save them," said Uzma Kahn, Asia Coordinator of the WWF River Dolphin Initiative. "By doing so we'll save so much more, since hundreds of millions of people and countless other species depend on the health" of similar rivers around the world.

Researchers specialised in psychiatry and psychology at the University of Helsinki investigated the effects of depression on visual perception. The study confirmed that the processing of visual information is altered in depressed people, a phenomenon most likely linked with the processing of information in the cerebral cortex.

The study was published in the Journal of Psychiatry and Neuroscience.

In the study, the processing of visual information by patients with depression was compared to that of a control group by utilising two visual tests. In the perception tests, the study subjects compared the brightness and contrast of simple patterns.

"What came as a surprise was that depressed patients perceived the contrast of the images shown differently from non-depressed individuals," says Academy of Finland Research Fellow Viljami Salmela.

Patients suffering from depression perceived the visual illusion presented in the patterns as weaker and, consequently, the contrast as somewhat stronger, than those who had not been diagnosed with depression.

"The contrast was suppressed by roughly 20% among non-depressed subjects, while the corresponding figure for depressed patients was roughly 5%," Salmela explains.

Identifying the changes in brain function underlying mental disorders is important in order to increase understanding of the onset of these disorders and of how to develop effective therapies for them.

This is why the researchers consider it necessary to carry out further research on altered processing of visual information by the brain caused by depression.

"It would be beneficial to assess and further develop the usability of perception tests, as both research methods and potential ways of identifying disturbances of information processing in patients," Salmela says.

Perception tests could, for example, serve as an additional tool when assessing the effect of various therapies as the treatment progresses.

"However, depression cannot be identified by testing visual perception, since the observed differences are small and manifested specifically when comparing groups," Salmela points out.

KANSAS CITY, MO--Since the beginning of the pandemic, a loss of smell has emerged as one of the telltale signs of COVID-19. Though most people regain their sense of smell within a matter of weeks, others can find that familiar odors become distorted. Coffee smells like gasoline; roses smell like cigarettes; fresh bread smells like rancid meat.

This odd phenomenon is not just disconcerting. It also represents the disruption of the ancient olfactory circuitry that has helped to ensure the survival of our species and others by signaling when a reward (caffeine!) or a punishment (food poisoning!) is imminent.

Scientists have long known that animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Now, in two related studies, researchers from the Yu Lab at the Stowers Institute for Medical Research show how that ability, known as innate valence, is encoded. The findings, published in the journals Current Biology and eLife, indicate that our sense of smell is more complicated--and malleable--than previously thought.

Our current understanding of how the senses are encoded falls into two contradictory views--the labeled-line theory and the pattern theory. The labeled-line theory suggests that sensory signals are communicated along a fixed, direct line connecting an input to a behavior. The pattern theory maintains that these signals are distributed across different pathways and different neurons.

Some research has provided support for the labeled-line theory in simple species like insects. But evidence for or against that model has been lacking in mammalian systems, says Ron Yu, PhD, an Investigator at the Stowers Institute and corresponding author of the reports. According to Yu, if the labeled-line model is true, then the information from one odor should be insulated from the influence of other odors. Therefore, his team mixed various odors and tested their impact on the predicted innate responses of mice.

"It's a simple experiment," says Qiang Qiu, PhD, a research specialist in the Yu Lab and first author of the studies. Qiu mixed up various combinations of odors that were innately attractive (such as the smell of peanut butter or the urine of another mouse) or aversive (such as the smell of rotting food or the urine of a predator). He then presented those odor mixtures to the mice, using a device the lab specially designed for the purpose. The device has a nose cone that can register how often mice investigate an odor. If mice find a particular mixture attractive, they poke their nose into the cone repeatedly. If they find the mixture aversive, they avoid the nose cone at all costs.

To their surprise, the researchers discovered that mixing different odors, even two attractive odors or two aversive odors, erased the mice's innate behavioral responses. "That made us wonder whether it was simply a case of one odor masking another, which the perfume industry does all the time when they develop pleasant scents to mask foul ones," says Yu. However, when the team looked at the activity of the neurons in the olfactory bulb that respond to aversive and attractive odors, they found that was not the case.

Rather, the patterns of activity that represented the odor mixture were strikingly different from that for individual odors. Apparently, the mouse brain perceived the mixture as a new odor identity, rather than the combination of two odors. The finding supports the pattern theory, whereby a sensory input activates not just one neuron but a population of neurons, each to varying degrees, creating a pattern or population code that is interpreted as a particular odor (coyote urine! run!). The study was published online March 1, 2021, in Current Biology.

But is this complicated neural code hardwired from birth, or can it be influenced by new sensory experiences? Yu's team explored that question by silencing sensory neurons early in life, when mice were only a week old. They found that the manipulated mice lost their innate ability to recognize attractive or aversive odors, indicating that the olfactory system is still malleable during this critical period of development.

Interestingly, the researchers found that when they exposed mice during this critical period to a chemical component of bobcat urine called PEA, the animals no longer avoided that odor later in life. "Because the mice encountered this odor while they were still with their mothers in a safe environment and found that it did not pose a danger, they learned to not be afraid of it anymore," says Yu. This study was published online March 26, 2021, in eLife.

Though the COVID-19 pandemic has warped the sense of smell in millions of people, Yu does not predict that it will have significant implications for most adults who recover from the disease. However, he thinks this altered sensory experience could have a major impact on affected infants and children, especially considering the role that many odors play in social connections and mental health.

"The sense of smell has a strong emotional component to it--it's the smell of home cooking that gives you a feeling of comfort and safety," says Yu. "Most people don't recognize how important it is until they lose it."

Other co-authors from Stowers include Yunming Wu, PhD Limei Ma, PhD, Wenjing Xu, PhD, Max Hills, and Vivekanandan Ramalingam, PhD.

The work was funded by the Stowers Institute for Medical Research and the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health (award numbers R01DC008003, R01DC014701, and R01DC016696). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Lay Summary of Findings

Animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Two new studies from the lab of Investigator Ron Yu, PhD, at the Stowers Institute for Medical Research uncover details about how this ability--known as innate valence--is encoded in the nervous system of mice.

In a study published online March 1, 2021, in the journal Current Biology, the researchers showed that whether a particular odor is attractive or aversive is communicated through a complicated computational code, in which different olfactory neurons are activated to varying degrees to spell out the odor's valence. In a separate study published online March 26, 2021, in the journal eLife, the research team found that this coding for innate valence is not hardwired at birth, but rather is malleable and can be shaped by exposure to different odors during a critical period early in life.

One specific protein may be a master regulator for changing how cancer cells consume nutrients from their environments, preventing cell death and increasing the likelihood the cancer could spread, a study from the University of Notre Dame has shown.

The study, published in Cell Reports, was completed in the laboratory of Zachary Schafer, the Coleman Foundation Associate Professor of Cancer Biology in the Department of Biological Sciences.

Schafer and collaborators found a protein called SGK1, known to be activated in a variety of cancer cell types, signals the cell to take up nutrients. These nutrients include glucose, which allows the cell to survive after it detaches from the scaffold of proteins it had been attached to, called the extracellular matrix. Non-cancerous cells often die after detaching from the extracellular matrix, but SGK1 activity promotes survival and therefore increases the chances that the cancer could spread, or metastasize.

"If you better understand precisely how cancer cells that are potentially metastatic survive in these sorts of foreign environments, then you can potentially antagonize those survival pathways and selectively cause those cells to die," said Schafer, also an affiliate member of Notre Dame's Harper Cancer Research Institute.

More than 90 percent of cancer deaths are caused by metastasis of cancer cells from one location to another, Schafer said. For instance, breast cancer can metastasize to the brain, and metastatic cancer cells need to adapt to the new environment there.

There are unique circumstances where the SGK1 protein is critically important, so there might be a vulnerability that researchers can target and alter the way the cells process their nutrients, said Schafer.

This discovery appears to be broadly relevant across many different types of cancer, Schafer said, with research in this paper focused on breast and colon cancer cells grown in cultures under different conditions. The research took place over a number of years, and in addition to a collaboration with the Duke University School of Medicine and Northwestern University Feinberg School of Medicine, several Notre Dame postdoctoral, graduate and undergraduate researchers assisted with the work.

The next step in the research is to complete a "proof of principle" study, which is an early-stage investigation of how this knowledge could be leveraged for clinical benefit. Such a study could reveal if different agents -- which could become therapeutics -- could potentially eliminate the cells in question.

"If you can kill those cells that are potentially metastatic, then potentially you can get to a point where you can block cancer dissemination," Schafer said.

March 29, 2021 - Acute kidney injury (AKI) occurred in nearly 20 percent of patients who underwent surgery with implantation of antibiotic-loaded "spacers" and intravenous (IV) antibiotics for the treatment of deep infections after total knee arthroplasty, reports a study in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

Patients with preexisting chronic kidney disease (CKD) are at particularly high risk of AKI, according to the new research by Matthew P. Abdel, MD, and colleagues of the Mayo Clinic, Rochester, Minn.

High doses of antibiotics in bone cement linked to higher risk of AKI

Deep, periprosthetic joint infections are a devastating complication of failed total knee arthroplasty. The most common treatment is two-stage exchange arthroplasty, in which the knee implant is removed to enable treatment of the infection. This is often followed by placement of antibiotic-loaded bone cement (ALBC) spacers, which deliver high doses of antibiotics directly and continuously to the site of the infection. Once the infection has been eradicated, another operation is performed to place a new knee prosthesis.

However, there is a risk that high doses of antibiotics from the spacers, in addition to IV antibiotics, may result in a toxic effect on the kidneys. This toxicity could contribute to AKI: a serious complication marked by a sudden decline in kidney function. Orthopaedic surgeons have little evidence about the risk of AKI related to ALBC spacers and IV antibiotics, and even less evidence regarding the long-term outcomes of patients who develop AKI.

Dr. Abdel and colleagues analyzed the rates, risk factors, and outcomes of AKI in 424 patients who underwent two-stage exchange arthroplasty with ALBC spacers and IV antibiotics for chronically infected knee replacements. The patients were managed at the Mayo Clinic between 2000 and 2017. Before surgery, 15 percent of patients had preexisting CKD.

Overall, 19 percent of patients developed AKI while the ALBC spacers were in place and IV antibiotics were administered. Patients with preexisting CKD were significantly more likely to develop AKI compared with patients without preexisting CKD (45 percent versus 14 percent). After adjusting for other factors, patients with CKD were five times more likely to develop AKI (odds ratio 5.0).

The study identified several risk factors for AKI, including high doses of antibiotics used in the ALBC spacers (especially the commonly used antibiotics vancomycin and aminoglycoside). Certain factors linked to reduced blood flow to the kidneys, including high blood pressure, low blood volume, and atrial fibrillation (a heart rhythm disorder), also predicted an increased risk of AKI. Diabetes was another important risk factor.

Most patients who developed AKI regained kidney function. However, at an average of 6 years postoperatively, eight patients had developed CKD while four were on dialysis.

Acute kidney injury is a relatively common complication of many medical conditions and procedures, including orthopaedic surgery and heart surgery. The study provides new evidence on AKI in a large series of patients treated for infected total knee replacements at a single medical center.

The findings highlight the particularly high risk of AKI among patients with preexisting CKD. Dr. Abdel and colleagues emphasize the importance of screening to identify patients with possible decreases in kidney function before two-stage exchange arthroplasty.

The study also draws attention to the risk of AKI related to toxicity from ALBC spacers and IV antibiotics. Dr. Abdel and coauthors have taken steps to limit the doses of certain antibiotics used in spacers. However, they add, "While higher antibiotic doses in ALBC spacers can lead to AKIs, these doses are also a crucial factor for infection eradication."

The study, published in Nature Geoscience, produced a global model mapping pollution risk caused by 92 chemicals commonly used in agricultural pesticides in 168 countries.

The study examined risk to soil, the atmosphere, and surface and ground water.

The map also revealed Asia houses the largest land areas at high risk of pollution, with China, Japan, Malaysia, and the Philippines at highest risk. Some of these areas are considered "food bowl" nations, feeding a large portion of the world's population.

University of Sydney Research Associate and the study's lead author, Dr Fiona Tang, said the widespread use of pesticides in agriculture - while boosting productivity - could have potential implications for the environment, human and animal health.

"Our study has revealed 64 percent of the world's arable land is at risk of pesticide pollution. This is important because the wider scientific literature has found that pesticide pollution can have adverse impacts on human health and the environment," said Dr Tang.

Pesticides can be transported to surface waters and groundwater through runoff and infiltration, polluting water bodies, thereby reducing the usability of water resources.

"Although the agricultural land in Oceania shows the lowest pesticide pollution risk, Australia's Murray-Darling basin is considered a high-concern region both due to its water scarcity issues, and its high biodiversity," said co-author Associate Professor Federico Maggi from the School of Civil Engineering and the Sydney Institute of Agriculture.

"Globally, our work shows that 34 percent of the high-risk areas are in high-biodiversity regions, 19 percent in low-and lower-middle-income nations and five percent in water-scarce areas," said Dr Tang.

There is concern that overuse of pesticides will tip the balance, destabilise ecosystems and degrade the quality of water sources that humans and animals rely on to survive.

The future outlook

Global pesticide use is expected to increase as the global population heads towards an expected 8.5 billion by 2030.

"In a warmer climate, as the global population grows, the use of pesticides is expected to increase to combat the possible rise in pest invasions and to feed more people," said Associate Professor Maggi.

Dr Tang said: "Although protecting food production is essential for human development, reducing pesticide pollution is equivalently crucial to protect the biodiversity that maintains soil health and functions, contributing towards food security."

Co-author Professor Alex McBratney, Director of the Sydney Institute of Agriculture at the University of Sydney, said: "This study shows it will be important to carefully monitor residues on an annual basis to detect trends in order to manage and mitigate risks from pesticide use."

"We recommend a global strategy to transition towards a sustainable, global agricultural model that reduces food wastage while reducing the use of pesticides," said the authors of the paper.

Superconductivity is known to be easily destroyed by strong magnetic fields. NIMS, Osaka University and Hokkaido University have jointly discovered that a superconductor with atomic-scale thickness can retain its superconductivity even when a strong magnetic field is applied to it. The team has also identified a new mechanism behind this phenomenon. These results may facilitate the development of superconducting materials resistant to magnetic fields and topological superconductors composed of superconducting and magnetic materials.

Superconductivity has been used in various technologies, such as magnetic resonance imaging (MRI) and highly sensitive magnetic sensors. Topological superconductors, a special type of superconductor, have been attracting great attention in recent years. They are able to retain quantum information for a long time and can be used in combination with magnetic materials to form qubits that may enable quantum computers to perform very complex calculations. However, superconductivity is easily destroyed by strong magnetic fields or magnetic materials in close proximity. It is therefore desirable to develop a topological superconducting material resistant to magnetic fields.

The research team recently fabricated crystalline films of indium, a common superconducting material, with atomic-scale thickness. The team then discovered a new mechanism that prevents the superconductivity of these films from being destroyed by a strong magnetic field. When a magnetic field is applied to a superconducting material, the magnetic field interacts with electron spins. It causes the electronic energy of the material to change and destroys its superconductivity. However, when a superconducting material is thinned to a two-dimensional atomic layer, the spin and the momentum of the electrons in the layer are coupled, causing the electron spins to frequently rotate. This offsets the effect of the changes in electronic energy induced by the magnetic field and thus preserves superconductivity. This mechanism can enhance the critical magnetic field--the maximum magnetic field strength above which superconductivity disappears--up to 16-20 Tesla, which is approximately triple the generally accepted theoretical value. It is expected to have a wide range of applications as it was observed for an ordinary superconducting material and does not require either special crystalline structures or strong electronic correlations.

Based on these results, we plan to develop superconducting thin films capable of resisting even stronger magnetic fields. We also intend to create a hybrid device composed of superconducting and magnetic materials that is needed for the development of topological superconductors: a vital component in next-generation quantum computers.

Sumitomo Rubber Industries, Ltd (SRI) and Tohoku University teamed up to increase the speed of 4-Dimensional Computed Tomography (4D-CT) a thousand-fold, making it possible to observe rubber failure in tires in real-time.

This breakthrough will accelerate the development of new tire materials to provide super wear resistance, greater environmental friendliness, and longer service life. It will also aid significantly in the advancement of smart tires.

SRI initially developed 4D-CT as part of the ADVANCED 4D NANO DESIGN, a new materials development technology unveiled in 2015 that enables highly accurate analysis and simulation of the rubber's internal structure from the micro to nanoscale. This analysis ultimately leads to enhanced rubber wear performance in terms of fuel efficiency, wet grip, and wear resistance.

Since the birth of ADVANCED 4D NANO DESIGN, SRI has undertaken new materials development using the technology available at the SPring-8 synchrotron radiation research facility. However, the existing 4D-CT technique still took several seconds to capture a single 3D image.

Wataru Yashiro, associate professor at Tohoku University, had previously developed a new method to produce higher quality CT images within milliseconds. The technology, which used intense synchrotron radiation, made the breakthrough feasible. It became possible to observe rubber failure as it occurs at varying speeds, allowing a better approximation of a tire's rubber wear.

"As a result of this research, we have increased the speed of imaging by approximately a thousand-fold, meaning that a 3D image can now be captured in around 1/100 of a second," said Yashiro.

Looking ahead, SRI hopes to use this technology in conjunction with machine learning and other advanced data processing techniques to analyze the enormous amounts of data that this imaging technique will generate. On the collaborative side, SRI and Tohoku University will continue to serve as participants in the Japan Science and Technological Agency's Core Research for Evolutionary Science and Technology Program (CREST).

An evolutionary mystery that had eluded molecular biologists for decades may never have been solved if it weren't for the COVID-19 pandemic.

"Being stuck at home was a blessing in disguise, as there were no experiments that could be done. We just had our computers and lots of time," says Professor Paul Curmi, a structural biologist and molecular biophysicist with UNSW Sydney.

Prof. Curmi is referring to research published this month in Nature Communications that details the painstaking unravelling and reconstruction of a key protein in a single-celled, photosynthetic organism called a cryptophyte, a type of algae that evolved over a billion years ago.

Up until now, how cryptophytes acquired the proteins used to capture and funnel sunlight to be used by the cell had molecular biologists scratching their heads. They already knew that the protein was part of a sort of antenna that the organism used to convert sunlight into energy. They also knew that the cryptophyte had inherited some antenna components from its photosynthetic ancestors - red algae, and before that cyanobacteria, one of the earliest lifeforms on earth that are responsible for stromatolites.

But how the protein structures fit together in the cryptophyte's own, novel antenna structure remained a mystery - until Prof. Curmi, PhD student Harry Rathbone and colleagues from University of Queensland and University of British Columbia pored over the electron microscope images of the antenna protein from a progenitor red algal organism made public by Chinese researchers in March 2020.

Unravelling the mystery meant the team could finally tell the story of how this protein had enabled these ancient single-celled organisms to thrive in the most inhospitable conditions - metres under water with very little direct sunlight to convert into energy.

Prof. Curmi says the major implications of the work are for evolutionary biology.

"We provide a direct link between two very different antenna systems and open the door for discovering exactly how one system evolved into a different system - where both appear to be very efficient in capturing light," he says.

"Photosynthetic algae have many different antenna systems which have the property of being able to capture every available light photon and transferring it to a photosystem protein that converts the light energy to chemical energy."

By working to understand the algal systems, the scientists hope to uncover the fundamental physical principles that underlie the exquisite photon efficiency of these photosynthetic systems. Prof. Curmi says these may one day have application in optical devices including solar energy systems.

EATING FOR TWO

To better appreciate the significance of the protein discovery, it helps to understand the very strange world of single-celled organisms which take the adage "you are what you eat" to a new level.

As study lead author, PhD student Harry Rathbone explains, when a single-celled organism swallows another, it can enter a relationship of endosymbiosis, where one organism lives inside the other and the two become inseparable.

"Often with algae, they'll go and find some lunch - another alga - and they'll decide not to digest it. They'll keep it to do its bidding, essentially," Mr Rathbone says. "And those new organisms can be swallowed by other organisms in the same way, sort of like a matryoshka doll."

In fact, this is likely what happened when about one and a half billion years ago, a cyanobacterium was swallowed by another single-celled organism. The cyanobacteria already had a sophisticated antenna of proteins that trapped every photon of light. But instead of digesting the cyanobacterium, the host organism effectively stripped it for parts - retaining the antenna protein structure that the new organism - the red algae - used for energy.

And when another organism swallowed a red alga to become the first cryptophyte, it was a similar story. Except this time the antenna was brought to the other side of the membrane of the host organism and completely remoulded into new protein shapes that were equally as efficient at trapping sunlight photons.

EVOLUTION

As Prof. Curmi explains, these were the first tiny steps towards the evolution of modern plants and other photosynthetic organisms such as seaweeds.

"In going from cyanobacteria that are photosynthetic, to everything else on the planet that is photosynthetic, some ancient ancestor gobbled up a cyanobacteria which then became the cell's chloroplast that converts sunlight into chemical energy.

"And the deal between the organisms is sort of like, I'll keep you safe as long as you do photosynthesis and give me energy."

One of the collaborators on this project, Dr Beverley Green, Professor Emerita with the University of British Columbia's Department of Botany says Prof. Curmi was able to make the discovery by approaching the problem from a different angle.

"Paul's novel approach was to search for ancestral proteins on the basis of shape rather than similarity in amino acid sequence," she says.

"By searching the 3D structures of two red algal multi-protein complexes for segments of protein that folded in the same way as the cryptophyte protein, he was able to find the missing puzzle piece."

A study led by scientists at Hong Kong Baptist University (HKBU) has decoded the genomes of the deep-sea clam (Archivesica marissinica) and the chemoautotrophic bacteria (Candidatus Vesicomyosocius marissinica) that live in its gill epithelium cells. Through analysis of their genomic structures and profiling of their gene expression patterns, the research team revealed that symbiosis between the two partners enables the clams to thrive in extreme deep-sea environments.

The research findings have been published in the academic journal Molecular Biology and Evolution.

Due to the general lack of photosynthesis-derived organic matter, the deep-sea was once considered a vast "desert" with very little biomass. Yet, clams often form large populations in the high-temperature hydrothermal vents and freezing cold seeps in the deep oceans around the globe where sunlight cannot penetrate but toxic molecules, such as hydrogen sulfide, are available below the seabed. The clams are known to have a reduced gut and digestive system, and they rely on endosymbiotic bacteria to generate energy in a process called chemosynthesis. However, when this symbiotic relationship developed, and how the clams and chemoautotrophic bacteria interact, remain largely unclear.

Horizontal gene transfer between bacteria and clams discovered for the first time

A research team led by Professor Qiu Jianwen, Associate Head and Professor of the Department of Biology at HKBU, collected the clam specimens at 1,360 metres below sea level from a cold seep in the South China Sea. The genomes of the clam and its symbiotic bacteria were then sequenced to shed light on the genomic signatures of their successful symbiotic relationship.

The team found that the ancestor of the clam split with its shallow-water relatives 128 million years ago when dinosaurs roamed the earth. The study revealed that 28 genes have been transferred from the ancestral chemoautotrophic bacteria to the clam, the first discovery of horizontal gene transfer--a process that transmits genetic material between distantly-related organisms --from bacteria to a bivalve mollusc.

The following genomic features of the clam were discovered, and combined, they have enabled it to adapt to the extreme deep-sea environment:

(1) Adaptions for chemosynthesis

The clam relies on its symbiotic chemoautotrophic bacteria to produce the biological materials essential for its survival. In their symbiotic relationship, the clam absorbs hydrogen sulfide from the sediment, and oxygen and carbon dioxide from seawater, and it transfers them to the bacteria living in its gill epithelium cells to produce the energy and nutrients in a process called chemosynthesis. The process is illustrated in Figure 1.

The research team also discovered that the clam's genome exhibits gene family expansion in cellular processes such as respiration and diffusion that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, the transfer of small molecules and proteins within the symbiont, and the regulation of the endosymbiont population. It helps the host to obtain sufficient nutrients from the symbiotic bacteria.

(2) Shift from phytoplankton-based food

Cellulase is an enzyme that facilitates the decomposition of the cellulose found in phytoplankton, a major primary food source in the marine food chain. It was discovered that the clam's cellulase genes have undergone significant contraction, which is likely an adaptation to the shift from phytoplankton-derived to bacteria-based food.

(3) Adaptation to sulfur metabolic pathways

The genome of the symbiont also holds the secrets of this mutually beneficial relationship. The team discovered that the clam has a reduced genome, as it is only about 40% of the size of its free-living relatives. Nevertheless, the symbiont genome encodes complete and flexible sulfur metabolic pathways, and it retains the ability to synthesise 20 common amino acids and other essential nutrients, highlighting the importance of the symbiont in generating energy and providing nutrients to support the symbiotic relationship.

(4) Improvement in oxygen-binding capacity

Unlike in vertebrates, haemoglobin, a metalloprotein found in the blood and tissues of many organisms, is not commonly used as an oxygen carrier in molluscs. However, the team discovered several kinds of highly expressed haemoglobin genes in the clam, suggesting an improvement in its oxygen-binding capacity, which can enhance the ability of the clam to survive in deep-sea low-oxygen habitats.

Professor Qiu said: "Most of the previous studies on deep-sea symbiosis have focused only on the bacteria. This first coupled clam-symbiont genome assembly will facilitate comparative studies that aim to elucidate the diversity and evolutionary mechanisms of symbiosis, which allows many invertebrates to thrive in 'extreme' deep-sea ecosystems."

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2021.0007, Sharen Lee and Gary Tse from Laboratory of Cardiovascular Physiology, Hong Kong, HKG, China, Second Hospital of Tianjin Medical University, Tianjin, China and Xiamen Cardiovascular Hospital, Xiamen, China consider a case of atezolizumab-induced autoimmune diabetes mellitus presenting with diabetic ketoacidosis.

Atezolizumab, an immune checkpoint inhibitor, is a humanized monoclonal, anti-programmed death ligand 1 (PD-L1) antibody used for the treatment of metastatic urothelial carcinoma that has progressed after chemotherapy. PD-L1 inhibitors can induce type 1 diabetes, and patients can present with diabetic ketoacidosis. Blood glucose levels should be regularly monitored in patients who are prescribed these medications.

The authors describe a patient with a known history of urothelial carcinoma who presented with diabetic ketoacidosis 6 weeks following his second cycle of atezolizumab. His serum lactate level was slightly elevated and his β-hydroxybutyrate level was elevated. High anion gap metabolic acidosis secondary to diabetic ketoacidosis was diagnosed. Subsequent testing demonstrated hemoglobin A1c level of 9.9%, positivity for antiglutamic acid decarboxylase antibody and suppressed C-peptide level in the absence of detectable anti-islet antigen 2 (IA-2) or anti-insulin antibodies.

His initial management included cessation of atezolizumab treatment, intravenous sodium chloride administration, and insulin pump infusion, after which metabolic acidosis gradually resolved. The insulin pump was subsequently switched to Protaphane at 18 units before breakfast and 8 units before dinner, together with metformin at 1000 mg twice daily. Four weeks later his medication was changed to human isophane insulin plus neutral insulin. Linagliptin at 5 mg was added 1 month later. His hemoglobin A1c level declined to 8.1% 1 year later.

The use of artificial intelligence (AI) is becoming more common in many branches of industry and online retailing. Traditional lines of work, such as transport logistics and driving, are developing in a similar direction although mainly out of public view. Scientists at the University of Göttingen have now investigated how efficient the use of AI can be in the commercial management of trucks. Their answer: the best option is an intelligent combination of human decision-making and AI applications. The study was published in the International Journal of Logistics Management.

"As has happened in the private sector, digital applications - as well as machine learning, a kind of AI - are increasingly permeating operations and processes in the transport and logistics sector," explains Professor Matthias Klumpp from the Faculty of Economics. "The question in the commercial sector, however, is whether or not this contributes to achieving goals and efficiency in companies."

To answer this question, the researchers compared the work efficiency of truck drivers in relation to their use of AI applications such as dynamic real-time navigation systems, cruise control and automated gear-shifting based on speed and topography and others. Looking at retail trade delivery by truck, they studied three comparison groups: the first drove exclusively following human decision-making patterns; the second used a combination of human and machine; and the third relied exclusively on fully automated decisions.

The researchers from the Production and Logistics Research Group concluded that an intelligent combination of human work and decision-making capabilities with AI applications promises the highest transport and driving efficiency: "On average, the second group achieved the most efficient transport trips, with the fewest interventions and deviations from the optimal path," the authors said. "Clearly, neither a purely human decision-making structure nor a fully automated driving system can promise to meet current logistics requirements."

The scientists therefore deduce that despite the progress of AI in the field of transportation by truck, human experience and decision-making capabilities will still be necessary in the longer term. "However, extensive training and qualification needs will occur by working with AI applications, especially for simple logistics activities," the authors conclude. "Technology and AI innovations are therefore not a question for management alone. In particular, efficiency and competitive advantages can be achieved through their application in operational transport."

Bottom Line: Various genetic alterations in circulating tumor cells (CTCs) were associated with clinical outcomes and resistance to hormone therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC).

Journal in Which the Study was Published: Molecular Cancer Research, a journal of the American Association for Cancer Research

Author: Andrew Armstrong, MD, MSc, a medical oncologist at the Duke Cancer Institute Center for Prostate and Urologic Cancers at Duke University

Background: While only a minority of men with mCRPC have primary resistance to the androgen receptor (AR) inhibitors enzalutamide (Xtandi) or abiraterone acetate (Yonsa or Zytiga), most men will develop acquired resistance within several years, explained Armstrong.

In the previously published PROPHECY study, Armstrong and colleagues found that the presence of the AR-V7 splice variant in CTCs from patients with mCRPC was associated with fewer responses and shorter progression-free and overall survival after treatment with enzalutamide or abiraterone. Based on these results, the National Comprehensive Cancer Network incorporated suggested AR-V7 testing into the clinical practice guidelines for patients with mCRPC who have progressed after one hormonal therapy, Armstrong noted.

"While these findings were encouraging, only about 5 to 40 percent of patients with mCRPC have CTCs that are positive for AR-V7, depending on the disease context, suggesting that other genetic alterations may play a role in drug resistance," he added.

How the Study was Conducted: The latest study is a retrospective secondary analysis of the PROPHECY study. In this new analysis, Armstrong and colleagues identified genomic alterations in AR-V7-negative CTCs of patients with mCRPC and examined associations between these alterations and clinical outcomes.

Armstrong and colleagues analyzed individual patient pooled CTC DNA vs. germline DNA for whole genomic copy number alterations--indicating the gain or loss of genetic material--in 73 liquid biopsy samples collected over time from 48 men with mCRPC treated with AR inhibitors in the PROPHECY Study. They also looked for novel genomic alterations associated with acquired resistance over time by performing individual patient pooled CTC vs. matched germline whole-exome sequencing on 22 samples taken before and after progression on enzalutamide or abiraterone.

Results: In addition to confirming previous work that suggested that poor outcomes to AR inhibition were associated with PTEN loss, MYCN gain, AR gain, and TP53 mutations in CTCs, the investigators identified several novel alterations associated with response to AR inhibitors. Gains of ATM, NCOR2, and HSD17B4 were associated with sensitivity to AR inhibitors, while gains of BRCA2, APC, KDM5D, CYP11B1, and SPARC, and losses of CHD1, PHLPP1, ERG, ZFHX3, and NCOR2 were associated with primary resistance to AR inhibitors.

Patients who benefited from AR inhibitors (defined as having a progression-free survival of at least six months) were more likely to have CTCs with alterations in genes involved in DNA repair, steroid metabolism, lineage plasticity, and PI3K and WNT signaling. In addition, chromatin and epigenetic gains linked to a loss of CHD1 and a gain of KDM5D were also observed in patients who benefited from AR inhibition. In contrast, patients who progressed on AR inhibitors showed clonal evolution of CTCs with gains of the ATM, FOXA1, UGT2B17, KDM6A, CYP11B1, and MYC genes, and acquired losses of NCOR1, ZFHX3, and ERG.

Author's Comments: "We were surprised to observe that a gain of BRCA2 was associated with worse outcomes in mCRPC resistant to AR inhibitors, as that has not been described before. Typically, loss of BRCA2 has been associated with poorer outcomes," said Armstrong. "Our finding may explain some resistance to DNA damaging agents and AR therapies that has not been well understood and requires further mechanistic investigation." The present study is also the first to confirm that the loss of CHD1 in CTCs is associated with worse outcomes for patients with mCRPC in a clinical setting, Armstrong added. Loss or mutations in CHD1 were previously shown to promote lineage plasticity in prostate cancer.

"Our study reinforces that analyzing CTC genomics has potential for identifying and tracking disease resistance or efficacy with AR inhibitors over time," Armstrong said. "The novel alterations we identified will need to be validated by further research but may represent priority candidates for new drug targets."

Study Limitations: Limitations of this study include the small sample size, which limited researchers' ability to perform statistical testing between individual alterations and clinical outcomes. Disease burden and differences in the sensitivity of genomic assays at different time points due to changes in CTCs in response to therapy and at progression may have biased genomic findings. Finally, some alterations identified may represent low-level passenger change related to disease burden or genomic instability, rather than cancer drivers. The identified genomic alterations require mechanistic studies to determine their biologic and clinical relevance for treatment, Armstrong noted.

International genomics research led by the University of Leicester has used artificial intelligence (AI) to study an aggressive form of cancer, which could improve patient outcomes.

Mesothelioma is caused by breathing asbestos particles and most commonly occurs in the linings of the lungs or abdomen. Currently, only seven per cent of people survive five years after diagnosis, with a prognosis averaging 12 to 18 months.

New research undertaken by the Leicester Mesothelioma Research Programme has now revealed, using AI analysis of DNA-sequenced mesotheliomas, that they evolve along similar or repeated paths between individuals. These paths predict the aggressiveness and possible therapy of this otherwise incurable cancer.

Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester and Director of the Leicester Mesothelioma Research Programme, said:

"It has long been appreciated that asbestos causes mesothelioma, however how this occurs remains a mystery.

"Using AI to interrogate genomic 'big data', this initial work shows us that mesotheliomas follow ordered paths of mutations during development, and that these so-called trajectories predict not only how long a patient may survive, but also how to better treat the cancer - something Leicester aims to lead on internationally through clinical trial initiatives."

While use of asbestos is now outlawed - and stringent regulations in place on its removal - each year around 25 people are diagnosed with mesothelioma in Leicestershire and 190 are diagnosed in the East Midlands. Cases of mesothelioma in the UK have increased by 61% since the early 1990s.

Until very recently, chemotherapy was the only licenced choice for patients with mesothelioma. However, treatment options start to become limited once people stop responding to their treatment.

Professor Fennell in collaboration with the University of Southampton recently made a major breakthrough in treating the disease by demonstrating that use of an immunotherapy drug called nivolumab increased survival and stabilised the disease for patients. This was the first-ever trial to demonstrate improved survival in patients with relapsed mesothelioma.

Atomically dispersed catalysts have received extensive research attention, because they exhibit excellent activity and unique selectivity for many important catalytic reactions. The atomically dispersed nature of these metal catalysts confers their unique electronic structures as well as designated coordination-unsaturated environments for the optimized adsorption/activation of the reactants. One grand challenge faced by these atomically dispersed catalysts is that the supported isolated metal \atoms are usually thermally unstable and tend to aggregate into large clusters/particles at evaluated reaction temperatures. As a result, most reported atomically dispersed catalysts have an extremely low metal loading below 1.5wt%. Because of the extremely low metal loading, many atomically dispersed catalysts suffer from low mass-specific activity, which is often considered more crucial, especially in industrial applications. Therefore, developing new strategies for constructing atomically dispersed catalysts with high metal loading, high thermal stability, and high catalytic performance is of great importance.

In order to achieve high metal loading and high thermal stability, the support material should have a high specific surface area with abundant surface sites that could provide strong anchoring to the supported metal species. Meanwhile, for optimizing the catalytic performance, the support material should also be carefully chosen to tune the electronic properties of the supported species, and to participate in catalyzing the reaction. In a new article published in the Beijing-based National Science Review, scientists at the College of Chemistry and Molecular Engineering of Peking University in Beijing, China, and at University of Chinese Academy of Sciences in Beijing, China, and at University of Science and Technology of China in Hefei, China report a facile synthesis of a thermally stable atomically dispersed Ir/MoC catalyst with metal loading as high as 4 wt%, an unusually high value for carbide supported metal catalysts. The strong interaction between Ir and the MoC substrate enables high dispersion of Ir on the MoC surface, and modulates the electronic structure of the supported Ir species. Using quinoline hydrogenation as a model reaction, Ir/MoC catalyst exhibits remarkable reactivity, selectivity, and stability. The presence of high-density isolated Ir atoms is the key to achieve high metal-normalized activity and mass-specific activity, whereas MoC substrate contributes to block the unselective hydrogenation of benzene ring in quinoline at harsh reaction conditions. Based on theoretical calculations, the authors show that water-promoted quinoline hydrogenation mechanism is preferred over the Ir/MoC, which contributes to high selectivity towards 1,2,3,4-tetrahydroquinoline.

Noteworthy is that the authors pointed out the importance of metal loading for atomically dispersed catalyst based on their reaction data as "We can draw the conclusion that the Ir1 species on α-MoC surface are more reactive than Ir clusters or Ir NPs in this reaction, giving the highest metal-normalized activity on 0.5-4% Ir/α-MoC catalysts (Figure 1). We need to point out that very low metal loading of a supported metal catalyst can result in an extremely low mass-specific activity, which is a drawback in practical applications. In our view, high-loading atomically dispersed catalyst (e.g. 4% Ir/α-MoC) and catalyst with the highest density of isolated metal atom (e.g. 7% Ir/α-MoC) are significant for both academia and chemical industry."