Earth

A team of researchers led by Patrick E. H. Jackson at the Myles H. Thaler Center for HIV and Human Retrovirus Research, University of Virginia, Charlottesville, Virginia, USA, has published a review on the subject of the HIV-1 Rev Regulatory complex (dubbed the HIV-1 Rev Regulatory Axis) in the journal, Current HIV Research. HIV-1 Rev Regulatory Axis is comprised of 2 key components which are necessary to transport viral mRNAs out of the nucleus into the cytoplasm. These components are Rev - a viral protein, and an RNA secondary structure found in called the Rev Response Element (RRE). The RRE is found in all HIV mRNA sequences, and it binds with Rev (to form the Rev-RRE ribonucleoprotein complex), in combination with various cellular factors to overcome cellular defense mechanisms that normally block the exit of foreign mRNA molecules.

The researchers note in their review that genetic variations in HIV-1 may account for differences in the sequences of the Rev-RRE complex, which, in turn affects its potency to enable viral mRNA export from a cell nucleus. Some primary isolates of components from infected cells show differences in Rev-RRE activity and a few studies have observed a correlation between lower Rev-RRE activity and slower progression of clinical disease. Lower Rev-RRE activity has also been associated with the evasion by affected cells from cytotoxic T lymphocyte mediated killing.

The team notes that this HIV-1 Rev-RRE regulatory axis is an understudied mechanism which enables viral adaptation to diverse immune milieus. "There is evidence that this adaptation may play a role in HIV pathogenesis, particularly in immune evasion and HIV latency, but further studies with larger sample sizes are required," concludes Jackson.

Beijing, 31 March 2020: the journal Cardiovascular Innovations and Applications (CVIA) has just published a new issue, Volume 4 Issue 3 with an invitation to join the International Brugada Electrocardiographic Indices Registry

This issue brings together important research papers from leading cardiologists in US, China and Europe in a combination of reviews, original research and case reports.

A very important paper included in the issue invites cardiologists worldwide to contribute to the International Brugada Electrocardiographic indices Registry
( An Open Invitation to Join the International Brugada Electrocardiographic Indices

Registry (DOI 10.15212/CVIA.2019.0568). This group already has over 39 investigators in 18 countries and is looking to recruit new members to make a contribution to the evaluation of the disease life course, risk factors, and prognosis in a large series of Brugada patients and provide insights for improving risk stratification.

Other papers in the issue are as follows:

ORIGINAL ARTICLE

Jiapeng Liu, Xin Du, Mengmeng Li, Zhaoxu Jia, Shangxin Lu, Sanshuai Chang, Ribo Tang, Rong Bai, Jianzeng Dong, Gregory Y. H. Lip, and Changsheng Ma

Frailty and Anticoagulant Therapy in Patients Aged 65 Years or Older with Atrial Fibrillation (DOI: 10.15212/CVIA.2019.0562)

REVIEWS

Sanshuai Chang, Yi He, Hui Wang, Fei Guo, Qiang Lv, Junping Kang, Rong Bai, Xiaohui Liu, Xin Du, Changsheng Ma, and Jianzeng Dong

The Temporal Relation between Cardiomyopathy and LBBB and Response to Cardiac Resynchronization Therapy: Case Series and Literature Review (DOI: 10.15212/CVIA.2019.0560)

Shiqin Yu, Chen Cui, Minjie Lu, and Shihua Zhao

Diagnostic Accuracy of Three-Dimensional Whole-Heart Magnetic Resonance

Angiography to Detect Coronary Artery Disease with Invasive Coronary Angiography as a Reference: A Meta-Analysis (DOI: 10.15212/CVIA.2019.0561)

Turan Erdo?an, Hakan Duman, Mustafa Çetin, Sava? Özer, Göksel Çinier, Ece Usta, Mustafa Usta, and Tuncay K?r??

Impact of Postdilation on Intervention Success and Long-Term Major Adverse Cardiovascular Events (MACE) among Patients with Acute Coronary Syndromes (DOI: 10.15212/CVIA.2019.056)

Lutfu Askin, Kader Eliz Uzel, Okan Tanriverdi, Serdar Turkmen

Serum Irisin: Pathogenesis and Clinical Research in Cardiovascular Diseases (DOI: 10.15212/CVIA.2019.0569)

CASE REPORTS

Yichao Xiao, Zhenfei Fang, Xinqun Hu, Qiming Liu, Zhaowei Zhu, Na Liu, Xiaofan Peng, and Shenghua Zhou

A Giant Right Atrial Myxoma with Blood Supply from the Left and Right Coronary Arteries: Once in a Blue Moon (DOI: 10.15212/CVIA.2019.0566)

Fabian Guenther, Andreas Seitz, Valeria Martínez Pereyra, Raffi Bekeredjian, Udo Sechtem, Peter Ong

Does Coronary Microvascular Spasm Exist? Objective Evidence from Intracoronary Doppler Flow Measurements During Acetylcholine Testing (DOI: 10.15212/CVIA.2019.0570)

RESEARCH PAPER

Lutfu Askin, Okan Tanriverdi, Hakan Tibilli, and Serdar Turkmen

Associations between Vaspin Levels and Coronary Artery Disease (DOI 10.15212/CVIA.2019.05650)

COMMENTARIES

C. Richard Conti
Function of the Right Ventricle (DOI 10.15212/CVIA.2019.0018)

C. Richard Conti
Randomized Clinical Trials: Failure to Enter Patients (DOI 10.15212/CVIA.2016.0064)

Scientists from the laboratory of Dr. Natalia Kononenko at the CECAD Center of Excellence in Aging Research at the University of Cologne have found out that autophagy - the process of cellular self-recycling, or waste clearance - is dispensable for the survival of the neurons in mice. The new findings suggest that autophagy in fact also fulfils a different important function: The proteins classically associated with waste clearance in cells regulate the speed of intracellular transport. This transport is achieved by microscopic hollow tubes, so-called microtubules. The article 'Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons' appeared in the current issue of Nature Communications.

Autophagy cleans the cells by breaking down and removing the damaged proteins and organelles, cell areas with a specific function. It is hardly surprising that this process is particularly important for long-lived cells such as neurons, since neurons are no longer capable of cell division ('post-mitotic') and are therefore particularly vulnerable to accumulating unfavorable proteins and damaged organelles. In their new study, the scientists show that neurons in the mouse brain do not need autophagy to survive. Instead, these specialized cells use autophagy proteins to regulate the microtubule-dependent transport of molecules crucial for learning and memory.

The fact that autophagy is crucial for the well-being of the brain is supported by scientific discoveries made over the last decade. Many studies have identified defective autophagy as one of the pathological causes of neurodegenerative diseases, including Alzheimer's (AD), Parkinson's and Huntington's disease. In this context, the novel function of autophagy the scientists discovered suggests that the therapeutic modulations of autophagy activity in patients might not only promote the waste clearance in the brain, but also alter the cognitive abilities by changing the efficiency of the intracellular transportation system.

Z-form nucleic acids are double-stranded DNA and RNA molecules with an unusual left-handed double helix structure, as opposed to the classical right-handed Watson-Crick double helix. Z-nucleic acids were discovered more than 40 years ago, but their biological function has remained poorly understood. The group of Professor Manolis Pasparakis at the CECAD Cluster of Excellence in Aging Research of the University of Cologne cooperated with scientists from the University of Texas Health Science Center and the Francis Crick Institute in London to study the role of Z-DNA Binding Protein 1 (ZBP1), one of only two proteins in mammals that senses Z-nucleic acids. ZBP1 was previously shown to sense the genetic material of certain viruses and induce the death of the infected cells to prevent viral spread.

Curiously, in their earlier studies, the researchers obtained evidence that ZBP1 can also cause cell death and inflammation in the absence of viral infection. They had found that when the function of RIPK1 - a protein inhibiting ZBP1 - was compromised, ZBP1 was activated and triggered an inflammatory type of cell death, called necroptosis. A key question behind the current study was how ZBP1 can be activated in the absence of incoming viral infection. Using experimental mouse models, the scientists found that the proinflammatory activity of ZBP1 depended on its ability to bind Z-nucleic acids, suggesting that it is activated by Z-form nucleic acids that existed within the cell. The next question was what type of endogenous nucleic acids are bound by ZBP1. 'We could show that ZBP1 binds to double-stranded RNA', Pasparakis said. 'Although we currently lack the experimental methodology to demonstrate that this has the Z-conformation, based on all available structural studies, our interpretation of our results is that ZBP1 binds to endogenous Z-RNA via its Za domains.'

Double-stranded RNA (dsRNA) is uncommon in cells but forms during the replication of certain viral genomes, and is thought to provide the ligand activating ZBP1 during viral infection. The scientists hypothesized that cellular dsRNA could be produced by endogenous retroelements, which are forms of parasitic DNA derived either from ancient retroviral infections or from active retrotransposons or 'jumping genes', which constitute over half of the human and mouse genomes. To address the possible role of endogenous retroelements as sources of dsRNA, the team of Manolis Pasparakis collaborated with George Kassiotis' Retroviral Immunology Laboratory at the Francis Crick Institute. Indeed, computational analysis of RNA sequencing data from mouse skin showed that most complementary, putatively double-stranded, RNA was derived from particular groups of endogenous retroelements.

These findings suggested that sensing of cellular dsRNA, most likely derived from endogenous retroelements, activates ZBP1, inducing cell death and inflammation. This mechanism may be relevant for the pathogenesis of inflammatory pathologies in humans, particularly in patients with mutations of proteins inhibiting ZBP1 such as RIPK1.
'Z-form nucleic acids have remained mysterious for so many years', Pasparakis remarked. 'Currently, our only means to investigate their function is by studying the proteins that sense them. We made some progress, but the challenge ahead would be to understand why, where and how they form within a cell and what the purpose of this is.'

A particularly fascinating aspect is the link to endogenous retroelements. 'We currently understand very little about how these genomic parasites affect our health. It appears that over the course of evolution, some retrotransposons, which can mimic viral infection, have been recruited as useful partners in the response of our cells to damage, stress or true infection, but this partnership can also go wrong, causing disease', Kassiotis commented.

'Just like during viral infection, sensing of Z-RNA produced by endogenous retroelements by ZBP1 could provide a potent trigger for cell death and inflammation, and cause disease. These are early days and we have a long way to go, but understanding the underlying mechanisms may one day lead to novel therapies for human diseases', Pasparakis concluded.

A high-end race car engine needs all its components tuned and working together precisely to deliver top-quality performance. The same can be said about the processor inside a quantum computer, whose delicate bits must be adjusted in just the right way before it can perform a calculation. Who's the right mechanic for this quantum tuneup job? According to a team that includes scientists at the National Institute of Standards and Technology (NIST), it's an artificial intelligence, that's who.

The team's paper in the journal Physical Review Applied outlines a way to teach an AI to make an interconnected set of adjustments to tiny quantum dots, which are among the many promising devices for creating the quantum bits, or "qubits," that would form the switches in a quantum computer's processor.

Precisely tweaking the dots is crucial for transforming them into properly functioning qubits, and until now the job had to be done painstakingly by human operators, requiring hours of work to create even a small handful of qubits for a single calculation.

A practical quantum computer with many interacting qubits would require far more dots -- and adjustments -- than a human could manage, so the team's accomplishment might bring quantum dot-based processing closer from the realm of theory to engineered reality.

"Quantum computer theorists imagine what they could do with hundreds or thousands of qubits, but the elephant in the room is that we can actually make only a handful of them work at a time," said Justyna Zwolak, a NIST mathematician. "Now we have a path forward to making this real."

A quantum dot typically contains electrons that are confined to a tight boxlike space in a semiconductor material. Forming the box's walls are several metallic electrodes (so-called gates) above the semiconductor surface that have electric voltage applied to them, influencing the quantum dot's position and number of electrons. Depending on their position relative to the dot, the gates control the electrons in different ways.

To make the dots do what you want -- act as one sort of qubit logic switch or another, for example -- the gate voltages must be tuned to just the right values. This tuning is done manually, by measuring currents flowing through the quantum dot system, then changing the gate voltages a bit, then checking the current again. And the more dots (and gates) you involve, the harder it is to tune them all simultaneously so that you get qubits that work together properly.

In short, this isn't a gig that any human mechanic would feel bad about losing to a machine.

"It's usually a job done by a graduate student," said graduate student Tom McJunkin of the University of Wisconsin-Madison's physics department and a co-author on the paper. "I could tune one dot in a few hours, and two might take a day of twiddling knobs. I could do four, but not if I need to go home and sleep. As this field grows, we can't spend weeks getting the system ready -- we need to take the human out of the picture."

Pictures, though, are just what McJunkin was used to looking at while tuning the dots: The data he worked with came in the form of visual images, which the team realized that AI is good at recognizing. AI algorithms called convolutional neural networks have become the go-to technique for automated image classification, as long as they are exposed to lots of examples of what they need to recognize. So the team's Sandesh Kalantre, under supervision from Jake Taylor at the Joint Quantum Institute, created a simulator that would generate thousands of images of quantum dot measurements they could feed to the AI as a training exercise.

"We simulate the qubit setup we want and run it overnight, and in the morning we have all the data we need to train the AI to tune the system automatically," Zwolak said. "And we designed it to be usable on any quantum dot-based system, not just our own."

The team started small, using a setup of two quantum dots, and they verified that within certain constraints their trained AI could auto-tune the system to the setup they desired. It wasn't perfect -- they identified several areas they need to work on to improve the approach's reliability -- and they can't use it to tune thousands of interconnected quantum dots as yet. But even at this early stage its practical power is undeniable, allowing a skilled researcher to spend valuable time elsewhere.

"It's a way to use machine learning to save labor, and -- eventually -- to do something that human beings aren't good at doing," Zwolak said. "We can all recognize a three-dimensional cat, and that's basically what a single dot with a few properly-tuned gates is. Lots of dots and gates are like a 10-dimensional cat. A human can't even see a 10D cat. But we can train an AI to recognize one."

WASHINGTON--Thyroid hormone replacement therapy in older adults is associated with a higher risk of death compared with no treatment, a large study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

When people have too little thyroid hormone, called hypothyroidism, they usually require lifelong treatment with levothyroxine to supplement the body's thyroid hormone, thyroxine (T4). Some people have subclinical hypothyroidism, which occurs when the thyroid gland needs more stimulation to produce adequate thyroid hormone levels. These individuals will have modest elevations in thyroid-stimulating hormone (TSH), which stimulates thyroid hormone production.

Subclinical hypothyroidism is a mild or early form of thyroid disease, and these patients also routinely receive thyroid hormone replacement, said the study's principal investigator, Jennifer Mammen, M.D., Ph.D., an assistant professor at Johns Hopkins University in Baltimore, Md. However, Mammen notes that this interpretation of high TSH with normal T4 levels may not be correct in all older adults.

"Many older adults have an elevation in TSH with normal thyroid levels. Our earlier research showed that this can reflect developing hypothyroidism in some, while in others, it is a form of adaptation to age-related changes in health instead of thyroid disease," Mammen said. "As a result, some of these older people may be receiving inappropriate or excessive thyroid hormone therapy, treatment that may counteract important adaptations needed for healthy aging."

The researchers studied the effects of levothyroxine therapy on survival in adults ages 65 and older. They used data from 1,054 participants of the Baltimore Longitudinal Study of Aging, a long-running observational study from the National Institute on Aging. All participants had at least one TSH and T4 measurement since 2003. Mammen's research team looked at the risk of dying during one-year intervals from 2003 to 2018 and adjusted their statistical analyses for multiple demographic and health factors that may influence survival.

They found that among older adults, use of thyroid hormone increased risk of death 60% year over year (hazard ratio 1.6). They also limited the analysis to compare individuals with normal TSH levels, reflecting normal thyroid function, to those on thyroid hormone with normal TSH levels, who were therefore treated to target, and found those on treatment had almost double the risk of dying compared with untreated persons (hazard risk 1.9), Mammen reported.

Despite studies showing that hormone treatment of an isolated high TSH may not benefit older people, Mammen said, "we were surprised that we were able to demonstrate harm associated with thyroid hormone supplementation. Our work supports the growing calls to use age-specific TSH reference intervals to determine the threshold for thyroid hormone treatment."

Mammen also recommended repeating testing after finding an isolated elevation of TSH in older adults, because levels can fluctuate. "We advocate being cautious and conservative when considering thyroid hormone treatment," she said.

WASHINGTON--Adults who work long hours are more likely to have hypothyroidism, which is an underactive thyroid, according to study results accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

"Overwork is a prevalent problem threatening the health and safety of workers worldwide," said principal investigator Young Ki Lee, M.D., of the National Cancer Center in Goyang-si, South Korea. "To our knowledge, this study is the first to show that long working hours are associated with hypothyroidism."

Lee said the researchers found a higher risk of hypothyroidism with long working hours regardless of the workers' socioeconomic status or sex, even though this common thyroid disorder affects women more than men.

They conducted the study using data from 2,160 adult full-time workers who participated in the Korea National Health and Nutrition Examination Survey from 2013 to 2015. The investigators identified hypothyroidism from records of the participants' thyroid bloodwork.

Hypothyroidism occurred at more than twice the rate in participants who worked 53 to 83 hours weekly versus those who worked 36 to 42 hours each week (3.5% versus 1.4%), the researchers reported. For each 10-hour increase in the workweek, individuals who worked longer hours had an increased odds for hypothyroidism compared with those who worked 10 hours less (odds ratio 1.46), Lee said.

Lee stressed the need for further studies to determine whether long working hours cause hypothyroidism, which is a known risk factor for heart disease and diabetes.

"If a causal relationship is established," he said, "it can be the basis for recommending a reduction in working hours to improve thyroid function among overworked individuals with hypothyroidism. Additionally, screening for hypothyroidism could be easily integrated into workers' health screening programs using simple laboratory tests."

South Korea passed a law in 2018 that reduced the maximum number of working hours from 68 to 52 per week. "If long working hours really cause hypothyroidism," Lee said, "the prevalence of hypothyroidism in Korea might decrease slightly as the working hours decrease."

Hypothyroidism can cause tiredness, depression, feeling cold, and weight gain. However, Lee said most of the study participants with hypothyroidism had a mild (subclinical) form that often does not yet cause symptoms.

WASHINGTON--Three in four hypothyroidism patients who chose desiccated thyroid extract (DTE) over the standard therapy said this option was more effective than other thyroid hormone medications, according to an analysis of comments in online patient forums accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

Patients commenting in the forums on DTE use most frequently mentioned an improvement in symptoms and overall well-being as benefits, said researcher Freddy J.K. Toloza, M.D., of the University of Arkansas for Medical Sciences (Little Rock, Ark) and Mayo Clinic (Rochester, Minn).

This alternative treatment--also known as nature thyroid, thyroid USP or Armour thyroid--is made from dehydrated pig thyroid glands. An estimated 10%-25% of people with hypothyroidism--an underactive thyroid--use this treatment, although it is a medication that hasn't been approved by the U.S. Food and Drug Administration.

"Among people with hypothyroidism, some may prefer thyroid extract over other guideline-recommended thyroid hormone replacement therapies for many reasons, including better perceived effectiveness, improvement in symptoms such as fatigue and weight gain, and improvement in overall well-being," Toloza said. He noted that nearly half (45%) of people who wrote about using DTE in online patient forums reported that a clinician initially drove their interest in trying DTE, even though treatment guidelines do not recommend the use of this medication.

Hypothyroidism affects 0.5%-2% of the U.S. population. Levothyroxine (LT4), a synthetic thyroid hormone, is the recommended treatment for patients with hypothyroidism.

The researchers analyzed patient-reported information from online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. They searched the 10 most popular patient forums based on the number of users using the following key terms: desiccated thyroid extract, desiccated thyroid treatment, thyroid USP, commercial names of DTE (Armour Thyroid® or Natural Thyroid®), thyroid extract, and hypothyroidism.

They retrieved and analyzed 1,235 unique posts from those websites between each forum's inception and March 2018. After the initial screening, they selected 673 posts from three of these forums (WebMD, Patients Like Me, and Drugs.com) based on the completeness of the available information.

Patients described many reasons for switching from a previous thyroid treatment to DTE, including lack of improvement in symptoms (58%) and the development of side effects (22%). Among a majority of patients, DTE was described as moderately-to-majorly effective overall (81%) and more effective than other thyroid hormone medications (77%). The most frequently described benefits associated with DTE use were an improvement in clinical symptoms such as fatigue and weight gain (56%), as well as a change in overall well-being (34%). One-fifth of people also described side effects related to the use of DTE.

"The findings underscore the need for clinicians to individualize therapy approaches for hypothyroidism," Toloza said.

CHAMPAIGN, Ill. -- This is the story of three bird species and how they interact. The brown-headed cowbird plays the role of outlaw: It lays its eggs in other birds' nests and lets them raise its young - often at the expense of the host's nestlings. To combat this threat, yellow warblers have developed a special "seet" call that means, "Look out! Cowbird!"

In a new study, researchers at the University of Illinois at Urbana-Champaign report that red-winged blackbirds respond to the seet call as if they know what it means. (Watch a video about the research.)

"Does this mean red-winged blackbirds understand that the call is specific to cowbirds or are they just responding to a general alarm?" said graduate student Shelby Lawson, who led the study with Mark Hauber, a professor of evolution, ecology and behavior at the U. of I. The researchers sought to answer that question by playing back the calls of several bird species in warbler and blackbird territories to see how the birds reacted.

They report their findings in the journal Communications Biology.

"We know that eavesdropping on the calls of other species is common across the animal kingdom," Lawson said. "Birds do it. Mammals do it. There are studies of different primates that do it - and even birds that listen in when they do."

In the rainforests of Ivory Coast, for example, tropical birds known as hornbills have deciphered some of the calls of the Diana monkey. The hornbills ignore the monkeys' alarm calls for ground predators, which are no threat to the birds, but heed the monkeys' calls for hawks, which are predators of hornbills.

"Chickadees have very general alarm calls that we now know signal the size of different predators," Lawson said. "A lot of birds will listen to these calls and respond based on the danger posed to them. There's also a study of nuthatches listening to chickadee calls."

But all these studies look at alarm calls directed at predators that can kill adult animals, Lawson said.

"Yellow warblers are the only bird we know about that has developed a specific call for a brood parasite," she said. "When they see a brown-headed cowbird, yellow warblers will make the seet call and then females that hear the call will go back to their nest and sit on it tightly to protect their eggs. They only do this with cowbirds. They don't seet at predators or anything else."

In an earlier study, Lawson and her colleagues were playing audio of seet calls to study warbler behavior when they noticed that red-winged blackbirds were also responding aggressively to the calls. This prompted the new study.

To learn what the red-winged blackbirds understood about the calls, the researchers played a variety of bird calls in red-wing and yellow warbler territories and watched how the birds responded. They found that the red-winged blackbirds responded identically to the seet calls, the sound of cowbird chatter and blue jay calls - all of which signal a threat to their nests.

"They responded very aggressively to these calls, more so than they did to the warbler 'chip' call, which is just a general antipredator call," Lawson said. When red-wings heard the warblers seeting, they flew close to the loudspeaker and looked around for the threat, she said.

When red-winged blackbirds see any kind of predator in their territory, they swoop at it and dive bomb it. Male red-wings have so many mates in so many nests that they must defend a wide territory from interlopers and threats, Lawson said. This is why red-winged blackbirds are known as the "knights of the prairie."

In defending their own nests from predators, they end up helping out other bird species - in particular, yellow warblers. Previous research shows that yellow warblers that nest near red-winged blackbirds suffer less from cowbirds laying their eggs in their nests.

The warblers also appear to help the blackbirds by warning of nest predators, the researchers said.

"We found that the red-winged blackbirds that nest really close to the warblers respond more strongly to the seet calls than those that nest far away," Lawson said.

The researchers have more work to do to determine whether the blackbirds understand that the seet call means "cowbird," specifically, or if it is just interpreted as a general danger to the nest. In a future study, the researchers will play the seet call to re-wings at the end of the nesting season to see if the blackbirds respond as aggressively to the sound after their eggs have hatched. Yellow warblers stop making the seet call when their nestlings are secure and too old to be bothered by cowbirds.

"This is the first report of a bird eavesdropping on another species' warning of a brood parasite," Hauber said. "We don't yet know if the red-winged blackbirds understand that the warning is specific to cowbirds, but it's obvious they understand that the call represents a threat to the nest - and that benefits them."

From birth, we acquire information and learn through interacting with others; that is why it is so important to be able to identify the most suitable individuals to interact with. To interact with others, it is important to understand and predict their actions. It is known that at around six months of age, infants already understand that actions are carried out to achieve certain goals, that is, when someone does an action, they do so to get something.

"For example, if infants see someone extending their arm to get a glass of water, they process the movement in relation to the goal of getting the glass. Once they have identified the goal that motivates the action, they expect the person to act efficiently to get it. For example, if the glass of water is two metres from the person, a rational action would be to get up from the chair, walk a few metres and then stretch out the arm to get the glass. If, however, the glass is nearby, the rational action would be to directly stretch out the arm. From an early age, infants are already surprised if they see someone performing more actions that required or making a greater effort than needed", explains Marc Colomer, first author of a study published in the advanced online edition of the Journal of Experimental Child Psychology on March 6.

Based on this idea, it has been proposed that one of the pillars on which social cognition is built is the principle of rationality: through assuming that individuals try to act efficiently to achieve a goal, we can determine the goal that motivates their actions.

This study conducted by Marc Colomer with Jesús Bas and Núria Sebastián Gallés, researchers with the Center for Brain and Cognition (CBC) at the Department of Information and Communication Technologies (DTIC) of UPF, has shown that, already at 15 months, infants take into account the efficiency of the actions of others in order to identify who is and who is not rational.

"We wanted to study whether the efficiency of the actions of others influences the infants' preferences. Our initial hypothesis was that the principle of rationality would not only allow the infants to predict and understand the actions of others, but would also allow them to identify which individuals act rationally and which do not and, therefore, who it makes more sense to interact with", explain Colomer and Bas, co-authors of the work and doctoral students with the research group in Speech Acquisition and Perception, led by Núria Sebastián Gallés.

This is an example of the stimuli that were used. The order of the actions of each doll (who acts first), its role (efficient or inefficient) and the order of the test (who the yellow joins first) was offset. That is, each participant was presented with slightly different stimuli, manipulating these three variables. Offsetting allows controlling that the results obtained are not due to a preference, for example, for a specific doll.

As the authors of the study explain: "to answer our question, we designed a study involving children between 14 and 15 months. The infants watched a video with three dolls: one yellow, one blue, one red. First, one of the dolls (the yellow one, for example) watched how the other two dolls (the blue and the red one, for example) jumped over a fence to get a ball. Then, the same yellow doll interacted with the other two dolls separately. Next, a gate opened in the fence through which it was easier to get to the ball. In this new scenario, one of the dolls went straight through the gate to get the ball (efficient doll), while the other kept jumping over the fence (inefficient doll). In the end, the infants were presented with the test: the blue and red dolls went to fetch the yellow doll and the latter had to decide whether to interact with the one that had gone through the gate (Efficient test) or the one that had jumped over the fence, taking a longer path than necessary (Inefficient test)".

"To find out whether the infants expected the yellow doll to prefer to interact with the efficient or the inefficient doll, we used the Violation of Expectation paradigm", the authors explain. This is based on the fact that the infants watch the screen for longer when they are presented with an unexpected stimulus which, therefore, takes them longer to process. All the infants saw the Efficient test and the Inefficient test and we measured the time they spent looking at the screen after each test. The results showed that in general, they all looked for significantly longer at the Inefficient test than at the Efficient test. That is, they were surprised when the yellow doll interacted with the inefficient doll rather than the efficient one".

The participating infants preferred to look at the efficient doll

"In addition, we measured the infants' visual preferences when the blue and the red dolls went to fetch the ball together. We acquired this information using the Eye-tracker, a camera that records the participants' visual behaviour. With these data, we found that the participants preferred to look at the efficient doll", explains Jesús Bas, co-author of the study.

These results show that already at 15 months, infants take into account the efficiency of the actions of others in order to identify who is and who is not rational They use this information to predict the preference of others, and it even modifies the attention the infants pay to others. This link between the principle of rationality and social preference may be highly relevant when starting to negotiate the world selectively from an early age, choosing who we prefer to learn from and who prefer to interact with.

Entanglement, a powerful form of correlation among quantum systems, is an important resource for quantum computing. Researchers from the Quantum Optomechanics group at the Niels Bohr Institute, University of Copenhagen, recently entangled two laser beams through bouncing them off the same mechanical resonator, a tensioned membrane. This provides a novel way of entangling disparate electromagnetic fields, from microwave radiation to optical beams. In particular, creating entanglement between optical and microwave fields would be a key step towards solving the long-standing challenge of sharing entanglement between two distant quantum computers operating in the microwave regime. The result is now published in Nature Communications.

In a future quantum internet, that is the internet of quantum computers, entanglement needs to be shared between two distant quantum computers. This is typically done with electromagnetic links like optical fibers. Presently, one of the most advanced quantum systems is based on superconducting circuits, which work in the microwave regime. As advanced as it is, connecting such computers in networks still poses a steep challenge: microwaves can't propagate far without loss which is harmful to quantum computing tasks. One way of alleviating this problem is to first entangle microwaves with optical fields, then use optical links, with far lower loss, for long-distance communication. However, due to large difference in wavelengths (millimeters for microwaves and micrometers for light), this conversion remains a challenge.

Objects vibrate when bombarded by light particles

When an electromagnetic field, i.e. a laser beam, is reflected off a vibrating object, it can read out the vibration. This is a widely used effect in optical-based sensing. On the other hand, an electromagnetic field is composed of photons, energy bullets of light. As the light is bounced off the object, the photons bombard it, leading to additional vibration. This additional vibration is called quantum backaction. Reflection of two electromagnetic fields upon the same mechanical object provides an effective interaction between the fields. Such interaction takes place irrespective of the wavelength of the two fields. Then, this interaction can be exploited to create entanglement between the two fields, independently of their wavelengths, e.g. between microwave and optics. Though quantum backaction can be prominent for objects as small as an atom, only in recent years, researchers have been able to make macroscopic mechanical devices that are so sensitive to observe this effect.

Ultra-sensitive mechanical device mediates entanglement

In their now reported work, researchers from the Quantum Optomechanics group use a thin membrane, 3x3 mm wide, made of silicon nitride and pierced with a pattern of holes that isolates the motion of the central pad. This makes the device sensitive enough to show quantum backaction. They shine two lasers on the membrane simultaneously, where one laser sees the quantum backaction of the other, and vice versa. In this way, strong correlations, and indeed entanglement, is generated between two lasers. "You could say that the two lasers 'talk' through the motion of the membrane", says Junxin Chen, who has been working on the project during his PhD, and is one of the primary authors of the scientific article.

"The membrane oscillator functions as an interaction media, because the lasers don't talk to each other directly - the photons don't interact themselves, only through the oscillator." Junxin Chen further says, "the interaction between photons and the membrane is wavelength independent, allowing in principle microwave-optical entanglement." Further experimental work will be necessary to do this - in particular operation of the membrane at a temperature close to absolute zero, at which superconducting quantum computers work today. Experiments along these lines are underway at the Niels Bohr Institute.

CORVALLIS, Ore. - A study that included the first-ever winter sampling of phytoplankton in the North Atlantic revealed cells smaller than what scientists expected, meaning a key weapon in the fight against excess carbon dioxide in the atmosphere may not be as powerful as had been thought.

Thus, commonly used carbon sequestration models might be too optimistic.

The Oregon State University research into the microscopic algae, part of NASA's North Atlantic Aerosols and Marine Ecosystems Study, was published this week in the International Society for Microbial Ecology Journal.

The findings are significant because the spring phytoplankton bloom in the North Atlantic "is probably the largest biological carbon sequestration mechanism on the planet each year, and the size of cells determines how fast that carbon sinks," said the study's corresponding author, OSU College of Science microbiology researcher Steve Giovannoni.

OSU postdoctoral researcher Luis Bolaños is the lead author.

Phytoplankton are microscopic organisms at the base of the ocean's food chain and a key component of a critical biological carbon pump. Most float in the upper part of the ocean, where sunlight can easily reach them.

The tiny plants have a big effect on the levels of carbon dioxide in the atmosphere by sucking it up during photosynthesis. It's a natural sink and one of the largest ways that CO2, the most abundant greenhouse gas, is scrubbed from the atmosphere. Understanding how and why phytoplankton bloom every spring is critical to learning how the Earth's living systems could respond to global climate change.

As the ocean pulls in atmospheric carbon dioxide, phytoplankton use the CO2 and sunlight for photosynthesis: They convert them into sugars the cells can use for energy, producing oxygen in the process.

The phytoplankton cells absorb that CO2 eventually sinking to the bottom of the ocean as they die. The planet's ecological health depends on regular plankton blooms such as the spring event in the North Atlantic in which huge numbers of phytoplankton accumulate over thousands of square miles.

The larger project that Bolaños and Giovannoni were part of, the North Atlantic Aerosols and Marine Ecosystems Study, was led by Michael Behrenfeld of the OSU College of Agricultural Sciences. The team used ship- and aircraft-based measurements and satellite and ocean sensor data to help clarify the annual phytoplankton cycles and their relationship with atmospheric aerosols.

Aerosols are minute particles suspended in the atmosphere that can affect the Earth's climate and radiation budget - by bouncing sunlight back into space and, in the lower atmosphere, by modifying the size of cloud particles, which changes how clouds reflect and absorb sunlight.

Bolaños, Giovannoni and their collaborators sampled phytoplankton in the western North Atlantic in both early winter and spring to try to get a handle on how the phytoplankton community transitioned between those seasons.

In earlier research, Behrenfeld found that the increase in numbers of phytoplankton, shown by chlorophyll and carbon concentrations, begins in midwinter when growth conditions are at their worst rather than being started by the onset of spring weather.

"The surface layer of the North Atlantic is deeply mixed in winter by storms and temperature-dependent 'convective' mixing," Behrenfeld explained. "This causes phytoplankton to be spread more thinly in the water, making it tough for the tiny animals that eat phytoplankton to track their prey. The reduction in feeding enables the phytoplankton to get a head start in growth as an opening act to the massive bloom that occurs once the winter storms fade and conditions for growth get better. By spring's end, the grazers have made up the lost ground, eating the phytoplankton as it grows and bringing the bloom to an end."

About half of the organisms in the spring bloom that the researchers sampled could not be genetically traced to the winter samples, Bolaños said.

"This suggests that there are life history strategies by which phytoplankton that are undetectable in winter can rise to high numbers in the spring, or there is a quick community turnover due to the circulation of water masses," he said.

Bolaños added that diatoms, thought to dominate phytoplankton blooms in the North Atlantic, often were not a big part of the samples' genetic profiles, and when they were a big part, the cells were small - either of the nano-phytoplankton variety or at the smaller end of the micro-phytoplankton scale.

"Biogeochemical models are often influenced by the perception that North Atlantic phytoplankton blooms are composed of large cells," he said. "That perception has been perpetuated by models that assume that diatoms are uniformly large cells. But they're not."

Algorithms that predict carbon export from satellite-sensed chlorophyll tend to assign high export rates to phytoplankton blooms on the belief, based on observations from the eastern North Atlantic, that large diatoms dominate at their climax.

The findings of this study, Giovannoni said, suggest that extrapolating those observations to the western North Atlantic may not be a valid practice.

"We're not certain whether our new observations of small phytoplankton in the western North Atlantic are due to physical differences between the western and eastern North Atlantic, ocean warming and higher atmospheric CO2 concentrations, or constraints of earlier research methods," he said. "There's also a chance our observations were an anomaly, a coincidence. We don't know for sure."

Cells less than 20 micrometers in diameter made up most of the phytoplankton biomass in the study samples. Diatoms were important contributors but not the main component of biomass.

"We found that diverse, small phytoplankton taxa were unexpectedly common in the western North Atlantic and that regional influences play a large role in community transitions during the seasonal progression of blooms," Giovannoni said. "The profoundly contrasting composition of the winter community, and the domination by small taxa that we found in the spring, are system features that alter our perspective and are areas for future research. Our results could have major implications for understanding how the blooms affect regional carbon biogeochemistry - the multispecies blooms we describe can have lower carbon export efficiencies than the models typically allow for."

The existence of coral reefs, in all their abundant biodiversity and beauty, relies largely on a complex symbiosis between reef-building corals and microalgae. This finely tuned, fragile, partnership is constantly under threat from environmental stress - most notably the twin effects of warming waters and ocean acidification caused by climate change. But scientists say a third driver, that of ocean deoxygenation, could pose a greater and more immediate threat to coral reef survival.

A perspective paper published in Nature Climate Change brings together existing
biological, ecological, and geochemical evidence to consider the broader role for ocean deoxygenation in global coral reef degradation. The University of Technology Sydney (UTS) led study has found that the threat of ocean deoxygenation to coral reefs has largely been ignored and remains unaccounted-for in predictions about future reef health. This is despite reef-building corals underpinning both the ecological and economic value of the world's coral reef ecosystems.

Lead author, Dr David Hughes, a Research Associate at the UTS Climate Change Cluster, said that measurements taken over the last 50 years showed oxygen levels in the world's oceans have already declined by around 2% "largely due to the dual forces of global climate change and coastal pollution caused by nutrient runoff".

"Our oceans are slowly suffocating and although we have some understanding about deoxygenation in the open ocean this process has been largely overlooked in coastal tropical reef systems.

"Although oxygen is a relatively easy environmental variable to measure, there is surprisingly very little data available for coral reefs," he said.

The authors, who also include scientists from the University of Copenhagen, Denmark and University of Konstanz, Germany, say this lack of data makes it very difficult to assess what normal oxygen levels are on coral reefs or the dissolved oxygen threshold at which areas might become "dead zones".

"We simply don't know what constitutes lethal or sub-lethal oxygen thresholds within coral reefs or the role such thresholds will play in determining what future reefs will look like," Dr Hughes said.

Associate Professor David Suggett, senior author and leader of the Future Reefs Research Program at UTS said it's likely that understanding the impact of deoxygenation for places like the Great Barrier Reef "holds the key to being able to more accurately predict the future for coral reefs."

"Oxygen fundamentally sustains reef life.

"It's possible that declining oxygen availability has amplified, and will continue to amplify, the impact of catastrophic events such as heat-wave driven mass coral bleaching. Capacity for organisms to resist stressors is severely compromised under reduced oxygen availability. It's why we give oxygen to humans under trauma", he said.

"Identifying thresholds of low oxygen tolerance and how they vary across coral reef-associated species and environmental history is arguably the key step in understanding
how reef communities will respond to continued ocean deoxygenation," Associate Professor Suggett said.

The authors say that unlike the deep knowledge gained over the past 30 years around the twin impacts of temperature and pH levels, there wasn't the same depth of knowledge about ocean deoxygenation and, therefore, how this will shape reef ecologies.

Suggett and Hughes say establishment of an oxygen sensor network on the GBR would be a good place to start and could help develop an oxygen inventory of the reef to enable new approaches and management practices.

A positive outcome from the study is the sign that local management is crucial to preventing further deoxygenation in coastal waters.

"The resources being mobilised to improve agricultural and catchment management on the GBR are good examples of practices to ensure the oxygen stocks of coastal reefs," Associate Professor Suggett said.

"Everyone has a role to play to ensure our reefs don't suffocate further," he said.

HOUSTON -- New findings from researchers at The University of Texas MD Anderson Cancer Center about how some cancer cells become "addicted" to glucose could open up fresh approaches to therapy strategies for cancers with high levels of an amino acid transporter called solute carrier family 7 member 11 (SLC7A11). This includes lung cancer and renal cell carcinoma, the most common type of kidney cancer.

The study, led by Boyi Gan, Ph.D., of the Department of Experimental Radiation Oncology, explored metabolic reprogramming, cancer, and published findings in the March 30 online issue of Nature Cell Biology.

"Metabolic reprogramming often renders cancer cells highly dependent on specific nutrients for survival," said Gan. "Limiting the supply of such nutrients or blocking their uptake or metabolism through pharmacological means may selectively kill 'addicted' cancer cells without affecting normal cells. Our understanding of nutrient dependency in cancer cells can provide great insights for targeting metabolic vulnerabilities in cancer therapies."

The chemistry behind cancer cell "addictions"

Gan noted the example of asparaginase treatment for acute lymphoblastic leukemia, which, unlike normal cells, lacks the ability to produce the amino acid asparagine, and must depend on extracellular sources to obtain asparagine in order to survive. The treatment disrupts asparagine supply and ensures the cancer cells cannot gain access to this vital amino acid, resulting in cancer cell death.

Cancer cells depend on another amino acid known as cystine to ensure strong antioxidant defenses. Most cancer cells obtain cystine via the SLC7A11 transporter. Once inside cells, cystine is converted to a related amino acid called cysteine, which is then used to build up glutathione, the most common antioxidant produced in the body, which in turn, allows cancer cells to survive.

"SLC7A11 is frequently overexpressed in cancers and has a well-established role in maintaining glutathione levels which reduce cancer cell death," said Gan. "However, in this study we found that actively importing cystine into cells represents a risky business for cancer cells. Cystine is among the least soluble amino acids and accumulating too much cystine inside cells is toxic. Therefore, cancer cells are forced to quickly convert cystine to cysteine. Consequently, cancer cells with high levels of SLC7A11 and high demand for cystine become dependent on glucose for survival."

These findings revealed a metabolic vulnerability associated with high SLC7A11 expression in cancer cells, which suggests corresponding therapeutic strategies. The research team showed that therapies known as glucose transporter (GLUT) inhibitors cut off glucose supply, leading to toxic buildup of cystine inside cells. This selectively kills SLC7A11-high cancer cells and suppresses SLC7A11-high tumor growth. This study therefore suggests using GLUT inhibitors to treat tumors with high expression of this key amino acid transporter.

Water ice is one of the most abundant solid substances in nature and hydrated protons on the ice surfaces critically influence physical and chemical properties of ices. Hydrated protons are easily doped into the hydrogen-bond (HB) networks when acidic impurities are present. In contrast, in pure water molecular systems, they are generated solely by the thermal ionization of water molecules (H2O⇆H+hyd + OH-hyd). Therefore, the proton activity inherent to water ice is determined by the amount and mobility of hydrated protons derived from the autoionization (Figure 1).

Considerable discussions have been made, yet not been settled, on whether the activity of hydrated protons is substantially enhanced at the surface of water ice. This is crucially important problem for understanding the impact of ice surface ubiquitous in nature on a wide variety of heterogeneous phenomena, such as charge generation, separation and trapping in a thunder storm, photochemical destruction of the earth's ozone layer, and even the molecular evolution in space, etc.

Very recently, researchers led by Toshiki Sugimoto, Associate Professor at the Institute for Molecular Science, succeeded in directly and quantitatively demonstrating that the proton activity is significantly enhanced at the surfaces of low-temperature ice. On the basis of simultaneous experimental observation of the H/D isotopic exchange of water molecules at the surface and in the interior of double-layer crystalline-ice films composed of H2O and D2O (Figure 2), they reported three major discoveries of the unique enhancement of surface proton activity: (1) proton activity proved by the H/D exchange (Figure 1) at the topmost surface is at least three orders of magnitude higher than in the interior even below 160 K; (2) the enhanced proton activity is dominated by autoionization process of water molecules rather than proton transfer process at ice surface; (3) as a consequence of surface promoted autoionization, the concentration of surface hydrated protons is estimated to be more than six orders of magnitude higher than that in the bulk.

Correlating these results with molecular-level structure and dynamics of the low-temperature ice surface, they discussed that the cooperative structural fluctuations allowed in the undercoordinated surface molecules (Figure 3) but inhibited in the fully coordinated interior molecules facilitate the autoionization and dominate the proton activity at the ice surface. Because the lower limit of temperature of the earth's atmosphere is ~120 K around the mesopause, the surface of crystalline ice on earth is unlikely to be solidly ordered but would inevitably be highly fluctuated. In nature, such dynamic features facilitate the autoionization of water molecules and thus enhance the proton activity at the surface of crystalline ice. "Our results not only advance the physical chemistry of interfacial hydrogen bonds but also provide a firm basis for elucidating the key properties of ice surface that are of great interest in a variety of phenomena relevant to the dynamics of hydrated protons," says Sugimoto.