Culture

Tokyo, Japan - Researchers at the Institute of Industrial Science at The University of Tokyo sifted through experimental data to probe the possibility that supercooled water has a liquid-to-liquid phase transition between disordered and tetrahedrally structured forms. They found evidence of a critical point based on the cooperative formation of tetrahedra, and show its minor role in water's anomalies. This work shows that water's special qualities--which are essential for life--originate predominantly from the two-state feature.

Liquid water is indispensable for life as we know it, yet many of its properties do not conform with the way other fluids behave. Some of these anomalies, such as water's maximum density at 4°C and its large heat capacity, have important implications for living organisms. The origin of these features has sparked fierce debates in the scientific community since the time of Röntgen.

Now, researchers at The University of Tokyo have utilized a two-state model that posits the dynamical coexistence of two types of molecular structures in liquid water. These are the familiar disordered normal-liquid structure and a locally favored tetrahedral structure. As with many other phase transitions, there may be a "critical point" at which the correlation between tetrahedra takes on a power-law form, which means there will no longer be any "typical" length scale.

Using computer simulations of water molecules, along with a comprehensive analysis of experimental structural, thermodynamic, and dynamic data--including X-ray scattering, density, compressibility, and viscosity measurements--the researchers were able to narrow down where a critical point should be, if it exists.

"If the formation of tetrahedral structures in liquid water is cooperative under these conditions, then a liquid-liquid phase transition with a critical point is possible," lead author Rui Shi says.

The team showed that this occurs around a temperature of ?90°C and a pressure of about 1,700 atmospheres. Experiments in this range are exceedingly difficult: because the water is so far below its normal freezing, ice crystals can quickly form. However, samples can remain liquid in a metastable "supercooled" state at these very high pressures.

"We saw evidence that the critical point is real, but its effect is almost negligible in the experimentally accessible region of liquid water because it is too far from the critical point. This means that water's anomalies come from the two-state feature and not from criticality," senior author Hajime Tanaka says. The scientists anticipate that this project will lead to the convergence of the long debate on the origin of water's anomalies and more experimental research to access the second critical point of water.

The professional perception of vitamin D as a medicine, rather than as a key nutrient, is constraining practice and jeopardising the health of elderly care home residents in England, conclude researchers in the journal BMJ Nutrition Prevention & Health.

At a time when the vulnerability of elderly care home residents is under the spotlight because of the impact of COVID-19, an urgent review is needed of the nutritional guidelines and regulations around the use of the vitamin, they argue.

The main source of vitamin D is exposure to sunlight, levels of which plummet during the winter in many countries in the northern hemisphere. With few major food sources, it's difficult to get enough vitamin D from diet alone, and vitamin D deficiency in care homes is widespread in many parts of the world, say the researchers.

Vitamin D is essential for good bone health and is thought to have a role in immunity, cardiovascular health, neurological conditions, respiratory infections, lung function and cancer. Most recently, it has been linked to susceptibility to, and severity of, COVID-19.

People who spend less time outdoors, such as the elderly in residential care, or who regularly cover up their skin, or who have darker skin tones, are all at heightened risk of vitamin D deficiency.

Vitamin D supplements have been recommended for care home residents for nearly 30 years. In 2016, recommendations for daily vitamin D supplements were extended to the entire population in the winter months, and throughout the year for those living in care homes.

National bodies from around the world have issued similar recommendations for care home residents, including Australia, Canada, France, Norway, New Zealand and the USA.

In a bid to better understand thinking and practice around the use of vitamin D, the researchers conducted semi-structured interviews with 13 people involved in elderly residential care in two different areas of South East England.

Participants included 4 family doctors (GPs), 4 care home managers, a dietician, a falls specialist, 2 public health practitioners/managers, and a senior doctor in elderly care.

None was aware of any care home routinely prescribing vitamin D supplements to its residents. And although vitamin D supplements are regulated as foods, they were nevertheless regarded as medicines.

Interviewees considered that GPs were responsible for the vitamin D status of elderly care home residents, with prescriptions only written in response to falls or a diagnosis of vitamin D deficiency or osteoporosis rather than as maintenance or preventive treatment, which reflects current NHS guidance.

Care home staff said they would feel vulnerable to malpractice allegations if they routinely provided over-the-counter vitamin D supplements to their residents: they felt this was beyond the scope of their role and expertise.

And there was considerable ambiguity about who should provide and bear the cost of these supplements, although most felt this was GPs' responsibility as prescribers, and that any change would have financial implications for care homes or the residents and their families.

What's more, NHS guidance advises against routine prescription of vitamin D because supplements can be bought easily and cheaply over the counter.

Apart from the dietitian, none of the interviewees seemed familiar with the recommendation that all elderly care home residents should receive vitamin D supplements without the need for a confirmatory blood test, which itself costs more than a year's supply of supplements.

And not everyone was aware that diet and sunlight can't provide adequate vitamin D levels even for the general population in the UK during winter months.

Current nutritional recommendations for supplementary vitamin D also heavily rely on personal responsibility, the researchers point out.

"It is questionable whether this is appropriate in populations with limited autonomy," they say, especially as it effectively creates "a two-tier system, discriminating against those with the least cognitive independence."

The researchers acknowledge the small size of their study, but the fact that participants referred to national policy drivers as key determinants of current practice suggests the finding may be generalisable more widely in England, they suggest.

"The COVID-19 pandemic has brought conditions in care homes into the public eye and on to the political agenda. While practices in care homes are in the spotlight there is an urgent need for action to ensure vitamin D recommendations can be applied in care homes," they write.

"The medical framing of vitamin D supplements in care homes is a practical barrier to implementation of longstanding nutrition guidelines. A paradigm shift is needed so that vitamin D is understood as a protective nutrient as well as a medicine, and a public health as well as a medical responsibility," they conclude.

Commenting on behalf of the NNEdPro Global Centre for Nutrition and Health, the think tank which co-founded this journal, Professor Sumantra Ray, its Executive Director, said: "This research re-emphasises the role of vitamin D in health, an issue that has become even more relevant, given the growing body of evidence, including research published in this journal suggesting that it may help lower the risk of COVID-19 infection and/or ease the severity of symptoms, particularly among those at highest risk."

Shane McAuliffe, Science Comms Lead for the NNEdPro COVID19 Taskforce, which was set up to translate nutritional evidence into best practice in the pandemic, adds: "We also know that an adequate level of vitamin D is key to the maintenance of good general health, and deficiencies can only be picked up by proactive testing, or when this isn't feasible, by adopting a preventive approach in line with Public Health England guidelines.

"This means providing those who may not be able to obtain sufficient vitamin D through sunlight alone with vitamin D supplements throughout the year. That includes care home residents and certain ethnic minority groups."

What The Study Did: The risk of mother-to-newborn transmission of SARS-CoV-2 infection was examined in this study.

Authors: Cynthia Gyamfi-Bannerman, M.D., M.Sc., and Melissa S. Stockwell, M.D., M.P.H., of the Columbia University Irving Medical Center in New York, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.4298)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study and commentary are linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2020.4298?guestAccessKey=10117155-99d5-40cd-9254-10dadbdc7b8b&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=101220

Exploration of new leukemia antigens and construction of appropriate delivery systems using FDA-approved material are important strategies for developing leukemia vaccines for clinic use.

Researchers from the Institute of Process Engineering (IPE) of Chinese Academy of Sciences and Zhujiang Hospital of Southern Medical University have developed a new type of precise therapeutic vaccine against leukemia. It utilizes self-healing polylactic acid microcapsules for co-encapsulating a new epitope peptide and PD-1 antibody.

The study was published in Nature Biomedical Engineering on October 12.

Although the possibility of treating leukemia through vaccination has been established, therapeutic performance still falls short of expectations in clinic.

"Our clinical findings revealed the high expression of EPS8 and PD-1/PD-L1 in leukemia patients, which could be respectively used as a new type of leukemia antigen and a checkpoint target for a leukemia vaccine," said Prof. LI Yuhua from Zhujiang Hospital.

In the novel vaccine, epitope peptides and PD-1 antibodies can be simply, mildly and efficiently loaded into polylactic acid microcapsules, facilitated by the unique self-healing feature of the microcapsule.

After a single vaccination, the deposition and degradation of microcapsules at the local injection site lead to recruitment of activated antigen-presenting cells and sustained release of both cargos.

"With the synergism of these two aspects, we observed a significant improvement in specific Cytotoxic T Lymphocyte (CTL) activation," said Prof. WEI Wei from IPE.

The researchers also verified the availability of the novel vaccine using various epitope peptides in different models, such as murine leukemia, humanized cell line-derived leukemia xenograft (CDX) and patient-derived leukemia xenograft (PDX) models.

The microcapsule-based formulation demonstrated its superior performance over that of the ISA adjuvant (commercialized adjuvant) in all leukemia therapeutic models, showing the promise of the microcapsule-based vaccine for use against various leukemia antigens in clinic.

"With the advantages of FDA-approved polylactic acid material, convenience in preparing the vaccine formulation, diversity of vaccine components, and excellent therapeutic effect, the microcapsule-based vaccine exhibits great potential for clinical translation," said Prof. MA Guanghui from IPE.

A peer reviewer from Nature Biomedical Engineering described the study as "comprehensive for a new platform". The reviewer also emphasized that the work is "exciting and convincing".

Researchers have charted the activity of tens of thousands of genes in mouse immune cells over the course of an infection. The study from the University of Melbourne, Australia, the Wellcome Sanger Institute, and their collaborators created the first full dynamic map of how cells learn to fight microbes and then preserve a memory of this for future infections.

The findings, published in the journal Nature Immunology, could help scientists develop new vaccines and therapeutics for a range of diseases by guiding their research into a particular set of immune cells, known as CD4+ T cells, that are essential for generating immunity.

The international research team studied the CD4+ T cells during an experimental infection of mice with malaria-causing parasites, which invade and multiply inside red blood cells. With the aid of machine learning techniques, the research team combined the gene activity data over four weeks of infection to generate a comprehensive map of the developmental journeys taken by CD4+ T cells.

Dr Ashraful Haque, co-lead author from the University of Melbourne's Doherty Institute, said: "We traced thousands of individual genes to generate a map from initial infection to periods when cells firstly 'decide' between various immune roles for fighting the infection, and secondly preserve memories of that encounter. Our map revealed several novel genes that were active - in particular, in a type of CD4+ T cells called T follicular helper cells. These are essential for making antibodies that protect against malaria but have not yet been well studied."

The scientists have shared their data through a freely available digital resource. This map allows immunology researchers worldwide to track the response of individual genes after infection.

Dr Sarah Teichmann, co-lead author from the Wellcome Sanger Institute, said: "Importantly, while our map was generated using an experimental model of malaria, it will be useful for studying T cell responses in almost any infectious or non-infectious disease, or treatment in which T cells are involved. Further investigations are needed to confirm that human cells have a similar map to mouse CD4+ T cells. However, we hope this discovery can point researchers in the right direction towards developing new vaccines for infectious diseases, new immune-therapies for certain cancers, and novel ways to prevent auto-immune conditions."

What The Study Did: The association between the COVID-19 pandemic and health care-related data collection is examined in this Viewpoint article.

Authors: Makoto Mori, M.D., of the Yale School of Medicine in New Haven, Connecticut, is the  corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.5542)

Editor's Note: The article includes conflict of interest disclosure. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

WINSTON-SALEM, N.C. - October 12, 2020 - Scientists at Wake Forest School of Medicine have recorded real time changes in dopamine and serotonin levels in the human brain that are involved with perception and decision-making. These same neurochemicals also are critical to movement disorders and psychiatric conditions, including substance abuse and depression.

Their findings are published in the Oct. 12 edition of the journal Neuron.

"This study provides us a unique window into the human brain that has been inaccessible until now," said principal investigator Kenneth T. Kishida, Ph.D., assistant professor of physiology and pharmacology and neurosurgery at Wake Forest School of Medicine, part of Wake Forest Baptist Health. "Almost everything we have known mechanistically about these neurochemicals was from work done in preclinical animal models, not from direct evidence from humans."

Having a clearer understanding of how these brain chemicals actually work in people may lead to improved medications or treatments for disorders like Parkinson's disease, substance use disorder or depression, Kishida said.

In this observational study, the neurotransmitters dopamine and serotonin were tracked in five patients using fast scan cyclic voltammetry, an electrochemical technique used to measure dopamine and serotonin, adapted for use in patients. Dopamine and serotonin are chemical messengers used by the nervous system to regulate countless functions and processes in the body.

Study participants - two with Parkinson's and three with essential tremor - were patients at Wake Forest Baptist who were scheduled to receive a deep brain stimulating implant to treat their condition. Working closely with neurosurgeons, Stephen B. Tatter, M.D., and Adrian W. Laxton, M.D., Kishida's team was able to piggyback on the standard surgical mapping process to insert a carbon fiber microelectrode deep into the brain to detect and record serotonin and dopamine released from neurons. The patients with essential tremor were important to the study because, unlike Parkinson's disease which is caused by loss of dopamine-producing neurons, essential tremor is not believed to be caused by changes in dopamine or serotonin function.

While the patients were awake in the operating room, they performed decision-making tasks similar to playing a simple computer game. As they performed the tasks, measurements of dopamine and serotonin were taken in the striatum, the part of the brain that controls cognition, reward and coordinated movements.

Kishida described the game as a series of dots on a computer screen that moved through a "cross-hair" reference point positioned in the center of the screen. Patients had to decide which way the dots were moving. Sometimes the dots would move in the same direction and at other times the dots would move more chaotically making the decision harder.

The dots then disappeared and the patient had to choose which way the dots had moved - clockwise or counter clockwise - relative to a fixed point. This experimental design, created by Kishida's collaborators and co-authors Dan Bang and Stephen M. Fleming, at University College London, allowed the team to tease apart different aspects of how the human brain decides what it has perceived.

This sequence was repeated 200 to 300 times per patient, varying how the dots moved and thus how difficult it was for the patient to decide what they saw. Occasionally, the patients had to indicate how confident they were in their choices.

The test was designed to track the patient's ability to perceive the dots' movement and the patient's confidence in correctly identifying the direction of that movement as a way to determine how dopamine and serotonin actually behaved. The trials were randomized so that predictability from one test trial to the next would be minimized, Kishida said.

The findings showed that the more uncertain the patient was about the direction of the dots, the higher the serotonin levels became. When their certainty increased, serotonin levels decreased.

The study also revealed that, prior to the act of choosing, dopamine rose in anticipation of the choice and serotonin levels fell, and when both reached a certain level, the person made their choice. It's as if dopamine acted like a gas pedal and serotonin acted like a brake and only when both systems were committed was the act of choice (a button press) allowed, Kishida said.

"This study sheds light on the role these neurochemicals play in learning, brain plasticity and how we perceive the environment," Kishida said. "We now have more detailed insight into how our brains build what we perceive, use those perceptions to make decisions, and interpret the consequences of the choices we make. Dopamine and serotonin appear to be critical in all of these processes.

"Importantly, studies like this will help us and other scientists develop a better understanding of how drugs or medications like serotonin reuptake inhibitors affect cognition, decision-making, and impact psychiatric conditions like depression."

BLOOMINGTON, Ind. -- An examination of racial differences in the disciplining of police officers in three of the largest U.S. cities consistently found that Black officers were more frequently disciplined for misconduct than White officers, despite an essentially equal number of allegations being leveled. This included allegations of severe misconduct.

"We found a consistent pattern of racial differences in the formal recording of disciplinary actions in three different major metropolitan cities: Chicago, Philadelphia and Los Angeles," wrote a group of six management professors at the Indiana University Kelley School of Business. "Our results showed that Black officers were more likely to have recorded cases of misconduct, despite there being no difference between Black and white officers in the number of allegations made against them.

"It is impossible to know whether these differences are due to racial bias versus some other unmeasured factors. However, it is noteworthy that the pattern of results is in line with what theories of racial bias would predict and with evidence of racial disparities in punishment in other settings.

Authors of the article, "The Race Discipline Gap: A Cautionary Note on Archival Measures of Behavioral Misconduct," are Sheri Walter, Eric Gonzalez-Mulé, Cristiano Guarana, Ernest O'Boyle Jr., Chris Berry and Tim Baldwin. All are in Kelley's Department of Management and Entrepreneurship. The article is forthcoming in the journal Organizational Behavior and Human Decision Processes.

Using archival data, they found that Black officers in Chicago were disciplined at a 105 percent higher rate than white officers. In Philadelphia, Black officers were 48 percent more likely than white officers to have been disciplined. Allegations of misconduct include lack of service and verbal or physical assault.

After controlling for the number of allegations of misconduct, they found that Black officers were disciplined at an even higher rate -- 132 percent more often than white officers.

"Just as organizational leaders have implemented policies and procedures to mitigate adverse impact in hiring, they may need to implement checks to ensure that there is no adverse impact in the detection and enforcing of organizational misconduct," the Kelley professors wrote. "Just as bias by police against citizens has been very slow to change, it is likely that any bias within police departments has also been slow to change."

The professors analyzed archival information from the Citizens Police Data Project, which features information collected by the Chicago Police Department from 2001 to 2008 and 2011 to 2015, as well as administrative records from the Philadelphia Police Department from 1991 to 1998.

They also used data collected by the Analysis Group for the City of Los Angeles in 2003 and 2004 to assess whether there are race differences in the number of allegations made against officers. The results of their analysis of data from Chicago and Los Angeles found no differences in allegations between Black and white officers. Results were mixed for Hispanic and Asian officers.

The purpose of the study was to examine the use of archival organizational records as measures of behavioral misconduct. Given prior studies that Black people are more likely to be arrested, receive longer prison sentences and be suspended from school, the researchers set out to study whether Black employees -- when compared to white employees -- were subject to systematic differences in the documentation of misconduct.

"Similar to the issues facing the criminal justice and education systems, where racial disparities in punishment are well-documented, organizations face a difficult challenge in detecting and enforcing misconduct," researchers wrote. "Even when organizations adopt seemingly objective policies for addressing misconduct, it is still possible for certain groups to be disproportionately accused of misconduct and/or disciplined.

The problem of waste management has become persistent. It is a challenge that is growing in bounds and depths as the world's population surges. Are we at our wits' end?

Waste management would need a radical change. According to Beatrice Obule-Abila's doctoral dissertation at the University of Vaasa, Finland, this change could be achieved through the application of knowledge management tools and approaches in the waste management.

Daily, each of the 7.8 billion people inhabiting Earth generates approximately one kilogram of waste, which translates into 5.8 million metric tons of waste. This is about nineteen super-tankers. The problem is not being reduced. Waste generation is bound to continue to increase as the population and urbanization increases, and so are the challenges associated with managing waste, says Obule-Abila.

The doctoral dissertation by Beatrice Obule-Abila focuses on changing the paradigm of waste management by exploring the adoption of knowledge management framework, developing and deploying more knowledge management tools, systems, and approaches in seeking solutions to the problem of waste: so that waste no longer constitutes a nuisance, but a valuable resource.

Are financial incentives or socio-psychological factors the motive for the recycling of waste?

In developing the knowledge management framework that will spur the change in paradigm, Beatrice Obule-Abila answered several germane questions in her thesis. For example, are financial incentives or socio-psychological factors key drivers in promoting recycling and sustainable waste management?

The survey results affirmed that financial incentives are important in accelerating the recycling of municipal solid waste. It was also established that intrinsic and extrinsic factors related to socio-psychology can stimulate consumers' behavior towards adopting recycling and other methods of managing waste sustainably.

It is illuminating to discover that in Finland, incentivization, particularly financial incentives, plays an indispensable role in promoting sustainable recycling of municipal solid waste. Thus, financial incentives are prerequisites for attaining the European Union recycling target for municipal solid waste in Finland, says Obule-Abila.

The study further revealed that both income-earning and non-income-earning groups of consumers show interest in monetary incentives, as a factor spurring their recycling behavior.

The major driver in the recycling of municipal solid waste is a belief in the benefits of recycling waste while the minor driver for the recycling of waste is relative to its attached financial incentive.

Over all, consumers' behavior for the recycling of municipal solid waste is more driven by socio-psychological factors in Finland.

Knowledge management approach as a prerequisite for sustainable waste management

According to Obule-Abila, the knowledge management bridges the knowledge gaps in waste management through its integration to all the aspects of waste management.

The key outcome of the research - a waste knowledge management conceptual framework - lays the foundation for understanding the linkage and applicability of knowledge management in waste management.

The researcher outlined the various paths through exploration and adoption of knowledge management process towards attaining the various goals of waste management - which includes material recovery, energy generation, and the attainment of social, economic, and environmental sustainability.

This dissertation advances the insight of researchers, waste companies, government, particularly at the municipal levels, and a broad array of stakeholders to visualize the knowledge management tools, systems, and approaches used in the management of waste as the foundation of knowledge management.

The dissertation consists of six publications. Four publications apply literature review and synthesis, and two publications employ survey method.

Public Defence

The public examination of M.Sc. Beatrice Obule-Abila's doctoral dissertation "Knowledge management approach for sustainable waste management: Evolving a conceptual framework" will be held on Wednesday 14 October 2020 at noon.

New research shows that sunspots and other active regions can change the overall solar emissions. The sunspots cause some emissions to dim and others to brighten; the timing of the changes also varies between different types of emissions. This knowledge will help astronomers characterize the conditions of stars, which has important implications for finding exoplanets around those stars.

An international research team led by Shin Toriumi at the Japan Aerospace Exploration Agency added up the different types of emissions observed by a fleet of satellites including "Hinode" and the "Solar Dynamics Observatory" to see what the Sun would look like if observed from far away as a single dot of light like other stars.

The team investigated how features like sunspots change the overall picture. They found that when a sunspot is near the middle of the side of the Sun facing us, it causes the total amount of visible light to dim. In contrast, when the sunspots are near the edge of the Sun the total visible light brightens because at that viewing angle bright structures known as faculae surrounding the sunspots are more visible than the dark centers.

In addition, X-rays which are produced in the corona above the solar surface grow brighter when a sunspot is visible. The coronal loops extending above the sunspots are magnetically heated, so this brightening appears before the sunspot itself rotates into view and persists even after the sunspot has rotated out of view.

Because the changes in the overall solar emissions and their timings carry information about the location and structure of features on the surface of the Sun, astronomers hope to be able to deduce the surface features of other stars such as starspots and magnetic fields. This will help astronomers to better recognize dimming caused by the shadow of an exoplanet. With better knowledge about the effects of starspots, we can estimate the parameters, such as the radii and orbits, of exoplanets more accurately.

As in-depth investigations into the Sun proceed, a better understanding of the detailed mechanisms of atmospheric heating and flare eruptions will be gained. Toriumi comments, "To this end, the next-generation solar-observing satellite Solar-C(EUVST), being developed by Japan in close collaboration with US and European partners, aims to observe the Sun in emissions that probe the chromosphere, transition region, and corona as a single system."

Researchers at Kumamoto University, Japan generated mice lacking the estrogen receptor beta (ERβ) gene, both fiber-specific and muscle stem cell-specific, which resulted in abnormalities in the growth and regeneration of skeletal muscle in female mice. This was not observed in male mice that lacked the ERβ gene, suggesting that estrogen and its downstream signals may be a female-specific mechanism for muscle growth and regeneration.

In humans, skeletal muscle mass generally peaks in the 20s with a gradual decline beginning in the 30s, but it is possible to maintain muscle mass through strength training and a healthy lifestyle. Skeletal muscle can be damaged through excessive exercise or bruising, but it has the ability to regenerate. The muscle stem cells that surround muscle fibers are essential for this regeneration; they also play a part in increasing muscle size (hypertrophy). Muscle stem cell dysfunction is thought to be associated with various muscle weakness, such as age-related sarcopenia and muscular dystrophy. Although basic research on skeletal muscle has progressed rapidly in recent years, most studies were conducted on male animals and gender differences were given much consideration.

Estrogen is a female hormone that maintains the homeostasis of various tissues and organs. A decrease in estrogen levels due to amenorrhea, menopause, or other factors can lead to a disturbance in biological homeostasis. When estrogen binds to estrogen receptors (ERs) in cells, it is transferred into the nucleus and binds to genomic DNA to induce the expression of specific genes as transcription factors. There are two types of ERs, ERα and ERβ. While both ERα and ERβ have high binding capacity to estrogen, their tissue distribution is different, they do not have a common DNA-binding domain, and they may act as antagonists to each other, suggesting that they have different roles. Furthermore, estrogen's effects on cells can be both ER-mediated and non-ER-mediated.

An epidemiological study of pre and postmenopausal women in their 50s indicated an association between decreased blood estrogen levels and muscle weakness. A research group at Kumamoto University previously showed that estrogen is important for skeletal muscle development and regeneration using an ovariectomized estrogen deficiency mouse model (Kitajima and Ono, J Endocrinol 2016). They also examined the effectiveness of nutritional interventions in estrogen-deficient conditions (Kitajima et al., Nutrients 2017). However, whether estrogen acts directly on the ER of muscle fibers and muscle stem cells to regulate skeletal muscle growth and regeneration, or whether it acts indirectly through other tissues and organs was unclear. In this study, the researchers generated mice with either myofiber-specific or muscle stem cell-specific ERβ gene deletion and analyzed the function of ERβ in skeletal muscle.

To clarify the role of ERβ in the growth of skeletal muscle, researchers generated mice (mKO) in which the action of the ERβ gene could be turned off in myofibers with the administration of the drug doxycycline. ERβ deficiency was induced at 6 weeks of age, and muscle fiber area and strength of the tibialis anterior muscle was measured at 10-12 weeks. Compared to control mice, both indices were reduced in female mKO mice but not in male mice. Since there was no change in the expression of muscle atrophy-related genes, this reduced growth of female mice was not thought to be due to an increase in muscle atrophy. Ovariectomy-induced estrogen deficiency is known to be associated with muscle quality changes, such as a relative increase in the proportion of fast-type fibers (Kitajima and Ono, J Endocrinol 2016), but no such qualitative changes were observed in mKO mice. It was therefore suggested that, while it may have a direct effect on myofiber growth via ERβ (as expressed in myofibers), estrogen may also regulate the quality of myofibers in a non-ERβ-mediated manner.

To determine the function of ERβ in muscle stem cells, the researchers generated scKO mice in which the ERβ gene could be deleted in muscle stem cells with the administration of the drug tamoxifen. They then evaluated muscle regenerative capacity by locally inducing muscle damage. While muscle regeneration was efficient in control mice, the regenerated muscle tissue of female scKO mice showed thin regenerated muscle fibers, fibrosis caused by collagen deposition, and significantly reduced muscle regenerative capacity. Muscle regeneration in male scKO mice, however, was not impaired. Because impaired muscle regeneration in females was not exacerbated by ovariectomies that made them estrogen deficient, the researchers thus thought that estrogen regulates muscle regeneration via ERβ expressed by muscle stem cells.

To further investigate the cause of reduced muscle regenerative capacity, researchers isolated and cultured muscle stem cells for evaluation. ERβ in cells from scKO mice was evaluated in several experiments using siRNAs and inhibitors. ERβ was found to contribute to the promotion of muscle stem cell proliferation and the inhibition of cell death. Gene expression analysis (RNA-seq) of scKO muscle stem cells showed that the expression of "niche"-related genes, which are required for the maintenance of stem cell properties, was reduced in scKO muscle stem cells. Therefore, the researchers hypothesize that the inactivation of ERβ may have affected the proliferation and survival of muscle stem cells by inhibiting the formation of stem cell niches.

This study is thought to be the first to show that ERβ in genetic mouse models plays an important role in the growth and regeneration of skeletal muscle through its function in both muscle fibers and muscle stem cells. However, the role of ERβ in male mice has not yet been elucidated and remains to be addressed even though its expression in both male and female mice is comparable.

"Amenorrhea is induced in female athletes through rigorous training or excessive dieting and has become one of three major problems, together with low energy availability and osteoporosis, faced by female athletes worldwide," said study leader Associate Professor Yusuke Ono. "Although the animal findings of this study cannot be directly applied to humans, they do suggest that decreased estrogen during amenorrhea may suppress ERβ activity in muscle fibers and muscle stem cells. For female athletes, this may lead to poor athletic performance and delayed recovery from injuries, and puts them at risk for adverse competitive conditions. Our plan is to continue investigating the pathogenesis of age-related sarcopenia and muscular dystrophy by targeting ERβ and its downstream signals with the goal of developing treatments."

Tokyo, Japan -- The continuing progress in miniaturization of silicon microelectronic and photonic devices is causing cooling of the device structures to become increasingly challenging. Conventional heat transport in bulk materials is dominated by acoustic phonons, which are quasiparticles that represent the material's lattice vibrations, similar to the way that photons represent light waves. Unfortunately, this type of cooling is reaching its limits in these tiny structures.

However, surface effects become dominant as the materials in nanostructured devices become thinner, which means that surface waves may provide the thermal transport solution required. Surface phonon-polaritons (SPhPs) - hybrid waves composed of surface electromagnetic waves and optical phonons that propagate along the surfaces of dielectric membranes - have shown particular promise, and a team led by researchers from the Institute of Industrial Science, the University of Tokyo has now demonstrated and verified the thermal conductivity enhancements provided by these waves.

"We generated SPhPs on silicon nitride membranes with various thicknesses and measured the thermal conductivities of these membranes over wide temperature ranges," says lead author of the study Yunhui Wu. "This allowed us to establish the specific contributions of the SPhPs to the improved thermal conductivity observed in the thinner membranes."

The team observed that the thermal conductivity of membranes with thicknesses of 50 nm or less actually doubled when the temperature increased from 300 K to 800 K (approximately 27°C to 527°C). In contrast, the conductivity of a 200-nm-thick membrane decreased over the same temperature range because the acoustic phonons still dominated at that thickness.

"Measurements showed that the dielectric function of silicon nitride did not change greatly over the experimental temperature range, which meant that the observed thermal enhancements could be attributed to the action of the SPhPs," explains the Institute of Industrial Science's Masahiro Nomura, senior author of the study. "The SPhP propagation length along the membrane interface increases when the membrane thickness decreases, which allows SPhPs to conduct much more thermal energy than acoustic phonons when using these very thin membranes."

The new cooling channel provided by the SPhPs can thus compensate for the reduced phonon thermal conductivity that occurs in nanostructured materials. SPhPs are thus expected to find applications in thermal management of silicon-based microelectronic and photonic devices.

Electronic data is being produced at a breath-taking rate.

The total amount of data stored in data centres around the globe is of the order of ten zettabytes (a zettabyte is a trillion gigabytes), and we estimate that amount doubles every couple of years.

With 8% of global electricity already being consumed in information and communication technology (ICT), low-energy data-storage is a key priority.

To date there is no clear winner in the race for next-generation memory that is non-volatile, has great endurance, highly energy efficient, low cost, high density, and allows fast access operation.

The joint international team comprehensively reviews 'multi-state memory' data storage, which steps 'beyond binary' to store more data than just 0s and 1s.

MULTI-STATE MEMORY: MORE THAN JUST ZEROES AND ONES

Multi-state memory is an extremely promising technology for future data storage, with the ability to store data in more than a single bit (ie, 0 or 1) allowing much higher storage density (amount of data stored per unit area.

This circumvents the plateauing of benefits historically offered by 'Moore's Law', where component size halved abut every two years. In recent years, the long-predicted plateauing of Moore's Law has been observed, with charge leakage and spiralling research and fabrication costs putting the nail in the Moore's Law coffin.

Non-volatile, multi-state memory (NMSM) offers energy efficiency, high, nonvolatility, fast access, and low cost.

Storage density is dramatically enhanced without scaling down the dimensions of the memory cell, making memory devices more efficient and less expensive.

NEUROMORPHIC COMPUTER MIMICKING THE HUMAN BRAIN

Multi-state memory also enables the proposed future technology neuromorphic computing, which would mirror the structure of the human brain. This radically-different, brain-inspired computing regime could potentially provide the economic impetus for adoption of a novel technology such as NMSM.

NMSMs allow analog calculation, which could be vital to intelligent, neuromorphic networks, as well as potentially helping us finally unravel the working mechanism of the human brain itself.

THE STUDY

The paper reviews device architectures, working mechanisms, material innovation, challenges, and recent progress for leading NMSM candidates, including:

Flash memory

magnetic random-access memory (MRAM)

resistive random-access memory (RRAM)

ferroelectric random-access memory (FeRAM)

phase-change memory (PCM)

While building a muscle damage model in a cultured system, a research collaboration between Kumamoto University and Nagasaki University in Japan has found that components leaking from broken muscle fibers activate "satellite" muscle stem cells. While attempting to identify the proteins that activate satellite cells, they found that metabolic enzymes, such as GAPDH, rapidly activated dormant satellite cells and accelerated muscle injury regeneration. This is a highly rational and efficient regeneration mechanism in which the damaged muscle itself activates the satellite cells that begin the regeneration process.

Skeletal muscle is made up of bundles of contracting muscle fibers and each muscle fiber is surrounded by satellite cells--muscle stem cells that can produce new muscle fibers. Thanks to the work of these satellite cells, muscle fibers can be regenerated even after being bruised or torn during intense exercise. Satellite cells also play essential roles in muscle growth during developmental stages and muscle hypertrophy during strength training. However, in refractory muscle diseases like muscular dystrophy and age-related muscular fragility (sarcopenia), the number and function of satellite cells decreases. It is therefore important to understand the regulatory mechanism of satellite cells in muscle regeneration therapy.

In mature skeletal muscle, satellite cells are usually present in a dormant state. Upon stimulation after muscle injury, satellite cells are rapidly activated and proliferate repeatedly. During the subsequent myogenesis, they differentiate and regenerate muscle fibers by fusing with existing muscle fibers or with together. Of these three steps (satellite cell activation, proliferation, and muscle differentiation), little is known about how the first step, activation, is induced.

Since satellite cells are activated when muscle fibers are damaged, researchers hypothesized that muscle damage itself could trigger activation. However, this is difficult to prove in animal models of muscle injury so they constructed a cell culture model in which single muscle fibers, isolated from mouse muscle tissue, were physically damaged and destroyed. Using this injury model, they found that components leaking from the injured muscle fibers activated satellite cells, and the activated cells entered the G1 preparatory phase of cell division. Further, the activated cells returned to a dormant state when the damaged components were removed, thereby suggesting that the damaged components act as the activation switch.

The research team named the leaking components "Damaged myofiber-derived factors" (DMDFs), after the broken muscle fibers, and identified them using mass spectrometry. Most of the identified proteins were metabolic enzymes, including glycolytic enzymes such as GAPDH, and muscle deviation enzymes that are used as biomarkers for muscle disorders and diseases. GAPDH is known as a "moonlighting protein" that has other roles in addition to its original function in glycolysis, such as cell death control and immune response mediation. The researchers therefore analyzed the effects of DMDFs, including GAPDH, on satellite cell activation and confirmed that exposure resulted in their entry into the G1 phase. Furthermore, the researchers injected GAPDH into mouse skeletal muscle and observed accelerated satellite cell proliferation after subsequent drug-induced muscle damage. These results suggest that DMDFs have the ability to activate dormant satellite cells and induce rapid muscle regeneration after injury. The mechanism by which broken muscle activates satellite cells is a highly effective and efficient tissue regeneration mechanism.

"In this study, we proposed a new muscle injury-regeneration model. However, the detailed molecular mechanism of how DMDFs activate satellite cells remains an unclear issue for future research. In addition to satellite cell activation, DMDF moonlighting functions are expected to be diverse," said Associate Professor Yusuke Ono, leader of the study. "Recent studies have shown that skeletal muscle secretes various factors that affect other organs and tissues, such as the brain and fat, into the bloodstream, so it may be possible that DMDFs are involved in the linkage between injured muscle and other organs via blood circulation. We believe that further elucidation of the functions of DMDFs could clarify the pathologies of some muscle diseases and help in the development of new drugs."

In addition to the financial statements and balance sheet, an investor should also go through the notes and understand their content, says Juha Mäki, M.Sc.(Eng.), M.Sc.(Econ. & Bus. Adm.), who is defending his doctoral dissertation in University of Vaasa.

For example, the valuation of a company's investment properties in the financial statements may bring surprises depending on whether the company has performed the valuation itself or used an external party for it.

According to Mäki's dissertation, an external appraiser provides more conservative, i.e., more careful values for investment properties than when the company prepares the valuation. In this case, the financial statements of companies that value their investment properties themselves may give a more positive impression about the financial situation.

"Indeed, it will be interesting to see measures after the current pandemic, when, as a result of possibly changed buying behaviour, the values of shopping centres and, because of increased recommendations for remote working, the values of office real estate, should be decreased", says Mäki.

In his dissertation, Mäki has reviewed the possibility to select the valuation and reporting of the value of investment properties between the traditional depreciation method or the so-called fair value method.

"When applying the fair value method, the consequences of changes in the valuation of investment properties can be significant, because a decreased value is recorded directly as "expense" in the financial statements and correspondingly, an increase as "income". In the investment property business, there are examples of companies whose result exceeds their turnover", says Mäki.

In the European Union, publicly listed companies prepare their financial statements in accordance with the IFRS standards (International Financial Reporting Standards). The guidelines regulate about the basic principles for preparing financial statements but also provide opportunities for selecting between various reporting methods.

Reporting requirements a compromise between the best and excessive information as well as the expenses incurred

According to Mäki, the easiest solution from the standpoint of stakeholders, such as investors and financers, would be a requirement to only use an external party for determining fair value in the preparation of financial statements and reporting all the relevant information in the notes.

The preparers of the IFRS standards must, however, take into account the amount of reporting costs and readers of annual reports possibly getting tired of excessive information. The key is to identify the most essential information for investors and to present it in a concise way.

The purpose of the balancing is, after all, to increase the ease of adopting IFRS and therefore increase its use globally.

Use of IFRS is the sum of a company's internal and external factors

It was also discovered in Mäki's dissertation that companies tend to select the traditional depreciation method in cases where the annual report does not have a significant impact with regard to communication with stakeholders.

In other words, a company's diversified ownership has a positive impact on selecting the fair value model in the valuation of real estate investments. The same phenomenon is to an extent visible in financial sector companies. On the other hand, companies in Scandinavia and Great Britain use fair value reporting more often compared with the rest of the European Union. The reason for this is likely to be legislation history before the adoption of the IFRS standards.

Development of the guidelines (here, IFRS 13) has, on the other hand improved the quality of financial statements, however, a simple, briefer reporting may be as effective from the standpoint of stakeholders.

"Using external parties for determining fair value seems to also have a positive impact on the amount of information asymmetry, i.e., on how equal a position investors at different levels are as regards the necessary underlying information. Therefore, the impact of external valuators as experts is similar to that of large audit firms (Big 4)", Mäki estimates.