Earth

Throughout the gastrointestinal tract there are specialized hormone-producing cells called enteroendocrine cells and, although they comprise only a small population of the total cells, they are one of the most important moderators of communication between the gut and the rest of the body. Studying these cells, however, has been difficult.

"Enteroendocrine cells are extremely challenging to study because we just don't have a lot of cells," said co-corresponding author Dr. Joseph M. Hyser, assistant professor of virology and microbiology and member of the Alkek Center for Metagenomics and Microbiome Research and the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. "They represent less than 1 percent of all the cells in the intestinal epithelium."

"To circumvent this limitation, researchers have used cancer-derived cell lines," said Dr. Alexandra L. Chang-Graham, co-first author of the paper, who was a student in the Medical Scientist Training Program (M.D./Ph.D.) in the Hyser lab while she was working on this project. "However, although the cancer-derived models recapitulate some of the abilities of the enteroendocrine cells, it is uncertain how much they really reproduce them."

'Raising the volume'

Looking to find a strategy that would enable them to study these cells, Hyser and Chang-Graham partnered up with other researchers at Baylor and Texas Children's Hospital to develop a strategy that would increase the number of cells.

They worked with a type of human intestinal epithelial cell culture system called enteroids that is set up in Dr. Mary Estes's lab at Baylor to grow and study norovirus. These multi-cellular cultures are made from adult intestinal stem cells from patient tissues, which naturally contain few enteroendocrine cells.

To expand the population of enteroendocrine cells, the researchers built on previous work showing that overexpressing transcription factor neurogenin-3 drives stem cells in the gut into becoming enteroendocrine cells.

"We genetically engineered human intestinal enteroids to express gene neurogenin-3 that is inducible by doxycycline," Chang-Graham said. "Doxycycline worked as a switch. When added to the cultures, it turned on the production of neurogenin-3, which in turn triggered the expression of many other genes and the development of endocrine enteroid cells. This strategy resulted in an expansion of the endocrine enteroid cell population from one to 40 percent, while the numbers of other cell types of the epithelium remained largely unchanged."

The expanded endocrine enteroid cell population responded to hormonal and viral stimuli as native endocrine cells in the intestine do; they secreted serotonin and other hormonal and neurotransmitter mediators, but now their levels were easily detectable.

Opening the doors to new research opportunities

"Now we can generate more endocrine cells that we can study under the microscope and measure their physiological responses," Chang-Graham said.

"We have developed a system that enables us to study how the gut communicates with the rest of the body via whispered messages," Hyser said. "Our system has 'raised the volume' of the chemical whispers facilitating our investigations of the effects of the gut on health and disease and the testing of interventions to improve human health. For example, we can use our system to study how viral pathogens such as rotavirus regulate the responses of these endocrine gut populations and test strategies to modulate those responses."

"The development of this model system also will allow researchers to begin investigating the complex interactions of the microbiome and diet with enteroendocrine cell function. Since several of the hormones and effector molecules released by enteroendocrine cells are already targets for the treatment of diseases such as type 2 diabetes and irritable bowel syndrome, we expect this model to aid in identifying novel therapeutics to treat these and other human diseases," said co-corresponding author Dr. Robert Britton, professor of molecular virology and microbiology and member of the Alkek Center for Metagenomics and Microbiome Research and the Dan L Duncan Comprehensive Cancer Center at Baylor.

"This project was a revealing learning experience," Chang-Graham said. "As the sole graduate student in the project, I had the opportunity to interact with postdocs and principal investigators directly and learn how collaborative science works and how to put together a paper like this."

A new study explains why lung cancer spreads faster in patients with certain genetic changes, and suggests that taking vitamin E, long thought of as preventive, may cause the same spread.

Led by researchers at NYU School of Medicine and Perlmutter Cancer Center, experiments in mice and human tissue revealed how mechanisms that protect cancer cells from the byproducts of their own aggressive growth are connected by the protein BACH1 to cancer cell migration and tissue invasion.

Published online on June 27 in the journal Cell, the study results reflect the nature of cancer cells, which arise in one place, but often spread (metastasize) and take root elsewhere. Lung cancer metastasis is the leading cause of cancer death in the United States.

About 40 percent of lung cancers are adenocarcinomas, which form from mucous-producing cells, and which have already spread beyond lung tissue in 22 percent of cases by the time they are diagnosed.

"Our results finally clarify the web of mechanisms surrounding the BACH 1 signal, and suggest that an already approved drug class may counter cancer spread in about 30 percent of lung adenocarcinoma patients," says senior study author Michele Pagano, MD, chair of the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine.

The Price of Fuel

The newly published work revolves around random changes, called mutations, which occur continually throughout the DNA code. While many are weeded out, some persist to either make no difference, cause disease, or help cells to better survive changing conditions as part of evolution.

Such changes are known to, for instance, help lung adenocarcinoma cells survive oxidative stress, a process where highly-reactive, cell-damaging molecules (oxidants) are made as a side effect of "burning" fuel to make energy. Cancer cells need extra fuel to support aggressive growth, produce more oxidants, and depend more on naturally occurring antioxidants to neutralize them.

Along these lines, past studies have shown that about 30 percent of non-small cell lung cancers (which include adenocarcinomas) thrive by acquiring mutations that ether increase levels of the protein NRF2 - known to turn on genes that increase antioxidant production - or that disable KEAP1, which targets NRF2 for destruction.

Complicating matters, oxidative stress is known to cause the release a chemical compound called heme. Best known for its role in hemoglobin - the oxygen-carrying red blood cell pigment - heme, in its free form, also amplifies oxidative stress. Cells protect themselves from the heme-driven wave of oxidants by making more of the enzyme heme oxygenase-1 (HO1), which neutralizes heme.

By engineering mice with lung adenocarcinoma cells that lacked Keap1 gene (and thereby increasing levels of NRF2), the study authors were able to show that too high NRF2 levels, and the related overproduction of antioxidants, encourages HO1 production. More HO1 activity means lower amounts of active heme.

This became even more important when the researchers discovered that heme partners with the protein FBOX22 to cause the breakdown of BACH1, explaining how increased NRF2 activity increases BACH1 levels.

Normally, say the authors, NRF2-driven, antioxidant-dependent increases in BACH1 levels are short-lived, activated only during brief blasts of oxidative stress, and possibly not rising to levels that trigger cell migration through BACH1. But the new data suggest that big enough increases override mechanisms that would otherwise limit BACH1 levels.

Furthermore, analyses of human tumor tissue revealed that HO1 and BACH1 are found in significantly higher levels in human lung cancer cells that have spread, and in lung cancers of advanced stage and grade. One theory holds that oxidative stress defenses and migration evolved to overlap so that cells faced with extreme stress locally could migrate in search of a better home.

Moving forward, the team seeks to explore whether HO1 inhibitors - already FDA approved the treatment of inherited disorders called porphyrias - could be tested in a clinical trial to slow or prevent lung cancer spread.

Importantly, a second paper publishing in the same edition of Cell, and led by Martin Bergo of the Department of Biosciences and Nutrition at Karolinska Institutet in Sweden, suggests that vitamin E taken as part of a dietary supplement also increases the chances of lung cancer spread through its effect on BACH1.

"For lung cancer patients, taking vitamin E may cause the same increases in cancer's ability to spread as the NRF2 and KEAP1 mutations that our team has linked to shorter survival," says study author Thales Papagiannakopoulos, PhD, assistant professor in the Department of Pathology at NYU School of Medicine. "We hope these findings help to dispel the myth that antioxidants like vitamin E help to prevent every type of cancer."

Much greater awareness, improved diagnosis and enhanced treatment are all required in order to reduce the burden on society of the severe behavioural condition conduct disorder, according to a new expert review led by the University of Bath (UK).

Conduct Disorder (CD), which is a common and highly impairing psychiatric disorder, usually emerges in childhood or adolescence and is characterized by severe antisocial and aggressive behaviour, including physical aggression, theft, property damage and violation of others' rights.

Its prevalence is estimated at around 3% in school-aged children and it is a leading cause of referral to child and adolescent mental health services. Yet paradoxically it is one of the least widely recognised or studied psychiatric disorders, and funding for research into CD lags far behind many other childhood disorders.

What the evidence shows is that CD is associated with an exceptionally high individual, societal and economic burden. The health and personal burden of CD is seven times greater than that of attention-deficit/hyperactivity disorder (ADHD), a much more widely known disorder. Whilst it is likely that children diagnosed with ADHD may also show signs of CD, very few will be diagnosed or receive treatment for the CD. CD is also associated with a greater health burden than autism.

This failure to tackle and treat CD in children and adolescents led the researchers to write the new Nature Reviews paper which calls for a greater awareness of the condition, and more funding to improve our understanding and ability to treat the disorder.

The review - a comprehensive overview of all aspects of CD, its diagnosis, clinical management and long-term impact - highlights the negative consequences and adult outcomes that can occur if it is not correctly diagnosed or treated.

In particular it reveals the high physical and mental health burden on patients and their families. In children, CD is associated with a higher risk of developing ADHD, oppositional defiant disorder and developmental language disorders; while for teenagers, comorbidities can include depression, anxiety, alcohol and substance abuse. Up to 50% of individuals with CD develop antisocial or borderline personality disorder in adulthood, along with more serious criminal behaviour and gang involvement.

It also finds that young people with CD are more likely to have children earlier, with more unplanned pregnancies, to become dependent on benefits, homeless or even to attempt suicide. Such behaviours have a huge detrimental effect on an individual and their families. In addition, those with CD display parenting problems which often mean that their own children are at higher risk for developing CD.

However, the researchers suggest that with the correct diagnosis, management for the condition is possible with the support of Child and Adolescent Mental Health Services (CAMHS). Their study highlights the value of both training parents in better supporting children with CD, and skills training for children and adolescents with the condition to help them improve their social and problem-solving skills and their ability to regulate emotions. Combined, the authors suggest, these approaches can have profound impacts on a patient's well-being and longer-term life chances.

Lead author Dr Graeme Fairchild from Bath's Department of Psychology hopes the study can act as a catalyst to improve the diagnosis and treatment of children with CD, and to highlight the societal impact of the condition which he suggests requires more government funding and charity involvement.

He explains: "Despite the fact that it is associated with a very high personal, familial, and societal burden, Conduct Disorder is under-recognised and frequently goes undiagnosed and untreated. The government have committed to increasing the funding for the treatment of child and adolescent mental health problems. They should take this opportunity to improve the diagnosis and treatment of children and teenagers with Conduct Disorder by investing in training in evidence-based treatments for this condition and ensuring that the families in question can access Child and Adolescent Mental Health Services. Research in other European countries and the United States has shown that this kind of investment will pay for itself over time."

Recent other publications from Dr Fairchild have identified brain wiring differences in children with conduct disorder as well as altered brain activity in antisocial girls.

A new computational modeling method uses snapshots of which types of microbes are found in a person's gut to predict how the microbial community will change over time. The tool, developed by Liat Shenhav, Leah Briscoe and Mike Thompson from the Halperin lab, University of California Los Angeles, and colleagues at the Mizrahi lab at Ben-Gurion University, Israel, is presented in PLOS Computational Biology.

The types and relative amounts of microbes found in a person's gut can reflect and affect the state of their health. Knowing how this microbial community composition changes over time could provide key insights into health and disease. However, it is unclear to what degree the microbial community composition of a person's gut at a given moment determines its future composition.

To address this question, Shenhav and colleagues developed Microbial community Temporal Variability Linear Mixed Model (MTV-LMM), a new method for modeling temporal changes in the microbial composition of the gut. When tested against real-world data, the new tool makes more accurate predictions than do other models previously developed for the same purpose.

The researchers then used MTV-LMM to surface new insights into microbiome dynamics. For instance, they demonstrated that, in both infants and adults, gut microbiome community composition can indeed be accurately predicted based on earlier observations of the community. They also applied the model to data from 39 infants and revealed a key shift around the age of 9 months in how the gut microbiome changes over time.

Looking forward, MTV-LMM could be applied to explore temporal dynamics of the gut microbiome in the context of disease, which could lead to improved diagnosis and treatment. It could also be useful for understanding other types of temporal microbiome processes, such as those occurring during digestion.

"Our approach provides multiple methodological advancements, but this is still just the tip of the iceberg," Shenhav says. In the future, she and her colleagues will work to further improve the prediction accuracy of the model and explore additional applications. "Modeling the temporal behavior of the microbiome is a fundamental scientific question, with potential applications in medicine and beyond."

A new artificial-intelligence tool captures strategies used by top players of an internet-based videogame to design new RNA molecules. Rohan Koodli and colleagues at the Eterna massive open laboratory present the tool, called EternaBrain, in PLOS Computational Biology. Eterna is directed by the lab of Prof. Rhiju Das at the Stanford University School of Medicine in California.

Found naturally in all living cells, RNA molecules perform essential biological functions. Recent years have seen strong interest in designing new RNA structures for use in cancer treatment, CRISPR gene editing, and more. However, every RNA structure consists of a long sequence of four building blocks, and determining the precise sequence needed to build a given structure can be computationally difficult.

In the new study, Koodli, Das, and colleagues carried out research through the Eterna internet-based videogame, a citizen-science initiative to tackle the computational challenges of RNA design. Eterna presents each player with a target RNA structure, and the player attempts to discover an RNA sequence that allows the finished molecule to fold into the desired shape. Some players outperform the best computer-automated methods in solving these challenges.

Using a dataset of 1.8 million design choices made by Eterna players, the researchers discovered an artificial neural network that captures some of the predilections and strategies of these experts. Called EternaBrain, this approach can predict the choices of the best players with significantly better accuracy than achieved by random guessing. An extended EternaBrain algorithm performs similarly or better than previously developed algorithms in solving Eterna challenges.

"Our findings suggest that it should be possible to create automatic algorithms for computer RNA design that emulate or outperform human RNA designers," Das says. "But we're not there yet; we still have a lot to learn from both gamers and AI researchers."

Next, the researchers will see if they can outperform top players by integrating EternaBrain with other computational approaches to RNA design. "We also hope to apply EternaBrain to more complicated problems being tackled by Eterna players, including the design of RNA computers and 3D machines, and the learning of design rules from actual wet-lab data," Das says.

EVANSTON, Ill. -- A new form of electron microscopy allows researchers to examine nanoscale tubular materials while they are "alive" and forming liquids -- a first in the field.

Developed by a multidisciplinary team at Northwestern University and the University of Tennessee, the new technique, called variable temperature liquid-phase transmission electron microscopy (VT-LPTEM), allows researchers to investigate these dynamic, sensitive materials with high resolution. With this information, researchers can better understand how nanomaterials grow, form and evolve.

"Until now, we could only look at 'dead,' static materials," said Northwestern's Nathan Gianneschi, who co-led the study. "This new technique allows us to examine dynamics directly -- something that could not be done before."

The paper was published online this week in the Journal of the American Chemical Society.

Gianneschi is the Jacob and Rosaline Cohn Professor of Chemistry in Northwestern's Weinberg College of Arts and Sciences, professor of materials science and engineering and biomedical engineering in the McCormick School of Engineering, and associate director of the International Institute for Nanotechnology. He co-led the study with David Jenkins, associate professor of chemistry at University of Tennessee, Knoxville.

After live-cell imaging became possible in the early 20th century, it revolutionized the field of biology. For the first time, scientists could watch living cells as they actively developed, migrated and performed vital functions. Before, researchers could only study dead, fixed cells. The technological leap provided critical insight into the nature and behavior of cells and tissues.

"We think LPTEM could do for nanoscience what live-cell light microscopy has done for biology," Gianneschi said.

LPTEM allows researchers to mix components and perform chemical reactions while watching them unfold beneath a transmission electron microscope.

In this work, Gianneschi, Jenkins and their teams studied metal-organic nanotubes (MONTs). A subclass of metal-organic frameworks, MONTs have high potential for use as nanowires in miniature electronic devices, nanoscale lasers, semiconductors and sensors for detecting cancer biomarkers and virus particles. MONTs, however, are little explored because the key to unlocking their potential lies in understanding how they are formed.

For the first time, the Northwestern and University of Tennessee team watched MONTs form with LPTEM and made the first measurements of finite bundles of MONTs on the nanometer scale.

The white matter structure in the brain reflects music sensitivity, according to a study by the research group on Cognition and Brain Plasticity of the Institute of Neurosciences of the University of Barcelona (UB) and the Bellvitge Biomedical Research Institute (UB-IDIBELL).

The study, published in Journal of Neuroscience, shows that white matter connectivity, the tissue through which the different areas in the central nervous system communicate, is essential to understand why we like or dislike music. Also, it shows that brain reward structures have to work with perception structures so that people enjoy music.

UB researcher Josep Marco-Pallarés leads a study in which Antoni Rodríguez-Fornells (UB-IDIBELL-ICREA), Noelia Martínez-Molina, from the University of Helsinki (Finland), and Ernest Mas-Herrero and Robert Zatorre, from the McGill University (Canada)- have taken part.

People who do not feel any pleasure with music

Listening to music is regarded as a satisfying activity, but previous studies by this group showed there is an individual unevenness: there are people who could not live without music, and others who do not enjoy it at all, a condition that has been called specific musical anhedonia. According to Josep Marco-Pallarés, "this phenomenon occurs to healthy people, without any pathology. Therefore, people with specific musical anhedonia enjoy other stimuli (such as food, or money rewards), but they are not sensitive to a musical reward".

The study of the specific musical anhedonia determined that individual differences regarding musical rewards were related to the functional connectivity (different patterns of neuronal activation in different brain regions) in the auditory cortex, specifically the supratemporal auditory cortex, and a key area in the rewarding process, the ventral striatum. Thus, musical sensitivity depended on the work of these two areas together.

The objective of the new study was to find out whether musical sensitivity was defined by how perception process areas and reward system areas were connected. The experiment was conducted with thirty-eight healthy volunteers using imaging-functional magnetic resonance, which enables the reconstruction of the structure of the brain white matter, the white matter bundles that connect different brain regions.

Participants' musical sensitivity was determined through the obtained score in a questionnaire created by the same research group, the Barcelona Music Reward Questionnaire (BMRQ), which defined their musical sensitivity. After that, during the magnetic resonance session, participants had to listen to extracts from classical music songs and provide pleasure values ranging from 1 to 4 in real time. To control their brain response in other types of rewards, participants had to play in a money bet activity in which they could win or lose real money. None of the participants showed a low score in the general reward scale, showing that individual differences in the reward process are limited to music and not other stimuli.

The results of the experiment show there is a relation between the white matter structures connecting the musical cortex and the activity in the reward system. According to Josep Marc-Pallarés, "the study shows musical sensitivity is related to white matter structures that connect, on the one hand, the supratemporal auditory cortex with the orbitofrontal cortex, and on the other, the orbitofrontal cortex with the ventral striatum".

Why there is only musical anhedonia?

These results highlight the need to widen the study focus to understand the functioning of the brain reward systems. "We cannot study only the reward network, we need to know how stimuli access the reward system. This could be the key to understand why there are specific anhedonia for a specific stimulus like music but not for other stimuli like games or food, which could have other applications for the understanding of several pathologies that are related to specific addictions or specific anhedonia for a certain stimulus", concludes Josep Marco-Pallarés.

Main sequence star, red giant, white dwarf - in the course of their lifespan covering millions or even billions of years, stars pass through different stages of stellar evolution - all differing greatly in appearance. Yet, stars do not reveal their ages easily, at least not at first glance. The duration of each phase differs too greatly from star to star. With deeper look, however, researchers can reconstruct the star's life story. Various methods now make it possible to reliably determine the age of a star.

But there are tricky cases: Four years ago, two groups of researchers led by the Leibniz Institute for Astrophysics and the Max Planck Institute for Astronomy discovered confusing red giant stars. The results of different age measurements diverged by a full four billion years. "The stars seemed to be old and young at the same time," Dr. Saskia Hekker from MPS and the University of Aarhus in Denmark, who was part of both discovery teams at the time and is now the first author of the new study, recalls. "This apparent paradox has intrigued me ever since", she adds. Together with her colleague Dr. Jennifer A. Johnson from Ohio State University, she has now solved the mystery of some of these stars. Both researchers are convinced that the strange stars only feign youthfulness.

The red giants' building material points to an ancient age of more than 10 billion years. The stars contain comparatively little iron, an element that in the course of galactic evolution was produced only slowly. Old stars therefore contain little iron compared to other substances such as magnesium, silicon, and calcium, while young stars contain more. In order to determine these elements' ratios scientists split the light from the respective star into its individual wavelengths. In this so-called spectrum, each element found within the star leaves a characteristic fingerprint. Another method of age determination looks at the oscillations of a star. With methods of asteroseismology it is possible to then deduce the star's mass.

Since particularly high temperatures prevail inside heavy stars, their fuel burns comparatively quickly. Heavy stars therefore have a much shorter life expectancy than low-mass ones. The red giants in question proved to be true heavyweights. The asteroseismic method therefore yields ages of less than 6 billion years.

The new investigation now solves this contradiction. The researchers were able to show that some of the stars look back on an extremely eventful past. "Some of the mysterious stars must have merged with others during or after their transformation into red giants," Dr. Saskia Hekker summarizes the results. "Their large mass is not an original property and therefore not suitable for age determination," she adds. "The stars are indeed old."

Key to these results were the amounts of carbon, nitrogen, and oxygen found at the surface of the stars. These elements allow for an indirect look into the stellar interior. When so-called main sequence stars, i.e. those in the same stage of development as the Sun, turn into red giants towards the end of their life, their inner workings change: carbon, nitrogen, and oxygen, which are formed in the nucleus, can be dredged up to the surface in huge plasma currents and can then be detected. Depending on how hot - and thus massive - the star in question is, the elements can be found in different ratios.

In some of their measurements, the researchers found values typical for low-mass stars. "Before they became red giants, these stars must have been comparatively light," concludes Dr. Jennifer Johnson from the Ohio State University. "Their current high mass can be explained by the fact that as red giants they have merged with other stars," she argues.

The explanation does not apply to all the stars studied. For some, the high mass determined years ago by means of asteroseismology coincides well with the presence of carbon, nitrogen, and oxygen at their surface. "These stars could have merged with others at an earlier stage of development before nuclear material was swirled to the surface," says Hekker. A final explanation is still pending.

The new study also offers a new approach to the question of how often stars collide and merge as a result. Red giants with such a turbulent past could now be tracked down via the detour of age determination.

Finnish researchers have compiled guidelines for international use for utilising music to support the development of spoken language. The guidelines are suitable for the parents of children with hearing impairments, early childhood education providers, teachers, speech therapists and other rehabilitators of children with hearing disabilities, as well as the hearing-impaired themselves.

When developing a music playschool designed for children using a cochlear implant, University Lecturer of Logopedics and speech therapist Ritva Torppa noticed that music, especially singing, benefits the brain of hearing-impaired children and their spoken language. The goal of the music playschool, speech-music group, is to improve the perception of speech and spoken language.

In an article published in the Hearing Research journal, Torppa and Professor of Education, brain researcher Minna Huotilainen assembled their own findings and those of other researchers which demonstrate that musical activities develop children's perception of prosody, such as rhythm and pitch variation, and spoken language.

"These skills make children's lives easier," Torppa explains. "Listening to speech, for example, in noisy surroundings becomes less stressful, while communicating with others and absorbing information in school and everyday life also becomes easier."

Employing music in education benefits all

Huotilainen emphasises the principle of equality. Employing music in early childhood education and basic education benefits all and safeguards the right to high-quality learning for children with language disorders, those learning Finnish as a second language and children with developmental disabilities.

"The use of musical methods in teaching intensifies learning and is in line with the results of the latest brain research," Huotilainen notes.

According to her, music also gives every child and young person a voice of their own, a channel for self-expression and the chance to be heard. Huotilainen is hoping for musical skills to be better acknowledged in the training of early childhood educators and basic education teachers.

"It would be great if the musical skills already acquired before university studies could be acknowledged at the entrance examination stage," she suggests.

Basic guidelines for using music are included in the article published in Hearing Research. The guidelines are suitable for everyone regardless of the type of hearing disability.

The oceans are losing oxygen. Numerous studies based on direct measurements in recent years have shown this. Since water can dissolve less gas as temperatures rise, these results were not surprising. In addition to global warming, factors such as eutrophication of the coastal seas also contribute to the ongoing deoxygenation. Will the oceans become completely oxygen-depleted at some point in the future if global warming continues? Such anoxic phases have actually occurred several times in the Earth's history, combined with major mass extinction events. They were also accompanied by high carbon dioxide concentrations in the atmosphere and high global temperatures.

Today, scientists of the GEOMAR Helmholtz Centre for Ocean Research Kiel published model simulations in the international journal Nature Communications on the development of the oxygen content of the oceans up to the year 8000. In their scenario, they assume that a large part of the fossil resources will be burnt, that emissions will continue to rise until the end of the century and then decrease to zero by the year 2300. In the model, the planet heats up by a further 6 degrees, and temperatures remain at this high level until the end of the simulation.

The surprising result concerns the oxygen content of the ocean: After a further decrease over several hundred years, the oxygen inventory of the ocean rises again and even reaches a higher level than before industrialization in just under 4000 years. At first glance, it seems paradoxical that despite the expected further expansion of the already existing oxygen minimum zones in the world's oceans, the model yields an unexpected increase in oxygen as global temperatures rise.

It is known from investigations of the Kiel Collaborative Research Centre 754 that such oxygen-poor areas are death zones for larger organisms such as fish or cephalopods. However, certain bacteria that breathe nitrate instead of oxygen thrive there very well. "They draw their energy from a chemical process we call denitrification. It is an important component of the nitrogen cycle, that results in less oxygen being consumed during respiration of organic material than that produced during photosynthesis" explains Professor Oschlies.

In the new model simulation, the researchers have for the first time consistently coupled the oxygen cycle with the nitrogen cycle in such long-term global simulations. The researchers found that due to the extended oxygen minimum zones, more and more organic material is no longer respired with oxygen but with nitrate through denitrification. After several thousand years, the associated oxygen savings exceed the oxygen loss of the oceans caused by warming. "However, we cannot speak of a recovery, since the extensive oxygen minimum zones near the sea surface would stay. A large part of the additional oxygen goes into the deep ocean," says Angela Landolfi, co-author of the study.

However, there is a new problem: the anoxic phases that have occurred in Earth's history during warm climatic conditions are even more difficult to explain with the new findings. There are obviously factors and feedback processes in the complex interactions of biological, physical and chemical processes in the ocean that are not yet fully understood. "This is why the study is also important for the present. It points to knowledge gaps, such as the interaction of denitrification and nitrogen fixation, that can also be relevant for ongoing ocean changes," says Andreas Oschlies, summarising the significance of the study.

Imagine if your printer had an “unprint” button that used pulses of light to remove toner, curbing environmental impacts compared with conventional paper recycling.

A Rutgers-led team has created a new way to unprint paper that, unlike laser-based methods, can work with the standard, coated paper used in home and office printers. The new method uses pulses of light from a xenon lamp, and can erase black, blue, red and green toners without damaging the paper, according to a study in the Journal of Cleaner Production.

"Our method makes it possible to unprint and then reprint on the same paper at least five times, which is typically as many times paper can be reused with conventional recycling. By eliminating the steps involved in conventional recycling, our unprinting method could reduce energy costs, pollution and greenhouse gas emissions," said study coauthor Rajiv Malhotra, an assistant professor in the Department of Mechanical and Aerospace Engineering in the School of Engineering at Rutgers University-New Brunswick.

Conventional recycling of coated paper is a major contributor to climate change emissions, chemical pollution and energy use, according to the study. Extending the life of paper while avoiding these recycling steps would yield significant environmental benefits.

The engineers' next steps are to further refine the method by testing additional toner colors on a wider range of paper types. Unprinting can be done with simple equipment and a wipe with a very small amount of benign alcohol, and the engineers are working to integrate unprinting with typical office and home printers.

Vienna, 26 June 2019: Intracytoplasmic sperm injection (ICSI), the world's favoured means of fertilisation in assisted reproduction, offers no benefit over conventional in vitro fertilisation in fertility treatments without a male factor indication, according to results of a large multicentre study.

ICSI was developed throughout the 1990s as a specific treatment for infertility of male cause.(1) Until then, men with poor quality or insufficient sperm cells in their ejaculate had little chance of fathering their own children. But now, in the hands of the ICSI embryologist and beneath powerful microscopes, just one sperm cell might be enough for conception.

Since its development, however, ICSI has been adopted as a fertilisation technique for all types of sub-fertility, and not just of male cause. Globally, ICSI cycles now outnumber conventional IVF cycles by around two to one, and in some countries - in the Middle East, for example - assisted reproduction cycles are entirely ICSI.(2)

Now, a large population-based study of almost 5000 patients in Belgium and Spain being treated with ICSI or standard IVF has found no benefit from ICSI in terms of fresh and cumulative live birth rate in non-male factor cases. The results of the study are presented today at the Annual Meeting of ESHRE by Dr Panagiotis Drakapoulos from UZ Brussels, the pioneering Belgian centre at which ICSI was developed more than 25 years ago. The study was a collaboration between the Brussels centre and 14 IVI clinics in Spain.

This important study did not just compare outcomes in ICSI and IVF in non-male factor cases but also in different kinds of patient response to ovarian stimulation. 'There has been a worldwide increase in the use of ICSI for all causes of infertility,' explained Dr Drakapoulos. 'The rationale for this seems to be that ICSI is associated with a higher likelihood of fertilisation and an increased number of embryos - but this is controversial. For example, ICSI is the first choice for fertilisation in many centres in patients who respond mildly to ovarian stimulation and have few eggs retrieved. But there is currently no evidence on the comparative effectiveness of ICSI and IVF according to the number of oocytes retrieved in patients with non-male factor infertility. This study for the first time aimed to provide that evidence using a large sample size.'

Results firstly showed no overall difference in outcome (fertilisation rate, live birth rate and cumulative live birth rate) in the ICSI or standard IVF cycles. Moreover, these comparable findings were also evident in four different patient response categories ranging from poor responders (1-3 eggs retrieved) to high responders (more than 15 eggs retrieved). 'It's clear from these results,' said Dr Drakapoulos, 'that the number of oocytes retrieved has no value in the selection of the insemination procedure in cases of non-male infertility', confirming that ICSI will not improve outcome in cycles in which only a few eggs are retrieved.

Both global and European registry figures show that around 70% of all reported cycles were ICSI in 2015, with a slightly higher pregnancy rate found in the IVF cycles (27.7% IVF and 25.5% ICSI). However, these usage rates varied from region to region, with high rates of ICSI evident in many countries of Eastern and Mediterranean Europe. More modest use, with a roughly 50-50 split between IVF and ICSI, was found in some Nordic countries, UK and France. In its latest review of treatment trends in the UK, the HFEA reported that ICSI use 'continued to increase until 2014, but it is now in decline, possibly due to clinical opinion that it's not needed in all contexts of IVF'.

This is indeed the clinical message from this study, which, according to Dr Drakapoulos, found 'no justification for the use of ICSI in non-male factor infertility'. He added that the number of eggs retrieved 'should not play any role in selecting the insemination method'.

'The rationale for the high use of ICSI in non-male factor cases,' he said, 'is based on a wrong assumption that ICSI may be associated with a higher likelihood of fertilisation and an increased number of available embryos. However, our results show that this assumption is misplaced.'

Dr Drakapoulos described these results as sufficiently robust 'to convince clinicians not to propose ICSI in all infertile patients', adding that the extra financial cost of ICSI over IVF should also be considered in the absence of male factor infertility.

DALLAS, June 26, 2019 -- Binge watching TV may be a greater risk factor for heart disease and premature death among African Americans than sitting at a desk job, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.

According to the author, these latest findings suggest that television-watching may be the most harmful sedentary behavior. Moreover, the findings revealed that the amount of television watched made a difference. African Americans who watched more than four hours of television every day faced a 50% greater risk of heart disease and premature death compared with those who watched less than two hours.

Exercise also made a difference. Researchers discovered that the link between television watching and heart disease was not found in African Americans who engaged in moderate to vigorous physical activity 150 minutes per week, the current national recommendations for physical activity, suggesting that exercise could offset the risks from TV viewing.

African Americans experience disproportionately high rates of heart disease and stroke and face a greater risk for cardiovascular disease at all ages of life, as well as a lower life expectancy by about five years compared with whites. Growing evidence has also demonstrated that sedentary behavior is linked to several heart disease and stroke risk factors including high blood pressure, obesity and type 2 diabetes.

Researchers wanted to compare the effects of occupational sitting such as desk jobs with television-watching, and to see if physical activity had any effect on sitting. They reviewed data on 3,592 adults enrolled in the Jackson Heart Study, a large on-going community-based study following African Americans living in Jackson, Mississippi. Television habits, hours spent sitting at a desk and exercise were self-reported. During a follow-up period of more than eight years, there were 129 cardiovascular disease events, such as heart attacks, and 205 deaths.

Study participants who reported spending more time sitting at work were more likely to be female, younger, have a higher body mass index (BMI), higher family income, eat a healthier diet, engage in more moderate physical activity, and less likely to be smokers or drink a lot of alcohol.

Those who watched several hours of television, on the other hand, were more likely to report lower incomes and education status, less physical activity, have a higher BMI, be a current smoker, eat unhealthy, drink heavier amounts of alcohol, and have high blood pressure. Nearly one-third reported watching less than two hours of television daily; another 36% reported watching two to four hours; and 31% said they watched more than four hours of television.

"TV watching may be associated with heart health risks more than sitting at work do with the time of day people watch TV and the other lifestyle habits surrounding TV watching," said lead study author Jeanette Garcia, Ph.D., a professor of kinesiology and physical therapy at the University of Central Florida in Orlando, Florida.

"TV watching occurs at the end of the day where individuals may consume their biggest meal, and people may be completely sedentary with hours of uninterrupted sitting until they go to bed," said Garcia. "Eating a large meal and then sitting hour hours at a time could be a very harmful combination." Snacking may also be an issue and, unfortunately, individuals typically are not snacking on fresh fruits and vegetables, but rather potato chips or other sweet or salty, high-calorie foods. At a desk job, workers are often getting up, going to a copy machine, talking with a colleague, going to a meeting or to the break room. It's not hours of uninterrupted sitting."

Researchers said TV watching is likely harmful for any racial or ethnic group, and they plan to further study why TV watching may be a more harmful sedentary behavior. Meanwhile, said Garcia, doctors may want to ask their patients about their TV watching habits, and those who like to watch TV can still take preventive measures, such as taking a brisk walk or jog, to offset the health risks from too much TV time.

Bystanders will intervene in nine-out-of-ten public fights to help victims of aggression and violence say researchers, in the largest ever study of real-life conflicts captured by CCTV.

The findings overturn the impression of the "walk on by society" where victims are ignored by bystanders.

Instead, the international research team of social scientists found that at least one bystander - but typically several - did something to help. And with increasing numbers of bystanders there is a greater likelihood that at least someone will intervene to help.

A team of researchers from the University of Copenhagen, the Netherlands Institute for the Study of Crime and Law Enforcement and Lancaster University examined unique video recordings of 219 arguments and assaults in inner cities of Amsterdam (Netherlands), Lancaster (UK) and Cape Town (South-Africa).

Lead author Dr Richard Philpot of Lancaster University and University of Copenhagen, said: "According to conventional wisdom, non-involvement is the default response of bystanders during public emergencies. Challenging this view, the current cross-national study of video data shows that intervention is the norm in actual aggressive conflicts. The fact that bystanders are much more active than we think is a positive and reassuring story for potential victims of violence and the public as a whole. We need to develop crime prevention efforts which build on the willingness of bystanders to intervene."

Security cameras in the urban environments of Lancaster (UK), Amsterdam (Netherlands) and Cape Town (South-Africa) captured aggressive public conflicts. In 91% of situations, bystanders watching the incident intervened in several ways including:

physically gesturing for an aggressor to calm down

physically blocking an aggressor or pulling an aggressor away

consoling the victim

The research further showed that a victim was more likely to receive help when a larger number of bystanders was present.

Dr Philpot said: "The most important question for the potential victim of a public assault is 'will I receive help if needed?' While having more people around may reduce an individual's likelihood of helping (i.e., the bystander effect), it also provides a larger pool from which help-givers may be sourced."

The study also found NO difference in the rates of intervention between the three cities, even though inner city Cape Town is generally perceived to be less safe. Researchers suggest that it is not the level of perceived danger that sets the overall rate of helping, rather it is any signal that the situation is conflictual and requires intervention.

The consistent helping rate found across different national and urban contexts supports earlier research "suggesting that third-party conflict resolution is a human universal, with a plausible evolutionary basis".

In contrast to the idea that we live in a 'walk-on by society' - where people never get involved - the high levels of intervention found in this study across different national and urban contexts suggests that intervention is the norm in real-life inner-city public conflicts.

Over 1,700 children die from child abuse each year in the U.S., and far more sustain injuries that result in hospitalization. These deaths and severe injuries are preventable, but effective strategies require a deeper understanding of the caregivers causing the harm and the circumstances surrounding the child's injuries.

The odds of child physical abuse vs. accidental injury increased substantially when the caregiver at the time of injury was male, according to a new study published in The Journal of Pediatrics. When the male was the boyfriend of the mother or another caregiver, the odds of abuse were very high. Injuries were also much more severe when the child was with a male caregiver. In contrast, abuse as the cause of injury was substantially less likely when a female caregiver was present, with the exception of a female babysitter. Caregiver arrangements that were different than usual also were associated with increased risk of abuse. These findings may help improve early recognition of abuse when a young child is injured and may also inform future abuse prevention strategies.

"Given that we found strong associations between certain caregiver features and the likelihood of abuse, it is vitally important for clinicians evaluating the child to ask about who was present at the time of injury," says study author Mary Clyde Pierce, MD, from Ann & Robert H. Lurie Children's Hospital of Chicago, who is the Principal Investigator on the Bruising Clinical Decision Rule study that supplied the data. Dr. Pierce is a Professor of Emergency Medicine at Northwestern University Feinberg School of Medicine. "Through a better understanding of caregiver features, screening for child abuse can be refined, evidence-informed clinical decisions can be made, prevention efforts can be focused on populations at greatest risk, and policies can be tailored accordingly."

The study examined data on 1,615 children younger than 4 years of age who presented to a pediatric emergency department with an injury. Twenty-four percent of these children were determined to be physically abused. The majority of severe injuries were classified as abuse (77 percent), and nearly all cases of severe injury in which fathers and boyfriends were present involved abuse.

"Child abuse prevention efforts frequently target mothers, but our study confirms previous research that the presence of male caregivers poses a greater risk of abuse, so the focus must shift for prevention strategies to be successful," says Dr. Pierce. "Future prevention strategies also should educate parents that leaving their young children in the care of people unfamiliar with the challenges of caregiving, even for brief periods of time, can be dangerous."