Culture

University of Groningen Professor of Drug Design, Alexander Dömling, has devised a method to rapidly synthesize thousands of new molecules and evaluate their properties as potential drugs. In a paper published by Science Advances on 5 July, he shows that this method works well when applied to boronic acid chemistry, an important technique in synthetic organic chemistry. The study also produced an inhibitor of the phosphatase MptpB, a virulence factor of Mycobacterium tuberculosis, which had previously been considered an 'undruggable' target.

'We use a miniaturized technology to perform organic chemistry at the nanolitre scale for drug discovery', explains Dömling. 'This allows us to create large numbers of variants of drug candidates and screen them for the required properties in a high-throughput system.' He calls the system he presented earlier this year 'unprecedented' for organic chemistry: 'This field has not yet embraced the high-throughput methods that are common elsewhere.'

Building blocks

Dömling uses acoustic dispensing, a technique that was introduced in cell biology and biochemistry in the mid-2000s. Reagents are stored in small wells in the source plates. Ultrasound pulses are used to shoot a small, nanolitre droplet up from the wells into another well on an inverted plate above it, the so-called destination plate. The tiny droplet sticks to this new well. A computerized system positions the destination plate to collect four different reactants, each with a different chemical building block. These are then left to react with each other.

'This method allows us to quickly synthesize thousands of variant molecules by using a large number of slightly different building blocks', says Dömling. For a molecule made from four building blocks, with 1,000 versions for each, the number of different molecules you will get is 1012. 'Using ordinary organic chemistry methods, this would take an impossibly long time to synthesize and assess.'

One-pot approach

In Dömling's system, large numbers of variants are produced in nanolitre volumes in the wells. These wells are then sampled and analysed using mass spectrometry, to see whether the desired molecule has been produced. 'This is our quality control, and it also provides information on the reactivity of the building blocks.' Finally, the synthesized molecules are tested for a required property.

In two previously published papers, Dömling described this approach for the synthesis of isoquinoline and indole derivatives. Now, he demonstrates that the method also works for boronic acid chemistry, which has become a very important tool in organic chemistry. Boronic acids are used as intermediates in creating different carbon bonds and are also of interest as potential protein inhibitors.

In this new study, Dömling and his co-workers show that the boronic acid reactions work well. 'We use a one-pot approach with mild conditions. This has the added advantage that no protective groups are needed for the boronic acid, which makes the synthesis easier.' As project leaders Dr. Neochoritis and Dr. Shaabani explain, traditionally, boronic acid synthesis is sequential, synthetically demanding and time-consuming.

Tuberculosis

The study also shows that the nanomole reactions can be scaled up to millimol quantities, providing good yields. The screening of the end products in the destination plates lead to an interesting compound that acts as an inhibitor of the phosphatase MptpB, a virulence factor of Mycobacterium tuberculosis. 'Until now, this class of phosphatases has been regarded as undruggable due to its highly charged active site.'

In summary, the new experiments show that the one-pot reaction with boronic acid under mild conditions at nanomole scale has a high success rate and produces good yields. 'We believe our approach will widen the accessibility of the boronic acid chemical space markedly for applications in synthesis, chemical biology, and drug discovery', says Dömling. The outcomes also demonstrate that the high-throughput method works for different chemical reactions. 'Our long-term target is to develop this into an automated system where artificial intelligence is used to refine and optimize drug candidates.'

Predators are not only a deadly threat to many animals, they also affect potential prey negatively simply by being nearby. Researchers at Lund University in Sweden have studied what happens to the prey's immune system when they are forced to expend a large amount of their energy on avoiding being eaten.

To protect themselves, certain animals switch colour, while others change their body shape. An example of the latter is the fish species crucian carp, which changes shape when coexisting with their natural predator, the northern pike. Instead of its normal oblong body shape, the crucian carp increases in height and resembles a discus. This makes it considerably more difficult for the pike to eat it, and increases the carp's chances of survival.

The researchers in Lund studied whether this type of body change for protection against predators affects the prey's immune system. The results are clear: animals at risk of being attacked by predators generally have an weaker immune system compared with animals that are not threatened.

The presence of predators can thus have hidden but potentially important effects on the prey's chances of survival.

"They are potentially more susceptible to viruses and bacteria, and have an increased risk of illness", says Jerker Vinterstare, doctoral student at the Department of Biology at Lund University.

The reason for the impairment of central parts of the immune system is unclear, but the researchers think that stress is likely to be a contributory factor. Previous research has shown that chronic stress can result in an impaired immune system, and the presence of predators nearby probably entails a high level of stress.

The research team used crucian carp as its model animal, but think that predators can have a similar effect on the immune system of other prey.

A surprising result was that the individuals that increased in height the most displayed a better immune system than individuals whose height did not increase as much, and therefore had a weaker defence against predatory fish.

According to the researchers, it would have been less surprising if the opposite effect had been observed, as changing body shape is expected to incur energetic costs. An individual that increases more in height should quite simply have less energy to devote to its immune system.

"It's surprising, but I think it may be linked to the personality of different individuals. We knew previously that bold crucian carp protect themselves more against pike attacks by increasing in height to a greater extent than their more cautious conspecifics", says Jerker Vinterstare, who continues:

"Having a bold personality is synonymous with having an exploratory nature. A bold crucian carp that moves over large areas is at greater risk of running into danger, both in the form of hungry predatory fish and microorganisms that cause disease. Such individuals have a greater need to invest in an effective defence", he concludes.

A hard tackle on the football-field, a crash on your bike or a fall from a ladder in your home can easily cause a concussion, which eventually can cost your job - especially if you are in your thirties, and have a higher education.

These are some of the findings in a large new register-based data research study from a team of researchers at the University of Copenhagen in Denmark led by PhD student in Public Health, Heidi Graff, and neuropsychologist Hana Malá Rytter from the Department of Psychology.

Each year 25,000 people in Denmark are diagnosed in hospitals with concussion (mild traumatic brain injury) that make up roughly 90% of all injuries causing trauma to the head. Although mortality is low, and surgical intervention rarely required, up to 15% of patients suffer from persistent symptoms and functional impairment following the injury, that may have severe personal costs and often make it hard to resume their normal jobs and lives.

The Danish study includes all groups of patients and is representative for the general population in Denmark in terms of age, geography, education, family background and marital status.

Using register data from 19,732 Danes between the ages of 18 and 60 that were all diagnosed with a concussion, researchers traced the patients' attachment to the labour market during five years and compared the data to an equally sized control group of people without concussion.

They found that people with concussion have a markedly higher risk of being out of a job five years after the trauma. Instead they are unemployed, receiving payments due to disability or early pension or working part-time supported by social benefits.

Especially two groups of patients were severely struck by long-term symptoms: Those in their thirties and those with a higher education.

Five years of labour market data

The researchers did not examine the patients physically or screen their medical records to assess the patients´ medical symptoms following the concussion. They merely looked at their labour market data six months and five years after the head trauma respectively. Accordingly, they were surprised to find out that people between the ages of 30-39 and those with a higher education are much more likely to have lost their connection to a normal job following a concussion.

While people with low education levels (that is having 9 years of primary education and no other education after that) have a 30% higher risk of leaving the normal labour market following a concussion than people without concussion. The same risk is over 215% for people with higher education (that is having 12 or more years of education, for instance studies at college or university level)

- It is surprising, that the effect of a concussion has such severe consequences for this group of people and their ability to maintain a normal job even five years after the trauma. Long-term symptoms like fatigue and difficulties in concentrating can of course afflict anyone regardless of their level of education. What stands out is that those with a higher education are in such higher risk of losing their job. It could be due to the fact, that they often hold jobs where they plan and prioritise their tasks and the workload by themselves, and that the mental surplus and overview required to do so are some of the skills that are often severely impaired in the aftermath of a concussion, explains Hana Malá Rytter, Associate Professor in Neuropsychology at the University of Copenhagen and Head of the Danish Concussion Center.

Not able to do the same

Even though it might sound like a great advantage to be able to plan your workday yourself whilst recovering from a head trauma, it is in fact often an advantage for these patients, if someone else takes charge and hands out simple, well defined job tasks to be completed one at a time. This may be one of the reasons, why researchers find that people with low education levels are better able to keep their job.

-People with higher education often hold positions, where they are required to multi-task, engage in teamwork and shift focus between different tasks while making decisions and taking responsibility. Skills that are often challenged, when long-term symptoms after concussion impair the ability to concentrate. Our data indicate that part of these patients must face that they simply are not able to do the same, as they used to before, says Hana Malá Rytter.

The study is the first register data-based study that analyses patients' labour market activity up to five years after a concussion, and it is the first study to reveal what specific groups of patients are affected the most in terms of their employment status in the aftermath of a concussion.

Worst for the 30-somethings

The researchers also identified another specific group of patients that were markedly more at risk of leaving the labour market following a concussion: People between the ages of 30-39. Data showed that their risk of having left a regular job five years after a concussion was twice as high, compared to people of the same age in the control group without concussion. According to Hana Malá Rytter, this may have to do with the life situation in which people in their thirties often find themselves.

- Men and women in their thirties have often completed their education a few years earlier and are just establishing themselves in their professional life and as a family too. In this phase of life, people often make high demands on themselves both in and outside their workplaces. Moreover, becoming parents is a challenging and stressful process for young families. Expectations regarding the capacity of the individual are often towering - both from employers, colleagues, family members and from the individuals themselves. So once they are struck by long-term consequences of a concussion that often reduce their mental surplus and their ability to focus. Their whole life situation suffers so much harder, than if this happened later in life. And this seems to make some of them give up on their job, explains Hana Malá Rytter.

For people in their fourties, the risk of losing a job following a concussion is raised approximately 30% compared to peers without concussion, while the researchers hardly saw any increase in people leaving the workforce following a concussion in the group of 50-59-year-olds.

- Senior professionals may have a more relaxed attitude to what they are supposed to accomplish in life in general and in their professional career in particular. From other studies we also know that it is easier to adjust to a long-lasting disease, if this happens later in life, says Hana Malá Rytter.

Better advice for patients

According to Hana Malá Rytter, patients should receive better and more precise advice from both doctors, nurses and other professionals in the health and social care system following a concussion. It is important that the patients' entire life situation is taken in to account.

Patients with concussion rarely receive actual treatment, as the brain primarily needs time and rest in order to heal. In general, patients are advised to merely go home and take it easy for a few weeks - and to pay attention to what level of activity they feel they are able to handle. And that can create a false expectation that they are soon back in business.

- It differs greatly how much activity people expect of themselves, and health professionals need to draw attention to the cognitive and mental limitations that often strike the young professionals and those with higher education in the wake of a concussion. They need to be told, that this may take many weeks or even months, before they can expect to be back at full speed in the way they were prior to the head trauma. If not, they may strain their mental capacities and that can delay the healing of the traumatized brain, explains Hana Malá Rytter and continues:

- Furthermore, they may experience defeat, when the exhaustion causes symptoms to worsen again and they have to give up. This can cause stress and we know from other studies that this will delay the healing process.

The researchers also identified two other groups that are at particular high risk of losing attachment to the labor market: Patients with chronic diseases (i.e. diabetes, heart- or liver disease or HIV) prior to the concussion, and patients that were of non-Danish origin. This is not surprising, as plenty of research points to the fact that chronic disease in itself has a very negative effect on a person's perceived life quality. In addition, being part of a minority group is linked to a series of problems that increase the risk of early retirement and receiving disability payment.

Cheetah experts in many zoos around the world are at a loss. Despite all their efforts, these cats often do not reproduce in the desired manner. Researchers from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), together with colleagues from the Allwetterzoo Münster, have now found a key to the issue: the age of the mothers at the first pregnancy is the decisive factor. In contrast to the wild, felines kept in zoos are often bred only years after they have reached sexual maturity. From the study results, the researchers derive recommendations for keeping cheetahs in zoological gardens. The study was published in the journal "Journal of Zoo and Aquarium Research".

It's not the stress. This was shown by the scientific team in a study of 12 female cheetahs from zoos in Denmark, Germany, Portugal, Austria and Switzerland, whose entire lives they followed. The concentration of their "stress" hormones - measured over several weeks as metabolites in the faeces - was as high in mothers as in females who had no offspring. Instead, the age of the mothers is the decisive factor. "We saw from the stud books that the reproduction failed when the females were six years or older at their first introduction to a male," says Bettina Wachter from Leibniz-IZW, head of the study.

There are mainly logistical reasons why zoological gardens are often late in "family planning". In order to keep the gene pool as diverse as possible, felines are usually not mated within a facility. "For this, males are sometimes transported between countries," says Carsten Ludwig of the Allwetterzoo Münster, first author of the study and doctoral student at Leibniz-IZW. "But it can take one to two years until the breeding permit of the European Endangered Species Programme (EPP) and all official documents for import and export have been obtained."

Cheetah females become sexually mature at approximately two years of age. They have a three-week cycle and are ready for conception for two to four days during oestrus. "We know that this cat species mates in the wild as soon as the females become sexually mature," says Bettina Wachter. Three months later, the cheetahs give birth to their young and suckle them for approximately four months. "Then their cycle sets in again. However, they usually only allow the males to mate again when the cubs are approximately one and a half years old. The zoo study also showed that females that had offspring for the first time at a young age still became pregnant at an advanced age. Late first mothers are the exception - similar to humans. "Early pregnancy gives the reproductive system a boost, which makes it easier to become pregnant again in advanced years," says Bettina Wachter.

"These results indicate that one can create the best conditions in the zoo for cheetahs: If the female only meets a male for the first time when she is six years old or older, it's usually too late," concludes Carsten Ludwig. Dissections of deceased captive cheetahs without offspring revealed that the oestrogen fluctuations caused by the cycle, which were uninterrupted for years, can damage the internal reproductive organs and lead to cysts, for example. "There are animal species that react very sensitive to such long-lasting fluctuations in oestrogen. Elephants and rhinoceros are among them. And also cheetahs," emphasizes Wachter, who published a study on this topic in cheetahs in 2011 together with Thomas Hildebrandt and Robert Hermes from the Leibniz-IZW.

What recommendations can be derived from these study results? "As soon as the females are sexually mature, there is an ideal timeframe of two and a half to three years to breed them. If zoos can organise this in terms of time and logistics, they should have higher breeding successes," explains Carsten Ludwig. A regular exchange programme of male cheetahs between the institutions could be helpful.

"We have also shown that reproductive suppression can occur when female cheetahs are kept together in a single enclosure: the dominant female might suppress the cycle of the others," says Ludwig. "How exactly this suppression takes place, which has already been observed by American colleagues, is not yet known, but presumably through hormonal mechanisms." Therefore, cheetah females - who are solitary anyways - should not be kept together with other adult females. Before a female is to be mated, she should also not be housed together for a while with male cheetahs. "It seems that otherwise the sexual stimulation is missing," says Bettina Wachter.

For a successful cheetah breeding, there are thus some aspects to consider. "Zoos with successful cheetah breeding apparently implemented one or more of these aspects into their cheetah husbandry management."

WASHINGTON, D.C., July 9, 2019 -- Microfluidics and learning-on-a-chip research -- involving the manipulation of small amounts of fluids to run miniaturized experiments in physics, chemistry, biology and medicine -- are a prolific research field. But, so far, there aren't many published examples of how to teach it in an easily understandable way to students or how to communicate the numerous significant advances within the field to public audiences in a relatable manner.

To address this, in the journal Biomicrofluidics, from AIP Publishing, a group of researchers presents a review of published literature about microfluidics education and provides methods and suggestions for anyone who wants to improve their own microfluidics teachings and outreach.

"Science education and outreach are both popular right now, and public outreach is also increasingly important, because taxes fund a significant amount of research," said Nicole Pamme, at the University of Hull. "Public awareness of scientific advances is important for good policymaking within democratic societies."

Microfluidics is a term that encompasses a broad range of tools used to manipulate extremely small volumes of fluids, ranging from attoliters (one quintillionth of a liter) to microliters (a microliter is one millionth of a liter; a can of Coke, for example, is 355,000 microliters in volume). This technology is useful, because it allows scientists to miniaturize experiments, which enables lower consumption of chemicals and reagents, smaller sample volumes, and smaller, more portable instrumentation.

"Many experiments can be carried out faster or more efficiently and with precise control of local conditions, which is impossible to achieve in large petri dishes or reaction vessels," said Darius Rackus, a co-author at ETH Zürich. "One of the goals of microfluidics is to mirror the history and advances of computer science by going from dedicated rooms and facilities for computing to miniaturized, hand-held computers that can be used anywhere for the chemical and life sciences."

The most common microfluidics format is microchannels, which are essentially small plumbing systems with a width or height of at least 1 to 10 of micrometers. At this length scale, the fluids have a low Reynolds number (the ratio of inertial to viscous forces), which means that they exhibit laminar flow (as opposed to turbulent flow).

"One implication of this is that fluids flowing together don't mix but rather continue in the direction of flow," Rackus said. "This is a useful phenomenon that many researchers capitalize on to precisely control the placement of fluids and particles within a microfluidic device."

In the group's review, they determined that most examples of including microfluidics with teaching or outreach are broadly split into two categories: teaching about microfluidics or teaching with microfluidics. Many examples of teaching about microfluidics focus on the physics and engineering of microfluidic systems.

"These could be demonstrations that explain concepts, such as flow behavior or design projects, where students create a microfluidic device to solve a particular problem," said Pamme. "In cases of teaching with microfluidics, we found examples where microfluidics was used more as a means to an end to study physical, chemical or biological phenomena."

The group hopes more student exposure to microfluidics will increase interest in the multidisciplinary field of microfluidics, and ultimately lead to more researchers in the field.

"We hope that our paper will equip educators to include microfluidics in their curricula -- both in playful and serious ways -- and to share ideas of how to engage citizens about medicine and clinical diagnostics developments, environmental analysis, chemical synthesis, which are all underpinned by concepts of engineering and physics," said co-author Ingmar Rieldel-Kruse, at Stanford University. "Given the limited reports within the literature, we'd like to encourage more sharing -- either formal or informal -- of ideas and activities for teaching microfluidics."

A deep learning-powered computational framework, 'DeepEC,' will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions.

A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner.

DeepEC takes a protein sequence as an input and accurately predicts EC numbers as an output. Enzymes are proteins that catalyze biochemical reactions and EC numbers consisting of four level numbers (i.e., a.b.c.d) indicate biochemical reactions. Thus, the identification of EC numbers is critical for accurately understanding enzyme functions and metabolism.

EC numbers are usually given to a protein sequence encoding an enzyme during a genome annotation procedure. Because of the importance of EC numbers, several EC number prediction tools have been developed, but they have room for further improvement with respect to computation time, precision, coverage, and the total size of the files needed for the EC number prediction.

DeepEC uses three convolutional neural networks (CNNs) as a major engine for the prediction of EC numbers, and also implements homology analysis for EC numbers if the three CNNs do not produce reliable EC numbers for a given protein sequence. DeepEC was developed by using a gold standard dataset covering 1,388,606 protein sequences and 4,669 EC numbers.

In particular, benchmarking studies of DeepEC and five other representative EC number prediction tools showed that DeepEC made the most precise and fastest predictions for EC numbers. DeepEC also required the smallest disk space for implementation, which makes it an ideal third-party software component.

Furthermore, DeepEC was the most sensitive in detecting enzymatic function loss as a result of mutations in domains/binding site residue of protein sequences; in this comparative analysis, all the domains or binding site residue were substituted with L-alanine residue in order to remove the protein function, which is known as the L-alanine scanning method.

This study was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 20, 2019, entitled "Deep learning enables high-quality and high-throughput prediction of enzyme commission numbers."

"DeepEC can be used as an independent tool and also as a third-party software component in combination with other computational platforms that examine metabolic reactions. DeepEC is freely available online," said Professor Kim.

Distinguished Professor Lee said, "With DeepEC, it has become possible to process ever-increasing volumes of protein sequence data more efficiently and more accurately."

Dolomite is widely in the metal industry as a fireproof material and in construction, such as for joint grouting in panel building. Of course, dolomite is also known as a collector of hydrocarbons.

"Carbonate platforms which formed on Earth from late Archaean to Neoproterozoic era have one distinctive feature," comments Miroslaw Slowakiewicz, co-author and Research Associate of Kazan University. "The ratio of dolomites in them is usually higher than in Mesozoic or Cenozoic samples. Our research confirms that Precambrian dolomites could form by direct depositing from sea water. This leads us to conclude that we are dealing with primary dolomite."

The scientists used various methods and geochemical proxies to study sedimentation in the Paleoproterozoic oceans. Preserved ooids and bacterial structures allow theorizing that dolomites might have been directly deposited from sea water or crystallized from the liquid inside the sediments. Thus, dolomite oceans are proved to be dominant in the Proterozoic.

The immune system is indispensable for defense against invading pathogens, but its aberrant activation may lead to autoimmune diseases. Regulatory T cells play a crucial role in preventing excess immune activation; mice without enough Treg function develop autoimmune disorders and are susceptible to immune diseases.

"Treg cells have been attracting much attention due to their unique suppressive function, but how Treg cells are generated in our bodies is not fully understood. In a mouse model for human ulcerative colitis, mice lacking JunB developed severer symptoms due to reduction of Treg cell number. JunB-deficient T cells exhibited an impairment of IL-2 production and IL-2 signaling. In addition, injection of a high dose of IL-2 into JunB-deficient mice mitigated colitis by expansion of Treg cells," explained the lead author of the paper, Takaharu Katagiri, M.D., who is a graduate student at Toho University to become a physician-scientist.

"We hope these findings will lead to the development of a novel strategy to treat inflammatory diseases by manipulating the function of JunB," said the senior authors of the study, Soh Yamazaki, Ph.D, Associate Professor and Hiroyasu Nakano, M.D., Ph.D. Professor of the Toho University School of Medicine. Their finding was published online on July 8th 2019 in the journal Mucosal Immunology.

WASHINGTON -- Researchers at the U.S. Naval Research Laboratory (NRL) developed a new technique that could enable future advancements in quantum technology.

The technique squeezes quantum dots, tiny particles made of thousands of atoms, to emit single photons (individual particles of light) with precisely the same color and with positions that can be less than a millionth of a meter apart.

"This breakthrough could accelerate the development of quantum information technologies and brain-inspired computing," said Allan Bracker, a chemist at NRL and one of the researchers on the project.

In order for quantum dots to "communicate" (interact), they have to emit light at the same wavelength. The size of a quantum dot determines this emission wavelength. However, just as no two snowflakes are alike, no two quantum dots have exactly the same size and shape -- at least when they're initially created.

This natural variability makes it impossible for researchers to create quantum dots that emit light at precisely the same wavelength [color], said NRL physicist Joel Grim, the lead researcher on the project.

"Instead of making quantum dots perfectly identical to begin with, we change their wavelength afterwards by shrink-wrapping them with laser-crystallized hafnium oxide," Grim said. "The shrink wrap squeezes the quantum dots, which shifts their wavelength in a very controllable way."

While other scientists have demonstrated "tuning" of quantum dot wavelengths in the past, this is the first time researchers have achieved it precisely in both wavelength and position.

"This means that we can do it not just for two or three, but for many quantum dots in an integrated circuit, which could be used for optical, rather than electrical computing," Bracker said.

The wide breadth of researcher expertise and science assets at NRL allowed the team to test various approaches to making this quantum dot breakthrough in a relatively short amount of time.

"NRL has in-house facilities for crystal growth, device fabrication, and quantum optical measurements," Grim said. "This means that we could immediately coordinate our efforts to focus on rapidly improving the material properties."

According to Grim and Bracker, this milestone in the manipulation of quantum dots could lay the groundwork for future strides in a number of areas.

"NRL's new method for tuning the wavelength of quantum dots could enable new technologies that use the strange properties of quantum physics for computing, communication and sensing," Bracker said. "It may also lead to 'neuromorphic' or brain-inspired computing based on a network of tiny lasers."

Applications in which space and power-efficiency are limiting factors may also benefit from this breakthrough approach, researchers said.

A new study from researchers at the University of North Carolina at Chapel Hill's Carolina Population Center found that the risk of dying between the ages of 1 and 24 is substantially higher for children whose parents have lower levels of education, lower levels of income, or for those who live in a single-parent family.

"This is an extremely important finding because it shows that the risk of losing a child has independent associations with a mother's and father's education, the amount of income parents earn, and both single mother and single father households," said David B. Braudt, a doctoral candidate in the UNC-Chapel Hill sociology department and pre-doctoral trainee at the Carolina Population Center, and lead author on the study. "And while the overall incidence of dying between the ages of 1 to 24 has decreased in the last 40 years, the fact that such large gaps continue to exist between the most advantaged and least advantaged families is tragic."

The study, published July 4 in the Maternal and Child Health Journal, used survey data on more than 350,000 children across the nation who were followed for as many as 16 years to determine whether they lived or died during the study period.

This research adds to our understanding of the associations between family factors and early-life death, but due to data limitations it could not evaluate why these associations exist. Further research is needed to understand the exact mechanism that link family resources and an increased risk of death before age 24.

Compared to children and youth living with mothers who earned college degrees, those living with mothers who attended but did not graduate from college, finished high school, or never graduated high school experience 28, 37, and 40 percent higher risk of early-life death over the follow-up period, respectively. Similarly, compared to children whose father obtained a bachelor's degree or more education, children living with fathers who attended but did not graduate from college and those that did not complete high school are at 23 and 41 percent higher risk of dying young, respectively.

Independent of education, compared to children who lived in high-income families at the time of the survey, those living in families close to or below the Census-defined poverty line, which were 23 and 19 percent of all children in the study respectively, experienced a 38 percent higher risk of dying during the course of the study.

Some of the largest increases in the risk of dying young are associated with being raised by only one parent. Children raised without a father present in the home experience 40 percent higher risk of dying between the ages of 1 to 24, while those without a mother present have a 48 percent higher risk.

Though previous research has uncovered differences in early-life mortality by looking at socioeconomic status measures in aggregate areas such as zip codes, little work has been done to examine these socioeconomic disparities at the individual level. This is the first study in over two decades that has examined the association between parental socioeconomic measures and early-life mortality.

"Understanding the associations between the resources of parents and families and the risk of their child dying before age 25 provides crucial information that can help policymakers and practitioners develop targeted interventions that may improve the overall mortality rate in the U.S. and, more importantly, save the lives of children," said Braudt.

Robert A. Hummer, the Howard W. Odum Distinguished Professor of Sociology and a Faculty Fellow at the Carolina Population Center, is a co-author of the study. Other collaborators on this study include Elizabeth Lawrence of the University of Nevada, Las Vegas; and Andrea Tilstra and Richard Rogers of the University of Colorado Boulder.

Poor quality social relationships that contribute to psychosocial stress may be associated with bone loss in postmenopausal women, suggests research published online in the Journal of Epidemiology & Community Health.

Psychosocial stress is a well-established risk factor for many chronic diseases and previous research has suggested that a number of psychosocial stressors, such as increased major life events, lower levels of optimism, life satisfaction and education, and may be associated with fractures.

Psychosocial stress refers to the emotional and physiological reactions experienced when an individual confronts a situation in which the demands go beyond their coping resources. Other examples of stressful situations include marital problems, death of a loved one, abuse, health problems, and financial crises.

The premise of this work was that psychosocial stress may increase fracture risk through degradation of bone mineral density (BMD). The authors suggest that psychosocial stress may alter BMD through changes in hormone levels, including cortisol, thyroid hormones, growth hormone and glucocorticoids.

However, few studies have examined the association between psychosocial stress and BMD so the researchers set out to do this.

They evaluated data on 11,020 postmenopausal women enrolled in the Women's Health Initiative (WHI) - a long term US health study launched in 1993 to assess strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

The women were part of a sub study looking at bone density, so data on bone density had been collected at enrolment and at a follow up visit six years later.

The women completed a questionnaire at enrolment which included information about psychosocial stress related to their social environment, specifically on social strain, social support and social functioning.

Social strain measures negative social interactions and relationships, social support measures positive relationships, and social functioning measures limitations in social activity.

The relationship between these three measures of psychosocial stress and percentage change in BMD over 6 years were examined.

High social stress was found to be associated with lower BMD over 6 years, after adjusting for potential influencing factors, including age, education, existing conditions, weight (BMI), smoking status, alcohol use, hormone therapy use, age at menopause, physical activity and history of fracture after age 55.

The authors say: "We identified specific psychosocial stressors pertaining to the social environment that were associated with bone loss."

Higher social strain was associated with greater BMD loss of the total hip, lumbar spine (lower back) and femoral neck (just below the ball of the ball-and-socket hip joint) over 6 years of follow-up. Social functioning stress was associated with greater bone loss at the total hip and femoral neck.

The social strain scores given by the women ranged from 4 to 20 with higher scores indicating more strain, and each point higher was associated with 0.082% greater loss of femoral neck BMD, 0.108% greater loss of total hip BMD and 0.069% greater loss of lumbar spine BMD.

This is an observational study, and as such, can't establish cause, and the authors point out that psychosocial stress levels may have been lower than average because participants in the Women's Health Initiative were healthy individuals living in the community. What's more, psychosocial stress levels were self-reported at the start of the study and may have changed over the follow-up period.

Nevertheless, they say: "We found that bone loss is among the physiological stress responses more strongly related to the quality of social relationships than quantity."

Taken together with prior evidence, "the results support community-building social stress interventions in postmenopausal women to potentially limit bone loss," they conclude.

Most dog and cat owners are not aware of pet blood donation schemes and animal blood banks, finds a survey of pet owners published in Vet Record.

However, the majority of owners in this study said they would be willing to allow their pets to donate blood, suggesting that just like human blood donation, raising awareness could help to increase donor numbers, say the researchers.

The need for small animal blood is growing in veterinary practice. The proportion of pets that donate blood is unknown, but is likely to be very small, and the demand for blood is probably greater than the supply available.

So researchers at the Royal Veterinary College set out to investigate pet owners' awareness of small animal blood donation and their attitude and motivations towards their pet being a blood donor.

Their findings are based on data from 158 dog and cat owners over the age of 18 who attended a veterinary clinic for an appointment over a 10-day period.

Owners were asked to fill out an anonymous questionnaire on their awareness of pet blood donation, whether they would be happy for their pet to donate blood if suitable, and motivations and concerns about their pet taking part in blood donation.

Of the 158 people who completed the questionnaire, 110 (70%) were not aware that pets could donate blood and 118 (75%) were unaware that pet blood banks existed.

One hundred and forty (89%) stated they would be willing to let their pets donate blood if they were suitable, while 18 (11%) stated that they would not.

There was no significant difference between the proportion of male and female owners willing to let their pet donate. However, cat owners were less likely to let their pets donate than dog owners, as were owners aged 71 years or more, and those who worked full time.

When responses were analysed into themes, 'beneficence' (the desire to help others or save lives) was the most common motivation noted by owners willing to let their pets donate blood.

This was followed by 'necessity of service' (a recognition of the need for blood products) and 'reciprocity' (a hope that if they took part this would result in blood products being available for their pet).

The theme of 'reservations and concerns' included animal welfare implications (predominantly from cat owners who thought their pet would experience anxiety) and the need for further information on the procedures involved.

The researchers point out that this was a relatively small survey limited to one clinic, so views may not represent the larger pet-owning public. However, they say this is "an important starting point in understanding the opinions and awareness of the pet-owning population regarding pet blood donation."

This study suggests that donor recruitment "could be markedly increased by improving the awareness of pet owners about pet blood donation," they conclude.

Commenting on the findings, British Veterinary Association Junior Vice President Daniella Dos Santos said: "This paper throws up interesting findings about awareness levels about pet blood donation and factors motivating owners to let their pets donate.

"While donor blood can be vital in saving lives of critically ill or injured pets, using animals for blood donation raises certain ethical questions, as highlighted in the study. Although the practice is legally permissible, it is very important that pet owners are aware of the risks involved and give informed consent for their pet to donate blood.

"Not all cats and dogs will be suitable for blood donation and the risk of complications is far higher in cats than in dogs. Any potential donors should meet strict criteria - including a physical examination by a vet- before they can donate blood."

Gorillas have more complex social structures than previously thought, from lifetime bonds forged between distant relations, to "social tiers" with striking parallels to traditional human societies, according to a new study.

The findings suggest that the origins of our own social systems stretch back to the common ancestor of humans and gorillas, rather than arising from the "social brain" of hominins after diverging from other primates, say researchers.

Published in the journal Proceedings of the Royal Society B, the study used over six years of data from two research sites in the Republic of Congo, where scientists documented the social exchanges of hundreds of western lowland gorillas.

"Studying the social lives of gorillas can be tricky," said lead author Dr Robin Morrison, a biological anthropologist from the University of Cambridge. "Gorillas spend most of their time in dense forest, and it can take years for them to habituate to humans."

"Where forests open up into swampy clearings, gorillas gather to feed on the aquatic vegetation. Research teams set up monitoring platforms by these clearings and record the lives of gorillas from dawn to dusk over many years."

Some data came from a project in the early 2000s*, but most of the study's observational data was collected from the Mbeli Bai clearing**, run by the Wildlife Conservation Society, where scientists have recorded gorilla life stories for over 20 years.

Gorillas live in small family units - a dominant male and several females with offspring - or as solitary male "bachelors". Morrison, who has worked at Mbeli, used statistical algorithms to reveal patterns of interaction between family groups and individuals in the datasets.

By analysing the frequency and length of "associations", she found hitherto undetermined social layers. Beyond immediate family, there was a tier of regular interaction - an average of 13 gorillas - that maps closely to "dispersed extended family" in traditional human societies e.g. aunts; grandparents; cousins.

Beyond that, a further tier of association involved an average of 39 gorillas, similar to an "aggregated group" that spends time together without necessarily being closely related. "An analogy to early human populations might be a tribe or small settlement, like a village," said Morrison.

Where dominant males ("silverbacks") were half-siblings they were more likely to be in the same "tribe". But over 80% of the close associations detected were between more distantly related - or even apparently unrelated - silverbacks.

"Females spend time in multiple groups throughout their lives, making it possible for males not closely related to grow up in the same natal group, similar to step-brothers," said Morrison. "The bonds that form may lead to these associations we see as adults."

"If we think of these associations in a human-centric way, the time spent in each other's company might be analogous to an old friendship," she said.

Occasionally, when lots of young males "disperse" from their families at the same time but are not yet ready to strike out on their own, they form "all-male bachelor groups" for a while. The researchers suggest this could be another bond-forming period.

The team uncovered hints of an even higher social tier of "periodic aggregations", similar to an annual gathering or festival based around "fruiting events", although these are too infrequent to detect with certainty from this study's data.

In fact, Morrison and colleagues argue that sporadic fruiting schedules of the gorillas' preferred foods may be one reason why they - and consequently maybe we - evolved this "hierarchical social modularity".

"Western gorillas often move many kilometres a day to feed from a diverse range of plants that rarely and unpredictably produce fruit," said Morrison. "This food is easier to find if they collaborate when foraging."

"Gorillas spend a lot of their early life in the family group, helping to train them for foraging. Other long-term social bonds and networks would further aid cooperation and collective memory for tracking down food that's hard to find."

A small number of mammal species have a similar social structure to humans. These species also rely on "idiosyncratic" food sources - whether forest elephants hunting irregular fruitings, or the mercurial fish schools sought by dolphins - and all have spatial memory centres in their brain to rival those of humans.

Before now, the species on this short list were evolutionarily distant from humans. Our closest relatives, chimpanzees, live in small territorial groups with fluctuating alliances that are highly aggressive - often violent - with neighbours.

As such, one theory for human society is that it required the evolution of a particularly large and sophisticated "social brain" unique to the hominin lineage.

However, Morrison and colleagues say the addition of gorillas to this list suggests the simplest explanation may be that our social complexity evolved much earlier, and is instead merely absent from the chimpanzee lineage.

"The scaling ratio between each social tier in gorillas matches those observed not just in early human societies, but also baboons, toothed whales and elephants," added Morrison, from Cambridge's Department of Archaeology.

"While primate societies vary a lot between species, we can now see an underlying structure in gorillas that was likely present before our species diverged, one that fits surprisingly well as a model for human social evolution."

"Our findings provide yet more evidence that these endangered animals are deeply intelligent and sophisticated, and that we humans are perhaps not quite as special as we might like to think."

A new study conducted by researchers in Leicester and Nottingham has shown the potential for a new blood test to not only diagnose human tuberculosis (TB) but also identify those at most risk of developing the disease, according to findings published in medical journal Clinical Infectious Diseases.

Despite recent reductions, England still has one of the highest rates of TB in Western Europe . While TB cases have been declining overall in the UK, the rate of TB in some of the most deprived areas remains more than seven times higher than in the least deprived . TB is a serious bacterial infection, which can be life threatening if not properly treated with antibiotics. Pulmonary TB of the lungs or throat is contagious although TB can affect any part of the body.

The research, carried out at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC) and the University of Nottingham's School of Biosciences, used new blood test called Actiphage to look for the presence of the bacteria that cause TB (Mycobacterium tuberculosis; MTB). The study involved 66 participants in four groups: those with active pulmonary TB, those with latent TB, a control group of patients referred for suspected TB but found not to have the disease, and a control group of healthy individuals.

The new blood test was used to test all of the patients twice, 12 months apart. Actiphage tested positive in 73 per cent of people that we subsequently diagnosed with TB - for an experimental study this was a much higher level than expected. None of the participants in the control groups tested positive with Actiphage and none of the patients with latent TB who tested negative with Actiphage went on to develop active TB.

Intriguingly, two of the three participants with latent TB infection who tested positive with Actiphage went on to develop the disease more than six months later, suggesting the test may have a predictive role in identifying people with the infection at risk of developing the disease.

Senior author of the paper, Dr Pranabashis Haldar, Clinical Senior Lecturer at the University of Leicester and Consultant in Respiratory Medicine at Leicester's Hospitals, said:

"TB is the leading cause of death from an infectious disease. It most commonly affects the lungs and from this site is transmitted to others by coughing and sneezing. As there is a lack of diagnostic tools for people unable to bring up sputum, diagnosis is delayed, increasing the likelihood that the disease is spread."

Around a quarter of the world's population carry the infection. In the vast majority, this is in the form of latent TB, which does not affect their health, but carries a risk of progressing to the active form of TB in around ten per cent of those infected. The mechanism for this is poorly understood.

Dr Haldar continued: "Our observations provide new insights into how human TB develops and support recent evidence of the existence of a transitional state of TB infection called incipient TB that does not produce symptoms but carries a high risk of progressing to active TB. There is potential for Actiphage to be developed, both as a mainstream blood test to diagnose TB and as a test used in screening programmes to help us identify and treat people with latent infection.

"As a blood test, it is particularly suitable for patients unable to produce sputum, including children, and may help support diagnosis in underserved groups that struggle to access freely available healthcare resources."

The new Actiphage test has been developed by the University of Nottingham in conjunction with the UK's Royal Veterinary College and commercialised by PBD Biotech for major diseases in livestock, primarily as a blood or milk test for bovine TB and Johne's disease. This is the first time the blood test has been trialled in humans.

Unlike many common bacterial infections, detection of the bacteria that cause TB is limited by the fact that Mycobacterium tuberculosis (MTB) is very slow growing, making traditional culture methods inefficient. More rapid molecular tests that detect MTB DNA are limited due to its tough cell wall that makes DNA extraction difficult. The new test uses a specific bacteriophage that infects live MTB and breaks open the cells to release DNA. The whole testing process can be completed in as little 6 hours.

Study co-author Dr Catherine Rees, Associate Professor in Microbiology at the University of Nottingham and Chief Scientific Officer at PBD Biotech, said:

"Actiphage is a novel blood test for mycobacteria that was developed to identify mycobacterial infections in farmed animals, helping farmers to control these difficult diseases.

"The data from our initial study in humans suggest that following infection, MTB is circulating in the blood at levels that were previously undetectable, and that the immune system may be failing to effectively contain the bacteria within the lungs.

"While we are cautious about generalising from a small sample size, we are optimistic that these initial findings indicate that Actiphage can be used as a tool to help us better understand the dynamics of the infection in humans.

"The new Actiphage blood test offers the potential to target those at risk of TB and allow treatment to start early. This is a very exciting development that invites further study."

The paper, 'A novel high-sensitivity bacteriophage-based assay identified low M. tuberculosis bacteraemia in immunocompetent patients with active and incipient TB', can be accessed at Clinical Infectious Diseases academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz548/5522421?

Goats can probably distinguish subtle emotional changes in the calls of other goats, according to a new study led by Queen Mary University of London.

The researchers measured behavioural and physiological changes in goats to determine if they can differentiate between calls linked to positive and negative emotions.

They found that when the emotion of a call changed, the likeliness of the goats to look towards the source of the sound also changed suggesting that they can distinguish the emotional content of calls of another goat.

The study, published in the journal Frontiers in Zoology, also shows that the goats' heart-rate variability - the variation in time between each heartbeat - was greater when positive calls were played compared to when negative calls were played.

Together, these results provide the first strong evidence that goats are not only able to distinguish call variants based on the emotion that they convey, but also that their own emotions are potentially affected.

The study was carried out in collaboration with the University of Roehampton, ETH Zurich and University of Turin.

Luigi Baciadonna, lead author of the study from Queen Mary University of London, said: "Despite its evolutionary importance, social communication of emotions in non-human animals is still not well understood. Our results suggest that non-human animals are not only attentive, but might also be sensitive to the emotional states of other individuals."

Many social animals live under environmental conditions where individuals are not always in visual contact with one another during the day or night, and therefore, could acquire an evolutionary advantage through the discrimination of the emotional content of the calls of others from their species.

Elodie Briefer, co-corresponding author of the study, who was based at ETH Zurich during the research and is now at the University of Copenhagen, said: "Expressing emotions using vocalisations and being able to detect and share the emotional state of another animal from the same species may facilitate coordination among the individuals in a group and strengthen social bonds and group cohesion."

Dr Alan McElligott who led the study at Queen Mary University of London and is now based at the University of Roehampton, added: "Perceiving the emotional state of another individual through its vocalisations and being affected by those vocalisations has important implications for how we care for domestic animals, and in particular livestock species."

In the study, the researchers recorded calls of goats which conveyed either positive or negative emotions. They then played one of these calls through a loudspeaker to another goat. They subsequently exposed that goat to a variant of the same call type associated with the opposite emotion. This was followed by a final call which was randomly selected.

The researchers also controlled variables often neglected in this field of research by assessing the emotional state of both the caller and the receiver. In addition, only contact calls were used so that the reaction of the receiver would be purely dependent on the encoded emotions, rather than the function of vocalisations.

Livio Favaro, another author of the study from University of Turin, said: "These findings can contribute to our understanding of the evolution of emotion perception in non-human animals."