Sleep Is Irreplaceable for the Recovery of the Brain (Neuroscience)

Active recovery processes take place in the brain during sleep that cannot be replaced by rest.

Sleep is ubiquitous in animals and humans and vital for healthy functioning. Thus, sleep after training improves performance on various tasks in comparison to equal periods of active wakefulness. However, it has been unclear so far whether this is due to an active refinement of neural connections or merely due to the absence of novel input during sleep. Now researchers at the Medical Center – University of Freiburg have succeeded in showing that sleep is more than rest for improving performance. The findings, which were published in the journal SLEEP on January 6, 2021, provide important information for planning periods of intensive learning or training.

“Sleep is irreplaceable for the recovery of the brain. It cannot be replaced by periods of rest for improved performance. The state of the brain during sleep is unique,” says Prof. Dr. Christoph Nissen, who headed the study as research group leader at the Department of Psychiatry and Psychotherapy at the Medical Center – University of Freiburg and is now working at the University of Bern, Switzerland. In earlier studies, Nissen and his team provided evidence for the notion that sleep has a dual function for the brain: Unused connections are weakened and relevant connections are strengthened.

In the current study, the researchers conducted a visual learning experiment with 66 participants. First, all participants were trained distinguishing certain patterns. Afterwards, one group was awake watching videos or playing table tennis. The second group slept for one hour and the third group stayed awake, but was in a darkened room without external stimuli and under controlled sleep laboratory conditions.

However, it has been unclear so far whether this is due to an active refinement of neural connections or merely due to the absence of novel input during sleep. Image is in the public domain

Not only did the group that slept perform significantly better than the group that was awake and active, but the sleep group also performed significantly better than the group that was awake, but deprived from any external stimuli. The improvement in performance was linked to typical deep-sleep activity of the brain, which has an important function for the connectivity of nerve cells.

“This shows that it is sleep itself that makes the difference,” says co-study leader Prof. Dr. Dieter Riemann, head of the sleep laboratory at the Department of Psychiatry and Psychotherapy at the Medical Center – University of Freiburg. In control experiments, the Freiburg researchers ensured that fatigue and other general factors had no influence on the results.

The study shows that sleep cannot be replaced by rest during phases of intensive performance demands at work or in everyday life.

Reference: Christoph Nissen, Hannah Piosczyk, Johannes Holz, Jonathan G Maier, Lukas Frase, Annette Sterr, Dieter Riemann, Bernd Feige, Sleep is more than rest for plasticity in the human cortex, Sleep, 2021, zsaa216,

Provided by University of Freiburg

Faulty Metabolism of Parkinson’s Medication in the Brain Linked to Severe Side Effects (Neuroscience)

Until now, the reason why the drug levodopa (L-Dopa), which reduces the motor symptoms of Parkinson’s disease, declines in efficacy after a few years’ use has been unknown. A side effect that then often occur is involuntary movements. A Swedish–French collaboration, led from Uppsala University, has now been able to connect the problems with defective metabolism of L-Dopa in the brain. The study is published in Science Advances.

“The findings may lead to new strategies for treating advanced Parkinson’s,” says Professor Per Andrén of the Department of Pharmaceutical Biosciences at Uppsala University. He and Dr Erwan Bézard of the University of Bordeaux, France, headed the study jointly.

Parkinson’s disease (PD) is caused by the slow death of nerve cells that produce the key neurotransmitter dopamine. This results in the typical symptoms, such as rigidity and tremor. Treatment with L-Dopa, a precursor to dopamine, initially works very well as a rule; but after a few years, the effect of each dose becomes progressively more short-lived. Adverse side effects, such as rapid alternation between rigidity and uncontrolled movements that become increasingly severe over time, are very common. Finally, the benefits of L-Dopa treatment are jeopardised and the symptoms can become debilitating. Which neurochemical mechanisms cause these side effects is unknown. The involuntary movements are collectively known as “L-Dopa-induced dyskinesia”.

Using a new method, “matrix-assisted laser desorption/ionisation mass spectrometry imaging” (MALDI-MSI), the researchers were able to map numerous neurotransmitters and other biomolecules directly in non-human primate brain tissue, which had not been possible before. The samples came from a French biobank.

Thus, they were able to compare in detail, and identify the differences between, the brains of two groups of parkinsonian animals. One group was suffering from motor complications caused by long-term L-Dopa treatment. In the second group were individuals who had PD symptoms to the same degree, and were receiving identical L-Dopa treatment, but in whom the medication had not caused the motor side effects.

In the group with motor disorders, abnormally elevated levels of both L-Dopa and 3-O-methyldopa were detected. The latter, a metabolite, is a product formed when L-Dopa is converted to dopamine. This was seen in all the brain regions examined, except – to the researchers’ surprise – the particular part of the brain known as the striatum, which is thought to be involved in L-Dopa-induced movement disorders.

This suggests that brain mechanisms other than those that were previously recognised may underlie the motor disorders. Instead of originating in the striatum, these problems are most likely triggered by a direct effect of L-Dopa or dopamine, or a combination of the two, in some other part of the brain.

“Although there seems to be a direct connection between L-Dopa and motor complications, the mechanism that brings about the involuntary movements is still unclear and subject to further research. On the other hand, the new results show a direct role for L-Dopa in this motor disorder – independently from dopamine. And this indicates that L-Dopa may also act on its own in the brain,” Andrén says.

Reference: Elva Fridjonsdottir et al., Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA–induced dyskinesia, Science Advances, 2020. DOI: 10.1126/sciadv.abe5948

Provided by Uppsala University

Ancient DNA Analysis Reveals Asian Migration and Plague (Archeology)

Northeastern Asia has a complex history of migrations and plague outbursts. That is the essence of an international archaeogenetic study published in Science Advances and lead from the Department of Archaeology and Classical Studies at Stockholm University. Genomic data from archaeological remains from 40 individuals excavated in northeastern Asia were explored in the study.

The Yenisei River basin, which includes Lake Baikal. Graphic by Kmusser, Wikipedia Commons.

“It is striking that we find everything here, continuity as well as recurrent migrations and also disease-related bacteria,” says Anders Götherström, professor at the Center for Palaeogenetics at Stockholm University and one of the Principal investigators of the study.

The scientists discovered that there were demographic events in the past common for the whole Lake Baikal region. For example, around 8300 years ago there was a migratory event discernible both east and west of Lake Baikal. But there were also events specific for each of the two areas. While the areas west of Lake Baikal provides evidence for recurrent migrations and intense mobility, the areas east of Lake Baikal preserved a long-term continuity for thousands of years, apparently with limited mobility from other areas.

“It is intriguing that our data reveals complex and contrasting patterns of demographic change in one of the least populated regions on earth; including notable gene flow and at the same time a genetic continuity without major demographic changes in the two areas around Lake Baikal,” says lead-author Gulsah Merve Kilinc, former postdoctoral researcher at the Department of Archaeology and Classical Studies at Stockholm University and currently Lecturer at Department of Bioinformatics at Hacettepe University in Ankara.

The study also provides some new clues to the history of the Paleo-Inuit groups, the people who inhabited northern Greenland and Canada. While it has been suspected that the so called Belkachi-complex, a cultural group in the Baikal area, played a part in the early history of Paleo-Inuits, it has not been possible to evaluate this in detail. The analyses of remains of an individual associated with the Belkachi cultural-complex, dated to more than 6000 years before present now show that there is an association to a previously published Paleo Inuit (Saqqaq) individual (dated c.4000 yrs BP) on Greenland.

“This is the first genetic evidence of a link between a Neolithic period human group in Yakutia and the later Palaeo-Inuit groups, and this will inspire to new of research on the demographic development,” says Jan Storå, Professor at Osteoarchaeological Research Laboratory at the Department of Archaeology and Classical Studies at Stockholm University.

Finally, the study provides new data on the most eastern occurrences of the bacteria Yersinia pestis, the plague. One individual from the Lena basin, dated to c. 3800 years ago, and buried with individuals that proved to be close kin genetically, carried DNA from Yersinia pestis. Also, an individual dated to c. 4400 years ago from the area west of Lake Baikal hosted Yersinia pestis. Interestingly, the population west of Lake Baikal seems to have decreased in size around 4400 years ago, judging from the genomic data.

“Despite a need for more data, our discovery of the decrease in effective population size that coincided with the appearance of Yersinia pestis points to a possible presence of a prehistoric plague — possibly a pandemic. However, this is just as an educated guess which needs to wait for confirmation,” says Emrah K?rdök, former postdoctoral researcher at the Department of Archaeology and Classical Studies at Stockholm University and currently Lecturer at Mersin University in Turkey.

Reference: Gülşah Merve Kılınç, Natalija Kashuba, Dilek Koptekin, Nora Bergfeldt, Handan Melike Dönertaş, Ricardo Rodríguez-Varela, Dmitrij Shergin, Grigorij Ivanov, Dmitrii Kichigin, Kjunnej Pestereva, Denis Volkov, Pavel Mandryka, Artur Kharinskii, Alexey Tishkin, Evgenij Ineshin, Evgeniy Kovychev, Aleksandr Stepanov, Love Dalén, Torsten Günther, Emrah Kırdök, Mattias Jakobsson, Mehmet Somel, Maja Krzewińska, Jan Storå, Anders Götherström. Human population dynamics and Yersinia pestis in ancient northeast Asia. Science Advances, 2021; 7 (2): eabc4587 DOI: 10.1126/sciadv.abc4587

Provided by Stockholm University

Per­ceiv­ing Pros­thesis as Lighter Thanks to Neur­o­feed­back (Biology)

Trans­mit­ting sens­ory sig­nals from pros­theses to the nervous sys­tem helps leg am­putees to per­ceive pros­thesis as part of their body. While am­putees gen­er­ally per­ceive their pros­theses as heavy, this feed­back helps them to per­ceive the pros­theses as sig­ni­fic­antly lighter, ETH re­search­ers have shown.

Signals from tact­ile sensors un­der the sole of the pros­thetic foot and from angle sensors in the elec­tronic pros­thetic knee joint are passed on to the nervous sys­tem. (Visu­al­isa­tions: ETH Zurich)

Leg am­putees are of­ten not sat­is­fied with their pros­thesis, even though the soph­ist­ic­ated pros­theses are be­com­ing avail­able. One im­port­ant reason for this is that they per­ceive the weight of the pros­thesis as too high, des­pite the fact that pros­thetic legs are usu­ally less than half the weight of a nat­ural limb. Re­search­ers led by Stan­isa Raspop­ovic, a pro­fessor at the De­part­ment of Health Sci­ences and Tech­no­logy, have now been able to show that con­nect­ing the pros­theses to the nervous sys­tem helps am­putees to per­ceive the pros­thesis weight as lower, which is be­ne­fi­cial for their ac­cept­ance.

To­gether with an in­ter­na­tional con­sor­tium, Raspop­ovic has de­veloped in re­cent years pros­theses that provide feed­back to the wearer’s nervous sys­tem. This is done via elec­trodes im­planted in the thigh, which are con­nec­ted to the leg nerves present there. In­form­a­tion from tact­ile sensors un­der the sole of the pros­thetic foot and from angle sensors in the elec­tronic pros­thetic knee joint are con­ver­ted into pulses of cur­rent and passed in to the nerves.

“To trick an above-​knee am­putee’s brain into the be­lief that the pros­thetic leg was sim­ilar to his own leg, we ar­ti­fi­cially re­stored the lost sens­ory feed­back,” says ETH pro­fessor Raspop­ovic. In a study pub­lished last year, he and his team showed that wear­ers of such neur­o­feed­back pros­theses can move more safely and with less ef­fort.

Be­ne­fi­cial in­volve­ment

In a fur­ther study, the sci­ent­ists were now able to show that neur­o­feed­back also re­duces the per­ceived weight of the pros­thesis. They pub­lished the res­ults in the journal Cur­rent Bio­logy.

In or­der to de­term­ine how heavy a trans­femoral am­putee per­ceives their pros­thetic leg to be, they had a vol­un­tary study par­ti­cipant com­plete gait ex­er­cises with either neur­o­feed­back switched on or off. They weighed down the healthy foot with ad­di­tional weights and asked the study par­ti­cipant to rate how heavy he felt the two legs were in re­la­tion to each other. Neur­o­feed­back was found to re­duce the per­ceived weight of the pros­thesis by 23 per­cent, or al­most 500 grams.

The sci­ent­ists also con­firmed a be­ne­fi­cial in­volve­ment of the brain by a motor-​cognitive task, dur­ing which the vo­lun­teer had to spell back­wards five-​letter words while walk­ing. The sens­ory feed­back not only al­lowed him to have a faster gait but also to have a higher spelling ac­cur­acy.

“Neur­o­feed­back not only en­ables faster and safer walk­ing and pos­it­ively in­flu­ences weight per­cep­tion,” says Raspop­ovic. “Our res­ults also sug­gest that, quite fun­da­ment­ally, it can take the ex­per­i­ence of pa­tients with an ar­ti­fi­cial device closer to that with a nat­ural limb.”

Ref­er­ence: Preatoni G, Valle G, Pet­rini FM, Raspop­ovic S: Light­en­ing the per­ceived pros­thesis weight with neural em­bod­i­ment pro­moted by sens­ory feed­back. Cur­rent Bio­logy, 7 Janu­ary 2021, doi: 10.1016/j.cub.2020.11.069

Provided by ETH Zurich

Making Babies – Existential Dreams (Biology)

Since the first test-tube baby was born in 1978, reproductive medicine has made great strides. Although many couples with fertility problems have benefitted, the ability to have a child is still not guaranteed.

She loves to stand “in the midst of life at its most colorful”. There’s no doubt about it: in practicing her profession, Brigitte Leeners comes face to face with all of life’s major themes – children, family and birth, as well as the despair, and especially the hope, felt by couples for whom conceiving a child has so far proved impossible. Leeners is director of the UniversityHospital Zurich’s Fertility Center and professor of medicine at UZH. In her offices at Frauenklinikstrasse 10, she and her team welcome couples from all over Switzerland, and from all different cultures. What they all have in common is the —as yet unfulfilled — desire to have a baby of their own. “What we’re dealing with at the center are existential dreams,” says Brigitte Leeners. In trying to make these dreams come true, the couples have often been through a lot together. Not being able to conceive a child can lead to tremendous stress. Why isn’t it working? And who is to blame? Questions such as these can be highly testing for a relationship. For many couples, the decision to seek help with reproductive medicine is often their last hope in making the dream of having a child of their own come true.

“We have many ways of helping couples become parents today, but whether it actually works always remains to be seen. The beginning of life will forever be a miracle.”, said Bruno Imthurn, doctor.

There are many medical reasons for the inability to conceive, including missing or damaged fallopian tubes, hormone-induced failures in egg cell maturation, too few sperm, or too few motile sperm. Involuntary childlessness was officially recognized as a disease by the World Health Organization (WHO) in 1967. Today we know that it is just as often the man as the woman who is responsible for the couple’s childlessness. This was not always the case. “In the past, it was believed that women were usually to blame for fertility problems,” says Brigitte Leeners’ predecessor Bruno Imthurn. “They could then be sent away for a water cure to become fertile. And it often worked; the women became pregnant. However, the reason was not the cure itself, but a romantic tryst with a “cure companion”. “Heterologous insemination is what we call it in medicine,” says Bruno Imthurn.

Perfectly normal test-tube baby

Imthurn has had a pivotal impact on the development of reproductive medicine in Switzerland over the past decades. Under his leadership, several thousand babies have been born at the USZ Fertility Center. In summer, he was made professor emeritus.

Prof. Bruno Imthurn © University of Zurich

A momentous year for the development of reproductive medicine was 1978, when British researchers celebrated their first in vitro fertilization success. This led to the birth of Louise Brown, the first test-tube baby. Across the world, the event was hailed as a scientific breakthrough and was to profoundly change the possibilities of reproductive medicine. Up till then, doctors had mostly prescribed hormone therapies to boost fertility – with rather modest success. In vitro fertilization, on the other hand, opened up completely new perspectives for using modern techniques to conceive babies, and to grant couples with fertility problems the chance to have children, too.

As with many scientific and technical innovations, critical voices were raised at Louise Brown’s birth. “A step towards homunculus” was the title of the German news magazine Der Spiegel, and the then Archbishop of Canterbury even claimed it to be the work of the devil in an article he published in the papal newspaper Osservatore Romano. Reproductive medicine continues to be a red rag to the Catholic church. Louise Brown, on the other hand, has been able to lead a quite normal life over the last 40 years – once the media hype at her birth had died down. She is mother of two children and has an office job in Bristol, England. In the meantime, thousands of children have been conceived in test tubes. In vitro fertilization is nothing out of the ordinary: In Switzerland, around 2,000 children are born this way every year.

Hoping for a miracle

In vitro fertilization procedures have steadily improved over the last four decades, in part thanks to research conducted by Brigitte Leeners and Bruno Imthurn. “We are able to carry out each step of the artificial insemination process with ever greater precision,” says Imthurn. As a result, the chance of a successful pregnancy and the birth of a child – Imthurn calls this the “take-the-baby-home rate” – has risen from an initial 10 percent to 70 percent today. In other words, a good two-thirds of all couples undergoing treatment at the USZ leave in threes – or in fours. This is because the chance of a twin birth continues to be slightly higher with in vitro fertilization. However, multiple births are no longer as common as in the early days of the procedure. Here too, research and medicine have made considerable progress.

However, there is still no guarantee of couples being able to have a child. “We have many ways of helping couples become parents today,” says Bruno Imthurn. “But whether it actually works always remains to be seen. The creation of a child is and forever will be a miracle”. This is the miracle that the couples sitting in Brigitte Leeners’ office for their initial consultation are hoping for. The strength of the USZ Fertility Center is the personalized nature of the discussion, says Leeners. “Ultimately, it’s all about personal dreams and goals. That’s why we aim to find the right path for each individual couple.”

Prof. Brigitte Leeners © University of Zurich

At the beginning of a treatment, the first thing to be examined is why the couple has not been able to conceive. The reasons are usually biological and are only rarely related to excessive stress or psychological problems. However, medical clarification is only one aspect; social and psychological issues are another. “We take a holistic approach,” says Leeners, who is also trained in psychotherapy. In the consultation, she also has to verify that the couple is capable of taking on the role of parents and that the relationship is stable. “If the treatment works, parents will be responsible for taking care of the child at least until the age of 18 and must be present in the child’s life,” says Leeners.

Parents at 60?

Such responsibility is difficult for some couples – due to social and health reasons, such as alcohol or drug addiction, for example, or if the relationship is abusive. If in doubt, the reproductive medicine specialists assess the risk factors and collaborate with other specialists to find solutions. Leeners remembers an incident where a woman came to the clinic three times in a row, each time with a new partner – a far cry from the stable conditions needed for starting a family. Health problems can also seriously question the viability of having children: a serious illness such as multiple sclerosis, for example, or if the woman suffers from heart problems in combination with other diseases. Since pregnancy already puts a strain on the body, this condition could become life-threatening if the woman were to carry a baby. The decision for a pregnancy is therefore taken with the utmost care. Where the constellation of factors is critical, an analysis is made by a whole team of doctors, nurses, embryologists, psychologists and ethicists together. Ultimately, they are the ones who decide whether fertility treatment is appropriate. “There are cases where we have to turn a couple down,” says Leeners, “but they are rare.” Everything focuses on the welfare of the future child. This also applies when older couples want to use reproductive technology to have children at a later stage in life. Becoming parents at 60 carries high risks, the doctor says, and is also extremely questionable from the children’s perspective. Here, she says, constructive decisions must be made as to what is appropriate.

Men may feel guilty

Once the decision for treatment has been made, couples often face a long journey until they can hold their baby in their arms. In vitro fertilization is more complex for the woman than for the man. This can make men feel guilty – especially if they are the cause of the fertility problems. After hormone treatment, which aims to promote the growth and maturation of several eggs, a small operation is performed to extract the eggs, a procedure that takes around 15 minutes. A fine hollow needle is used to aspirate them from the ovaries together with the follicular fluid.

In the laboratory, the eggs are then fertilized with previously separated motile sperm and cultivated in an incubator for up to five days. Then one or, more rarely, two embryos are transferred to the uterus — the moment when the couple start to build their hopes. “The chance that a pregnancy will occur in a cycle is 35 to 40 percent,” Brigitte Leeners says. If it doesn’t work, the process is repeated. Since the eggs can be frozen, the woman is under less physical stress in the following cycles than when the eggs were initially retrieved. If, after the third attempt, there is still no success, the parties then decide whether or not to proceed – or to discontinue the treatment.

In vitro fertilization leads to a rollercoaster of emotions ranging from hope, uncertainty, despair and disappointment to sometimes also guilt. It can put severe strain on a relationship. “In order to survive the ordeal, it is important that the couple sees artificial insemination as a joint project,” says couple and family psychologist Guy Bodenmann. “They must be equally convinced of the path they are taking, and they must take it together. This will increase their chances of success.” This commitment from both sides can help ease the stress. And may ultimately lead to the happiness, joy and euphoria of finally giving birth to their long-awaited baby. Thanks to the potential of reproductive medicine, the chance of this happening now has never been greater.

Bidding the dream farewell

However, for about one-third of the couples treated, there is no resulting pregnancy and they must finally bid farewell to their long-cherished dream. “This is often no easy step,” says Bruno Imthurn. For Guy Bodenmann, it takes a certain humility, even if people are less willing to hear this today. Because the feasibility of a pregnancy exists, expectations are high – but, in the end, a child is still a gift of nature, says the psychologist. Partnerships cannot be planned, and the dream of parenthood cannot always be fulfilled, despite all the medical resources available. “It’s easier to come to terms with the situation when the two partners give each other mutual support,” says the psychologist.


Reproductive medicine glossary

Social freezing and egg donation

1) In vitro fertilization (IVF)

In classic in vitro fertilization, the eggs and sperm are placed in a test tube together. Fertilization takes place spontaneously to enable the natural selection of motile and fast sperm.

2) Intracytoplasmic sperm injection (ICSI)

Intracytoplasmic sperm injection (ICSI) is a variant of in vitro fertilization. It is used when IVF does not work or is not possible. In ICSI, a single sperm is injected into the egg.

3) Preimplantation genetic diagnosis (PGD)

Preimplantation genetic diagnosis (PGD) is the process of examining artificially created embryos for genetic changes before they are transferred to the uterus. PGD is used to detect hereditary diseases. However, it can also be used to identify other hereditary factors.

4) Polar body diagnostics (PBD)

In polar body diagnostics (PBD), it is not the embryo that is examined but the retrieved egg. It serves as an alternative to PGD, which (in Switzerland) is only permitted under certain conditions.

5) Social freezing

Social freezing is the freezing of egg and sperm cells. The objective is to preserve a woman’s fertility, which decreases sharply after the age of 35, and to enable a possible pregnancy at a later date. For this purpose, the cells should be retrieved as early as possible, because young eggs and sperm are healthier and stronger.

6) Egg donation

Egg donation is the process by which eggs are retrieved from the donor. These are then fertilized in vitro or by intracytoplasmic sperm injection and transferred to the recipient. Egg donation is not permitted in Switzerland today.

Provided by University of Zurich

Transition Metal ‘Cocktail’ Helps Make Brand New Superconductors (Material Science)

Concept of high entropy alloys provides a discovery platform for new superconductors.

Researchers from Tokyo Metropolitan University mixed and designed a new, high entropy alloy (HEA) superconductor, using extensive data on simple superconducting substances with a specific crystal structure. HEAs are known to preserve superconducting characteristics up to extremely high pressures. The new superconductor, Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2, has a superconducting transition at 8K, a relatively high temperature for an HEA. The team’s approach may be applied to discovering new superconducting materials with specific desirable properties.

Schematic of the CuAl2-type crystal structure of the newly created superconducting Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2 compound, with an HEA-type Tr site. © Tokyo Metropolitan University

It’s been over a hundred years since the discovery of superconductivity, where certain materials were found to suddenly show minimal resistance to electrical currents below a transition temperature. As we explore ways to eliminate power waste, a way to dramatically reduce losses in power transmission is a fascinating prospect. But the widespread use of superconductivity is held back by the demands of existing superconductors, particularly the low temperatures required. Scientists need a way to discover new superconducting materials without brute-force trial and error, and tune key properties.

A team led by Associate Professor Yoshikazu Mizuguchi at Tokyo Metropolitan University have been pioneering a “discovery platform” that has already led to the design of many new superconducting substances. Their method is based on high entropy alloys (HEAs), where certain sites in simple crystal structures can be occupied by five or more elements. After being applied to heat resistant materials and medical devices, certain HEAs were found to have superconducting properties with some exceptional characteristics, particularly a retention of zero resistivity under extreme pressures. The team surveys material databases and cutting-edge research and finds a range of superconducting materials with a common crystal structure but different elements on specific sites. They then mix and engineer a structure that contains many of those elements; throughout the crystal, those “HEA sites” are occupied by one of the elements mixed (see Figure 1). They have already succeeded in creating high entropy variants of layered bismuth-sulfide superconductors and telluride compounds with a sodium chloride crystal structure.

(a) Temperature dependence of resistivity of the new CuAl2-type Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2 in magnetic fields of different strengths. (b) Temperature dependence of electronic specific heat Cel/T. © Tokyo Metropolitan University

In their latest work, they focused on the copper aluminide (CuAl2) structure. Compounds combining a transition metal element (Tr) and zirconium (Zr) into TrZr2 with this structure are known to be superconducting, where Tr could be Sc, Fe, Co, Ni, Cu, Ga, Rh, Pd, Ta, or Ir. The team combined a “cocktail” of these elements using arc melting to create a new HEA-type compound, Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2, which showed superconducting properties. They looked at both resistivity and electronic specific heat, the amount of energy used by the electrons in the material to raise the temperature, and identified a transition temperature of 8.0K. Not only is this relatively high for an HEA-type superconductor, they confirmed that the material had the hallmarks of “bulk” superconductivity.

The most exciting aspect of this is the vast range of other transition metals and ratios that can be tried and tuned to aim for higher transition temperatures and other desirable properties, all without changing the underlying crystal structure. The team hopes their success will lead to more discoveries of new HEA-type superconductors in the near future.

This work was supported by a JSPS KAKENHI Grant (Grant Number: 18KK0076) and a grant under the Advanced Research Program of the Human Resources Funds of Tokyo [Grant Number: H31-1].

Reference: Yoshikazu Mizuguchi, Md. Riad Kasem & Tatsuma D. Matsuda (2021) Superconductivity in CuAl2-type Co0.2Ni0.1Cu0.1Rh0.3Ir0.3Zr2 with a high-entropy-alloy transition metal site, Materials Research Letters, 9:3, 141-147, DOI: 10.1080/21663831.2020.1860147

Provided by Tokyo Metropolitan University

Child Marriage is Legal And Persists Across Canada (Psychology)

Over 3,600 marriage certificates were issued to children under the age of 18 between 2000 and 2018.

Canada is at the forefront of global efforts to end child marriage abroad. Yet this practice remains legal and persists across the country. In Canada, more than 3,600 marriage certificates were issued to children, usually girls, under the age of 18 between 2000 and 2018, according to a new study from researchers at McGill University. In recent years, an increasing number of child marriages have been common-law unions.

Child marriage, defined as formal or informal (common-law) marriage before the age of 18, is a globally-recognized indicator of gender inequality because the negative consequences for health and personal development disproportionately affect girls. While much research has focused on developing countries, in wealthier nations like Canada, child marriage practices are overlooked and understudied.

Using data from vital statistics agencies and recent censuses, the researchers found that child marriage remains in practice from coast to coast, with the highest estimates of formal marriage found in Alberta (0.03%) and Manitoba (0.04%), and the highest estimates of any type of child marriage (formal or common-law) in Saskatchewan (0.5%) and the territories (1.7%). The study, published in Population and Development Review, is the first to shed light on how common child marriages are in the country.

“Our results show that Canada has its own work to do to achieve its commitment to the United Nations Sustainable Development Goals, which call for an end to child marriage by the year 2030,” says co-author Alissa Koski, Assistant Professor in Department of Epidemiology, Biostatistics and Occupational Health at McGill University.

The researchers found that Canadian-born children are slightly more likely to marry than those born outside of the country. More than 85% of all marriage certificates granted to children were issued to girls, who typically wed much older spouses. This gendered patterning is consistent with child marriage practices observed across the globe, according to the researchers.

Figure: Trends in the number of children granted marriage certificates per 10,000 16-17-year-olds in five provinces between 2000 and 2018 © Alissa Koski and Shelley Clark

Common-law unions more prevalent

The study shows most child marriages in recent years have been common-law. In 2006, formal marriage accounted for more than half of all child unions. By 2016, formal marriage accounted for only 5 percent and common-law unions were twenty times as prevalent.

“While the number of marriage certificates issued to children across the country has declined, it’s possible that individuals are opting for more informal unions in response to growing social disapproval of child marriage,” say the authors. This makes it increasingly challenging to determine to what extent child marriage has actually decreased or whether concerns about social or legal consequences have led to changes in reporting behaviors.

Informal unions can be just as harmful as formal marriages, the researchers say. In fact, informal unions often provide less social, legal and economic protection. In Quebec, for example, individuals in common-law unions are not entitled to alimony or division of property if the union ends. This raises questions about how best to address the issue. Preventing common-law unions among children will require different and innovative approaches that address the deeper motivations for this practice.

“The persistence of this practice within Canada highlights some of the inherent challenges to fully eradicating child marriage and reveals an important inconsistency between Canada’s domestic laws and its global policies” says co-author Shelley Clark, James McGill Professor of Sociology at McGill University. The next steps will be to examine the mental health consequences of child marriage in Canada and to investigate motivations for the practice.

Reference: “Child Marriage in Canada” by Alissa Koski and Shelley Clark is published in Population and Development Review. DOI:

Provided by McGill University

About McGill University

Founded in Montreal, Quebec, in 1821, McGill University is Canada’s top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

Botulism Breakthrough? Taming Botulinum Toxin to Deliver Therapeutics (Medicine)

A modified botulinum toxin efficiently targets and enters nerve cells, delivering a miniature antibody that reversed paralysis in mice.

While rare, botulism can cause paralysis and is potentially fatal. It is caused by nerve-damaging toxins produced by Clostridium botulinum — the most potent toxins known. These toxins often lurk in contaminated food (home canning being a major culprit). Infants can also develop botulism from ingesting C. botulinum spores in honey, soil, or dust; the bacterium then colonizes their intestines and produces the toxin.

A new botulism treatment may reverse paralysis after it occurs. (Image: Adobe Stock)

Once paralysis develops, there is no way to reverse it, other than waiting for the toxins to wear off. People with serious cases may need to go on ventilators for weeks or months. But a new botulism treatment and delivery vehicle, described today in Science Translational Medicine, could change that.

“Currently, there are anti-toxins, but these only work before the toxins enter the motor neurons,” says Min Dong, PhD, a researcher in the Boston Children’s Hospital Department of Urology and corresponding author on the paper. “What we have developed is the first therapy that can eliminate toxins after they get inside neurons.”

If proven in humans, the approach would represent a breakthrough in treating botulism. In mice, the treatment successfully got inside neurons and reversed muscle paralysis within hours. It also enabled mice to withstand doses of botulinum toxin that would otherwise be lethal.

A botulism treatment, steered by a toxin

Dong and his colleagues needed to surmount two technical barriers that have so far thwarted effective botulism treatment. Intriguingly, their solution lay in botulinum toxin itself.

“One barrier to treatment has been getting across the cell membrane, which is difficult for protein drugs,” explains first author Shin-Ichiro Miyashita, PhD, a postdoctoral fellow in Dong’s lab. “The other is targeting specific cell types, and in this case specificity toward motor neurons and nerve terminals. We took advantage of the fact that botulinum neurotoxins naturally target motor neurons and can deliver a protein cargo across cell membranes.”

The toxin-based delivery platform consists of the modified botulinum toxin at upper left (protease domain in gold, translocation domain in blue, and receptor-binding domain in purple) and the nanobody (the pink tag). When this nanobody-toxin fusion protein binds to the receptor (cyan) on the neuron surface, the cell takes it in through the process of endocytosis, corralling the fusion protein inside a vesicle (light green circle). The toxin’s protease domain, carrying the nanobody, then crosses into the interior of the cell. (Image: Sicai Zhang/Dong Lab, Boston Children’s Hospital)

The treatment harnesses a botulinum toxin (detoxified through introduced mutations) as the delivery vehicle. The cargo — the active drug — is a mini-antibody derived from the antibodies of camels, developed by collaborator Charles Shoemaker, PhD, at Tufts University.  Two of these so-called nanobodies can be delivered in tandem into neurons, neutralizing botulinum toxins type A and B at one go, the team showed.

Taming the toxin

But there was one more problem to solve.

“This approach had been attempted, but it was difficult to completely get rid of toxicity,” says Dong, “until we identified botulinum neurotoxin X in 2017. Unlike other botulinum toxins, this new toxin shows no toxicity after we introduce mutations, and serves as a safe delivery tool.”

Botox reversal

Besides botulism, Dong thinks the new treatment could be useful as a “botox reversal” agent. Botox injections, using tiny quantities of the type A botulinum toxin, can safely treat wrinkles and many other medical conditions like neck spasms, excessive sweating, or overactive bladder. However, when the injection goes awry, botox can cause unwanted muscle paralysis as a side effect, and patients have to live with the paralysis for months.

“We can potentially inject our therapeutic protein and get rid of botox in neurons and paralysis within a few hours,” Dong says.

A general delivery platform for neuroactive drugs?

The toxin-guided approach may offer a platform for getting biologic drugs into neurons to treat other disorders, Dong believes. Currently, most biologic drugs act only on cell-surface targets and cannot get into the cell’s interior.

“We provide a protein-based drug delivery platform that achieves highly specific targeting of neurons and efficient penetration of cell membranes,” Dong says. “Combined with nanobodies, which can be developed fairly readily against any protein of interest, this platform can be used to develop therapeutics that modulate proteins and biological processes inside neurons. Its modular nature even allows us to target cell types other than neurons by switching the cell-targeting domain. This could present a general approach for precision drug delivery into cells.”

Jie Zhang and Sicai Zhang of Boston Children’s Hospital and Charles Shoemaker of Tufts University are co-authors. The National Institutes of Health and Intelligence Advanced Research Projects Activity (IARPA) supported the research.

Reference: Shin-Ichiro Miyashita, Jie Zhang, Sicai Zhang, Charles B. Shoemaker, Min Dong, “Delivery of single-domain antibodies into neurons using a chimeric toxin–based platform is therapeutic in mouse models of botulism”, Science Translational Medicine  06 Jan 2021: Vol. 13, Issue 575, eaaz4197 DOI: 10.1126/scitranslmed.aaz4197

Provided by Boston Children’s Hospital

Tiny Wireless Device Sheds Light on Combating Obesity (Medicine)

Texas A&M researchers have designed a device that stimulates the endings of the vagus nerve, which is responsible for the regulation of food Intake.

Gastric bypass surgery is sometimes the last resort for those who struggle with obesity or have serious health-related issues due to their weight. Since this procedure involves making a small stomach pouch and rerouting the digestive tract, it is very invasive and prolongs the recovery period for patients. In a new study, researchers at Texas A&M University have described a medical device that might help with weight loss and requires a simpler operative procedure for implantation.

Dr. Sung II Park’s paddle-shaped device consists of a harvestor that contains microchips for wireless communication. The harvestor also produces currents to power LEDs inserted near the end of the Shaft. © Texas A&M University College of Engineering

Researchers said their centimeter-sized device provides the feeling of fullness by stimulating the endings of the vagus nerve with light. Unlike other devices that require a power cord, their device is wireless and can be controlled externally from a remote radio frequency source.

“We wanted to create a device that not only requires minimal surgery for implantation but also allows us to stimulate specific nerve endings in the stomach,” said Dr. Sung II Park, assistant professor in the Department of Electrical and Computer Engineering. “Our device has the potential to do both of these things in the harsh gastric conditions, which, in the future, can be hugely beneficial to people needing dramatic weight-loss surgeries.”

Further details about their device are published in the January issue of Nature Communications.

Obesity is a global epidemic. Furthermore, its associated health problems have a significant economic impact on the U.S. health care system, costing $147 billion a year. Additionally, obesity puts people at risk for chronic diseases such as diabetes, heart disease and even some cancers. For those with a body mass index greater than 35 or who have at least two obesity-related conditions, surgery offers a path for patients to not only lose the excess weight but maintain their weight over the long term.

In recent years, the vagus nerve has received much attention as a target for treating obesity since it provides sensory information about fullness from the stomach lining to the brain. Although there are medical devices that can stimulate the vagus nerve endings and consequently help in curbing hunger, these devices are similar in design to a pacemaker, that is, wires connected to a current source provide electrical jolts to activate the tips of the nerve.

However, Park said wireless technology, as well as the application of advanced genetic and optical tools, have the potential to make nerve stimulation devices less cumbersome and more comfortable for the patient.

“Despite the clinical benefit of having a wireless system, no device, as of yet, has the capability to do chronic and durable cell-type specific manipulation of neuron activity inside of any other organ other than the brain,” he said.

To address this gap, Park and his team first used genetic tools to express genes that respond to light into specific vagus nerve endings in vivo. Then, they designed a tiny, paddle-shaped device and inserted micro LEDs near the tip of its flexible shaft, which was fastened to the stomach. In the head of the device, called the harvester, they housed microchips needed for the device to wirelessly communicate with an external radio frequency source. The harvester was also equipped to produce tiny currents to power the LEDs. When the radio frequency source was switched on, the researchers showed that the light from the LEDs was effective at suppressing hunger.

The researchers said they were surprised to uncover that the biological machinery coordinating hunger suppression in their experiments was different from conventional wisdom. In other words, it is widely accepted that when the stomach is full, it expands and the information about stretch is conveyed to the brain by mechanoreceptors on the vagus nerve.

“Our findings suggest that stimulating the non-stretch receptors, the ones that respond to chemicals in the food, could also give the feeling of satiety even when the stomach was not distended,” said Park.

Looking ahead, he said that the current device could also be used to manipulate nerve endings throughout the gastrointestinal tract and other organs, like the intestine, with little or no modifications.

“Wireless optogenetics and identifying peripheral neural pathways that control appetite and other behaviors are all of great interest to researchers in both the applied and basic fields of study in electronics, material science and neuroscience,” said Park. “Our novel tool now enables interrogation of neuronal function in the peripheral nervous systems in a way that was impossible with existing approaches.”

Other contributors to the research include Woo Seok Kim, Sungcheol Hong and Milenka K. Gamero from the electrical and computer engineering department; Dr. Vivekanand Jeevakumar, Clay M. Smithhart and Dr. Theodore J. Price from The University of Texas at Dallas; and Dr. Richard D. Palmiter and Dr. Carlos Campos from the University of Washington.

This work has been supported by grants from the interdisciplinary X-Grants Program, a NARSARD Young Investigator Award from the Brain and Behavior Research Foundation, the National Science Foundation’s Engineering Research Center for Precise Advanced Technologies and Health Systems (PATHS-UP) and the University of Washington Diabetes Research Center and the National Institutes of Health.

Reference: Kim, W.S., Hong, S., Gamero, M. et al. Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways. Nat Commun 12, 157 (2021).

Provided by Texas A&M University