ARTIFICIAL CELLS TAKE THEIR STEPS MOVABLE CYTOSKELETON MEMBRANE FABRICATED FOR THE FIRST TIME

 Using only a few ingredients, the biophysicist Prof. Andreas Bausch and his team at the Technische Universität München (TUM) have successfully implemented a minimalistic model of the cell that can change its shape and move on its own. They describe how they turned this goal into reality in the current edition of the journal Science, where their research is featured as cover story

Cells are complex objects with a sophisticated metabolic system. Their evolutionary ancestors, the primordial cells, were merely composed of a membrane and a few molecules. These were minimalistic yet perfectly functioning systems.

Thus, "back to the origins of the cell" became the motto of the group of TUM-Prof. Andreas Bausch, who is member of the cluster of excellence "Nanosystems Initiative Munich (NIM)" and his international partners. Their dream is to create a simple cell model with a specific function using a few basic ingredients. In this sense they are following the principle of synthetic biology in which individual cellular building blocks are assembled to create artificial biological systems with new characteristics.

The vision of the biophysicists was to create a cell-like model with a biomechanical function. It should be able to move and change its shape without external influences. They explain how they achieved this goal in their latest publication in Science.

The magic ball

The biophysicists' model comprises a membrane shell, two different kinds of biomolecules and some kind of fuel. The envelope, also known as a vesicle, is made of a double-layered lipid membrane, analogous of natural cell membranes. The scientists filled the vesicals with microtubules, tube-shaped components of the cytoskeleton, and kinesin molecules. In cells, kinesins normally function as molecular motors that transport cellular building blocks along the microtubules. In the experiment, these motors permanently push the tubules alongside each other. For this, kinesins require the energy carrier ATP, which was also available in the experimental setup.

From a physical perspective, the microtubules form a two-dimensional liquid crystal under the membrane, which is in a permanent state of motion. "One can picture the liquid crystal layer as tree logs drifting on the surface of a lake," explains Felix Keber, lead author of the study. "When it becomes too congested, they line up in parallel but can still drift alongside each other."

Migrating faults

Decisive for the deformation of the artificial cell construction is that, even in its state of rest, the liquid crystal must always contain faults. Mathematicians explain these kinds of phenomena by way of the Poincaré-Hopf theorem, figuratively also referred to as the "hairy ball problem." Just as one can't comb a hairy ball flat without creating a cowlick, there will always be some microtubules that cannot lay flat against the membrane surface in a regular pattern. At certain locations the tubules will be oriented somewhat orthogonally to each other -- in a very specific geometry. Since the microtubules in the case of the Munich researchers are in constant motion alongside each other due to the activity of the kinesin molecules, the faults also migrate. Amazingly, they do this in a very uniform and periodic manner, oscillating between two fixed orientations.

Spiked extensions

As long as the vesicle has a spherical shape, the faults have no influence on the external shape of the membrane. However, as soon as water is removed through osmosis, the vesicle starts to change in shape due to the movement within the membrane. As the vesicle loses ever more water, slack in the membrane forms into spiked extensions like those used by single cells for locomotion.

In this process, a fascinating variety of shapes and dynamics come to light. What seems random at first sight is, in fact, following the laws of physics. This is how the international scientists succeeded in deciphering a number of basic principles like the periodic behavior of the vesicles. These principles, in turn, serve as a basis for making predictions in other systems.

"With our synthetic biomolecular model we have created a novel option for developing minimal cell models," explains Bausch. "It is ideally suited to increasing the complexity in a modular fashion in order to reconstruct cellular processes like cell migration or cell division in a controlled manner. That the artificially created system can be comprehensively described from a physical perspective gives us hope that in the next steps we will also be able to uncover the basic principles behind the manifold cell deformations."

WORLDS FIRST CHILD BORN AFTER UTERUS TRANSPLANTATION

In a ground-breaking research project at the University of Gothenburg, seven Swedish women have had embryos reintroduced after receiving wombs from living donors. Now the first transplanted woman has delivered a baby -- a healthy and normally developed boy. The world-unique birth was acknowledged in The Lancet on 5 October.

The uterus transplantation research project at the University of Gothenburg started in 1999 and has been evaluated in over 40 scientific articles. The goal of the Gothenburg project is to enable women who were born without a womb or who have lost their wombs in cancer surgery to give birth to their own children.

Live donors

Nine women in the project have received a womb from live donors -- in most cases the recipient's mother but also other family members and close friends. The transplanted uterus was removed in two cases, in one case due to a serious infection and in the other due to blood clots in the transplanted blood vessels.

The seven remaining women have in 2014 tried to become pregnant through a process where their own embryos, produced through IVF, are reintroduced to the transplanted uterus.

First child from a transplanted uterus

The first early pregnancy was confirmed in the spring after a successful first pregnancy attempt in a woman in her mid-30s, a little over a year after her transplantation.

In early September, the woman successfully delivered a baby by caesarean section, making her the first woman in the world to deliver a child from a transplanted uterus. Her uterus was donated by a 61-year-old unrelated woman.

The caesarean section had to be performed earlier than planned: the woman developed preeclampsia in week 32 of her pregnancy and the CTG indicated that the baby was under stress. A caesarean section was performed in accordance with normal clinical routines so as not to risk the health of the mother and child.

Developing normally

According to Professor Mats Brännström, who performed the caesarean section, the perfectly healthy newborn boy is developing normally. The baby weighed 1,775 grams (3 lbs 14.6 oz) at birth, which is normal size considering the gestational age at delivery.

'The baby screamed right away and has not required any other care than normal clinical observation at the neonatal unit. The mother and child are both doing well and have returned home. The new parents are of course very happy and thankful,' says Professor Mats Brännström, who is leading the research project.

'The reason for the woman's preeclampsia is unknown, but it may be due to her immunosuppressive treatment combined with the fact that she is missing one kidney. The age of the donated womb may also be a factor. Also, preeclampsia is generally more common among women who have become pregnant through IVF treatment.'

Mild rejection episodes

The woman has had three mild rejection episodes since the transplant, one of which occurred during the pregnancy. The rejection episodes, which are often seen also in other types of transplants, could be stopped with immunosuppressive treatment.

Followed closely

The research team followed the pregnancy closely, carefully monitoring the growth and development of the foetus with a special focus on the blood supply to the uterus and umbilical cord.

'There were concerns that the blood supply may be compromised since we had reattached the blood vessels to the womb. But we did not notice anything unusual concerning the function of the uterus and the foetus, and the pregnancy followed all normal curves,' says Brännström.

Major step

The successful delivery is considered a major step forward.

'It gives us scientific evidence that the concept of uterus transplantation can be used to treat uterine factor infertility, which up to now has remained the last untreatable form of female infertility. It also shows that transplants with a live donor are possible, including if the donor is past menopause,' says Brännström.

Several research teams around the world have been awaiting the results of the Gothenburg study in order to launch similar observational studies. The pregnancy attempts are ongoing with the other six women in the project.

FIRST WHO REPORT ON SUICIDE PREVENTION

More than 800 000 people die by suicide every year – around one person every 40 seconds, according to WHO's first global report on suicide prevention, published today. Some 75% of suicides occur in low- and middle-income countries.

Pesticide poisoning, hanging and firearms are among the most common methods of suicide globally. Evidence from Australia, Canada, Japan, New Zealand, the United States and a number of European countries reveals that limiting access to these means can help prevent people dying by suicide. Another key to reducing deaths by suicide is a commitment by national governments to the establishment and implementation of a coordinated plan of action. Currently, only 28 countries are known to have national suicide prevention strategies.

Suicide is a global phenomenon

Suicide occurs all over the world and can take place at almost any age. Globally, suicide rates are highest in people aged 70 years and over. In some countries, however, the highest rates are found among the young. Notably, suicide is the second leading cause of death in 15-29 year-olds globally.

“This report is a call for action to address a large public health problem which has been shrouded in taboo for far too long” said Dr Margaret Chan, Director-General of WHO.

Generally, more men die by suicide than women. In richer countries, three times as many men die by suicide than women. Men aged 50 years and over are particularly vulnerable.

In low- and middle-income countries, young adults and elderly women have higher rates of suicide than their counterparts in high-income countries. Women over 70 years old are more than twice as likely to die by suicide than women aged 15-29 years.

Suicides are preventable

Reducing access to means of suicide is one way to reduce deaths. Other effective measures include responsible reporting of suicide in the media, such as avoiding language that sensationalizes suicide and avoiding explicit description of methods used, and early identification and management of mental and substance use disorders in communities and by health workers in particular.

Follow-up care by health workers through regular contact, including by phone or home visits, for people who have attempted suicide, together with provision of community support, are essential, because people who have already attempted suicide are at the greatest risk of trying again.

 “No matter where a country currently stands in suicide prevention”, said Dr Alexandra Fleischmann, Scientist in the Department of Mental Health and Substance Abuse at WHO, “effective measures can be taken, even just starting at local level and on a small-scale”.

WHO recommends countries involve a range of government departments in developing a comprehensive coordinated response. High-level commitment is needed not just within the health sector, but also within education, employment, social welfare and judicial departments.

“This report, the first WHO publication of its kind, presents a comprehensive overview of suicide, suicide attempts and successful suicide prevention efforts worldwide. We know what works. Now is the time to act,” said Dr Shekhar Saxena, Director of the Department of Mental Health and Substance Abuse at WHO.

The report’s launch comes just a week before World Suicide Prevention Day, observed on 10 September every year. The Day provides an opportunity for joint action to raise awareness about suicide and suicide prevention around the world.

Working towards a global target

In the WHO Mental Health Action Plan 2013-2020, WHO Member States have committed themselves to work towards the global target of reducing the suicide rate in countries by 10% by 2020. WHO’s Mental Health Gap Action Programme, launched in 2008, includes suicide prevention as a priority and provides evidence-based technical guidance to expand service provision in countries.