A cure for balding could be on the horizon after scientists have found a new way to make hair grow.

Increasing lactate production genetically accelerates the stem cells in dormant hair follicles to get them growing again, a study on mice showed.

Researchers believe the discovery may lead to new drugs to help people who suffer from alopecia, the medical term for hair loss.

Receding hairlines and thinning crowns can becaused by aging, genetics, hormone imbalance, stress, illness and medications. It may be temporary or permanent.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said William Lowry, a professor of molecular, cell and developmental biology at the University of California, Los Angeles (UCLA).

Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

In the study, the researchers found that the metabolic process that takes place in hair follicle stem cells is different from that which takes place in other skin cells.

They discovered that these cells convert glucose into a molecule called pyruvate but this metabolite can take one of two paths.

In can be sent to the powerhouse of a cell (the mitochondria) and used as energy, or the cells can convert it to a different metabolite called lactate the same substance produced during really intense exercise that causes a burning sensation in muscles.

The researchers suspected altering the chemical course of the glucose metabolites could change the behavior of inactive follicles.

Our observations prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Dr Heather Christofk, UCLA associate professor of biological chemistry and molecular and medical pharmacology.

To test their theory, the team examined mice that had been genetically engineered to not produce lactate along with those that had been altered to increase lactate production.

They found that blocking lactate prevented hair follicle stem cells from being activated while increasing lactate upped the production of hair.

The team identified two experimental drugs that, when applied to the skin of mice, accelerate hair growth in this way.

These are called RCGD423 and UK5099 and, while they work in different ways, both increased lactate production.

The researchers whose work was published in the journal Nature Cell Biology stress that these medications were used in preclinical tests only.

They have not been tested on humans or approved by the Food and Drug Administration as safe and effective.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Professor Lowrys lab and first author of the study.

The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss.

I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

Alopecia is the general medical term for hair loss. There are many types of hair loss with different symptoms and causes. Some of the more common types include:

Male-pattern baldness is most common type of hair loss, affecting around half of all men by 50 years of age. It usually starts around the late 20s or early 30s.

It generally follows a pattern of a receding hairline, followed by thinning of the hair on the crown and temples.

It is hereditary and thought to be caused by oversensitive hair follicles, linked to having too much of a certain male hormone.

As well as affecting men, it can sometimes affect women (female-pattern baldness) when hair usually only thins on top of the head.

The causes in women are less well understood, but tends to affect them post menopause.

Alopecia areata causes patches of baldness about the size of a large coin. It can occur at any age, but mostly affects teenagers and young adults. It is caused by a problem with the immune system and has a genetic element.

In most cases, hair will grow back in a few months. But some people go on to develop a more severe form of hair loss, such as:

This is usually caused by complications of another condition, such asdiscoid lupus or scleroderma.

In this type, the hair follicle is completely destroyed and the hair wont grow back.

It occurs in both males and females and mainly adults. It accounts for about 7% of hair loss cases.

This is widespread hair loss that can affect your scalp, face and body.

One of the most common causes of this type of hair loss is chemotherapy. In some cases, other cancer treatments including immunotherapy and radiotherapy may also cause hair loss.

In most cases, hair loss in anagen effluvium is temporary.

This is a common type of alopecia where there is widespread thinning of the hair, rather than specific bald patches. Your hair may feel thinner, but youre unlikely to lose it all and your other body hair isnt usually affected.

It can be caused by your body reacting to hormonal changes, (such as pregnancy), intense emotional stress, intense physical stress, such as childbirth, illness,changes in your diet or some medications.

In most cases, your hair will start to grow back within six months.

Source: NHS Choices

View original post here:
Drug could cure balding by activating follicle cells - Gears Of Biz

A drug-like molecule developed by Duke Health researchers appears to intercede in an inflammatory response that is at the center of a variety of diseases. Credit: Duke Health

A drug-like molecule developed by Duke Health researchers appears to intercede in an inflammatory response that is at the center of a variety of diseases, including some cancers, rheumatoid arthritis and Crohn's disease.

The molecule, called Takinib, works on a cell-signaling protein called tumor necrosis factor alpha, or TNF-alpha, which is a major contributor to tissue inflammation. In recent years, several biological drugs have been developed to interfere with TNF-alpha and treat both auto-immune disorders and some cancers, but patients often develop resistance or side effects.

The Duke team, lead by Timothy Haystead, Ph.D., a professor in the Department of Pharmacology and Cancer Biology, and Emily Derbyshire, Ph.D., assistant professor in the Department of Chemistry, conducted cell-based experiments to learn how the Takinib molecule influences a series of events to suppress cell death. Their work appears in the Aug. 17 issue of the journal Cell Chemical Biology.

The researchers found that Takinib inhibits an enzyme called TAK-1, which serves as a switch controlling cell survival in the TNF-alpha signaling process.

"The delicate balance between survival and death is often disrupted in disease, and this molecule is able to target the process," Haystead said. "This compound could potentially enhance the positive parts of TNF-alpha by only targeting tumor cells or inflammatory cells."

The compound also appears to be effective in small amounts, potentially reducing the toxicity that has been shown in biological compounds targeting the same inflammatory pathway.

Derbyshire said additional studies are underway to test Takinib in animals, focusing first on the molecule's effects in rheumatoid arthritis to determine whether it could have therapeutic benefit and then expanding to other diseases, including malaria.

"Takinib is unique for its ability to selectively target a pathway, since many inhibitors shut everything down," Derbyshire said. "It appears to have a more surgical ability to inhibit this pathway."

Explore further: Stem cells edited to fight arthritis: Goal is vaccine that targets inflammation in joints

Continue reading here:
Lab tests show molecule appears to spur cell death in tumors, inflammation - Phys.Org

BERKELEY, CA, Aug. 17, 2017 About 500 people gathered this week at the University of California Berkeley to assess the rapid adoption of gene editing techniques that appear to hold immeasurable promise for human, animal and plant health and growth.

The two-day conference, CRISPRcon, is named for new techniques Clustered Regularly Interspaced Short Palindromic Repeats called CRISPR-Cas systems.

Over the years, researchers have found various methods of editing the genes of organisms. They involve amending the DNA within an organisms nucleus, rather than inserting transgenic materials from other organisms into the nucleus. Since 2013, scientists have been pursuing an efficient approach of directly targeting sites in a cells chromosomes. The technique uses the cells own bits of RNA strands to guide its Cas proteins in ways that apply highly specific amendments to the DNA, thus altering the organism itself.

In agriculture, scientists are now increasingly applying genome editing to vanquish diseases and enable great leaps forward: for example, to develop resistance to citrus greening for citrus trees or to bestow immunity to porcine epidemic diarrhea virus (PEDv) for pigs.

Jennifer Doudna, a UC Berkeley professor of chemistry and cell biology who spoke at the conference, described the cells nucleus as its instruction manual. She lauded researchers for learning to cut and paste bits of text guiding its life functions. The wondrous feature of the new techniques, she said, is that they can be readily used in every aspect of biology; every type of organism.

I have never seen science move at the pace as it is now in the arena of genetics advancements, Doudna said, in part because CRISPR is such a democratizing tool, available and inexpensive for scientists worldwide to employ.

Participants included a range of genome editing proponents hungry to develop its benefits. Thomas Titus, an Illinois pig farmer, said he thinks first about the potential of CRISPR techniques in eliminating, or improving resistance to, swine diseases. He notes that gene editing for resistance to PEDv has already been accomplished by researchers at Kansas State University, and if we would eradicate diseases like that, it would be just astronomical.

Gene editing will have great impact on the future of farming, and especially on livestock production, Titus said. What it comes down to is how we can utilize this technology for the greater good.

Not all at the conference were ready to rush into CRISPR, though. An instant online survey of the auditorium full of attendees, for example, found 46 percent viewing CRISPR systems as a tremendous tool for the benefit of all mankind, while the rest took a more suspicious or nuanced view.

Many commented on the typically long lag between discovery of biological innovations and their acceptance by society. Doudna noted the torturous history of so-called golden rice, which is loaded with Vitamin A but hasnt earned regulatory approval because the trait is transgenic. The costs of implementing some promising genome editing discoveries may slow them, she said.

Dana Perls, a food technology campaigner for Friends of the Earth, said that she sees agricultural industry giants investing in gene editing and promoting its benefits, and she thinks that calls for caution.

The potential benefits is what we hear about, Perls said. However, it is equally important, if not more important, to look at the potential risks.

Potential effects on climate change, human health and food safety, she said, must be examined before genome editing advances are accepted.

#30

For more news, go to http://www.Agri-Pulse.com

Go here to read the rest:
Summit peers into the future of gene editing - Agri-Pulse (subscription)

A cluster of spring-loaded daggers inside a bacterium. Green shows them in their 'loaded' form, red after the dagger has been launched. Credit: Leo Popovich

Bacteria have to watch out for amoeba. Hungry amoebae hunt them: they catch them with their pseudopodia and then absorb and digest them.

However, some bacteria know how to defend themselves. One of these is Amoebophilus, which was discovered by researchers at the University of Vienna a few years ago. This bacterium cannot only survive inside amoebae, but also thrive: the amoeba has become its favourite habitat.

Together with the Viennese discoverers of the bacterium, scientists from ETH Zurich have now found a mechanism that they assume is crucial for the survival of Amoebophilus inside the amoeba. The bacterium has devices to shoot micro-daggers. It can use the daggers to pierce the amoeba from inside and thus escape digestion.

Escape from the amoeba's gut

The shooting mechanism consists of a sheath attached to the bacterium's inner membrane by a baseplate and an anchoring platform. Joo Medeiros, a doctoral student in Professor Martin Pilhofer's group at ETH, explains the mechanism: "The sheath is spring-loaded and the micro-dagger lies inside it. When the sheath contracts, the dagger is shot outwards extremely quickly through the bacterial membrane."

Bacteria absorbed by the amoeba end up in a special digestive compartment surrounded by a membrane. "Our results suggest that the bacteria are able to shoot the dagger into the membrane of the amoeba's digestive compartment," says Dsire Bck, also a doctoral student in Pilhofer's group and lead author of the study published in the journal Science. This results in disintegration of the compartment, which is an inhospitable environment for the bacteria, and release of the bacteria. Once outside the digestive compartment but still inside the amoeba, the bacteria can survive and even multiply.

The process by which the digestive compartment is destroyed is not yet known. "It may be that rupture of the membrane is due solely to mechanical reasons," says Pilhofer. However, it is conceivable that the daggers of the Amoebophilus bacteria are impregnated with a kind of arrow poison - with membrane-degrading enzymes. The blueprints for such enzymes are contained in the bacteria's genome, as Matthias Horn, professor at the University of Vienna, and his colleagues were able to show.

Precise milling

The scientists applied a completely new method, used only by a handful of research laboratories worldwide - including that of Pilhofer - to determine the three-dimensional structure of the daggers and their shooting mechanisms at high resolution. Bck froze amoebae after they had absorbed bacteria at minus 180C.

Much like a palaeontologist using a hammer and chisel to free fossils from stone, Medeiros then used a focused ion beam as a "nano-chisel" to work on the frozen specimens. With impressive precision, he was able to mill away the amoeba and the bulk of the bacterium, excavating the molecular daggers and their shooting devices in order to finally produce a three-dimensional electron tomogram.

First image of the overall structure

Systems related to the micro-daggers are also found elsewhere in biology: viruses that specialise in the infection of bacteria (bacteriophages) use such systems to inject their genome into microorganisms. Some bacteria can even release similar micro-devices into their surroundings to fight off competing microorganisms.

The scientists present for the first time the complete spatial structure of a shooting mechanism inside a cell in its natural context. They also show for the first time details of the baseplate and membrane anchor. "In the past, cell biologists investigated the function of such systems and structural biologists elucidated the structure of individual components," says Pilhofer. "With the cryo-focused ion beam milling and electron cryo-tomography technologies that we have established at ETH Zurich, we can now close the gap between cell biology and structural biology."

Multi-barrel guns

Micro-daggers had previously been found only as individual devices. In Amoebophilus, however, the scientists from Zurich and Vienna have now found apparatuses that occur in clusters of up to 30. "You could call them multi-barrel guns," says Pilhofer.

The researchers also used genomic comparisons to investigate how Amoebophilus evolved its daggers. "The relevant genes are very similar to those of the bacteriophage injection systems," says Pilhofer. "We assume that the genes from ancestors of today's bacteriophages established themselves in the bacteria's genome a long time ago."

Also present in other bacteria

Genomic comparisons suggest that the micro-daggers occur not only in Amoebophilus, but also in numerous other bacterial species from at least nine of the most important bacterial groups. The researchers have yet to investigate whether these bacteria also use their daggers in order to avoid digestion by amoebae, or whether the daggers serve quite different purposes. They have their work cut out for a long time to come.

Finally, the scientists would like to use the new method of cryo-focused ion beam milling to elucidate the structure of other complex molecular systems. "The technique could help to address many other questions in cell, infection and structural biology. We are already working with other research groups and offering them our expertise," says Medeiros.

Explore further: Plague bacteria take refuge in amoebae

More information: "In situ architecture, function, and evolution of a contractile injection system" Science (2017). science.sciencemag.org/lookup/ 1126/science.aan7904

Journal reference: Science

Provided by: ETH Zurich

Originally posted here:
Bacteria stab amoebae with micro-daggers - Phys.Org