Category Archives: Biology

Biology News

Cholesterol treatment used in treatment of hepatitis C?

Posted on by

By Kathryn Higgins

A molecule that is known to take up cholesterol into a cell has recently been identified to allow entry of the hepatitis C virus (HCV) into liver cells. This may lead the way for new therapies to be developed.

Hepatitis C is a disease that primarily affects the liver. It is caused by HCV, which is spread by blood-to-blood contact. Once infected, HCV can persist in the liver causing scarring and ultimately leading to liver failure or cancer. The World Health Organisation (WHO) estimates that three per cent of the world’s population (about 170 million) have hepatitis C, and although treatment is available, more effective therapies are needed. Liver transplantation is one such treatment, but infected patients find the virus attacks the new liver.

Previous studies have shown the involvement of cholesterol in HCV infection, thus it was hypothesised by researchers at the University of Illinois at Chicago that a cell surface molecule (a receptor) called Niemann-Pick C1-like 1 (NPC1L1), which is known to facilitate the uptake of cholesterol into the cell, may also be involved in trafficking the virus into the cell.

The research team headed by Susan Uprichard, assistant professor of Medicine, Microbiology and Immunology, conducted experiments to determine the role of NPC1L1 on viral uptake. Experiments involved blocking the receptor and reducing expression by using knock-out models. The results demonstrated that blockade or knock-out of NPC1L1 impaired liver cell infection with HCV.

To confirm these studies further, an inhibitor of NPC1L1 called ezetimibe, which is clinically used to lower cholesterol levels, was also tested. Results validate previous findings showing blockade of HCV uptake into the cells and preventing infection.

Current drugs used to treat hepatitis C are known to be toxic, and cannot be used by transplant patients, therefore ezetimibe may provide a solution as a new anti-hepatitis agent. Therapy with ezetimibe alone or in combination with current drugs may improve patient treatment by targeting the receptor NPC1L1 and preventing HCV entry into liver cells.

Reference:
Sainz et al, (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nature Medicine. Ahead of print.

The paper can be found at: http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.2581.pdf

Transparent tissues offer a window into the brain

Posted on by

By Kathryn Higgins

 

A revolutionary reagent has been developed that can literally turn biological tissues transparent. Researchers from the RIKEN Brain Science Institute in Japan have developed a reagent which allows 3D imaging of the neuronal network deep inside a mouse brain.

Imaging and labelling of cell populations deep within tissue has been a challenge for scientists for many years. Although advances have been made in cell imaging there are still many obstacles to overcome. Tissues often have to be sliced 1mm thick for viewing under a microscope to dissect networks since imaging within deep tissues leads to many problems due to the lack of transparency of the tissue. Several clearing solutions have been developed but these have disadvantages such as expense and quenching of fluorescently labelled proteins that are often used in cell research to visualise the structures.

A research team led by Atsushi Miyawaki, however, have recently developed a reagent, after a chance observation, which may revolutionise deep tissue imaging by obtaining 3D images that are valuable for improving our understanding of biological organisms and how they function.

The reagent, called ScaleA2, is a highly effective clearing reagent, greatly improving the transparency of tissues, and stabilising fluorescently labelled proteins. This allows imaging to be done at a much greater depth than currently possible, providing detailed 3D visualisation of neuronal networks within the brain than has ever been managed before.

Current research using ScaleA2 was done using dead embryo tissue for imaging neurones and blood vessels deep inside the mouse brain. Miyawaki and his research team, however, believe that the scope for using ScaleA2 in other tissues and organisms is not limited, and are currently trying to optimise the reagent for use in live tissue. This would open the door to experiments that have never before been possible.

 

Image shows two murine embryos. The left embryo was placed in PBS, whilst the embryo on the right was incubated for 2 weeks in ScaleA2 solution.

 

 

Reference:

Hama et al, (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience. Ahead of print.

The paper can be found at:

http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn.2928.pdf

Credit card diagnoses HIV & Syphilis

Posted on by

Written by Iain Stewart

An article published in Nature Medicine, 4th August 2011, has shown scientists from Columbia University, New York, have created a new tool for efficient and reliable diagnosis of both HIV and syphilis.

Samuel Sia and his team of researchers have adapted the ‘ELISA’ technique into a portable and cheap procedure that can be used in remote parts of the world, giving results in under twenty minutes. ELISA (or enzyme-linked immunosorbent assay) is a well-known method, routinely used in laboratories, to detect the presence of antigens using antibodies.

Antigens are molecules, which when present in the blood, trigger an immune response from the body. Every cell in our body carries its own antigens, which are recognized as ‘self’, but foreign antigens from bacteria, viruses, and cells that are not our own, stimulate new antibody production.

Sia and colleagues scaled down the recognition of antigens into a plastic tool they term ‘mChip’ (microfluidic chip). All that is required is a microlitre of blood, taken directly from a pinprick, which is then passed through extremely narrow channels in a credit card sized device. The disease antigens are present where the channels form tight loops. When blood from an individual who has the virus flows through these loops, specific antibodies from the blood bind. Next, antibodies attached to silver particles are washed through and bind to the antibodies present, with the result of solid silver loop indicating the patient is positive for the specific disease.

This new tool displays many advantages over the current diagnostic strategies. It is low cost, as the mChip and reagents cost pennies to make. It can diagnose both HIV and syphilis in the same test, taking under twenty minutes compared to previous hours, days and even weeks. Its portable design allows it to be operated at the point-of-care, making it accessible anywhere in the developing world. A microlitre of whole blood is all that is necessary from the patient, while its ease of use requires minimal training for the operator. The result can be read without hi-tech optical equipment, is not open to interpretation, and has been shown to be as reliable as current techniques.

Exposing unborn children to the sexually transmitted disease, syphilis, leads to miscarriages, stillbirths and death of newborns. Fast diagnosis of pregnant mothers, and therefore treatment of syphilis with a single dose of penicillin, can significantly increase the survival of the unborn infant by preventing disease transmission through the placenta. Sia and colleagues’ data suggest 5000 syphilis-related deaths could be avoided in Rwanda alone, whilst the World Health Organisation estimates that the disease is responsible for 500,000 perinatal deaths in sub-Saharan Africa every year. 

As well as the obvious impact this technique could have on diagnosing HIV and syphilis at the point-of-care, this test can be used for pre-screening blood donations, and could eventually be used to diagnose a range of infectious diseases in poorly equipped areas all over the world.

Chin, C. et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nature Medicine. 4th Aug 2011, doi:10.1038/nm.2408

http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.2408.html

http://www.who.int/reproductivehealth/topics/rtis/syphilis/en/index.html


credit card sized device.

doi:10.1038/nm.2408

channel loops, scale bar 1mm.

doi:10.1038/nm.2408  

A woman bathes an infant in rural Manara, Tanzania. Taken from www.who.int.

Blood Groups Could Become a Thing of the Past

Posted on by

 

Written by Matt Farley

 

New research from McGill University in Canada could do away with the need to classify blood by ‘type’, following a new technique to prevent mismatched blood from being rejected after a transfusion.

Along with the well-known A, B and O blood groups, there are a further 26 different blood types which have to be matched carefully when carrying out a blood transfusion – a mismatch can lead to the donated blood being rejected by the body which can be fatal. The ideal situation is for a ‘universal’ blood type which would be compatible with any recipient blood type.

Rejection occurs when the antigens on the surface of the donor red blood cells are of a different type to those on the recipient’s cells – previous attempts at avoiding this have focused on either removing the surface antigens from the donated blood using enzymes, or producing the blood outside the body from stem cells. These techniques have shown some success, but are hindered by their expense and complexity. The latest method, presented by Dr. Maryam Tabrizian and colleagues, instead aims to cover up the antigens and hide them from the host immune system – known as ‘immunocamouflage’.

Red blood cells from a selection of volunteers were coated in a layer of polyelectrolytes – small repeating units which self-assemble on the cell surface. Previous attempts at coating cells in this way using yeast and E.coli had shown promise, but it remained to be seen whether the delicate red blood cells would be able to withstand the process.

After coating, the cells were exposed to their opposite antibody and observed for any agglutination, or clumping of cells, that occurred. The coated cells were shown to remain free after addition of the antibody, suggesting that the antibodies had failed to recognise and bind the cell surface antigens. This was in contrast to the uncoated cells, which clumped together in the manner normally seen when mismatched blood samples are mixed.

Perhaps most importantly, the red blood cells showed no significant reduction in their ability to take up oxygen, implying that they would still be able to carry out their function within the body. The cells were also seen to produce ATP, an energy carrier – a good sign that metabolism was also functioning as normal.

It remains to be seen whether the technique will be as effective when tested in a living organism, but the results obtained so far appear promising. If effective, future blood transfusions could become a lot easier, and a lot less dangerous.

The paper accompanying this article is available online:

http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/bm101200c

Red blood cells

Losing DNA made us human

Posted on by

 

Written by Olivia O’Sullivan

 

A study has shown that it may be DNA we have lost which sets humans apart from our nearest primate relatives. 

The majority of mutations in DNA are harmful, and a loss of genetic information might be assumed to be catastrophic. In a paper published last week in Nature, a team of researchers from Stanford University in California have challenged this by identifying the loss of particular regions of non-coding DNA to be a key factor in shaping our unique minds and bodies, thus setting us apart from chimpanzees and the rest of the animal kingdom.

By conducting a genetic comparison of the human genome with that of a chimp and a macaque the team found 510 DNA sequences missing in humans that were present in chimps, almost all of these sequences were from the non-coding region of DNA, i.e. chunks of DNA responsible for turning genes on or off . Two regions of particular interest were the androgen receptor (AR) gene and ‘GADD45G’ – a tumour suppressor gene involved in brain development.

The AR gene is implicated in the production of hard, keratinized penile spines which are found in many mammals and play different roles in different species. It is thought that penile spines may have been used as a way of competing with other males for mating partners by removing the sperm of competitors. It is believed that the molecular changes resulting in a loss of human penile spines has allowed us as a species to form more complex social structures by adopting monogamous reproductive relationships.

Another ‘lost section of DNA’ in humans was found to code for a tumour suppressor gene that normally acts to suppress brain growth, putting an evolutionary brake on the growth of specific brain structures zones in our primate relatives. This ultimately paved the way for the evolution of a larger human brain, giving us an intellectual edge over our fellow animals.

The results of this study certainly underlines the fact that genetic information is both gained and lost during evolution and that despite sharing approximately 96% of our DNA with chimpanzees, it is thought that this genetic divergence may have occurred more than 800,000 years ago when our ancestors split from the Neanderthal lineage. This is an exciting finding, opening up new areas for discovery through the analysis of the remaining 508 DNA sequences which promise to reveal further secrets about the molecular basis of human individuality.

 

References:

McLean, C. Y. et al. Nature 471, 216-219 (2011)

What? A molecule that enables hearing

Posted on by

 

By Kathryn Vaughan

Researchers at the University of Sheffield have identified a molecule that underlies mechanisms of hearing loss and deafness.

In the inner ear ‘cochlear hair cells’ are responsible for receiving sound as sensory information before it can be converted into electrical nerve signals to be sent to the brain, and these hair cells mature during embryonic development. To examine the mechanisms that regulate cochlear hair cell maturation, researchers led by Walter Marcotti from the University of Sheffield have investigated the role of a molecule named miR-96. The molecule miR-96 is a microRNA, a short genetic sequence that regulates the expression of a range of genes, and is itself highly expressed in developing cochlear hair cells.

Mice that do not express miR-96, referred to as ‘knockouts’, were compared with control mice that do express miR-96. To examine differences in structure, hair cells from the two groups of mice were observed under a microscope and measurements were taken of both cell length and sensitivity to a neurotransmitter. By placing a speaker 20cm directly in front of each mouse and recording a ‘Preyer reflex’, whereby a mouse flicks its ear in the direction of sound, the researchers also measured auditory brainstem responses, which reflect the activity of the hair cell.

The researchers found that the cochlear hair cells of the mice that do not express miR-96 were thinner, shorter in length and more immature when compared to hair cells of control mice, identifying a role for miR-96 in the maturation of cochlear hair cells. To investigate the activity of the hair cells by measuring the auditory brainstem responses, the knockout mice could not be used since they have no auditory response at all. Instead, mice with limited miR-96 expression were compared with control mice and were found to be less responsive, indicating a defect in their hearing due to the limited miR-96 expression.

Measurements were also recorded to examine the sensitivity of hair cells to a neurotransmitter called acetylcholine. Acetylcholine is a molecule released from nerve endings and can act upon cochlear hair cells to initiate the conversion of an auditory response into an electrical nerve signal. Sensitivity to acetylcholine was reduced in knockout mice whilst control mice responded as usual, implicating miR-96 in hair cell activity.

These results indicate that in the maturation of cochlear hair cells, which is vital for the fundamentals of hearing, miR-96 plays an essential role. By understanding these mechanisms the researchers propose that the research “could provide us with clues to help develop therapies to ameliorate the effects associated with nonsyndromic progressive hearing loss”.

Cochlear hair cells in a Guinea Pig

 References:

Kuhn et al (2011) miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells. Proc Natl Acad Sci USA, 108 (6), 2355-2360.

The paper can be found at:

http://www.pnas.org/content/108/6/2355.full.pdf+html

Fluorescent probes make nerves glow during surgery

Posted on by

 

Claire Tree-Booker

Scientists at the San Diego School of Medicine, University of California have developed fluorescent protein fragments, also known as peptides, which specifically label nerves. It is hoped this new technology will help surgeons avoid damaging nerves during surgery.

Accidental damage to nerves during surgery can cause many problems including pain, numbness and even paralysis.

The scientists report, in the 6 February 2011 edition of Nature Biotechnology, that when the fluorescent peptides were injected into mice, nerves were labelled within two hours; this created a ten-fold contrast compared to other body tissues, allowing the nerves to be easily seen.

The fluorescent labelling was found to have no effect on the activity of the nerves or the animals’ behaviour.

Whilst surgeons can identify nerves by their appearance or by electrical stimulation, they can sometimes be missed if they are buried or have a different appearance.  Dr Quyen T. Nguyen, carrying out the study, said “if surgery is required in the setting of trauma or infection, the affected nerves might not look as they normally would, or their location may be distorted”.

 “We have yet to test the peptide in patients, but we have shown that the fluorescent probe also labels nerves in human tissue samples”, says Nguyen.

Damaged nerves were also fluorescently labelled, suggesting that this technique could be useful in nerve repair surgery in the future.

The paper can be found at http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1764.html

New ancestor to modern humans found in Siberia

Posted on by

Jamie Kendrick

Scientists have discovered that the exceptionally preserved finger bone found in Denisova Cave in the Altai Mountains of southern Siberia belongs to a distinct group of ancient human-like individuals that roamed the Asian continent alongside modern humans and the Neanderthals.

The study also showed that the Denisovans – the ancient group’s assigned name – probably interbred with an ‘Out of Africa’ migrating population of our own species and are responsible for an estimated 4-6% of the genome (entire DNA) of modern day Melanesians.

The revelations, published in articles in Nature, have transformed common knowledge of the relationships of our own species Homo sapiens and have yet again updated the continually growing tree of human evolution.

Dr Ian Tattersall, curator at the American Museum of Natural History, New York said, “the evidence is accumulating that the human evolutionary tree is quite luxuriantly branching. There were multiple species that competed in the evolutionary arena.”

Only 7 months after it was confirmed that Neanderthal DNA survives in present day Europeans, this outstanding new research has come to light to provide more evidence of our human ancestor’s involvement in interbreeding.

The finger bone, initially discovered in 2008 alongside body ornaments such as a bracelet and modern tools including microblades, was used to extract DNA for analytical tests by Professor Svente Pääbo’s team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Results show that the individual to whom the bone pertains was female and possessed DNA and an evolutionary history significantly distinct from ourselves and the Neanderthals. The Denisovan group to which the female ‘X-woman’ belongs shared a common ancestor with the Neanderthals and modern humans H. sapiens around 1 million years ago (MYA).

The Denisovan DNA diverged first from the H. sapiens lineage about 800 thousand years ago (KYA) and again 640 KYA from their Neanderthal sister group to create the family tree shown below.

Comparing the DNA from modern humans of diverse ethnicities with samples from Neanderthals and Denisovans reveals the connection between modern day Melanesians and X-woman’s group that is interpreted as a classic signature of interbreeding.

Professor Chris Stringer from the Natural History Museum in London hailed the discovery as “nothing short of sensational” and described the Denisovans as a “new lineage of humans in Asia which we can relate to a particular group of people alive today.”

A tooth uncovered in the same cave back in 2000 was also found to contain DNA remarkably similar to that from the finger bone indicating that it derives from a shared population now dubbed the ‘Denisovans’ who inhabited Asia to an unknown range.

Dr David Reich from Harvard Medical School suggested that “these populations must have been spread across thousands and thousands of miles.”

The tooth possesses distinguishable features outside the variation and unlike anything seen in either our own species or the Neanderthals, prompting claims of a new species.

However, the authors chose against speculating on the exciting subject of whether the Denisovans constitute a new archaic human species, although Johannes Krause a member of Pääbo’s team commented that “the evidence is already very strong that we are looking at a previously unknown hominin, and possibly a new species.”

 

The research and information presented in this article can be found in -
Reich, D et al. 2010. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, pp 105

New campaign launched to save coral reefs

Posted on by

Jamie Kendrick

The Zoological Society of London (ZSL) has announced a plan to protect some of the world’s most important and precious coral reef species. The society has selected ten of the most evolutionary distinct and genetically endangered (EDGE) corals which face a high risk of immediate extinction.

The corals chosen include a range of rarities; from functionally important reef-builders – the elkhorn coral Acropora palmata, architecturally elaborate forms – the elliptical star coral Dichocoenia stokesii, and ocean oddities such as the ctenella coral Ctenella chagius – which resembles a human brain and is found only around a small island chain in the Indian ocean called the Chagos Archipelago.

Rachel Jones, senior aquarium keeper at London Zoo explained that, “having a top ten focuses attention on individual species and holds them up as flagships for the habitats they represent”.

According to the ZSL’s project co-ordinator Catherine Head, corals could be subject to “functional extinction in twenty to fifty years due predominantly to climate change”.

The project will adopt a regional approach and help fund, train and support conservationists with the aim of improving the resilience of the world’s most diverse coral species so that they flourish in the future.

Coral reefs – dubbed ‘marine rainforests’ – cover less than 1% of the Earth’s surface yet support an astounding one third of all marine biodiversity and provide invaluable ecosystem services to a variety of life.

However as is well documented, human mismanagement and over-exploitation are driving reefs and their constituent species towards extinction. Pollution, ocean acidification and overfishing all pose severe threats to the future of the world’s reefs. The projected 1∙5-4.5 degree rise in temperature expected by the end of the century could account for ninety five per-cent of all reefs, say the World Wildlife Federation (WWF).

Projects and collaborations such as the ZSL’s action plan and the recent Coral Triangle Initiative represent contrasting but valiant attempts to safeguard the future of the iconic reefs. Currently the prospects look bleak, but with further international co-operation and implemented protection measures put into place, these wondrously rich keystone ecosystems could yet be cherished in years to come and rescued from the brink.

Life, but not as we know it

Posted on by

 

Michaela Livingstone


A newly discovered bacterium uses the deadly arsenic to grow and live.


The only organism able to use a different chemical from the accepted fundamental building blocks of life has been found living in a lake in California, substituting phosphorus for the usually poisonous element arsenic, opening up questions on what other forms of life might be possible in the universe.


Until now, all life on Earth has been found to use the same basic building blocks for life, the elements carbon, hydrogen, oxygen, nitrogen, phosphorus and sulphur. These elements make up the various cellular parts and machinery from DNA to proteins and lipids.


The bacterial strain, named the not-so-exotic GFAJ-1, was isolated from mud samples collected from the shores of the briny Mono Lake in California, known to have high levels of arsenic, by NASA researcher Felisa Wolfe-Simon and was reported in a research article in this week’s issue of the journal Science.

Phosphorus is contained in a phosphate form (phosphorus and oxygen) in the backbone of DNA and RNA, as well as energy-carrying molecules such as ATP. There had been suggestions that arsenic in the form of arsenate could be used by life as it is chemically similar to phosphate, which is why it is usually deadly.


The bacterium was shown to have arsenate incorporated in to its DNA and other cellular parts when grown in media lacking phosphorus but containing a relatively high level of arsenic. The organism was however still able to grow faster in the presence of phosphorus.


Some researchers have hailed this as evidence that it is possible for life elsewhere in the universe to use different chemicals as their building blocks, opening up many possibilities for extraterrestrial environments where life could thrive, where before it was thought impossible. It suggests that anything is possible and that alien life may look very different from what we have assumed, if we ever come face to face with it.


Others say it opens up questions as to how, and how many times, life may have evolved here on Earth speculating that life may have evolved in harsh environments with high levels of arsenic such as volcanic vents on sea beds before later incorporating phosphorus.


Clara Chan, a geomicrobiologist from the University of Delaware, Newark was reported by the journal Science as saying that the strongly held belief is that the chemistry of life is so specific that any changes would not be tolerated, “The implication of this work is that life can be quite different from what we know.”


Other scientists are less convinced by the data, withholding belief that the organism really is able to use arsenate in place of phosphate until more data is produced to show that the arsenate isn’t simply being stored in the bacterium.


GFAJ-1 at least shows that is possible for life to exist in the absence of phosphorus. Wolfe-Simon hopes now to find bacteria growing naturally in high-arsenic but low phosphate-containing environments to find proof of life that depends on arsenic.

 

Find the original research article here:

http://www.sciencemag.org/content/early/2010/12/01/science.1197258