Cholesterol treatment used in treatment of hepatitis C?

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

Ancient Humans: Becoming human

There can be only one

No I’m not referring to Highlander I am referring to species of humans. Out of many species that fall under the umbrella term of the genus Homo we are the only one that has survived- Homo sapiens. The mystery behind this has had religious, philosophical and scientific ramifications over the ages that have been debated to this day. But who were these other humans? And can we really consider them to be human?

From the archaeological record we know a fair bit about these other humans which may be able to tell us just how human they were by identifying sociality, intelligence, technology and culture.

Homo habilis Stringer and Andrews 2005 P. 68

Robin Dunbar found a relationship between a part of the brain known as the neo-cortex and theory of mind. Theory of mind refers to a level of sociality- the first level dictates that person A knows something about person B. The second level dictates that person A knows that person B knows something about person C; and so on. Therefore the higher the level, the higher the capacity for an individual to comprehend what a group knows. This type of intelligence becomes important when we start to consider how a group functions within a landscape; they form social bonds which is crucial for group activity. Seeing this hallmark within primates, Robin Dunbar extrapolated the size of the neo-cortex within extinct humans from archaeological remains, and use it to infer upon theory of mind and sociality. What he found was a general clumping of all the extinct Homo species around the Homo sapiens mark. The lineage that led to the genus Homo diverged 6 million years ago from chimpanzees. The first Homo species that appeared on the scene was Homo habilis at 3 million years ago. It is very likely that by then, H. habilis had the intelligence to understand social situations.

While H. habilis was the first Homo species to make and use tools (which led to their alternative and rather informal name Handy Man), Australopithecus afarensis was actually the first species to do so. A. afarensis was an earlier species that walked on legs as opposed to knuckle-walking, and it is possible that the Homo lineage came from this species. The earliest evidence of tool use on bones comes from Ethiopia dated at 3.39 million years ago where it is known that A. afarensis inhabited this region. Clearly by the time of H. habilis, we start to see the beginnings of a rather primitive form of intelligence that enabled them to form social groups and use their own type of technology, which was known as the Oldowan tool industry.

Nariokotome Boy. Stringer and Andrews 2005 P. 139
Homo erectus

Eugene Dubois, a Dutch palaeo-anthropologist, was in Java (S.E Asia) in 1890 when he found a set of skeletal remains. He had found what was later called Homo erectus. This species was clearly the first member of the Homogenus to have migrated out of Africa. One of the most important finds belonging to this species was Nariokotome Boy found in Kenya in 1984. What was particularly interesting about this find was that the individual was thought to be just a little bit older than 11 years old and, from his remains, it could be seen that he was about 6 foot tall! This is a species that was very well adapted to the hot climate of Africa; H. erectus was tall, gracile and slender with long legs that enabled them to travel for long distances, which ultimately they did.

 

Homo heidelbergensis
Neanderthals

To perfectly complement how H. erectus was adapted to the hot climate of Africa, H. heidelbergensis illustrates adaptations to a cold climate. Likely to diverged from H. ergaster as well (and thus be a sister group to H. erectus), H. heidelbergensis was the last common ancestor of Neanderthals and modern humans. But it was also the first Homo species to move into Europe. The commonly held theory is that H. heidelbergensis evolved into Neanderthals in Europe. As such Neanderthals appeared to be very well adapted to the cold; they were short, stocky and well-built when compared to the tall and more graceful modern humans.

They had a wide distribution across Europe and Asia; from Israel to Wales, and as far north as Siberia and south as Gibraltar. Vast amounts of archaeology have shown that Neanderthals had their own culture and technology, and existed together in their own social groups. But all good things come to an end. By the time the Neanderthals had settled into their life in Europe, at 60,000 years ago, the climate got severely worse. Before the start of the Ice Age at approximately 28,000 years ago, modern humans had already arrived and settled themselves, and the Neanderthals had become extinct.

Cave painting from France
Figurine from Germany

The arrival of modern humans into Europe from 50,000 years ago is part of the next hallmark in our evolution: the Upper Palaeolithic Revolution. This revolution saw a cultural explosion. A wide variety of art has been attributed to the Upper Palaeolithic. Such examples include ornaments, figures and cave art, but it also included technology for acquiring and processing food. While the Neanderthals had their own technology for the same reasons, modern humans had a much more diverse toolkit. But as far as we know, no art found has been associated with Neanderthals.

In 2010, DNA analyses suggested that Neanderthals and modern humans interbred just outside of Africa before modern humans spread around the world. Following on from this, a few other studies have suggested that interbreeding was occurring between other human species, such as between H. erectus, and a possible new human species the Denisovans, and between modern humans and the Denisovans. While many more analyses need to be done to confirm this, this claim has immediate implications as to what we consider a species. A species is defined as a group of individuals that can only reproduce with each other. If Neanderthals and modern humans were interbreeding with each other, then this suggests that Neanderthals and modern humans are the same species, and that we (current modern humans) are descended from this interbreeding. More work however needs to be done. Ancient DNA is a field fraught with difficulties but as DNA technology improves we will have more data to look at.

By now we see a picture emerging as what we could consider as “being human”: the capacity for sociality and intelligence, use of technology and the element of culture. At the same time the lines between these various humans are beginning to blur. If the DNA evidence holds up, as more studies are carried out, then perhaps we should start to consider all of these humans under just one species name and designate each one by sub-species. The archaeological evidence certainly suggests that many of these types of humans had a level of intelligence that meant they could establish technology and culture which appears to be just as different from each other as they are morphologically. We are so willing to find the point in time where we can say “here is where we became human!”  The truth is we can’t. We, Homo sapiens, may have arisen around 200,000 years ago, but humanity could have begun much earlier. So when natural selection and bad luck killed off the other types of humans, it left us- the sole human survivor. This then leaves us with just one question:

For how long, in this changing world, can we survive?

For more information:

  • Dunbar, R. 2003. The Social Brain: Mind, Language and Society in Evolutionary Perspective. Annual Review of Anthropology 32, 163-181
  • Green et al. 2010. A Draft Sequence of the Neandertal Genome. Science 328 (5979) 710-722
  • Stringer, C. Andrews, P. 2005. The Complete World of Human Evolution. Thames and Hudson, UK.
  • Oppenheimer, S. 2004 Out of Eden. Robinson, London

This article was written to complement the presentation “Ancient Humans: Who were they? And who got it on?” that was given on the 5th December 2011 for the Natural History Society. For more details on the author, see http://independent.academia.edu/DanaeDodge

 

2011′s top Physics and Astronomy Stories

Einstein Wronged?

One of the physics stories this year that made it’s way significantly into the
media was that from the OPERA collaboration which observed Neutrinos travelling
faster than the speed of light. When this report broke back in September it was
met with a certain amount of trepidation from both the scientists involved and
the scientific community with the possibility that if confirmed it is a result
that would put ends to the underpinning concept of general relativity that
nothing can travel faster than the speed of light! In the months up to now the
scientists involved have been running the experiment again with the same results
and offering the challenge to other scientist to try and see what is wrong with
their experiment/result.

Currently although it hasn’t been able to be disproved the likelihood of this
being correct is low, one only has to apply the apparent difference in neutrino
and light speeds to the supernova of 1987. Under the OPERA speeds we should have
detected neutrinos from supernova 1987a 4 years before the light arrived, this
however wasn’t the case and they more or less arrived at the same time. The jury
is still out on this one and it’ll be interesting to see what experiments are
devised in 2012 to test these results.

Hints of Higgs.

In December CERN held a press conference regarding the Higgs Boson with much
excitement surrounding it. The rumours and speculations as to what results were
to be announced seemed to mirror most people’s hopes of the conference, that the
Higgs had finally been found at the LHC, this however was not necessarily the
case. Scientists at CERN couldn’t specifically say they had found the Higgs
Boson with significant certainty, however two experiments (ATLAS and CMS) had
seen hints of what was believed to be a Higgs signal around 125
gigaelectronvolts.

Although from experiments it cannot be stated if the Higgs exists or if the
signal observed is true 2012 holds hopes for the scientists involved. When the
LHC gets back up and running after the Christmas break scientists will be
hunting and acquiring as much data as possible to identify with significant
certainty where the Higgs signature lies. Expect by the end of 2012 to have an
answer as to whether the Higgs Boson exists!

The end of the Shuttle Program.

July brought the end of NASA’s 30 year shuttle program with the successful
launch and return of shuttle Atlantis. Funding strains and austerity measures
introduced by NASA grounded the fleet after 135 missions which brought massive
rewards into space research and technology developments. Sadly however measures
put into action in the period after the Columbia shuttle tragedy has seen NASA
aiming to shift it’s regular space travel to that of private investors to save
the limited amount of money already received from the US government. 2012 is
expected to see the first private companies staking claims in space exploration
with private space craft making the launch into space in the coming months.

Fukushima Fallout

It was hard to miss coverage of the events that took place on the East coast of
Japan back in March where a country best prepared for a tsunami was overwhelmed
by the result or 9.0 magnitude Earthquake.Luckily most of the nuclear fallout
was carried out to sea by winds although this didn’t stop mandatory evacuation
zones around the reactors. It took 9 months from the initial reactor meltdowns
to ensure that the reactors were safely in cold fusion and accordingly shut down
although the clean up of the site will take decades still at high cost.

The fukushima meltdown had significant effects on research and energy policy in
some nations. Compared to the Chernobyl disaster (occurring 25 years previously)
researchers could assess how a release of radioactive material effected the
environment and occupants in a wealthier nation such as Japan. The research also
aided the Japanese people with the lessons learnt previously from Chernobyl
being applied to prevent conditions caused by radiation. The disaster also had
an impact on policy with (understandably) Japan, Germany, Switzerland and Italy
taking an abrupt turn away from nuclear, Germany proposing to shut down all
reactors by 2020s. The coming years will be interesting to see if other
technologies come through for energy production or if these nations resume their
faith in nuclear energy.

The growing Universe

This years Nobel prize in Physics was awarded in October to Saul Perlmutter,
Brian Schmidt and Adam Reiss for their work on using supernovae to chart the
expansion of the universe. By using distant supernovae with standard intensity
the team were able to chart from their light how far away and how fast the
points were moving away from us on Earth. From this deductions and calculations
of the universe’s expansion could be ascertained as well as inferences made for
the effects of dark energy on matter in the universe. This year’s Nobel prize in
Physics was an odd one as the lauretes were relatively young compared to many
that have come before indicating potential shifts in those taking up scientific
research.

New Earths

2011 was an extraordinary year for NASA’s Keplar mission encompassing ground and
space based telescopes in a search for extrasolar planets. Although there was no
sign of Earth’s twin exactly, over 700 planets have been identified with some
strong candidates that may contain life. The mission identifies planets by
looking at stars. Measurements map out the light intensity observed from these
stars, periodic reductions in this intensity are sometime observed and it is
this which indicates that there is a body orbiting with a defined orbit. This
can data can also be applied in such ways to calculate the size of planets and
other properties.

Notable mentions of planets discovered by the Keplar mission are ‘Keplar 22-b’
which was the first planet observed which was inside of the habitable zone, a
region around a star where life may exist. Another one was a planet orbiting two
suns which was aptly named Tatooine.

To boldly go…

In November 6 men returned to Earth from a mission to Mars, however they never
actually left the Earth. The simulated mission that took place in a Russian
warehouse came to an and proved to a point that the human body could at least
cope with the mental strain of isolation and close quarter living that would be
encountered on a manned mission to Mars. Whilst locked away in a mock space
craft the astronauts practised space walks, experiments on mars and simulated
repairs necessary to keep the craft going. This paved the way for future space
exploration and although a Mars mission won’t occur just yet it’s a tantalising
glimpse into what may be possible in regards to the human body.

Goodnight Tevatron.

As the LHC was colliding particles and obtaining data to probe into the origins
of the universe and evidence for the Higgs Boson, an older particle accelerator
came to the end of it’s functioning life. With over 25 years colliding particles
Fermilab’s Tevatron particle accelerator closed in September with most of the
scientists using it packing up to move to the bigger and more powerful LHC.
Although not as powerful, Tevatron was actively hunting for the Higg’s Boson and
helping to eliminate some of the mass energy ranges that it could reside in.
Flurries of particles were identified and greater understanding into the
standard model governing particle physics came with the experimental
observations for the predictions that it made. With the LHC going strong
hopefully the work conducted at Tevatron shalln’t be forgotten and who knows
what the last scraps of data will hold.

Biolaser.

A report in June in the journal Nature photonics reported and experiment where
biological components were turned into lasers. Fluorescent proteins from
jellyfish were inserted into the genome of mammalian cells which were suspended
between two mirrors. The effect of the living cells suspended between saw an
amplification of an inserted photon inducing a lasing process. The significance
of this was that the cell and the proteins survived which is often not observed
when fluorescent proteins undergo continuous light excitation. With the
development of this technique the biological lasers may be seen in future in
nanotechnology and other more familiar regions as CD/DVD players. In regards to
these biological systems it is very much watch this space.

James Webb Space telescope vs politics.

More delays and issues arose in regards to the Hubble telescopes successor this
year, the James Webb Telescope. The telescope which when complete will reside in
a region 1.5 million kilometres away from Earth far away from any communication
disturbances, it will also comprise of a set of mirrors exceeding the size of
Hubble allowing for far higher resolution. The telescope however has come under
fire due to spiralling costs of $8.7 billion and rising. With the rising costs
the House appropriations committee in the US have declared that given the chance
they would prefer to cancel the project rather than provide more funding to
sustain it until launch in 2018. Some members of the senate have come out in
support of the telescope and NASA have also hit back saying it could be made
cheaper with more money spent now to have it readied prior to the current
estimated completion date. 2012 will tell whether the project survives and if
the completion date changes at all.

And to commemorate the Shuttle here’s an awesome video by Nature with Sheffield’s finest 65daysofstatic providing the music.

http://www.youtube.com/watch?v=II7QBLt36xo