Transplant Spectroscopy

=Yellow and black bile were considered by the ancients as two of the four vital humours of the human body along with phlegm and blood. Ancient and mediaeval Greco-Roman alternative medicine. Imbalances in these humours caused illness. The Greek names for the terms gave rise to the words “choler” (bile) [the prefix in cholesterol, of course] and “melancholia” (black bile). Excessive bile was supposed to produce an aggressive temperament, known as “choleric” and cause “biliousness.” Depression and other mental illnesses (melancholia) were ascribed to a bodily surplus of black bile.

We now know that bile is far more complex than that. The liver secretes bile into the gall bladder, which concentrates it and releases it into the duodenum. It is mainly composed of bile acids, which are an essential component of the digestive juices needed to absorb fats, proteins and fat-soluble vitamins. Bile also plays an excretory role in getting rid of cholesterol, bilirubin and worn out proteins, eliminating drugs, metabolites, toxins and heavy metals.

Bile also contains phospholipids (predominantly phosphatidylcholine), proteins, amino acids, nucleotides, vitamins, bilirubin and other organic anions and various inorganic substances. The overall composition is regulated by the liver but liver disease and malignancy of the biliary system can disrupt its chemical makeup. Now, researchers are looking at the NMR spectra of bile and other bodily fluids to help them diagnose and monitor illness and potentially to improve the outcome for liver transplant surgery.

I report details of the study in the new issue of SpectroscopyNOW’s NMR ezine.

The study is just a small part of a much bigger project where we are examining the usefulness of metabonomics to monitor the outcome of liver transplants,” team member John Lindon of Imperial College London told me. “We have already published a paper on using NMR spectroscopy of intact human liver tissue biopsies in Analytical Chemistry (using high resolution magic-angle-spinning proton NMR) and we have several more publications submitted and in preparation,” he added.

The bile research is part of a collaboration between Lindon’s team at IC, Elaine Holmes and her team and the Liver Transplant team at King’s College Hospital, London. Colleagues from Portugal, with funding from the British Council, visited IC and also worked on the project there, as well as doing some of the analysis back in Portugal.

This particular study provides a baseline so that researchers know precisely what constitutes bile. “We plan to look for differences between biles from livers before transplantation and after transplantation,” adds Lindon, “knowing clinically what the liver status is.” This work could reveal biomarkers that could be used to distinguish between good graft function and poor function.

The metabolic profile of any biofluid is very complex and changes in this can be used for disease diagnosis or for looking at the beneficial effects of drugs or the detrimental effects of toxins. The changes can be subtle and complex and so the researchers use cheminformatics, in the form of multivariate statistics, to tease out the most significant effects. They are also studying the liver tissue itself and blood plasma.

Research Blogging IconIola F. Duarte, Cristina Legido-Quigley, David A. Parker, Jonathan R. Swann, Manfred Spraul, Ulrich Braumann, Ana M. Gil, Elaine Holmes, Jeremy K. Nicholson, Gerard M. Murphy, Hector Vilca-Melendez, Nigel Heaton, John C. Lindon (2009). Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS Molecular BioSystems DOI: 10.1039/b814426e

Leukemia Tweezers

stained-leukemia-cellsThe first 2009 issue of SpectroscopyNOW is now available:

Tweezing out leukemia spectra – US researchers have used laser tweezers Raman spectroscopy (LTRS) to help them characterize the effects of different chemical fixation procedures on the spectra of healthy cells and leukemia cells and to avoid the misinterpretation of data.

Crime and punishment – A truly interdisciplinary collaboration between biology, law and neuroscience at Vanderbilt University has used functional magnetic resonance imaging, fMRI, to watch how the brain changes when a person thinks about crime and punishment.

Folding issues – NMR spectroscopy is helping US chemists work out shorter and simpler routes to protein-based drugs for treating a wide range of illnesses including diabetes, cancer, and hepatitis.

By Jove, it’s hot and steamy – In 2007, astronomers discovered that a scorching-hot gas planet beyond 63 light years from our solar system is steaming with water vapour, now, it seems the planet, a hot Jupiters, also suffers from high carbon dioxide levels in its atmosphere.

Opal reversal – Electrochemically oxidizing and reducing an inverse polymer-gel opal causes it to swell and shrink, which alters the wavelength of the light it diffracts brightly, from ultraviolet through the visible to the near infrared, the material could pave the way to new display and monitor technologies.

X-rayed dinobird – Researchers at the SLAC National Accelerator Laboratory used the Stanford Synchrotron Radiation Lightsource (SSRL) to shine intense X-ray beams on the so-called “dinobird” to reveal chemical secrets that have been hidden from view for millions of years.

Flu Structure, Mp3s, and Magnetic Minestrone

You can read my latest science news updates in spectroscopynow.com:

One flu over – X-ray studies have revealed details of the structure of a protein used by the avian influenza, H5N1, that allows it to hide its RNA from the infected host’s immune system. The structure could provide a new target for the development of antiviral drugs against this potentially lethal virus

Minestrone and magnetic resonance – Researchers in the US and France may have overturned decades of theory in magnetic resonance studies by spotting a discrepancy in the way nuclear spins behave. Their new mathematical model of the process improves our understanding of atomic behaviour and could lead to better NMR spectra, sharper magnetic resonance images, and perhaps one day a fully portable MRI machine.

Organic soil matters – Could the earth beneath our feet hold the key to climate change? According to scientists at the University of Toronto Scarborough their NMR results show that global warming is changing the molecular structure of organic matter in soil.

Battery capacity is full of holes – Researchers in Korea have developed a novel material for the anode in rechargeable batteries, which they say could make them much more efficient and extend significantly the length of time between charges.

And on ChemWeb for science news with a chemical element:

First on the list in this week’s Alchemist, more on the new anode material, which is potentially good news for the iPod generation. In analytical research, HPLC has been used to spot dummy tequila and in medical chemistry US radiologists suggest that a dose of modified vitamin D could protect citizens from a dirty bomb attack. Next up, a new approach to addressing qubits allows for faster measurements that could take us a step closer to a quantum computer, while Yorkshire chemists are working out the best mix of starting materials to get the maximum height yield on their tasty products. Finally, this week’s award is a record breaker in the State where big is everything.

Election Special

barack-obamaCongratulations to Barack Obama and well done America, you should feel proud to voted for your 44th President in Barack Obama. But, now that’s done and dusted on with the real news:

In Issue 100 of the relaunched ChemWeb Alchemist, we report on energy is top of the agenda with a record-breaking solar cell material from Australia. New insights into the ripening of bananas reveals they get the blues while crystallography has been thrown a curveball as scientists discover the active sites in many models of protein receptors are not what they seemed to be. The chemistry of alternative medicine sits toxically under the glare of the Alchemist’s lamp and revelations about yet another small molecule with a crucial role to play in cellular control. Finally, a double ACS award for research on the structure and reactivity of molecular oxygen binding to copper and iron complexes, which could have future energy applications.

In SpectroscopyNOW this week, rather than designing and building new instrumentation from bespoke components, researchers in Canada have turned to the laser-based optical read-write technology of DVD and CD players to create a biomedical diagnostics system that requires no hardware modifications. Hua-Zhong “Hogan” Yu and his colleagues Yunchao Li, Lily M. L. Ou in the Department of Chemistry, at Simon Fraser University, in Burnaby, British Columbia, Canada, are all for recycling. They have now developed a digital signal readout protocol for screening disc-based bioassays that uses a standard optical drive (CD/DVD) from an ordinary desktop computer.

blue-bananasAlso, this week “Yes, we have blue bananas!” – Forget the so-called morning banana diet, blue is the new yellow and researchers in Europe and the US have no intention of slipping up when it comes to explaining why ripened bananas glow blue under ultraviolet light.

A gold star for SERS – Scientists at the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland, are using surface-enhanced Raman spectroscopy (SERS) to test the properties of star-shaped gold nanoparticles. They have found that these particles have optical qualities that outshine the competition and could make them useful in chemical and biological sensing and imaging.

Athletic support – Researchers have used NMR to show that endurance-trained athletes have a higher resting muscle metabolism than couch potatoes. The work suggests that the dissociation of oxidation and adenosine triphosphate (ATP) production could be another route by which exercise improves insulin sensitivity and burns excess energy and may have implications for understanding the development of type 2 diabetes.

Crystals foxed – Obtaining a high-resolution crystal structure of a protein, a receptor or an enzyme, for instance, has been at the forefront of the drug design field for many years. Finding small molecules that will dock with the active site of the protein and either stimulate it or inhibit it is the basis on which many pharmaceutical products were built and are thought to work. But, what if that fundamental concept were wrong? This is the sobering and at the same time very important conclusion made by researchers at Leiden University in The Netherlands and the Scripps Institute, La Jolla, California

Explosive News

In my SpectroscopyNOW.com column this week: US researchers have used NMR to help them develop a new high explosive material that can be melt cast into a charge with any shape (and presumably whose explosions could be monitored by the blast-proof thermometer).

Nanotubes and geckos caught the eye of The Alchemist this week as US chemists describe a way to out-gecko the gecko by developing a new material that simulates the animal’s hairy feet but is ten times as sticky. Adhering with the theme of sticking, European researchers have found a way to tether prions to a model cell membrane that could open up new research into diseases such as Creutzfeldt-Jakob, BSE and scrapie.

explosive-newsIn environmental news, recent insights into dust from the Sahara could improve our understanding of climate change. Finally, dust of another kind is being used in an entirely different way, by British researchers to protect a new type of thermometer used to measure the 3000 Kelvin temperatures of an explosion.

The crystal structure of a cancer-killing virus has been revealed. The 3D structure of the recently discovered Seneca Valley Virus-001 shows that it is unlike any other known member of the Picornaviridae viral family (which includes the common cold viruses), and confirms its recent designation as a separate genus “Senecavirus”.

Morbid tales for Waco CSI reveals how cheminformatics forensic scientists might use spectroscopy on skeletal remains to determine post-mortem interval, how long the corpse has been dead, in other words.

Under the Spotlight, over on Intute:

Oily fungus helps reduce acid rain – Researchers in Iran have discovered a fungus that can metabolise and absorb sulfur from crude oil and so reduce one of the major sources of air pollution when petroleum products are burned…

Radio samples – More than 20 years after Chernobyl, US researchers have travelled to Sweden and Poland to gain insight into how radioactive elements spewed out by the reactor fire have undergone “downward migration” into the soil…

The dark energy illusion – What if Copernicus were wrong and the earth actually has a special place in the universe? Not some metaphysical, philosophical, supernatural special place, but just special in that the local environment is not the same as other local environments across the reaches of space?

Anti Cocaine, Heroin Test, and Excited Brains

heroin-userThe latest issue of my SpectroscopyNOW column is now online. In this issue, having sampled a little cannabis chemistry last month, I turned to cocaine, and enzymes to beat addiction, and new techniques for testing the purity, or otherwise of street heroin.

Anti cocaine – A mutant enzyme that breaks down cocaine in the bloodstream 2000 times faster than the body’s natural enzymes could lead to a rapid-response treatment for acute overdose or lead to a new therapeutic approach to treating drug addiction.

Testing times for street heroin – Impure forms of illicit drugs are almost as big a problem as the drugs themselves. Now, researchers in Spain have used diffuse reflectance near-infrared spectroscopy (DR-NIR) to quickly determine the purity of heroin.

Sooty balloons – Nothing more sophisticated than a lump of graphite, a roll of sticky tape, and a wafer thin sliver of silica are needed to inflate ideas about nanochemistry. Raman spectroscopy and other techniques have been used to reveal the details of the DIY construction of a balloon-like membrane of graphene.

Stellar chemistry – Astroscientists are using various spectroscopic techniques to root out relatively complex molecules lurking in the interstellar medium. The complexity of naphthalene, discovered in space, and corannulene, could provide new evidence of a cosmic origin for the precursor molecules of life on Earth

Analytical compromise reveals protein folding secrets – A new X-ray technique, time-resolved wide-angle X-ray scattering (TR-WAXS) could defeat even high-field NMR spectroscopy in allowing researchers to monitor very fast, nanosecond-scale movements in the context of the overall three-dimensional protein structure.

Finally, this week, functional magnetic resonance imaging (fMRI) has revealed a reason why the excitement of unwrapping presents dwindles as our brains get older and more jaded. According to a new study, a biochemical pathway is responsible for mellowing our expectations. I cannot say I’ve noticed to be honest, I still get just as excited as the kids at Christmas unwrapping presents…although I’ve moved on from playing with the packaging now, most times.

To effectively reverse any harmful heroin addiction, a patient must undergo detoxification and treatment.

Spectral Analysis

amplitude-spectroscopyThis week in my SpectroscopyNOW column, I have four new posts covering, as usual, a wide range of solutions to scientific and technical problems. First up, is the discovery that compounds found in cannabis could lead to novel antibiotics that are less susceptible to resistance than conventional drugs. Then, we have a new type of spectroscopy that allows scientists to carry out broadband analysis of artificial atoms held at temperatures close to absolute zero. Next, is word from chemists that they have developed a new type of reaction flask that can carry out reactions in the solid state. Finally, this week, we hear of testing times for biomass, where modern spectral analysis could help in the processing of old, treated wood as a renewable fuel resource.

Doping the superbugs – Substances found in cannabis could be used to fight potentially lethal superbugs, such as antibiotic-resistant bacteria, without the mood-altering effects, according to researchers in Italy and the UK. Cannabis sativa (L. Cannabinaceae) extracts may also provide an alternative to synthetic antibacterial substances used in personal hygiene products, including hand wash and cosmetics.

Diamond amp – A new spectroscopic approach to measuring the energy levels of an atomic system has been developed by US researchers. Amplitude spectroscopy can be used to measure the energies of certain natural and artificial atoms and molecules over extremely broad bandwidth by scanning the amplitude of the applied radiation rather than its frequency. The new technique allows the characterization of multiple energy levels in the system, and so overcomes a key challenge to realization of powerful quantum computers. It is applicable to systems with strong coupling to external fields, including artificial atoms, spin systems, cold atoms and molecules, and molecular magnets.

Littlest test-tube – Chemists in Japan have synthesized a new porous material that acts as a microscopic solid-state reaction vessel. Chemical changes taking place in each pore can be tracked using X-ray crystallography the team explains.

Testing times for biomass – Spectroscopy can be used to determine the amount of ash and char present in various types of biomass derived from wood, according to researchers in Japan and the US. Their analytical approach could help in the development of renewable resources for fuels to replace fossil fuels.

Invisible Fishnets and Baby Boomer Pain

fishnetsIt’s that time of the month again, so here’s the latest round-up from my column over on SpectroscopyNOW, covering a whole range of science and medical news with a spectral twist from magnetic resonance to Raman by way of fishnets and infra-red.

Fishnet invisibility cloak – It is what fans of science fiction and technologists have been waiting for since HG Wells’ Invisible Man first came into view – or not, as the case may be. Scientists at the University of California, Berkeley, have engineered three-dimensional meta materials that can reverse the natural direction of visible and near-infrared light, which could one day lead to an invisibility device.

Bending MRI to diagnose joint disease – Osteoarthritis has turned out to be the bane of the Baby Boom generation, causing joint pain and disability for millions of people, more than half of those over the age of 65 in fact. Unfortunately, current approaches to diagnosing the disease cannot provide definitive results until the disease is in the advanced stages. This is often when symptoms have become severe and irreversible joint damage may already have occurred. Magnetic resonance imaging could provide an early diagnosis of osteoarthritis (OA), the most common form of arthritis, according to scientists speaking at the recent ACS meeting.

Universal detector – A team in Japan has used UV spectroscopy and microscopy to study the interaction between liposome clusters and endocrine-disrupting chemicals (EDCs) as a model of how living cell plasma membranes might be affected. The work could lead to the development of a universal detector for EDCs

Dance of the xenons – An NMR study of xenon atoms has demonstrated a fundamental new property – what appears to be chaotic behaviour in a quantum system ? in the magnetic spin of these frozen atoms. The work could lead to improvements in our understanding of matter as well as in magnetic resonance imaging.

Handling chirality with X-rays – X-rays are rather useful in determining the structure of materials and biomolecules, but are relatively insensitive to chirality. Now, a team of scientists in Japan has shown that circularly polarized X-rays at an appropriate wavelength can distinguish ‘left’ from ‘right’ in alpha-quartz. The work could have implications for studies of other inorganic organometallic materials, including industrial catalysts, liquid crystals, biomolecules, and pharmaceutical products.

Hybrid technology – Surface-Enhanced Raman Scattering (SERS) was first used in 1977 and since the has proven itself as an extremely sensitive analytical technique requiring only small volumes of sample and with wide application. Researchers have suggested that it is so sensitive that it could be used as a new tool in single molecule detection to augment or even displace techniques such as laser-induced fluorescence, frequency-modulated optical absorption at low temperature, and electrochemical detection of redox-active species. SERS of silicon nanostructures coated with a gold-silver substrate can be used to detect DNA hybridisation for taxonomic, biomedical and medical diagnostics purposes, according to a new study by researchers in Singapore.

Oh, and speaking of fishnets…anyone been thinking about the modelling career of John McCain’s running mate Sarah Palin?

How to Discover Our Universe

Our Undiscovered UniverseApparently, scientific thought needs rekindling, seemingly it has run out of kindle and needs a new flame if it is to burn brighter. In steps Terence Witt with the concept of null physics. Witt has now self-published a hefty tome by the name of Our Undiscovered Universe.

According to the press blurb that came with my review copy of the book, he’s a visiting scientist at Florida Institute of Technology. Now, I can find FIT on the web, but I cannot find Witt at FIT. Anyway, he puts forward a not entirely original, idea that modern physics requires a paradigm shift back to common sense thinking and a logical reconnection between observation and theory.

There is, Witt says, a disconnect between the two in our current Big Bang theory of the origins of the universe. In Our Undiscovered Universe, Witt puts forward the hypothesis that the universe is static and not expanding, and rouses various equations to explain away the red shift of distant cosmic objects and concepts such as dark matter and dark energy.

Perhaps there are almost as many loopholes in modern physics as there are wormholes and maybe it is possible to tangle up any scientific model with enough string to fill a universe. But, Witt’s is too comfortable a conclusion, that the universe does not rely on any unknowable precursors in the untestable past and will not grow old, collapse or die, but is an unimaginably large cosmic engine. Moreover, his null hypothesis suggests that “our universe actually is, the only thing it could possibly be: the internal structure of nothingness.”

So, you might ask, what is Witt’s evidence for this concept? He explains that evidence of the Null Axiom is everywhere:

  • Matter and antimatter are always created in equal, yet opposite amounts whose electrical sum is zero
  • Positive and negative electric fields sum to a neutral universe with zero net electrical charge
  • Energy is conserved in all interactions; the magnitude of the universe’s energy has zero change
  • Space is a collection of points, little bits of nothingness itself, which embodies a geometric zero – Null
  • Charge must be conserved in particle interactions; the sum of the difference between charges is zero
  • Momentum is conserved, so the universe’s net momentum remains constant at zero

I put a few questions to Witt on behalf of Sciencebase readers just on the off-chance that a paradigm shift really is pending. First off, I asked him to describe null physics briefly.

Null physics is a bottom-up theory built upon the solution to the ontological dilemma: why does the universe exist [instead of nothing]? The solution – that our universe is composed of nothing – leads directly to the four-dimensional geometry of which energy and space are composed. Null physics is the study and quantification of this geometry and its larger ramifications. In contrast to modern physics’ top-down, heuristic approach, which uses measurements and mathematical symmetries to build models that conform to empirical reality, null physics derives empirical reality, such as the magnitude of unit elementary charge and the range and strength of the strong force, through calculations applied to the topology of a fully known underlying geometry.

I put it to Witt that because his theory is a blend of philosophy and science, that might be a double-edged sword?

Not at all. What we currently call physics originally began as natural philosophy. Physics replaced natural philosophy because it provided an accurate mathematical description of the macroscopic scale of the physical world. This set the stage for untold advances in engineering and technology, but many of the foundational questions that natural philosophy confronted, such as why the universe exists and why matter is composed of discrete particles, were lost in this transition, leaving us with empty mathematical models. Null physics is the best of both worlds, fusing a deep understanding of physical reality (as geometry) with empirical validation. The geometry used in Null physics is derived using logic and reasoning similar to that employed by natural philosophy, but has no philosophical component in its final geometric formulation.

Of course, there are other theories around that suggest the universe did not begin with the Big Bang, I asked Witt, what makes his stand out among them?

Sweeping unification and empirical validation. Unlike other non-Big Bang theories, null cosmology is falsifiable, provides testable predictions, and gives a full accounting of the many nuanced properties of the intergalactic redshift and CMB. It also, unlike any cosmology before it (including the Big Bang), provides a logical reason for the universe’s existence and a clear framework that unifies a wide variety of known galactic properties with the large-scale universe. And in keeping with true scientific progress, the unification provided by null cosmology illuminates a number of currently unknown galactic properties, such as the vortical motion of a galaxy’s disk material.

Finally, I was still curious about the philosophical implications and asked about what this theory can tell us of our place in the universe.

It tells us everything about our place in the universe. It tells us why and how we exist on a finite scale that, because of space’s intrinsic symmetry, must exist precisely midway between infinite largeness and smallness. It tells us that the universe is, through causality and sheer size, large enough to contain its own history. In fact the universe must contain its own history, because each and every moment of our lives is integral to ultra-large-scale structure. Perhaps most importantly, null physics demonstrates that our existence is neither accident nor design – it is inevitable.

Witt’s theory also closes the door on a designer. If the universe has always existed and always will exist, then how could a creator have any role to play at all? I suspect that an atheist agenda might underlie many of the static universe theories that are springing up at regular intervals, but they could be simply replacing unsubstantiated nonsense with another form of unsubstantiated nonsense. It’s just not good enough to ask, why are we here? And to answer, because we’re here!

Sexy Worms, an E-Tongue, and Kita Running

Spectroscopynow.comHere is a sneak preview of the various science news items I have scheduled to appear on August 15 over on SpectroscopyNOW.com

Stay young and beautiful – NMR spectroscopy has been used uncovered the secret of eternal youth and the ability to attract sexual partners almost at whim. The results suggest it all hinges on a novel group of pheromones. Unfortunately, before you head for the local pharmacy to stock up, these are pheromones of the lab-technician’s favourite worm, the nematode Caenorhabditis elegans, so they are likely to have no effect whatsoever on human behaviour or longevity.

Electronic wine tasting – The wine buff’s palate is a complicated multisensory organ as anyone who knows their Bordeaux from their Beaujolais knows. Now, researchers have taken a step towards an artificial nose based on a system amenable to multivariate analysis. The system integrates a multisensor to test wine and grape juice samples for adulteration or vintage fraud.

The Kita runners – Protein folding is one of the great conundrums of the twenty-first century. How exactly does a linear string of amino acids “know” into what three-dimensional cross-linked structure to fold itself? Moreover, how might molecular biologists predict this folding from first principles and how might the misfolding seen in prionic diseases, Alzheimer’s and other disorders be prevented or even reversed? A new clue about the folding of proteins comes from studies with a novel technique known as kinetic terahertz absorption spectroscopy (KITA).

Green and peasant landscape – There’s also a bonus item on science in art. Post-impressionist artist was rich beyond his wildest dreams but only posthumously. He may have chopped off part of one ear, but he had double vision. At least that’s the idea that emerges from new X-ray studies of one his more mundane paintings – Patch of Grass – which reveals a portrait of a peasant woman beneath.