Category: Sciencebase

Oxytocin, the nurturing hormone involved in child-birth and breast-feeding, apparently plays a role in how we recognize faces, according to a paper in the Journal of Neuroscience. Researchers gave volunteers a nasal dose of oxytocin and found that they all had improved recognition memory for faces, but not for inanimate objects.

In humans, oxytocin, which comes from the Greek meaning “quick birth”, increases social behaviors like trust, but its role in social memory has been unclear. “Recognizing a familiar face is a crucial feature of successful social interaction in humans,” said Peter Klaver, of the University of Zurich, Switzerland. In this study undertaken with Ulrike Rimmele, of New York University and colleagues, the team investigated for the first time the systematic effect of oxytocin on social memory in humans.

“This is the first paper showing that a single dose of oxytocin specifically improves recognition memory for social, but not for nonsocial, stimuli,” said Ernst Fehr, who has studied oxytocin’s effect on trust and is unaffiliated with the new study. “The results suggest an immediate, selective effect of the hormone: strengthening neuronal systems of social memory,” Fehr said.

A fast and inexpensive melamine detector is reported in the RSC’s journal ChemComm this week. The research follows hot on the heels of the melamine in milk scandal of 2008 and the petfood contamination in 2007 and earlier. The two techniques are based on mass spectrometry and could be adapted to provide on-site kits that would require little training to use.

Melamine, commonly used as a fire retardant and polymerized to a plastic resin, was added to milk during processing to artificially boost its apparent protein content.

David Muddiman, professor of mass spectrometry at North Carolina State University, Raleigh, US, describes the techniques as “marvellous examples of how innovative, direct analysis ionisation methods, when coupled with mass spectrometry have the ability to address contemporary problems facing the world. The [researchers have removed all the major obstacles allowing for mass spectrometry not only to compete, but to take the lead in these types of analyses.”

More details here.

What is safest? (a) The risk of daily and then weekly injections of an untested compound targeted at activating your pigment cells to give you an all-over suntan without having to spend time in the sun or on a UV sunbed or (b) The great outdoors and a healthy approach to sun exposure?

For a group of delightful young women in Northern England, where the sun shines strongly only rarely I can tell you having grown up there, the answer was obvious – (a) the regular injections.

But, what are they injecting daily for a week and then weekly thereafter? What is this compound that stimulates a higher than normal skin pigmentation level and gives the young women the appearance of having just returned from a fortnight lounging by the pool somewhere much warmer and sunnier than oop north? Well, it is called Melanotan and it’s illegal in the UK, i.e. it has not received approval from the medical authorities. It is nevertheless, being sold illegally over the internet and in some tanning salons and body building gyms.

So, is it worrying is that melanotan has not gone through the full gamut of safety tests required of pharmaceutical products, and yet the young women seem unconcerned when confronted with that fact in the following BBC news video clip.

There is the possibility that it is perfectly safe and if not perfectly safe then safer than ultraviolet tanning beds, and according to cancer charities possibly a whole lot safer than chronic sunbathing. The Medicines and Healthcare products Regulatory Agency (MHRA) has said that injecting Melanotan could have serious side-effects. But, given that full clinical trials have not yet been completed, they could just as easily have said that it could have no serious side-effects.

Melanotan purportedly boosts the body’s production of melanin, the natural pigment produced by the skin on exposure to the sun’s ultraviolet rays. To be honest, to my eye, none of the young women in the video even looked particularly tanned.

Apparently, there are two versions of the injectable suntan – melanotan I and melanotan II and both are analogs of the naturally occurring peptide hormone alpha-melanocyte stimulating hormone. I’d certainly never consider injecting with any hormone except under doctor’s orders and certainly not for the sake of getting an artificial tan. If the health experts are right and there are safety problems with melanotan, then who’s to say these girls aren’t putting themselves at risk of some nasty effects, melanoma in a syringe, perhaps?

But, like I say, I much prefer the great outdoors and a sensible attitude to sun exposure. (Oh, except for that time I got burnt on that warmer and sunnier fortnight).

Researchers at the Gladstone Institute of Neurological Disease at the University of California San Francisco have found that removing a brain enzyme that regulates the concentration of arachidonic acid, a fatty acid, reduces cognitive deficits in a mouse model of Alzheimer’s disease (AD). The discovery, reported in Nature Neuroscience, may one day lead to a novel therapeutic strategy for the disease.

Alzheimer’s causes a progressive loss brain cognitive functions and is a terminal disease. There are treatments that can alleviate symptoms, but there is no cure.

“Several different proteins have been implicated in Alzheimer’s disease,” explains GIND’s Lennart Mucke, “but we wanted to know more about the potential involvement of lipids and fatty acids.”

Fatty acids are rapidly taken up by the brain and incorporated into phospholipids, a class of fats that form the membrane or barrier that shields the content of cells from the external environment. The scientists used a large scale profiling approach (“lipidomics”) to compare many different fatty acids in the brains of normal mice with those in a mouse model of Alzheimer’s disease that develops memory deficits and many pathological alterations seen in the human condition.

The most striking change discovered was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer’s disease. Arachidonic acid is thought to wreak havoc in the brains of the mice by causing too much excitation, damaging neurons. By lowering arachidonic acid levels, the researchers found they could allow neurons to function normally.

In general, fatty acid levels can be regulated by diet or drugs, which could have important therapeutic implications. A lot more work is needed before this strategy can be tested in humans.

Rene O Sanchez-Mejia, John W Newman, Sandy Toh, Gui-Qiu Yu, Yungui Zhou, Brian Halabisky, Moustapha Cissé, Kimberly Scearce-Levie, Irene H Cheng, Li Gan, Jorge J Palop, Joseph V Bonventre, Lennart Mucke (2008). Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease Nature Neuroscience DOI: 10.1038/nn.2213

Once again, the BBC is reporting on herbal highs. This time, it tells us that while most legal high pills are based on a group of drugs called piperazines, of which BZP (benzyl piperazine) is the most common and will be banned in the UK under a European directive, it is cathinone, the active ingredient in the plant khat, a widely used stimulant in East Africa that is the focus of today’s news. Cathinone is beta-ketoamphetamine.

Although so-called “legal highs” are marketed as a safe alternative to illegal, classified drugs, they are not without risks. “A high heart rate, high temperature, high blood pressure, and more severe effects such as heart attacks and strokes,” can happen, consultant toxicologist Paul Dargan, clinical director of the Guy’s and St Thomas’ Poisons Unit London, told the BBC.

Worryingly, there various legal herbal highs available that claim not to contain the likes of BPZ, but toxicologists frequently find these potentially lethal compounds in such products.

There a dozen compounds being black-marketed widely, the law hasn’t caught them all yet, but, says the BBC, legal doesn’t mean safe.

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A century-old rule used throughout the pharma industry may have been overturned by new research in the UK. Researchers at the University of Warwick have demonstrated that drug transport rates across cell membranes may be hundreds of times slower than are predicted by Overton’s Rule, which could have serious implications for developing and testing new drugs.

Put simply, Overton’s Rule says that the more lipophilic a compound is, the faster it will enter a cell. The Rule was first outlined in the 1890s by Ernst Overton of the University of Zürich. He quantified the rule to allow biochemists and others to predict how fast the membrane crossing would take place. One of the key parameters in his equation is K, lipophilicity. Bigger K, faster transport.

For over a century, medicinal chemists have used this relationship to shape their studies and clinical trials.

Now, a confocal microscopy study used in conjunction with an ultramicroelectrode led by Patrick Unwin has allowed the team to follow every step of the membrane-crossing process. The results are stunning. While the test compounds (acids) did diffuse across a lipid membrane, they did so at rates that were diametrically opposed to those prediction by Overton’s Rule. The researchers studied four acids (acetic, butanoic, valeric, and hexanoic) that had increasingly larger “acyl” (or carbon) chains. The longer the carbon chain, the easier the chemical dissolves in lipids and, therefore, according to Overton, the faster they should diffuse across a lipid membrane.

The Warwick work showed instead that the most lipophilic molecules were actually transported the slowest.

REFERENCE: Proc Natl Acad Sci: Quantitative visualization of passive transport across bilayer lipid membranes

Some people would pay anything for a quickfix pill for their sex lives or to slow the inevitable aging process. Now, US scientists have found a new class of small molecule in the molecular biologist’s favorite nematode worm, Caenorhabditis elegans, a blend of which apparently not only attract mates but also slow the development of larvae for months.

The soil-dwelling nematode is used as a model organism for lots of human diseases and in aging research because despite the apparent differences between ourselves and the nematode, we share much of our underlying biology with the worm.

Writing in Nature, Frank Schroeder, of Cornell University, Jagan Srinivasan, of California Institute of Technology, and colleagues describe the new compounds, ascarosides, and reveal data that show how they extend lifespan in C. elegans as well as acting as sex pheromones for the wriggly critter. The work essentially ties together at the molecular level two superficially disparate life processes – sex and death.

So, are we likely to see a human version of the ascarosides for attracting a sex partner and warding off old age. Short answer is no. Although we share some of the molecular biology of this nematode, there are a few too many differences to make such a pill even remotely possible…at any price.

Srinivasan, J., Kaplan, F., Ajredini, R., Zachariah, C., Alborn, H.T., Teal, P.E., Malik, R.U., Edison, A.S., Sternberg, P.W., Schroeder, F.C. (2008). A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature DOI: 10.1038/nature07168

The US Food and Drug Administration (FDA) has approved Tysabri (Natalizumab), a monoclonal antibody for the treatment of moderate to severe Crohn’s disease in patients with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional Crohn’s disease therapies. So reports MediceNews.net.

Crohn’s disease is an inflammatory bowel disorder that can affect the whole of the gastrointestinal tract from mouth to anus. It leads to a wide variety of symptoms, primarily abdominal pain, diarrhea, vomiting, or weight loss. It can also cause serious complications outside the gastrointestinal tract such as skin rashes, arthritis and eye inflammation.

Crohn’s disease patients using the newly approved drug must be enrolled in a special restricted distribution program called the Crohn’s Disease—Tysabri Outreach Unified Commitment to Health (CD TOUCH) Prescribing Program.

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One of the important components of the extracellular matrix is collagen, which comprises the major structural protein component of higher organisms. However, it remains a major challenge to emulate the unique structural and biological properties of native collagenous biomaterials in synthetic analogues. Consequently, numerous opportunities exist for synthetic collagens in biomedical applications as extracellular matrix analogues, if the appropriate materials could be constructed that retain and expand upon the desirable properties of native collagen fibrils.

The exploration of chemical and molecular genetic techniques to design and synthesize collagen-mimetic polypeptides and fibers that are competent for self-assembly into structurally defined protein fibrils is an intriguing avenue for exploration. In this context, Shyam Rele and colleagues have been leading the efforts in the de novo design of nanostructured biological materials through self-assembly of peptides and proteins.

Rele, together with Elliot Chaikof and Vince Conticello in the Laboratory of Bio/Molecular Engineering and Advanced Vascular Technologies at Emory University School of Medicine have been successful in designing and synthesizing the first ever Synthetic Collagen Peptide system which is a 36 amino acid long unit which self-assembles into a fibrous structure with well-defined periodicity reminiscent of native collagen observed in the human body.

Specifically, the synthesized peptide protomer which is made up of three heterotrimeric peptide repeat units contains a hydrophobic proline-hydroxyproline-glycine core flanked on both the sides by distinct sets of peptide repeats containing either negatively (Glutamic acid) or positively (Arginine) charged amino acid residues. When positioned appropriately, these charged amino acids bias and adopt the triple helical self-assembly which undergoes fibrillogenesis at physiological temperatures producing D-periodic microfibers driven through electrostatic interactions.

Transmission electron microscopy on annealed samples revealed that fiber growth proceeded within several hours by initial formation of smooth fibrils that were hundreds of nanometers in length and tens of nanometers in diameter. These fibrils displayed tapered tips similar to the tactoidal ends of native collagen fibers from which continued fiber growth is thought to occur. The D-periodicity of the synthetic collagen-mimetic microfibers was approximately 18 nm. Significantly, the collagen mimic shows a high propensity for self-association following a nucleation-growth mechanism even at lower concentrations (<1.0 mg/mL) and neutral pH. This following discovery for making human collagen in the laboratory is pathbreaking in the field of nanotechnology and bio-inspired biomaterials. Several scientists for the past three decades have been trying to synthesize and emulate collagen's remarkable properties and have failed in their attempts to mimic the long, fibrous molecules found in nature. The ability of Rele, Chaikof and Conticello to generate a synthetic collagen in a laboratory (in vitro) on a nanomolecular level for the first time, therefore represents an important milestone in nanotechnology and biomaterial development. Such self-assembling peptides may have broad applications in medicine, neurodegenerative diseases, protein folding catalyst design, bio-nanotechnology, tissue engineering and origins of life research. Furthermore, generation of such nanostructured molecules which mimic native structural proteins will lay the future ground work for unraveling complex phenomena including collagen fiber formation in protein conformational diseases and for the design of new materials with biological, chemical, and mechanical properties that exceed those of currently available synthetic polymers.

The propensity to generate such self-assembling, biologically compatible peptide scaffolds to arrange themselves into fibers, tubules, and a variety of geometrical layers, establishes an important substrates for cell growth, differentiation, and biological function, and will have an important impact in the treatment of cardiovascular, orthopedic, and neurological disease.

Adapted from a write-up supplied by Rele. Further details can be found in JACS, vol 129, 14780-14787.

Astronomers have detected for the first time in the ultraviolet region the spectroscopic signature of the carbon monoxide molecule in a galaxy located almost 11 billion light-years away. This molecule has eluded astronomers for a quarter of a century.

The detection now allows them to obtain the most precise measurement of the cosmic temperature just 1.5 billion years after the Big Bang (give or take 25 years). The team used the UVES spectrograph on ESO’s Very Large Telescope (it does what it says on the tin) to record the signal from a well-hidden galaxy whose light has taken 4 fifths the age of the Universe to reach Earth. Apparently, it was at a rather balmy (compared to today’s temperatures) 9-and-a-bit Kelvin.

More details from the European Southern Observatory site.