Boxing Day Boredom and Monkey Proteins

Monkey proteinsIt’s Boxing Day and you’re probably seriously bored playing the “normal” game of Pick-up Monkeys. Rather than heading for the Wii or the PS3, how about adding a little monkey magic, or more seriously some wire binders and following Dr N. Michael Green, Division of Mathematical Biology, of the UK’s prestigious Medical Research Council (MRC) National Institute for Medical Research to do a little bit of science education with those colourful plastic monkeys.

“Pick up Monkeys’ was originally produced as a children’s game (1965) and they have proved very versatile,” Green explains, “I discovered in 1968 that they were ideal models for protein subunits, being asymmetric, having multiple interaction sites and available in several colours. This exhibition illustrates their use in modelling the geometry of multi—subunit protein structures.”

Stop monkeying around, take a look at Green’s site to get the hang [pun intended!] of proteins. It’s a great idea for a science fair project too.

Sniffing out our sense of smell

How we smellOur sense of smell is much better than we give it credit for. A report in Nature Neuroscience puts paid to the notion that the human reputation for having a poor sense of smell compared to other animals.

Noam Sobel and colleagues laid down scent trails in a grassy field, and asked human subjects to find the trail and track it to the end. Subjects were blindfolded and wore thick gloves and earplugs to force them to rely exclusively on smell. Contrary to expectations, the volunteers exhibited some of the same tracking strategies used by dogs and were certainly capable of following the trail.

In follow-up experiments, the authors also demonstrated that this ability partially depends on comparisons of odour information in each nostril, it’s almost like smelling in stereo.

When subjects had one nostril plugged their tracking performance was much worse.

Admittedly, the volunteers were much slower than dogs at following the scent trail, but with practice they got quicker.

the findings raise the intriguing possibility that our sense of smell is far better than we think and that using it more effectively is simply a skill we don’t teach our children so it gives us the impression that we don’t have it.

For more on a provocative theory of how we smell check out this page from the Sciencebase archives.

YAFSE – train your beady eye on EB-eye

The European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI) this week launched its new website. Apparently, the web interface has been streamlined on the basis of user feedback. Nothing too exciting in that, except they have also upgraded their search engine and describe it as being at the centre of the site and exhaustive in its breadth.

Underpinning the new site is “EB-eye”, a trendy-sounding and powerful search engine allowing instant searches of all the EBI’s databases from a single query. “If you can use Google you can use this,” explains associate directory Graham Cameron, latching on to the “proper-verb” of the day.

Seriously though, the new site architecture should allow much swifter navigation between databases, so that you can get from genomes to genes, proteins to structures and biological functions from a single, simple interface.

Intriguingly for an organisation that goes by the monicker of EMBL-EBI acronyms (and jargo, allegedly) have been banished from the site wherever possible. You’re unlikely to hear scientists say, “I’ve just EB-eye’d it,” just yet. But, it might make more sense for specialists to do just that rather than “Googling” for their information needs.

Too much protein increases cancer risk

Earlier this week scientists reported a strong correlation between obesity and the risk of common cancers, such as cancer of the colon and breast cancer. Today, initial findings from a US study suggest that eating less protein could be a way to protect some people from cancers that are not directly associated with obesity.

The research is published in the December issue of the American Journal of Clinical Nutrition (2006, 84, 1456), shows that lean people on a long-term, low-protein, low-calorie diet or participating in regular endurance exercise training have lower levels of plasma growth factors and certain hormones linked to cancer risk. “However, people on a low-protein, low-calorie diet had considerably lower levels of a particular plasma growth factor called IGF-1 than equally lean endurance runners,” says Luigi Fontana of Washington University, “That suggests to us that a diet lower in protein may have a greater protective effect against cancer than endurance exercise, independently of body fat mass.”

“Our findings show that in normal weight people IGF-1 levels are related to protein intake, independent of body weight and fat mass,” Fontana says. “I believe our findings suggest that protein intake may be very important in regulating cancer risk.”

Fontana says most of us don’t eat nearly enough fruits and vegetables or enough whole-grains, cereals or beans. “Many people are eating too many animal products – such as meat, cheese, eggs and butter – as well as refined grains and free sugars,” he says. “Our intake of vegetables and fruits is low, and beans are vastly underconsumed in the U.S. and Europe these days.”

He believes diets would be healthier if we ate more whole grains, beans, fruits and vegetables and far fewer animal products. He recommends mostly fish, low-fat dairy products and, occasionally, some red meat. Such a diet would both cut total calories and reduce the amount of protein we consume to healthier levels.

“Eating too many calories increases our risk of developing obesity, diabetes, cardiovascular disease and of certain types of cancer related to obesity,” Fontana adds, “We hope to further clarify what happens to cancer risk when we are chronically eating more protein than we need.”

Expanding proteins

Expanding proteinsA new study reveals that the static snapshots recorded in protein crystallography may be missing the bigger picture. Investigations of a bacterial protein using cryomicroscopy shows the protein in a balloon-like mode previously hidden from sold state studies. The discovery suggests that techniques complementary to X-ray crystallography are essential if molecular biology is to gain a complete understanding of protein structure.

Steven Ludtke, assistant professor of biochemistry and molecular biology and co-director of the National Center for Macromolecular Imaging at Baylor College of Medicine and colleagues Dong-Hua Chen and Wah Chiu there and Jiu-Li Song and David Chuang at The University of Texas Southwestern Medical Center in Dallas, studied a mutant protein and came to this perhaps not so startling conclusion. The protein GroEL chaperones misfolded proteins and nudges them into their active folded state in the cell. Protein misfolding is implicated in a number of neurodegenerative diseases, such as Alzheimer’s disease and the prion diseases including Creutzfeldt-Jakob disease.

The full story is now available at SpectroscopyNOW

CiteXplore

What is it with software and websites and scientific tools that they all have to have these mixed case acronyms, abbreviations, and odd spelling?

Anyway, today sees the launch of another odd spelling from the European Molecular Biology Laboratory’s European Bioinformatics Institute – CiteXplore. This is a freely accessible literature resource service that melds data from the peer-reviewed scientific literature with key biological data such as DNA and protein sequences, functions and structures of molecules and microarray data.

The tool essentially searches Medline abstracts, patent abstracts, and Chinese Biological Abstracts and links to publisher websites. But, the crucial difference between this and any other literature search tool is that it cross-links to EMBL-EBI’s biological databases.

‘When you are reading an abstract describing a specific gene or protein, typically you want more information on it, for example its sequence or its function, as well as easy access to the full paper,’ says Peter Stoehr, who coordinates CiteXplore. Built-in text-mining tools allow “touch of a button” or more aptly, “click-of-a-(lab)-mouse” access to the specific record for a molecule of interest.

This is just the kind of system that chemists Peter Murray-Rust and Henry Rzepa have been aiming for the chemical sciences. Once again, the bio guys seem to have stolen a march on chemistry.

Genetic Variation on a Theme

What does it mean to be human? We thought that the Human Genome Project had set the limites on the genetic make-up of our species. But, according to Steve Connor, writing in the Independent today, much of the genetic variation between individuals can best be explained by the presence of multiple copies of certain key genes rather than variations in the genome sequence.

The research suggests that whereas previously we thought all people shared 99.9% of their DNA, it could be that two individuals can differ by ten times that. The research has important implications for our understanding of inherited traits and genetic disease.

The findings appear in three simultaneous papers in three leading science journals, including Nature and were reported by teams from thirteen different research centres in the UK and the US.

Brainy pictures

It always surprises me what visitors to the site are searching for when they hit these pages. A common search this month is for brain pictures. Now, from the search keywords it’s not possible to tell whether it’s a photo of the brain, an MRI scan, or a schematic that the searchers are looking for. So, to cover all bases, here are a few links that might help:

All these images are hosted under the US government domain (.gov) and so should be copyright free, but don’t take my word for it if you plan to use them in your science project or for anything other than personal use. Google Images, of course, would have been my first port of call for finding brain pictures.

Rare cattle and human hybrids

Human cattle hybridIs it just me or is there a certain irony to be found in the timing of a rare cattle and other animal breeds conservation initiative being announced in the UK and stem cell researchers at Newcastle University requesting authorisation to hybridize nuclear-free eggs from cows with a human skin cell nucleus?

Ironic or not, both are issues that will inevitably attract great controversy over coming days.

The rare breeds initiative will build a database of livestock breeds across the UK to help. Announcing the launch of this genetic “Noah’s Ark”, the Department for Environment, Food and Rural Affairs sets out recommendations for how the industry and Government can improve and maintain the diversity of the UK’s livestock genetic material in the future. Among its detailed recommendations are the maintenance of an advisory body that better informs the public, industry and policymakers on the country’s farm animal breeds, the collection of high-quality information on genetic resources to provide effective ways for their future use, and support for the prioritisation, development and implementation of projects to conserve genetic diversity.

‘This plan is important economically, socially and culturally,’ says Food and Farming Minister Jeff Rooker, ‘We have a fine tradition in this country of breeding a diverse range of farm animals which in many cases can be found across the world.

‘However, there are growing concerns over genetic diversity as growing economic pressures have lead to a few specialised breeds spreading across the globe. The threat of exotic diseases is also a threat to diversity in some breeds.”

On the same day, scientists at the University of Newcastle upon Tyne sought regulatory approval to fuse an egg from a cow that has had its nucleus removed, with the nucleus of a human tissue cell, from skin for instance. The resulting hybrid, which would essentially be 99.9% human with only a tiny amount of mitochondrial DNA from the cow remaining. The egg could then be cultured and stem cells that are human to all intents and purposes, harvested from the growing chimera. The hybrid embryo would, the researchers say, be destroyed once the stem cells were collected.

They point out that human eggs are a precious and scarce a commodity, whereas there is a glut of cow eggs. Cow eggs are also a lot easier to handle than the eggs from the conventional source of laboratory test eggs, the mouse.

The UK’s Human Fertilisation and Embryology Authority (HFEA) is yet to grant permission although teams at Edinburgh University and King’s College London are also seeking approval for similar research.

The aim of creating such a human-cow hybrid is to develop the techniques that will eventually be used to create 100% human stem cells in the laboratory without having to expend years of human eggs honing the necessary skills that will ultimately make stem cell production routing.

Both strands of research, the genetic conservation program and the human-cow hybrid are already provoking a reaction from those who consider such efforts a violation of animal rights, another example of human exploitation of animals, and the lobbyists who want an outright ban on stem cell research.

Stephen Minger of King’s College London told journalists that, “We feel that the development of disease-specific human embryonic stem cell lines from individuals suffering from genetic forms of neurodegenerative disorders will stimulate both basic research and the development of new medicines to treat these horrific brain diseases.”

PS Before anyone says, yes, I know it’s a picture of a bullock not a cow and that, yes, you’d be hard pushed to extract cattle eggs from him, hybridised or not!

Male pill

Despite Carl Djerassi’s prediction (some years ago) that we would never see a “male pill”, it looks like just such a contraceptive treat is coming at last.

The new drug, Adjudin, is currently in early clinical trials and is a long way from human use. However, the very fact that drug companies are taking a male oral contraceptive seriously suggests a sea change iin attitudes. It’s not ten years ago that I heard Djerassi speak on this very subject and point out how the likelihood of a chemical contraceptive for men would never arrive.

Apparently, Adjudin triggers re-absorption of immature sperm cells so that they never reach the seminal point of no return infamously faced by Woody Allen in his notorious tale of sex. Chuen-yan Cheng of the Population Council’s Center for Biomedical Research in New York has tested the drug on lab rats and found there to be no obvious side effects other than that the males became infertile. Imporantly, the process is entirely temporary and just 20 weeks off the pill gets the sperm fighting fit once more.

Already, the concept of such a contraceptive has those opposed to any form of contraception chomping at the bit and arguing as to whether such a form of contraceptive contravenes religious doctrine or not. When one considers every sperm as sacred, biblically speaking, then are these immature fledgling sperm being “wasted” or not?

Of course, there are much more serious issues to consider, such as sexual health.

Over on Digg, a comment from “mizzack” in response to the CBS News article on this drug announcement goes like this:

Guy: “Hey, wanna go back to my place?”
Girl: “Sure”
[back at the house]
Girl: “Do you have condoms?”
Guy: “Oh, no, don’t need ’em. I’m on the pill”
Girl: “Riggggggght. Do you have condoms?”

Perhaps even more important than putative problems couples may face in the distant future should this male pill ever reach market is the fact that Cheng’s team previously reported that animal tests had shown Adjudin, to be toxic when given orally, causing liver problems and muscle wasting. Not exactly two happy things to happen to a guy. In the current trial, Adjudin has been conjugated with follicle-stimulating hormone to purportedly preclude such toxicity. It worked but only when the conjugate was administered intravenously.

So, the choice would be muscle wasting, which may or may not reduce your chance of a date, liver damage or regular injections into the belly to keep babies at bay, the need for a hormone adjuvant, and no intrinsic protection from HIV, chlamydia, syphyllis, gonnorhea, and any of several other STDs.

So, perhaps Djerassi was right after all and we may never see a marketable male pill. Caps off to the father of the pill.