WEIGHT LOSS compass

Khoury had always been a big bloke who liked his fast food.

When his family bought a takeaway pizza business, it was like handing the keys to a Maserati to an impetuous P-plater. He regularly ate three pizzas a day and had a similar appetite for KFC. “I could eat three meals in one sitting, no problem at all,” he says. He could also put away the booze big time on nights out.

As time went on, his delivery- boy diet left him feeling increasingly lethargic. “I knew something was wrong when I started feeling tired during the day,” he says.

THE CHANCE

Khoury has a family history of heart disease, high cholesterol and type 2 diabetes. With that in mind, he visited the doctor, who confirmed his blood pressure was elevated. Khoury walked out of the clinic and straight to the gym, where he began by forcing out 90 minutes on the cross-trainer and walking laps of the pool.

The health scare also gave him the motivation he needed to curb his pizza and KFC binges, and he went from eating bacon and eggs for breakfast seven days a week to five. “I made small changes, as I thought they would be more likely to be long-lasting,” he says.

After a year, Khoury introduced light resistance training to his routine, before switching to high- intensity heavy lifting sessions once the weight started to come off. “I tried a lot of things, and if they didn’t work, I tinkered until I discovered what worked for me,” he says. “I found I needed weight training to burn fat.”

THE RESULT

Khoury lost 20 kilograms in the first 12 months and another 20kg the next, dropping from size 46 jeans to 34 in the process. These days, it’s salmon, poached eggs and mushrooms for breakfast, and lean protein and steamed vegies at lunch and dinner.

After changing his wardrobe once, Khoury now faces a new dilemma. With the switch to

weight training, he’s lost more than six centimetres from his waist and bulked up on top. “I’m starting to get the V-shape back and my shirts are getting tight around the arms,” he says.

Not surprisingly, he now has a can-do attitude. “When you drop a lot of weight, you approach life more head-on because you’ve come from so far back.”

THE ADVICE

You can do it. “Before I started training I couldn’t do a push-up. Now I’m doing 60.”

Look and learn. “Watch what other people are doing and what they’re eating,” says Khoury. “I’ve got a lot of tips and motivation over the years from randoms in the gym.”

DRILL TO YOUR CORE

Use timed circuit training to burn fat as you build your upper body

SURE, YOU COULD prep for a shirtless beach debut by working your upper back and core, but that may not burn the flab in front of those muscles. That’s what this workout can do. “Done as a timed circuit, these three exercises have a metabolic component that can help you grow lean,” says its creator, strength and conditioning coach Chris Bathke.

THE SQUAT SUPERCHARGED

SQUATS COME IN many variations, so how can you tell which one is right for you? We asked Dr Chris Proulx, professor of movement science at Westfield State University in the US, to help sort them out. Proulx and his students tested five different squats: the four freestanding versions shown here, plus one machine exercise. (See “What about Machines?”, below.) Volunteers performed the exercises standing on force platforms – hi-tech devices that measure the pressure exerted through a lifter’s feet. The researchers also attached electrodes to the volunteers’ legs to see how hard the moves made their quadriceps and hamstrings work. Their pain, your gain.

BEST FOR …

FUNCTIONAL LOWER-BODY
STRENGTH

Decades of sports
science have correlated
squat strength with
speed, power and athletic

performance. With the back
squat, you generate a lot of force
through your leg muscles – so,
with practice, you’ll be able to
squat a lot of weight.

AVOID IF …

you’ve had back pain or injury.
The bar on your shoulders
compresses your disks.

BEST FOR …

PURE STRENGTH AND
LOWER-BODY MUSCLE
DEVELOPMENT

The wide stance
brings your inner-thigh

muscles into the exercise,
allowing you to lift heavier
weights and build muscle
more quickly.

FRONT SQUAT

BEST FOR …

CORE STRENGTH AND LOWER- BODY MUSCLE DEVELOPMENT

By placing the bar on the front of your shoulders, you force your torso to stay upright. This requires and builds core strength and stability.

GET YOUR MOTOR RUNNING

Use V8 Supercar driver James Courtney’s workout
to rev up your metabolism, build core strength and

develop quick, oncoming-concrete-wall reactions

HOW FIT DO YOU need to be to triumph on the
race track? In a typical two-hour race, Holden
Racing Team driver James Courtney endures

cockpit temperatures of up to 60°C, maintains a
heart rate of 180 beats per minute and shifts a
25-kilogram gear stick while applying brake-pedal
force of up to 100kg. It’s no wonder Courtney’s
fitness was recently rated alongside elite
footballers’ by Exercise Research Australia.

“It’s like doing a CrossFit session in a sauna
with 28 guys throwing concrete blocks at you,”
says Courtney, who won the 2010 V8 Supercars
championship and will race in the upcoming
Sydney Telstra 500 (v8supercars.com.au).

In a typical training week Courtney cycles up to
400 kilometres and combines two weights circuits
with boxing and swim sessions, plus multiple
workouts on trainer Phil Young’s speed and
reaction apparatus, the BATAK machine.

Get cockpit cut with this circuit performed three
times a week. Repeat the circuit three times with
two minutes’ rest in-between.

nBALL BEARINGS

Throw a Super Reaction
Ball ($9.95; ausport.com.au)
into the air, let it fall and catch
on the first bounce. Repeat for
three minutes. Next, stand two
metres from a wall and throw

the ball against it and catch. Repeat
for three minutes, stepping closer to
the wall with each throw. “A good
alternative to the BATAK machine,”
says Young.

 

REAL DEAL WINS OUT

An online “affair” may give cheaters a thrill initially, but it appears it won’t scratch that itch forever, according to a study by the University of Nebraska and Washburn University.

Researchers surveyed 5187 users of infidelity website AshIeyMadison.com. They found that about two-thirds of adulterers hadchcated online (by sending explicit messages and images of themselves to another person), but more than three quarters had done so in real life. The respondents reported being more interested in finding real-life partners, for both dating and sexual encounters, than online-only partners.

The authors say it’s probably because, “ultimately, humans are social creatures”.

LISTEN TO YOUR HEART

We’ll say this loudly and slowly so you don’t miss it: high
cholcstcrol could hamper your hearing’.

Researchers from the University of Sydney looked at hearing
loss and dietary data for almost 3000 people over 50, and

found that those with a cholesterol intake of390 milligrams

a day (a large egg contains around 200mg) had a 33

per cent higher risk of hearing loss than those who

consumed 190mg.

While more research is needed, the study
recommends cutting back on cholesterol

and uppingyour intake of
monounsaturated fat, found
in vegetable oils, nuts,
seeds, olives and

avocados. Your
ticker will thank
you, too.

A mandarin a day may keep the heart doctor away. A study by Jichi Medical School found that people who ate citrus fruit nearly every day had a lower risk of cardiovascular disease than those who rarely did.

The high antioxidant levels in citrus may block the formation of free radicals and repair existing damage, according to the study. Try orange, mandarin or grapefruit sections in salad, or substitute diced citrus for tomatoes in salsa to use as a

2011 Best Method of the year

In our annual toast to biological research methods and to the scientists who develop them, we have chosen genome editing with engineered nucleases as our Method of the Year 2011.

Perhaps the most reliable way to learn about the function of a gene or protein is to specifically perturb it and monitor what happens. This reverse genetic approach is routinely applied in many species, but, with a few exceptions, it is challenging or even impossible to make targeted changes at endogenous genomic loci, arguably the most elegant method of genetic perturbation. Instead, the experimenter must settle for more indirect approaches: overexpressing the modified gene from a heterologous location or knocking it down, often only partially, with an approach such as RNA interference. Engineered nucleases—which can be designed, in principle, to cut at any location in the genome of any species and thus to introduce tailored modifications into the endogenous sequence—are set to change this. We provide a brief Primer on these tools on page 27.

From the perspective of methods development, the trajectory of the engineered nucleases has been a compelling one, as reported in a News Feature on page 23. All three major classes of these enzymes—zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered meganucleases—stand on the shoulders of very basic studies, a testament, yet again, to the necessity of basic research and the difficulty in predicting whence technological leaps will come. Engineering the first ZFN to modify an endogenous gene in an organism (the fruit fly, as it appositely turns out), required that three strands of knowledge, gained from many decades of research in many laboratories, be drawn together: how restriction endonucleases work, how DNA breaks are repaired by the cell and how DNA-binding proteins achieve specificity in the vastness of genomic sequence space.

This said, it has undoubtedly been the potential clinical utility of these tools—to correct mutations in monogenic human disease, for instance—that has primarily driven the intense effort put into developing them over the past decades. The fortuitous consequence, however, is that very powerful basic research tools have been generated in the process.

Engineered nucleases can be used to knock out or knock in genes, to make allelic mutants, to change gene-regulatory control and to add reporters or epitope tags, all in the endogenous genomic context. Matthew Porteus discusses these and other exciting research applications of these tools in a Commentary on page 28.

Although the first ZFN was reported more than a decade ago, the pace of work in this field has picked up remarkably in the past year. This is in no small part because of the development of TALENs. ZFNs remain the best-characterized tools, but they are not always easy to design, as Mark Isalan discusses in a Commentary on page 32. The recent discovery of TAL effectors in plant pathogenic bacteria and the realization that their properties—notably their apparently simpler DNA-binding code—should mitigate some of the existing problems with engineering robust tools, has given a real boost to the field. Gene-editing nucleases will achieve their full potential when they can be easily and quickly designed, in practice, to specifically modify any sequence of any genome; having more than one technology available will help achieve this goal.

In addition, commercially available ZFNs are dropping in price at the same time as methods developers are assembling tools to help researchers design their own nucleases. Meanwhile, TALENs and engineered meganucleases are also already commercially available. Which technology will dominate is not yet clear: there are still many unknowns, in particular about TALEN function as discussed in several of the pieces in this issue. But the price at which researchers in regular research labs can obtain good tools is likely to play a role.

You can also hear about genome editing with engineered nucleases in a short video, and we include in this issue, as in previous years, a section of Methods to Watch in the future (p. 35).

To all our readers, a happy, successful 2012!