New View Of Human Nerve Cells Opens Door To Potential Drug Targets

ScienceDaily (Dec. 9, 2008) — VIB researchers connected to the Katholieke Universiteit Leuven have discovered an important new mechanism with which cells can detect nutrients. This happens in the same way - and with the same effects – as when cells receive a message from a hormone. This finding can teach us more about how food affects our body; and, furthermore, it can form the basis for new candidate targets for medicines.

By applying the new method to a type of nerve cell critical to regulating body temperature, the authors found more than 400 "receptors" (structures that bind other molecules, triggering some effect on the cell) responding to neurotransmitters, hormones, and other chemical signals. This represents 20 to 30 times more receptors than previous studies had identified.

The technique, described in detail in a review article in the March 11, 2011 issue of the journal Pharmacology and Therapeutics, may be applied to finding "hidden" receptors in other types of nerve cells, expanding the repertoire of potential drug targets for diseases ranging from schizophrenia to Parkinson's disease.

"This technique will enable people to uncover many more drug targets," said Tamas Bartfai, chair of the Department of Molecular and Integrative Neuroscience at Scripps Research. "That may be a game changer for some diseases."

Uncovering Rare Receptors

Receptors found on cells are among the most important targets for the development of drugs because of the key roles they play in the communication circuits regulating various body functions. So far scientists have identified only a few of the receptors present on different types of nerve cells.

Bartfai's group has long been interested in a class of nerve cells in the brain called "warm sensitive neurons." These cells sense and respond to changes in body temperature, acting like a thermometer inside the brain. As body temperature increases, warm sensitive neurons become more active, telling the body to bring its temperature down. Without this regulation, body temperature could reach dangerous levels, even leading to death.

In the past 60 years, scientists had identified about a dozen receptors on warm sensitive neurons that regulate these nerve cells' activity. But Bartfai wanted to find additional receptors to better understand how the cells function.

To do so, he turned to long-time collaborator University of Pennsylvania Professor James Eberwine. Eberwine had pioneered a number of techniques to identify genes active in individual cells.

Sequencing Single Neurons

Bartfai and Eberwine took a unique approach to indentifying gene activity.

Scientists know a gene is "on" in a cell if its messenger RNA (which carries information from genes to sites of protein synthesis) is present. To study gene activity in warm sensitive cells, Eberwine and Bartfai isolated single cells and extracted their RNA. They then made cDNA copies of the messenger RNAs and determined the sequence of the nucleotide bases (adenine, guanine, cytosine, and thymine) in each cDNA molecule.

By matching the DNA sequences obtained to published sequences, the scientists were able to identify the corresponding genes, and thus which genes are turned "on" in the nerve cells.

The technique differs from commonly used methods for studying gene activity. Typically researchers "pool" neurons of one type and examine them as a group, rather than studying single cells. In addition, current techniques generally rely on searching for active genes using microarrays -- a technique that relies on the preferential binding of sequences in the messenger RNAs /cDNAs to matching DNA sequences "spotted" on the microarray. However, these methods only detect RNAs for which "probes are present on the microarray," in other words, those that are expected. Also, because of the lower sensitivity of this technique than sequencing, only the cDNAs cells produce in relatively large amounts are detected.

"Using single cells, rather than pooling, and sequencing, rather than microarrays, uncovers many more receptors active in neurons," says Bartfai. "With other methods you miss receptors present in only a few copies. But that does not mean that they are not important."

Revealing Neurons' Complexity

Using their new method Bartfai and Eberwine identified more than 400 receptors active in warm sensitive neurons. About one-third of the receptors are so-called "orphan" receptors, meaning the chemicals they bind to are unknown. The rest were receptors whose ligands (substances they bind to) are known -- among them, the authors found a few surprises.

For example, Bartfai and Eberwine discovered that the receptor responsible for binding insulin is active on warm sensitive neurons -- something no one had previously suspected.

The insulin receptor is known to be involved in regulating a person's metabolism. Follow-up studies by Bartfai's group have now shown that insulin binds to receptors on warm sensitive neurons to decrease their activity, causing an increase in body temperature, or hyperthermia. Thus, insulin is a key regulator for both body metabolism and temperature.

"This study highlights the complexity of these cells by showing us the large number of different RNAs that are present," said Eberwine.

Game-Changing Research

In addition to providing important insights into the complexity of nerve cells, the study has implications for identifying potential drug targets for diseases that currently have few or no treatments.

"We would like to repeat similar studies for key neurons involved in Parkinson's disease and schizophrenia," explained Bartfai. "If we again discover 400 receptors, we could then ask which ones are reasonably selectively expressed in these neurons." Any receptor active primarily in one class of neurons involved in a particular disease process represents a possible target for developing drugs to affect the course of that disease.

Research for the study was supported by the Harold L. Dorris Neurological Research Institute and the Skaggs Institute of Chemical Biology at Scripps Research, the National Institutes of Health, National Alliance for Research on Schizophrenia and Depression, and The Commonwealth of Pennsylvania.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by The Scripps Research Institute.

Near-Real-Time Map Of Japan Quake Aftershocks

Screenshot of map of near-real-time aftershocks from the Japan quake. (Credit: Image courtesy of Texas Tech)

ScienceDaily (Mar. 11, 2011) — Researchers at Texas Tech's Center for Geospatial Technologies have created a near-real-time map of the aftershocks occurring globally following the 8.9 magnitude earthquake that rocked Japan Friday.

Kevin Mulligan, director of the center, said the map was developed today following a lack of new information presented on major news outlets. The map connects to near-real-time remote feeds from the United States Geological Survey's Earthquake Hazards Center and the National Oceanic and Atmospheric Administration's Tsunami Warning Center.

"This map is a dynamic map surface that shows the distribution of recent earthquakes from a USGS live remote feed," Mulligan said.

"It provides map information, satellite imagery and location of recent earthquakes. As part of this major earthquake, there are hundreds of aftershocks that follow."

The map site can be viewed at mapserver.gis.ttu.edu/japanquake/.

For more on the Center for Geospatial Technology, visit www.gis.ttu.edu/center/.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Texas Tech. The original article was written by John Davis.

Large Earthquake Hits Chile, Generates Tsunami Across Pacific

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Shakemap of the Feb. 27, 2010 earthquake that struck off the coast of Chile. (Credit: Image courtesy of USGS)

ScienceDaily (Feb. 27, 2010) — An 8.8 magnitude earthquake struck off the coast of central Chile early morning on Saturday, February 27, 2010 at 3:34 a.m. local time, about 200 miles southwest of the Chilean capital of Santiago, killing several hundred people and exposing millions of people to strong shaking that toppled many buildings.

Tsunami warnings were issued for Hawaii, as well as Australia, New Zealand, Indonesia, Japan, and other countries along the Pacific coastline, as the giant waves triggered by the earthquake reverberated through the entire ocean.

This earthquake occurred at the boundary between the Nazca and South American tectonic plates. The two plates are converging at a rate of 80 mm per year. The earthquake occurred as thrust-faulting on the interface between the two plates, with the Nazca plate moving down and landward below the South American plate.

Coastal Chile has a history of very large earthquakes. Since 1973, there have been 13 events of magnitude 7.0 or greater. The February 27 shock originated about 230 km north of the source region of the magnitude 9.5 earthquake of May, 1960 -- the largest earthquake worldwide in the last 200 years or more. This giant earthquake spawned a tsunami that engulfed the Pacific Ocean. An estimated 1600 lives were lost to the 1960 earthquake and tsunami in Chile, and the 1960 tsunami took another 200 lives among Japan, Hawaii, and the Philippines.

Approximately 870 km to the north of the February 27 earthquake is the source region of the magnitude 8.5 earthquake of November, 1922. This great quake significantly impacted central Chile, killing several hundred people and causing severe property damage. The 1922 quake generated a 9-meter local tsunami that inundated the Chile coast near the town of Coquimbo; the tsunami also crossed the Pacific, washing away boats in Hilo harbor, Hawaii.

The magnitude 8.8 earthquake of February 27, 2010 ruptured the portion of the South American subduction zone separating these two massive historical earthquakes.

A large vigorous aftershock sequence can be expected from this earthquake.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by U.S. Geological Survey/Earthquake Hazards Program.

Pacific Northwest Faces Nearly Identical Risks To Japanese Quake

ScienceDaily (Mar. 11, 2011) — It's being called one of the largest recorded earthquakes in world history. Also, according to Robert Yeats, "This is our wake up call."

Japan today is struggling with the aftermath of a massive 8.9 earthquake on a subduction zone, a short distance offshore, which unleashed a devastating tsunami that killed hundreds and has turned large parts of cities into rubble.

Yeats, a professor emeritus of geology at Oregon State University, said that if people didn't already get the message from recent disasters in Sumatra and Chile, they should pay attention now.

"This is an earthquake of the same type, with about the same magnitude and proximity that we face here in the Pacific Northwest from the Cascadia Subduction Zone," Yeats said. "What you are seeing in Japan today is what you will also see in our future. Except they are better prepared than we are."

One of the world's leading experts on the Cascadia Subduction Zone, OSU marine geologist Chris Goldfinger, got an up-close, personal preview of the forces he's been studying -- he was in Tokyo when the earthquake hit, ironically attending a meeting on the Sumatra earthquake.

"I'm in the northern outskirts of Tokyo and rode through the quake and continuous aftershocks ever since," said Goldfinger, a professor in OSU's College of Oceanic and Atmospheric Sciences. "The main shock lasted an entire five minutes. We were in the middle of a talk and just bailed and went outside. Here in Chiba, you could literally feel the plates grinding; the high-frequency P-wave arrival was like nothing I've ever felt.

"Then five minutes of S-waves and feeling sort of seasick," he added. "There hasn't been too much damage in Tokyo that I've seen, but watching the tsunami come in live on television in Sendai and Iwaki -- with ships washing into the town -- was amazing."

Despite the tragic loss of life and billions of dollars in damage that will result from the Japanese earthquake, Yeats said, they are as or better prepared for a disaster such as this as anyone in the world. Their technology, building codes, public education and other programs for earthquake preparation are exemplary, with scientific initiatives that date back to the 1890s.

And even though it may seem like there has been an unusually large number of earthquake disasters in recent years, Yeats said, the past decade or so doesn't really stand out all that much in a historic sense.

"It's not completely regular, there are a few clusters of disasters at some times more than others," Yeats said. "But the real message here is that the Earth is very active and sometimes violent, it always has been and always will be. We can't predict these events so we have to prepare for them."

Harry Yeh, a professor of engineering at OSU and an internationally recognized expert on tsunami propagation, also watched the events unfold on television -- with an eye toward the potential of "vertical evacuation" in coastal cities.

"It's too early to tell if vertical evacuation on a large scale would be effective in a massive earthquake such as this, though I did see many people evacuated to the top of buildings -- for example, Sendai Airport and some school buildings," Yeh said. "Japanese television repeatedly mentioned the idea and led people to evacuate to strong concrete buildings on the third floor or higher."

OSU experts have worked closely with officials in Cannon Beach, Ore., in an initiative to build what would be the nation's first structure designed specifically to resist tsunami wave forces and save lives through this concept of "vertical evacuation." Those efforts are ongoing.

Meanwhile, experts at OSU and across the Pacific Northwest are continuing to learn what they can from each disaster of this type to gain insights that might one day help save lives here.

"This is a good rehearsal for us," said Solomon Yim, a professor of ocean engineering at OSU and director of the university's Hinsdale Wave Research Laboratory, which includes one of the world's most sophisticated wave basins specifically designed to study tsunamis. "The take home message is that what just happened in Japan is going to happen here. It's just devastating.

"The forces you're seeing in Japan are similar to what happened in Indonesia," Yim said. "You saw cars and boats and debris slamming into structures and bridges, those are the types of forces we need to learn more about in building tsunami resistant structures."

Improvements in understanding subsea bathymetry would be helpful, OSU experts said, as well as how wave forces will translate into onshore runup once they hit land. More work with public outreach and ocean mapping are also needed, they said.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Oregon State University.

Keys To Long Life? Not What You Might Expect

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People working. "Don't work too hard, don't stress," doesn't work as advice for good health and long life. Subjects who were the most involved and committed to their jobs did the best. Continually productive men and women lived much longer than their more laid-back comrades. (Credit: iStockphoto/Daniel Laflor)

ScienceDaily (Mar. 12, 2011) — Cheer up. Stop worrying. Don't work so hard. Good advice for a long life? As it turns out, no. In a groundbreaking study of personality as a predictor of longevity, University of California, Riverside researchers found just the opposite.

"It's surprising just how often common assumptions -- by both scientists and the media -- are wrong," said Howard S. Friedman, distinguished professor of psychology who led the 20-year study.

Friedman and Leslie R. Martin , a 1996 UCR alumna (Ph.D.) and staff researchers, have published those findings in "The Longevity Project: Surprising Discoveries for Health and Long Life from the Landmark Eight-Decade Study" (Hudson Street Press, March 2011).

Friedman and Martin examined, refined and supplemented data gathered by the late Stanford University psychologist Louis Terman and subsequent researchers on more than 1,500 bright children who were about 10 years old when they were first studied in 1921. "Probably our most amazing finding was that personality characteristics and social relations from childhood can predict one's risk of dying decades later," Friedman concluded.

The Longevity Project, as the study became known, followed the children through their lives, collecting information that included family histories and relationships, teacher and parent ratings of personality, hobbies, pet ownership, job success, education levels, military service and numerous other details.

"When we started, we were frustrated with the state of research about individual differences, stress, health and longevity," Friedman recalled. "It was clear that some people were more prone to disease, took longer to recover, or died sooner, while others of the same age were able to thrive. All sorts of explanations were being proposed -- anxiety, lack of exercise, nerve-racking careers, risk-taking, lack of religion, unsociability, disintegrating social groups, pessimism, poor access to medical care, and Type A behavior patterns." But none were well-studied over the long term. That is, none followed people step-by-step throughout their lives.

When Friedman and Martin began their research in 1991, they planned to spend six months examining predictors of health and longevity among the Terman participants.

But the project continued over the next two decades -- funded in part by the National Institute on Aging -- and the team eventually involved more than 100 graduate and undergraduate students who tracked down death certificates, evaluated interviews, and analyzed tens of thousands of pages of information about the Terman participants through the years.

"We came to a new understanding about happiness and health," said Martin, now a psychology professor at La Sierra University in Riverside. "One of the findings that really astounds people, including us, is that the Longevity Project participants who were the most cheerful and had the best sense of humor as kids lived shorter lives, on average, than those who were less cheerful and joking. It was the most prudent and persistent individuals who stayed healthiest and lived the longest."

Part of the explanation lies in health behaviors -- the cheerful, happy-go-lucky kids tended to take more risks with their health across the years, Friedman noted. While an optimistic approach can be helpful in a crisis, "we found that as a general life-orientation, too much of a sense that 'everything will be just fine' can be dangerous because it can lead one to be careless about things that are important to health and long life. Prudence and persistence, however, led to a lot of important benefits for many years. It turns out that happiness is not a root cause of good health. Instead, happiness and health go together because they have common roots."

Many of the UCR findings fly in the face of conventional wisdom. For example:

• Marriage may be good for men's health, but doesn't really matter for women. Steadily married men -- those who remained in long-term marriages -- were likely to live to age 70 and beyond; fewer than one-third of divorced men were likely to live to 70; and men who never married outlived those who remarried and significantly outlived those who divorced -- but they did not live as long as married men.
• Being divorced is much less harmful to women's health. Women who divorced and did not remarry lived nearly as long as those who were steadily married.
• "Don't work too hard, don't stress," doesn't work as advice for good health and long life. Terman subjects who were the most involved and committed to their jobs did the best. Continually productive men and women lived much longer than their more laid-back comrades.
• Starting formal schooling too early -- being in first grade before age 6 -- is a risk factor for earlier mortality. Having sufficient playtime and being able to relate to classmates is very important for children.
• Playing with pets is not associated with longer life. Pets may sometimes improve well-being, but they are not a substitute for friends.
• Combat veterans are less likely to live long lives, but surprisingly the psychological stress of war itself is not necessarily a major health threat. Rather, it is a cascade of unhealthy patterns that sometimes follows. Those who find meaning in a traumatic experience and are able to reestablish a sense of security about the world are usually the ones who return to a healthy pathway.
• People who feel loved and cared for report a better sense of well-being, but it doesn't help them live longer. The clearest health benefit of social relationships comes from being involved with and helping others. The groups you associate with often determine the type of person you become -- healthy or unhealthy.

It's never too late to choose a healthier path, Friedman and Martin said. The first step is to throw away the lists and stop worrying about worrying.

"Some of the minutiae of what people think will help us lead long, healthy lives, such as worrying about the ratio of omega-6 to omega-3 fatty acids in the foods we eat, actually are red herrings, distracting us from the major pathways," Friedman said. "When we recognize the long-term healthy and unhealthy patterns in ourselves, we can begin to maximize the healthy patterns."

"Thinking of making changes as taking 'steps' is a great strategy," Martin advised. "You can't change major things about yourself overnight. But making small changes, and repeating those steps, can eventually create that path to longer life."

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of California - Riverside.

Food Can Affect A Cell In The Same Way Hormones Do

ScienceDaily (Dec. 9, 2008) — VIB researchers connected to the Katholieke Universiteit Leuven have discovered an important new mechanism with which cells can detect nutrients. This happens in the same way - and with the same effects – as when cells receive a message from a hormone. This finding can teach us more about how food affects our body; and, furthermore, it can form the basis for new candidate targets for medicines.

Receptors

Every living thing is composed of cells - and, via receptor proteins on their outer surface, cells communicate with each other and with the outside world. Receptors are found on skin cells (pain and pressure receptors, for example) as well as on the cells of other tissues and organs. By binding with certain substances, such as hormones, the receptors pick up signals from outside the cell. They transmit the signal to the interior of the cell, where it can induce all kinds of reactions. Receptors can be stimulated or blocked to evoke or prevent a certain effect. Foreign substances, such as medicines, can also bind to a receptor and cause a particular effect. For some time now, scientists have suspected that cells can also detect the presence of food via one or another receptor - but no one has known how that happens.

Sensing and transporting

In addition to receptors, cells also have transport proteins that can carry nutrients through the cell membrane to the inside of the cell, where they can be put to use. Furthermore so-called 'transceptors' have been discovered that sense and transport food simultaneously.

Now, VIB researcher Griet Van Zeebroeck and her colleagues in Johan Thevelein's group have shown for the first time how one of these transceptors (called Gap1) works. Gap1 transports amino acids (a protein's building blocks) to the inside of a cell. At the same time, via the same mechanisms that cells use to transmit signals from hormones, Gap1 sends the cell a signal that food is present. The transceptor apparently uses the same binding site to recognize the food as it uses to grasp the food for transport.

Yeast vs. humans

This research has been conducted on yeast cells, as yeast (Saccharomyces cerevisiae) is a micro-organism that is used as a model organism. Yeast cells are surprisingly similar to human cells, but they are easier to cultivate and manipulate. Very often, proteins that are found in yeast - transport proteins and receptors, for example - have similar variants in human cells.

Importance of this research

This research can have important implications for the development of medicines. About half of all medicines are transmitted to cells via receptors, because receptors are located on the cells' exterior surface and are therefore the best targets for medicines. If these newly discovered transceptors are also found in humans, then an unexpected new group of candidate targets for medicines becomes available - offering promising possibilities for the treatment of metabolic diseases.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by VIB (the Flanders Institute For Biotechnology), via AlphaGalileo.

Thrill-Seeking Females Work Hard For Their Next Fix, Rat Study Suggests

ScienceDaily (Mar. 10, 2011) — It seems that women become addicted to cocaine more easily than men and find it harder to give up. New research published in BioMed Central's open access journal Biology of Sex Differences reinforces this position by showing that the motivation of female rats to work for cocaine is much higher than males.

Researchers from the Molecular and Behavioral Neuroscience Institute, University of Michigan, found that rats bred to have an elevated stress response and increased impulsiveness are more easily trained to reward themselves with cocaine. They are also more determined, than similar rats with low impulsivity and lower stress responses, in pursuit of their next fix.

While cocaine dependency has something to do with thrill seeking and impulsivity, it is also affected by the differences between males and females. At a low dose, for both sets of rats, it was the females who were quickest to learn self-administration and were the most willing to work harder for their next fix. At higher doses, the differences in behaviour between the male and female rats were less apparent.

Whilst certain personality types are perhaps predisposed towards drug addiction Dr Jennifer Cummings explained, "An individual's sex continues to increase the likelihood of drug abuse."

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by BioMed Central, via EurekAlert!, a service of AAAS.

Reroute Your Career

Use Current Knowledge and Expertise to Take Your Career on a 'Detour'

If your career prospects have stalled or you've lost your passion for your work, you might not need to make a radical change to new industry. You may be able to take an alternative route in your current career -- by using your industry expertise in a new way, advises career expert and author Laurence Shatkin. "In almost any industry where you have an insider's knowledge, you can make a change within that field and maybe earn more," he says.

If want to reroute your career, you could:

Teach It

Teachers are everywhere -- in schools, colleges and all types of companies. Larger corporations use trainers to instruct employees in company procedures, benefits and software use. Being able to conduct distance learning or other kinds of online instruction may make you especially marketable. You'll likely need some sort of teaching experience, whether one-on-one, in a classroom or in a seminar. In some training careers, additional coursework and certification are necessary.

For example, a sales manager could become a sales-training manager, or a software-development manager could become an IT trainer.

Advocate It

Activists, trade organizers and lobbyists are all advocates. You can find these opportunities with public-relations firms, trade organizations, unions and special-interest groups. Public-service jobs for consumer advocates are available at all levels of government, from federal to municipal. An assertive personality helps, and industry expertise is often more important than a specific college degree. To gain experience and visibility, start by volunteering with a citizens' group or a nonprofit consumer organization.

For example, a malpractice attorney could become a healthcare lobbyist, or a food-industry sales manager could become a food-safety expert.

Communicate It

There are many opportunities to communicate what you know. For instance, technical writing is a growing and lucrative field for professionals in fields such as software development, computer-systems design and engineering. Insiders in a variety of industries could write about it for advertising agencies or as nonfiction authors. Beef up your writing skills with a class or two, and gain experience by volunteering to write for industry newsletters. Or start a blog (but post news about your industry, not about your cat).

For example, a computer programmer could become a software-documentation writer, or a financial planner could become a financial reporter.

Sell It

If you have a strong understanding of your industry, there may be something you could sell. If you don't think you're the "selling type," look for opportunities to be a broker, bringing buyers and sellers together. Sales jobs usually don't require specific college degrees (although some industries require licenses). More important are persuasiveness and persistence. Some experience with sales, as well as a thick skin and a gregarious personality, will also help.

For instance, an insurance-claims adjuster could become an insurance broker, or a retail-industry marketing manager could become a sales manager.

Analyze It

Federal and state governments, large universities and major industries have think tanks employing a variety of policy analysts in a wide range of topics, such as public health, education and water rights, just to name a few. For-profit companies need a variety of analysts to forecast budgets, assess risks and project changes in the industry. Extensive experience in some aspect of your field and a related (usually advanced) degree are required. Experience in conducting research or writing and presenting reports is helpful.

For instance, a tax accountant could become a corporate analyst, or a hospital administrator could become a disease-prevention policy analyst.

Preparing to Take a Detour

Making a career change within the same industry may be easier than starting a new career, but it does require some homework. Experts suggest several ways to prepare:

• Gain Experience Now: "Experience can come not only from paid work, but also from hobbies, volunteering and independent consulting, so it's important to actually do what you're wanting to do before you take the career side step," says career coach Deborah Brown-Volkman.
   
• Get Training: This doesn't necessarily mean an extra degree or even a year of classroom time. It could mean a one-day sales seminar or an evening writing class.
   
• Tailor Your Resume: Brown-Volkman says that professionals must use their resume to demonstrate that they can do the job they want to have. "If a recruiter, for example, wants to shift to training, maybe he or she has done some teaching already, such as a seminar or informal training of associates" she says. "It's all valid."
   
• Start Where You Work: If you have a job, the easiest way to take a new route is to do so within your own company, according to Shatkin. "The people already know you and presumably like you," he says. "If there is a need for someone in the position you want, they may even train you to do it on their dime."

When you're taking your career in a new direction, the key is flexibility and creative thinking, Shatkin says. "If there's a need for your expertise, there's a career for you -- even if you have to design your own career," he says.

By Larry Buhl, for Yahoo! HotJobs / Thanks to Career-Advice.Monster

Overqualified? Six Tips To Shed The Label

In a tight job market, mid- and late-career professionals often consider openings that are less lucrative and less prestigious than their last job. Sometimes employers are glad to hire seasoned workers at a bargain, but others dismiss the candidate as overqualified.

What's behind the overqualified label is an employer's fear that if you're hired, you'll be searching for a better job before you learn where the restrooms are. But if you really want the job, there are ways of countering the perception that you're too good for it.

Reread the Job Description

Just because you earned more and had more responsibility in the past doesn't mean you're overqualified for this job. If you meet or exceed every criterion, consider yourself highly qualified. On the other hand, if you don't meet all the requirements -- you would be using a new technology you've never heard of, for example -- you may actually be underqualified.

"Too many job seekers think, 'If I can do this big thing, then surely I can do those smaller things,'" says Laura DeCarlo of Career Directors International. "Maybe they can do them, but it will be a tougher sell."

Fine-Tune Your Resume

"A resume is not a document set in stone," says John M. O'Connor, president of Career Pro. "You should always rewrite your resume to fit that particular job, and that may mean taking down the tone a notch and emphasizing exactly the skills needed in the new job." To tune your resume and cover letter, also consider the company culture and include relevant words, phrases and technologies, O'Connor adds.

Don't Lie About Your History

It's true that some screeners go right to the salary to weed out the too-expensive candidates. If you were an executive earning six figures, don't say you were a junior accountant earning $40,000. Then again, unless you're filling out an online form that requires your salary history, a sin of omission just to get in the door is fine.

Experts recommend addressing salary in a cover letter or interview by giving a wide range of income you would consider, or by saying you assume the company will pay competitive salary for the job.

"You want to steer the conversation to the tasks of the job and your history of longevity in other companies and away from dollar figures," says Barbara Safani, president of Career Solvers. "If you can explain how previous lateral moves benefited you, that can diffuse their fear you'll be looking for a higher-paying job."

Check Your Sense of Entitlement at the Door

Are you miffed at applying for a job "beneath" your abilities or ticked at defending a career that began when the interviewer was in diapers? Those attitudes won't do you any favors.

"People read energy and attitude," O'Connor says. One way to turn around your negative attitude and impress the interviewer at the same time, O'Connor recommends, is to come prepared with incisive questions about the job duties and the company. "Show you are in touch and engaged and understand their needs," he says.

Clearly Explain Why the Job Will Be Good for You

"If you hire me now, I won't lose my house" may be true, but it won't impress an interviewer. Have good reasons the job would benefit you personally and professionally. "If the position is in your area of passion, say so," DeCarlo advises. "You can make the case that even though you had a management job, for example, you want to move away from management. If the job is a good career fit, the employer will be much more impressed."

Make Circumstantial Evidence Work for You

Remember, the employer is looking for a good fit, and that means cultural and personal fit in addition to hard skills. Do you have volunteer experience or community commitments that would interest a hiring manager at a young, hip company? Emphasize them.

Likewise, your network can speak volumes for your ability to fit in. But make sure those contacts are recent, O'Connor says. Referrals from people who haven't seen you in 20 years could give the impression your most productive days are behind you.

What about the age issue? Career coaches admit age discrimination exists, but it may not be as widespread as seasoned job seekers believe. An updated wardrobe, newer hairstyle or current cultural references could hedge against ageism, or they could make you look silly. Experts agree that the best way to impress a hiring manager is showing how well you understand her immediate problem and how you're the solution.

That's true for job seekers at any stage of their careers.

By Larry Buhl, for Yahoo! HotJobs / Thanks to Career-Advice.Monster

50 Stunning Pictures Of The Japan Earthquake And Tsunami

1.

A small boat gets stuck in a tsunami whirlpool.

2.

A person on the third floor of a Japanese airport photographs damage and debris.

3.

An explosion at an oil refinery after the earthquake.

4.

Cars and other debris swept away by tsunami tidal waves are seen in Kesennuma in Miyagi Prefecture, northern Japan.

5.

Residents look at a massive crack in the ground.

6.

Japan's Prime Minister Naoto Kan reacts after he feels the earthquake during a committee meeting in parliament in Tokyo.

7.

Houses are swept by a tsunami in Natori City.

8.

A tsunami carries buildings across waters in Kamaishi city port.

9.

Houses swallowed by the tsunami burn in Sendai, Miyagi.

10.

People watch the aftermath of the tsunami tides from a bridge.

11.

Waves of tsunami topple trees.

12.

Light planes and vehicles mashed together.

13.

Houses, cars and other debris are washed away by tsunami tidal waves in Kesennuma in Miyagi Prefecture, northern Japan.

14.

Ships and boats are washed ashore in Hachinohe, Aomori Prefectur, Japan.

15.

A close-up of the last picture.

16.

Houses are swept out to burn at sea.

17.

The tsunami goes over an inter-coastal canal.

18.

Sludge from the tsunami creeps inland.

19.

Two men look at smoke rising over the Tokyo skyline after the earthquake struck.

20.

Cars collide with storage crates.

21.

Vehicles are crushed by a collapsed wall at a carpark in Mito City.

22.

Collapsed tombstones on a hill in Kure, Japan.

23.

Oarai town submerged in water and debris.

24.

A man wades through a flooded street.

25.

Fire smokes billow from residences.

26.

Parts of a beer factory's facilities are collapsed as the employees gather on the rooftops.

27.

Residents walk through rubble.

28.

A wave from the tsunami heads to the coast in Miyagi Prefecture on the north east coast of Japan.

29.

Smokes rise from houses in Soma, Fukushima, northern Japan.

30.

A tsunami surge carrying debris sweeps between houses to reach poly tunnels on farmland near Sendai in Miyagi Prefecture Japan.

31.

A tsunami surge throws boats against a building in Hachinoche, Aomori Prefecture, Japan.

32.

A tsunami surge sweeps boats, cars and other debris over a highway in the Sendai City area.

33.

Water surrounds the airport building at Sendai Airport.

34.

Houses, cars and debris are swept towards a highway.

35.

A wave from the tsunami heads to the coast in Miyagi Prefecture.

36.

A wave from the tsunami sweeps boats inland.

37.

Boats are swept by a wave after a tsunami and earthquake in Asahikawa city.

38.

Cars are washed away in a coastal area of Kamaishi, Iwate prefecture Japan.

39.

Sendai Airport.

40.

A boat is caught in a tsunami whirlpool.

41.

People at a book store react as the store's ceiling falls.

42.

A collapsed pedestrian road.

43.

This sidewalk used to be level.

44.

A whirlpool swirls offshore.

45.

Sendai Airport.

46.

Houses, cars and other debris are washed away by tsunami tidal waves in Kesennuma in Miyagi Prefecture, northern Japan

47.

Vehicles ready for shipping are carried away by a tsunami tidal wave.

48.

Tsunami tidal waves are seen moving upstream the Naka river.

49.

The oncoming tsunami strikes the coast in Natori City.

50.

A car gets swept away by the tsunami tides.

Thanks to BuzzFeed