Chuck Bednar for redOrbit.com – Your Universe Online

The same device that helps keep you from getting lost on long trips has inspired scientists to track the metal ions in enzymes essential for metabolism and the synthesis of biological products, according to research published in the latest edition of the journal Angewandte Chemie.

Professor Dr. Olav Schiemann of the Institute for Physical and Theoretical Chemistry at the University of Bonn and his colleagues are developing novel methods for exploring the structure of enzymes that were inspired by the global positioning system (GPS), which is used to detect where people are and to reliably guide them from one place to another.

Enzymes are essential to life on Earth, as they enable and control a variety of biochemical reactions, including digestion and the duplication of genetic information. While complex in structure, enzymes contain a “protein knot” or “active center” that is usually comprised of at least one metal ion to which substances undergoing change in chemical reactions attach.

The metal ion facilitates the breaking or reforming of one of more bonds in the attached substance, causing it to be converted into a new substance through the enzyme. One example of these processes takes place in our stomachs, where food is regularly broken down into substances that can be easily absorbed by the human body.

Scientists are studying how these essential enzymes work, but to do so, they have to know exactly how individual atoms are arranged within the biomolecules. When they the location of the metal ion, they can better understand precisely how the reactions proceed, Schiemann explained. To make that happened, they developed a method similar to a car’s navigation system.

“The structure of enzymes is frequently, at first glance, just as confusing as the maze of traffic during rush hour,” he explained. Similar to how a single vehicle is difficult to point out on a busy highway, the metal ion is initially hard to spot in the folds and coils of the enzyme. Even so, just as GPS makes it easy to know a car’s location, the new technique helps them spot the metal ion.

Whereas GPS systems use orbiting satellites, the novel method of hunting metal ions uses “spin labels,” or tiny organic molecules which have an unpaired electron and are stable, explained University of Bonn doctoral student Dinar Abdullin. They distributed six of these “molecular satellites” in their enzyme model “azurine” (a blue protein that contains a copper ion).

Next, they used computer programs to first track the “orbits” of these “satellites,” then determined the distance between them and a metal ion using a spectroscopic method. They were able to successfully determine metal ion’s exact position of the enzyme’s active center using this technique.

While the method was developed for basic research purposes, Professor Schiemann said that it can also be used “to clarify the structure of other enzymes.” As a result, the tool could lead to improved industrial drug manufacturing or other fields that could benefit from a better understanding of substance conversions at active centers, the study authors added.

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Chuck Bednar for redOrbit.com – Your Universe Online
The same device that helps keep you from getting lost on long trips has inspired scientists to track the metal ions in enzymes essential for metabolism and the synthesis of biological products, according to research published in the latest edition of the journal Angewandte Chemie.
Professor Dr. Olav Schiemann of the Institute for Physical and Theoretical Chemistry at the University of Bonn and his colleagues are developing novel methods for exploring the structure of enzymes that were inspired by the global positioning system (GPS), which is used to detect where people are and to reliably guide them from one place to another.
Enzymes are essential to life on Earth, as they enable and control a variety of biochemical reactions, including digestion and the duplication of genetic information. While complex in structure, enzymes contain a “protein knot” or “active center” that is usually comprised of at least one metal ion to which substances undergoing change in chemical reactions attach.
The metal ion facilitates the breaking or reforming of one of more bonds in the attached substance, causing it to be converted into a new substance through the enzyme. One example of these processes takes place in our stomachs, where food is regularly broken down into substances that can be easily absorbed by the human body.
Scientists are studying how these essential enzymes work, but to do so, they have to know exactly how individual atoms are arranged within the biomolecules. When they the location of the metal ion, they can better understand precisely how the reactions proceed, Schiemann explained. To make that happened, they developed a method similar to a car’s navigation system.
“The structure of enzymes is frequently, at first glance, just as confusing as the maze of traffic during rush hour,” he explained. Similar to how a single vehicle is difficult to point out on a busy highway, the metal ion is initially hard to spot in the folds and coils of the enzyme. Even so, just as GPS makes it easy to know a car’s location, the new technique helps them spot the metal ion.
Whereas GPS systems use orbiting satellites, the novel method of hunting metal ions uses “spin labels,” or tiny organic molecules which have an unpaired electron and are stable, explained University of Bonn doctoral student Dinar Abdullin. They distributed six of these “molecular satellites” in their enzyme model “azurine” (a blue protein that contains a copper ion).
Next, they used computer programs to first track the “orbits” of these “satellites,” then determined the distance between them and a metal ion using a spectroscopic method. They were able to successfully determine metal ion’s exact position of the enzyme’s active center using this technique.
While the method was developed for basic research purposes, Professor Schiemann said that it can also be used “to clarify the structure of other enzymes.” As a result, the tool could lead to improved industrial drug manufacturing or other fields that could benefit from a better understanding of substance conversions at active centers, the study authors added.
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Chuck Bednar for redOrbit.com – Your Universe Online
Well-meaning family members who are critical of a relative’s weight could be doing more harm than good, new research suggests.
The study, which appears in the December edition of the journal Personal Relationships, specifically looked at women. It found that those who received a higher number of “acceptance messages” about their weight were better able to maintain it or even drop a few pounds versus those who did not receive positive messages from those closest to them.
“We all know someone who points out our weight gain or offers to help us lose weight. Our results suggest that these comments are misguided,” said lead author Christine Logel, a professor from Renison University College at the University of Waterloo.
She explained that feeling pressure from loved ones about losing weight was not helpful for women that already had concerns about their bodies. In fact, it even caused some women that did not already have weight-related worries to even pack on a few extra pounds.
“When we feel bad about our bodies, we often turn to loved ones – families, friends, and romantic partners – for support and advice,” she added. “How they respond can have a bigger effect than we might think.”
Logel and her colleagues studied university-age women, a demographic they claim is often dissatisfied with personal weight. They asked each subject about their height and weight, as well as their feelings about what they saw when they stepped on the scale.
Five months later, they asked if they had addressed their weight-related concerns with their families, and if so, what response they had received. Approximately three more months later, they tracked changes to both the women’s weight and their concerns about it.
“On average, the women in the study were at the high end of Health Canada’s BMI recommendations, so the healthiest thing is for them to maintain the weight they have and not be so hard on themselves,” Logel said. “But many of the women were still very concerned about how much they weigh, and most talked to their loved ones about it.”
Overall, the women that took part in the study gained weight, but those that received positive feedback from their families maintained or even lost a small amount of weight. In comparison, those receiving fewer acceptance messages gained an average of 4.5 pounds.
“When women concerned about their weight heard that their loved ones accepted them as they are, they felt better about their bodies and subsequently they did not gain like other women did,” the researchers said in a statement. “The research suggests that feeling better about themselves caused the women to be more active or eat more sensibly. Receiving unconditional acceptance might have lowered their stress, a known cause of weight gain.”
“Lots of research finds that social support improves our health,” Logel added. “An important part of social support is feeling that our loved ones accept us just the way we are.”
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Chuck Bednar for redOrbit.com – Your Universe Online
From candy canes to special flavored coffees to any number of seasonal products, peppermint is all over the place during the holiday season. And no matter how cold and snowy it gets, we can’t seem to get enough of its unique, cool and refreshing flavor.
As it turns out, there’s a scientific reason for that, according to University of Southern California neurobiologist David McKemy. In a new video, McKemy explains how the chemical menthol in peppermint tricks our brains into this sensation by activating the same receptor on nerve endings that is involved in sensing cold, said Maanvi Singh of National Public Radio (NPR).
McKemy and his colleagues used menthol to conduct research on how the human brain detects the difference between hot and cold, and how it reacts to each of those sensations, according to a Tech Times story published Friday. In their findings, they found a protein in the chemical that sends an electrical signal to the brain indicating coldness, causing the brain to respond to nerve receptors in the mount with that information.
“For some reason, we seem to be hard-wired to enjoy the refreshing, cooling sensation of menthol in our mouths,” Singh explained. “Research shows that menthol’s effects on cold receptors may satiate thirst, ease breathing and help us feel alert – which helps explain why it’s so popular not just in candy but also in cigarettes and cold medicine.”
McKemy told NPR that cold drinks quench thirst more quickly than room-temperature beverages, and people typically find it easier to breath when the air is cool. Furthermore, research by psychologists that was published in 1990 found that peppermint can actually cause people to feel more alert and focused.
As for why people got hooked on candy canes and other peppermint products during the holidays, the answer is more historical than scientific in nature. Prior to air conditioning, candy makers created hard candy during the winter months, when sugary creatures were less likely to melt during their creation or have their texture spoiled due to summertime humidity.
Somewhere along the way, candy makers began adding peppermint to candy canes, which themselves were fashioned by a German choirmaster who wanted to create a sweet treat in the shape of a shepherd’s cane to commemorate the Christian Nativity.
“Peppermint is also thought to have health benefits,” Singh said. “Although scientific research is still lacking in this area, most experts believe it relieves indigestion, soothes certain skin conditions and that the menthol in it helps relieve congestion caused by colds. There is also current research investigating the potential anti-cancer effects of peppermint.”
Menthol has previously been linked to increased alertness and reduced fatigue among drivers by researchers at Wheeling Jesuit University in West Virginia. In addition, Dr. Bryan Raudenbush and his colleagues reported that it and cinnamon can both reduce their anxiety and frustration.
That study built on previous work by Raudenbush’s team that suggested that stimulating the nervous system using peppermint and cinnamon odors enhanced motivation and performance, increase alertness, and decrease fatigue among athletes and clerical office workers.
The researchers tested the effects of those smells on drivers by having 25 undergraduate students sniff peppermint, cinnamon, or a non-odor control for 30 seconds every 15 minutes in the midst of a driving simulation. While prolonged driving typically led to increased anger and fatigue, driver frustration ratings fell significantly when peppermint or one of the other scents were used.
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Chuck Bednar for redOrbit.com – Your Universe Online
If you’ve ever wondered, “Where on Earth did I put my dentures?” there’s now a scientific reason behind why you did it.
New research published in the Journal of the American Geriatrics Society has linked age-related tooth loss with a decline in physical and cognitive ability.
The study was led by experts from the University College London Department of Epidemiology and Public Health, who looked at 3,166 English Longitudinal Study of Ageing (ELSA) participants over the age of 60 ), and compared their performances in tests of memory and walking speed. The researchers found that those who no longer had any of their original teeth performed approximately 10 percent worse in both exams than those people with teeth.
Furthermore, the Indo-Asian News Service (IANS) reported that the association between older UK adults losing all of their natural teeth and having poorer memory and worse physical capabilities within the next decade were more apparent in those between the ages of 60 and 74 than in those who were 75 years of age or older.
“Tooth loss could be used as an early marker of mental and physical decline in older age, particularly among 60-74 year-olds,” lead author Dr Georgios Tsakos explained in a statement. “We find that common causes of tooth loss and mental and physical decline are often linked to socioeconomic status, highlighting the importance of broader social determinants such as education and wealth to improve the oral and general health of the poorest members of society.”
Dr. Tsakos and his colleagues were able to explain the link between total tooth loss and memory after adjusting for sociodemographic characteristics, existing health problems, physical health, health behaviors (including smoking, drinking and depression) and socioeconomic status. However, even after accounting for all of those factors, those without teeth still walked somewhat more slowly than those who still had their bicuspids and incisors.
“Regardless of what is behind the link between tooth loss and decline in function, recognizing excessive tooth loss presents an opportunity for early identification of adults at higher risk of faster mental and physical decline later in their life,” the doctor said. “There are many factors likely to influence this decline, such as lifestyle and psychosocial factors, which are amenable to change.”
Earlier this month, researchers from the University of Adelaide reported that people who had experienced tooth loss did not necessarily need dentures, as those who had a certain number and type of teeth remaining did not suffer from a reduced quality of life without dental plates.
In technical terms, the researchers said that those patients are considered to have “shortened dental arches,” which means that they still have functional use of many teeth. There is a point at which tooth loss interferes with quality of life, but dentures are only required when patients pass that threshold.
“For years it has been taken for granted that if people experience tooth loss, they will need dentures, bridges, implants or other corrective processes to replace the missing teeth,” explained lead author Dr. Haiping Tan. “What we’ve found is that it really depends on the position of the teeth that have been lost, as well as the number.”
“Most people have 28 adult teeth, plus the four wisdom teeth, but it is possible to have significantly less teeth as long as people have them in the right positions and in the right numbers,” she added. “It’s about getting the right balance of biting and cutting teeth at the front of the mouth with enough of the chewing teeth at the back.”
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Chuck Bednar for redOrbit.com – Your Universe Online
The secret to combating AIDS and the HIV virus could lie in one of the last places you would ever think to look: the immune systems of llamas, researchers from the Scripps Research Institute and University College London reported Thursday in the journal PLOS Pathogens.
While the medical community has been making strides in the search for an effective vaccine against HIV, they have yet to successfully complete a serum capable of neutralizing antibodies against the pathogen. However, the new study indicates that using a combination of antibodies from the South American camel relative has proven effective at neutralizing the virus.
According to the UK Press Association, the experiments indicated that llamas inoculated using genetic material from HIV produced unusual antibodies that destroyed dozens of different strains of the virus. The antibodies produced by the creature are smaller than those produced by humans and other mammals, but they still proved capable of neutralizing every HIV strain tested.
Several types of known neutralizing antibodies target a specific part of the virus that binds to the CD4 receptor on the human target cells, the researchers explained. Biologists have indicated that this site is a narrow groove, and since antibodies in most mammals are relatively large proteins, their size could help explain why these neutralizing ones tend to be rare.

Llamas contribute to the fight against AIDS.

John Hopton for redOrbit.com – Your Universe Online

For most people, bullying used to be confined to the schoolyard and was an issue we did not have to face up to unless we or our children were attending school. But now the Internet is one big schoolyard of cyberbullying. How much do we really know about it?

The American Academy of Pediatrics has stressed that bullying can present a serious health risk for adolescents, and cyberbullying has elements to it that can potentially make the problem even worse. The anonymity of the Internet reduces the restraint of those doing the bullying, and constant access to and dependence on online social groups means that it is difficult for the victim to get any respite. The study notes that: “Because of their networked nature and anytime-anywhere access… online microsystems are often connected to and embedded in offline microsystems, such as the family and school.”

A study from Taylor and Francis recently published in the journal of Information, Communication & Society analysed 1094 comments left on a blog written by singer-songwriter Amanda Palmer, regarding the suicide of 15-year-old Amanda Todd as a result of online bullying. Palmer had herself been a victim of bullying and came across Amanda Todd’s case while researching. The comments shed light on the different reasons why people are targeted as well as the coping mechanisms they use.

In line with past research, the investigation showed that the top reason for being abused was physical appearance, followed by sexual orientation and an involvement in non-mainstream interests. Only 25 percent of all the bullying stories made reference to cyberbullying, but a lot of commenters stressed that technology exacerbated the problem of bullying in general.  The researchers said that cyberbullying “is rooted in traditional bullying, the distinctive properties of online environment (such as anonymity, constant connectivity, and a vague and vast audience) introduce new dynamics.” This includes “the difficulty to escape one’s tormentors and identify them.”

The findings identified two major types of coping strategies: behavioural and cognitive. The former included techniques such as seeking social support and ignoring the bully, and the latter focused on shaping individuals’ microsystem and drawing in their own personal supportive resources. Not many of the contributors in the comments said anything favorable about the role of technology in bullying, but those that did emphasized the potential for a supportive online community that victims can turn to.

It may not be reasonable to tackle every negative comment we see from one stranger to another online, but the study shows that we can help by tipping the scales in favor of the victim and building a culture that reassures them that the fault is with the aggressor, not themselves. An unrelated study recently found that the amount of abusive language used in online comments sections decreased when a recognized journalist joined in. If abusers are reminded that their comments are being scrutinized, whether by a recognized journalist or the online community, rather than just floating out into the faceless sea of the Internet, it might remind them of the need for self-censorship, self-consciousness and restraint.

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UK health officials have given the go-ahead for doctors to test a new treatment derived from the cannabis plant in children suffering from certain forms of severe epilepsy.

The new treatment is known as Epidiolex, and it does not contain the ingredient responsible for creating the high associated with recreational marijuana use, researchers from the University of Edinburgh explained. Instead, it is based off of one of the plant’s non-psychoactive components, cannabidiol (CBD), the health benefits of which have been examined in clinical trials.

The university explained that early studies conducted in the US have indicated that some epileptic children treated with CBD could experience less frequent and less severe seizures.

This will mark the first time that the treatment method has been tested in the UK, and it will involve a randomized controlled trial at the University of Edinburgh’s Muir Maxwell Epilepsy Centre. In addition, the Royal Hospital for Sick Children in Glasgow and Alder Hey Children’s Hospital in Liverpool will be involved in trial, as will facilities in the US, France and Poland.

“Many children with serious forms of epilepsy do not respond to the medications that we currently have available,” said Dr Richard Chin, Director of the Muir Maxwell Epilepsy Centre. “We need new means of treating these conditions so that we can give back some quality of life to these children and their families.”

“I welcome the launch of these trials as it marks an important milestone in our long journey towards understanding the condition and improving the treatment of those suffering this severe form of epilepsy,” added Ann Maxwell, founder of the Muir Maxwell Trust pediatric epilepsy charity. “As the mother of a teenager with this life altering condition, I strongly support the exploration of ground breaking medications that could seek out new ways to improve patients’ life quality.”

The initial focus of the research will be on children suffering from a rare, difficult-to-treat form of epilepsy known as Dravet Syndrome. Dravet Syndrome typically begins in infancy and causes seizures that often last for more than five minutes at a time. Patients are also at risk of a number of issues involving speech, growth, balance, movement and even sudden, unexplained death.

Some children participating in the study will receive Epidiolex, which was developed by British biotechnology company GW Pharmaceuticals, while others will be given a placebo. Future phases of the trial will study the treatment’s effects on Lennox-Gastaut Syndrome, a severe form of epilepsy which usually begins around age four and can be caused by brain malformations, severe head injury, central nervous system infection or inherited degenerative conditions.

“The 40,000 children with epilepsy in the UK have many different genetic causes for their seizures,” said Dr Sameer Zuberi, Clinical Lead of the Glasgow Epilepsy Genetics Service and Epilepsy Specialist at the Royal Hospital for Sick Children. “The opportunity to trial new treatments in children with specific gene changes gives families hope for better and more focused therapies.”

Professor Helen Cross, chief UK clinical investigator of the initial part of the trial, said that the study will give researchers the opportunity to “accurately test the viability of treatment with CBD in a safe and controlled way,” while Dr. Richard Appleton of Alder Hey Children’s Hospital in Liverpool noted that it was “crucial that research in children with epilepsy is undertaken far earlier than it has been in the past.”

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A new report co-authored by experts from Princeton and Harvard Universities to mark the 50th anniversary of the controversial “Moynihan Report” is asking the question: was the sociologist and future New York senator right in his assessment of the children of unmarried mothers?

In his 1965 study, Daniel Patrick Moynihan argued that growing up in homes which did not have a male breadwinner present led to children winding up in a life of poverty, joblessness and crime – especially among African Americans. The study was widely denounced at the time, but five decades later, the researchers decided to re-examine the trends that it predicted would occur.

Writing in the journal EducationNext, authors Sara McLanahan of Princeton and Christopher Jencks of Harvard reported that the percentage of children raised by unmarried mothers has more than doubled amongst both blacks and whites since 1965, and over half of all American children will live in fatherless homes at some point before their 18th birthday.

The percentage of children under age 18 living with an unmarried mother has increased substantially since the 1960s, with the largest increase seen among blacks. (Credit: EducationNext)

Over the past 50 years, the percentage of children raised by unmarried mothers has risen from 25 to 50 percent among blacks and 7 to 19 percent among whites, McLanahan and Jencks wrote. They added that the absence of a biological father increases the likelihood that a child of any race will exhibit antisocial behaviors like aggression, rule-breaking and delinquency, and that as a result, those youngsters are 50 percent less likely to finish high school or attend college.

The ratio of single-mother families in terms of race has changed little over the years, the authors noted. In 1970, 31 percent of single-mother families were black, 68 percent were white and the remaining one percent were “other race.” In 2013, 30 percent of single-mother families were black, while 62 percent white and 8 percent “other race,” based on the findings of the Princeton-led Fragile Families and Child Wellbeing study.

One thing that has changed over the years, according to McLanahan and Jencks, is the meaning of single motherhood. Modern single mothers are far less likely than their predecessors to have ever been married, they wrote, and single motherhood is far more likely to occur earlier in a child’s life than in the past. Furthermore, the offspring of modern single mothers are far more likely than ever before to have multiple male father-figures enter and exit their lives.

“Both the departure of a father and the arrival of a mother’s new partner disrupt family routines and are stressful for most children, regardless of whether the father was married to the mother or just living with her,” explained McLanahan, director of the Bendheim-Thoman Center for Research on Child Wellbeing at Princeton’s Woodrow Wilson School of Public and International Affairs. “Likewise, this shift to never-married motherhood has probably weakened the economic and emotional ties between children and their absent fathers.”

An increasing number of single mothers have not completed their high-school or college education as well, the researchers report. Among whiles, the percentage of single mothers lacking a high-school diploma has remained fairly constant (around 18 percent from 1980 through 2010), but among African Americans, it has increased from 56 percent in 1980 to 66 percent just 30 years later.

Poverty rates were much lower in two-partner families than in those headed by an unmarried mother, according to McLanahan and Jencks. In 2013, the poverty rate among families with children was 40 percent in families headed by an unmarried mother, but only 8 percent in those headed by a married couple. Similar rates were reported among blacks (46 percent vs. 12 percent), Hispanics (47 percent vs. 18 percent) and whiles (32 percent vs. 4 percent).

The percentage of births to unmarried mothers is twice as high for blacks as for whites, and across all groups the rate has increased over the last 50 years. (Credit: EducationNext)

“The fact that single motherhood is increasing faster among women with less than a college degree means that children growing up with a single mother are likely to be doubly disadvantaged,” said McLanahan. “They spend less time and receive less money from their biological fathers than children who live with their fathers.”

“At the same time, the mother – who is now the primary breadwinner – has lower earnings than the typical mother in a married-parent family,” she added, noting that changing these trends would require helping less-educated women invest their time time in education and career-related endeavors, to encourage the use of more reliable contraceptive methods, and to find a way to improve the economic prospects of the fathers of these children.

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In a new “proof of concept” experiment, scientists have managed to edit the genome of sperm-producing adult stem cells, creating a break in the DNA strands of a mutant gene in mouse cells then repairing it by replacing flawed segments with corrected ones.
The process utilized in the study is known as homologous recombination, and researchers from Indiana University, Stanford University and the University of Texas used spermatogonial stem cells (the building blocks for the production of sperm and the only adult stem cells that contribute genetic information to the next generation) to demonstrate their technique.
By repairing flaws in these cells, the study authors said that experts could prevent mutations from being passed onto to future generations. The technique, which is detailed in a recent edition of the journal PLOS One, has tremendous potential for gene therapy as well as basic research.
“We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated,” co-author Christina Dann, an associate scientist in the Indiana University (IU) Department of Chemistry, said in a statement Monday. “This technique corrects the mutation, theoretically leaving no other mark on the genome.”
Dann, lead author and former IU research associate Danielle Fanslow, and their colleagues had to overcome a number of difficulties in their research – including the fact that spermatogonial stem cells are difficult to isolate, culture and work with. They were only able to create the correct conditions in which to maintain and propagate the cells following years worth of work by scientists at multiple laboratories.
“A primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material,” the university explained. “The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.”
Stem cells that were modified in the laboratory were then transplanted into the testes of sterile mice where they grew or colonized, indicating that the stem cells were viable. However, the researchers were unable to breed the mice, though they are do not know if it was abnormalities in the transplanted cells or the recipient testes led to the rodents’ failure to produce sperm.
“We demonstrated that gene-corrected cells maintained several properties of spermatogonial stem/progenitor cells including the ability to colonize following testicular transplantation,” the study authors wrote. “This proof of concept for genome editing… impacts both cell therapy and basic research given the potential for GS [germline stem] cells to be propagated in vitro, contribute to the germline in vivo following testicular transplantation or become reprogrammed to pluripotency in vitro.”
“This research is a first step to allowing men carrying potentially harmful mutations, such as cystic fibrosis or Huntington disease, to have children naturally without concern about passing on their disease to their offspring,” said Dr. James West, a researcher Vanderbilt University who is also conducting similar experiments. “The methodology they are using guarantees no harmful side effects elsewhere in the genome, and so if it is going to be done therapeutically, the method they are using is the best bet.”
In related research published earlier this month, scientists from multiple institutions in China used a different technique in order to edit a faulty gene in spermatogonial stem cells of mice. In that study, the rodents were able to successfully reproduce following transplantation of cells carrying the corrected gene.
“The research developments could open doors for better understanding of stem cells and advances in gene therapy,” Indiana University explained. “The ability to edit the genome could facilitate analysis of gene function and the processes by which sperm cells divide and differentiate. The techniques could be used, for instance, to test the functional importance of a genetic mutation implicated in reproductive failure.”
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Chuck Bednar for redOrbit.com – Your Universe Online

In a new “proof of concept” experiment, scientists have managed to edit the genome of sperm-producing adult stem cells, creating a break in the DNA strands of a mutant gene in mouse cells then repairing it by replacing flawed segments with corrected ones.

The process utilized in the study is known as homologous recombination, and researchers from Indiana University, Stanford University and the University of Texas used spermatogonial stem cells (the building blocks for the production of sperm and the only adult stem cells that contribute genetic information to the next generation) to demonstrate their technique.

By repairing flaws in these cells, the study authors said that experts could prevent mutations from being passed onto to future generations. The technique, which is detailed in a recent edition of the journal PLOS One, has tremendous potential for gene therapy as well as basic research.

“We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated,” co-author Christina Dann, an associate scientist in the Indiana University (IU) Department of Chemistry, said in a statement Monday. “This technique corrects the mutation, theoretically leaving no other mark on the genome.”

Dann, lead author and former IU research associate Danielle Fanslow, and their colleagues had to overcome a number of difficulties in their research – including the fact that spermatogonial stem cells are difficult to isolate, culture and work with. They were only able to create the correct conditions in which to maintain and propagate the cells following years worth of work by scientists at multiple laboratories.

“A primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material,” the university explained. “The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.”

Stem cells that were modified in the laboratory were then transplanted into the testes of sterile mice where they grew or colonized, indicating that the stem cells were viable. However, the researchers were unable to breed the mice, though they are do not know if it was abnormalities in the transplanted cells or the recipient testes led to the rodents’ failure to produce sperm.

“We demonstrated that gene-corrected cells maintained several properties of spermatogonial stem/progenitor cells including the ability to colonize following testicular transplantation,” the study authors wrote. “This proof of concept for genome editing… impacts both cell therapy and basic research given the potential for GS [germline stem] cells to be propagated in vitro, contribute to the germline in vivo following testicular transplantation or become reprogrammed to pluripotency in vitro.”

“This research is a first step to allowing men carrying potentially harmful mutations, such as cystic fibrosis or Huntington disease, to have children naturally without concern about passing on their disease to their offspring,” said Dr. James West, a researcher Vanderbilt University who is also conducting similar experiments. “The methodology they are using guarantees no harmful side effects elsewhere in the genome, and so if it is going to be done therapeutically, the method they are using is the best bet.”

In related research published earlier this month, scientists from multiple institutions in China used a different technique in order to edit a faulty gene in spermatogonial stem cells of mice. In that study, the rodents were able to successfully reproduce following transplantation of cells carrying the corrected gene.

“The research developments could open doors for better understanding of stem cells and advances in gene therapy,” Indiana University explained. “The ability to edit the genome could facilitate analysis of gene function and the processes by which sperm cells divide and differentiate. The techniques could be used, for instance, to test the functional importance of a genetic mutation implicated in reproductive failure.”

—–

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Human children remain dependent on their parents far longer than other animals, and elderly people live a comparably long time after their reproductive cycles have come to an end.

What causes this unusual phenomenon? Researchers from New York University (NYU) and Vanderbilt University believe that a person’s microbiome, or the bacteria and other organisms making their home inside his or her body, could be the cause of these uniquely human traits.

Martin Blaser, professor of medicine and microbiology at the NYU Langone Medical Center, and Vanderbilt mathematics professor Glenn Webb report their findings in research published online Tuesday in mBio, the official journal of the American Society for Microbiology.

Every living thing, whether plant or animal, is home to a vast and distinctive group of microorganisms. In fact, there are approximately 100 trillion microbial cells in the human microbiome, and those organisms outnumber actual human cells by a 10:1 ration, the study authors explained.

It had long been thought that these microorganisms had an extremely limited impact on their human hosts, but recent studies have shown that their sphere of influence involves more than just assisting with digesting food and producing bodily odors. Our microbiomes also assist in the development of our brain, help our reproductive systems and protect us against infections.

These recent findings have led to the development of the hologenomic theory of evolution, which submits that the object of Darwinian natural selection is not just the individual organism, but the organism and its associated microbial community as well.

Blaser said that the idea that microbes had a significant impact on human age structure came from his longtime analysis of Helicobacter pylori, a bacterium found in the stomachs of half of the global population. H. pylori typically co-exists peacefully in a person’s stomach, and can even help regulate stomach acid levels, but is also one of the primary causes of stomach cancer.

“I began thinking that a real symbiont is an organism that keeps you alive when you are young and kills you when you are old. That’s not particularly good for you, but it’s good for the species,” Blaser explained. He recruited Webb to develop a mathematical model capable of describing dynamic biological processes in order to test this concept.

The duo decided to develop a model of an early hunter-gather population to analyze the role which the microbiome might have played during their lives. They divided their simulations into three different age groups – juvenile, reproductive and senescent – and looked at how the population would respond to different combinations of fertility or mortality rates.

This enabled they to develop a baseline case using the best estimates of these rates they could find. They then added the risk of mortality based on various microbial profiles, including one based on the diarrhea-causing bacteria Shigella that increased mortality among children, and another involving an H. pylori-type mortality factor that increased with age.

Blaser and Webb found that this decreased the percentage of the senescent population, which ultimately helped the younger populations by reducing the elderly’s demand on food and other resources. The end result, they said, was stronger-than-baseline population growth and stability – findings consistent with the belief that evolution may have influenced the human microbiome in order to favor bacteria that target the aging.

The study authors went on to double the fertility rate in one simulation, and found that the population became unstable and experienced “catastrophic boom-bust cycles” in response to events that caused major population loss. Another variation found that even slight increases in the elderly population caused the hunter-gatherer population to begin declining.

“In addition to providing validation to the proposition that the microbiome may be shaping the human age structure, Webb observed that the modeling effort also reveals an underlying truth about human population growth,” officials from Vanderbilt University explained. “We have the right fertility and mortality rates to support our unusual age structure.”

“If you go back 30,000 to 40,000 years ago, there were only 30,000 to 40,000 people in the world and they were scattered over Africa, Europe and parts of Asia,” added Webb. “Are we lucky just to be here? Or did we survive because our ancestors were robust enough to handle all the environmental changes and natural disasters they encountered? According to our equations, it was because they were robust enough.”

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Chuck Bednar for redOrbit.com – Your Universe Online
The amount of mitochondrial DNA (mtDNA) found in a person’s blood could be used to predict his or her overall risk of frailty and death from any cause 10 to 15 years before the first symptoms appear, researchers from The Johns Hopkins University say in a new study.
Mitochondrial DNA, the cellular organelles that help convert food into chemical energy for cells, can be used to enhance our scientific understanding of aging, the study authors explained. Their findings, which were published online earlier this month in the  Journal of Molecular Medicine, could be used to develop a new test to identify at-risk individuals.
Dr. Dan Arking, an associate professor of genetic medicine at the university, said that he and his colleagues “don’t know enough yet to say whether the relationship is one of correlation or causation, but either way, mitochondrial DNA could be a very useful biomarker in the field of aging.” It could be used to identify people who could benefit health-wise from lifestyle changes.
Unlike other cell structures, mitochondria (which are also known as “power houses” since they are responsible for generating the majority of a cell’s energy) contain their own DNA separate from those enclosed in the nucleus. Their DNA comes in the form of between two and 10 small, circular chromosomes which code for 37 genes necessary for mitochondrial function.
Previous research from Dr. Arking’s laboratory has found a link between genetic differences in mtDNA and the reduced muscle strength and increased frailty experienced by older men and women. In medical terms, frailty refers to a highly recognizable set of aging symptoms, including weakness, decreased energy, reduced activity and weight loss, the study authors added.
In order to further study this correlation, the investigative team analyzed the amount of mtDNA in blood samples collected for a pair of large studies that began during the late 1980s. They monitored the health of individuals for up to 20 years and calculated the amount of mtDNA each sampled contained relative to the amount of nuclear DNA.
Dr. Arking and his colleagues then reviewed measures of frailty and health status gathered on the studies’ participants over time. They found that, on average, study participants that met the criteria for frailty had nine percent less mtDNA than nonfrail participants. Furthermore, white participants in the bottom one-fifth of the study population in terms of mtDNA were 31 percent more likely to be clinically frail than participants in the top one-fifth.
“The researchers also analyzed the age at which participants died. In one of the studies, high levels of mtDNA corresponded to a median of 2.1 extra years of life compared to those with the lowest levels of mtDNA,” the university said.
“Using data from both studies, the team found that those with mtDNA levels in the bottom one-fifth of the population were 47 percent more likely to die of any cause during the study period than were those in the top one-fifth,” the institution added. “They also found that women had an average of 21 percent more mtDNA than men.”
Dr. Arking explained that the link between decreased mtDNA and negative health outcomes should come as no surprise, since our energy reserve decrease as we age and we become more susceptible to disease and other ailments. He added that the gender-based finding could also help explain why women live an average of two to four years longer than men.
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Chuck Bednar for redOrbit.com – Your Universe Online

Conceiving children often involves, ahem, “fireworks.” (At least we hope so.)

But according to new research published in Nature Chemistry on Monday, the fertilization of a mammalian egg actually does produce “zinc sparks,” caused by the release of thousands of zinc atoms required to induce the egg-to-embryo transition.

(This movie shows zinc being released from the egg during a zinc spark. In this movie, hot spots of fluorescence at the cell surface demonstrate how groups of zinc-rich packages are released from the egg during fertilization, resulting in a zinc spark.)

The authors of the study were able to capture the first images of these molecular fireworks using newly-developed technology. In doing so, they discovered that the sparks originate from miniature, tiny zinc-rich packages just below the egg’s surface – a discovery which should help improve upon current in vitro fertilization methods.

“The amount of zinc released by an egg could be a great marker for identifying a high-quality fertilized egg, something we can’t do now,” Northwestern University professor Teresa K. Woodruff, an expert in ovarian biology and one of two corresponding authors of the paper, said in a statement. “If we can identify the best eggs, fewer embryos would need to be transferred during fertility treatments. Our findings will help move us toward this goal.”

Woodruff, a professor in obstetrics and gynecology and director of the Women’s Health Research Institute at Northwestern University Feinberg School of Medicine, fellow corresponding author and Northwestern University Chemistry of Life Processes Institute director Thomas V. O’Halloran, and their colleagues said that their research provides the first quantitative physical measurements of zinc localization in single cells in a mammal.

The investigative team used a combination of four different physical methods to determine the amount of zinc contained in an egg, as well as its location both during the time of fertilization and in the two hours period immediately afterwards. Using sensitive imaging techniques, they were able to observe and count individual zinc atoms in egg cells and visualize zinc spark waves in three dimensions.

They also developed a novel vital fluorescent sensor that they used for live-cell zinc tracking, and by using it, they were able to discover nearly 8,000 compartments in the egg. Each of those compartments contained approximately one million zinc atoms, and those packages released the chemical simultaneously in a concerted process, comparable to neurotransmitter release in a person’s brain or insulin release in the pancreas.

The findings were later confirmed using chemical methods that trapped cellular zinc stores and allowed the substance to be mapped on a nanometer scale using an electron microscope that was custom-made specifically for this project. Additional high-energy X-ray imaging experiments enabled Woodruff, O’Halloran and their fellow scientists to precisely map the location of zinc atoms in both two and three dimensions.

“On cue, at the time of fertilization, we see the egg release thousands of packages, each dumping a million zinc atoms, and then it’s quiet. Then there is another burst of zinc release,” said O’Halloran, according to Daily Mail. “Each egg has four or five of these periodic sparks. It is beautiful to see, orchestrated much like a symphony. We knew zinc was released by the egg in huge amounts, but we had no idea how the egg did this.”

The newly-published paper is the culmination of six years of work, and establishes how eggs compartmentalize and distribute zinc to control the developmental processes which allow it to become a healthy embryo, the researchers said. They said that zinc played a key role in allowing an egg to grow and change into a new genetic organism, and the release of these zinc sparks is essential for embryo formation during the first two hours post-fertilization.

“The egg first has to stockpile zinc and then must release some of the zinc to successfully navigate maturation, fertilization and the start of embryogenesis,” O’Halloran said. “But exactly how much zinc is involved in this remarkable process and where is it in the cell? We needed data to better understand the molecular mechanisms at work as an egg becomes a new organism.”

“We had to develop a slew of methods to be convinced we were seeing the right thing,” he added. “Science is about testing and retesting ideas. All of our complementary results point to the same conclusion: the zinc originates in packages called vesicles near the cell’s surface.”

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Chuck Bednar for redOrbit.com – Your Universe Online
Conceiving children often involves, ahem, “fireworks.” (At least we hope so.)
But according to new research published in Nature Chemistry on Monday, the fertilization of a mammalian egg actually does produce “zinc sparks,” caused by the release of thousands of zinc atoms required to induce the egg-to-embryo transition.

(This movie shows zinc being released from the egg during a zinc spark. In this movie, hot spots of fluorescence at the cell surface demonstrate how groups of zinc-rich packages are released from the egg during fertilization, resulting in a zinc spark.)
The authors of the study were able to capture the first images of these molecular fireworks using newly-developed technology. In doing so, they discovered that the sparks originate from miniature, tiny zinc-rich packages just below the egg’s surface – a discovery which should help improve upon current in vitro fertilization methods.
“The amount of zinc released by an egg could be a great marker for identifying a high-quality fertilized egg, something we can’t do now,” Northwestern University professor Teresa K. Woodruff, an expert in ovarian biology and one of two corresponding authors of the paper, said in a statement. “If we can identify the best eggs, fewer embryos would need to be transferred during fertility treatments. Our findings will help move us toward this goal.”
Woodruff, a professor in obstetrics and gynecology and director of the Women’s Health Research Institute at Northwestern University Feinberg School of Medicine, fellow corresponding author and Northwestern University Chemistry of Life Processes Institute director Thomas V. O’Halloran, and their colleagues said that their research provides the first quantitative physical measurements of zinc localization in single cells in a mammal.
The investigative team used a combination of four different physical methods to determine the amount of zinc contained in an egg, as well as its location both during the time of fertilization and in the two hours period immediately afterwards. Using sensitive imaging techniques, they were able to observe and count individual zinc atoms in egg cells and visualize zinc spark waves in three dimensions.
They also developed a novel vital fluorescent sensor that they used for live-cell zinc tracking, and by using it, they were able to discover nearly 8,000 compartments in the egg. Each of those compartments contained approximately one million zinc atoms, and those packages released the chemical simultaneously in a concerted process, comparable to neurotransmitter release in a person’s brain or insulin release in the pancreas.
The findings were later confirmed using chemical methods that trapped cellular zinc stores and allowed the substance to be mapped on a nanometer scale using an electron microscope that was custom-made specifically for this project. Additional high-energy X-ray imaging experiments enabled Woodruff, O’Halloran and their fellow scientists to precisely map the location of zinc atoms in both two and three dimensions.
“On cue, at the time of fertilization, we see the egg release thousands of packages, each dumping a million zinc atoms, and then it’s quiet. Then there is another burst of zinc release,” said O’Halloran, according to Daily Mail. “Each egg has four or five of these periodic sparks. It is beautiful to see, orchestrated much like a symphony. We knew zinc was released by the egg in huge amounts, but we had no idea how the egg did this.”
The newly-published paper is the culmination of six years of work, and establishes how eggs compartmentalize and distribute zinc to control the developmental processes which allow it to become a healthy embryo, the researchers said. They said that zinc played a key role in allowing an egg to grow and change into a new genetic organism, and the release of these zinc sparks is essential for embryo formation during the first two hours post-fertilization.
“The egg first has to stockpile zinc and then must release some of the zinc to successfully navigate maturation, fertilization and the start of embryogenesis,” O’Halloran said. “But exactly how much zinc is involved in this remarkable process and where is it in the cell? We needed data to better understand the molecular mechanisms at work as an egg becomes a new organism.”
“We had to develop a slew of methods to be convinced we were seeing the right thing,” he added. “Science is about testing and retesting ideas. All of our complementary results point to the same conclusion: the zinc originates in packages called vesicles near the cell’s surface.”
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