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Bicarbonate Linked To Sticky Mucus In Cystic Fibrosis

ScienceDaily (Aug. 27, 2009) — A hallmark of cystic fibrosis, a disease caused by mutations in the CTFR gene, is the accumulation of abnormally thick and sticky mucus in the lung, intestine, and various other organs. Although the accumulation of this mucus is thought likely to play a central role in the development of disease, how mutations in the CTFR gene lead to mucus accumulation have not been determined.
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Reference

* Saliva
* Epithelium
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* Exocrine gland

However, Paul Quinton and colleagues, at the University of California at San Diego, La Jolla, have now provided insight into this issue by studying mouse small intestine segments ex vivo, according to a paper to be published in the August 24 issue of the Journal of Clinical Investigation. In an accompanying commentary, Robert DeLisle, at the University of Kansas School of Medicine, Kansas City, highlights the importance of the study and the potential new take on how mutations in the CTFR gene lead to mucus accumulation and disease.

One of the functions of the CTFR protein generated by the nonmutated CTFR gene is to transport bicarbonate (HCO3–) out of cells. In their study, Quinton and colleagues developed a new ex vivo system for monitoring mucus release from the mouse small intestine to investigate whether defects in this function of CFTR might affect mucus secretion. Although basal rates of mucus release were similar in the presence or absence of bicarbonate, mucus release stimulated by natural chemicals such as serotonin was markedly decreased in the absence of bicarbonate. Interestingly, in a mouse model of cystic fibrosis, mucus release stimulated by natural chemicals was minimal in the presence or absence of bicarbonate. The authors therefore suggest that normal mucus release requires concurrent bicarbonate secretion and that the abnormally thick and sticky mucus that characterizes cystic fibrosis might be caused by defective bicarbonate secretion.

Journal references:

1. Garcia et al. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38662
2. Robert C. De Lisle. Pass the bicarb: the importance of HCO3– for mucin release. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI40598

Adapted from materials provided by Journal of Clinical Investigation, via EurekAlert!, a service of AAAS.
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Tropical Storms Endure Over Wet Land, Fizzle Over Dry

ScienceDaily (Aug. 27, 2009) — If it has already rained, it's going to continue to pour, according to a Purdue University study of how ocean-origin storms behave when they come ashore.
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More than 30 years of monsoon data from India showed that ground moisture where the storms make landfall is a major indicator of what the storm will do from there. If the ground is wet, the storm is likely to sustain, while dry conditions should calm the storm.

"Once a storm comes overland, it was unclear whether it would stall, accelerate or fizzle out," said Dev Niyogi, Indiana state climatologist and associate professor of agronomy and earth and atmospheric sciences. "We found that whether a storm becomes more intense or causes heavy rains could depend on the land conditions - something we'd not considered. Thus far we've looked at these storms based mainly on ocean conditions or upper atmosphere."

Niyogi said tropical storms gain their strength from warm ocean water evaporation.

"The same phenomenon - the evaporation from the ocean that sustains the storms - could be the same phenomenon that sustains that storm over land with moisture in the soil," he said. "The storm will have more moisture and energy available over wet soil than dry."

Niyogi's team's findings were published in the August edition of the journal Geophysical Research Letters.

Storm data fed into a model showed that higher levels of ground moisture would sustain Indian monsoon depressions. The model's prediction was proven when compared to ground conditions for 125 Indian monsoons over 33 years, where storms sustained when the ground was wet at landfall.

Knowing the sustainability of a storm could lead to better predictions on flooding and damage inland before a monsoon or a hurricane makes landfall.

"We think the physics is such that we could see similar results more broadly, such as in the United States," Niyogi said.

The National Science Foundation and NASA funded the research. The Purdue led-team also consisted of researchers from the National Center for Atmospheric Research, NASA-GSFC/ESSIC, the University of Georgia, the Indian Space Research Organization and the Indian Institute of Technology Delhi.

Niyogi said the next step is to use the model and ground moisture data to test these theories for hurricanes in the United States.

Journal reference:

1. Chang et al. Possible relation between land surface feedback and the post-landfall structure of monsoon depressions. Geophysical Research Letters, 2009; 36 (15): L15826 DOI: 10.1029/2009GL037781

Adapted from materials provided by Purdue University.
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Taking Up Music So You Can Hear

ScienceDaily (Aug. 27, 2009) — Anyone with an MP3 device -- just about every man, woman and child on the planet today, it seems -- has a notion of the majesty of music, of the primal place it holds in the human imagination.
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Reference

* Hearing impairment
* Tinnitus
* Learning disability
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But musical training should not be seen simply as stuff of the soul -- a frill that has to go when school budgets dry up, according to a new Northwestern University study.

The study shows that musicians -- trained to hear sounds embedded in a rich network of melodies and harmonies -- are primed to understand speech in a noisy background, say in a restaurant, classroom or plane.

It is the first demonstration of musical training offsetting the deleterious effects of background noise, and the implications are provocative.

"The study points to a highly pragmatic side of music's magic," said Nina Kraus, Hugh Knowles Professor of Communication Sciences and Neurobiology and director of Northwestern's Auditory Neuroscience Laboratory, where the research was done.

The findings strongly support the potential therapeutic and rehabilitation use of musical training to address auditory processing and communication disorders throughout the life span.

Hearing speech in noise is difficult for everyone. But the difficulty is particularly acute for older adults, who are likely to have hearing and memory loss, and for poor readers who have normal hearing but whose nervous systems poorly transcribe sounds that ultimately are critical to good reading skills.

"Many older adults will say, 'I can hear what you're saying, but I don't understand you,'" Kraus said. "So they might have a little bit of a hearing loss, but often not enough to warrant the difficulty that a lot of older adults report."

Such populations could benefit from the reordering of the nervous system that occurs with musical training, according to the study. Because the brain changes with experience, musicians have better-tuned circuitry -- the pitch, timing and spectral elements of sound are represented more strongly and with greater precision in their nervous systems.

"Musical training makes musicians really good at picking out melodies, the bass line, the sound of their own instruments from complex sounds," Kraus said. Now, for the first time, this study has confirmed that such fine tuning of the nervous system also makes musicians highly adept at translating speech in noise.

The finding has particular implications for hearing certain consonants which are vulnerable to misinterpretation by the brain and are a big problem for some poor readers in a noisy environment. The brain's unconscious faulty interpretation of sounds makes a big difference in how words ultimately will be read.

Thirty-one study participants, with normal hearing and a mean age of 23, were divided into one group with music experience and another without it. They had to listen to sentences presented in increasingly noisy conditions and repeat back what they heard.

Better perception in noise was linked with better working memory and tone discrimination ability. The results imply that musical training enhances the ability to hear speech in challenging listening environments by strengthening auditory memory and the representation of important acoustic features.

In one of the tests, for example, participants had to repeat back "The square peg will settle in the round hole." Such longer sentences that are syntactically correct but lack familiar cues measure working memory as well as the ability to distinguish sounds in noise.

The Auditory Neuroscience Lab at Northwestern has helped establish the relationship between sound encoding in the brain and linguistic abilities by showing that the very neural sound transcription processes that are deficient in children with dyslexia are enhanced in people with musical experience. Based on this collective work, poor readers may show greater benefits from training programs that include music as well as speech sounds.

By reinforcing the pervasive effects that musical experience has on sound-processing abilities, Kraus stressed, this study underscores the importance of music education being more accessible to the general population.

Journal reference:

1. Alexandra Parbery-Clark, Erika Skoe, Carrie Lam and Nina Kraus. Musician Enhancement for Speech-in-Noise. Ear and Hearing, (in press)

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Northwestern University (2009, August 27). Taking Up Music So You Can Hear. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090817142857.htm
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Musicians -- trained to hear sounds embedded in a rich network of melodies and harmonies -- are primed to understand speech in a noisy background, say in a restaurant, classroom or plane. (Credit: iStockphoto)
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Molecular Link Found Between Insulin Resistance And Inflammation

ScienceDaily (Aug. 27, 2009) — An exploration of the molecular links between insulin resistance and inflammation may have revealed a novel target for diabetes treatment, say scientists at the John G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh of UPMC. Their findings were published earlier this month in the online version of Diabetes, one of the journals of the American Diabetes Association.
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Signs of low-grade systemic inflammation are not uncommon among people who have the pre-diabetic condition known as metabolic syndrome, as well as in animal models of obesity and type 2, or insulin-resistant, diabetes, said senior author H. Henry Dong, Ph.D., assistant professor, Department of Pediatrics, University of Pittsburgh School of Medicine.

"But it's not yet clear if there is a cause-and-effect relationship between chronic exposure to low-grade inflammation and the onset of insulin resistance," he explained. "Other studies have shown that in patients who have inflammation and diabetes, insulin-sensitizing drugs seem to reduce inflammation while anti-inflammatory therapies improve sensitivity to insulin."

Dr. Dong's team examined the role played by a protein called Forkhead Box 01 (Fox01), which his previous research showed contributes to elevations in triglycerides in an animal model of obesity and diabetes.

In the current paper, the researchers found in cultured cells and mouse experiments that Fox01 stimulates inflammatory white blood cells called macrophages, which migrate to the liver and adipose, or fat, tissue in insulin-resistant states, to increase production of a cytokine called interleukin-1 beta (IL-1B). The cytokine in turn interferes with insulin signaling. Insulin typically inhibits Fox01, setting up a feedback loop in healthy tissues that helps regulate insulin levels.

"The findings suggest that when there is a lack of insulin or when cells such as macrophages are resistant to its presence, there are no brakes on Fox01's stimulation of IL-1B and its further interference with insulin signaling," Dr. Dong said. "That might explain why chronic inflammation often is coupled with obesity and type 2 diabetes. Also, a drug that acts on Fox01 might be able to better control blood sugar."

According to the ADA, an estimated 24 million Americans have type 2 diabetes, formerly known as adult-onset diabetes. As obesity becomes more common, however, the prevalence is rising in children. In type 2 diabetes, the body becomes resistant to the effect of insulin, leading to elevated blood sugar levels.

Co- authors of the paper include lead author Dongming Su, M.D., Gina M. Coudriet, Dae Hyun Kim, Ph.D., German Perdermo, Ph.D., Shen Qu, M.D., Sandra Slusher, Hubert M. Tse, Ph.D., Jon Piganelli, Ph.D., and Nick Giannoukakis, Ph.D., all of the Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC and Pitt School of Medicine, and Yi Lu, Ph.D., and Jian Zhang, M.D., Division of Hematology and Oncology, Department of Medicine, Pitt School of Medicine.

The study was funded by the American Diabetes Association and the National Institutes of Health.
Adapted from materials provided by University of Pittsburgh Schools of the Health Sciences, via EurekAlert!, a service of AAAS.
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People Vary Widely In Ability To Eliminate Arsenic From The Body

ScienceDaily (Aug. 27, 2009) — Large variations exist in peoples' ability to eliminate arsenic from the body, according to a new study that questions existing standards for evaluating the human health risks from the potentially toxic substance. The study found that some people eliminate more than 90 percent of the arsenic consumed in the diet. Others store arsenic in their bodies, where it can have harmful effects.
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The research, based on the first application of new methods for studying arsenic, is scheduled for the Sept. 21 issue of ACS's Chemical Research in Toxicology.

In the study, Kevin Francesconi and colleagues point out that drinking water in many parts of the world, including some regions of the United States, contain amounts of arsenic that exceed the World Health Organization's maximum acceptable levels. Consumption of seafood, the article notes, is another major source of arsenic contamination. Health effects from chronic arsenic exposure include skin and internal cancers, cardiovascular disease, and possibly diabetes, it adds.

The scientists describe monitoring arsenic excretion in the urine of human volunteers. They found that ability to eliminate arsenic from the body varied greatly, with some participants excreting up to 95 percent of the ingested arsenic but others eliminating as little as four percent. "This observed individual variability in handling [arsenic] exposure has considerable implications for the risk assessment of arsenic ingestion," the paper states. It adds that further study is needed to assess potential risks to humans consuming seafood products. "The data presented here suggest that the long held view that seafood arsenic is harmless because it is present mainly as organoarsenic compounds needs to be reassessed."

Journal reference:

1. Reingard Raml, Georg Raber, Alice Rumpler, Thomas Bauernhofer, Walter Goessler, Kevin A. Francesconi. Individual Variability in the Human Metabolism of an Arsenic-Containing Carbohydrate, 2',3'-Dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-ß-D-riboside, a Naturally Occurring Arsenical in Seafood. Chemical Research in Toxicology, September 21, 2009 DOI: 10.1021/tx900158h

Adapted from materials provided by American Chemical Society, via EurekAlert!, a service of AAAS.
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Large variations exist in people's ability to eliminate arsenic (sample shown) from the body, a new study shows. (Credit: Wikimedia Commons)
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Short Stature: Both A Specific Gene, And Its Abnormal Regulation, Can Trigger The Condition

ScienceDaily (Aug. 27, 2009) — A specific gene is particularly frequently involved in the development of short stature. Researchers in Heidelberg have now discovered that sequences of genetic material on the X and Y chromosome that regulate this gene are also crucial for growth in children. These gene regulators determine how frequently a gene is copied, thus how effective it is. In many cases, the mutation of one regulatory sequence of the SHOX gene is sufficient to give rise to the full-blown syndrome.
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* Genes
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* Personalized Medicine
* Human Biology

Reference

* Huntington's disease
* Vector (biology)
* Rett syndrome
* Growth hormone

Professor Gudrun Rappold, Director of the Department of Human Molecular Genetics at Heidelberg University Hospital and her team of researchers have published their results in the Journal of Medical Genetics. These results could open up new possibilities for diagnosing the cause of short stature and initiating treatment before it is too late.

The so-called SHOX gene (short stature homeobox gene) is responsible for the normal growth of bones and is often mutated in short-stature patients. Short stature is considered when final height of an individual is no more than 160 cm (men) or 150 cm (women). There are many causes, e.g. hormone disorders, malnutrition, chronic disease, or a genetic disorder. If, in addition to short stature, other symptoms such as short forearms and lower legs or other bone malformations also occur, it is considered a syndrome. However, often no exact cause can be determined and other typical features are lacking – this is then known as idiopathic short stature.

SHOX gene mutation is frequently the cause of short stature

Professor Rappold’s team discovered back in 2007 that in over 4 percent of children with idiopathic short stature, the trigger for the disorder was a mutation in the SHOX gene. This gene lies on the X chromosome and is responsible for growth in the epiphyseal plate, where the long bones of the arms and legs grow in length. After puberty, epiphyseal fusion takes place. When there is a mutation of the SHOX gene, patients reach a height up to 20 cm less than expected. Up to about 15 cm can be regained if the disease is diagnosed early enough and treated with growth hormones. The SHOX gene is involved in various other syndromes with growth disorders (Léri-Weill, Langer, Ullrich-Turner syndrome).

Genetic material from 893 persons with short stature examined

The researchers’ latest studies show that not only the gene itself, but its regulators as well can be crucial for developing the disease. Regulatory sequences ensure that the respective gene is copied more or less frequently and thus is more or less effective.

The researchers in Heidelberg examined the genetic material from a total of 893 subjects. About 5 percent of the patients with idiopathic short stature and 80 percent of the patients with Léri-Weill syndrome had mutations in the segment either including or around the SHOX gene. Some patients had an intact SHOX gene but an unexpectedly high number of mutations in its enhancer sequences: for 26 percent of patients with SHOX deficiency and idiopathic short stature and for 45 percent of patients with SHOX deficiency and Léri-Weill syndrome, the disease could be attributed solely to a genetic mutation of the enhancer sequence. “The astounding thing is that this enhancer mutation is quite far away from the affected gene and yet it still leads to the exact same clinical symptoms as a mutation in the gene itself,” says Professor Rappold.

Treatment with growth hormones

Genes that are responsible for growth and development are needed more or less frequently in different phases of growth. In these genes in particular, mutations in the regulatory sequences can be the decisive factor for illness. The researchers hope that their results will give them a better understanding of the causes of the disease and allow them to optimize the diagnostic possibilities for patients with SHOX gene mutations.

“Patients who suffer from their short stature often have a great need to be able to name the cause. Even if it is not possible to treat the cause, patients with mutations of the SHOX gene can benefit from a treatment of the symptoms with growth hormones,” explains Professor Rappold.

Journal reference:

1. Jianjun Chen, Gabriele Wildhardt, Zilin Zhong, Ralph Roeth, Birgit Weiss, Daniela Steinberger, Jochen Decker, Werner F Blum, Gudrun A Rappold. Enhancer mutations of the SHOX gene as a frequent cause of short stature - the essential role of a 250 kb downstream regulatory domain. Journal of Medical Genetics, 2009; DOI: 10.1136/jmg.2009.067785

Adapted from materials provided by University Hospital Heidelberg.
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University Hospital Heidelberg (2009, August 27). Short Stature: Both A Specific Gene, And Its Abnormal Regulation, Can Trigger The Condition. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090825100701.htm
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