24.08.2008

ДНКовые катапульты!

Эозинофилы "выплёвывают" свою нуклеиновую кислоту, чтоб победить инфекцию. Об этом пишут на
http://www.eurekalert.org/pub_releases/2008-08/uouh-wbc081308.php:
Contact: Gerald J. Gleich, M.D.
801-581-6465
University of Utah Health Sciences

White blood cell uses DNA 'catapult' to fight infection
Eosiniphils help prevent uncontrolled bacterial invasion
SALT LAKE CITY – U.S. and Swiss scientists have made a breakthrough in understanding how a type of white blood cell called the eosinophil may help the body to fight bacterial infections in the digestive tract, according to research published online this week in Nature Medicine.

Hans-Uwe Simon, from the University of Bern, Switzerland, Gerald J.Gleich, M.D., from the University of Utah School of Medicine, and their colleagues discovered that bacteria can activate eosinophils to release mitochondrial DNA in a catapult-like fashion to create a net that captures and kills bacteria.

"This is a fascinating finding," says Gleich, professor of dermatology and internal medicine at the University of Utah and a co-author of the study. "The DNA is released out of the cell in less than a second."

Eosiniphils, which comprise only 1 to 3 percent of human white blood cells, are known to be useful in the body's defense mechanisms against parasites. But their exact role in the immune system is not clear. Unlike other white blood cells, which are distributed throughout the body, eosinophils are found only in selected areas, including the digestive tract. Mitochondria – often referred to as the power plants of the cell – are components within cells that are thought to descend from ancient bacteria. Although most cellular DNA is contained in the nucleus, mitochondria have their own DNA.

Previous research has shown that eosinophils secrete toxic granule proteins during parasite infections and that these granule proteins kill bacteria. Simon, Gleich, and their colleagues found that when eosinophils are stimulated by infection, such as E. coli, they rapidly secrete mitochondrial DNA. This DNA binds to the granule proteins and forms a net that is able to trap and kill bacteria. The researchers also found higher levels of eosinophils were linked to improved survival and lower numbers of bacteria in the blood of mice with widespread bacterial infections.

The toxic proteins released by eosinophils are not always helpful to the body, however, and can damage nearby tissues. The inflammation in some types of asthma and Crohn's disease, a chronic inflammatory disease of the bowel, is attributed to eosinophils. In fact, Simon and his team first found evidence of these DNA-protein traps in tissue taken from the digestive tracts of people with Crohn's disease.

Earlier studies suggested another type of white blood cell – the neutrophil – also expels DNA and granule proteins to kill bacteria. However, this DNA comes from the nucleus and its release causes the neutrophil to die. The eosinophil is able to survive after expelling its mitochondrial DNA.

The researchers hope to learn more about how eosiniphils expel mitochondrial DNA. They speculate that the explosive mechanism might rely on stored energy, similar to the way plants release pollen into the air. "We don't know how eosinophils are capable of catapulting mitochondrial DNA so quickly," says Gleich.

Future investigation may focus on how this energy is generated and how this new knowledge can be applied to the treatment of bacterial infections and inflammatory diseases related to eosinophils.

Митохондриальная ДНК - новая информация.

Загадки митохондриальной ДНК - это нечто... Пишут о ней много, часто мнения очень противоречивы. Вот - немного новых данных, которые я читала на http://www.biologynews.net/archives/2008/08/12/large_reservoir_of_mitochondrial_dna_mutations_identified_in_humans.html:

Researchers at the University of Newcastle, England, and the Virginia Bioinformatics Institute at Virginia Tech in the United States have revealed a large reservoir of mitochondrial DNA mutations present in the general population. Clinical analysis of blood samples from almost 3,000 infants born in north Cumbria, England, showed that at least 1 in 200 individuals in the general public harbor mitochondrial DNA mutations that may lead to disease. The findings, which highlight the need to develop new approaches to prevent the transmission of mitochondrial diseases, were published in The American Journal of Human Genetics.

Mitochondria, the "engines" present in each cell that produce adenosine triphosphate, are passed from mother to offspring. Mutations in mitochondrial DNA inherited from the mother may cause mitochondrial diseases that include muscle weakness, diabetes, stroke, heart failure, or epilepsy. In almost all mitochondrial diseases caused by mutant mitochondrial DNA, the patient's cells will contain a mixture of mutant and normal mitochondrial DNA. The proportion of mutant mitochondrial DNA in most cases determines the severity of disease.

Previous estimates from epidemiological studies suggested that mitochondrial diseases affect as many as one person in 5,000. However, the incidence of new mitochondrial mutations and the prevalence of those carrying these mutations were never fully established due to limitations in the methods used. Most of the earlier estimates of the frequency of mitochondrial DNA mutations in the general population, for example, have depended on identification of clinically affected patients and subsequent retracing of inheritance on the maternal side of the family. This approach fails to detect the gradual accumulation of mutations in some members of the population, including those individuals who harbor mitochondrial DNA mutations but who otherwise do not show the symptoms of disease.

Dr. David Samuels, Assistant Professor at the Virginia Bioinformatics Institute and an author on this study, commented: "We know from many clinical studies of patients and their families that our cells can tolerate a rather large amount of mutant mitochondrial DNA with no significant loss of function. From that observation we have suspected that there may be a large number of people in the general population who carry pathogenic mitochondrial DNA mutations, but who are not obviously ill with a mitochondrial disease. This study gives us, for the first time, a measurement of the number of these carriers of pathogenic mitochondrial DNA mutations in the general population. One in every 200 individuals is a lot of people – around 1.5 million people in the United States alone. "

The scientists looked at 10 mitochondrial DNA mutations (arising from single nucleotide replacements) often found in patients with mitochondrial disease. By taking advantage of a high-throughput genotyping system that uses mass spectrometry measurements, the researchers were able to detect mutated mitochondrial DNA at high sensitivity. In each positive case, DNA cloning and sequencing were used to confirm the findings. By looking at differences in tissue samples from mother and child, the researchers were also able to estimate the rate at which new DNA mutations had arisen in the population. The incidence of new mutations was close to 100 for every 100, 000 live births.

Dr. Samuels commented: "These new clinical measurements have given direct evidence for the widespread incidence of pathogenic mitochondrial DNA mutations in the human population. These findings emphasize the pressing need to develop effective ways to interrupt the transmission of these mutations to the next generation."

Source : Virginia Tech

23.08.2008

22 волшебных гена.

22 - моё любимое число. :) А стволовые клетки - одна из любимых тем. Данная статейка - объединяет эти позитивы. Судьба и "выбор ориентации" стволовых клеток - актуальнейшая область клеточной и молекулярной биологии. Поэтому - читайте, найденную на http://www.scientificblogging.com/news_releases/22_genes_that_control_embryonic_stem_cell_fate_identified заметку:

22 Genes That Control Embryonic Stem Cell Fate Identified

Submitted by News Staff on 10 July 2008 - 12:00am. Developmental
Scientists have identified about two dozen genes that control embryonic stem cell fate. The genes may either prod or restrain stem cells from drifting into a kind of limbo, they suspect. The limbo lies between the embryonic stage and fully differentiated, or specialized, cells, such as bone, muscle or fat.

By knowing the genes and proteins that control a cell's progress toward the differentiated form, researchers may be able to accelerate the process – a potential boon for the use of stem cells in therapy or the study of some degenerative diseases, the scientists say.

Their finding comes from the first large-scale search for genes crucial to embryonic stem cells. The research was carried out by a team at the University of California, San Francisco and is reported in a paper in the July 11, 2008 issue of Cell.

"The genes we identified are necessary for embryonic stem cells to maintain a memory of who they are," says Barbara Panning, PhD, associate professor of biochemistry and biophysics at UCSF, and senior author on the paper. "Without them the cell doesn't know whether it should remain a stem cell or differentiate into a specialized cell."

The scientists used a powerful technique known as RNA interference, or RNAi, to screen more than 1,000 genes for their role in mouse embryonic stem cells. The technique allows researchers to "knock down" individual genes, reducing their abundance in order to determine the gene's normal role.

The research focused on proteins that help package DNA. In the nucleus, DNA normally wraps around protein complexes called nucleosomes, forming a structure known as chromatin. This is what makes up chromosomes.

They found 22 proteins, each of which is essential for embryonic stem cells to maintain their consistent shape, growth properties, and pattern of gene expression.

Most of the genes code for multi-protein complexes that physically rearrange, or "remodel" nucleosomes, changing the likelihood that the underlying genes will be expressed to make proteins.

The main player they identified is a 17-protein complex called Tip60-p400. This complex is necessary for the cellular memory that maintains embryonic stem cell identity, Panning explains. Without it, the embryonic stem cells turned into a different cell type, which had some features of a stem cell but many features of a differentiated cell.

The scientists believe that Tip60-p400 is necessary for embryonic stem cells to correctly read the signals that determine cell type. These findings are not only important for understanding cellular memory in embryonic stem cells, but will also likely be relevant to other cell types, they say.

Inactivation of other genes disrupted embryonic stem cell proliferation. These genes were already known to have only slight influence on viability of mature cells in the body. This suggests that embryonic stem cells are "uniquely sensitive to certain perturbations of chromatin structure," the scientists report.

If other types of stem cells are also found to be sensitive to these chromatin perturbations, this could lead to novel cancer therapies in the future, Panning says.

Lead author on the paper is Thomas G. Fazzio, PhD, a postdoctoral fellow. Co-author is Jason T. Huff, BSc, a graduate student. Both are in Panning's lab.

The research is supported by the National Institutes of Health.

Свободные радикалы и аппетит.

Свободные радикалы - одни из самых высокоактивных соединений. Они играют ключевую роль в процессах окислительного стресса. Именно поэтому я ими и интересуюсь. Понравилась статья на http://www.scientificblogging.com/news_releases/free_radicals_linked_to_appetite, которая описывает интересный аспект биологического влияния свободных радикалов:

Free Radicals Linked To Appetite


Submitted by News Staff on 30 July 2008 - 2:00am. Clinical Genetics
Researchers at Yale School of Medicine have found the brain's appetite center uses fat for fuel by involving oxygen free radicals—molecules associated with aging and neurodegeneration. The findings suggest that antioxidants could play a role in weight control.

The study's lead authors were Sabrina Diano and Tamas Horvath, who are an associate professor and professor, respectively, in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Neurobiology. Horvath is also chair of the Section of Comparative Medicine.

"In contrast to the accepted view, the brain does use fat as fuel," said Horvath. "Our study shows that the minute-by-minute control of appetite is regulated by free radicals, implying that if you interfere with free radicals, you may affect eating and satiety."

The results also imply, added Horvath, "that each time a feeling of fullness or satiety is reached during a meal, you may be chipping away some time from your maximum lifespan as the most free radicals are produced when satiety-promoting brain cells are active."

Diano, Horvath and colleagues conducted the study in mice to better understand how the brain mediates neuronal activation in response to ghrelin, a hormone produced in the stomach and previously associated with growth hormone release, appetite, learning and memory.

They found that ghrelin-induced increase in appetite is driven by burning fat in hypothalamic mitochondria, which produces free radicals that are scavenged by a mitochondrial protein called uncoupling protein 2 (UCP2)

"The timing of taking antioxidants may be critical for the control of appetite," said Diano. "If taken on an empty stomach antioxidants may further increase appetite, however when taken with food, they may affect satiety. Further studies are needed to determine whether any regiment of orally taken antioxidants could be used to control appetite in animals and humans."

Other authors on the study included Zane B. Andrews, Zhong-Wu Liu, Nicholas Walllingford, Derek M Erion, Erzsebet Borok, Jeffrey M. Friedman, Matthias H. Tschöp, Marya Shanabrough, Gary Cline, Gerald I. Shulman, Anna Coppola and Xiao-Bing Gao.

Citation: Nature Vol. 454, 7204 (July 30, 2008)

GPCR и этим всё сказано! Божественно! Видео.

Эти рецепторы - просто чудо! С ними связано столько полезного! Не даром мы изучали их строение и функции дольше всех других типов рецепторов... :) А вот и отличное видео:


Нашла на http://scienceblogs.com/clock/2008/07/g_protein_receptor.php

GABA и контроль веса.

Нейротрансмиттеры - такие загадочные субстанции! Оказывается, GABA может влиять на процессы ожирения и похудения. Прочитала на http://www.scientificblogging.com/news_releases/gaba_neurocircuitry_gets_a_look_in_weight_gain_and_decline и вам советую:

GABA Neurocircuitry Gets A Look In Weight Gain (And Decline)


Submitted by News Staff on 10 August 2008 - 12:00am. Research
Controlling body weight is a complicated process but scientists investigating the brain's intricate neurocircuitry and its role in maintaining energy balance are forming a clearer picture of the myriad events that lead to weight gain ... and weight loss.

Writing in Nature Neuroscience, a study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) identifies another piece of this complex puzzle, demonstrating that the neurotransmitter GABA --one of the master communicators among neurons – plays a role in controlling energy balance.

"Body weight maintenance is made up of three basic stages," explains the paper's senior author Bradford Lowell, MD, PhD, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC whose laboratory is working to identify the specific neurocircuits responsible for controlling food intake and/or energy through functional neuroanatomical mapping studies.

"In the first stage, the brain receives sensory input from the body [including information provided by circulating hormones such as leptin and ghrelin and from fuels such as glucose and fatty acids]," says Lowell, who is also a Professor of Medicine at Harvard Medical School.

In the second stage, he adds, the brain integrates this sensory information with cues it has received from the environment (such as aromas and other enticements) along with information gathered from the organism's emotional state. Then, in the final stage, the brain's neurocircuitry takes over, enabling the brain to make appropriate alterations in food intake and energy expenditure in order to maintain energy balance – and prevent weight gain and obesity.

Previous work had primarily focused on identifying the neuropeptides involved in this process. And indeed, this group of neurotransmitters often proves essential to maintaining energy balance – but not always.

"It is well known that AgRP [Agouti-related protein] neurons play a critical role in feeding and energy balance regulation," explains Qingchun Tong, PhD, a postdoctoral fellow in the Lowell laboratory and the study's first author. "However, the deletion of AgRP and NPY [two neuropeptides released from the AgRP neurons] produces little metabolic effect."

An alternate theory proposed that release of the GABA neurotransmitter was mediating the function of AgRP neurons, an idea that had long been postulated but never examined.

To test this hypothesis, Tong and his colleagues generated a group of mice with disrupted release of GABA specifically from the AgRP neurons. As predicted, the genetically altered mice exhibited profound metabolic changes.

"The mice with AgRP neuron-specific disruption of GABA release were lean, had higher energy expenditure and showed resistance to diet-induced obesity," says Tong. "We also found that these animals showed reduced food intake response to the hormone ghrelin. This suggests to us that the neurocircuit engaging GABA release from the AgRP neurons mediates at least part of ghrelin's appetite-stimulating action."

A series of studies to examine the function of glutamate and GABA release from other groups of neurons are currently underway as investigators continue to dissect the brain's neurocircuitry.

"As these new findings demonstrate, GABA release is an important component that mediates the function of AgRP neurons," says Tong. "Discoveries such as this will ultimately help us to design an efficient strategy to tackle the current epidemic of obesity and metabolic disease."

This work was funded, in part, by grants from the National Institutes of Health and support from the North American Association for the Study of Obesity.

In addition to Lowell and Tong, coauthors include BIDMC investigators Chian-Ping Ye and Juli Jones and University of Texas Southwestern Medical Center investigator Joel Elmquist.

Brian May из Queen пишет научные работы.

С детства обожаю группу Куин. Поэтому всегда радуюсь успехам Брайана Мэя, гитариста и астрофизика. Хорошая статья об этом опубликована на http://blog.wired.com/wiredscience/2008/08/queen-guitarist.html:

The PhD thesis of Brian May, founder and guitarist of Queen, has just been published.

May started his research into Zodiacal Light -- the triangular glow visible after sunset in the West and before sunrise in the East -- in 1970, then took a 30-year rock star break. He finished it in 2007 at Imperial College London.

Entitled A Survey of Radial Velocities in the Zodiacal Dust Cloud, May's thesis, as described by academic publishing house Springer, is not a "popular astronomy book," but "a rigorous, academic examination of the Zodiacal Light [that] documents the building of a pressure-scanned Fabry-Perot Spectrometer, equipped with a photomultiplier and pulse-counting electronics, and its deployment at the Observatorio del Teide at Izaña in Tenerife."

Get 'em while they're hot!

Антидепрессанты для домашних питомцев!

Да... До чего дошёл прогресс! :) Информация с http://scienceblogs.com/cortex/2008/07/prozac_pets.php:

Prozac Pets
Category: Life Science
Posted on: July 9, 2008 2:50 PM, by Jonah Lehrer

I don't know how I feel about this new trend of giving household pets human anti-depressants. Here's James Vlahos in the Times Magazine:

The practice of prescribing medications designed for humans to animals has grown substantially over the past decade and a half, and pharmaceutical companies have recently begun experimenting with a more direct strategy: marketing behavior-modification and "lifestyle" drugs specifically for pets. America's animals, it seems, have very American health problems. More than 20 percent of our dogs are overweight; Pfizer's Slentrol was approved by the F.D.A. last year as the country's first canine anti-obesity medication. Dogs live 13 years on average, considerably longer than they did in the past; Pfizer's Anipryl treats cognitive dysfunction so that absent-minded pets can remember the location of the supper bowl or doggy door. For lonely dogs with separation anxiety, Eli Lilly brought to market its own drug Reconcile last year. The only difference between it and Prozac is that Reconcile is chewable and tastes like beef.
On the one hand, it's one of those bourgeois habits that's all too easy to mock. We think we're helping our animals - most pills are prescribed for "separation anxiety" - but we're actually indulging in some reckless experimentation. A dog can't tell us that he'd rather not take the little blue pill, or that he preferred his mindset before we started slipping tricyclics into his doggie bowl. It's the kind of foolishness that makes me wish Evelyn Waugh were still around.

And yet, as a pet-owner, I completely understand the urge to do everything possible to make these animals happy. As I write this post, my African Grey parrot is standing on her perch saying "I love people!" (I'm not joking - that's her favorite refrain.) She feels like a member of the family, so it's easy to understand how, if my vet diagnosed her with some emotional disorder, I'd be tempted to put some Prozac in her foodbowl. (That is, if my vet recommended such a thing.)

In the end, though, I find this paragraph pretty compelling:

Pharmacological treatments, furthermore, are sometimes more for the convenience of owners than they are for the health of pets. When the dog bites, when the cat pees -- "a lot of the 'behavior problems' we see are actually normal behaviors for the animal," Dodman says. Cats aren't mentally ill if they attack a new feline in the household or claw furniture to mark their domain. Food guarding and aggression toward strangers boost a dog's survival rate in the wild but don't cut it in the living room. And both cats and dogs demarcate territory with urine. "If a dog goes to the bathroom on a bush outside, you don't mind as long as it's not your bush," Dodman says. "But when he comes back to the house and lifts his leg on your chair, it's like, 'Is the dog mentally sick?' "

О занятиях спортом, окислительном стрессе и повреждениях ДНК.

Очень классная статья! Меня очень интересует окислительный стресс и его влияние на генетический материал (сама пишу работы на эту тему), поэтому не могу не запостить данный материал. Источник - http://www.scientificblogging.com/news_releases/extreme_fitness_oxidative_stress_and_training_your_dna

Extreme Fitness, Oxidative Stress And Training Your DNA

Submitted by News Staff on 21 August 2008 - 12:00am. Clinical Genetics
Unusually high levels of physical exertion do cause oxidative stress, but this does not result in any long-term damage to DNA, say the results of a new research project.

As part of the project, 42 male athletes took part both in a triathlon and an extensive biomedical study, which examined numerous physiological values parameters during the period from two days before to 19 days after the triathlon.

The range of personal views on the benefits - or otherwise - of physical activity covers everything from "sport is good for you" to "sport is a killer" - not very scientific.

There is no doubt that regular sporting activity has physiological benefits but there is no evidence that there are benefits of extreme endurance sports. Indeed, there are indications that ultra distance runners, for example, may suffer increased health risks due to high oxidative stress, which generates aggressive oxygen radicals and metabolites which can damage cells and cell components.

The question of whether this exercise induced stress also causes the DNA damage often observed as a consequence was addressed by the Austrian Science Fund FWF project.

The project comprised 42 male participants in the Ironman Austria competition. Of these, 24 participants were then used to investigate possible DNA damage.

Head of the study, Prof. Karl-Heinz Wagner of the Department of Nutritional Sciences at the University of Vienna, comments on the results: "Reactive oxygen species lead to oxidative stress in the body which can also cause DNA damage. We were able to gather clear evidence of a short-term increase in certain indicators for oxidative stress during the competition and have already published these results. However, now we were also able to demonstrate that, despite this increase, no notable and persistent damage was caused to the athletes' DNA. This is a surprising result which initially appears to contradict the data gathered in similar studies."

Recently, other studies showed that runners in an ultra marathon experienced increased DNA damage during the race. This was also true of marathon runners immediately after the race. However, these studies did not consider competitions which required a period of physical exertion lasting longer than 8 hours, nor was data collected over such an extended timeframe as in Prof. Wagner's project.

In total, the Austrian research team took blood samples from the triathletes at five different time points - 2 days prior to the race, then 20 minutes and 1, 5 and 19 days after the race.

In response to these apparent contradictions, Stefanie Reichhold, who supervised the operational side of the project alongside Oliver Neubauer, explains: "The comparable studies analysed different biomarkers for predominantly short-lived DNA damage. Our study focused primarily on damage to DNA that was subsequently evident in daughter cells following cell division and could therefore be of long-term detriment to the body. However, we can sound the all-clear in this respect - our study clearly shows that, in this case, extreme competitive sport did not result in any increase in DNA damage."

For Prof. Wagner's team, this result shows that a well-trained body responds to increased oxidative stress - and the associated risk of DNA damage - by intensifying the activation of counter mechanisms. These could be mechanisms for repairing DNA, but they could also be means of combating the causal reactive oxygen species.

This interpretation is consistent with other recently published results of this study which show that the body experiences a very rapid and extremely inflammatory reaction during the period of exertion - and that these physiological processes subside equally rapidly. Overall, the results of the FWF project indicate that the effects of extreme sport are very much dependent on the fitness of the individual up to the molecular level.

Funded by the Austrian Science Fund FWF.

Article: S. Reichhold, O. Neubauer, V. Ehrlich, S. Knasmüller & K.-H. Wagner, 'No acute and persistent DNA Damage after an Ironman Triathlon', Cancer Epidemiol Biomarkers Prev 2008, 17(8), 1913-1919. doi: 10.1158/1055-9965.EPI-08-0293

Great Video! :)




The pilot episode of a new science show, Chemical Explorers, is oozing information about fuel cells and catalysts, and it makes several complicated chemistry concepts easy to understand.
It will take you into the Nocera lab at MIT, where postdoctoral scholar Matt Kanan has developed a remarkable new material for hydrogen production.
That substance, a cobalt catalyst, reduces the amount of energy that is necessary to break water molecules, and could be the solution to a longstanding problem: how to safely and efficiently feed fuel cells.
Since it is quite explosive, carrying huge tanks of hydrogen in your car would be dangerous. In theory, it would be possible to bring a jug of water instead and produce little bits of the gas on demand. By passing an electrical current through the ubiquitous liquid, anyone can make tiny bubbles of the earth-friendly fuel, but it takes a lot of energy to do that.
When one of the electrodes is covered with a thin layer of the nifty black substance, breaking hydrogen-oxygen bonds becomes much easier. So easy that the feeble current provided by a solar cell can do it.
If Nocera and his team can further improve upon the catalyst, we may start to see a lot of fuel cells on the road.
Although the first installment of Chemical Explorers, which aired on Monday, feels like a news segment, it has a timeless quality and thus could be a useful part of science lessons for years to come. Crammed with fancy graphics and footage from within a lab at MIT, the new show makes chalkboards seem as obsolete as fossil fuels



From http://blog.wired.com/wiredscience/2008/08/this-video-will.html