Dissecting the genomes of crop plants to improve breeding potential

Posted by Biomechanism 

Scientists on the Norwich Research Park, working with colleagues in China, have developed new techniques that will aid the application of genomics to breeding the improved varieties of crop needed to ensure food security in the future. By dissecting the complicated genome of oilseed rape they have been able to produce maps of the genome that are needed for predictive breeding.

Caption: This is oilseed rape in flower. Credit: John Innes Centre

Traditional breeding involves crossing two varieties and selecting the best performing among the progeny. Predictive breeding is a more advanced technique where specific parts of the genome most likely to contain beneficial genes are identified.

Genomic sequencing and the availability of genetic linkage maps can play a major part in predictive breeding efforts by linking beneficial traits to specific parts of the genome. Researchers and breeders use genetic markers to construct linkage maps, which help to identify useful genes. They are also vital to marker-assisted crop breeding, where the maps and markers can greatly accelerate the breeding in of new improved traits.

However, for key crops such as bread wheat and oilseed rape, the use of this kind of genomics-based predictive crop breeding is severely hampered due to the complicated genomes that these species possess. Many important crop plants are polyploid, possessing several sets of chromosomes. Bread wheat, for example, contains three pairs of chromosomes derived from multiple hybridisation events that occurred between two other wheat species relatively recently in its ancestry. To try to overcome this problem, a team from the John Innes Centre and The Genome Analysis Centre (TGAC), which are strategically supported by the BBSRC, combined sequence data from different sources to construct genetic linkage maps.

The team led by Professor Ian Bancroft worked on oilseed rape, which as well as being an important oil crop also plays a key role in crop rotation strategies. Its oil has industrial applications and its straw can be used for biofuel production. Like bread wheat, oilseed rape (Brassica napus) has a complicated genome, having recently been formed from related speciesBrassica rapa and Brassica oleracea.

The strategy adopted by the group involves integrating the available sequence data for oilseed rape with that of its ancestral progenitors, and also that of a more distantly-related species for which high-quality genome sequence data is available, in this case the model plant Arabidopsis thaliana.

Instead of trying to sequence the DNA, the team focussed on the RNA transcribed from the DNA when the genetic code is expressed. The complete set of all of this transcribed RNA is known as the transcriptome.

TGAC used the Illumina GAII platform for the study, producing a series of consistently high quality sequence datasets from expressed genes.

The team analysed the transcriptome in juvenile leaves, which gives an overview of all of the genes that are expressed in that tissue. Using the sequence variation the researchers were able to construct genetic linkage maps in oilseed rape, eventually identifying over 23,000 markers. This allowed them to align the oilseed rape genome with that of Arabidopsis thaliana and also to sequence data from oilseed rape’s two progenitor species.

This method of dissecting the genome of polyploid crops is likely to be equally applicable to other important crops. Bread wheat is a prime candidate for this, using the model grass Brachypodium distachyon in the place of Arabidopsis.

“Dissecting the genome of oilseed rape like this opens up the possibility of using predictive breeding techniques that will really help with the production of improved varieties” said Prof. Bancroft.

____________________

This study was published in Nature Biotechnology and funded by the BBSRC, the Department for Environment, Food and Rural Affairs and the China National Basic Research and Development Program.

Using a ‘systems biology’ approach to look under the hood of an aggressive form of breast cancer

Posted by Biomechanism 

CANCER RESEARCH: Study is the first to examine how blood protein levels change as cancer develops — long before the disease is clinically detectable.

Using a “systems biology” approach – which focuses on understanding the complex relationships between biological systems – to look under the hood of an aggressive form of breast cancer, researchers for the first time have identified a set of proteins in the blood that change in abundance long before the cancer is clinically detectable.

The findings, by co-authors Christopher Kemp, Ph.D., and Samir Hanash, M.D., Ph.D., members of Fred Hutchinson Cancer Research Center’s Human Biology and Public Health Sciences divisions, respectively, are published online ahead of the Aug. 1 print issue of Cancer Research.

Studying a mouse model of HER2-positive breast cancer (cancer that tests positive for a protein called human epidermal growth factor receptor 2) at various stages of tumor development and remission, the researchers found that even at the very earliest stages the incipient tumor cells communicate to normal tissues of the host by sending out signals and recruiting cells, while the host tissues in turn respond to and amplify the signals. 

“It is really a ‘systems biology’ study of cancer, in that we simultaneously examined many genes and proteins over time – not just in the tumor but in blood and host tissues,” Kemp said. “The overall surprising thing we found was the degree to which the host responds to cancer early in the course of disease progression, and the extent of that response. While a mouse – or presumably a human – with early-stage cancer may appear normal, our study shows that there are many changes occurring long before the disease can be detected clinically. This gives us hope that we should be able to identify those changes and use them as early detection tools with the ultimate goal of more effective intervention.”

Traditionally, it has been thought that tumor cells shed telltale proteins into the blood or elicit an immune response that can lead to changes in blood-protein levels. “What is new here is that the predominant protein signals we see in blood originate from complex interactions and crosstalk between the tumor cells and the local host microenvironment,” Kemp said.

Until now, such tumor/host interactions have been primarily studied one gene at a time locally, within the tumor; this is the first study to monitor the systemic response to cancer in a preclinical tumor model, tracking the abundance of cancer-related proteins throughout tumor induction, growth, and regression. Of approximately 500 proteins detected, up to a third changed in abundance; the number increased with cancer growth and decreased with tumor regression.

“We found a treasure trove of proteins that are involved in a variety of mechanisms related to cancer development, from the formation of blood vessels that feed tumors to signatures of early cancer spread, or metastasis,” Kemp said.

Proteins associated with wound repair were most prevalent during the earliest stages of cancer growth, which could point to a potential target for early cancer detection. “Rather than blindly search for cancer biomarkers, an approach based on comprehensive understanding of the systems biology of the disease process is likely to increase the chances to identify blood-based biomarkers that will work in the clinic,” Kemp said.

The next steps will involve selecting the most promising protein candidates found in mice and determining whether the same circulating proteins are markers of early breast cancer development in humans, with the ultimate goal of designing a blood test for earlier breast cancer detection.

Researchers discover the mechanism that determines cell position in the intestinal epithelium

Posted by Biomechanism

(“Biomechanism.com“) — How do cells know where to position themselves and where to accumulate in order to carry out their functions correctly within each organ?

Researchers with the Colorectal Cancer Lab at IRB Barcelona have revealed the molecular mechanisms responsible for organizing the intestinal epithelium into distinct comportments, defined by frontiers or territories.

The study, headed by Eduard Batlle, coordinator of the Oncology Programme at IRB Barcelona and ICREA Research Professor, is published in today’s online version of the Journal Nature Cell Biology, part of the prestigious editorial group Nature.

A high-magnification view of intestinal epithelium shows the increased numbers of goblet cells and the simple columnar epithelium of a few interspersed absorptive cells. -ucsd.edu

The organization of tissues and organs in the human body can be compared to a very complex and sophisticated engine, whose structure is maintained by positioning its components (cells) in a very precise way. Errors in the assembly (location) of the components might lead to changes in the function of the engine (tissue or organ).

New protein complexes that position cells in the right place

Complex tissues and organs require the separation of diverse cells types into separate zones in order to maintain their architecture. In the case of the intestinal epithelium, the lower part of the invaginations formed by the epithelium, called crypts, contains stem cells that regenerate tissue, while the upper part holds differentiated cells that are responsible for nutrient absorption.

The so-called EphB receptors, present in the cells at the bottom of the crypts, bind to Ephrin ligands located mainly in differentiated cells in the upper part of the intestinal epithelium. The ligand-receptor binding occurs at the frontier between the two cell populations and controls cell positioning in the tissue. However, until now, the way in which these ligand-receptor bindings instruct cells to position themselves in one place or another was unknown.

The results of this study demonstrate that EphB-ephrin bindings activate the metaloprotease ADAM10, which destroys the binding between distinct cell types, such as between cells from the bottom and surface of crypts. It is the destruction of these binding between cells from distinct compartments that prevents cell mixing, thus impeding once cell type from entering the wrong territory. In the words of Guiomar Solanas, first author of the article, “we have found the molecular mechanisms by which EphB receptors and their ligands tell each cell where it has to be throughout its life: from its generation from stem cells in the crypt bottom until its differentiation”.

The loss of cell organization in a tissue is often associated with cancer. In addition to the loss of EphB receptor function in tumors is associated with a worse prognosis for patients. This new regulatory mechanism of affinity between cells types and territory maintenance could be key to our understanding of how less aggressive tumors evolve into malignant ones.

Study: 70 percent of 8-month-olds consume too much salt

Posted by Biomechanism 

Seventy per cent of eight-month-old babies have a salt (sodium chloride) intake higher than the recommended UK maximum level, due to being fed salty and processed foods like yeast extract, gravy, baked beans and tinned spaghetti.

We need to understand that human breast milk provides nutrition, hydration, and protection against infection and disease, as well as comfort, warmth, and security. -Biomechanism.com

Many are also given cows’ milk, which has higher levels of salt than breast or formula milk, as their main drink despite recommendations that it should not be used in this way until babies are at least one year old. High levels of salt can damage developing kidneys, give children a taste for salty foods and establish poor eating practices that continue into adulthood and can result in health problems later in life.

These are the latest findings from researchers at the University of Bristol based on almost 1,200 participants in the Children of the 90s study and just published online by the European Journal of Clinical Nutrition.

The researchers found that the majority of infants were first introduced to solids around 3-4 months, with the mean salt intake for the highest group at 8 months more than double the maximum recommendation for that age group (400mg sodium per day up to 12 months). Infants in this top group often consumed cows’ milk as a main drink, which has a higher sodium content at 55mg per 100g than breast (15mg per 100g) or formula (15-30mg per 100ml) milk. They also ate three times the amount of bread compared to the lowest group, and were given salty flavourings such as yeast extract and gravy.

In the UK, the majority of salt consumed by individuals is added to food during manufacturing, with a relatively small proportion added during cooking or at the table and current intakes in both children and adults are far higher than NICE (National Institute for Health and Clinical Excellence) guidelines.

Speaking about the findings, Dr Pauline Emmett and Vicky Cribb, the nutritionists who conducted the research, said:

‘These findings show that salt intakes need to be substantially reduced in children of this age group. Infants need foods specifically prepared for them without added salt, so it is important to adapt the family diet.

‘This research suggests that clear advice is needed for parents about what foods are suitable for infants. This should be given to all parents and carers and should include the important advice not to use cows’ milk as a main drink before 12 months of age.’

They added that:

‘Given that three-quarters of salt in the diet comes from processed adult foods, successful salt-reduction strategies can only be achieved with the co-operation of the food industry. Manufacturers have a responsibility to reduce the salt content of food products. This process has already started in UK but much more needs to be done. If this study were repeated today it is likely that there would be some improvement but not enough to safeguard the health of all babies. ‘

The researchers studied three-day dietary records (completed by the mothers) of 1,178 8-month-old infants born in 1991/92 and involved in the Children of the 90s study at the University of Bristol. Infants were categorised into four groups of increasing salt intake.

Put the brakes on using your brain power

by Biomechanics 

German researchers have used drivers' brain signals, for the first time, to assist in braking, providing much quicker reaction times and a potential solution to the thousands of car accidents that are caused by human error. 

A brain-computer interface (BCI) device based on electroencephalography (EEG) technology.Using electroencephalography (EEG) – a technique that attaches electrodes to the scalp –, the researchers demonstrated that the mind-reading system, accompanied with modern traffic sensors, could detect a driver's intention to break 130 milliseconds faster than a normal brake pedal response. 

Driving at 100km/h, this amounts to reducing the braking distance by 3.66 meters - the full length of a compact car or the potential margin between causing and avoiding accidents. 

The study, published today, 29 July 2011, in IOP Publishing's Journal of Neural Engineering, identified the parts of the brain that are most active when braking and used a driving simulator to demonstrate the viability of mind-reading assisted driving. 

A detailed video of one of the subjects driving the simulator can be seen here. 

As well as EEG, the researchers, from the Berlin Institute for Technology, also chose to examine myoelectric (EMG) activity which is caused by muscle tension in the lower leg and can be used to detect leg motion before it actually moves to the brake pedal. 

Whilst sat among conventional driving controls, the study's 18 participants were asked to drive a car that was displayed on a screen in front of them whilst a series of electrodes were attached to their scalp to measure brain activity. 

They were asked to stay within a 20 metre distance of a computer-controlled lead vehicle along a road that contained sharp curves and dense oncoming traffic, to recreate real driving conditions, whilst maintaining a speed of 100km/h.

At random intervals, emergency braking situations were triggered by the rapid braking of the lead vehicle in front, accompanied by the flashing of its braking lights. 

At this point, when the subjects reacted, the data was collected from the EEG and EMG. For comparison, the researchers also recorded information on the time it took to release the gas pedal and press the brake pedal, the deceleration of both vehicles and the distance between the two vehicles. 

Using the initial EEG recordings, the researchers were able to determine what parts of the brain are most sensitive in a braking scenario and therefore tweak the detection system accordingly. 

A recent development, implemented into this study, are hybrid systems where external lasers and sensors are able to sense when a potential crash is upcoming so that as soon as the break pedal is touched, the vehicles goes into an emergency braking procedure; however these systems still rely on a human physical response, which is where a mind-reading system could benefit. 

Lead author of the study Stefan Haufe said, "Averaged over all potential detection thresholds, a system that uses all available sensors detects emergency situations 130 milliseconds earlier than a system that doesn't use EEG and EMG. We can safely say that it is mainly EEG that leads to the early detection. 

"We are now considering to test the system online in a real car however if such a technology would ever enter a commercial product, it would certainly be used to complement other assistive technology to avoid the consequences of false alarms that could be both annoying and dangerous."

2 AUG;SRIVILLIPUTTUR;SRI ANDAL& PERUMAL SAYANA THIRUKOLAM;JAYA TV;ADDS S...

அமெரிக்காவை விட அதிகளவு இருப்பு வைத்துள்ள ஆப்பிள் நிறுவனம்

அமெரிக்க தகவல் தொழில்நுட்ப நிறுவனமான ஆப்பிளிடம் உள்ள ரொக்க இருப்பு அமெரிக்க அரசின் ரொக்க இருப்பை விட அதிகம் என செய்திகள் தெரிவிக்கின்றன. ஆப்பிள் நிறுவனத்திடம் 75.87 பில்லியன்(ஒரு பில்லியன்=100 கோடி) டொலர் ரொக்க இருப்பு உள்ளது. ஆனால் அமெரிக்க அரசின் கருவூலத்தில் 73.76 பில்லியன் டொலர் மட்டுமே ரொக்க இருப்பு உள்ளது. அமெரிக்க அரசு தனது கடன் உச்சவரம்பை உயர்த்த வேண்டும் என்று குடியரசு, ஜனநாயக கட்சிகள் கோரிவருவதற்கு பதிலளிக்கும் வகையில் அமெரிக்காவின் கருவூலம் அளித்த பதிலில் இருந்து இந்த விவரம் பெறப்பட்டுள்ளது. அமெரிக்க அரசிடம் உள்ள ரொக்க இருப்பு இந்த அளவிற்குத்தான் என்பதால் கடன் உச்ச வரம்பை உயர்த்த முடியாது என்று பதிலளித்துள்ளது. அமெரிக்க அரசிற்கு தற்போது 14.3 டிரில்லியன்(ஒரு டிரில்லியன்=1000 பில்லியன்) டொலர் உள்ளது. இதற்கு மேலும் கடன் வாங்கினால் அது அமெரிக்காவின் பொருளாதாரத்தை பாதித்துவிடும் என்று அமெரிக்க கருவூலம் கூறியுள்ளது. சந்தை மூலதனமாக 363.25 பில்லியன் கொண்டுள்ள ஆப்பிள் அமெரிக்காவின் மிகப் பெரும் எண்ணெய் நிறுவனமான எக்ஸான் மொபில் நிறுவனத்திற்கு அடுத்தப்படியாக மிகப் பெரிய நிறுவனமாகத் திகழ்கிறது. 3ஜி அலைபேசி வர்த்தகத்தில் அடியெடுத்து வைத்த பிறகு அதன் வளர்ச்சி அபரீதமான அளவிற்குச் சென்றுள்ளது.

Project will study the neural basis of psychopathy

 Psychology & Psychiatry 

A leading University of Chicago researcher on empathy is launching a project to understand psychopathy by studying criminals in prisons.

Jean Decety, the Irving B. Harris Professor in Psychology and Psychiatry, has received a $1.6 million grant from the National Institute of Mental Health to use fMRI technology to examine the neural circuitry of criminal psychopaths.

The research comes at a time of increased awareness about the role that mental health plays in crime, including questions about the suspects accused in recent mass murders in Norway and in Arizona.

Through the project, Decety and his colleagues intend to study mental health by measuring the activity of brain networks necessary to experience empathy among a prison population and compare the results with data from healthy individuals.

Although only one percent of the general population has psychopathy, between 20 and 30 percent of the prison population are psychopaths. Criminal psychopaths are disproportionately responsible for crime and typically commit five major crimes by the time they are 40, research shows.

Little is understood about psychopathy, and almost no treatments have been developed that have been effective.

"If psychopathy is to be treated effectively, targeted therapies and interventions must be developed based on the underlying causes of the disorder," Decety said.

Other attempts at studying psychopathy have been inadequate because they were based on inferences about brain functioning not based on neuroimaging, or they had small sample sizes, Decety pointed out.

"Our project will correct all of these issues and be the first to be in a position to adequately address the underlying neurological differences characterizing psychopathic offenders with respect to empathic processing," he said.

Decety has conducted extensive studies on empathy with children, adolescents and adults that have shown, for instance, that the brain circuitry among bullies is different from that of other children.

In his studies on empathy, Decety shows subjects video clips of intentional and unintentional harm and measure responses in their brain circuits, particularly the insula, amygdala and orbitofrontal cortex. A similar approach will be used in the psychopath study, to be conducted in New Mexico prison facilities, where he will work with Kent Kiehl, Professor of Translational Neuroscience at the University of New Mexico.

The Kiehl Lab at the MIND Research Network has an established relationship with the New Mexico correctional system and is conducting ongoing research in three of the 10 state correctional facilities.

Participation rates among the prison population have been excellent, with 85 percent of the population volunteering to participate.

Decety's project will cover four years and will include collecting data on 160 men with varying levels of psychopathy. The results will be compared with those of a control group of non-criminals with similar socioeconomic backgrounds and histories of drug use and psychiatric problems.

Provided by University of Chicago

"Project will study the neural basis of psychopathy." August 1st, 2011. http://medicalxpress.com/news/2011-08-neural-basis-psychopathy.html

Posted by
Robert Karl Stonjek