The Year of the Dragon – What Its Genome Tells Us
According to the Chinese zodiac, 2012 is the Year of the Dragon. Dragons often appear in Chinese traditional beliefs as a large lizard, symbolising power, magic and prosperity. These creatures are also found in other cultures, from mythical European legends to spiritual Indian epics.
It is impossible to sequence and study the genome of such dragons, the obvious reason being, of course, because they are legendary creatures only found in storybooks but not in nature. However, assuming that the dragon is closely related to the lizard, we could only imagine what its genetic make-up would be like by looking at the first reptile genome made available.
Anolis carolinensis, or more commonly known as the green anole lizard, is the first non-avian reptile to have its genome sequenced. Amniotes, the first terrestrial vertebrates, diverged from other animals some 320 million years ago to form the mammalian and reptilian lineages, and reptiles further branched to lizards and birds. Results from the analysis of its genome, and the comparative analysis against birds and mammals, were published in August 2011. The results highlighted unusual features of the lizard genome, and revealed some extraordinary findings that could shed light on certain evolutionary mysteries.
Anoles are known to have good colour vision, including the ability to see in the ultraviolet range and to distinguish between similar colours and patterns. Anoles rely on colour vision to identify choice mates by recognising the vividly coloured flaps of skin beneath their necks. Thus, the family of genes that contributes to their excellent colour vision, known as opsins, is also responsible for their hyperdiversity.
In the anole lizard genome, scientists found an uncommon number of genes associated with colour vision. They uncovered 11 opsin genes that have no mammalian orthologues, yet all mammalian opsins have orthologues in anoles.
Using SynaSearch™, we can confirm the absence of an opsin gene in mammals and also examine the orthologues in other species. The pineal gland, or the ‘third eye’, of the lizard is used to detect irradiance and temperature. Mammals also have the pineal gland, but without the ability for photosensitivity. Therefore P-opsin (pineal gland-specific opsin) is expected to be absent in mammals.
From the SynaSearch™ results, it can be seen that anole P-opsin is highly similar to the opsin genes in chickens and frogs, besides other known lizards. To focus on the study of the evolution of reptiles, we can use SynaCompare™ and SynaTate™ to further compare the chicken and lizard P-opsin genes.
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Click here, to submit your queries in SynaSearch™.

Select ‘Protein-Protein’ for query type.

Click submit.

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Results show the top hits for anole P-opsin gene in NR-BLAST protein database:

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Click on link under score of results number 9 (pinopsin Gallus gallus) to view its alignment.

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Burkitt’s Lymphoma
Burkitt’s lymphoma is an aggressive cancer of the white blood cells which occurs most often in children and young adults. It is a common form of malignancy in children in Equatorial Africa, and is also frequently associated with immunocompromised individuals, such as those suffering from AIDS.
This disease is associated with a chromosomal translocation, between chromosomes 8 and 14 of the myc gene. This gene is a regulator gene that codes for a transcription factor. In most cases of Burkitt’s lymphoma, the reciprocal translocation shifts the proto-oncogene myc from its normal position on chromosome 8 to a location closer to the enhancers of the antibody heavy chain genes on chromosome 14.
This t(8;14)(q24;q32) translocation causes the myc gene to be persistently expressed, resulting in continuous cell division without control or order. A defining feature of Burkitt’s lymphoma is the presence of this translocation between the myc gene and the IgH gene.
SynaSV™ is an MGRC online tool specifically designed to visualise structural variations. This powerful application can be used to visualise translocation mutations.
Here, we showcase how SynaSV™ can be used to view and identify structural variations in the IgH-myc gene fusion.
With MGRC’s genetic screening services, mutations such as the IgH-myc gene fusion are detected for common and rare genetic disorders. Early screening of this disease will enable the cancer to be identified when it is still localised. This would enable target therapy to be more effective.
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Click here, to submit your query.
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On the result page, it is displayed that the two highest scoring matches are two different targets. Select these targets by clicking on the respective check boxes. A structural variation graph will appear.

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From the graph, it can be observed that that the query (middle) is split across a breakpoint, where the first part matches to chromosome 8 (top) and the second part to chromosome 14 (bottom).

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In the structural variation graph, the statistics table indicates that the structural variation is an inter-chromosomal translocation.

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Can We Detect Non-Halal Elements in Food?
It was recently reported that the Department of Islamic Development Malaysia (JAKIM) had confirmed that a particular brand of dairy product was non-halal after it was found to contain porcine DNA. This discovery not only affects consumers of the product but also renders other products, which use it as an ingredient, non-halal. This clearly highlights a case of inaccurate food labelling, an issue which is of great concern to most consumers of edible products.
Consumers come from various backgrounds and unique lifestyles, especially in a multicultural country like Malaysia. Many people are committed to observing food restrictions, which could be due to religious principles, lifestyle, food allergies or medical requirements. For these consumers, food labels are imperative in helping them make the right purchase. With this in mind, it is essential that food manufacturers accurately and truthfully label their products. To protect the rights of consumers, the sources and composition of all products have to be properly tested and verified prior to the products being sold. For this purpose, DNA-based methods can be employed to identify and detect traces of contamination in a product. Using specific DNA sequence regions, primers or probes unique to specific meat or plant species can be designed.
A suitable sequence region to use for probe design is the mitochondrial DNA (mtDNA) of various animals or plants. The mtDNA sequence is often used in population genetics studies as its gene content is believed to be strongly conserved. The existence of multiple copies of mtDNA in the cell also makes DNA amplification relatively easier. Using the cytochrome b sequence of Sus scrofa (wild pig) as an example, users can submit the sequence as a query on SynaProbe™ to design unique probe sequences to detect traces of pork. The specificity of these probes can be further verified with SynaHybridise™ to ensure accurate identification and detection of the targeted porcine species. In the example, the hybridisation of the probe to various breeds and isolates of the meat samples highlights the success of the probe in identifying the meat species, regardless of its breed.
The designed short sequences display much flexibility in terms of their application. Polymerase chain reaction (PCR) is already commonly employed in laboratory testing to provide specific and sensitive detection of trace contaminants in food products. While PCR is a hugely popular option, users may also consider microarray testing. The inclusion of hundreds to thousands of probes per microarray chip might potentially allow for the simultaneous detection of multiple contaminants within a product, resulting in a shortened testing time.
To design unique probe sequences specific to an animal or plant species:
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Click here, then click on .

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On the results page, click on to verify the specificity of the selected probe sequence.

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Results generated show the number of matches to the probe accompanied by a list of matches. From the list of hits, the probe is demonstrated to match all types of Sus scrofa isolates and breeds.

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Fatty Foods Make You Want to Munch!
If you love French fries, burgers or deep-fried snacks, you had better read on.
A group of researchers has shown that eating fatty foods may make you want to munch even more. In the study, rats that tasted fat in their food kept on eating, thanks to endocannabinoids. Endocannabinoids are the body’s equivalent of cannabinoids, the active ingredient in marijuana, and are reportedly released in the brain and body.
Rats on a fat diet registered an increase in endocannabinoid activity, thus demonstrating a link to binge-eating. When given compounds that blocked the cellular ‘buttons’ triggered by the endocannabinoids, the rats stopped eating immediately. According to the lead researcher in this study, the findings may prove pivotal in assisting scientists to develop drugs that can combat binge-eating and similar weight-related conditions.
SynaTate™ is an online application that annotates and interrogates data to identify structural and functional motifs in query sequences with patterns stored in SynaBASE™, MGRC’s proprietary database. The analysis of the cannabinoid receptor 1 gene (endocannabinoid receptor) using SynaTate™ revealed that it has a potentially active region on the third forward reading frame. This frame encodes for the melanocyte-stimulating hormone receptor which produces the melanocyte-stimulating hormone (MSH). MSH is found in the brain and has been shown to have an effect on appetite. The findings open up the possibility of developing drugs that block the metabolism of intestinal endocannabinoids to treat binge-eating, obesity and other eating disorders.
Subsequently, the gene was compared against the SwissProt database using SynaCompare™. The comparison showed that the conserved region is the same in both rat and mouse, thus making the latter a suitable model for expression studies of the cannabinoid receptor 1 gene. This is especially useful as mice are cheaper and easier to obtain, and are ideal for genetic research.
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Click here to submit query.

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The results page shows that significance is predicted on the third forward reading frame, F3. Select the significance region on F3 by left clicking and dragging across. Right clicking within the selection will display a list of options. Select ‘Annotate nucleotide sequence’.

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The results show that the cannabinoid receptor 1 gene encodes for the melanocyte-stimulating hormone receptor. The receptor produces melanocyte-stimulating hormone (MSH) which has the ability to control appetite.

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Click here to compare the cannabinoid receptor 1 gene against the SwissProt database.

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The results show that mouse has the closest homology to rat. Click on the ‘Show’ button to view the respective graphs.

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The dot-plot graph shows a diagonal line, which indicates that there is homology between rat and mouse. These regions could be useful for studying the expression of the gene, with the aim of developing drugs to overcome weight-related problems.

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Rescuing Parkinson’s Dying Neurons
Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. Though this debilitating disease affects approximately 1% of the world’s population over the age of 60, the onset can occur as early in life as adolescence. The progressive loss of dopaminergic neurons from the mid-brain causes degeneration of the central nervous system due to impaired dopaminergic input. Since dopamine is crucial in sending signals for human movement coordination, this disorder affects the motor system, causing postural instability, trembling in limbs and impaired balance, for example.
Current treatments, which include neurotrophic factors and transplantation of dopamine-producing cells, have thus far only been partially effective. However, researchers in Sweden have now found that a protein, platelet-derived growth factor-BB (PDGF-BB), is effective in counteracting behavioural, tissue and biochemical effects caused by PD.
Treating rodent models with PD using PDGF-BB has resulted in the increased survival of dopaminergenic cells and the proliferation of neural progenitor cells. These findings suggest a new approach in repairing dysfunctional dopaminergic systems within PD patients. PDGF-BB has been shown to counteract the effects of PD in the experimental models and, depending on clinical trials, could soon be a candidate drug for treating PD in humans.
Both rat PDGF-B and human PDGF-B can be annotated using SynaTate™. SynaTate™, a free online bioinformatics application, displays predicted functions of PDGF-B based on protein structural motifs according to the SWISSPROT database. The structural functions in rat and human PDGF-B, respectively, have to be compared in order to better understand the homologues’ gene expression, protein-protein interaction and their role in pathways. It is widely believed that further analysis could help bring scientists closer to treating PD in humans.
Source : Science Daily
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Click here to submit your Query 1.

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Select the respective reading frames containing predicted significance.

To find out what the function is, select the region of interest by holding the left-click and dragging it across. Right click within the selection and click ‘Annotate nucleotide sequence’.

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The results page will show the annotated protein structure.

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Click here to submit the sequence for Query 2.

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‘Drinker’ Gene Identified
Are alcoholic habits determined by genes?
A recently published study has revealed that a gene related to autism, called autism susceptibility candidate 2, or AUTS2, is linked to increased alcohol consumption. The AUTS2 gene is most active in parts of the brain that deal with ‘reward’ mechanisms and influence a person’s decision whether to have another drink or not.
In a study of more than 47 000 people, researchers discovered that there are two variants of the AUTS2 gene, where one variant is three times more common than the other. The study also found that individuals with the less common of the two variants drank on an average five percent less alcohol than those with the more common version.
After identifying AUTS2, the researchers examined the levels of messenger RNA present in post-mortem human brain tissue. Gene expression analysis confirms that there is a direct correlation between levels of the mRNA for AUTS2 and lower alcoholic tendencies.
To measure gene expression levels of AUTS2, a suitable and specific probe for the AUTS2 gene has to be designed. SynaProbe™ designs and selects suitable oligomer probes for a gene of interest, in this case, AUTS2. This free online application is especially more effective when used with SynaHybridise™ which verifies the specificity of the selected probe sequence.
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Click here to submit your query.

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On the results page, click on to verify specificity of probe sequence.

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The result demonstrates that the selected probe is specific, with only one possible binding site in the genome.

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Edging Closer Towards Understanding Alzheimer’s
Understanding four new genes for Alzheimer’s disease through SynaBlast-Mega, a bulk search application
Researchers from a consortium of 44 universities and research institutions in the United States have identified four new genes linked to Alzheimer’s disease (AD). These genes could provide clues to the causes of the disease and subsequently lead to the discovery of more effective drugs to treat or cure this degenerative disease. Genetic studies could also help scientists better understand the mechanisms that occur in the brain even before the symptoms are observed.
The genes mentioned in the paper are MS4A, CD2AP, CD33, and EPHA1.
SynaBlast-Mega™ is a multiple sequence alignment tool that enables users to search for several protein or nucleotide sequences simultaneously. This tool makes it easier for researchers to analyse bulk sequences as it allows the submission of numerous sequences at any given time. Comprehensive alignment options are provided and the final results are presented in various alignment output formats. Researchers can use this application to discover protein homologs within other species of the multiple AD-susceptibility genes. This information would add value to studies on AD progression that use model organisms.
Source : Science Daily
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Click here to get the test sequence pre-loaded.

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Key in a name that you can easily remember in the ‘Job title’ box.

Click on the ‘Submit query’ button.

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Once your query submission has been completed, download your results file, which will be in a .zip format, by clicking on ‘Download result file’.

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The downloaded file can be extracted using programmes such as WinRAR or 7zip. You can right click on the file within the extractor and select ‘View file’ which will display the results of your alignments.

The file can also be viewed using WordPad.

Looking through the alignments, you can see that all the genes have close homologs within many other species.

These species can be used as model organisms to study the expression and interactivity of the genes within pathways that lead to AD.

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MGRC Celebrates the Year of the Rabbit
A Chinese folklore tells of a Jade rabbit that lives on the moon as a companion to the Moon Goddess. It is also said that the rabbit consistently pounds herbal medicine in a mortar, manufacturing elixirs of life for the goddess.
Today, we can conclusively say that the rabbit’s involvement in the medical field is not restricted to folklore. In recent years, scientists have also come to recognise the importance of these cute creatures to biomedical research, especially in the study of immunology. The European rabbit genome (Oryctolagus cuniculus) was first sequenced and assembled at 2x coverage in 2005. Subsequently in April 2009, the genome was sequenced again, this time with a completed higher quality draft assembly of 7x coverage. Rabbits suffer from many sicknesses similar to human diseases and have the ability to rapidly produce large amounts of highly specific antibodies in response to foreign disease agents, making them great models for the study of human autoimmune diseases.
An example of the use of rabbits as research models is in the study of Systemic Lupus Erythematosus (SLE), an autoimmune disease which occurs in both rabbits and humans. SLE results in an overactive immune response which attacks otherwise healthy cells and tissues, sometimes leading to the eventual death of the patient. To date, the cause of SLE is still unknown and there is no cure for it.
However, over the past decade, scientists have made good progress in the efforts to cure SLE, focussing on the targeting and elimination of B-cells. B-cells are triggered by the B-cell activating factor (BAFF) and are responsible for tissue damage through the generation of antibodies. Scientists have turned to the rabbit SLE model to better understand the function of BAFF and its receptors. For this purpose, a comparison of sequences from human and rabbit BAFF homologues is necessary to ensure confident research correlation.
With SynaTate™, researchers can locate regions of significance within a sequence. In this example, the rabbit BAFF was queried against an NR database, revealing a region of interest in the first forward reading frame. The specific region in the rabbit BAFF sequence was then selected and searched against the SwissProt database with SynaSearch™, indicating that the closest match to rabbit BAFF is the tumour necrosis factor ligand superfamily member 13B (TNFSF13B) protein in humans. As expected, TNFSF13B is also involved in the stimulation of B- and T-cell functions in the human immune system. With this knowledge, researchers would be able to design inhibition or knockout experiments in rabbits to further study the potential of TNFSF13B reduction in curing SLE disease.
As more associations are formed between the human and rabbit genomes, the rabbit model is expected to play a significant role in biomedical studies of diseases and in the eventual development of cures and vaccines.
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To locate regions of significance within a sequence of the rabbit’s B-cell activating factor:
Click here, then click on .

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From the results, a region of significance is observed in the first forward reading frame. Select the region of interest by left-clicking and dragging across the entire selection. A right-click within the selection will give a list of options. Select ‘Search nucleotide sequence’.

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Within SynaSearch™, set ‘Nucleotide-Protein’ as the query type and SwissProt UPKB as the target SynaBASE. Select ‘Submit query’.

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The top match with the highest score is the human tumour necrosis factor ligand superfamily member 13B protein (TNFSF13B). Click on the corresponding score to bring up a sequence alignment of the target sequence to the query sequence.

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Sequence alignment shows the percentage of identity between the two sequences. The report also states the respective start and end positions of the aligned region on the target strand.

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Cancer’s Favourite Gene
Notorious Gene Protects Tumour Cells against Chemotherapy
The astrocyte elevated gene-1, or AEG-1, is well-known for its involvement in tumour cell development and metastasis. However, researchers at the Virginia Commonwealth University have now discovered that this notorious gene has another sinister function – it protects cancer cells from the effects of chemotherapy.
The new study shows that via its molecular mechanism, AEG-1 has the ability to induce chemoresistance, which is an important characteristic of aggressive cancers that contributes to cancer cell survival. In the advanced stages of many cancers, AEG-1 expression is elevated. Hence it most likely plays an important role in regulating cancer progression and ultimately, metastasis.
Yet all is not lost, thanks to emerging bioinformatics technologies. It is believed that by inhibiting the expression of this gene, new effective approaches for treating aggressive cancers may be developed. Researchers can now investigate how AEG-1 promotes resistance to chemotherapy and enhances cancer cell survival. With this knowledge they will be able to design experiments that aim to knock out the AEG-1 function by targeting the functional regions of the protein. This can then be used in molecular modelling studies to design leads that could inhibit this gene and its regulated pathways, thereby uncovering potential therapeutic targets for enhancing the ability of anti-cancer drugs to fight tumours.
SynaTate™ is a free bioinformatics tool designed by MGRC to annotate next generation sequencing data. Using this application against an NR protein database, we can confirm that the protein-encoding region (CDS) is as expected within the first forward reading frame. Searching this CDS region against the SwissProt database reveals that AEG-1’s closest match is the LYRIC protein. LYRIC proteins are known inducers of tumour cell expansion and metastasis, as well as chemoresistance within those cells.
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Click here, then click on .

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The results page clearly displays that significance is predicted on the first forward reading frame.

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To find out what the function is, select the region by holding the left-click and dragging it across the entire selection as shown. Right click within the selection to bring up a menu, on which you should click ‘Search nucleotide sequence’.

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In the following link within SynaSearch, select ‘Nucleotide-Protein’ as your query type and select SwissProt UPKB as your target SynaBASE. Select ‘Submit query’.

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The SynaSearch results page indicates that the top three matches belong to LYRIC proteins. It can be seen that LYRIC is the common conserved region in different organisms as it is 91% identical to Mus musculus. Researchers can further investigate the chemoresistance mechanism by knocking out the LYRIC gene, thus finding new therapeutic targets to design novel drugs for fighting cancer.

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To retrieve sequence alignment, click on the score.

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Breathing Life into the Fight Against Cancer
An Approach Towards Personalised Treatment for Lung Cancer Patients
Lung cancer is a major cause of death throughout the world with 1.3 million new cases diagnosed every year. The overall survival rate of lung cancer patients is about 16% within five years. Lung cancer occurs due to uncontrolled growth of aberrant cells across the epithelial lining of the breathing tubes and surface of the lungs. Main causes of lung cancer include cigarette smoking, which is responsible for 90% of cases, passive smoking and exposure to asbestos fibres.
Since a major category of lung cancer, non-small cell lung carcinoma (NSCLC), has subtypes with complex patterns of mutations in different genes, treatment is largely ineffective. Pharmaceuticals are typically targeted to individual proteins – for example, some drugs target epidermal growth factor receptors (EGFRs) to block EGF attachment. Moreover, tumours with similar clinical characteristics (location, pathology, size, stage) may respond differently to the same drug.
Pathway-targeted chemotherapeutic agents are new, more effective molecules for lung cancer treatment. A protein kinase inhibitor, AZD6244, is recommended for treating advanced NSCLC, where it inhibits mitogen-activated protein kinase (MEK) in a well-studied cellular survival pathway to cause apoptosis, thus killing off the cancer cells.
AZD6244 seems to be a godsend for some patients but not all NSCLC cases are sensitive to this drug. Scientists now think they know why.
One of the observable differences between AZD6244-sensitive cells and their insensitive counterparts is the high levels of phosphorylated AKT. AKT is activated by phosphorylation to inhibit cell apoptosis through a separate pathway. Since AZD6244 and AKT are involved in two parallel pathways, AZD6244 does not work on patients with abnormal constitutively active (phosphorylated) AKT.
The phosphorylation of AKT is negatively regulated by the phosphatase PTEN. Thus, an abnormally low level of expression of PTEN indicates the presence of constitutively active AKT, which leads to insensitivity to AZD6244.
Using SynaProbe™, oligonucleotide probes can be designed to evaluate the level of expression of PTEN in patients for quick prognosis of drug sensitivity. With this, a more personalised cancer treatment becomes possible, thus reducing the chances of erroneous prescriptions of drugs and improving more lives through the delivery of appropriate treatments. Instead of grasping at straws through trials with different therapeutic drugs, more lung cancer patients can now see hope in the near future.
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Click here, then click on .

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Click to select the probe of interest. Here we selected Probe 1, which has the highest score.

Click on the SynaHybridise icon at the right corner.

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The result shows that the probe has high specificity and uniquely matches PTEN.

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