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chanon chiarnpattanodom

Cancer epigenetics takes center stage - 1 views

    • chanon chiarnpattanodom
       
      DNA methylation is a chemical process where a methyl group is added on either the cytosine ring or the adenine ring, used in "higher leveled" organisms. Important in cell differentiation since methylation will cause cells to "remember" and remain differenciated instead of expressing other genes. 
  • Epigenetics is defined as modifications of the genome, heritable during cell division, that do not involve a change in the DNA sequence.
  • Epigenetic alterations in cancer include global hypomethylation
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  • the promoters of housekeeping genes that are generally protected from methylation.
  • may lead to aberrant silencing of tumor suppressor genes
  • discovered loss of imprinting (LOI) in cancer
  • Genomic imprinting, the subject of the report by Nakagawa et al. (2), is an epigenetic modification of a specific parental allele of a gene, or the chromosome on which it resides, in the gamete or zygote, leading to differential expression of the two alleles of the gene in somatic cells of the offspring.
  • we found that LOI can occur in the normal colonic mucosa of colorectal cancer patients with LOI in their tumors
  • This LOI was linked to cases showing microsatellite instability (MSI) in the tumors
  • However, these patients do not have mutations in mismatch repair genes
  • One potential cause of MSI in these sporadic cancers is hypermethylation and epigenetic silencing of the hMLH1 mismatch repair gene
  • Nakagawa et al. (2) now confirm the original study of Cui et al. that LOI occurs in both tumor and normal tissue of patients
  • The present study (2) also offers an intriguing mechanistic hypothesis to explain the relationship between H19 DMR methylation and LOI in these patients
  • Nevertheless, the study calls attention to this remarkable highly conserved multifunctional protein,
  • The potential link to CTCF suggested by this study also calls our attention to the link among DNA methylation, epigenetics, and chromatin.
  • A clue to the link between MSI and epigenetics may be provided by another sometimes overlooked common thread in epigenetics, namely DNA replication
  • repeat-induced gene silencing is thought to be propagated through hemimethylated intermediates during DNA replication
  • The studies of Cui et al. (11), Nishihara et al. (20), and Nakagawa et al. (2) suggest a new and provocative view of the timing of epigenetic changes in cancer.
  • Studies of transgenic mice with constitutive biallelic expression of IGF2, comparable to LOI, show reduced apoptosis and increased tumor formation
  • I conclude by noting that the distinction between cancer genetics and epigenetics has blurred considerably in recent years
  • Many conventional “genetic” mechanisms directly affect proteins that regulate chromatin,
adisa narula

Breaking the Silence: The Rise of Epigenetic Therapy - 0 views

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    Cancer epigenetics is hot. At the annual meeting of the American Association for Cancer Research in April, once-obscure principal investigators were feted by gaggles of admirers and many poster presenters mobbed by the curious. "It's one of the hottest areas of basic biology," said Paul Workman, Ph.D., director of cancer therapeutics at Cancer Research U.K.
Paige Prescott

Old Cancer Drugs Offer New Tricks - Science News - 0 views

  • Drugs that alter some chemical tags on DNA make cancer cells behave more like normal cells
  • And the drugs seem to make cancer cells more susceptible to chemotherapy and attacks from the immune system.
  • drugs called azacitidine and decitabine, when used in low doses, change gene activity in leukemia and breast cancer cells in the lab. If DNA is a cell’s hard drive, then chemical tags attached to the DNA or DNA-packaging proteins called histones serve as software packages to tell the hard drive how to function. This type of chemical programming is called epigenetics.
Kaoko Miyazaki

Long Intergenic Noncoding RNAs: New Links in Cancer Progression - 1 views

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    The newly discovered and currently being researched lincRNAs are seen to be one of the causes of cancer. The function of lincRNAs to control gene expression by regulating the number of histones according to specific chromatin, may cause cancer when done wrong or are altered in some way. The epigenetic alterations that occur when this function is done wrong may lead to the disease and the inheritance of it. Which could be hypothesized as to why people with a history of cancer (and other diseases) within their families have higher likelihood to being diagnosed with the disease. But because lincRNA is a very recent discovery and only less than 1% of it has has been characterized in the human body, evidence of this is still being researched, tested and studied.
Kantham Hongdusit

Improved Understanding Of Cancer Progression - 0 views

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    Researchers in IMIM have discovered the function of the enzyme LOXL2, which is one of the factor causing cancer. The enzyme interacts with histone H3, and changes the DNA sequence around that histone, eliminating the lysine 4 amino acid group, which favors tumor development
Sasicha Manupipatpong

Divergent evolution illuminated: Light shed on reasons behind genome differences betwee... - 0 views

  • divergent evolution of the genomes of different groups of species
  • three large domains: Archaea, Bacteria and Eukarya
  • genomes of each group have evolved towards distinct structures that have favored their separation
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  • connection between the function of enzymes and the composition of the genomes shed light on the evolution and structure of genes
  • analyzed the distribution and abundance of transfer RNA genes
  • structure of genomes was adapted to the activity of some enzymes, which differ for Bacteria and for Eukarya and are absent in Archaea
  • activity of these enzymes modifies tRNAs, allowing them to recognize up to three distinct codons
    • Sasicha Manupipatpong
       
      Prior to the study, it was understood that tRNA's have a specific anti-codon sequence which would recognize a single mRNA codon with the complementary sequence. Does this mean that the tRNA also attaches to different amino acids as well? How does the tRNA differentiate between the different amino acids it is at that moment carrying and the codon it matches with on the mRNA--does it change shape according to which amino acid is attached to it?
  • activity of the bacterial and eukaryal enzymes is different, which explains why the genomes and the gene composition of bacteria, eukarya, and archaea have diverged
  • relation between genome structure and the speed of protein synthesis from its genes
  • demonstrates how organisms have evolved in a different manner to achieve better adaptations and to have optimum protein translation efficiency
  • biotechnology as the discovery of the relevance of these modifications will allow an improvement in the industrial production of proteins
  • another parameter with which to optimize the synthesis of proteins from a gene
  • human insulin is "manufactured" in bacteria and our discovery would allow this production to be increased if we take into account the activity of these enzymes
  • relevant for the study of cancer: "it is possible that these modification enzymes are over-represented in some kinds of cancer. In fact, this would be logical because cancer cells are highly efficient in producing proteins."
  • greater the abundance of a protein in a cell the higher the number of triplets found in its gene sequence that can be read by modified tRNAs
  • don't exactly know why these enzymes appear or why they are different in bacteria and in eukaryotes but it's clear that they contribute to the separation of genomes of these two groups
  • genetic code is the same
  • what has changed is the relative importance of different codons of the code
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    A recent study uncovers the reasons for the divergent evolution of the genomes of different species. The findings provide information about tRNA modifications which may prove useful in the field of biotechnology, specifically in the industrial production of proteins
Nickyz P.

GEN | Magazine Articles: Firm Focuses Operations on Gene Silencing - 0 views

  • It is developing therapeutics to prove the validity of ddRNAi in treating cancer, infectious diseases, and disorders of the central nervous system.
  • The ddRNAi platform focuses on the long-term downregulation of genes, making it suitable for targeting chronic life-threatening diseases. “We are silencing genes instead of introducing new genes, which separates us from traditional gene therapy companies,” Dr. French asserts.
  • “This targeted treatment markedly enhanced the benefits of radiation therapy in both cellular and tumor models,” the researchers concluded. Other radiotherapy-resistant tumors may benefit from the shRNAs created for the prostate cancer study.
Nitchakan Chaiprukmalakan

Missing Lincs - Science News - 6 views

    • Nitchakan Chaiprukmalakan
       
      Scientists are finding more information about the importance of the non coding RNAs, lincRNAs.
  • Only now have scientists begun identifying the previously invisible contractors who make sure that materials get where they are supposed to be and in the right order to build a human being or any other creature. Some of these little-known workers belong to a class of molecules called long intergenic noncoding RNAs.
  • And the lincRNAs originate in what scientists used to view as barren wastelands between protein-coding genes. But new research is showing that these formerly underappreciated workers have important roles in projects both large and microscopic.
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  • In the last few years, scientists have learned that lincRNAs, as well as other RNAs that are long and noncoding but not intergenic, perform a variety of jobs. Some serve as guides showing proteins where to go, while others tether proteins to different types of RNA, or to DNA. Some work as decoys, distracting regulatory molecules from their usual assignments. Some may even have multiple roles, all the while chattering away to other RNA within cells. (It is not idle gossip; RNA communication within cells may ward off diseases such as cancer.) And as the ultimate multitaskers, lincRNAs keep proper cellular development ticking along and help define what makes mice mice and people people.
  • That archive contains about 3 billion genetic letters, far more than the genomes of less complex organisms such as roundworms and fruit flies.
  • In 2005, the research revealed that even though genes that code for proteins make up only 1.5 percent of the mouse genome, more than 63 percent of the genome’s DNA is copied into RNA. In humans the number is even higher, with up to 93 percent of the genome made into RNA, even though protein-coding genes make up less than 2 percent of the genome.
  • At first, many scientists didn’t know what to make of the excess RNA. Some thought it was overexuberance on the part of the DNA-copying machinery. But gradually researchers began to realize that many of those extra RNAs had important jobs to do.
  • Some, though, appear to act like general contractors — not hammering in the nails and pouring the foundations of cells themselves, but dictating how the job should be done.
  • One of the most famous long noncoding RNAs, known as XIST, is also one of the most hands-on. XIST is in charge of shutting down one of the X chromosomes in every single cell of women and girls
  • XIST doesn’t have a long commute to work; it coats whichever X chromosome makes it, preventing other genes on the chromosome from being activated
  • One of the most well-studied linc­RNAs, named HOTAIR, wasn’t lucky enough to get a job close to home. It is copied from DNA on chromosome 12 but has to travel to chromosome 2 to shut down several genes in a group known as the HOXD cluster, genes important for proper development of an organism
  • Not only does HOTAIR help direct development, but it is also important throughout life to help cells pinpoint their location in the body.
  • Whether promoting health or mis­directing cells, lincRNAs don’t necessarily act alone.
  • A lincRNA known as HOTTIP also works with a crew of histone modifiers, but instead of shuttering genes, HOTTIP’s crews hang grand-opening signs to attract gene-activating machinery
  • In the recipe for humans, lincRNAs are in the thick of things from the very beginning. At least 26 different lincRNAs need to be on to keep an embryonic stem cell a stem cell
  • Just how lincRNAs choose which genes to turn on and off isn’t yet known. But Pier Paolo Pandolfi, a geneticist at Beth Israel Deaconess and Harvard Medical School, suspects that the lincRNAs are whispering to each other and to other RNAs, keeping tabs on all a cell’s goings-on. Pandolfi laid out his hypothesis for how this chatter might help control protein production and other processes in the Aug. 5 Cell.
  • The Columbia team and Pandolfi’s team independently found that tweaking levels of a few messenger RNAs that distract microRNAs from PTEN messenger RNA can lead to prostate cancer or a type of brain tumor called glioblastoma. Just messing with levels of a messenger RNA from another gene known as ZEB2 throws off PTEN protein levels and can lead to melanoma in mice, Pandolfi’s group reported in another paper in the Oct. 14 Cell.
  • Losing one noncoding RNA may be disastrous for a cell, but for want of noncoding RNAs whole species may never have evolved, argues Queensland’s Mattick. He and others say the real function of lincRNAs is to give evolution a sort of molecular clay from which to mold new designs.
  • Humans have several lincRNAs that are found in no other species. Many of those RNAs are made in the brain, leading scientists to speculate that the molecules may be at least partially responsible for that important organ’s evolution.
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    Is RNA the most important molecule in the cell? There is a lot of evidence leading to new understandings of RNA and it's role in many different mechanisms within a cell.
Sasicha Manupipatpong

DNA sequencing helps identify cancer cells for immune system attack - 1 views

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    DNA sequences from tumor cells can be used to direct the immune system to attack cancer, according to scientists. The immune system relies on an intricate network of alarm bells, targets and safety brakes to determine when and what to attack.
Sea Maskulrath

Shocking pictures show group of 14-year-old schoolboys puffing on shisha pipes in bar |... - 0 views

  • A video of a group of 14-year-olds smoking shisha pipes in a bar has emerged online, horrifying parents and anti-smoking campaigners.
  • They want to warn shisha enthusiasts it isn't a safe alternative to cigarettes - smoking a pipe for an hour is the the equivalent of puffing away on 100 cigarettes.
  • ‘Smoke from tobacco contains a number of carcinogens which damage the DNA in cells,’
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  • ‘Just one damaged cell can divide and multiply uncontrollably and quite quickly develop into a large tumour. This is what causes lung cancer,
  • around from person to person, this raises the risk of transmitting diseases such as tuberculosi
  • As the mouthpiece is passe
  • nd hepatitis.
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    WOW, I guess we know we had to stop shisha right? unbelievable 
nidthamsirisup

Mysterious Noncoding DNA: 'Junk' or Genetic Power Player? | PBS NewsHour - 0 views

  • Genes represent only a tiny fraction -- 1 percent -- of our overall genetic material. Then there's the other 99 percent of our DNA -- the stuff that doesn't make protein
  • Researchers have found that some of this noncoding DNA is in fact essential to how our genes function and plays a role in how we look, how we act and the diseases that afflict us.
  • Embedded in this 99 percent is DNA responsible for the mechanics of gene behavior: regulatory DNA. Greg Wray of Duke University's Institute for Genome Sciences and Policy describes the regulatory DNA as the software for our genes, a set of instructions that tells the genome how to use the traditional coding genes.
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  • "It's like a recipe book," Wray said. "It tells you how to make the meal. You need to know the amounts. You need to know the order. The noncoding DNA tells you how much to make, when to make it and under what circumstances."
  • common diseases are probably more influenced by regulatory differences, Harismendy said. These include Type 2 diabetes, Crohn's disease, Alzheimer's Disease and a variety of cancers, including breast, colon, ovarian, prostate and lung.
  • According to Wray, research has shown that diseases like bipolar syndrome and clinical depression may be associated with noncoding mutations that determine whether the brain is producing too much or not enough of a particular neurotransmitter. One noncoding mutation gives a person almost complete protection against the nasty malaria parasite, plasmodium vivax.
  • Another piece of noncoding DNA regulates the enzyme responsible for lactose tolerance, the ability to digest milk. Research by Wray and other scientists has shown that in four populations where dairy consumption is a vital part of the diet, new mutations have appeared that essentially keep the gene that produces the lactase enzyme from switching off.
  • And recent research done by evolutionary biologists suggests that differences in regulatory DNA may represent a major part of what separates us from chimpanzees.
nidthamsirisup

Epigenetics: DNA Isn't Everything - 0 views

  • Research into epigenetics has shown that environmental factors affect characteristics of organisms. These changes are sometimes passed on to the offspring.
  • A certain laboratory strain of the fruit fly Drosophila melanogaster has white eyes. If the surrounding temperature of the embryos, which are normally nurtured at 25 degrees Celsius, is briefly raised to 37 degrees Celsius, the flies later hatch with red eyes.
  • crossed the flies for six generations. In this experiment, they were able to prove that the temperature treatment changes the eye colour of this specific strain of fly, and that the treated individual flies pass on the change to their offspring over several generations. However, the DNA sequence for the gene responsible for eye colour was proven to remain the same for white-eyed parents and red-eyed offspring.
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  • Epigenetics examines the inheritance of characteristics that are not set out in the DNA sequence.
  • important factors are the histones, a kind of packaging material for the DNA, in order to store DNA in an ordered and space-saving way. It is now clear that these proteins have additional roles to play. Depending on the chemical group they carry, if they are acetylated or methylated, they permanently activate or deactivate genes.
  • New methods now allow researchers to sometimes directly show which genes have been activated or deactivated by the histones
  • The genetic information of the DNA is passed on along with the relevant epigenetic information for the respective cell type.
  • A similar question remains for the inheritance of the epigenetic characteristics from parents to offspring. They now know that when the gametes are formed, certain epigenetic markers remain and are passed on to the offspring. The questions, which are currently being researched, are how much and which part of the epigenetic information is preserved and subsequently inherited.
  • Diet and epigenetics appear to be closely linked. The most well known example is that of the Agouti mice: they are yellow, fat and are prone to diabetes and cancer. If Agouti females are fed with a cocktail of vitamin B12, folic acid and cholin, directly prior to and during pregnancy, they give birth to mainly brown, slim and healthy offspring. They in turn mainly have offspring similar to themselves.
  • Environmental factors, which change the characteristics of an individual and are then passed on to its offspring, do not really fit into Darwin’s theory of evolution. According to his theory, evolution is the result of the population and not the single individual. “Passing on the gained characteristics fits more to Lamarck’s theory of evolution”, says Paro.
Oranicha Jumreornvong

EBSCOhost: "BUT IT DOESN'T RUN IN MY FAMILY" - 1 views

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    health right now Closing the GAPS in your knowledge of YOUR FAMILY TREE can quite literally save your LIFE SARA McGREGOR never worried about getting breast cancer. Neither did her two older sisters. After all, their mother and maternal grandmother never had the disease.
Kaoko Miyazaki

Genetics as Rorschachs: Pondering Our Genes and Our Fate | Psychology Today - 0 views

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    Even today scientists find the study of genes an ambiguous topic. The randomness of the genes being passed down or not, whether one child has a mutations while the other does not or if your sister has a higher risk of getting breast cancer than you is still being tested.
Nitchakan Chaiprukmalakan

Biotechdaily - Human Mitochondrial Mutations Repaired by New Technique - 2 views

  • researchers have identified a generic approach to correct mutations in human mitochondrial DNA by targeting corrective RNAs,
  • In adults, many aging disorders have been associated with defects of mitochondrial function, including diabetes, Parkinson’s disease, cancer, heart disease, stroke, and Alzheimer’s disease.
  • The introduction of nucleus-encoded small RNAs into mitochondria is critical for the replication, transcription, and translation of the mitochondrial genome,
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  • The study defined a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria. Reducing the expression--or output--of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the mitochondrial electron transport chain that consumes oxygen during cell respiration to produce energy. With reduced PNPASE, unprocessed mitochondrial-encoded RNAs accumulated, protein translation was inhibited, and energy production was compromised, leading to stalled cell growth.
  • Geng Wang developed a strategy to target and import specific RNA molecules encoded in the nucleus into the mitochondria and, once there, to express proteins needed to repair mitochondrial gene mutations.
  • First, the researchers had to find a way to stabilize the reparative RNA so that it was moved out of the nucleus and then localized to the mitochondrial outer membrane. This was accomplished by modifying an export sequence to direct the RNA to the mitochondrion. Once the RNA was in the area of the transport machinery on the mitochondrial surface, then a second transport sequence was required to direct the RNA into the targeted organelle. With these two modifications, a wide range of RNAs were targeted to and imported into the mitochondria, where they worked to repair defects in mitochondrial respiration and energy production in two different cell line models of human mitochondrial disease.
    • Nitchakan Chaiprukmalakan
       
      This article shows the importance of the RNAs in making proteins for the mitochondria to work efficiently.  The article summarizes a method in repairing the mitochondria that is still being worked on.
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    Mutations in the mitochondrial genome inflicts diseases
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