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Sasicha Manupipatpong

Memory in adults impacted by versions of four genes - 2 views

  • advanced understanding of the genetic components of Alzheimer's disease and of brain development.
  • understanding of the genetic components of Alzheimer's disease and of brain development
  • certain versions of four genes may speed shrinkage of a brain region involved in making new memories
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  • hippocampus, normally shrinks with age, but if the process speeds up, it could increase vulnerability to Alzheimer's disease
  • two genes associated with intracranial volume -- the space within the skull occupied by the brain when the brain is fully developed in a person's lifespan
  • gene variants identified in the first study do not cause Alzheimer's, but they may rob the hippocampus of a kind of "reserve" against the disease
  • cause cell destruction and dramatic shrinkage of this key brain site
  • almost twice the Alzheimer's risk if he or she had these versions of the gene
  • if a person with one of these variants did get Alzheimer's, the disease would attack an already compromised hippocampus and so would lead to a more severe condition at a younger age than otherwise
  • Alzheimer's disease causes much of its damage by shrinking hippocampus volume
  • loses a greater-than-average amount of volume due to the gene variants we've identified, the hippocampus is more vulnerable to Alzheimer's
  • associations impacting intracranial volume, which is an indirect measure of the size of the brain at full development.
  • brain volume and intracranial volume are both highly heritable
  • no associations for brain volume
  • one of these genes has played a unique evolutionary role in human development, and perhaps we as a species are selecting this gene as a way of providing further advances in brain development
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    The shrinking of the hippocampus, which occurs with age in normal people, was found to be accelerated by certain versions of four genes, which could increase susceptibility to Alzheimer's disease, which also affects the volume of the hippocampus.
Pop karnchanapimonkul

Genetic adaptation of fat metabolism key to development of human brain - 0 views

  • 300,000 years ago humans adapted genetically to be able to produce larger amounts of Omega-3 and Omega-6 fatty acids. This adaptation may have been crucial to the development of the unique brain capacity in modern humans.
  • higher risk of developing disorders like cardiovascular disease.
  • investigated the genes for the two key enzymes that are needed to produce Omega-3 and Omega-6 fatty acids from vegetable oils.
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  • genetic adaptation for high production of Omega-3 and Omega-6 fatty acids is found only in humans
  • 300 000 years ago in the evolutionary line that led to modern humans
  • important factor for human survival in environments with limited dietary access to fatty acids
  • In today’s life situation, with a surplus of nourishment, this genetic adaptation contributes instead to a greater risk of developing disorders like cardiovascular disease
  • first study to show a genetic adaptation of human fat metabolism
  • thrifty gene
  • adaptation that contributed to enhanced survival in an earlier stage of human development, but in a life situation with an excess of food instead constitutes a risk factor for lifestyle diseases
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    This article explains how earlier genetic adaptations that help our survival is now harming us.
nidthamsirisup

Epigenetics Seeks Clues to Mental Illness in Genes' Life Story - Science in 2011 - NYTi... - 0 views

  • epigenetics, the study of how people’s experience and environment affect the function of their genes.
  • Studies suggest that such add-on, or epigenetic, markers develop as an animal adapts to its environment, whether in the womb or out in the world — and the markers can profoundly affect behavior.
  • In studies of rats, researchers have shown that affectionate mothering alters the expression of genes, allowing them to dampen their physiological response to stress. These biological buffers are then passed on to the next generation: rodents and nonhuman primates biologically primed to handle stress tend to be more nurturing to their own offspring, and the system is thought to work similarly in humans.
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  • the offspring of parents who experience famine are at heightened risk for developing schizophrenia, some research suggests — perhaps because of the chemical signatures on the genes that parents pass on.
  • in some people with autism, epigenetic markers had silenced the gene which makes the receptor for the hormone oxytocin. Oxytocin oils the brain’s social circuits, and is critical in cementing relationships; a brain short on receptors for it would most likely struggle in social situations.
  • In one large study of people with schizophrenia, researchers at Johns Hopkins are analyzing blood and other data to see whether the degree of epigenetic variation is related to the inherited risk of developing the disorder. In another, researchers at Tufts are studying the genes of animals dependent on opiates to see how epigenetic alterations caused by drug exposure affect the opiate sensitivity of the animals’ offspring.
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.
nidthamsirisup

Study suggests why some animals live longer - 1 views

    • nidthamsirisup
       
      A new method to detect proteins associated with longevity which helps further our understanding into why some animals live longer than others.
  • The study, led by Dr. Joao Pedro Magalhaes and postgraduate student, Yang Li, is the first to show evolutionary patterns in biological repair systems in long-lived animals and could, in the future, be used to help develop anti-ageing interventions by identifying proteins in long-lived species that better respond to, for example, DNA damage
  • these species have optimised pathways that repair molecular damage, compared to shorter-lived animals, such as mice
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  • found a similar pattern in proteins associated with metabolism, cholesterol and pathways involved in the recycling of proteins
  • Proteins associated with the degradation of damaged proteins, a process that has been connected to ageing, were also linked with the evolution of longevity in mammals.
  • If we can identify the proteins that allow some species to live longer than others we could use this knowledge to improve human health and slow the ageing process.
  • “We developed a method to detect proteins whose molecular evolution correlates with longevity of a species. The proteins we detected changed in a particular pattern, suggesting that evolution of these proteins was not by accident, but rather by design to cope with the biological processes impacted by ageing, such as DNA damage. The results suggest that long-lived animals were able to optimise bodily repair which will help them fend off the ageing process.”
Sasicha Manupipatpong

Identical DNA codes discovered in different plant species - 2 views

  • found identical sequences of DNA located at completely different places on multiple plant genomes
  • Although the scientists found identical sequences between plant species, just as they did between animals, they suggested the sequences evolved differently.
  • find identical sequences in plant DNAs
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  • identical sections weren't found at the same points
  • genomes of six animals (dog, chicken, human, mouse, macaque and rat)
  • six plant species (Arabidopsis, soybean, rice, cottonwood, sorghum and grape)
  • found long strings of identical code in different species of animals' DNA
  • expect to see convergent evolution, but we don't
  • Plants and animals are both complex multi-cellular organisms that have to deal with many of the same environmental conditions, like taking in air and water and dealing with weather variations, but their genomes code for solutions to these challenges in different ways
  • could help in the development of new medicines
  • used to find identical sequential patterns in an organism's entire set of proteins
  • lead to finding new targets for existing drugs or studying these drugs' side effects
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    A computer algorithm found identical sequences of DNA in different places of various plant species' genomes. The same has been found in animals. This could prove to be beneficial in the development of new medicines (for testing drug side effects).
avikan

New Hope Of a Cure For H.I.V. - NYTimes.com - 0 views

  • So people with H.I.V. now must take drugs every day for life, which some researchers say is not a sustainable solution for tens of millions of infected people.
  • CCR5,
  • This is what was done with the Trenton patient. Some of the man's white blood cells were removed from his body and treated with a gene therapy developed by Sangamo BioSciences. The therapy induced the cells to produce proteins called zinc-finger nucleases that can disrupt the CCR5 gene.
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    • avikan
       
      Millions of people worldwide are currently affected by HIV and many have died from AIDS. Scientists have been trying for many years to find a cure for the epidemic, but now many are trying to find a way to prevent the passing on of the virus for future generations. Although no definite treatment has been discovered yet, recent findings have shown promising results for the future. 
    • avikan
       
      With the fast developing biological technologies we are seeing today, scientists hope's are growing stronger.  Maybe one of us one day will be a part of the phenomenon, in search of a way to help the millions affected by the epidemic  
    • avikan
       
      CD4 cells initiate the body's response to infections.
    • avikan
       
      Many forms of HIV, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation known as CCR5 delta 32 in the CCR5 gene, protecting them against these strains of HIV.
    • avikan
       
      For over 30 years scientists have been trying to find a cure for the HIV/AIDs epidemic and so far have been unsuccessful 
    • avikan
       
      Incase some of us forgot, AIDs stands for Acquired immune deficiency syndrome, a disease in which there is a severe loss of the body's cellular immunity. And HIV stands for Human immunodeficiency virus, a virus that causes AIDs
Pop karnchanapimonkul

The Ballooning Brain: Defective Genes May Explain Uncontrolled Brain Growth in Autism: ... - 0 views

  • linked atypical gene activity to excessive growth in the autistic brain
  • autistic brain sprouts an excess of neurons and continues to balloon during the first five years of life, as all those extra neurons grow larger and form connections.
  • start to lose neural connections, faster than typical brains
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  • 67 percent more neurons in their prefrontal cortex (PFC) than typical children
  • executive functions"—high-level thinking, such as planning ahead, inhibiting impulses and directing attention.
  • In brain tissue from both autistic children and autistic adults, genes coding for proteins that identify and repair mistakes in DNA were expressed at unusually low levels. Additionally, all autistic brains demonstrated unusual activity levels for genes that determine when neurons grow and die and how newborn neurons migrate during early development
  • Some genes involved in immune responses, cell-to-cell communication and tissue repair, however, were expressed at unusual levels in adult autistic brains, but not in autistic children's brains
  • Errors accumulate.
  • autistic child develops in the womb, something—an inherited mutation or an environmental factor like a virus, toxin or hormone—muffles the expression of genes coding for proteins that usually fix mistakes in sequences of DNA
  • The genetic systems controlling the growth of new neurons go haywire, and brain cells divide much more frequently than usual, accounting for the excess neurons found in the PFC of autistic children.
  • autistic brain grow physically larger and form more connections than in a typical child's brain.
  • immune system reacts against the brain's overzealous growth,
  • Not all researchers, however, accept
  • If scientists definitively link autism to a characteristic sequence of changes in gene expression and unusual neural growth, then it becomes possible to target and reverse any one of the thousands of steps in that sequence.
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    Article about how genetic expression may be the cause for autism.
Mickey Tsai

Autism gender bias clue found - Health - CBC News - 0 views

  • four times more common among males than females.
  • rare family with four generations in which males carrying the glitch were affected but females were not.
  • When male fetuses are missing one copy of the gene, it throws off their developmental process enough to lead to autism but female biology differs enough that it doesn't matter.
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  • now that doctors know that the SHANK 1 gene is involved and it can be tested for, they'll know to follow affected males very closely and offer treatments early on.
  • lved and it can be tested for, they'll know to follow affected males very c
  •  
    Scientists have long wondered why autism is much more common among males than females. When males miss one copy of a gene it messes up the development process enough to cause autism but female biology differs enough to make it not matter. Now that scientists have identified that the SHANK 1 gene is involved they can test for it and could offer treatments early.
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
nidthamsirisup

Engineered stem cells seek out and kill HIV in living mice - 0 views

  • human stem cells can be genetically engineered into HIV-fighting cells
  • surrogate model
  • CD8 cytotoxic T lymphocytes -- the "killer" T cells that help fight infection -- from an HIV-infected individual and identified the molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells.
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  • cloned the receptor and used this to genetically engineer human blood stem cells.
  • mature T cells that can attack HIV in tissues where the virus resides and replicates.
  • CD4 cells are white blood cells that are an important component of the immune system, helping to fight off infections.
  • CD4 "helper" T cells
  • HIV in the blood decreased.
  • increased
  • engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model
    • wasin kusakabe
       
      Using mice as lab rats, researchers are able to produce a large amount of T cells that can fight off HIV more effectively.
  • Expanding on previous research providing proof-of-principle that human stem cells can be genetically engineered into HIV-fighting cells
  • The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.
  • In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.
  • increased, while levels of HIV in the blood decreased. CD4 cells are white blood cells that are an important component of the immune system, helping to fight off infections. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.
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    Stem cells that are engineered to produce T cells that can help fight off HIV.
Mickey Tsai

Parkinson's disease sufferer Sheila Roy can write for the first time in 15 years thanks... - 0 views

  • one of only 15 people worldwide to undergo the radical treatment, which involves inserting corrective genes into the brain
  • The genes provide the coded instructions for proteins needed to make dopamine, a brain chemical essential for proper control of movement.
  • Lack of dopamine leads to the symptoms of tremor, stiffness and poor balance associated with Parkinson’s.
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  • Mrs Roy is taking part in an early-stage study of the ProSavin therapy
  • Following her treatment Sheila Roy has been able to carry out tasks like writing, something she has been unable to do for 15 years
  • Gene therapies hold great promise for people with Parkinson’s in the future, as they could mean an end to the daily regime of drugs that most people with the condition currently face.
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    A woman with Parkinson's was able to write for the first time in 15 years because of gene therapy. Parkinson's includes symptoms such as tremors, loss of balance which makes it impossible to do even simple tasks. Doctors injected a modified virus carrying the genes to the motor centre of her brain which provide coded instructions for proteins needed to make dopamine. Lack of dopamine leads of the symptoms associated with Parkinson's. This is part of the ProSavin therapy developed by Oxford BioMedica. Gene therapies hold a lot of hope for people with Parkinson's that could end the daily routine of drugs that most of them go through.
orasa sukmark

Genetic adaptation of fat metabolism key to development of human brain - 0 views

  •  
    Genetic adaptation for high production of Omega-3 and Omega-6 fatty acids is found only in humans can show genetic adaptation of human fat metabolism.
Sea Maskulrath

Why having sex really IS the best thing to do: Gene mapping finally proves mating is be... - 0 views

  • Why having sex really IS the best thing to do
  • is better for evolution than self-reproduction
  • Having sex allows us to evolve more effectively than species which reproduce without a partner, according to tests that claim to finally prove the long-held theory.
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  • cording to the study by the University of Edinburgh.
  • Meanwhile, creatures who reproduce asexually are more likely to be lumbered with disease-causing genes
  • Combining the genes of two parents – rather than one in the case of fruit flies, stick insects and other animals – allows for damaging DNA to be removed within a few generations.
  • h longer, a
  • or muc
  • This is because individuals who inherit healthy genes tend to flourish and pass on their DNA to the next generatio
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    well, I guess SEX is the best way to develop a super human for the future + I know everyone gonna love it :) 
Nitchakan Chaiprukmalakan

Proteins and quantum transition: Instant shape-shifting - 0 views

  • The genetic code in DNA provides the template to manufacture protein into all the cells of an organism.
  • Proteins are made by stringing together amino acids. For general purposes there are twenty amino acids in protein and they can be put together in endless combinations, some in short chains (yeast averages 466 amino acids), some long chains (titins have nearly 27,000 amino acids) and everything in-between. The pattern of amino acids determines much of the functionality of the protein.
  • Proteins are three-dimensional puzzle pieces. They are generally very complicated in shape. Even a small protein of only 100 amino acids can theoretically have 10^100 (ten to the hundredth power) different configurations.
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  • most protein reconfigurations occur in nanoseconds
  • In research on proteins, it was assumed (given their chemical composition) proteins would uniformly fold as they cool down and unfold as they heat up. (Think of a balloon expanding and shrinking with the temperature of the air inside.) The experiments didn’t bear this out; the rate of folding or unfolding according to temperature change was unequal (asymmetric) and uneven (nonlinear).
  • In recent biochemistry a great deal of work is done with ‘tagging’ or ‘marking’ molecules with fluorescent and phosphorescent materials. It’s well known that fluorescence and phosphorescence are phenomena closely related to protein folding and they can only be understood in terms of quantum transition between molecules.
  • With a quantum transition, the protein could change configuration by ‘jumping’ – skipping all the transition steps – to the final configuration. They call this quantum folding and they developed a mathematical model that shows how the folding, which is virtually instantaneous, would react to change in temperature.
  • Their quantum transition model matched the folding curves for 15 different proteins and also provides an explanation for the different rates of folding and unfolding among these proteins.
  • Luo and Lu’s paper is short, a mere 16 pdf pages, and the model is unpretentious mathematically. (Luo has several other related papers on arXiv.) It comes from unknown researchers in an unknown corner of the academic world, and it’s published on the open-source arXiv system. The lack of pedigree means that it will take more time than usual for scientists around the world to learn of it, examine it, and possibly test it.
    • Nitchakan Chaiprukmalakan
       
      This is not accepted as a true fact yet and has to be proven.
Mickey Tsai

Study finds gene variants behind childhood obesity risk - USATODAY.com - 0 views

  • Scientists have discovered two gene variants that appear to play a critical role in the development of common childhood obesity
  • Obesity is the result of a complex interplay among biological, behavioral, cultural, environmental and economic factors
  • a highly heritable condition,
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  • a third of kids are obese or overweigh
  • gene research may provide insight into the biological pathways that contribute to obesity
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    Scientists have found two gene variants that are likely to cause childhood obesity. This could be useful in knowing how to treat and prevent it. Although there is a genetic component to obesity, it is not the only factor. Biological, behavioral, cultural, environmental and economic factors can all play a role in obesity.
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.
Rafael Chen

Scientists develop tools to make more complex biological machines from yeast - 0 views

  • creating a new type of biological "wire," using proteins that interact with DNA and behave like wires in electronic circuitry
  • it can be re-engineered over and over again
  • fundamental DNA components, called "promoters," which are needed for re-programming yeast
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  • Future applications of this work could include tiny yeast-based machines that can be dropped into water supplies to detect contaminants, and yeast that records environmental conditions during the manufacture of biofuels to determine if improvements can be made to the production process.
  • help to improve things such as pollution monitoring and cleaner fuels
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    Scientist uses yeast as the foundations in making more complex biological machines through genetic engineering.
nidthamsirisup

Stem Cell Treatment Spurs Cartilage Growth - Science News - 0 views

  • A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows
  • And treatment with kartogenin allowed many mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain.
  • Kartogenin steers the stem cells to wake up and take on cartilage-making duties. This is an essential step in the cartilage repair that falls behind in people with osteoarthritis, the most common kind of arthritis, which develops from injury or long-term joint use.
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  • The molecule turned on genes that make cartilage components called aggrecan and type II collagen. Tests of mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity.
  • kartogenin inhibits a protein called filamin A in the mesenchymal stem cells
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.
  •  
    WOW, I guess we know we had to stop shisha right? unbelievable 
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