Sunday, February 27, 2011

Microarrays Application

DNA Microarray technology helps in the identification of new genes, know about their functioning and expression levels under different conditions. Disease diagnosis of DNA Microarray technology helps researchers learn more about different diseases such as heart diseases, mental illness, infectious disease and especially the study of cancer. Until recently, different types of cancer have been classified on the basis of the organs in which the tumors develop. Now, with the evolution of microarray technology, it will be possible for the researchers to further classify the types of cancer on the basis of the patterns of gene activity in tumor cells. This will tremendously help the pharmaceutical community to develop more effective drugs as the treatment strategies will be targeted directly to the specific type of cancer.

Drug discovery: Microarray technology has extensive application in Pharmacogenomics. Pharmacogenomics is the study of correlations between therapeutic responses to drugs and the genetic profiles of the patients. Comparative analysis of the genes from a diseased and normal cell will help the identification of the biochemical constitution of the proteins synthesized by the diseased genes. The researchers can use this information to synthesize drugs which combat with these proteins and reduce their effect.

Toxicological research: Microarray technology provides a robust platform for the research of the impact of toxins on the cells and their passing on to the progeny. Toxicogenomics establishes correlation between responses to toxicants and changes in the genetic profiles of the cells exposed to such toxicants

RNA data Sequences to DNA

Proteins are not the only substances that are synthesized directly from data within the DNA. Some forms of RNA are specialized and also have their formula encoded directly in digital DNA formulae. Not all types of RNA are temporary intermediate forms with their form depending on whatever DNA they are copying. There are certain forms of RNA that have a particular form that is the same across all individuals. Some of these special-purpose RNA forms are,

tRNA - transfer RNA
rRNA - ribosome RNA

There are exactly 20 forms of tRNA one each transfer a particular amino acid. tRNA molecules contain about 75-80 bases. tRNA recognizes one of the 64 triplets and matches it one of the 20 amino acids. Since there are 20 tRNA types, and not 64, each tRNA molecule has to recognize more than one triplet ordering as a match. The DNA code contains multiple repetitions of codes for tRNA and rRNA. About 280 copies are spread over 5 chromosomes. Presumably, this allows each cell to make multiple copies of tRNA and rRNA molecules at once from its single copy of the DNA.

Grooves in the DNA

Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

DNA Base Pairing

Each type of base on one strand forms a bond with just one type of base on the other strand.This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines with A bonding only to T and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

GC DNA base pair-svg
AT DNA base pair-svg

Top a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashes lines.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, left). DNA with high GC-content is more stable than DNA with low GC-content, but contrary to popular belief, this is not due to the extra hydrogen bond of a GC base pair but rather the contribution of stacking interactions (hydrogen bonding merely provides specificity of the pairing, not stability). As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.

Sense and Antisense

A DNA sequence is called sense if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the antisense sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, anti sense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses overlapping genes increase the amount of information that can be encoded within the small viral genome.

Alternate structures of DNA

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level DNA sequence, the amount and direction of supercooling chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns and also B-DNA used analysis based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins act. all in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, Watson and Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.

Although the B-DNA form is most common under the conditions found in cells, it is not a well defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA the A-DNA form is a wider right handed spiral with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA while in the cell it may be produced in hybrid pairings of DNA and RNA strands as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription

Quadruplex structutrs of DNA

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase as the enzymes that normally replicate DNA cannot copy the extreme 3 ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed with the central set of four bases coming from either a single strand folded around the bases or several different parallel strands each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop the single stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop.

Boilogical Funtions Of DNA

DNA usually occurs as linear chromosomes in eukaryotes and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome. the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually this RNA copy is then used to make a matching protein sequence in a process called translation which depends on the same interaction between RNA nucleotides. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles here we focus on the interactions between DNA and other molecules that mediate the function of the genome.

Genomes and Genes

Genomic DNA is located in the cell nucleus of eukaryotes as well as small amounts in mitochondria and chloroplasts. In prokaryotes the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein coding exons with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size or C-value, among species represent a long-standing puzzle known as the C-value enigma. However, DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.
T7 RNA polymerase (blue) producing a mRNA (green) from a DNA template (orange)

Some non-coding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of non-coding DNA in humans are pseudogenes which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

DNA Binding Proteins

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best understood member of this family and is used in processes where the double helix is separated, including DNA replication recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.
The lambda repressor helix-turn-helix transcription factor bound to its DNA target

In contrast other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter this will change the accessibility of the DNA template to the polymerase.

As these DNA targets can occur throughout an organism genome changes in the activity of one type of transcription factor can affect thousands of genes. Consequently these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases allowing them to"read the DNA sequence. Most of these base-interactions are made in the major groove where the bases are most accessible.

Translation and Transcription of DNA

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three letter words called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3 letter combinations there are 64 possible codons (43 combinations). These encode the twenty standard amino acids giving most amino acids more than one possible codon. There are also three stop or nonsense codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.

Genatic Enginearing

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction and manipulate it in the laboratory such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins used in medical research or be grown in agriculture.

Forensics of DNA

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is called genetic fingerprinting, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents. On the other hand many convicted people have been released from prison on the basis of DNA techniques, which were not available when a crime had originally been committed.

Bioinformatics of DNA

Bioinformatics involves the manipulation, searching, and data mining of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters were developed to search for specific sequences of nucleotides. In other applications such as text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near worst case behaviour due to their small number of distinct characters. The related problem of sequence alignment aims to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes. worth of DNA sequences, such as those produced by the Human Genome Project are difficult to use without annotations, which label the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products in an organism even before they have been isolated experimentally.

Research Histry of DNA

DNA was first isolated by the Swiss physician Friedrich Miescher who in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1919, Phoebus Levene identified the base sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1928, Frederick Griffith discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carried genetic information—the Avery-MacLeod-McCarty experiment when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed that DNA is the genetic material of the T2 phage.

In 1953 James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases were paired—also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.

Experimental evidence supporting the Watson and Crick model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick mode; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Unfortunately, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the "Central Dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

DNA Binding Proteins

Saturday, February 19, 2011

HEMAGGLUTININ

I've just been infected with one of these...YES...the FLU VIRUS!

Such simple structures yet they are indeed formidable in making one feel so sick!

In general, viruses are composed of 2 main components - a protein envelope and a core composed of genetic material (which can either be DNA or RNA). It cannot survive on its own but is dependent on a host cell to replicate and propagate! Sigh...in my case...that's my cells!

Viruses are host specific. Meaning a plant virus cannot infect a bacterial cell. Neither can a bacterial virus infect a human cell. However, at times, mutation in the viral genome can occur which allows the virus to "cross" their host boundaries. That's when pandemics can arise. An example of this is the recent "Bird Flu virus"!

Well, I suppose I should be thankful that mine is just a case of the common influenza virus. So, back to bed for now and hopefully I'll be back on my feet in a couple of days!

Spotlight on Disease: Type 2 Diabetes

Diabetes results from a lack of a hormone that stimulates cells to take up (a type of sugar) from the bloodstream. Cells need glucose as fuel to produce energy. lack insulin because their immune systems destroy the pancreatic cells that produce it. Type 2 diabetics progress through two stages of the disease. In the first stage, called “insulin resistance”, cells no longer respond to insulin. The pancreas compensates for this resistance by producing more insulin. As insulin resistance persists, the pancreas cannot make enough insulin to keep up with the increased demand. The pancreas eventually shuts down insulin production altogether, resulting in type 2 diabetes.

Without sugar that can be converted to energy, cells starve and glucose levels build up in the blood, which can lead to life-threatening complications such as cardiovascular disease. Since fat interferes with the body’s ability to process insulin and overweight people are at increased risk for the disease, type 2 diabetes is sometimes called “obesity-related” diabetes. Type 2 diabetics are encouraged to carefully monitor their diet and exercise in order to prevent dangerous fluctuations in blood sugar levels.

New Insights into Scar Prevention

Dr. Erkki Ruoslahti

Bike accidents, C-sections and battlefield wounds can all leave scars. But those are only the scars you can see. Any tissue can scar (not just skin), making scar tissue more than a cosmetic problem. Heart muscle, for example, can scar after a heart attack, and the lungs, kidneys, the liver, and many other tissues can be damaged by inflammation. Current options for reducing scar formation require local intervention at the scarring site – plastic surgery, for example. But what if there was a pill you could take after an injury to prevent scar tissue from forming in the first place?
At Sanford-Burnham’s at and his team have developed a new prototype therapy that inhibits scarring in mice. The compound contains two elements discovered by the Ruoslahti laboratory. One is a peptide that homes in on new blood vessels that form during wound healing. The other is a naturally occurring protein called which they prevents the buildup of fibrous connective tissue that causes scarring. The combination of the peptide and protein turns out to be particularly powerful.

Protecting Beta Cells from the Immune System

A pancreatic beta cell. Image by Itkin-Ansari lab

is caused by an overactive immune response that kills off insulin-producing beta cells. While beta cells can be transplanted to replace the ones that have been lost, the immune system will eventually kill those off as well.
For transplantation to be a viable treatment, the immune system must be controlled. Current transplant recipients take immunosuppressive drugs to prevent their from attacking replacement presenting patients with a stark choice between diabetes and a suppressed immune system.
Sanford-Burnham adjunct assistant professor is taking a different approach. Her laboratory has placed human pancreatic precursor cells in an immuno-protective device and transplanted them into mice. She was testing whether precursor cells will mature into productive beta cells in the body and whether the encapsulation device, made from a material akin to Gore-Tex, could prevent the immune system from attacking transplanted cells.

Spotlight on Disease: Type 1 Diabetes

A model of an insulin molecule. Though insulin is an effective treatment for diabetes, it is not a cure. Image courtesy of Wikimedia Commons.

Type 1 diabetes is an – a person’s own immune system attacks found in the pancreas. Beta cells normally respond to high levels of sugar in the blood by releasing a protein hormone that acts like a key binding to a lock (or receptor) that is present on every cell in the body. When insulin binds to its receptor, it unlocks a door in cells that allows this sugar—known as to enter and be used for energy.
Since type 1 diabetics lack insulin-producing beta cells, glucose remains in the blood and cells starve. Even with insulin therapy, the level of blood glucose in type 1 diabetics is not normal. Glucose is a highly reactive molecule that damages the cells and tissues that it contacts, particularly the cells that line blood vessels. As a result, diabetes is a leading cause of blindness, kidney disease, limb amputation and heart disease. Because type 1 diabetes commonly manifests in childhood, it has traditionally been called “juvenile” diabetes. Type 1 diabetes treatment is life-long; diabetics must carefully monitor their blood sugar and receive daily insulin injections or wear an insulin-delivering pump.

The Truth About AMPK

Researchers at Salk and Sanford-Burnham used tiny C. elegans to study AMPK and autophagy.

You may not be familiar with the protein but if you exercise regularly, like to drink red wine, take certain diabetes medications or practice caloric restriction in hopes of extending your life, AMPK is very important to you. AMPK is a master switch that controls a number of key cellular mechanisms, and all the activities listed above stimulate AMPK signals.
Recently, at the with assistance from at Sanford-Burnham, published a showing how AMPK triggers a process called which recycles damaged parts when cells are low on energy. Problems with AMPK and autophagy are associated with type 2 diabetes, cancer, Alzheimer’s and other age-related diseases.

Crowdsourcing Science with TOPSAN

New advances in technology are allowing scientists to sequence genomes and determine the structures of the proteins they encode at a faster rate and lower cost than ever before. The centers, such as the (JCSG), have been instrumental in establishing the structures of hundreds of proteins each year. While this flood of new data is a boon to science, the time and resources needed to analyze it all has become a major bottleneck.
“We have become victims of our own success,” explains director of the Bioinformatics and Systems Biology program at Sanford-Burnham. “New protein structures are being determined all the time. And while it’s important to know what a protein looks like, we need to better leverage that information to improve our understanding of how a protein works and what biological functions it performs in a cell.” Moreover, knowledge of a protein’s structure and function is necessary for identifying its role in human health and disease, as well as unveiling its potential as a therapeutic target.
Several years ago, Dr. Godzik and his research team came up with an idea to protein structure annotation. In 2006, along with their JCSG colleagues, they launched (TOPSAN), a central portal for scientists to collect, share and distribute information about three-dimensional protein structures. TOPSAN embodies the idea that many can succeed where the individual cannot. No matter how much any one person knows about a particular protein, there are others in the scientific community who know more about other aspects of the same protein. Thus, the collective analyses from multiple experts around the world are far more informative than the localized information that any one individual – or even single research group – could contribute.

High-Impact Research

Dr. Sumit Chanda

Two years ago, Sanford-Burnham’s and colleagues collaborated on a aboutinfection. They were trying to figure out how the virus, with only nine genes that code for 15 proteins, could be so effective with such a small genetic payload. They knew the virus was hijacking human proteins to succeed, but they wanted to pinpoint exactly which proteins were affected. published October 3, 2008 in identified 295 host proteins involved in HIV infection. Since then, these findings have greatly impacted HIV research. In recognition of the paper’s significance, Thomson Reutershas named it a paper for January 2011. In the Drs. Chanda and Young said:

This was one of the first studies to combine genome-wide RNAi screening and bioinformatics to identify the repertoire of host cellular factors that help facilitate HIV replication in human cells. It represents a significant advance in our understanding of viral-host interactions, providing a blueprint of the machinery that is exploited by the virus.

The paper’s ripple effect is likely to continue - researchers are just now beginning to develop anti-HIV therapies that target some of these 295 host proteins.

DNA

Dr. Robert Rickert with Oxnard Foundation president Christopher Veitch

We are quite proud of the Sanford-Burnham scientists have made in 2010. Their work has led to new insights into and many other conditions. In addition to illuminating some of the fundamental mechanisms that cause disease, they have also worked to these findings into new therapies.
We would like to take this opportunity to thank our many supporters for helping us with this important work. Without you, we might not have the resources to pursue promising research.

DNA 101

In this image, cellular machinery (in yellow) is transcribing DNA (the chain on the right) into RNA (upper left). Illustration by Linda Nye

DNA is short for deoxyribonucleic acid. Two chains of four chemical bases (abbreviated A, T, C and G) make up DNA and act as a cell’s recipe book to make proteins. The particular sequence of a DNA chain – meaning the precise order of the four chemical bases – determines what will be made. A DNA segment beginning with ATTCGC would produce a very different protein than one that starts with CCGTAT. This can be likened to adjusting the order of letters in a word. Though the letters are the same, the meaning changes. For example, act means something very different than cat.
Not all DNA is destined to become a protein. Just as a recipe might contain more information than just a list of ingredients, only some regions of your DNA – called – are directly translated into proteins. Cellular machinery follows the instructions written in a gene’s recipe to create a corresponding sequence of which is chemically similar to DNA but acts as a messenger, carrying the recipe from the . Out in the cell’s the mRNA sequence is read by more machines, called Following the mRNA instructions, ribosomes string together the building blocks that make up proteins. Proteins do most of the work in the cell.
As producing two cells where there was once only one, the parent cell’s DNA is duplicated and the same protein-making recipe is passed on to the daughter cell.

Thursday, February 17, 2011

Parentage Testing

Paternity Test

A paternity test will tell you if a man is (or is not) the biological father of a child. This test includes the testing of the alleged father, the child, and the mother if you choose to include her. If you do choose to include the biological mother of the child in this test, the resultant accuracy will be higher, but her inclusion is not required. If you are having a test done for legal purposes, we do recommend that you include the biological mother, if possible.

Maternity Test

A maternity test will tell you if a woman is (or is not) the biological mother of a child. This test includes the testing of the alleged mother, the child, and the father if you choose to include him. If you do choose to include the biological father of the child in this test, the resultant accuracy will be higher, but his inclusion is not required.

What can I expect my result to say?

The results issued for a parentage test (paternity or maternity) will be either:
Exclusion -- the tested father/mother is NOT the biological parent of the tested child.
Consistent With -- the tested father/mother IS likely to be the biological parent of the tested child; this result will also have the statistical values calculated (and reported) for your particular case that indicate the strength of the consistent result.

Understanding this test

(Note: Explanations are based on a paternity test, but are also applicable to a maternity test.)
Every person receives half of their DNA from their mother and half from their father. In a case where the biological mother is included in the testing, the DNA extracted from the biological mother's sample is compared with that from the child. Any DNA the child has that the mother does not have must, therefore, have come from the biological father.

In a father/child test (where the biological mother is not included in the testing), the DNA from the father and child are compared to determine if there is a match or a mismatch, but without the benefit of knowing which DNA the child received from the mother (hence the decreased accuracy of a father/child test).

The child received either a 10 or an 11 from his/her father, and the alleged father in the example could have donated an 11 or a 13. In this example, this father has the necessary allele to fulfill the child's genetic profile in this particular region of their DNA.

Types of Samples

Our standard and preferred sample type is a buccal swab - this is a sponge on a stick that you rub on the inside of your cheek in order to collect skin cells. Your testing fee includes the swabs to take this type of sample. We can also accept bloodstain cards and whole blood as a standard sample (at no additional fee). However, we do recognize that there may be a need for more discrete testing and can therefore process other types of samples.

If you wish to submit a sample other than the buccal swab please contact us to discuss the sample options to ensure you are sending the best possible sample. We will gladly process your test order personally. Please note that these types of test orders cannot be processed through our website at this time.

Non-Standard Samples

toothbrush (used only by one person);
>5 hair roots (it is important that each hair has a root on it, as that is where we are getting the DNA from);
fingernail clippings;
any blood sample other than whole blood or bloodstain card.

Forensic Samples

clothing with bodily fluids (if you are having a semen or blood identification test done, that test fee includes the processing of this type of sample);
clothing with skin cells (baseball cap, gloves, etc.),
cigarette butts,
condom,
Q-tip with ear wax,
licked envelop/stamp,
used glass/can/bottle/pacifier.

ATYPYK PEZ

Funny, I seem to be behind every blog that is out there. I hope there are people out there that haven't seen this last year already, because these are some interesting ideas. I used to collect PEZ, and it would have never occurred to me to do these stuff.

ATYPYK are French artists who transformed PEZ into unique art. There are a couple of them that I thought were cool. Make sure to click on the arrows at the end of the gallery strip. It's easy to miss them because they blend with the background.

A Wacky Backpack!

I totally love Wacky Packages. I was browsing for the new Wacky Packages books in Amazon, and came across a Wacky Packages back pack. I wish there were more pictures and better description. It looks fairly small to me.

Snoopy The Flying Ace Visits The Intrepi

If you are in NYC and love Snoopy, hurry up and go to the Intrepid Museum in NYC to see the "Snoopy as the World War I Flying Ace” exhibition. I so wish I could fly over to see the exhibition but I can't afford a coast to coast trip. The exhibition is only until April 30th, so you have 9 days left if you want to see it. It is a traveling exhibition.

Blog - Breeds Of Small Dogs : Best Small Dog Breeds

I was glad to see this site, because I recently adopted a stray or an abandoned dog that was found about two blocks from my house. I took it to the vet to find out if he was chipped. Unfortunately, he was not. He didn't have a collar either and wasn't fixed. He wasn't even trained. I taught him how to "sit" in a few days and "stay". He still needs alot of training to do.

I have the feelings that he was abandoned at the park which is a block away. A lots of Chihuahuas have been abandoned in SF Bay Area and the East Bay (Oakland and north). I know someone who tried to catch three stray Chihuahuas without any luck. I don't know about other areas. He was not in a terrible condition. He just needs to gain about 3 lbs. I went to the SPCA and the Humane Society but no one reported him. I did leave my information. According to the law here, I cannot adopt a stray dog unless no one claims him or her 30 days after he was found. I didn't have the heart to leave him at the Humane Society. He could get sick there. So I fostered him instead. When no one claimed him after 30 days, I adopted him and took care of all his needs. So now he is living with me.

I don't know what type of dog he is, but he is obviously a Chihuahua mix. He has bonded with my black lab who is a service dog. She is fine with him. She likes cats since she was raised around cats. So she is fine with little dogs too. So I think she kinda treats him like he is a cat. She has no problem if he sleeps against her body or on her legs or something. He is not a perfect dog. He barks and I am hoping she isn't going to bark every time someone approach my house. He likes to get a hold of food any change he gets. I can't turn my head for a second without him grabbing food behind my back. Shelby isn't like that. I can leave food on the coffee table and she will never touch it. But with him now, I can't. So I am hoping she won't learn bad things from him, like stealing and barking. But she does love to play with him. Sometimes she licks him and once a while he'll lick her too.

What makes me chuckle is watching the little guy walking right under beneath her without any problem. The only other time that I've seen anything like that, was with a Great Dane

Anyway, I'm a bit off point. The reason I like this blog is because it's about small dogs and the new dog that adopted is small dogs. I am not used to dogs his size. He is actually bigger than a pure Chihuahua. He is clearly a Chihuahua mix. I am thinking of doing a DNA test. There is a hospital around here that only charges $48 for a DNA test!! That's the lowest fee I've ever heard of.

Hope you'll enjoy this blog and learn new thing as well. This blog is focused on breeds only. But I think it can be still useful for any little dog pure or not. One thing I noticed about this blog, that it doesn't list all small breed. So for I have not seen a Papillon nor the Yorkshire which surprised me because they aren't that rare.

The dog breed above is called Coton de Tulear. Isn't he a handsome fella?

Dog breeds

The blood test identifies genes from a base of 157 breeds, according to the Web site of Mars Inc., the company that offers the test through vets' offices. It costs about $200 but includes a veterinary appointment for reviewing the results.

Smith advocates for the blood-work test not only because it accesses more breeds but because, depending on the DNA results, some dog owners may need follow-up counseling.

"Some people might've been happy with what they thought they had, then something like 'Rottweiler' shows up," said Smith. "All of a sudden, they're looking at their dog through a completely different pair of eyes."

A veterinarian can reassure owners that "the dog you now have more information about is the dog you still love," she said.

Theresa Brady, a MetaMorphix marketing representative in Calverton, Md., said the two DNA tests are equally effective, even though her company's cheek-swab method tests for fewer breeds.

"DNA is DNA," she said. "The sampling method doesn't make a difference."

Smith and other vets caution that the DNA tests are "for fun and entertainment" — not for diagnostic purposes.

"It's just a test for owners," said vet Kelly Best of Arvada Flats Veterinary Hospital, in Colorado. "I don't know that it has any medical benefits at all."

Even for purebreds predisposed to certain diseases, their genetic dilution in a mutt makes concern about the diseases negligible, she said.

And no one has come knocking on her door asking for the test.

Smith, however, has run the blood test on many dogs.

"It's like Christmas day when (clients) get to open their results," she said. "A lot of times people are right, and a lot of times they're wrong."

DNA tests may yield surprise breeds in mutts

ARVADA, Colo. — When Will Colosimo adopted his dog Allie in 2003, he knew he was getting a mutt. She looked like a basenji, but the Colorado Basenji Rescue group in Denver, from where he retrieved her, said they didn't think she had any of that small, short-haired breed in her.

Curiosity got the better of him.

"We always knew she was beautiful, but we didn't know what all came together to make her," he said.

There are several types of DNA tests available for determining a mixed-breed dog's ancestry. Colosimo sent away for one that required swabbing the inside of his dog's cheek and mailing the sample to a lab. He learned that Allie, who is 8 or 9 years old, had both German shepherd and dachshund blood.

"It was hilarious," said Colosimo, 45. "So, the German shepherd I can totally see, but dachshund? That's crazy."

Owners’ guesses often way off
And not uncommon. Veterinarians advise owners that what they see in their dog is not always what they've got.

"We're really bad guessers at what dogs are," said Martha Smith, Director of Veterinary Medical Services at the Animal Rescue League of Boston.

The rescue league began using mixed-breed DNA blood testing when it appeared about four years ago, testing a few of its shelter dogs. "We found out from the handful of tests that we ran that we were way off base" in guessing breeds, Smith said. The test "proves dogs are individuals."

Karin Hendersin, 52, a market researcher in Denver, can speak to that. Her dog, Splash, resembles a pit bull, a breed banned in the Denver city limits. Hendersin recently learned that Splash, with her brown-brindled coat, is Chinese Shar-Pei, Labrador retriever and Dalmatian — and no pit bull.

Hendersin thinks the DNA test also helped explain some of the dog's behavior.

"It explains why she's such a runner," Hendersin said, noting the Dalmatian genes. "We take her to the dog park and a whole herd of dogs will chase her."

What’s available
There are two kinds of mixed-breed DNA testing: the inner-cheek swab method, which is a kit that can be bought at stores or online, a

nd a blood-drawn test, which is performed in a veterinarian's office.

The cheek-swab method, created by MetaMorphix Inc., a biotechnology company, is offered at two levels: The standard breed test (about $70) can identify from a range of about 50 dog breeds, while the "XL" breed test (about $120) identifies from about 100 breeds.

Grand Opening

So today I decided to finally get a blog and just post about my hacking progress of the game as well as my efforts to get the script dumped and translated (at least Japanese to English if not Japanese to German) and show some cool pics off.
On the right is the new titlescreen for Devil Children: Black Book =]

I've worked on that game now for some years, three namely, however, after I took break for a year in the US I decided to start over and make it even more prettier. It already features a full-blown vwf that is used for dialog and menus. However, flip side of the medal is, that I have to hack each and every menu on its own as they're all hardcoded into the game... Which... takes a lot effort and time I don't have right now^^"

Oh, and if anybody was wondering, I work on Black Book and Red Book simultaneously, however, I usually hack Black first... So now I'm stuck with some changes I made several months ago that I didn't hack into Red yet... Will happen soon. Tonight I'm gonna try my first script dump ever, and that's actually how I got the idea of opening a blog (like the BoF2 blog) in the first place.

Progress

So I finally got the code in Black Book working and put it into Red Book. Now I just need to apply the menu changes and all will be sweet. I busied myself with the DeviDas which I will call from now on "Devikon" (Devil + Lexikon) :)

So, I'll put a nice picture of the stuff I changed around here:

Rest of Work

I got military duty to do, so the translation work will have to wait approx. 9 months until I can pick it up at full pace again. Nevertheless, it will be actively seen thru to completion after that period of time.

I'm still thinking whether I will upload all of the dumped scripts somewhere or not, so translators can get an idea of what my dumps are like. Post comments, folks.

Black Book script translated :

Hi, so after a long time of not posting anything on my blog, the translator I found months ago has translated the full dialog script that is in Black Book :D
I will translate the remaining German script files and revise the already translated ones!

Also, the collaboration with Shadowsithe (see here) that began like ages ago will actually continue to bring out English versions of the two, possibly three, games :D
Hackingwise I'm a bit stalled at the moment, because of my duty. However, progress is being made :D Lastly, only special text strings used in menus only need to be dumped and translated :)

Updates :

So I'm finally back in Germany *yay* And hacking progress can continues... well... almost. I still don't have the "internets" at home, so that's like 2 more weeks of nothing feasible to do...
Then, I moved to Vista so that's a huge deal for some programs... Japanese locale for some as well. I already fixed thingy32 to work for me again (locale problems) but I'm actually thinking of porting it to VB.NET just for better compatibility with unicode (currently: none) and newer language seems better to me, anyway.
The old thingy32 does everything with strings, so that's why it's so slow :D

Then again, university has me cornered and I can't select "Run" - but that'll work out eventually. Right now I'm having a lot of free time to go thru all the stuff I did so far and finally compile some of my decumentations into something actually usable :D

Tom wants to see some progress with the insertion and English version of the game, so that will move on as well.
I'm kind of really big-time excited to actually finish up some loose ends on this one to move on to fixing Red Book up to the current status Black Book is at (not a huge deal tho).

So until then :D

EDIT: Oh yeah, pictures will follow shortly ^-^

2009!... Err...too late.

Yeah, so I thought I'd honor 2009 by at least posting a small update.

Right now, there's seriously much to do in uni, so I haven't been able to do anything at all with both Red Book and Black Book. I did a little comparison work to see what routines need to be updated for Red Book in order to "catch up" with Black Book hacking progress.

So far nothing that will make for good new pictures, sadly. Also, I'm thinking there is a bug in one of the battle routines that still persists and needs fixing. Something with centering strings *burr* So yeah, I'll see to that... sadly eventually :(

Some news on Red Book

Yeah, so just a quick update :D
I ported the text routine over to Red Book and it seems it's smooth sailing for that. Just need to fix the other million of routine and err... right ^^"
Anyway, I found some bugs that can be fixed in Black Book as well. As of now, nothing is functioning, but I'll keep you posted.

Here are some comparison screens of the battle menu and the status menu. Current Red Book on the left, current Black Book on the right.

Yes, quite a difference, ain't it?