Category Archives: Transhuman News

DNA is a large, complex molecule that allows cells to function and carries the genetic code that determines the traits of a living organism.

DNA is in every cell of every living thing. Some viruses also have DNA.

Life as we know it wouldnt exist without DNAit contains the instructions that cells need to function. DNA is found in the cell nucleus, and every cell in an organism has the exact same copy of DNA that is in every other cell. Each cell uses its copy of DNA whenever it needs to make a protein. Proteins have many essential jobs within a living thing. For example, your immune system produces proteins called antibodies to fight germs.

The information thats in DNA controls the development of specific traits, such as the shape of a leaf or the color of hair. Specifically, such traits are determined by genes, which are segments of DNA within strands called chromosomes. The set of all information contained in the DNA of any living thingall of its inheritable traitsis called its genome.

DNA is an abbreviation of deoxyribonucleic acid. It is a type of macromolecule (a very large moleculeone composed of hundreds of thousands of atoms) known as a nucleic acid. Nucleic acids are made of smaller molecules known as nucleotides, which are made of a phosphate, a sugar, and nitrogen bases. The four nitrogen bases in DNA are adenine (A), thymine (T), guanine (G), and cytosine (C).

DNA has a shape known as a double helix, which resembles a spiraled ladder. The DNA ladder is built from two very long strands of nucleotides with the nitrogen bases pairing together to form the rungs of the ladder. The bases form base pairs, with adenine always paired to thymine and guanine always paired to cytosine. The phosphate and sugar within the nucleotide act as the sides of the ladder.

Because DNA only exists within the cells nucleus, the genetic information must be distributed somehow. This is one of the roles of RNA, which is a macromolecule that works alongside DNA to make proteins. During this process, RNA acts as a kind of copy of the DNA that carries its genetic information outside of the cell nucleus.

We took a microscopic look at the differences between DNA, RNA, and mRNA, and their vital roles. Read all about it here!

Read more:
Dna | Definition of Dna at Dictionary.com

DNA can be a concern related to vaccines in two ways because it is the vacciness active ingredient, such as in adenovirus-based vaccines, or as a manufacturing byproduct following growth of vaccine virus in human fetal cells.

Because adenoviruses are DNA viruses, when they are used as a delivery vehicle during vaccination, the active ingredient is also DNA. This causes some to wonder whether the DNA delivered during vaccination can alter a persons DNA. In short, the answer is no. The reason that a persons DNA cannot be changed is that a necessary enzyme, called integrase, is not present.

We can be further reassured by the fact that when people get a cold from an adenovirus infection, the adenovirus cannot alter their DNA. As a family of viruses, this is not a role they can play.

Some people wonder whether the vaccines made using human fetal cells (chickenpox, rubella, hepatitis A, one version of the rabies vaccine, and one version of the COVID-19 vaccine) could cause harm if the DNA from the fetal cells mixes with the vaccine recipients DNA. This is not likely to happen:

Read more about the use of human fetal cells.

Yang H, Wei Z, Schenerman M. A statistical approach to determining criticality of residual host cell DNA.J Biopharm Stat 2015;25:234-246.The authors proposed a method for determining the quantity of residual host cell DNA regarding oncogenicity and infectivity. The authors created an equation to estimate the risk and applied that equation to a cell-based influenza vaccine manufactured using Madin Darby Canine Kidney (MDCK) cells. The calculated probability of having one cancer-causing or infective event based on the WHO/FDA limits is less than 10-15. If using limits of 800 base pairs and 40 ng DNA/dose, the risk is estimated to be 4.6 x 10-7.

Yang H.Establishing acceptable limits of residual DNA. PDA J Pharm Sci Technol 2013; 67(2):155-163.The author conducted a risk assessment on the WHO and FDA guidelines that recommended 10 ng/dose and 200 base pairs as the limits of residual DNA in the final biological product. The safety margin is defined as the number of doses needed to induce a cancer-causing or infective event in recipients. The author suggested that current safety margin estimates do not take into account DNA fractionation or DNA enzymatic inactivation. By incorporating the number of unfragmented potential cancer genes and accounting for DNA enzymatic inactivation, the author suggests that a more accurate safety margin can be calculated and that higher DNA content or base pair size would be acceptable.

Yang H, Zhang L, Galinski M. A probabilistic model for risk assessment of residual host cell DNA in biological products. Vaccine 2010;28:3308-3311.The authors assessed the cancer-causing and infective potential of residual DNA from a cell-based live, attenuated influenza vaccine that is manufactured in Madin Darby Canine Kidney (MDCK) cells. They determined that 230 billion doses of vaccine would need to be administered before a potential cancer gene dosage equivalent would be reached, and 83 trillion doses would need to be administered to induce an infective event.

Knezevic I, Stacey G, Petricciani J, et al.WHO Study Group on cell substrates for production of biologicals, Geneva, Switzerland, 11-12 June 2007. Biologicals 2008;36:203-211.The WHO Expert Committee on Biological Standardization adopted requirements for the use of animal cells as substrates for the production of vaccines and other biologicals in 1996. In 2006, a WHO Study Group on Cell Substrates was formed to initiate revision of WHO requirements. In 2007, the Study Group agreed that data generated on the possibility of cancer or an infection caused by DNA in vaccines were important in defining potential risk for vaccine recipients. It was considered highly likely that reduction of DNA fragment size reduced the risk from DNA and increased the safety margin, as the smaller the DNA fragments, the lower the probability that intact oncogenes and other functional sequences would be present. Studies performed at the Center for Biological Evaluation and Research (CBER) suggest that DNA fragments smaller than 200 base pairs will give substantial safety margins for products that meet the 10 ng/dose limit. Therefore, the margin of safety for vaccines can be found in the high fragmentation, and therefore very small size, of DNA.

WHO requirements for the use of animal cells as in vitro substrates for the production of biologicals. Biologicals 1998;26:175-193.Cell lines of human (e.g., WI-38, MRC-5) or monkey (FRhL-2) origin are non-tumorigenic and residual cellular DNA derived from these cells has not been, and is not, considered to pose any risk. Continuous cell line (CCL) substrates of human origin such as HeLa cells (derived from cervical cancer cells) or Namalva cells (derived from Burketts lymphoma) could have the potential to confer the capacity for unregulated cell growth or tumorigenic activity upon other cells. Risk assessment based on an animal oncogene model suggested that in vivo exposure to 1 ng (one-billionth of a gram) of cellular DNA where 100 copies of an activated cancer gene were present in the genome could give rise to a cancer-causing event 1 per 1 billion recipients. The risk associated with residual CCL DNA in a product is negligible when the amount of such DNA is 100 pg (a picogram is one-trillionth of a gram), which is the current maximal amount of CCL DNA allowed by the FDA.

Wierenga DE, Cogan J, Petricciani JC. Administration of tumor cell chromatin to immunosuppressed and non-immunosuppressed non-human primates. Biologicals 1995;23:221-224.The authors addressed the issue of how risky DNA may be as a residual impurity by injecting both normal and immunosuppressed monkeys with 100 million genome equivalents of DNA from a human tumor cell line that is one million times the DNA (1 mg) allowed by WHO in a single dose of biological product (100 pg). DNA from a human tumor, saline, or cyclosporine doses were administered intravenously, intramuscularly, or intracerebrally on either a daily, weekly or one-time basis. Animals were observed for 8 years, none of which showed any evidence of tumor formation.

Lower J. Risk of tumor induction in vivo residual cellular DNA: quantitative considerations. J Med Virol 1990;31:50-53.In 1987, the WHO Study Group compiled a list of experiments in which DNA of tumor viruses or DNA of the corresponding cancer genes were injected into experimental animals to determine the amount required to induce tumors in half of those tested. In this study, the author compared that information with the recommended residual cellular DNA limits (100 pg) in CCL biological products. The author determined that the number of cancer genes in 100 picograms cellular DNA is less than one-billionth of the amount needed to induce tumors in experimental animals.

Temin HM. Overview of biological effects of addition of DNA molecules to cells. J Med Virol 1990;31:13-17.A maximum cumulative probability of having a harmful effect is calculated to be less than 10-16to 10-19 per DNA molecule from a cell without activated precursor cancer genes or active viral cancer genes.

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Vaccine Ingredients DNA | Children's Hospital of ...

Vaccination consists of stimulating the immune system with an infectious agent, or components of an infectious agent, modified in such a manner that no harm or disease is caused, but ensuring that when the host is confronted with that infectious agent, the immune system can adequately neutralize it before it causes any ill effect. For over a hundred years vaccination has been effected by one of two approaches: either introducing specific antigens against which the immune system reacts directly; or introducing live attenuated infectious agents that replicate within the host without causing disease synthesize the antigens that subsequently prime the immune system.

Recently, a radically new approach to vaccination has been developed. It involves the direct introduction into appropriate tissues of a plasmid containing the DNA sequence encoding the antigen(s) against which an immune response is sought, and relies on the in situ production of the target antigen. This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture. As proof of the principle of DNA vaccination, immune responses in animals have been obtained using genes from a variety of infectious agents, including influenza virus, hepatitis B virus, human immunodeficiency virus, rabies virus, lymphocytic chorio-meningitis virus, malarial parasites and mycoplasmas. In some cases, protection from disease in animals has also been obtained. However, the value and advantages of DNA vaccines must be assessed on a case-by-case basis and their applicability will depend on the nature of the agent being immunized against, the nature of the antigen and the type of immune response required for protection.

The field of DNA vaccination is developing rapidly. Vaccines currently being developed use not only DNA, but also include adjuncts that assist DNA to enter cells, target it towards specific cells, or that may act as adjuvants in stimulating or directing the immune response. Ultimately, the distinction between a sophisticated DNA vaccine and a simple viral vector may not be clear. Many aspects of the immune response generated by DNA vaccines are not understood. However, this has not impeded significant progress towards the use of this type of vaccine in humans, and clinical trials have begun.

The first such vaccines licensed for marketing are likely to use plasmid DNA derived from bacterial cells. In future, others may use RNA or may use complexes of nucleic acid molecules and other entities. These guidelines address the production and control of vaccines based on plasmid DNA intended for use in humans. The purpose of these guidelines is to indicate:

It is recognized that the development and application of nucleic acid vaccines are evolving rapidly. Thus, their control should be approached in a flexible manner so that it can be modified as experience is gained in production and use. The intention of these guidelines is to provide a scientifically sound basis for the production and control of DNA vaccines intended for use in humans, and to assure their consistent ssafety and efficacy. Individual countries may wish to use these guidelines to develop their own national guidelines for DNA vaccines

Originally posted here:
DNA vaccines - WHO

1. DNA1.1 DNA basics / structure

DNA (deoxyribonucleic acid) is the genomic material in cells that contains the genetic information used in the development and functioning of all known living organisms. DNA, along with RNA and proteins, is one of the three major macromolecules that are essential for life. Most of the DNA is located in the nucleus, although a small amount can be found in mitochondria (mitochondrial DNA). Within the nucleus of eukaryotic cells, DNA is organized into structures called chromosomes. The complete 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.

DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (bases). It is the sequence of these four bases along the backbone that encodes information. The sequence of these bases comprises the genetic code, which subsequently specifies the sequence of the amino acids within proteins. The ends of DNA strands are called the 5(five prime) and 3 (three prime) ends. The 5 end has a terminal phosphate group and the 3 end a terminal hydroxyl group. One of the major structural differences between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by ribose in RNA.

Thestructure of DNA

Bases are classified into two types: the purines, A and G, and the pyrimidines, the six-membered rings C, T and U. Uracil (U), takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine.

In the DNA double helix, each type of base on one strand normally interacts with just one type of base on the other strand. This is complementary base pairing. Therefore, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G.

The central dogma of molecular biology is DNA makes RNA makes protein. This general rule emphasizes the order of events from transcription through translation and provides the basis for much of the genetic code research in the post double helix 1950s. The central dogma is often expressed as the following: DNA makes RNA, RNA makes proteins, proteins make us. Protein is never back translated to RNA or DNA. Furthermore, DNA is never translated directly to protein.

The Central Dogma of Molecular Biology

See also:The central dogma(external link).

Cell division is essential for cells to multiply and organisms to grow. As the final step in the Central Dogma, DNA replication must occur in order to faithfully transmit genetic material to the progeny of any cell or organism. When a cell divides, it must correctly replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. The two strands are separated and then an enzyme called DNA polymerase recreates each strands complementary DNA sequence. This enzyme makes the complementary strand by finding the correct base through complementary base pairing. As DNA polymerases can only extend a DNA strand in a 5 to 3 direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA. This process typically takes place during S phase of the cell cycle.

The process by which DNA achieves its control of cell life and function through protein synthesis is calledgene expression. A gene is a DNA sequence that contains genetic information for one functional protein. Proteins are essential for the modulation and maintenance of cellular activities. The formation of new protein molecules is made from amino acid building blocks based on information encoded in DNA/RNA. The amino acid sequence of each protein determines its conformation and properties (e.g. ability to interact with other molecules, enzymatic activity etc). Directed protein synthesis follows two major steps: gene transcription and transcript translation.

Transcription is the process by which the genetic information stored in DNA is used to produce a complementary RNA strand. In more detail, the DNA base sequence is first copied into an RNA molecule, called premessenger RNA, by messenger RNA (mRNA) polymerase. Premessenger RNA has a base sequence identical to the DNA coding strand. Genes consist of sequences encoding mRNA (exons) that are interrupted by non-coding sequences of variable length, called introns. Introns are removed and exons joined together before translation begins in a process called mRNA splicing. Messenger RNA splicing has proved to be an important mechanism for greatly increasing the versatility and diversity of expression of a single gene. It takes place in the nucleus in eukaryotes and in the cytoplasm in bacteria and archaea and leads to the formation of mature mRNA. Several different mRNA and protein products can arise from a single gene by selective inclusion or exclusion of individual exons from the mature mRNA products. This phenomenon is calledalternative mRNA splicing. It permits a single gene to code for multiple mRNA and protein products with related but distinct structures and functions1. Once introns are excised from the final mature mRNA molecule, this is then exported to the cytoplasm through the nuclear pores where it binds to protein-RNA complexes called ribosomes2. Ribosomes contain two subunits: the 60S subunit contains a single, large (28S) ribosomal RNA molecule complexed with multiple proteins, whereas the RNA component of the 40S subunit is a smaller (18S) ribosomal RNA molecule.

DNA transcription

Although every somatic cell in the human body contains the same genome, activation and silencing of specific genes in a cell-type-specific manner is necessary. Moreover, a cell must silence expression of genes specific to other cell types to ensure genomic stability. This type of repression must be maintained throughout the life of each cell in normal development. Epigenetic modifications that are defined as heritable, yet reversible changes that influence the expression of certain genes but with no alteration in the primary DNA sequence are ideal for regulating these events. The best studied epigenetic modification in human is DNA methylation, however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather occurs in the context of other epigenetic modifications such as the histone modifications.

Epigenetic Modifications

RNA, is another macromolecule essential for all known forms of life. Like DNA, RNA is made up of nucleotides. Once thought to play ancillary roles, RNAs are now understood to be among a cells key regulatory players where they catalyze biological reactions, control and modulate gene expression, sensing and communicating responses to cellular signals, etc.

The chemical structure of RNA is very similar to that of DNA: each nucleotide consists of a nucleobase a ribose sugar, and a phosphate group. There are two differences that distinguish DNA from RNA: (a) RNA contains the sugar ribose, while DNA contains the slightly different sugar deoxyribose (a type of ribose that lacks one oxygen atom), and (b) RNA has the nucleobase uracil while DNA contains thymine. Unlike DNA, most RNA molecules are single-stranded and can adopt very complex three-dimensional structures.

DNA and RNA similarities and differences

The universe of protein-coding and non-protein-coding RNAs (ncRNAs) is very diversevis--vis biogenesis, composition and function, and has been expanding rapidly59. Among the ncRNAs, microRNAs (miRNAs) represent the best-studied class to date and have been shown to regulate the expression of their protein-coding gene targets in a sequence-dependent manner1012.

An RNA molecule is said to be monocistronic when it captures the genetic information for a single molecular transcriptional product, e.g. a single miRNA precursor or a single primary mRNA. Most eukaryotic mRNAs are indeed monocistronic. On the other hand, rRNAs and some miRNAs are known to be polycystronic. In the case of polycistronic mRNAs, the primary transcript comprises several back-to-back mRNAs, each of which will be eventually translated into an amino acid sequence (polypeptide). Such polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequences are grouped into a single primary transcript, which in turn permits them to share a common promoter and to be regulated together.

One of the best known and best-studied classes of RNAs are messenger RNAs (mRNAs). MRNAs carry the genetic information that directs the synthesis of proteins by the ribosomes. All cellular organisms use mRNAs. The process of protein synthesis makes use of two more classes of RNAs, the transfer RNAs (tRNAs) and the ribosomal RNAs (rRNAs). The role of tRNAs is the delivery of amino acids to the ribosome where rRNAs link them together to form proteins.

The structure of an mRNA

RNA interference is a process that moderates gene expression in a sequence dependent manner. The RNAi pathway is found in all higher eukaryotes and was recently found in the budding yeast as well. Viruses have also been shown to be RNAi-aware in that they use their natural hosts RNAi pathway to their benefit.

RNAi is initiated by Dicer, a double-stranded-RNA-specific endonuclease from the RNase III protein family. Dicer cleaves double-stranded RNA (dsRNA) molecules into short fragments of ~21 nucleotides, with a two-nucleotide overhang at their 3 end, as well as a 5 phosphate and a 3 hydroxyl group. The RNAi pathway can be engaged by two types of small regulatory non-coding RNAs: a) small interfering RNAs (siRNAs), which are typically exogenous, and b) microRNAs (miRNAs), which are endogenous. SiRNAs are double-stranded ncRNAs that are mainly delivered to the cell experimentally by various transfection methods although they have been described to be produced form the cell itself15. MiRNAs are another type of small ncRNAs that are transcribed from the organisms DNA. After processing of the primary siRNAs and miRNAs by Dicer, typically one of the two strands is loaded onto the RNA-induced silencing complex (RISC), a complex of RNA and proteins that includes the Argonaute protein, whereas the other strand is discarded. The loaded siRNAs and miRNAs guide RISCs binding to specific mRNAs (targets). The sequence of the siRNA/miRNA determines the identity of the target. The resulting heteroduplex of the siRNA/miRNA and its target mRNA is characterized by base-pairing that generally spans much of the siRNA/miRNAs length. SiRNAs are typically designed to be perfectly complementary to their targets. On the other hand, miRNAs need not be fully-complementary to the mRNA that they target. This imprecise matching gives miRNAs the potential to target multiple endogenous mRNAs simultaneously. Whether induced by an siRNA or an miRNA, the downstream effect is the down-regulation of the targeted mRNA either via degradation or translational inhibition.

RNA interference in mammalian cells

Designer siRNAs are now widely used in the laboratory to down-regulate specific proteins whose function is under study. At the same time, the ability to engage the RNAi pathway in an on demand manner suggests the possibility that RNAi can be used in the clinic to reduce the production of those proteins that are over-expressed in a given disease context. Analogously, RNAi can also be used to sponge away excess amounts of an endogenous miRNA that would otherwise down-regulate a needed protein. The delivery method remains an important consideration for the development of RNAi-based therapies as the active molecule needs to be delivered efficiently and in a tissue-specific manner in order to maximize impact and diminish off-target effects.

See also:RNAi(external link).

The expression of proteins is determined by genomic information, and their presence supports the function of cell life. Parts of an organisms genome are transcribed in an orderly tissue- and developmental phase- specific manner into RNA transcripts that are destined to effect the eventual production of proteins.

Until fairly recently, it was believed that the molecules that are important for the function of a cell are those described by the Central Dogma of biology, namely messenger RNAs and proteins. Things began to change with the discovery of microRNAs more than 20 years ago in plants16and animals17,18. Subsequent research efforts have demonstrated that large parts of an organisms genome will be transcribed at one time point or another into RNA, but will not be translated into an amino acid sequence. These RNA transcripts have been referred to as ncRNAs and there is increased appreciation that many of them are indeed functional and affect key cellular processes.

There are many recognizable classes of ncRNAs, each having a distinct functionality. These include: transfer RNAs (tRNAs)19; ribosomal RNAs (rRNAs)20; the above-mentioned miRNAs17,18; small nucleolar RNAs (snoRNAs)21,22; piwi-interacting (piRNAs)2325; transcription initiation RNAs (tiRNAs)26; human microRNA-offset (moRNAs)27; sno-derived RNAs (sdRNAs)28; long intergenic ncRNAs (lincRNAs)29; etc. The full extent of distinct classes of ncRNAs that are encoded within the human genome is currently unknown but are believed to be numerous.

miRNA biogenesis

The biological role of long ncRNAs as a class remains largely elusive. Several specific cases have been shown to be involved in transcriptional gene silencing, and the activation of critical regulators of development and differentiation: these exerted their regulatory roles by interfering with transcription factors or their co-activators, though direct action on DNA duplex, by regulating adjacent protein-coding gene expression, by mediating DNA epigenetic modifications, etc.

Reverse transcription is the transfer of information from RNA to DNA (the reverse of normal transcription). This is known to occur in the case of retroviruses, such as HIV, as well as in eukaryotes, in the case of retrotransposons and telomere synthesis.

Post-transcriptional modification is a process in cell biology by which, primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA (mRNA), which includes splicing and occurs prior to protein synthesis. This process is vital for the correct translation of the genomes of eukaryotes as the human primary RNA transcript that is produced as a result of transcription contains both exons, which are coding sections of the primary RNA transcript and introns, which are the non coding sections of the primary RNA transcript.

Post-trancriptional modifications that lead to a mature mRNA include the (i) addition of a methylated guaninecapto the 5 end of mRNA and (ii) the addition of apoly-A tailto the other end. The cap and tail protect the mRNA from enzyme degradation and aid its attachment to the ribosome.In addition, (iii) introns(non-coding) sequences are spliced out of the mRNA andexons(coding) sequences are spliced together. The mature mRNA transcript will then undergotranslation64.

A protein is a molecule that performs reactions necessary to sustain the life of an organism. One cell can contain thousands of proteins.

Following transcription, translation is the next step of protein biosynthesis. In translation, mRNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or a polypeptide, that will later fold into a protein. Ribosomes read mRNA sequence in a ticker tape fashion three bases at a time, inserting the appropriate amino acid encoded by each three-base code word or codon into the appropriate position of the growing protein chain. This process is called mRNA translation. In particular, the mRNA sequence directly relates to the polypeptide sequence by binding to transfer RNA (tRNA) adapter molecules in binding pockets within the ribosome. Each amino acid is encoded by a sequence of three successive bases. Because thereare four code letters (A, C, G, and U), and because sequences read in the 53 direction have a different biologic meaning than sequences read in the 35 direction, there are 43=64, possible codons consisting of three bases. Some specialized codons serve as punctuation points during translation.The methionine codon (AUG), serves as the initiator codon signaling the first amino acid tobe incorporated. All proteins thus begin with a methionine residue, but this is often removed later in the translational process. Three codons, UAG, UAA, and UGA, serve as translation terminators, signaling the end of translation. The completed polypeptide chain then folds into a functional three-dimensional protein molecule and is transferred to other organelles for further processing or released into cytosol for association of the newly completed chain with other subunits to form complex multimeric proteins.

Protein translation

Post-translational modification is the chemical modification of a peptide that takes place after its translation. They represent one of the later steps in protein biosynthesis for many proteins. During protein synthesis, 20 different amino acids can be incorporated in order to form a polypeptide. After translation, the addition of other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates) to the proteins amino acids extends the range of functions of the protein modifying the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges). In addition, enzymes may remove amino acids from the amino end of the protein, or even cut the peptide chain in the middle. For instance, most nascent polypeptides start with the amino acid methionine because the start codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification. Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

See also:Inside a cell(external link).

Link:
DNA and RNA | Computational Medicine Center at Thomas ...

News Release

Thursday, March 25, 2021

Researchers at the National Institutes of Health (NIH) have discovered specific regions within the DNA of neurons that accumulate a certain type of damage (called single-strand breaks or SSBs). This accumulation of SSBs appears to be unique to neurons, and it challenges what is generally understood about the cause of DNA damage and its potential implications in neurodegenerative diseases.

Because neurons require considerable amounts of oxygen to function properly, they are exposed to high levels of free radicalstoxic compounds that can damage DNA within cells. Normally, this damage occurs randomly. However, in this study, damage within neurons was often found within specific regions of DNA called enhancers that control the activity of nearby genes.

Fully mature cells like neurons do not need all of their genes to be active at any one time. One way that cells can control gene activity involves the presence or absence of a chemical tag called a methyl group on a specific building block of DNA. Closer inspection of the neurons revealed that a significant number of SSBs occurred when methyl groups were removed, which typically makes that gene available to be activated.

An explanation proposed by the researchers is that the removal of the methyl group from DNA itself creates an SSB, and neurons have multiple repair mechanisms at the ready to repair that damage as soon as it occurs. This challenges the common wisdom that DNA damage is inherently a process to be prevented. Instead, at least in neurons, it is part of the normal process of switching genes on and off. Furthermore, it implies that defects in the repair process, not the DNA damage itself, can potentially lead to developmental or neurodegenerative diseases.

This study was made possible through the collaboration between two labs at the NIH: one run by Michael E. Ward, M.D., Ph.D. at the National Institute of Neurological Disorders and Stroke (NINDS) and the other by Andre Nussenzweig, Ph.D. at the National Cancer Institute (NCI). Dr. Nussenzweig developed a method for mapping DNA errors within the genome. This highly sensitive technique requires a considerable number of cells in order to work effectively, and Dr. Wards lab provided the expertise in generating a large population of neurons using induced pluripotent stem cells (iPSCs) derived from one human donor. Keith Caldecott, Ph.D. at the University of Sussex also provided his expertise in single strand break repair pathways.

The two labs are now looking more closely at the repair mechanisms involved in reversing neuronal SSBs and the potential connection to neuronal dysfunction and degeneration.

Michael E. Ward, M.D., Ph.D., investigator, NINDSAndre Nussenzweig, Ph.D., chief, Laboratory of Genomic Integrity, NCI

Wu W. et al. Neuronal enhancers are hot spots for DNA single-strand break repair. March 25, 2021. Nature. DOI: 10.1038/s41586-021-03468-5

This study was supported by the NIH/NINDS/NCI Intramural Research Programs, an NIH Intramural FLEX Award, U.S. Department of Defense, Chan Zuckerberg Initiative, Packard ALS Center, Alexs Lemonade Stand Foundation, UK Medical Research Council, Cancer Research-UK, ERC Advanced Investigator Award, Royal Society Wolfson Research Merit Award, and an Ellison Medical Foundation Senior Scholar in Aging Award.

This media availability describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NINDSis the nations leading funder of research on the brain and nervous system.The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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DNA damage hot spots discovered within neurons | National Institutes of Health - National Institutes of Health

Wonder Woman is supposed to be an Amazon, meaning whoever dreamed up her background got her ancestry wrong.Though the superheroine with the magic lasso is supposedly from the mythical Greek island of Themyscira, Amazons are thought to have beenScythian warrior women who rode out to battle and were fierce archers, much like Diana herself.

This wasnt the norm for ancient (mortal) Greek women despite two of the goddesses in their pantheon being warriors. But who were the legendary Scythians of the Iron Age, and from how did they emerge onto the Eurasian steppes?

Archeogeneticist Guido Alberto Gnecchi-Ruscone, who led a study recently published in Science Advances, worked with an interdisciplinary team of scientists to investigate Scythian DNA from 111 ancient individuals. While much about their origins are shrouded in mystery, the new research has found genetic evidence for where these enigmatic horselords possibly came from and how they fell.

The earliest Scythian burials are found in the Altai, followed by the Tasmola culture in north eastern Kazakhstan and then the other later groups, Gnecchi-Ruscone, told SYFY WIRE. The individuals from these cultures overall show a similar genetic ancestry profile that we defined as eastern gene pool and therefore hypothesized an Altai origin were we first saw it.

Scythian groups such as the Saka, the Pazyryk and the Tasmola are all believed to have ancestry in populations that first appeared in the Altai mountains. Burials in this region support this hypothesis. The frozen mummy of the now-famous Pazyryk ice maiden was found in a kurgan (grave mound) in the Altai. She was probably a storyteller or shaman of high status rather than a warrior, since she was not buried with any weapons, but with six of her horses. Whether she ever did ride them into battle might be lost to the grave.

What is especially fascinating is how quickly the Bronze Age populations of the steppe, mostly herders who did not travel far, would change as these people who had never come into contact with the Scythians before they were absorbed intro Scythian tribes through cultural exchange and intermarriage. It was the Scythians who created saddles and other implements for horseback riding. Whether it was they who introduced new technological advances to other peoples in the area, or whether it was the other way around, is still uncertain.

We might never know why and in detail how this process happened but whatever the reasons, the novelties and the advancements introduced by the Scythians occurred very likely also because of this encounters between different people and therefore different cultures, Gnecchi-Ruscone said.

As for Wonder Womans real ancestors, ancient chronicler Herodotus got several things wrong. He thought their language was Iranian, and while they had no written language, there are arguments for other origins. He also claimed that women training for battle would cut off one breast so they would have an edge in archery. There is no actual evidence for this. It is possible that they bound one breast to give them the advantage, and while no evidence for that has been found either, the bleeding and possible infection from the type of thing Herodotus suggested would have taken them out before they could even reach the battlefield.

These arent the only areas where the accounts of Herodotus are problematic. When he observed a funeral for a fallen Scythian king, he swore that mourners were smoking marijuana hardcore. Evidence from several gravesites has shown that they actually burned coriander to mask the smell of death.

Though the Scythians are revealing more of their genetic secrets, many remain buried with them. Russia, much which was known as Scythia during the Iron Age, is not as open to allowing scientists access to bones or mummies with invaluable DNA. The ice maiden caused political and ethical upheaval about whether her intricately tattooed body belonged in the kurgan or a museum. Hesitancy to allow excavations has caused frustration over unearthing more about these people, whom so little is known about. Gnecchi-Ruscone wants to hear the dead speak for themselves.

Despite these exciting findings, the genetic complexity of the Scythian epoch is far from being entirely described and analyzed, he said. Many questions are still open about the genetic structure of the westernmost Scythian groups that reached as far as eastern Europe and the Balkans. Also the genetic processed associated with their decline.

The decline of the Scythians was not some massive takeover or bloody battle. During the transitional period after the Iron Age, they were absorbed by other peoples just as they had absorbed the earlier herders. With the rise of the Persian empire along with the Xiongnu and Xianbei confederations, there was an influx of nomadic empires from the east and south into ancient Scythia. They also faded into other European groups, such as the Slavs. Some believe that they were proto-Slavs themselves.

Until the ghosts of the Scythians can tell us more, too bad it isnt possible to take a DNA sample from Wonder Woman.

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Wonder Womans ancestors? DNA is revealing how ancient Scythian warriors rose and fell - SYFY WIRE

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Over 50 millennia, at least five major immigration waves have successively populated the Philippines, the most comprehensive survey of genetic variations in the country to date shows. This Uppsala University study, published in the scientific journal PNAS, comprises 2.3 million DNA markers from some 1,000 individuals.

Our findings suggest that instead of farming, climate change may have played a more important role in driving the mass movement of populations in various directions, says Maximilian Larena, researcher at Uppsala Universitys Department of Organismal Biology and first author of the study.

The Philippines more than 7,000 islands have always been a link between Southeast Asia, Australia, New Zealand, and the Polynesian islands of the Pacific Ocean. For millennia, the archipelago has served as a corridor for migration from one continent to another.

In a new study, a group of researchers from Australia, Taiwan, the Philippines, and elsewhere, led by Uppsala University, reveal the huge scale and complexity of the Filipino populations origins, kinship patterns, and genetic diversity. By typing 2.3 million DNA markers that are variable in us humans, and then using computational methods, the scientists have investigated the Filipinos DNA. In doing so, they analyzed these markers from more than 1,000 individuals, representing 115 Filipino cultural groups.

The study shows that over the millennia, at least five major waves of immigration built up the population of the Philippines. Different ethnic groups arrived successively. Negritos, the first Filipinos, were followed by various groups, including those who call themselves the Manobo and Sama.

The last three population waves occurred between 15,000 and 7,000 years ago a period in which climate change caused geographical transformations of the region. Sea levels rose, for example. Sunda, until then a large, fertile land mass between Southeast Asia and Oceania, was inundated and the land bridge between Taiwan and southern China was submerged beneath the waters.

Our study debunks a view that has dominated research on human history: that language, ways of life, culture, and people move together as a single unit a Neolithic package, as its often called. Were able to show that new groups of people migrated to the Philippines more than seven millennia ago, and it was these groups that took the Austronesian languages with them. It wasnt until three thousand years later that agriculture was taken there, probably by related groups. So that happened a long time afterwards, says Professor Mattias Jakobsson, senior author of the study.

Reference: Multiple migrations to the Philippines during the last 50,000 years by Maximilian Larena, Federico Sanchez-Quinto, Per Sjdin, James McKenna, Carlo Ebeo, Rebecca Reyes, Ophelia Casel, Jin-Yuan Huang, Kim Pullupul Hagada, Dennis Guilay, Jennelyn Reyes, Fatima Pir Allian, Virgilio Mori, Lahaina Sue Azarcon, Alma Manera, Celito Terando, Lucio Jamero Jr, Gauden Sireg, Renefe Manginsay-Tremedal, Maria Shiela Labos, Richard Dian Vilar, Acram Latiph, Rodelio Linsahay Saway, Erwin Marte, Pablito Magbanua, Amor Morales, Ismael Java, Rudy Reveche, Becky Barrios, Erlinda Burton, Jesus Christopher Salon, Ma. Junaliah Tuazon Kels, Adrian Albano, Rose Beatrix Cruz-Angeles, Edison Molanida, Lena Granehll, Mrio Vicente, Hanna Edlund, Jun-Hun Loo, Jean Trejaut, Simon Y. W. Ho, Lawrence Reid, Helena Malmstrm, Carina Schlebusch, Kurt Lambeck, Phillip Endicott and Mattias Jakobsson, 22 March 2021, Proceedings of the National Academy of Sciences.DOI: 10.1073/pnas.2026132118

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Largest-Ever DNA Mapping of the Philippines Shows 5 Major Immigration Waves Over 50 Millennia - SciTechDaily

Generally thought of as fierce horse-warriors, the Scythians were a multitude of Iron Age cultures who ruled the Eurasian steppe, playing a major role in Eurasian history. A new study published inScience Advancesanalyzes genome-wide data for 111 ancient individuals spanning the Central Asian Steppe from the first millennia BCE and CE. The results reveal new insights into the genetic events associated with the origins, development and decline of the steppes legendary Scythians.Because of their interactions and conflicts with the major contemporaneous civilizations of Eurasia, the Scythians enjoy a legendary status in historiography and popular culture. The Scythians had major influences on the cultures of their powerful neighbors, spreading new technologies such as saddles and other improvements for horse riding. The ancient Greek, Roman, Persian and Chinese empires all left a multitude of sources describing, from their perspectives, the customs and practices of the feared horse warriors that came from the interior lands of Eurasia.

Still, despite evidence from external sources, little is known about Scythian history. Without a written language or direct sources, the language or languages they spoke, where they came from and the extent to which the various cultures spread across such a huge area were in fact related to one another, remain unclear.

Although many of the open questions on the history of the Scythians cannot be solved by ancient DNA alone, this study demonstrates how much the populations of Eurasia have changed and intermixed through time. Future studies should continue to explore the dynamics of these trans-Eurasian connections by covering different periods and geographic regions, revealing the history of connections between west, central and east Eurasia in the remote past and their genetic legacy in present day Eurasian populations.

Reference: Gnecchi-Ruscone GA, Khussainova E, Kahbatkyzy N, et al. Ancient genomic time transect from the Central Asian Steppe unravels the history of the Scythians. Sci Adv. 2021;7(13):eabe4414. doi:10.1126/sciadv.abe4414.

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DNA Offers New Insights Into the The Origins and Decline of the Scythians - Technology Networks