Category Archives: DNA

Biologists in the 1940s had difficulty in accepting DNA as the genetic material because of the apparent simplicity of its chemistry. DNA was known to be a long polymer composed of only four types of subunits, which resemble one another chemically. Early in the 1950s, DNA was first examined by x-ray diffraction analysis, a technique for determining the three-dimensional atomic structure of a molecule (discussed in Chapter 8). The early x-ray diffraction results indicated that DNA was composed of two strands of the polymer wound into a helix. The observation that DNA was double-stranded was of crucial significance and provided one of the major clues that led to the Watson-Crick structure of DNA. Only when this model was proposed did DNA's potential for replication and information encoding become apparent. In this section we examine the structure of the DNA molecule and explain in general terms how it is able to store hereditary information.

A DNA molecule consists of two long polynucleotide chains composed of four types of nucleotide subunits. Each of these chains is known as a DNA chain, or a DNA strand. Hydrogen bonds between the base portions of the nucleotides hold the two chains together (). As we saw in Chapter 2 (Panel 2-6, pp. 120-121), nucleotides are composed of a five-carbon sugar to which are attached one or more phosphate groups and a nitrogen-containing base. In the case of the nucleotides in DNA, the sugar is deoxyribose attached to a single phosphate group (hence the name deoxyribonucleic acid), and the base may be either adenine (A), cytosine (C), guanine (G), or thymine (T). The nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a backbone of alternating sugar-phosphate-sugar-phosphate (see ). Because only the base differs in each of the four types of subunits, each polynucleotide chain in DNA is analogous to a necklace (the backbone) strung with four types of beads (the four bases A, C, G, and T). These same symbols (A, C, G, and T) are also commonly used to denote the four different nucleotidesthat is, the bases with their attached sugar and phosphate groups.

DNA and its building blocks. DNA is made of four types of nucleotides, which are linked covalently into a polynucleotide chain (a DNA strand) with a sugar-phosphate backbone from which the bases (A, C, G, and T) extend. A DNA molecule is composed of two (more...)

The way in which the nucleotide subunits are lined together gives a DNA strand a chemical polarity. If we think of each sugar as a block with a protruding knob (the 5 phosphate) on one side and a hole (the 3 hydroxyl) on the other (see ), each completed chain, formed by interlocking knobs with holes, will have all of its subunits lined up in the same orientation. Moreover, the two ends of the chain will be easily distinguishable, as one has a hole (the 3 hydroxyl) and the other a knob (the 5 phosphate) at its terminus. This polarity in a DNA chain is indicated by referring to one end as the 3 end and the other as the 5 end.

The three-dimensional structure of DNAthe double helixarises from the chemical and structural features of its two polynucleotide chains. Because these two chains are held together by hydrogen bonding between the bases on the different strands, all the bases are on the inside of the double helix, and the sugar-phosphate backbones are on the outside (see ). In each case, a bulkier two-ring base (a purine; see Panel 2-6, pp. 120121) is paired with a single-ring base (a pyrimidine); A always pairs with T, and G with C (). This complementary base-pairing enables the base pairs to be packed in the energetically most favorable arrangement in the interior of the double helix. In this arrangement, each base pair is of similar width, thus holding the sugar-phosphate backbones an equal distance apart along the DNA molecule. To maximize the efficiency of base-pair packing, the two sugar-phosphate backbones wind around each other to form a double helix, with one complete turn every ten base pairs ().

Complementary base pairs in the DNA double helix. The shapes and chemical structure of the bases allow hydrogen bonds to form efficiently only between A and T and between G and C, where atoms that are able to form hydrogen bonds (see Panel 2-3, pp. 114115) (more...)

The DNA double helix. (A) A space-filling model of 1.5 turns of the DNA double helix. Each turn of DNA is made up of 10.4 nucleotide pairs and the center-to-center distance between adjacent nucleotide pairs is 3.4 nm. The coiling of the two strands around (more...)

The members of each base pair can fit together within the double helix only if the two strands of the helix are antiparallelthat is, only if the polarity of one strand is oriented opposite to that of the other strand (see and ). A consequence of these base-pairing requirements is that each strand of a DNA molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand.

Genes carry biological information that must be copied accurately for transmission to the next generation each time a cell divides to form two daughter cells. Two central biological questions arise from these requirements: how can the information for specifying an organism be carried in chemical form, and how is it accurately copied? The discovery of the structure of the DNA double helix was a landmark in twentieth-century biology because it immediately suggested answers to both questions, thereby resolving at the molecular level the problem of heredity. We discuss briefly the answers to these questions in this section, and we shall examine them in more detail in subsequent chapters.

DNA encodes information through the order, or sequence, of the nucleotides along each strand. Each baseA, C, T, or Gcan be considered as a letter in a four-letter alphabet that spells out biological messages in the chemical structure of the DNA. As we saw in Chapter 1, organisms differ from one another because their respective DNA molecules have different nucleotide sequences and, consequently, carry different biological messages. But how is the nucleotide alphabet used to make messages, and what do they spell out?

As discussed above, it was known well before the structure of DNA was determined that genes contain the instructions for producing proteins. The DNA messages must therefore somehow encode proteins (). This relationship immediately makes the problem easier to understand, because of the chemical character of proteins. As discussed in Chapter 3, the properties of a protein, which are responsible for its biological function, are determined by its three-dimensional structure, and its structure is determined in turn by the linear sequence of the amino acids of which it is composed. The linear sequence of nucleotides in a gene must therefore somehow spell out the linear sequence of amino acids in a protein. The exact correspondence between the four-letter nucleotide alphabet of DNA and the twenty-letter amino acid alphabet of proteinsthe genetic codeis not obvious from the DNA structure, and it took over a decade after the discovery of the double helix before it was worked out. In Chapter 6 we describe this code in detail in the course of elaborating the process, known as gene expression, through which a cell translates the nucleotide sequence of a gene into the amino acid sequence of a protein.

The relationship between genetic information carried in DNA and proteins.

The complete set of information in an organism's DNA is called its genome, and it carries the information for all the proteins the organism will ever synthesize. (The term genome is also used to describe the DNA that carries this information.) The amount of information contained in genomes is staggering: for example, a typical human cell contains 2 meters of DNA. Written out in the four-letter nucleotide alphabet, the nucleotide sequence of a very small human gene occupies a quarter of a page of text (), while the complete sequence of nucleotides in the human genome would fill more than a thousand books the size of this one. In addition to other critical information, it carries the instructions for about 30,000 distinct proteins.

The nucleotide sequence of the human -globin gene. This gene carries the information for the amino acid sequence of one of the two types of subunits of the hemoglobin molecule, which carries oxygen in the blood. A different gene, the -globin (more...)

At each cell division, the cell must copy its genome to pass it to both daughter cells. The discovery of the structure of DNA also revealed the principle that makes this copying possible: because each strand of DNA contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand, each strand can act as a template, or mold, for the synthesis of a new complementary strand. In other words, if we designate the two DNA strands as S and S, strand S can serve as a template for making a new strand S, while strand S can serve as a template for making a new strand S (). Thus, the genetic information in DNA can be accurately copied by the beautifully simple process in which strand S separates from strand S, and each separated strand then serves as a template for the production of a new complementary partner strand that is identical to its former partner.

DNA as a template for its own duplication. As the nucleotide A successfully pairs only with T, and G with C, each strand of DNA can specify the sequence of nucleotides in its complementary strand. In this way, double-helical DNA can be copied precisely. (more...)

The ability of each strand of a DNA molecule to act as a template for producing a complementary strand enables a cell to copy, or replicate, its genes before passing them on to its descendants. In the next chapter we describe the elegant machinery the cell uses to perform this enormous task.

Nearly all the DNA in a eucaryotic cell is sequestered in a nucleus, which occupies about 10% of the total cell volume. This compartment is delimited by a nuclear envelope formed by two concentric lipid bilayer membranes that are punctured at intervals by large nuclear pores, which transport molecules between the nucleus and the cytosol. The nuclear envelope is directly connected to the extensive membranes of the endoplasmic reticulum. It is mechanically supported by two networks of intermediate filaments: one, called the nuclear lamina, forms a thin sheetlike meshwork inside the nucleus, just beneath the inner nuclear membrane; the other surrounds the outer nuclear membrane and is less regularly organized ().

A cross-sectional view of a typical cell nucleus. The nuclear envelope consists of two membranes, the outer one being continuous with the endoplasmic reticulum membrane (see also Figure 12-9). The space inside the endoplasmic reticulum (the ER lumen) (more...)

The nuclear envelope allows the many proteins that act on DNA to be concentrated where they are needed in the cell, and, as we see in subsequent chapters, it also keeps nuclear and cytosolic enzymes separate, a feature that is crucial for the proper functioning of eucaryotic cells. Compartmentalization, of which the nucleus is an example, is an important principle of biology; it serves to establish an environment in which biochemical reactions are facilitated by the high concentration of both substrates and the enzymes that act on them.

Genetic information is carried in the linear sequence of nucleotides in DNA. Each molecule of DNA is a double helix formed from two complementary strands of nucleotides held together by hydrogen bonds between G-C and A-T base pairs. Duplication of the genetic information occurs by the use of one DNA strand as a template for formation of a complementary strand. The genetic information stored in an organism's DNA contains the instructions for all the proteins the organism will ever synthesize. In eucaryotes, DNA is contained in the cell nucleus.

Read more here:
The Structure and Function of DNA - Molecular Biology of ...

STONY BROOK, N.Y.--(BUSINESS WIRE)--Applied DNA Sciences, Inc. (NASDAQ: APDN) (the Company), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, announced today that its wholly-owned clinical laboratory subsidiary, Applied DNA Clinical Labs, LLC (ADCL), intends to deploy its Linea 1.0 COVID-19 Assay (the Linea 1.0 Assay or the Assay), part of ADCLs Linea COVID-19 diagnostics and testing portfolio, for the rapid detection of samples containing a mutation profile that is indicative of the BA.2 subvariant (BA.2) of Omicron in COVID-19-positive samples.

ADCL believes the Linea 1.0 Assay has clinical utility as a genomic surveillance solution to enable public health authorities to detect and assess BA.2 spread via the reflex testing of COVID-19 positive samples with the Linea 1.0 Assay. When used as a reflex test, the Company believes the Linea 1.0 Assay allows for the rapid and inexpensive identification of positive COVID-19 samples that are indicative of BA.2 relative to costly and time-consuming next-generation sequencing.

First identified in November 2021, BA.2 is a descendant of the Omicron variant (BA.1) but differs in some of its genetic traits, including certain mutations in the spike protein, which may make it somewhat harder to detect via S-gene target failure (SGTF") on certain third-party assays. SGTF was used globally to track the spread and prevalence of the Omicron variant (BA.1). In silico analysis of the BA.2 subvariant conducted by ADCL indicates that BA.2 will likely result in a unique detection signature on the Linea 1.0 Assay that is distinct from BA.1 and other currently circulating SARS-CoV-2 variants of concern and/or interest. The Linea 1.0 Assays ability to identify samples containing a mutation profile indicative of BA.2 via SGTF is possible due to the Assays unique double S-gene target design.

BA.2 has been identified in nearly 50 countries, including the U.S., U.K., Israel, and Denmark, where the subvariant accounts for almost half of Omicron cases. According to Denmarks Statens Serum Institute, the country's top infectious disease authority, preliminary calculations suggest BA.2 could be 1.5 times more infectious than BA.1. On January 27, 2022, the New York State Health Department, the State in which most ADCLs COVID-19 testing clients reside, confirmed its first cases of BA.2. The subvariant has been sequenced in at least 20 States.

Deploying Linea 1.0 Assay towards BA.2 potentially positions ADCL for incremental testing demand while also offering clinical utility to epidemiologists presently analyzing BA.2 to determine its characteristics and their clinical significance to understand better how the subvariant might shape the nations pandemic response going forward. As a result of the Assays double S-gene target design, we believe public health officials can be ahead of the curve in case of BA.2 prevalence, stated Dr. James A. Hayward, president and CEO of Applied DNA.

About Applied DNA Sciences

Applied DNA is commercializing LinearDNA, its proprietary, large-scale polymerase chain reaction (PCR)-based manufacturing platform that allows for the large-scale production of specific DNA sequences.

The LinearDNA platform has utility in the nucleic acid-based in vitro diagnostics and preclinical nucleic acid-based drug development and manufacturing market. The platform is used to manufacture DNA for customers as components of in vitro diagnostic tests and for preclinical nucleic acid-based drug development in the fields of adoptive cell therapies (CAR T and TCR therapies), DNA vaccines (anti-viral and cancer), RNA therapies, clustered regularly interspaced short palindromic repeats (CRISPR) based therapies, and gene therapies.

The LinearDNA platform also has non-biologic applications, such as supply chain security, anti-counterfeiting and anti-theft technology. Key end-markets include textiles, pharmaceuticals and nutraceuticals, and cannabis, among others.

Leveraging its deep expertise in nucleic acid-based technologies, the Company has also established safeCircle, a high-throughput turnkey solution for population-scale COVID-19 testing. safeCircle is designed to look for infection within defined populations or communities utilizing high throughput testing methodologies that increase testing efficiencies and provide for rapid turn-around-times.

Visit adnas.com for more information. Follow us on Twitter and LinkedIn. Join our mailing list.

The Companys common stock is listed on NASDAQ under ticker symbol APDN, and its publicly traded warrants are listed on OTC under ticker symbol APPDW.

Applied DNA is a member of the Russell Microcap Index.

Forward-Looking Statements

The statements made by Applied DNA in this press release may be forward-looking in nature within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Forward-looking statements describe Applied DNAs future plans, projections, strategies, and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to its history of net losses, limited financial resources, limited market acceptance, the possibility that Applied DNAs assay kits or testing services could become obsolete or have its utility diminished and the unknown amount of revenues and profits that will results from Applied DNAs testing contracts. Further, the uncertainties inherent in research and development, future data and analysis, including whether any of Applied DNAs or its partners future diagnostic candidates will advance further in the research process or receiving authorization, clearance or approval from the FDA, equivalent foreign regulatory agencies and/or the New York State Department of Health (NYSDOH), and whether and when, if at all, they will receive final authorization, clearance or approval from the FDA, equivalent foreign regulatory agencies and/or NYSDOH, the unknown outcome of any applications or requests to FDA, equivalent foreign regulatory agencies and/or the NYSDOH, the unknown limited duration of any EUAs from the FDA, changes in guidance promulgated by the CDC, FDA, CMS an/or NYSDOH relating to COVID-19 testing, whether and when, if at all, the FDA will review any EUA request, disruptions in the supply of raw materials and supplies, continued mutations of the SARS-CoV-2 virus, and various other factors detailed from time to time in Applied DNAs SEC reports and filings, including our Annual Report on Form 10-K filed on December 9, 2021, and other reports we file with the SEC, which are available at http://www.sec.gov. Applied DNA undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, unless otherwise required by law.

Read more:
Applied DNA to Deploy Linea 1.0 COVID-19 Assay for Rapid Detection of New Omicron Subvariant BA.2 - Business Wire

The Earth Biogenome Project, a global consortium that aims to sequence the genomes of all complex life on earth (some 1.8 million described species) in ten years, is ramping up.

The projects origins, aims, and progress are detailed in two multi-authored papers published on January 18, 2022. Once complete, it will forever change the way biological research is done.

Specifically, researchers will no longer be limited to a few model species and will be able to mine the DNA sequence database of any organism that shows interesting characteristics. This new information will help us understand how complex life evolved, how it functions, and how biodiversity can be protected.

The project was first proposed in 2016, and I was privileged to speak at its launch in London in 2018. It is currently in the process of moving from its startup phase to full-scale production.

The aim of phase one is to sequence one genome from every taxonomic family on earth, some 9,400 of them. By the end of 2022, one-third of these species should be done. Phase two will see the sequencing of a representative from all 180,000 genera, and phase three will mark the completion of all the species.

DNA sequence.

The grand aim of the Earth Biogenome Project is to sequence the genomes of all 1.8 million described species of complex life on Earth. This includes all plants, animals, fungi, and single-celled organisms with true nuclei (that is, all eukaryotes).

While model organisms like mice, rock cress, fruit flies, and nematodes have been tremendously important in our understanding of gene functions, its a huge advantage to be able to study other species that may work a bit differently.

Many important biological principles came from studying obscure organisms. For instance, genes were famously discovered by Gregor Mendel in peas, and the rules that govern them were discovered in red bread mold.

DNA was discovered first in salmon sperm, and our knowledge of some systems that keep it secure came from research on tardigrades. Chromosomes were first seen in mealworms and sex chromosomes in a beetle (sex chromosome action and evolution has also been explored in fish and platypus). And telomeres, which cap the ends of chromosomes, were discovered in pond scum.

Comparing closely and distantly related species provides tremendous power to discover what genes do and how they are regulated. For instance, in another PNAS paper, coincidentally also published on January 18, my University of Canberra colleagues and I discovered Australian dragon lizards regulate sex by the chromosome neighborhood of a sex gene, rather than the DNA sequence itself.

Scientists also use species comparisons to trace genes and regulatory systems back to their evolutionary origins, which can reveal astonishing conservation of gene function across nearly a billion years. For instance, the same genes are involved in retinal development in humans and in fruit fly photoreceptors. And the BRCA1 gene that is mutated in breast cancer is responsible for repairing DNA breaks in plants and animals.

The genome of animals is also far more conserved than has been supposed. For instance, several colleagues and I recently demonstrated that animal chromosomes are 684 million years old.

It will be exciting, too, to explore the dark matter of the genome, and reveal how DNA sequences that dont encode proteins can still play a role in genome function and evolution.

Another important aim of the Earth Biogenome Project is conservation genomics. This field uses DNA sequencing to identify threatened species, which includes about 28% of the worlds complex organisms helping us monitor their genetic health and advise on management.

Until recently, sequencing large genomes took years and many millions of dollars. But there have been tremendous technical advances that now make it possible to sequence and assemble large genomes for a few thousand dollars. The entire Earth Biogenome Project will cost less in todays dollars than the human genome project, which was worth about US$3 billion in total.

In the past, researchers would have to identify the order of the four bases chemically on millions of tiny DNA fragments, then paste the entire sequence together again. Today they can register different bases based on their physical properties, or by binding each of the four bases to a different dye. New sequencing methods can scan long molecules of DNA that are tethered in tiny tubes, or squeezed through tiny holes in a membrane.

Chromosomes consist of long double-helical arrays of the four base pairs whose sequence specifies genes. DNA molecules are capped at the end by telomeres.

But why not save time and money by sequencing just key representative species?

Well, the whole point of the Earth Biogenome Project is to exploit the variation between species to make comparisons, and also to capture remarkable innovations in outliers.

There is also the fear of missing out. For instance, if we sequence only 69,999 of the 70,000 species of nematode, we might miss the one that could divulge the secrets of how nematodes can cause diseases in animals and plants.

There are currently 44 affiliated institutions in 22 countries working on the Earth Biogenome Project. There are also 49 affiliated projects, including enormous projects such as the California Conservation Genomics Project, the Bird 10,000 Genomes Project and UKs Darwin Tree of Life Project, as well as many projects on particular groups such as bats and butterflies.

Written by Jenny Graves, Distinguished Professor of Genetics and Vice Chancellors Fellow, La Trobe University.

This article was first published in The Conversation.

Original post:
Monumental Project Underway To Sequence the Genome of Every Complex Species on Earth - SciTechDaily

Angelo Colon-Ortizs defense counsel announced in Worcester Superior Court Thursday an appeal of a judges recent pretrial ruling to admit DNA evidence allegedly linking the Worcester man to the murder of Vanessa Marcotte, who was killed while jogging in Princeton in 2016.

Ortiz-Colons attorneys John Gregory Swomley and Eduardo Masferrer announced the appeal in a Thursday morning status review in the case.

The appeal comes after Worcester Superior Court Judge Janet Kenton-Walker ruled to deny a motion from Colon-Ortizs defense to suppress DNA evidence collected from the defendant, which argued that state troopers who went to his home to collect the sample did not get his knowing and voluntary consent for the sample due to translation issues and seized the DNA without a search warrant or probable cause.

Marcotte, a 27-year-old Google employee who lived in New York, was visiting her mothers home in Princeton in August 2016 when she went out for a jog. She never returned home, and her body was found on Aug. 7 in the woods off Brooks Station Road, not far from her mothers home.

The sample collected from Colon-Ortiz later matched DNA found underneath Marcottes fingernails during an autopsy, according to officials. He has been charged with murder.

The defense last year said it believed that the DNA waiver police provided to their client was improperly and inadequately translated into Spanish and did not properly state the rights being waived or that consent was being given to police to obtain a DNA sample.

The DNA sample was collected from Colon-Ortiz on March 16, 2017, according to court records.

Police collected the DNA sample during a visit to Colon-Ortizs apartment from state troopers Robert Parr, Michael Travers and Thiago Miranda as part of an investigation into the death of Marcotte. A witness account and DNA profile led police to identify Colon-Ortiz as a person of interest in the case.

Kenton-Walker denied the motion on Jan. 11, but called the consent form Massachusetts State Police used to collect a buccal DNA swab from Colon-Ortiz, the product of carelessness, court records show.

Considering the totality of the circumstances in this case, the consent form, together with the interview with the police, conveyed that information, Kenton-Walker wrote. The other information in the form, while important and valuable, did not defeat Colon-Ortizs free and voluntary decision to consent to providing a DNA sample.

The next status review for Colon-Ortiz will be held on April 7.

Related Content:

The rest is here:
Angelo Colon-Ortiz appeals ruling on DNA that allegedly ties him to killing of Vanessa Marcotte - MassLive.com

The DNA of Star Trek creator Gene Roddenberry will accompany the ashes of his wife and the actor who played chief engineer Scotty when the first Vulcan rocket lifts off in a mission dubbed the Enterprise flight, scheduled for later this year.

Celestis, a Houston-based space memorial services company, said this week that the ashes of Canadian actor James Doohan and actress Majel Barrett Roddenberry, who died in 2008, will accompany the DNA samples of her late husband. Gene Roddenberrys ashes were scattered in space in 1997, six years after his death.

Were very pleased to be fulfilling, with this mission, a promise I made to Majel Barrett Roddenberry in 1997 that one day we would fly her and husband Star Trek creator Gene Roddenberry together on a deep space memorial spaceflight, said Charles M. Chafer, the CEO of Celestis.

They will be among more than 150 capsules that contain the cremated remains, DNA samples and messages of Star Trek fans who paid to be blasted into the final frontier after their deaths.

United Space Launch, a joint venture of Lockheed Martin and Boeing that services government contracts, has agreed to accommodate the remains as part of an unrelated mission.

What a fitting tribute to the Roddenberry family and the Star Trek fans to be a part of the maiden flight of Vulcan, our next-generation rocket, said Tory Bruno, president and CEO of the company based in Centennial, Colorado.

The maiden flight of the Vulcan Centaur rocket, delayed several times during the development of its BE-4 engine, has the primary purpose of launching Astrobotics Peregrine lunar lander. The human remains of the Enterprise flight will come along as a secondary payload.

Officials said the rocket will rendezvous with the moon, continue into deep space and orbit around the sun with the remains. The launch date has not been scheduled.

The Vulcan rocket bears the same name as the planet and race of Mr. Spock, one of the television franchises most beloved characters.

Doohan was a World War II veteran who participated in the D-Day landing at Juno Beach, where he lost his right middle finger and took pains to conceal its absence throughout a decades-long acting career. A linguist who created the Vulcan and Klingon languages for the franchise, he died in 2005.

Majel Roddenberry, who acted under the name Barrett, appeared in every incarnation of Star Trek produced during her lifetime. She married Gene Roddenberry, a Texas native and a veteran television producer, in 1969 the last year that the original Star Trek series aired.

Later in her career, she produced the science-fiction television shows Andromeda and Earth: Final Conflict, based on notes from her late husband.

The launch comes as private space flight has increasingly become a popular option for wealthy celebrities.

Last year, 90-year old Star Trek actor William Shatner, who played Capt. James T. Kirk in the show, traveled into space on Blue Origins New Shepard rocket.

Continue reading here:
First Vulcan flight to carry DNA of 'Star Trek' creator, ashes of wife and chief engineer Scotty - Washington Times

Greek mezedes. Credit: Garrett Ziegler/CC BY-NC-ND-2.0

Mezedes are the very DNA of Greek food.

By Giorgio Pintzas Monzani

A sip, a bite, a word. For those who know the world of mezedes closely, you can easily find yourself in this sentence. For those who are not yet fully familiar: you have a world to discover.

You can call them samplers, you can call them an aperitif. But you would have it wrong.

We could describe them as appetizers, only they do not precede any main course: they are the meal itself.

Mezedes are a way, a style of eating; a set of courses, of small to medium size, which accompany the real protagonist of those tables: the beverage.

Related: Giorgio Pintzas Monzanis Savory Vasilopita appetizers

Mezedes originate from the Balkans, Greece, Turkey, and from countries further south, such as Lebanon and Syria.

Their history runs through the centuries in the very DNA of these countries, thus going hand in hand with some of the most long-lived peoples in these, the lands of history and antiquity.

Their name comes from the Persian language, where mazzeh or mazidan meant taste, flavor. As if today it was a tasting.

The culture of mezedes is strongly connected to some fundamental principles of all the above-mentioned countries, especially of Greece. Conviviality and the characteristic hospitable attitude have found a practical metamorphosis in these banquets, where there are no personal courses, but only dishes to be shared.

This was true up until the beginning of the last century, when it was customary not even to bring plates to the diners, who would have served themselves directly from those of the course, to reinforce the idea that there should be no divisions within such a sacred gesture such as the meal.

As mentioned previously, the mezedes almost play a framing role during these distinctive meals. The real protagonists, the real focus of the gathering, are the drinks served with them. The list of spirits we find on these tables is extensive.

From raki, in Greece and Turkey, to arak, which is found in the Levant, up to the well-known ouzo and tsipouro.

They are all strong distillates and they are preferred cold. Some like theirs with ice and others with a drop of water.

In recent years, however, the consumption of beer and wine has seen increasing growth: also thanks to their taste, they are preferred by the new generations.

In short, the important thing is to eat well; but the fundamental thing is to drink well.

This liqueur is one of the most well-known symbols of Hellenic gastronomic culture.It is a brandy with a strong alcohol content, about 45 proof.

It has both the pure variant and the one flavored with aniseed: among Greek tables you will hear about tsipouro (me) and tsipouro ; that is with and without aniseed.

However, in reality, this distillate does not only represent a meal element, culturally speaking. Inside every sip of the liqueur is hidden a story of rebirth and hope.

In September of 1922, the Greek city of Smyrna was invaded by Turkish military forces and the entire Greek and Armenian quarters of the city were burned down a few days later.

This fact marks the end of the Greek-Turkish war, and in October of the same year was signed the armistice: which saw about a million Greeks having to leave the shores of Asia Minor and go to live in Greece.

This fact irrevocably stained the Greek history of the early 1900s.

The new immigrants who arrived in the city of Volos, a port city on the outskirts of Thessaly, began working in the local fishing boats and ships.

During their breaks from work, in the desperate search for a moment of serenity in their lives which had been turned upside down, they found themselves coming together to dine: everything revolved around the tsipouro, which not only gave them energy but above all a sense of being carefree.

They brought with them various delicacies as well, mainly the traditional recipes of Constantinople. Thats how the first establishments called (tsipouradika), or places of tsipouro, were born.

Where the only thing that could be ordered was the distillate, in various quantities, while the dishes were chosen by the cook and the host, according to availability. Places of gathering and a strong sense of identity, where the brandy was the common denominator between people in search of comfort as they fought against the oblivion of their past memories.

In short, a lifeline in a single sip.

One sip, one bite, one word.We are what we used to eat

Giorgio Pintzas Monzani is a Greek-Italian chef, writer and consultant who lives in Milan. His Instagram page can be found here.

Read more here:
Mezedes, the DNA of Greek Food - Greek Reporter

Dutchman Rene Meulensteen reckons Manchester United are still to recover from the shock of seeing their greatest-ever manager step away into retirement in 2013

Video Unavailable

Play now

Premier League title race: Man City maintain healthy lead at top

Former Manchester United coach Rene Meulensteen believes the Reds have lost their DNA.

Meulensteen, the Dutchman who was part of Sir Alex Fergusons backroom staff for 12 years either side of a brief spell as boss of Danish club Brondby, reckons United are still to recover from the shock of seeing their greatest-ever manager step away into retirement in 2013.

He says subsequent managers like David Moyes, Louis van Gaal, Jose Mourinho, Ole Gunnar Solskjaer and Ralf Rangnick have wasted the legacy left to them by Ferguson.

It says enough that the club has never won the championship since then, said Meulensteen, who spent the last six years of his time at Old Trafford as first-team coach until leaving with Ferguson when United won the last of their 13 Premier League titles.

Have Your Say! Have Man Utd lost their DNA? Tell us what you think here.

Image:

The worst part is that United have completely lost their identity. Everything Ferguson had built up over the years has been thrown overboard. United had their own way of playing, they played in an attractive, creative way. But that recognizable United football is gone.

If you want to be successful it is important to have continuity in your vision and a solid, stable organisation. United no longer have either of those things, while Liverpool with Jurgen Klopp and Manchester City with Pep Guardiola do have that stability. You can see that in their successes.

Moyes has since admitted it was a mistake to bring in his own personnel to replace Fergusons staff when he arrived to succeed the Scot.

Meulensteen believes Ferguson should have been given licence to remain as a guiding hand behind the scenes despite stepping away from the main job after 26 years at the helm.

There were two options, he said in an interview with Dutch newspaper De Telegraaf. "Get someone from the outside who would do things entirely differently at once.

"Or involve Ferguson in the new course, in which the staff he had built up over the years could also play a role. With the appointment of David Moyes, the first choice was made - and that meant the rest of the staff could also leave with Ferguson.

The Dutchman is now working as an assistant to Australia boss Graham Arnold but has been put in charge of the team for Tuesdays World Cup qualifier in Oman because the manager has been diagnosed with covid.

He is proud of what he achieved at Old Trafford after first moving to Manchester to work in Uniteds academy in 2001.

Meulensteen said: That was a fantastic time. It was great to work with a manager like Sir Alex Ferguson and be on the training pitch with players like Ruud van Nistelrooy, Edwin van der Sar, Ryan Giggs, the young Cristiano Ronaldo, Patrice Evrayou name it.

It was the most successful period in Uniteds club history. In six years we won four championships. One time, we missed out on the league championship by one point and the other time on goal difference.

In addition, during that period United have won the Champions League by beating Chelsea and twice lost a Champions League final to Barcelona. It was very special to be able to experience all of that. Now my big goal is to go to the World Cup with Australia.

Then I will have not only experienced the highest achievable in club football, but also in international football.

Read More

Read More

Read the original post:
Ex-Man Utd coach Rene Meulensteen tells Ralf Rangnick the Red Devils have lost their DNA - The Mirror

Researchers were able to detect DNA from elephants at the Copenhagen Zoo simply by sampling the air nearby. IDA MARIE ODGAARD/Ritzau Scanpix/AFP via Getty Ima hide caption

Researchers were able to detect DNA from elephants at the Copenhagen Zoo simply by sampling the air nearby.

A key part of protecting endangered species is figuring out where they're living. Now researchers say they have found a powerful new tool that could help: vacuuming DNA out of the air.

"This is a bit of a crazy idea," admits Elizabeth Clare, a molecular ecologist at York University in Toronto, Canada. "We are literally sucking DNA out of the sky."

But it works. Clare's group was one of two to publish papers in the journal Current Biology Thursday showing that dozens of animal species could be detected by simply sampling the air.

Using environmental DNA, or eDNA, to track species isn't new. For a few years now, researchers have been using DNA in water to track aquatic animals. They've also been able to pick up eDNA from plants floating in the air.

"One thing that we've discovered in eDNA research is really that any environmental medium (water, soil, snow, etc.) has the potential to harbor DNA that we can sample," Stephen F. Spear, a Research Biologist with the U.S. Geological Survey, wrote via e-mail. Spear has used eDNA to track a species of aquatic salamander known as the hellbender.

But the idea of using eDNA from air to track a large land animal like a rhinoceros or a giraffe still seemed "crazy" to Kristine Bohmann, a researcher at the GLOBE Institute at the University of Copenhagen in Denmark, and the lead author on the second paper in Current Biology.

Bohmann and her team thought up the idea independently from Clare's group a few years ago. She was trying to come up with a wacky research idea for a Danish foundation that funds far-out science.

"In the end I got so frustrated that I just blurted out, 'No! It has to be crazier! It has to be, like, vacuuming animal DNA out of air!'" she recalls.

The idea stuck, and she eventually got funding and hired a postdoc named Christina Lynggaard. Lynggaard's first job was to figure out what kind of device the team could use to vacuum eDNA from the air.

"We tried three different devices, and one of them was a vacuum cleaner, a commercial one," Lynggaard says.

It worked. They could sample DNA simply by using it, although it was "super noisy." Lynggaard also used some home-made samplers that used a small fan, like a computer blower fan, mounted in a 3-D printed housing. They worked just as well and were far quieter and more power efficient. Bohmann suspects they will be more useful in actual sampling in the wild.

To make the experiment successful the team also needed a good place to look for animal DNA.

"We realized we are based in Copenhagen... we had the Copenhagen Zoo," Bohmann recalls. It was almost like the zoo was custom-built for this experiment: Most of the animals are non-native, so they really stick out in a DNA analysis.

"If we detect a flamingo, well we're sure that it's not coming from anywhere else but that flamingo enclosure," she says.

The team took samples from around the zoo. And they were shocked. They picked up 49 animal species including rhinos, giraffes, and elephants.

"We even detected the guppy that was living in the pond in the rainforest house," Bohmann says. "It was just absolutely mind-blowing."

Meanwhile, Elizabeth Clare, who is also affiliated with Queen Mary University of London, was sampling at an outdoor zoo park in Cambridgeshire, UK.

Her team was able to detect 25 species, even some non-zoo animals: "Things like the Eurasian Hedgehog, which is critically endangered in the UK," Clare says. Zookeepers verified that hedgehogs have been seen wandering the area.

The two groups were nearing submission to a scientific journal when they learned of each other's work.

"I woke up to this flurry of text messages from my co-authors saying, 'There's another paper, have you seen this?'" Clare recalls.

Clare and Bohmann knew each other, and rather than compete to rush out a publication first, the two groups got in touch and decided to publish their findings as a pair.

"We are independently confirming this works to ourselves, and to everybody else," Clare says. "I think, we both thought, the papers are stronger together."

There are a lot of unanswered questions. For one thing, Clare says, researchers still aren't sure what the eDNA they're detecting actually is. It could be skin, saliva, or even urine or feces.

Also, "there were some species we simply never detected even though we know they were there," she notes. Her group missed maned wolves, even though she could smell them throughout the zoo park. Lynggaard says their team missed the Copenhagen Zoo's hippos.

"I see the current state of airborne eDNA as very similar to when the first papers on aquatic eDNA came out over a decade ago," says Stephen Spear, the USGS biologist who was not affiliated with either group.

He believes much more research will be needed to show just how air sampling of eDNA can be applied: "Will this technique work consistently for animals that are smaller or are more mobile? How does it compare to other methods such as camera traps? What's the best way to sample and collect eDNA from the air?"

For her part, Clare is eager to dive into answering these questions, and developing eDNA air sampling into a cornerstone technology for conservation.

"I have this vision of samplers that are deployed globally that can suck up the DNA from all these different sources, from soil and honey and rain and snow and air and water, sequence them on site, beam the data up to the servers," she says. The goal would be a global system of biomonitoring the world's animals. "We don't have a coordinated system for that."

Clare believes the answers to some of the toughest questions in conservation could literally be in front of our faces, hanging in the air.

View original post here:
Zoo studies show vacuuming DNA from air could help track endangered species - NPR

Our gut microbiome helps us out every day by processing the fiber we cant digest. The bacteria ferment the fiber into key chemicals known as short-chain fatty acids, or SCFAs, that are essential for human health. SCFAs fight inflammation, help kill dangerous bacteria, protect the lining of the gut, and can even help prevent cancer.

In a new study, the John Denu lab at the University of WisconsinMadisons Wisconsin Institute for Discovery has learned that the fatty acids butyrate and propionate also activate p300, a crucial human enzyme that promotes the unspooling of DNA. This unwound DNA allows more genes to become active and expressed, which ultimately affects human health.

Previous research had suggested that SCFAs might instead contribute to this process by inhibiting a different set of enzymes.

John Denu

Sydney Thomas

This new understanding opens the possibility of activating p300 in a diet-dependent way or even independently of the microbiome. Knowing how to target p300 is vital because it is implicated in a wide variety of physiological processes and diseases, such as propionic acidemia, autism spectrum disorder, and Alzheimers disease.

Knowing that butyrate and propionate directly interact with this protein opens up a lot of new areas of research that we didnt even think to look at before, because we thought that it was happening the opposite way than it actually is, says Sydney Thomas, a Denu lab graduate student and co-author on the paper.

Thomas and Denu, a professor of biomolecular chemistry, published their findings Oct. 22 in the journal eLife.

Earlier work in mice had shown that SCFAs are a crucial link between the microbiome and epigenetic states the modifications to DNA that affect how active any given gene is. These epigenetic modifications allow different cells to use the same DNA instructions to perform different tasks and can affect health.

One key mechanism of control that cells use is to organize the DNA so only certain parts of it can be accessed for the work at hand. To do this, cells wrap DNA around histone proteins, which act like spools for the DNA thread. Modifying histones changes the accessibility of the DNA wrapped around them, and ultimately changes which part of DNA a cell uses.

Science is most thrilling when you discover something unexpected and when the results challenge long-held beliefs. This work checks both those boxes.

John Denu

The mouse model work had left it unclear precisely how cells sense SCFAs and react by altering their histones to control gene expression. To address these outstanding questions, Thomas and Denu treated several human cell lines directly with SCFAs, bypassing the more complex mouse experiments.

Adding propionate or butyrate to the cells led to rapid changes in the cells histones. When they looked at how the compounds accomplished these changes, the team discovered that the fatty acids released the brakes on p300, which went on to modify histones in a way that opened up DNA to be used by the cell.

These findings largely replicated the results from the prior mouse work, indicating that the cells were an effective and simpler system to test how SCFAs alter the epigenome of the host.

We are hoping that now that we have a better understanding of how SCFAs work (and) can use this knowledge to create better drugs and a deeper understanding of how the microbiome interacts with the host, says Thomas.

For decades, textbook dogma held that butyrate and propionate altered chromatin by inhibiting the enzyme histone deacetylase. But the new findings that the fatty acids instead work by activating p300 call this old model into question.

Science is most thrilling when you discover something unexpected and when the results challenge long-held beliefs. This work checks both those boxes, adds Denu.

The research was funded by the National Institutes of Health.

See the article here:
New way to alter DNA, affect health circumvents gut bacteria - University of Wisconsin-Madison

Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 10711078 (2009).

ADS CAS Article Google Scholar

Lieber, M. R. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 79, 181211 (2010).

CAS Article Google Scholar

OConnor, M. J. Targeting the DNA damage response in cancer. Mol. Cell 60, 547560 (2015).

Article Google Scholar

Mohiuddin, I. S. & Kang, M. H. DNA-PK as an emerging therapeutic target in cancer. Front. Oncol. 9, 635 (2019).

Article Google Scholar

Sung, P. & Klein, H. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat. Rev. Mol. Cell Biol. 7, 739750 (2006).

CAS Article Google Scholar

Yang, F., Teves, S. S., Kemp, C. J. & Henikoff, S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim. Biophys. Acta Rev. Cancer 1845, 8489 (2014).

CAS Article Google Scholar

Davis, A. J., Chen, B. P. C. & Chen, D. J. DNA-PK: a dynamic enzyme in a versatile DSB repair pathway. DNA Repair 17, 2129 (2014).

CAS Article Google Scholar

Chang, H. H. Y., Pannunzio, N. R., Adachi, N. & Lieber, M. F. R. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat. Rev. Mol. Cell Biol. 18, 495506 (2017).

CAS Article Google Scholar

Jette, N. & Lees-Miller, S. P. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis. Prog. Biophys. Mol. Biol. 117, 194205 (2015).

CAS Article Google Scholar

Harnor, S. J., Brennan, A. & Cano, C. Targeting DNA-dependent protein kinase for cancer therapy. ChemMedChem 12, 895900 (2017).

CAS Article Google Scholar

Fok, J. H. L. et al. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat. Commun. 10, 5065 (2019).

Yang, H. et al. MTOR kinase structure, mechanism and regulation. Nature 497, 217223 (2013).

ADS CAS Article Google Scholar

Chaplin, A. K. et al. Dimers of DNA-PK create a stage for DNA double-strand break repair. Nat. Struct. Mol. Biol. 28, 1319 (2021).

CAS Article Google Scholar

Boulton, S., Kyle, S., Yalintepe, L. & Durkacz, B. W. Wortmannin is a potent inhibitor of DNA double strand break but not single strand break repair in Chinese hamster ovary cells. Carcinogenesis 17, 22852290 (1996).

CAS Article Google Scholar

Walker, E. H. et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell 6, 909919 (2000).

CAS Article Google Scholar

Hardcastle, I. R. et al. Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J. Med. Chem. 48, 78297846 (2005).

CAS Article Google Scholar

Goldberg, F. W. et al. The discovery of 7-methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor. J. Med. Chem. 63, 34613471 (2020).

CAS Article Google Scholar

Zenke, F. T. et al. Pharmacologic inhibitor of DNA-PK, M3814, potentiates radiotherapy and regresses human tumors in mouse models. Mol. Cancer Ther. 19, 10911101 (2020).

CAS Article Google Scholar

van Bussel, M. T. J. et al. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours. Br. J. Cancer 124, 728735 (2021).

Article Google Scholar

Wise, H. C. et al. Activity of M3814, an oral DNA-PK inhibitor, in combination with topoisomerase II inhibitors in ovarian cancer models. Sci. Rep. 9, 18882 (2019).

ADS CAS Article Google Scholar

Sibanda, B. L., Chirgadze, D. Y., Ascher, D. B. & Blundell, T. L. DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair. Science 355, 520524 (2017).

ADS CAS Article Google Scholar

Chen, X. et al. Structure of an activated DNA-PK and its implications for NHEJ. Mol. Cell 81, 801-810 (2021).

CAS Article Google Scholar

Sharif, H. et al. Cryo-EM structure of the DNA-PK holoenzyme. Proc. Natl Acad. Sci. USA 114, 73677372 (2017).

CAS Article Google Scholar

Chen, S. et al. Structural basis of long-range to short-range synaptic transition in NHEJ. Nature https://doi.org/10.1038/s41586-021-03458-7 (2021).

Yin, X., Liu, M., Tian, Y., Wang, J. & Xu, Y. Cryo-EM structure of human DNA-PK holoenzyme. Cell Res. 27, 13411350 (2017).

CAS Article Google Scholar

Chaplin, A. K. et al. Cryo-EM of NHEJ supercomplexes provides insights into DNA repair. Mol. Cell 81, 34003409 (2021).

CAS Article Google Scholar

Davis, A. J., Lee, K. J. & Chen, D. J. The N-terminal region of the DNA-dependent protein kinase catalytic subunit is required for its DNA double-stranded break-mediated activation. J. Biol. Chem. 288, 70377046 (2013).

CAS Article Google Scholar

Graham, T. G. W., Walter, J. C. & Loparo, J. J. Two-stage synapsis of DNA ends during non-homologous end joining. Mol. Cell. 61, 850858 (2016).

Radoux, C. J., Olsson, T. S. G., Pitt, W. R., Groom, C. R. & Blundell, T. L. Identifying interactions that determine fragment binding at protein hotspots. J. Med. Chem. 59, 43144325 (2016).

CAS Article Google Scholar

Hajduk, P. J., Huth, J. R. & Tse, C. Predicting protein druggability. Drug Discov. 10, 16751682 (2005).

CAS Google Scholar

Lai, A. C. & Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16, 101114 (2017).

CAS Article Google Scholar

Sun, X. et al. Protacs: great opportunities for academia and industry. Signal Transduct. Target. Ther. 4, 64 (2019).

Article Google Scholar

Liang, S. et al. Stages, scaffolds and strings in the spatial organisation of non-homologous end joining: insights from X-ray diffraction and cryo-EM. Prog. Biophys. Mol. Biol. 163, 6073 (2020).

Menolfi, D. & Zha, S. ATM, ATR and DNA-PKcs kinasesthe lessons from the mouse models: inhibitiondeletion. Cell Biosci. 10, 8 (2020).

Article Google Scholar

Bokori-Brown, M. et al. Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein. Nat. Commun. 7, 11293 (2016).

ADS CAS Article Google Scholar

Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 11461152 (2019).

CAS Article Google Scholar

Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. CryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290296 (2017).

CAS Article Google Scholar

Punjani, A., Brubaker, M. A. & Fleet, D. J. Building proteins in a day: efficient 3D molecular structure estimation with electron cryomicroscopy. IEEE Trans. Pattern Anal. Mach. Intell. 39, 706718 (2017).

Article Google Scholar

Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721745 (2003).

CAS Article Google Scholar

Pettersen, E. F. et al. UCSF Chimeraa visualization system for exploratory research and analysis. J. Comput. Chem. 25, 16051612 (2004).

CAS Article Google Scholar

Pettersen, E. F., et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70-82 (2021).

CAS Article Google Scholar

Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531544 (2018).

CAS Article Google Scholar

Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486501 (2010).

CAS Article Google Scholar

Original post:
Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs - Nature.com