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Scooped by Dr. Stefan Gruenwald!

Giant Filamentous Bacteria of 1 Millimeter Length Found in Mangrove Swamps Challenging Traditional Concepts of Biology

Giant Filamentous Bacteria of 1 Millimeter Length Found in Mangrove Swamps Challenging Traditional Concepts of Biology | Amazing Science |
Researchers describe a “’macro’ microbe” – a giant filamentous bacterium composed of a single cell discovered in the mangroves of Guadeloupe.


At first glance, the slightly murky waters in the tube look like a scoop of stormwater, complete with leaves, debris, and even lighter threads in the mix. But in the Petri dish, the thin vermicelli-like threads floating delicately above the leaf debris are revealed to be single bacterial cells, visible to the naked eye. The unusual size is notable because bacteria aren't usually visible without the assistance of microscope. "It's 5,000 times bigger than most bacteria. To put it into context, it would be like a human encountering another human as tall as Mount Everest," said Jean-Marie Volland, a scientist with joint appointments at the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab) and the Laboratory for Research in Complex Systems (LRC) in Menlo Park, Calif. In the June 24, 2022, issue of the journal Science, Volland and colleagues, including researchers at the JGI and Berkeley Lab, LRC, and at the Université des Antilles in Guadeloupe, described the morphological and genomic features of this giant filamentous bacterium, along with its life cycle.


For most bacteria, their DNA floats freely within the cytoplasm of their cells. This newly discovered species of bacteria keeps its DNA more organized. "The big surprise of the project was to realize that these genome copies that are spread throughout the whole cell are actually contained within a structure that has a membrane," Volland said. "And this is very unexpected for a bacterium."


Strange Encounters in the Mangroves

The bacterium itself was discovered by Olivier Gros, a marine biology professor at the Université des Antilles in Guadeloupe, in 2009. Gros' research focuses on marine mangrove systems, and he was looking for sulfur-oxidizing symbionts in sulfur-rich mangrove sediments not far from his lab when he first encountered the bacteria. "When I saw them, I thought, 'Strange,'" he said. "In the beginning I thought it was just something curious, some white filaments that needed to be attached to something in the sediment like a leaf." The lab conducted some microscopy studies over the next couple of years, and realized it was a sulfur-oxidizing prokaryote.


Silvina Gonzalez-Rizzo, an associate professor of molecular biology at the Université des Antilles and a co-first author on the study, performed the 16S rRNA gene sequencing to identify and classify the prokaryote. "I thought they were eukaryotes; I didn't think they were bacteria because they were so big with seemingly a lot of filaments," she recalled of her first impression. "We realized they were unique because it looked like a single cell. The fact that they were a 'macro' microbe was fascinating!"


"She understood that it was a bacterium belonging to the genus Thiomargarita," Gros noted. She named it Ca. Thiomargarita magnifica. "Magnifica because magnus in Latin means big and I think it's gorgeous like the French word magnifique," Gonzalez-Rizzo explained. "This kind of discovery opens new questions about bacterial morphotypes that have never been studied before."


Characterizing the Giant Bacterium

Volland got involved with the giant Thiomargarita bacteria when he returned to the Gros lab as a postdoctoral fellow. When he applied to the discovery-based position at the LRC that would see him working at the JGI, Gros allowed him to continue research on the project.


At the JGI, Volland began studying Ca. T. magnifica in Tanja Woyke's Single Cells Group to better understand what this sulfur-oxidizing, carbon fixing bacterium was doing in the mangroves. "Mangroves and their microbiomes are important ecosystems for carbon cycling. If you look at the space that they occupy on a global scale, it's less than 1% of the coastal area worldwide. But when you then look at carbon storage, you'll find that they contribute 10-15% of the carbon stored in coastal sediments," said Woyke, who also heads the JGI's Microbial Program and is one of the article's senior authors. The team was also compelled to study these large bacteria in light of their potential interactions with other microorganisms. "We started this project under the JGI's strategic thrust of inter-organismal interactions, because large sulfur bacteria have been shown to be hot spots for symbionts," Woyke said. "Yet the project took us into a very different direction," she added.

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3D visualization of macromolecule synthesis

3D visualization of macromolecule synthesis | Amazing Science |

Measuring nascent macromolecular synthesis in vivo is key to understanding how cells and tissues progress through development and respond to external cues. Researchers recently performed in vivo injection of alkyne- or azide-modified analogs of thymidine, uridine, methionine, and glucosamine to label nascent synthesis of DNA, RNA, protein, and glycosylation. Three-dimensional volumetric imaging of nascent macromolecule synthesis was performed in axolotl salamander tissue using whole-mount click chemistry-based fluorescent staining followed by light sheet fluorescent microscopy. They also developed an image processing pipeline for segmentation and classification of morphological regions of interest and individual cells, and applied this pipeline to the regenerating humerus. They were able to demonstrate that this approach is sensitive to biological perturbations by measuring changes in DNA synthesis after limb denervation. Taken together, this method provides a powerful means to quantitatively interrogate macromolecule synthesis in heterogenous tissues at the organ, cellular, and molecular levels of organization.

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Single-nucleosome imaging reveals steady-state motion of interphase chromatin in living human cells

Single-nucleosome imaging reveals steady-state motion of interphase chromatin in living human cells | Amazing Science |

Dynamic chromatin behavior plays a critical role in various genomic functions. However, it remains unclear how chromatin behavior changes during interphase, where the nucleus enlarges and genomic DNA doubles. While the previously reported chromatin movements varied during interphase when measured using a minute or longer time scale,  scientists now unveil that local chromatin motion captured by single-nucleosome imaging/tracking on a second time scale remained steady throughout G1, S, and G2 phases in live human cells. This motion mode appeared to change beyond this time scale. A defined genomic region also behaved similarly. Combined with Brownian dynamics modeling, these results suggest that this steady-state chromatin motion is mainly driven by thermal fluctuations. Steady-state motion temporarily increased following a DNA damage response. Taken together, these findings support the viscoelastic properties of chromatin. The research team proposes that the observed steady-state chromatin motion allows cells to conduct housekeeping functions, such as transcription and DNA replication, under maintenance of a similar environment during interphase.

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New tool speeds up development of vaccines by more than a 1,000,000-fold

New tool speeds up development of vaccines by more than a 1,000,000-fold | Amazing Science |

A new tool speeds up development of vaccines and other pharmaceutical products by more than one million times while minimizing costs.


The quest for pharmaceutical agents, such as new vaccines, leads industries to routinely scan thousands of related candidate molecules. But what if this process could take place on the nanoscale? Such a breakthrough would significantly minimize the use of materials and energy.


In search of pharmaceutical agents such as new vaccines, industry will routinely scan thousands of related candidate molecules. A novel technique allows this to take place on the nano scale, minimizing use of materials and energy. The work is published in the journal Nature Chemistry.  The new tool allows for more than 40,000 different molecules to be synthesized and analyzed within an area smaller than a pinhead, according to a press statement published by the University of Southern Denmark (SDU). The method, which works by using soap-like bubbles as nano-containers, is set to drastically reduce the amounts of material, energy, and economic cost for pharmaceutical companies by allowing them to speed up their processes by more than one million times.


The method works by using soap-like bubbles as nano-containers. With DNA nanotechnology, developed at SDU, multiple ingredients can be mixed within the containers. The technology uses DNA-barcodes similar to barcodes found on all consumer products to follow the identity of all compounds, reagents and chemical reactions carried out in parallel in thousands of ultra small nanoreactors, says SDU team leader Stefan Vogel, Associate Professor at Department of Physics, Chemistry and Pharmacy, University of Southern Denmark.

The volumes are so small that the use of material can be compared to using one liter of water and one kilogram of material instead of the entire volumes of water in all oceans to test material corresponding to the entire mass of Mount Everest. This is an unprecedented save in effort, material, manpower, and energy.

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How Do Gene Drives Work?

How Do Gene Drives Work? | Amazing Science |

Synthetic gene drive technology is a method of genetic engineering through which certain desired traits can be introduced to almost all individuals in a population. Researchers can either eliminate a species or alter the genetic makeup of living organisms through gene drive technology. Most gene drives are genetic elements that can quickly spread through populations of organisms and have nearly a 100% chance of passing the genes they carry to the next generation. 

How are gene drives generated?

Naturally occurring gene drives are found in almost all animals, including humans, plants, fungi and bacteria. They are selfish genetic elements that spread through inheritance from one generation to another. For example, homing endonuclease genes (HEGs) are site-specific selfish genes that spread by cleaving a homologous wild-type chromosome and copying themselves into the cut site through homology-directed repair (HDR). Meiotic drive is an intragenomic mechanism that interferes with meiotic processes so that the transmission of one or more alleles is favored over another. Manipulation of transposable elements, i.e., small DNA sequences that can move from one location in the genome to another, can also generate gene drives.


Earlier attempts to generate synthetic gene drives involved gene-editing techniques such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). However, mutations occurring in the repetitive elements limited the use of these technologies for the generation of gene drives, as they were often inactivated before being passed on to the next generation.

How do CRISPR-Cas9 gene drives work?

CRISPR-Cas9 gene drives consist of a drive allele, i.e., a genetic construct carrying genes encoding the desired trait, Cas9, and a guide RNA (gRNA), as well as flanking arms homologous to the sequences surrounding the target site in the wild type chromosome. When a homozygous gene drive-modified individual mates with an unmodified individual, the resulting offspring inherits one drive allele from the gene drive-modified parent and one non-modified version of the corresponding allele from the wild-type parent. The gRNA and the Cas9 genes are subsequently expressed in the cell, and the gRNA guides Cas9 to make a double-strand break in the wild-type chromosome at the target site. The drive allele then acts as a template for HDR, and the entire drive allele - including the gene of interest - is inserted into the wild-type chromosome. The cell is now homozygous for the drive allele, which will be passed to all gametes after meiosis, thus spreading the desired trait in the population.

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Using CRISPR-Cas9 in Cancer Cells: A New Avenue for Personalized Cancer Treatment?

Using CRISPR-Cas9 in Cancer Cells: A New Avenue for Personalized Cancer Treatment? | Amazing Science |

Researchers at Ulsan National Institute of Science and Technology in South Korea have developed a CRISPR-Cas9-based method to eliminate tumor cells. In this first proof-of-concept study, they confirm the feasibility of using CRISPR-Cas9 to selectively kill cancer cells in various disease models by targeting cancer-specific InDels.


Despite recent advances in cancer treatment using drugs that induce DNA damage or boost anti-tumor immune responses, eliminating tumor cells whilst leaving normal cells intact remains a major challenge.bIn a recent proof-of-concept study, researchers from the Institute of Basic Science and Ulsan National Institute of Science and Technology (UNIST), Republic of Korea, developed CINDELA, a new CRISPR-Cas9-based method for selectively inducing DNA damage and cell death in cancer cells.


»We developed an innovative CRISPR-Cas9-based approach to target multiple cancer-specific mutations that are accumulated in cancer cells during tumor development,« said Taejoon Kwon, PhD, Associate Professor at UNIST and first author of the study. »Using this method, we can introduce multiple DNA double-strand breaks (DSBs) and induce cell death selectively in cancer cells,« he added. The team’s findings were published in PNAS late last month.


Dr Kwon also noted that they validated the ability of CINDELA to selectively eliminate tumor cells in cancer cell lines, patient-derived cancer cells, mouse models, and patient-derived xenografts. This extensive validation makes him confident that the novel approach may open new avenues for personalized cancer treatment.


Dr Sandra Rodriguez-Perales, an expert in the use of CRISPR-Cas9 to engineer tumor cells, agrees that there is a clear need for new therapeutic alternatives that can selectively target cancer cells without affecting healthy cells. She is the head of the Molecular Cytogenetics Unit, Spanish National Cancer Centre (CNIO) and did not participate in the study. »This study has advanced a little further along the long road that could lead to the future treatment of different types of tumors,« she said.


Role of genomic instability in cancer

Most cancer cells exhibit a high degree of genomic instability, which leads to the accumulation of alterations in genes and regulatory regions of the genome in cancer cells. These alterations range from single-nucleotide mutations to large-scale structural rearrangements in chromosomes. Small insertions and deletions (InDels) are genomic alterations that are frequently found in cancer cells but not in neighboring non-malignant cells.


Genomic instability is therefore characterized as a hallmark of cancer, and Dr Kwon pointed out that this plays a key role in cancer cell evolution and tumor progression: »Most tumor cells accumulate thousands of InDels, providing an opportunity to selectively eliminate cancer cells by targeting InDels that are present in cancer cells but not in normal cells.«

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Smallest thermometer ever made from DNA

Smallest thermometer ever made from DNA | Amazing Science |

Tiny fragments of DNA combined with fluorescent probes can be used to take temperature at the nanoscale.


Scientists from the University of Montreal, Canada have developed the world’s smallest programmable thermometer, known as Nano-thermometer from DNA. This could recast nanotechnology. Scientists made this Nano-thermometer from actual DNA. This new device is nearly about 20,000 thousand times tinier as compared to human hair.


This new device is made from getting inspiration of “heated DNA always unfolds at a specific temperature”. It can be used in different sectors like Physics, Chemistry and atomic & molecular levels and engineering. This technology has become as a solution to the problem of checking temperature changes in nano-technology. Currently, these devices are so big for doing such things.


A scientist has cultivated DNA structure which can fold and unfold at a certain temperature. They got this idea from natural minute thermometers. Alexis Valle Belisle, Professor at University of Montreal said, “In recent years, biochemists also discovered that biomolecules such as proteins and RNA (Ribonucleic Acid, an important molecule with long chains of nucleotides, like DNA) are employed as Nano-thermometers in living organism and report temperature variation by folding or unfolding.”


Researchers are making some slight adjustment to the product so that it can be combined with new electronic devices. In the field of Science and Technology, this device allows the researcher to answer other problematical questions which have been gone unanswered for years. Were the questions like, can human body runs hotter than 37 degrees Celsius on the natural scale? Or what if naturally occurring Nanomachines overheat when operating at a high rate?


Arnaud Desrosiers, one of the researchers from the team, said, “By adding optical reporters to these DNA structures, we can, therefore, create 5nm wide thermometer that produces an easily detectable signal as a function of temperature.”

Some key feature of this Nano-thermometer:

  • It is 5 nanometres wide in the size which is 20,000 times smaller than a human hair.
  • It is reversible, robust and efficient.
  • It has different applications in different sectors like, in various nanotechnology fields: cell imaging, nano-fluidics, Nano-medicine, Nano-electronics, nano-material, and artificial biology.
  • It is used to create super strong structures, repairing cells and help Nano-computing to become more efficient.
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Scientists identify germline signature that predicts side effects from anti-PD1/PDL1 checkpoint therapy

Scientists identify germline signature that predicts side effects from anti-PD1/PDL1 checkpoint therapy | Amazing Science |

Investigators from UCLA Jonsson Comprehensive Cancer Center have identified a germline biomarker signature that successfully predicts which patients will suffer serious side effects that occur in up to 3 in ten patients on anti-PD1/PDL1 therapy, a promising new approach to treating cancer.


Checkpoint inhibitors that enhance the immune system against PD-1 and PD-L1 show great promise, having substantially improved the prognosis for patients with several advanced cancers, including melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and head and neck cancer.


As promising as they are, these therapies are also associated with a unique set of side effects, called immune-related adverse events (irAEs), believed to be the result of an immune system overstimulated by the therapy. While these side effects are generally treatable, they can in rare cases be very serious, even fatal. In addition, there's currently no way to predict which patients will develop irAEs before starting treatment, requiring clinicians to watch and wait after treatment begins. Notably, the toxicity from checkpoint therapy does not appear to be associated with a patient's cancer or their response to the treatment, supporting the idea that it is a patient-specific reaction.


With a growing need to identify which patients are at risk for irAEs, investigators led by Joanne B. Weidhaas, MD, PhD, MSM, of UCLA Jonsson Comprehensive Cancer Center, vice chair Department of Radiation Oncology, and director Division of Molecular and Cellular Oncology at UCLA Health, examined DNA signatures in 99 patients, looking for patterns that would indicate if inherited DNA biomarkers would predict toxicity. In findings published in Journal for Immunotherapy of Cancer, they report that they were able to identify a biomarker panel that predicts toxicity with 80% accuracy.


"These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly," said Dr. Weidhaas. "While we are still at the early stages of understanding the mechanisms by which these germline mutations regulate immunity and the systemic stress response, our repeated findings that these variant panels can predict systemic toxic responses to cancer therapy are potentially paradigm-shifting."

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90% still to be named: AI could help biologists to classify the world's insects and other invertebrates

90% still to be named: AI could help biologists to classify the world's insects and other invertebrates | Amazing Science |

With biodiversity in decline around the world, researchers are desperate to catalog all of Earth's insects and other invertebrates, which represent 90% of the 9 million species yet to be named. To do so, scientists typically face long hours in the lab sorting through the specimens they collected.


Enter DiversityScanner. The approach involves a robot, which plucks individual insects and other small creatures one at a time from trays and photographs them. A computer then uses a type of artificial intelligence known as machine learning to compare each one's legs, antennae, and other features to known specimens. The technology then imposes a color code, or heat map, over the image (see above). The warmer the color, say, red, the more the computer program depended on that body part to make a call on the type of insect it was. This heat map makes it easier for researchers checking the identification to see what the program's "thought" process was.


The robot then moves each insect into a plate with 96 tiny wells, readying these specimens for DNA sequencing. The resulting species-identifying piece of sequence—a "DNA barcode"—is linked to the image in a database of all the cataloged specimens. Although not quite as good as a human expert, the approach accurately classifies insects 91% of the time, the designers of the technology report in a study posted to the preprint server bioRxiv. That accuracy will improve as more specimens are added to the database, they note.


The researchers have made the software and 3D printing plans for the technology openly available. And, as the scientists describe in a second preprint, they have simplified the sequencing steps and software so that developing countries and small organizations can take advantage of it—96 insects at a time.

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200,000 whole genomes made available for biomedical studies by U.K. effort

200,000 whole genomes made available for biomedical studies by U.K. effort | Amazing Science |
UK Biobank offers easy access to genomic database for researchers around the world


In the largest single release of whole genomes ever, the UK Biobank (UKBB) this week unveiled to scientists the entire genomes of 200,000 people who are part of a long-term British health study.


The trove of genomes, each linked to anonymized medical information, will allow biomedical scientists to scour the full 3 billion base pairs of human DNA for insights into the interplay of genes and health that could not be gleaned from partial sequences or scans of genome markers. “It is thrilling to see the release of this long-awaited resource,” says Stephen Glatt, a psychiatric geneticist at the State University of New York Upstate Medical University.


Other biobanks have also begun to compile vast numbers of whole genomes, 100,000 or more in some cases (see table, below). But UKBB stands out because it offers easy access to the genomic information, according to some of the more than 20,000 researchers in 90 countries who have signed up to use the data.


“In terms of availability and data quality, [UKBB] surpasses all others,” says physician and statistician Omar Yaxmehen Bello-Chavolla of the National Institute for Geriatrics in Mexico City.


A number of efforts are releasing many thousands of whole genomes, with varying degrees of access, to accelerate biomedical research.

BIOBANK Completed whole genomes Release information UK Biobank 200,000 300,000 more in early 2023 Trans-Omics for Precision Medicine 161,000 National Institutes of Health (NIH) requires project-specific consent Million Veteran Program 125,000 Non–Veterans Affairs researchers get access in 2022 Genomics England’s 100,000 Genomes 120,000 Researchers must join collaboration All of Us 90,000 NIH expects to release by early 2022


Having enrolled 500,000 middle-age and elderly participants of mostly European ancestry from 2006 to 2010, UKBB is one of the largest genetics research databases in the world. It proved its worth even before releasing whole genomes. Studies of specific DNA markers that vary among participants have revealed hundreds of new disease risk genes. Since 2019 researchers have also been probing participants’ exomes, the 2% of the whole genome sequence (WGS) that encodes proteins; the exomes from nearly all participants became available in the past 2 months. Exome studies are yielding risk genes that are very rare and can’t be found with genotyping data.


But whole genomes will make it possible to explore the influence of noncoding DNA, which controls when genes are turned off or on, and of gene rearrangements, as well as missing, repeated, or extra stretches of DNA in genes. Such changes play a role in diseases such as Huntington disease.

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Prime Is the Newest Gene Editing Technology, and It’s Getting Better

Prime Is the Newest Gene Editing Technology, and It’s Getting Better | Amazing Science |

A technology at the leading edge of genetic medicine—known as prime editing—is getting ever closer to the clinic after researchers reported major improvements that could let them repair disorders unreachable by other genetic therapies.


Prime editing derives from the Nobel Prize-winning technique called Crispr-Cas9, which lets scientists reach into defective genes and snip the flawed DNA underlying a genetic disorder such as sickle cell disease. Crispr therapies are already being tested by Crispr Therapeutics (ticker: CRSP), Intellia Therapeutics (NTLA), Editas Medicine (EDIT), and Caribou Biosciences (CRBU).


Building on Crispr-Cas9's ability to zero-in on a specific stretch in our DNA’s 3-billion long string of “base” letters, Harvard University professor David Liu and his colleagues at the Broad Institute of MIT and Harvard introduced “base editing” in 2016. It can correct single-letter typos in DNA, with less disruption to the cell than Crispr-Cas9. The company Beam Therapeutics (BEAM) is bringing base edits into clinical trials.


Base editing can fix four of the 12 possible typos that can cause disease when there’s a single wrong letter in our DNA. In 2019, Liu and his team unveiled “prime editing”, which can correct all 12 typos—they account for 90% of genetic disorders. Prime editing can also insert, delete, or replace a string of several dozen DNA base letters—all without disruptively breaking both of the twisted strands that compose our DNA. This insertion capability might allow prime-editing to fix the flaws responsible for some kinds of cystic fibrosis.


Beam Therapeutics is applying prime-editing technology to repair sickle cell, while other applications of the new gene-editing technique are being pursued by the still-private Prime Medicine.


For all its promise, prime editing suffered shortcomings that left it less efficient than base editing, and kept it from working well in certain kinds of cells. A recent paper4 published in Cell shows that those problems are being overcome, though. Liu and collaborators from Princeton and the University of California, San Francisco, engineered new prime editors that work much more efficiently than earlier tools, with fewer unwanted byproducts.


In clearing away obstacles to prime editing, the technology gets closer to human trials, where it could address genetic flaws that can’t be treated by other kinds of gene editing—including cystic fibrosis and many neurological disorders. “These advancements,” said Prime Medicine CEO Keith Gottesdiener in a press release., “will broaden the areas where prime editing might work, potentially extending our reach to additional diseases that no gene editing approach has yet been able to address.”


Original Article

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Multigenerational memory transfer between individuals in C. elegans using a retrotransposon

Multigenerational memory transfer between individuals in C. elegans using a retrotransposon | Amazing Science |
Researchers Rebecca Moore, Rachel Kaletsky, Chen Lesnik, from Coleen Murphy’s laboratory, demonstrated that the microscopic worm C. elegans uses a retrotransposon called Cer1 to transfer a learned behavior (avoidance of a pathogenic bacterium) between worms.


When an organism encounters a threat in its environment, it is to the species’ advantage to warn others of the peril. The microscopic roundworm C. elegans regularly encounters dangers in its environment such as the pathogenic bacterium P. aeruginosa, which seems like an appealing food source but can sicken worms if eaten. C. elegans isn’t equipped to shout out warnings as a human would, but new work by researchers from Princeton researcher Coleen Murphy’s laboratory shows that worms who encounter P. aeruginosa can help others avoid the danger, and identifies a crucial part of the mechanism by which this is done.


In earlier work, Murphy’s lab discovered that mother worms who are sickened by P. aeruginosa learn to avoid the bacterium, and that they can impress this avoidance behavior upon their offspring for the next four generations. Mother worms who’ve eaten P. aeruginosa absorb a bacterial small RNA called P11 through their intestines, which touches off a signal in the worm’s germ line reproductive cells that is then transmitted to a neuron that controls behavior. Afterwards, the new behavior is conveyed to future progeny via changes made to germ line cells.


In their new paper, co-first authors Rebecca Moore, Rachel Kaletsky, and Chen Lesnik, and colleagues show that avoidance behavior can also be conveyed from trained worms to other, naïve adult worms. “We found that one worm can learn to avoid this pathogenic bacterium and if we grind up that worm, or even just use the media the worms are swimming in, and give that media or the crushed-worm lysate to naive worms, those worms now ‘learn’ to avoid the pathogen as well,” explains Murphy.


This finding suggests that worms secrete some signal that, when picked up by other worms, can modify their behavior. Interestingly, the progeny of worms “educated” by receipt of this signal also avoid pathogenic P. aeruginosa for the following four generations. This suggests that the secreted signal touches off the same learning pathway in recipient worms as in those directly exposed to the pathogen. Murphy’s group sought to identify the secreted signal. “What we discovered is that a retrotransposon called Cer1 that forms viral-like particles seems to carry a memory not only between tissues (from the worm's germline to its neurons) but also between individuals,” says Murphy.


A retrotransposon is a genetic element, similar to a virus, that has inserted itself into a host animal’s DNA. The researchers found that Cer1 is present in the DNA of the worms’ germ line cells, and that mother worms in whom the retrotransposon was knocked down by RNA interference could not learn avoidance of P. aeruginosa via exposure to P11; convey avoidance behavior to offspring; or educate nearby worms. In addition, adult recipient worms needed Cer1 to be present in their genome in order to learn to avoid the pathogen. The authors found that two wild worm strains that naturally lack Cer1 are incapable of doing these things, suggesting that in these strains, Cer1 is needed to establish, transmit and receive this avoidance behavior.


“We think that Cer1 may give worms an advantage in their battle with pathogens, even though acquiring Cer1 in its genome can be deleterious for the worm under non-pathogenic conditions,” says Murphy.

“The findings by Murphy et al. are provocative,” says Dr. Craig Mello, Professor of molecular medicine at the University of Massachusetts and co-discoverer of RNA interference. “This is another intriguing episode in a growing number of studies that have implicated systemic RNA signals in influencing behavior transgenerationally, and if this study is correct, now even horizontally.” Although other studies have shown that animals such as the sea slug Aplysia are capable of transferring memories between individuals, the work by Moore, Kaletsky, Lesnik and colleagues  is the first to suggest a mechanism by which such transfer can occur in nature. However, this study also raises a number of urgent questions. For example, as Mello points out, it’s now well established that worms use RNA signals to pass information to offspring, but it is currently unclear what Cer1 contributes to this pathway.

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USC Stem Cell scientists explore the latent regenerative potential of the inner ear

USC Stem Cell scientists explore the latent regenerative potential of the inner ear | Amazing Science |

Scientists from the USC Stem Cell laboratory of Neil Segil have identified a natural barrier to the regeneration of the inner ear’s sensory cells, which are lost in hearing and balance disorders. Overcoming this barrier may be a first step in returning inner ear cells to a newborn-like state that’s primed for regeneration, as described in a new study published in Developmental Cell.


“Permanent hearing loss affects more than 60 percent of the population that reaches retirement age,” said Segil, who is a Professor in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery. “Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”


In the inner ear, the hearing organ, which is the cochlea, contains two major types of sensory cells: “hair cells” that have hair-like cellular projections that receive sound vibrations; and so-called “supporting cells” that play important structural and functional roles. When the delicate hair cells incur damage from loud noises, certain prescription drugs, or other harmful agents, the resulting hearing loss is permanent in older mammals. However, for the first few days of life, lab mice retain an ability for supporting cells to transform into hair cells through a process known as “transdifferentiation”, allowing recovery from hearing loss. By one week of age, mice lose this regenerative capacity—also lost in humans, probably before birth.


Based on these observations, postdoctoral scholar Litao Tao, PhD, graduate student Haoze (Vincent) Yu, and their colleagues took a closer look at neonatal changes that cause supporting cells to lose their potential for transdifferentiation.  In supporting cells, the hundreds of genes that instruct transdifferentiation into hair cells are normally turned off. To turn genes on and off, the body relies on activating and repressive molecules that decorate the proteins known as histones.  In response to these decorations known as “epigenetic modifications,” the histone proteins wrap the DNA into each cell nucleus, controlling which genes are turned “on” by being loosely wrapped and accessible, and which are turned “off” by being tightly wrapped and inaccessible. In this way, epigenetic modifications regulate gene activity and control the emergent properties of the genome.


In the supporting cells of the newborn mouse cochlea, the scientists found that hair cell genes were suppressed by both the lack of an activating molecule, H3K27ac, and the presence of the repressive molecule, H3K27me3.  However, at the same time, in the newborn mouse supporting cells, the hair cell genes were kept “primed” to activate by the presence of yet a different histone decoration, H3K4me1.  During transdifferentiation of a supporting cell to a hair cell, the presence of H3K4me1 is crucial to activate the correct genes for hair cell development. Unfortunately with age, the supporting cells of the cochlea gradually lost H3K4me1, causing them to exit the primed state. However, if the scientists added a drug to prevent the loss of H3K4me1, the supporting cells remained temporarily primed for transdifferentiation. Likewise, supporting cells from the vestibular system, which naturally maintained H3K4me1, were still primed for transdifferentiation into adulthood.


“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing,” said Segil. “Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

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Ground zero for the Black Death finally found after 600 years

Ground zero for the Black Death finally found after 600 years | Amazing Science |

The origins of the deadly Black Death have been discovered more than 600 years after it entered the human population, scientists have said. The medieval, bubonic plague was first recorded in the 14th century and was the start of a near 500-year-long wave of killer diseases termed the Second Plague Pandemic. The Black Death killed millions and was considered one of the largest infectious disease catastrophes in human history. Despite years of research, the geographic and chronological origin of the disease remained a mystery. But now researchers believe the Black Death first originated in North Kyrgyzstan in the late 1330s. The team, from Scotland’s University of Stirling and Germany’s Max Planck Institute and University of Tubingen, analysed ancient DNA (aDNA) taken from the teeth of skeletons discovered in cemeteries near Lake Issyk Kul in the Tian Shan region of Kyrgyzstan.

They were drawn to these sites after identifying a huge spike in the number of burials there in 1338 and 1339, according to University of Stirling historian Dr Philip Slavin, who helped make the discovery. The team found the cemeteries, at Kara-Djigach and Burana, had already been excavated in the late 1880s, with about 30 skeletons taken from the graves, but were able to trace them and analyse DNA taken from the teeth of seven individuals.


The sequencing, which determines the DNA structure, showed three individuals carried Yersinia pestis, a bacterium which is linked to the beginning of the Black Death outbreak before it arrived in Europe. ‘Our study puts to rest one of the biggest and most fascinating questions in history and determines when and where the single most notorious and infamous killer of humans began,’ Dr Slavin said.

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Mutational signatures across 119 mutation classes are jointly shaped by DNA damage and repair

Mutational signatures across 119 mutation classes are jointly shaped by DNA damage and repair | Amazing Science |

Cells possess a variety of DNA repair pathways to counter DNA damage and prevent mutations. Scientists recently used C. elegans whole genome sequencing to systematically quantify the contributions of these factors to mutational signatures. They analyzed 2,717 genomes from wild-type and 53 DNA repair defective backgrounds, exposed to 11 genotoxins, including UV-B and ionizing radiation, alkylating compounds, aristolochic acid, aflatoxin B1, and cisplatin. Combined genotoxic exposure and DNA repair deficiency alters mutation rates or signatures in 41% of experiments, revealing how different DNA alterations induced by the same genotoxin are mended by separate repair pathways. Error-prone translesion synthesis causes the majority of genotoxin-induced base substitutions, but averts larger deletions. Nucleotide excision repair prevents up to 99% of point mutations, almost uniformly across the mutation spectrum. The findings show that mutational signatures are joint products of DNA damage and repair and suggest that multiple factors underlie signatures observed in cancer genomes.

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Viable offspring derived from single unfertilized mammalian oocytes

Viable offspring derived from single unfertilized mammalian oocytes | Amazing Science |

In mammals, a new life starts with the fusion of an oocyte and a sperm cell. Parthenogenesis, a way of generating offspring solely from female gametes, is limited because of problems arising from genomic imprinting. A research team from China now reports to have obtained live mammalian offspring derived from single unfertilized oocytes. This was achieved by targeted DNA methylation rewriting of seven imprinting control regions. Oocyte co-injection of catalytically inactive Cas9 (dCas9)-Dnmt3a or dCpf1-Tet1 messenger RNA (mRNA) with single-guide RNAs (sgRNAs) targeting specific regions induced de novo methylation or demethylation, respectively, of the targeted region. Following parthenogenetic activation, these edited regions showed maintenance of methylation as naturally established regions during early preimplantation development. The transfer of modified parthenogenetic embryos into foster mothers resulted in significantly extended development and finally in the generation of viable full-term offspring. Taken together, these data demonstrate that parthenogenesis can be achieved by targeted epigenetic rewriting of multiple critical imprinting control regions.

Via BigField GEG Tech
BigField GEG Tech's curator insight, March 30, 8:44 AM

In mammals, parthenogenesis is limited because of problems arising from genomic imprinting. Here, the scientists report live mammalian offspring derived from single unfertilized eggs. This was achieved by the targeted DNA methylation rewriting of seven imprinting control regions. By designing guide RNAs with protospacer adjacent motif (PAM) sequences matching one allele but not the other, dCas9-Dnmt3a or dCpf1-Tet1 enables targeted DNA methylation editing in an allele-specific manner. The success of parthenogenesis in mammals opens many opportunities in agriculture, research, and medicine.

sofia carlos's curator insight, April 10, 8:40 PM
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Ocean water samples yield treasure trove of RNA virus data

Ocean water samples yield treasure trove of RNA virus data | Amazing Science |

Ocean water samples collected around the world have yielded a treasure trove of new data about RNA viruses, expanding ecological research possibilities and reshaping our understanding of how these small but significant submicroscopic particles evolved.


Combining machine-learning analyses with traditional evolutionary trees, an international team of researchers has identified 5,500 new RNA virus species that represent all five known RNA virus phyla and suggest there are at least five new RNA virus phyla needed to capture them.


The most abundant collection of newly identified species belong to a proposed phylum researchers named Taraviricota, a nod to the source of the 35,000 water samples that enabled the analysis: the Tara Oceans Consortium, an ongoing global study onboard the schooner Tara of the impact of climate change on the world's oceans.


"There's so much new diversity here -- and an entire phylum, the Taraviricota,were found all over the oceans, which suggests they're ecologically important," said lead author Matthew Sullivan, professor of microbiology at The Ohio State University. "RNA viruses are clearly important in our world, but we usually only study a tiny slice of them -- the few hundred that harm humans, plants and animals. We wanted to systematically study them on a very big scale and explore an environment no one had looked at deeply, and we got lucky because virtually every species was new, and many were really new."


The study appears online today (April 7, 2022) in Science. While microbes are essential contributors to all life on the planet, viruses that infect or interact with them have a variety of influences on microbial functions. These types of viruses are believed to have three main functions: killing cells, changing how infected cells manage energy, and transferring genes from one host to another. Knowing more about virus diversity and abundance in the world's oceans will help explain marine microbes' role in ocean adaptation to climate change, the researchers say. Oceans absorb half of the human-generated carbon dioxide from the atmosphere, and previous research by this group has suggested that marine viruses are the "knob" on a biological pump affecting how carbon in the ocean is stored.


By taking on the challenge of classifying RNA viruses, the team entered waters still rippling from earlier taxonomy categorization efforts that focused mostly on RNA viral pathogens. Within the biological kingdom Orthornavirae, five phyla were recently recognized by the International Committee on Taxonomy of Viruses (ICTV).


Though the research team identified hundreds of new RNA virus species that fit into those existing divisions, their analysis identified thousands more species that they clustered into five new proposed phyla: Taraviricota, Pomiviricota, Paraxenoviricota, Wamoviricota and Arctiviricota,which, like Taraviricota, features highly abundant species -- at least in climate-critical Arctic Ocean waters, the area of the world where warming conditions wreak the most havoc.


Sullivan's team has long cataloged DNA virus species in the oceans, growing the numbers from a few thousand in 2015 and 2016 to 200,000 in 2019. For those studies, scientists had access to viral particles to complete the analysis. In these current efforts to detect RNA viruses, there were no viral particles to study. Instead, researchers extracted sequences from genes expressed in organisms floating in the sea, and narrowed the analysis to RNA sequences that contained a signature gene, called RdRp, which has evolved for billions of years in RNA viruses, and is absent from other viruses or cells.

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Hidden Regions Revealed in the First Complete Sequence of a Human Genome

Hidden Regions Revealed in the First Complete Sequence of a Human Genome | Amazing Science |

Parts of the human genome now available to study for the first time are important for understanding genetic diseases, human diversity, and evolution.

The first truly complete sequence of a human genome, covering each chromosome from end to end with no gaps and unprecedented accuracy, is now accessible through the UCSC Genome Browser and is described in six papers published today (March 31, 2022) in Science.

Since the first working draft of a human genome sequence was assembled at UC Santa Cruz in 2000, genomics research has led to enormous advances in our understanding of human biology and disease. Nevertheless, crucial regions accounting for some 8% of the human genome have remained hidden from scientists for over 20 years due to the limitations of DNA sequencing technologies.

Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, and Adam Phillippy at the National Human Genome Research Institute (NHGRI) organized an international team of scientists—the Telomere-to-Telomere (T2T) Consortium—to fill in the missing pieces. Their efforts have now paid off.

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Hopping DNA found as a cause for albinism in a baby wallaby

Hopping DNA found as a cause for albinism in a baby wallaby | Amazing Science |

Rogue DNA fragment causes pigmentation loss.


Kyoto University has discovered for the first time a genetic cause of albinism, or loss of pigmentation, in the small kangaroo-like wallaby. Wallabies naturally have a brown or gray coat, which is what geneticists call a wild-type gene expression, or phenotype. Research team leader Akihiko Koga noticed that cases of white baby wallabies being born to wild-type mothers were reported from different countries. "I wondered if there was a recent common ancestor as the source of albinism," says Koga.


The opportunity to investigate this hypothesis arrived on one fateful day in 2015 when a pale-skinned wallaby was born to a normal colored mother at Noichi Zoo in Kochi, Japan. The team examined the gene for the enzyme tyrosinase or TYR, known for its role in producing melanin, the natural skin pigment. In the TYR gene, they discovered that an extra DNA fragment led to the mutation, that is the loss of the last two-thirds portion of the gene protein.


This is akin to copying and pasting a word inside a tweet before posting it, causing an equal length of text at the end of the tweet to exceed the word count; this figuratively "pushes" the essential word off the end, rendering the tweet incomplete and confusing. The mutation was caused by a copy of the genetic material of a retrovirus, such as HIV, and inserted into the host wallaby. This copy is called an endogenous retrovirus, which was detected using a simple polymerase chain reaction, or PCR, test which is currently in common use for determining viral infections, such as sars-Covid.


Easier said than done as the mutant gene was elusive and challenging to find in mammalian albinos, including primates and racoon dogs. But the team succeeded with a marsupial. "We found this inserted fragment in a wallaby, which we fittingly named walb," mentions Koga.


The walb gene insertion is likely to have occurred by one of the following three processes:

  1. endogenization, which is infection by an exogenous virus -- derived from another organism;
  2. reinfection by an earlier generation virus; or
  3. retrotransposition, defined as a relocation of an endogenous retrovirus within a cell.


While the process has not yet been identified at this point, Koga's team has deduced that it is a recent evolutionary event. Such mutant genes tend to remove themselves from the family tree if its genetic expression is disadvantageous for the wallaby's survival in the wild.

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AI rapidly predicts how two proteins dock

AI rapidly predicts how two proteins dock | Amazing Science |
A new machine learning system can predict the structure formed when two proteins dock, in a process that’s between 50 to 800 times faster than some software-based methods. This could help scientists better understand biological processes or speed the development of new therapies.
Antibodies, small proteins produced by the immune system, can attach to specific parts of a virus to neutralize it. As scientists continue to battle SARS-CoV-2, the virus that causes Covid-19, one possible weapon is a synthetic antibody that binds with the virus' spike proteins to prevent the virus from entering a human cell.


To develop a successful synthetic antibody, researchers must understand exactly how that attachment will happen. Proteins, with lumpy 3D structures containing many folds, can stick together in millions of combinations, so finding the right protein complex among almost countless candidates is extremely time-consuming.


To streamline the process, MIT researchers created a machine-learning model that can directly predict the complex that will form when two proteins bind together. Their technique is between 80 and 500 times faster than state-of-the-art software methods, and often predicts protein structures that are closer to actual structures that have been observed experimentally. This technique could help scientists better understand some biological processes that involve protein interactions, like DNA replication and repair; it could also speed up the process of developing new medicines.


"Deep learning is very good at capturing interactions between different proteins that are otherwise difficult for chemists or biologists to write experimentally. Some of these interactions are very complicated, and people haven't found good ways to express them. This deep-learning model can learn these types of interactions from data," says Octavian-Eugen Ganea, a postdoc in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) and co-lead author of the recent paper.


Ganea's co-lead author is Xinyuan Huang, a graduate student at ETH Zurich. MIT co-authors include Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health in CSAIL, and Tommi Jaakkola, the Thomas Siebel Professor of Electrical Engineering in CSAIL and a member of the Institute for Data, Systems, and Society. The research will be presented at the International Conference on Learning Representations.


Protein attachment

The model the researchers developed, called Equidock, focuses on rigid body docking - which occurs when two proteins attach by rotating or translating in 3D space, but their shapes don't squeeze or bend. The model takes the 3D structures of two proteins and converts those structures into 3D graphs that can be processed by the neural network. Proteins are formed from chains of amino acids, and each of those amino acids is represented by a node in the graph.


The researchers incorporated geometric knowledge into the model, so it understands how objects can change if they are rotated or translated in 3D space. The model also has mathematical knowledge built in that ensures the proteins always attach in the same way, no matter where they exist in 3D space. This is how proteins dock in the human body.

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DNA offers a new look at how Polynesia was settled

DNA offers a new look at how Polynesia was settled | Amazing Science |
Modern genetic evidence suggests that statue builders on islands such as Rapa Nui, also known as Easter Island, had a shared ancestry.


Polynesian voyagers settled islands across a vast expanse of the Pacific Ocean within about 500 years, leaving a genetic trail of the routes that the travelers took, scientists say. Comparisons of present-day Polynesians’ DNA indicate that sea journeys launched from Samoa in western Polynesia headed south and then east, reaching Rarotonga in the Cook Islands by around the year 830. From the mid-1100s to the mid-1300s, people who had traveled farther east to a string of small islands called the Tuamotus fanned out to settle Rapa Nui, also known as Easter Island, and several other islands separated by thousands of kilometers on Polynesia’s eastern edge. On each of those islands, the Tuamotu travelers built massive stone statues like the ones Easter Island is famed for.


That’s the scenario sketched out in a new study in the Sept. 23 2021 Nature by Stanford University computational biologist Alexander Ioannidis, population geneticist Andrés Moreno-Estrada of the National Laboratory of Genomics for Biodiversity in Irapuato, Mexico, and their colleagues. The new analysis generally aligns with archaeological estimates of human migrations across eastern Polynesia from roughly 900 to 1250. And the study offers an unprecedented look at settlement pathways that zigged and zagged over a distance of more than 5,000 kilometers, the researchers say.


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Several new studies suggest 2-aminoadenine-containing genomes are more widespread in bacteriophages than thought

Several new studies suggest 2-aminoadenine-containing genomes are more widespread in bacteriophages than thought | Amazing Science |

Three teams working independently have found evidence that suggests the Z-genome in bacteria-invading viruses is much more widespread than thought. All three of the groups have used a variety of genomic techniques to identify parts of the pathways that lead development of the Z-genome in bacteria-invading viruses known as bacteriophages. The first team was made up of researchers from several institutions in China and one in Singapore, the second with members from several institutions in France; the third was an international effort. All three teams have published their results in the journal Science. Michael Grome and Farren Isaacs with Yale University have also published a Perspectives piece in the same journal issue outlining the work of all three teams.


Four nucleobases. adenine (A), cytosine (C), guanine (G), and thymine (T), are usually thought to be invariable in DNA. In bacterial viruses, however, each of the DNA bases have variations that help them to escape degradation by bacterial restriction enzymes. In the genome of cyanophage S-2L, A is completely replaced by diaminopurine (Z), which forms three hydrogen bonds with T and thus creates non–Watson-Crick base pairing in the DNA of this virus. Zhou et al. and Sleiman et al. determined the biochemical pathway that produces Z, which revealed more Z genomes in viruses hosted in bacteria distributed widely in the environment and phylogeny. Pezo et al. identified a DNA polymerase that incorporates Z into DNA while rejecting A. These findings enrich our understanding of biodiversity and expand the genetic palette for synthetic biology. For details see Science p. 512, 516, 520; see also p. 460.

In general, cells have two purine pathways that synthesize adenine and guanine ribonucleotides from phosphoribose via inosylate. A chemical hybrid between adenine and guanine, 2-aminoadenine (Z), replaces adenine in the DNA of the cyanobacterial virus S-2L. A group of scientists was able to show now that S-2L and Vibrio phage PhiVC8 encode a third purine pathway catalyzed by PurZ, a distant paralog of succinoadenylate synthase (PurA), the enzyme condensing aspartate and inosylate in the adenine pathway. PurZ condenses aspartate with deoxyguanylate into dSMP (N6-succino-2-amino-2′-deoxyadenylate), which undergoes defumarylation and phosphorylation to give dZTP (2-amino-2′-deoxyadenosine-5′-triphosphate), a substrate for the phage DNA polymerase. Crystallography and phylogenetics analyses indicate a close relationship between phage PurZ and archaeal PurA enzymes. This important work elucidates the biocatalytic innovation that remodeled a DNA building block beyond canonical molecular biology.

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Genetic Explanation for Low Cancer Incidence in Elephants

Genetic Explanation for Low Cancer Incidence in Elephants | Amazing Science |

Elephants possess two qualities that might make one expect they are at high risk of developing cancer; they are large and long-living.


A cell’s lifecycle involves repetitive rounds of cellular division, which allow for growth and repair.  Every time a cell replicates there is a chance a mutation will arise causing the cells to overgrow and develop into cancer.  Elephants live on average to at least 65 years.  The longer an organism lives, the more opportunities for an error to occur during cellular replication. In addition, elephants are the world’s largest land mammal. The average elephant consists of about a quadrillion (or 1,000 trillion) cells. In contrast, the human body consists of about 37 trillion cells. If all cells have an equal risk of becoming cancerous, one may think that animals with many cells may be at an increased risk of developing cancer.  


However, elephants rarely develop any form of cancer, suggesting they have evolved superior cancer prevention mechanisms despite their large size and long life expectancy. This paradox has encouraged scientists to characterize the mechanisms that underlie these evolutionary benefits. Research has concentrated on a the TP53 gene.  Humans carry just one copy of the TP53 gene, while elephants possess a staggering 20 copies.


A study published in eLife provides additional insight into the mechanisms underlying the low cancer incidence in elephants by providing a complete picture of the anti-tumor components contained within elephant DNA. One of the study’s authors, Vincent Lynch, explained that he and his co-author sought to “look at whether the entire elephant genome includes more copies of tumor suppressors than what you’d expect.”


The study analyzed the genome of different living elephant species, including the African savannah elephant, the African forest elephant, and the Asian elephant.  In addition, the researchers included the genomes of some extinct species like the Woolly mammoth in the analysis. 


The study identified a series of 13 genes that were duplicated in all three elephant species.  Notably, the researchers uncovered that the duplicated genes were highly expressed in pathways related to anti-cancer functions.  These included genes related to the cell cycle, DNA damage repair, telomere extension, and maintenance and apoptosis.  The researchers concluded the reduced risk of cancer due to extra copies of anti-tumor genes facilitated the evolution of elephants' increased size. 

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Novel imaging method reveals a surprising arrangement of DNA in the cell's nucleus

Novel imaging method reveals a surprising arrangement of DNA in the cell's nucleus | Amazing Science |

If you open a biology textbook and run through the images depicting how DNA is organized in the cell's nucleus, chances are you'll start feeling hungry; the chains of DNA would seem like a bowl of ramen: long strings floating in liquid. However, according to two new studies—one experimental and the other theoretical—that are the outcome of the collaboration between the groups of Prof. Talila Volk of the Molecular Genetics Department and Prof. Sam Safran of the Chemical and Biological Physics Department at the Weizmann Institute of Science, this image should be reconsidered. Clarifying it is essential since DNA's spatial arrangement in the nucleus can affect the expression of genes contained within the DNA molecule, and hence the proteins found in the cell.


This story began when Volk was studying how mechanical forces influence cell nuclei in the muscle and found evidence that muscle contractions had an immediate effect on gene expression patterns. "We couldn't explore this further because existing methods relied on imaging of chemically preserved cells, so they failed to capture what happens in the cell nuclei of an actual working muscle," she says.


To address this issue, Dr. Dana Lorber, a research associate in Volk's group, led the design of a device that makes it possible to study muscle nuclei in live fruit fly larvae. The device holds the tiny, translucent larva within a groove that allows it to contract and relax its muscles but keeps its movement constrained so that it can be scanned by a fluorescence microscope. Using the device, the researchers obtained images of the internal, linearly-organized complexes of DNA and its proteins (known as chromatin), surrounded by the membrane of the muscle nuclei.


Expecting a bowl full of ramen, Lorber and Dr. Daria Amiad-Pavlov, a postdoctoral fellow in Volk's group, were in for a surprise. Rather than filling up the entire volume of the nucleus, the "noodles," or long chromatin molecules, were organized as a relatively thin layer, attached to its inner walls. Similar to the outcome of the interaction between oil and water, what is known as "phase separation," the chromatin separated itself from the bulk of the liquid inside of the nucleus and found its place at its outskirts, while most of the fluid medium remained at the center.


The researchers realized that they were on their way to addressing a fundamental biological question, that is—how is chromatin, and hence DNA, organized in the nucleus in a living organism. "But the findings were so unexpected, we had to make sure no error had crept in and that this organization was universal," Lorber says.

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Exotic DNA-based detector might help scientists hunt for dark matter

Exotic DNA-based detector might help scientists hunt for dark matter | Amazing Science |
The XENON1T dark matter experiment consists of a giant vat of liquid xenon in an underground chamber beneath the Gran Sasso mountain in Italy. Its task is to search for evidence of dark matter that astronomers cannot see but think fills the universe.


Because the solar system is moving rapidly through the universe, Earth ought to be ploughing through this ocean of dark matter. So any dark matter collisions inside XENON1T should come from our direction of travel. But there is a problem with XENON1T, and other dark matter detectors like it. Although it ought to be able to see evidence of dark matter particles, it cannot tell which direction they are coming from. And that places significant constraints on what physicists can deduce from the data. What they’d like instead is a detector that can map the tracks that dark matter particles make as they pass through.

Now Ciaran O’Hare, at the University of Sydney in Australia, with colleagues, say they think they know how this can be done. The team is working on the design of an exotic new form of detector that can spot not only the presence of dark matter but also the direction in which it is traveling. The team have simulated for the first time how dark matter particles would interact inside the machine and say it has significant advantages over the current generation of detectors.


The new detector has a unique design based on DNA strands. It consists of a forest of double-stranded nuclei acids that hang from layers of gold metal sheeting. Each DNA strand is unique and its position within the detector known with nanometer resolution.

When a dark matter particle enters the detector, it slices through any DNA strands in its path, causing the broken segments to fall into a microfluidic collection system. “Since the sequences of base pairs in nucleic acid molecules can be precisely amplified and measured using polymerase chain reaction (PCR), the original spatial position of each broken strand inside the detector can be reconstructed with nanometer precision,” say the team. In this way, physicists can reconstruct the track of the dark matter particle through the machine.

The idea behind the DNA detector was put forward in 2012. The new work is the first simulation to test how the detection would work for dark matter particles of different types, energies and directions. “We conclude that a DNA detector could be a cost-effective, portable, and powerful new particle detection technology,” says O’Hare.

The new approach has other advantages over traditional dark matter detectors. The device is tiny compared to the behemoths used to detect dark matter today — portable even. It would also be significantly cheaper. However, it is by no means perfect. The DNA detector does not provide enough information to easily identify the type of dark matter particle involved or even its precise energy. For that reason, these detectors are likely to be used in conjunction with the data from traditional machines.

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