Cells harvested from urine may have diagnostic potential for kidney disease, find scientists

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Genes expressed in human cells harvested from urine are remarkably similar to those of the kidney itself, suggesting they could be an important non-invasive source of information on the kidney.

The news offers hope that doctors may one day be able to investigate suspected kidney pathologies without carrying out invasive procedures such as biopsies, raising the tantalizing prospect of earlier and simpler disease detection.

The impact of late detection of kidney disease can be severe and can lead to serious and sometimes life-threatening complications.

The team led by University of Manchester scientists measured the levels of approximately 20,000 genes in each cellular sediment sample of urine using a technique called transcriptomics.

The British Heart Foundation-funded study benefited from access to the world's largest collection of human kidney samples collected after surgery or kidney biopsy conducted before transplantation, known as the Human Kidney Tissue Resource, at The University of Manchester.

They extracted both DNA and RNA from each sample and connected information from their analysis, together with data from previous large-scale analyses of blood pressure (called genome-wide association studies), using sophisticated computational methods.

Inflammatory bowel disease after a stem cell transplant

Additional genetic testing could make bone marrow donations even safer.
Image Credit: Gerd Altmann

A stem cell donation saves a leukemia sufferer’s life. Five years later, the patient develops a chronic inflammatory bowel disease that occurs very rarely following a transplant. Researchers from the University of Basel and University Hospital Basel have studied the case and are calling for more extensive genetic analyses in bone marrow donors.

In many forms of blood cancer, a transplant of blood stem cells is the only chance of a cure. This procedure involves first eliminating the patient’s degenerated blood stem cells and then building up their immune system again with stem cells from a donor.

So that the new immune system doesn’t turn against the recipient’s body, a series of tissue markers must match the recipient and donor. This criterion is investigated as standard. Now, a research team led by Professors Petr Hrúz from Clarunis (University Digestive Health Care Center Basel) and Mike Recher from the University of Basel and University Hospital Basel has shown that it would also be sensible to carry out a more extensive genetic analysis.

Writing in the Journal of Clinical Immunology, the team describes the case of a man who developed a chronic inflammatory bowel disease (Crohn’s disease) five years after receiving a blood stem cell transplant for leukemia. Genetic analysis revealed that a mutation had been transplanted along with the blood stem cells from the donor. This mutation affected the operation of a factor called TIM-3, a key regulator of the immune system. The donor, on the other hand, was and remains in apparently good health.

UC Irvine-led research team discovers role of key enzymes that drive cancer mutations

“Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each,” says the study’s corresponding author, Rémi Buisson (center), UCI assistant professor of biological chemistry. He’s flanked by postdoctoral fellow Pedro Ortega (left) and graduate student Ambrocio Sanchez, UCI researchers who developed a new method to characterize the particular kind of DNA modified by the enzymes.
Photo Credit: UCI School of Medicine

A research team led by the University of California, Irvine has discovered the key role that the APOBEC3A and APOBEC3B enzymes play in driving cancer mutations by modifying the DNA in tumor genomes, offering potential new targets for intervention strategies.

The study, published today online in the journal Nature Communications, describes how the researchers identified the process by which APOBEC3A and APOBEC3B detect specific DNA structures, resulting in mutations at distinct positions within the tumor genome.

“It’s critical to understand how cancer cells accumulate mutations leading to hot spots that contribute to disease progression, drug resistance and metastasis,” said corresponding author Rémi Buisson, UCI assistant professor of biological chemistry. “Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each. This finding will allow us to develop novel therapies to suppress mutation formation by directly targeting each enzyme accordingly.”

All creatures great and small: Sequencing the blue whale and Etruscan shrew genomes

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The blue whale genome was published in the journal Molecular Biology and Evolution, and the Etruscan shrew genome was published in the journal Scientific Data.

Research models using animal cell cultures can help navigate big biological questions, but these tools are only useful when following the right map.

“The genome is a blueprint of an organism,” says Yury Bukhman, first author of the published research and a computational biologist in the Ron Stewart Computational Group at the Morgridge Institute, an independent research organization that works in affiliation with the University of Wisconsin–Madison in emerging fields such as regenerative biology, metabolism, virology and biomedical imaging. “In order to manipulate cell cultures or measure things like gene expression, you need to know the genome of the species — it makes more research possible.”

The Morgridge team’s interest in the blue whale and the Etruscan shrew began with research on the biological mechanisms behind the “developmental clock” from James Thomson, emeritus director of regenerative biology at Morgridge and longtime professor of cell and regenerative bBiology in the UW School of Medicine and Public Health.  It’s generally understood that larger organisms take longer to develop from a fertilized egg to a full-grown adult than smaller creatures, but the reason why remains unknown.

“It’s important just for fundamental biological knowledge from that perspective. How do you build such a large animal? How can it function?” says Bukhman.

Scientists develop a rapid gene-editing screen to find effects of cancer mutations

Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have developed a method to screen cancer-associated genetic mutations much more easily and quickly than any existing approach. This illustration, by Samuel Gould’s brother Owen Gould, is an artistic interpretation of the research and the idea of “rewriting the genome,” explains Samuel.
Illustration Credit: Owen Gould
(CC BY-NC-ND 4.0 DEED)

Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA.

Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily.

The researchers demonstrated their technique by screening cells with more than 1,000 different mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This method, which is easier and faster than any existing approach, and edits the genome rather than introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful than previously thought.

The researchers say this technique could also be applied to many other cancer genes, and could eventually be used for precision medicine, to determine how an individual patient’s tumor will respond to a particular treatment.

“In one experiment, you can generate thousands of genotypes that are seen in cancer patients, and immediately test whether one or more of those genotypes are sensitive or resistant to any type of therapy that you’re interested in using,” says Francisco Sanchez-Rivera, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.

MIT graduate student Samuel Gould is the lead author of the paper, which appears today in Nature Biotechnology.

AI research gives unprecedented insight into heart genetics and structure

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A ground-breaking research study has used AI to understand the genetic underpinning of the heart’s left ventricle, using three-dimensional images of the organ. It was led by scientists at the University of Manchester, with collaborators from the University of Leeds (UK), the National Scientific and Technical Research Council (Santa Fe, Argentina), and IBM Research (Almaden, CA).

The highly interdisciplinary team used cutting-edge unsupervised deep learning to analyze over 50,000 three-dimensional Magnetic Resonance images of the heart from UK Biobank, a world-leading biomedical database and research resource.

The study, published in the leading journal Nature Machine Intelligence, focused on uncovering the intricate genetic underpinnings of cardiovascular traits. The research team conducted comprehensive genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS), resulting in the discovery of 49 novel genetic locations showing an association with morphological cardiac traits with high statistical significance, as well as 25 additional loci with suggestive evidence.  

The study's findings have significant implications for cardiology and precision medicine. By elucidating the genetic basis of cardiovascular traits, the research paves the way for the development of targeted therapies and interventions for individuals at risk of heart disease.

How Proteins Control Genes to Prevent our Cells from Maldevelopment

Ole Nørregaard Jensen is a professor and head of research at the Department of Biochemistry and Molecular Biology.
Photo Credit: Stefan Kristensen

Every time a cell in our body prepares to divide, an extremely complex process begins to ensure that the mother cell's DNA is copied into a new daughter cell along with all the correct instructions for which genes on the DNA strand should be turned off and which should be activated.

If errors occur in this process and the new cell is not identical to the mother cell, damage and disease may occur.

Researchers are therefore interested in learning more about these processes and why the copying of DNA and instructions sometimes goes wrong.

Constant DNA replication of the cell

All humans have a unique DNA strand, originating from a single cell: the fertilized egg cell, which has divided and created the billions of cells that make up the whole human being. They all contain a copy of the DNA strand created at fertilization. However, different cells decode the DNA in different ways, allowing for the formation of more than 200 different cell types. Some cell types die quickly and need to be replaced many times during life; for example, skin cells and intestinal cells are renewed every few days. Each time a new cell is created, a copy of the unique DNA strand is made for the new cell.

When Plants Flower: Scientists ID Genes, Mechanism in Sorghum

Brookhaven Lab biologist Meng Xie and postdoctoral fellow Dimiru Tadesse with sorghum plants like those used in this study. Note that these plants are flowering, unlike those the scientists engineered to delay flowering indefinitely to maximize their accumulation of biomass.
Photo Credit: Kevin Coughlin/Brookhaven National Laboratory

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and Oklahoma State University have identified key genes and the mechanism by which they control flowering in sorghum, an important bioenergy crop. The findings, just published in the journal New Phytologist, suggest strategies to delay sorghum flowering to maximize plant growth and the amount of biomass available for generating biofuels and bioproducts.

“Our studies elucidate the gene regulatory network controlling sorghum flowering and provide new insights into how these genes could be leveraged to improve sorghum for achieving bioenergy goals,” said Brookhaven Lab biologist Meng Xie, one of the leaders of the research.

Sorghum is particularly well suited for sustainable agriculture because it can grow on marginal lands in semiarid regions and can tolerate relatively high temperatures. Like many plants, its growth and flowering (reproductive) cycles are regulated by the duration of daily sunlight. And once plants start to flower, they stop growing, which has important implications for the accumulation of biomass.

For example, one natural sorghum variety can reach nearly 20 feet in height, only transitioning to the reproductive flowering phase near the end of the summer growing season when the duration of daylight diminishes. Other “day-neutral” lines flower earlier, after reaching about three feet in height, producing less vegetation but more grain.

Researchers develop artificial building blocks of life

Structural comparison of DNA and the artificial TNA, a Xeno nucleic acid with the natural base pairs AT and GC and an additional base pair (XY).
Image Credit: Courtesy of University of Cologne

For the first time, scientists from the University of Cologne (UoC) have developed artificial nucleotides, the building blocks of DNA, with several additional properties in the laboratory. They could be used as artificial nucleic acids for therapeutic applications.

DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory. The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.

Research sheds light on new strategy to treat infertility

OHSU researchers are advancing a strategy based on somatic cell nuclear transfer to treat infertility through in vitro gametogenesis, or IVG. A study published today describes the science behind the technique demonstrated in a mouse model.
Photo Credit: OHSU/Christine Torres Hicks

New research from Oregon Health & Science University describes the science behind a promising technique to treat infertility by turning a skin cell into an egg that is capable of producing viable embryos.

Researchers at OHSU documented the technique, known as in vitro gametogenesis, or IVG, in a mouse model through preliminary steps that rely upon transferring the nucleus of a skin cell into a donated egg in which the nucleus has been removed. Using mice, the investigators coaxed the skin cell’s nucleus into reducing its chromosomes by half, so that it could then be fertilized by a sperm cell to create a viable embryo.

The study was published today in the journal Science Advances.

“The goal is to produce eggs for patients who don’t have their own eggs,” said senior author Shoukhrat Mitalipov, Ph.D., director of the OHSU Center for Embryonic Cell and Gene Therapy, and professor of obstetrics and gynecology, and molecular and cellular biosciences, in the OHSU School of Medicine.

The technique could be used by women of advanced maternal age or those who are unable to produce viable eggs due to previous treatment for cancer or other causes. It also raises the possibility of men in same-sex relationships having children who are genetically related to both parents.

Instead of attempting to differentiate induced pluripotent stem cells, or iPSCs, into sperm or egg cells, OHSU researchers are focused on a technique based on somatic cell nuclear transfer, in which a skin cell nucleus is transplanted into a donor egg stripped of its nucleus. In 1996, researchers famously used this technique to clone a sheep in Scotland named Dolly.

Marine algae implants could boost crop yields

Discovery could lead to more sustainable food supply
Photo Credit: Oktavianus Mulyadi

Scientists have discovered the gene that enables marine algae to make a unique type of chlorophyll. They successfully implanted this gene in a land plant, paving the way for better crop yields on less land. 

Finding the gene solves a long-standing mystery amongst scientists about the molecular pathways that allow the algae to manufacture this chlorophyll and survive. 

“Marine algae produce half of all the oxygen we breathe, even more than plants on land. And they feed huge food webs, fish that get eaten by mammals and humans,” said UC Riverside assistant professor of bioengineering and lead study author Tingting Xiang. “Despite their global significance, we did not understand the genetic basis for the algae’s survival, until now.”

The study, published in Current Biology, also documents another first-of-its-kind achievement: demonstrating that a land plant could produce the marine chlorophyll. Tobacco plants were used for this experiment, but in theory, any land plant may be able to incorporate the marine algae gene, allowing them to absorb a fuller spectrum of light and achieve better growth. 

Gene discovered that can protect against severe muscle disease

The researchers behind the study. Front row from the left: Hanna Nord, Fatima Pedrosa Domellöf, Jingxia Liu. Rear row: Abraha Kahsay, Nils Dennhag, Jonas von Hofsten
Photo Credit: Per Stål

A specific gene may play a key role in new treatments that prevent muscle in the body from breaking down in serious muscle diseases. This is shown in a new study at Umeå University, Sweden. Protein expressed by the gene naturally prevents the muscles around the eye from being affected when other muscles in the body are affected by muscular dystrophies. In the study the gene is expressed in all muscles. The effects were that muscular dystrophy was alleviated throughout the body.

"You could say that the eye muscles function both as an eye-opener for understanding the disease and as a door opener to a treatment for the whole body," says Fatima Pedrosa Domellöf, professor of eye diseases at Umeå University and one of the study's authors.

Muscular dystrophies are a group of congenital genetic diseases that affect muscle tissue and often lead to severe disability and greatly reduced life expectancy. Despite intensive research, there are still no effective treatments for patients suffering from muscular dystrophy.

DNA Aptamer Drug Sensors Can Instantly Detect Cocaine, Heroin and Fentanyl – Even When Combined with Other Drugs

Photo Credit: Nastya Dulhiier

Researchers from North Carolina State University have developed a new generation of high-performance DNA aptamers and highly accurate drug sensors for cocaine and other opioids. The sensors are drug specific and can detect trace amounts of fentanyl, heroin, and cocaine – even when these drugs are mixed with other drugs or with cutting agents and adulterants such as caffeine, sugar, or procaine. The sensors could have far-reaching benefits for health care workers and law enforcement agencies.

“This work can provide needed updates to currently used tests, both in health care and law enforcement settings,” says Yi Xiao, associate professor of chemistry at NC State and corresponding author of two studies describing the work.

“For example, drug field testing currently used by law enforcement still relies on chemical tests developed a century ago that are poorly specific, which means they react to compounds that may not be the drug they’re looking for,” Xiao says.

“And the existing aptamer test for cocaine isn’t sensitive and specific enough to detect clinically relevant amounts of the drug in biological samples, like blood. The sensors we developed can detect cocaine in blood at nanomolar, rather than micromolar, levels, which represents a 1,000-fold improvement in sensitivity.”

An evolutionary mystery 125 million years in the making

A bushel of tomatoes at the CSHL Uplands Farm.
Photo Credit: Courtesy of Cold Spring Harbor Laboratory

Plant genomics has come a long way since Cold Spring Harbor Laboratory (CSHL) helped sequence the first plant genome. But engineering the perfect crop is still, in many ways, a game of chance. Making the same DNA mutation in two different plants doesn’t always give us the crop traits we want. The question is why not? CSHL plant biologists just dug up a reason.

CSHL Professor and HHMI Investigator Zachary Lippman and his team discovered that tomato and Arabidopsis thaliana plants can use very different regulatory systems to control the same exact gene. Incredibly, they linked this behavior to extreme genetic makeovers that occurred over 125 million years of evolution.