. Scientific Frontline

Monday, February 6, 2023

Mapping How Singlet Oxygen Molecules Travel Along DNA Strands

A recent study has unveiled with unprecedented detail how singlet oxygen molecules diffuse along double strand DNAs, paving the way to more effective nucleic acid-targeting photodynamic therapy (PDT). A research team at Tokyo Tech used a novel photosensitizer and custom-made DNA sequences to shed light on the optimal position to anchor the photosensitizer to achieve the best oxidizing effect. This could help make this type of PDT more lethal to cancer cells.

Nucleic acid-targeting photodynamic therapy (PDT) is a promising type of targeted therapy that is being actively researched. This treatment relies on special photosensitizers, a type of drug that binds at specific locations in a cell's DNA. Once bound, the cells are irradiated at a precise frequency, which in turn causes the photosensitizer to produce reactive oxygen species (ROS) or singlet oxygen (1O2) molecules. These molecules tend to oxidize nearby nucleic acids, damaging the genetic material and ultimately killing the irradiated cell.

Although the overall process may sound straightforward, there are still many hurdles to overcome before this type of PDT is good enough for clinical practice. One of them is that even though type II oxidation (the one caused by 1O2) has certain advantages over type I oxidation (the one caused by ROS), there is very little information on how far 1O2 molecules can reach once generated. Because of this knowledge gap, it is difficult to decide which location in the DNA should be targeted to achieve the best effect.

New immunotherapy can be effective for ovarian cancer

Patients with ovarian cancer usually have a poor prognosis.
Photo Credit: National Cancer Institute

A certain type of immunotherapy in which the body's T cells are programmed to attack cancer cells, called CAR-T cell therapy, is effective in ovarian cancer mice. It shows a study published in The Journal for Immuno Therapy of Cancer by researchers from Karolinska Institutet who hope the findings pave the way for a clinical trial to see how effective the treatment is for women with the disease.

This treatment exists today for patients with blood cancer and we now want to investigate whether we can use the method to treat ovarian cancer. Despite many improvements in treatment, women with ovarian cancer have continued to have a poor prognosis, says Isabelle Magalhaes, associate professor at Department of Oncology-Pathology at Karolinska Institutet and shared the last author of the study. 

Sunday, February 5, 2023

St. Jude scientists create more efficient CAR immunotherapies using a molecular anchor

Senior author Stephen Gottschalk, M.D., (left) and corresponding author Peter Chockley, Ph.D., (right) both of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy.
Photo Credit: Courtesy of St. Jude Children's Research Hospital

Scientists at St. Jude Children’s Research Hospital added a molecular anchor to chimeric antigen receptors (CARs), increasing the anti-cancer activity of cellular immunotherapies in cancer models.

Adding a molecular anchor to the key protein that recognizes cancer in cellular immunotherapies can make treatments significantly more effective. Scientists at St. Jude Children’s Research Hospital found that immune cells with the anchored protein increased cancer killing, regardless of the cancer’s cell type or the form of cancer targeted. The molecular anchor concept is a new design for improving chimeric antigen receptor (CAR)-based-immunotherapies. CARs have shown some promise in the clinic but have yet to deliver widespread success across tumor types. The findings were published in Nature Biotechnology.

Menindee Lakes water savings project: study shows poor government consultation and decision-making

The Darling River flows from north to south, with water overflowing into the Menindee Lakes, including Lake Menindee (top right) and Lake Cawndilla (top middle), both forming important wetlands within Kinchega National Park.
Photo Credit: Richard Kingsford

A controversial project in the Murray-Darling Basin was ‘misguided and poorly framed’, UNSW scientists say.

A study led by researchers at the Centre for Ecosystem Science at UNSW Sydney has examined a large water-savings project at Menindee Lakes in News South Wales.

The Menindee Lakes are part of the Murray-Darling Basin – the largest basin in Australia, spanning one-seventh of the continent. 2.2 million people live across its area, and its surface water supplies about 40 per cent of Australia’s irrigated agricultural output.

“The Menindee Lakes project is among the key mechanisms devised by governments to deliver on the Murray-Darling Basin Plan – a major inter-government initiative to provide water for rivers and wetlands in the basin,” said UNSW Professor Richard Kingsford, Director of the Centre for Ecosystem Science and co-author of the study.

The $151.8 million project’s goal is to save water for the Basin Plan by implementing infrastructure measures and rule changes to reduce water lost to evaporation from Menindee Lakes.

Researchers develop elastic material that is impervious to gases and liquids

This image shows a container made of the new material that is elastic, flexible, and impervious to both gases and liquids. The material can be used to make ‘soft’ batteries for use with wearable electronics and other devices.
Photo Credit: Michael Dickey.

An international team of researchers has developed a technique that uses liquid metal to create an elastic material that is impervious to both gases and liquids. Applications for the material include use as packaging for high-value technologies that require protection from gases, such as flexible batteries.

“This is an important step because there has long been a trade-off between elasticity and being impervious to gases,” says Michael Dickey, co-corresponding author of a paper on the work and the Camille & Henry Dreyfus Professor of Chemical and Biomolecular Engineering at North Carolina State University.

“Basically, things that were good at keeping gases out tended to be hard and stiff. And things that offered elasticity allowed gases to seep through. We’ve come up with something that offers the desired elasticity while keeping gases out.”

A new understanding of reptile coloration

A small sample of variations in coloring seen in captive-bred ball pythons (Python regius).
Image Credit: McGill University

Snakes and mice don’t look alike. But much of what we know about skin coloration and patterning in vertebrates generally, including in snakes, is based on lab mice. However, there are limits to what mice can tell us about other vertebrates because they don’t share all of the same types of color-producing cells, known as chromatophores. For example, snakes have a type of chromatophore called iridophores that can generate iridescent colors by reflecting light.

To gain a better understanding of the genetic basis of coloration in vertebrates, a McGill University-led research team combined a range of techniques (whole gene sequencing, gene-editing, and electron microscopy) to look more closely at color variations and patterning in the skin shed by ball pythons bred in captivity. They were able to identify a particular gene (tfec) that plays a crucial role in reptile pigmentation generally and more specifically in a classic color variant found across vertebrates and distinguished by blotches of white, the piebald.

Breakthrough laboratory confirmation of key theory behind the formation of planets, stars and supermassive black holes

Pillars of Creation: By combining images of the iconic Pillars of Creation from two cameras aboard NASA’s James Webb Space Telescope, the universe has been framed in its glory. The pillars are the vast clouds of dust and gas in the foreground that swirl around and form celestial bodies. 
Hi-Res Zoomable Image
Photo Credit: JWST/NASA

The first laboratory realization of the longstanding but never-before confirmed theory of the puzzling formation of planets, stars and supermassive black holes by swirling surrounding matter has been produced at the Princeton Plasma Physics Laboratory (PPPL). This breakthrough confirmation caps more than 20 years of experiments at PPPL, which is based at Princeton University.

The puzzle arises because matter orbiting around a central object does not simply fall into it, due to what is called the conservation of angular momentum that keeps planets and the rings of Saturn from tumbling from their orbits. That’s because the outward centrifugal force balances out the inward pull of gravity on the orbiting matter. However, the clouds of dust and plasma called accretion disks that swirl around and collapse into celestial bodies do so in defiance of the conservation of angular momentum.    

The solution to this puzzle, a theory known as the Standard Magnetorotational Instability (SMRI), was first proposed in 1991 by University of Virginia theorists Steven Balbus and John Hawley. They built on the fact that in a fluid that conducts electricity, whether the fluid be plasma or liquid metal, magnetic fields behave like springs connecting different sections of the fluid. This allows ubiquitous Alfvén waves, named after Nobel Prize winner Hannes Alfvén, to create a turbulent back-and-forth force between the inertia of the swirling fluid and the springiness of the magnetic field, causing angular momentum to be transferred between different sections of the disk.

Rates of hatching failure in birds almost twice as high as previously estimated

Hatching failure rates in birds are almost twice as high as experts previously estimated, according to the largest ever study of its kind.
Photo Credit: Michaela Wenzler

New study from the University of Sheffield, IoZ, and UCL found more than one in six bird eggs fail to hatch. Hatching failure increases as species decline, so the new research could be used to predict what species are most at risk of extinction.

The work provides evidence that conservation managers can use to support their decision making, creating the best possible outcomes for threatened bird species recovery.

The new report highlights how conservationists can best support the recovery of threatened bird species, as it outlines how different conservation practices may affect hatching rates.

Researchers from the University of Sheffield, Institute of Zoology, and University College London (UCL) looked at 241 bird species across 231 previous studies to examine hatching failure. They found that nearly 17 per cent of bird eggs fail to hatch - almost double the figure reported 40 years ago of just over nine per cent.

Researchers identify the neurons that synchronize female preferences with male courtship songs in fruit flies

Researchers discovered the strength of the response of a specific component of the auditory neuron circuit (shown in green) partly explain the fruit flies’ preferences for specific rhythms.
Image Credit: Takuro S. Ohashi 

When it comes to courtship, it is important to ensure that one is interacting with a member of the same species. Animals use multiple sensory systems to confirm that potential mates are indeed suitable, with acoustic communication playing an important role in their decision making.   

Although these differences have previously been reported at the behavioral level, it is not known how the neuronal circuitry underlying this decision-making has diverged between species. Now, in a new publication in Scientific Reports, a research group at Nagoya University in Japan has investigated how the auditory processing pathway has evolved and diverged between fruit fly species.  

Males of several species of Drosophila (fruit flies), which are regularly used in neuroscience research, vibrate their wings rhythmically during courtship, producing a courtship song. The temporal components of these songs differ between species, allowing female flies to distinguish between potential mates. 

Decades-old crustaceans coaxed from lake mud give up genetic secrets revealing evolution in action

 An ancient Daphnia pulicaria individual resurrected from South Center Lake (Minnesota, USA). This individual was hatched from an egg recovered from sediments that date back to circa 1418-1301 A. D. OU scientists have recently studied other members of this species to understand rapid evolution to human-caused pollution in lake ecosystems.
Image Credit: Dagmar Frisch

Human actions are changing the environment at an unprecedented rate. Plant and animal populations must try to keep up with these human-accelerated changes, often by trying to rapidly evolve tolerance to changing conditions.

University of Oklahoma researchers Lawrence Weider, professor of biology, and Matthew Wersebe, a biology doctoral candidate, demonstrated rapid evolution in action by sequencing the genomes of a population of Daphnia pulicaria, an aquatic crustacean, from a polluted lake.  

The research, which was conducted as part of Wersebe’s doctoral dissertation, was recently published in the Proceedings of the National Academy of Sciences.  Wersebe and Weider revived decades-old Daphnia resting eggs from lake sediments, a method known as resurrection ecology, which has been refined in Weider’s lab over the past several decades. They then sequenced the entire genomes of 54 different Daphnia individuals from different points-in-time, allowing them to study the genetics and evolution of the population.

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