Joint study reveals how DNA unzipping machine works, shedding lights on cancer therapy

An initial open structure (IOS) is formed upon binding of human MCM double hexamer (hMCM-DH) to origin DNA.
Illustration Credit: Image modified from original illustration of Li et al, 2023 Cell 186, 1-14. Source/ Hong Kong University of Science and Technology

Scientists from The Hong Kong University of Science and Technology (HKUST), The University of Hong Kong (HKU) and Institut Curie, France have jointly uncovered a new mechanism of the human MCM2-7 complex in regulating replication initiation, which can be used as a novel and effective anticancer strategy with the potential for selective killing of cancer cells. The findings were recently published in the Cell journal.

Human life begins with a single fertilized egg in the mother’s womb. This egg propagates through cell divisions and develops into our multicellular body. During each cell division, our genome DNA, the blueprint of genetic information, is accurately replicated. Each cell carries roughly 2 meters of DNA organized into 23 pairs of chromosomes. In our lifetime (~70 years), our body will synthesize more than a light year’s length of DNA of ~1016 meters - the distance light travels in one year. The replication process requires the DNA duplex to be first melted and then separated into two single-stranded templates for DNA polymerases to synthesize as complement strands. Any misregulation of this process can cause dire consequences, such as tumorigenesis and inherited genetic disorders.

UC research shows people with latent tuberculosis infection are more prone to inflammation

Moises Huaman, MD, of the Division of Infectious Diseases in the Department of Internal Medicine at the UC College of Medicine
Photo Credit: University of Cincinnati

Study examines connection between inflammation, infection and cardiovascular risk

Newly published research from the University of Cincinnati finds that people with latent tuberculosis infection (LTBI) have more inflammation and could be at a higher risk for cardiovascular disease.

The research was published in Open Forum Infectious Diseases, a journal from the Infectious Diseases Society of America.

Roughly 25% of the world population has LTBI, a state where the individual has been exposed to tuberculosis but is not sick from it, says Moises Huaman, MD, of the Division of Infectious Diseases in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study.

“Developing countries have higher rates of LTBI,” says Huaman. “There are areas in the world where LTBI may affect 50% or so of the population. Here in the United States, the prevalence of LTBI is about 5%, which is still common. It is a global health problem.”

The Pacific Ocean’s oxygen-starved ‘OMZ’ is growing, new Princeton research finds

The Pacific Oxygen Minimum Zone in 3D Researchers created this visualization of the Pacific’s oxygen minimum zone from observations and the 2018 World Ocean Atlas. The colors approximately indicate the core (purple) that has almost no oxygen and is contracting, the low-oxygen outer layer (orange) that is expanding, and a transitional zone in between (pink).  
Animation Credit: by Julius Busecke in collaboration with Bane Sullivan

Areas of low-oxygen water stretch for thousands of miles through the world’s oceans. The largest of these “oxygen minimum zones” (OMZs) is found along the Pacific coast of North and South America, centered off the coast of Mexico.

Until recently, climate models have been unable to say whether OMZs will grow or shrink from climate change, in part because OMZs result from two opposing processes: oxygen supplied by ocean circulation and oxygen used by sea life.

Now, a team led by Princeton’s Laure Resplandy has confidently predicted that the boundaries of the Pacific OMZ, the planet’s largest, will expand by as much as 2 million additional cubic miles (8 million cubic kilometers) — both upward toward the sea surface and outward toward the coast — by the end of the century.

Organelles grow in random bursts

Shankar Mukherji, assistant professor of physics in Arts & Sciences
Photo Credit: Washington University in St. Louis

Eukaryotic cells — the ones that make up most of life as we know it, including all animals, plants and fungi — are highly structured objects.

These cells assemble and maintain their own smaller, internal bits: the membrane-bound organelles like nuclei, which store genetic information, or mitochondria, which produce chemical energy. But much remains to be learned about how they organize themselves into these spatial compartments.

Physicists at Washington University in St. Louis conducted new experiments that show that eukaryotic cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship that the scientists predict theoretically, their new framework suggests that organelles grow in random bursts from a limiting pool of building blocks.

The study was published Jan. 6 in Physical Review Letters.

“In our work, we suggest that the steps by which organelles are grown — far from being an orderly ‘brick-by-brick’ assembly — occur in stochastic bursts,” said Shankar Mukherji, assistant professor of physics in Arts & Sciences.

Controlled, localized delivery of blood thinner may improve blood clot treatment

Co-authors Atip Lawanprasert (left), doctoral student in biomedical engineering, Sopida Pimcharoen (center), undergraduate student in biomedical engineering and Scott Medina (right), Penn State associate professor of biomedical engineering, analyze results related to their study of combining the anticoagulant heparin with peptide to slow down the medication's delivery at the site of a blood clot.
Photo Credit: Jeff Xu / Pennsylvania State University

Heparin has long been used as a blood thinner, or anticoagulant, for patients with blood clotting disorders or after surgery to prevent complications. But the medication remains difficult to dose correctly, potentially leading to overdosing or underdosing.

A team of Penn State researchers combined heparin with a protein fragment, peptide, to slow down the release of the drug and convey the medication directly to the site of a clot. They published their findings in the journal Small.

“We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours,” said corresponding author Scott Medina, Penn State associate professor of biomedical engineering. “We also wanted to deliver the drug through the skin instead of through an IV.”

When mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin, forming a cache of material that is then diffused in the circulatory system and travels to blood clots when they appear. The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.

New study suggests Mayas utilized market-based economics

Obsidian collections from the site of Q'umarkaj and the surrounding region.
Photo Credit: Rachel Horowitz

More than 500 years ago in the midwestern Guatemalan highlands, Maya people bought and sold goods with far less oversight from their rulers than many archeologists previously thought.

That’s according to a new study in Latin American Antiquity that shows the ruling K’iche’ elite took a hands-off approach when it came to managing the procurement and trade of obsidian by people outside their region of central control.

In these areas, access to nearby sources of obsidian, a glasslike rock used to make tools and weapons, was managed by local people through independent and diverse acquisition networks. Over time, the availability of obsidian resources and the prevalence of craftsmen to shape it resulted in a system that is in many ways suggestive of contemporary market-based economies.

“Scholars have generally assumed that the obsidian trade was managed by Maya rulers, but our research shows that this wasn’t the case at least in this area,” said Rachel Horowitz, lead author of the study and an assistant professor of anthropology at Washington State University. “People seem to have had a good deal of economic freedom including being able to go to places similar to the supermarkets we have today to buy and sell goods from craftsmen.”

The brain’s ability to perceive space expands like the universe

New experiences are absorbed into neural representations over time, symbolized here by a hyperboloid hourglass.
Illustration Credit: Salk Institute

Salk researchers find that neural networks responsible for spatial perception change in a nonlinear manner and may have implications for neurodegenerative disorders like Alzheimer’s disease

Young children sometimes believe that the moon is following them, or that they can reach out and touch it. It appears to be much closer than is proportional to its true distance. As we move about our daily lives, we tend to think that we navigate space in a linear way. But Salk scientists have discovered that time spent exploring an environment causes neural representations to grow in surprising ways.

The findings, published in Nature Neuroscience show that neurons in the hippocampus essential for spatial navigation, memory, and planning represent space in a manner that conforms to a nonlinear hyperbolic geometry—a three-dimensional expanse that grows outward exponentially. (In other words, it’s shaped like the interior of an expanding hourglass.) The researchers also found that the size of that space grows with time spent in a place. And the size is increasing in a logarithmic fashion that matches the maximal possible increase in information being processed by the brain.

UCR scientists develop method to turn plastic waste into potentially valuable soil additive

Recent rain storms washed plastic waste into a creek bed in Riverside's Fairmount Park.
Photo Credit: David Danelski/UCR

University of California, Riverside, scientists have moved a step closer to finding a use for the hundreds of millions of tons of plastic waste produced every year that often winds up clogging streams and rivers and polluting our oceans.

In a recent study, Kandis Leslie Abdul-Aziz, a UCR assistant professor of chemical and environmental engineering, and her colleagues detailed a method to convert plastic waste into a highly porous form of charcoal or char that has a whopping surface area of about 400 square meters per gram of mass.

Such charcoal captures carbon and could potentially be added to soil to improve soil water retention and aeration of farmlands. It could also fertilize the soil as it naturally breaks down. Abdul-Aziz, however, cautioned that more work needs to be done to substantiate the utility of such char in agriculture.

The plastic-to-char process was developed at UC Riverside’s Marlan and Rosemary Bourns College of Engineering. It involved mixing one of two common types of plastic with corn waste — the leftover stalks, leaves, husks, and cobs — collectively known as corn stover. The mix was then cooked with highly compressed hot water, a process known as hydrothermal carbonization.

Lost in Translation: How "Risky" Amino Acids Abort Elongation in Protein Synthesis

Elongation, a crucial step in the translation process of protein synthesis, gets disrupted by amino acid sequences with an abundance of N-terminal aspartic and glutamic acid residues in eukaryotic cells, discovered researchers from Tokyo Tech and University of Hyogo. The team's findings show that these "risky" amino acids can destabilize the ribosomal machinery. As a consequence, most proteomes tend to avoid incorporating them at the N-terminals of peptide sequences, indicating a bias in amino acid distribution.

Life depends on the precise functioning of several proteins synthesized in cells by ribosomes. This diverse set of proteins, known as a proteome, is maintained by the robust translation elongation of amino acid sequences taking place in the ribosomes. The translation mechanisms which ensure that nascent chains of polypeptides—long chains of amino acids—are elongated without getting detached are conserved in all living organisms. However, the rates of elongation are not constant. Elongation is often interrupted by interactions between positively charged nascent polypeptides and negatively charged ribosomal RNA.

Astronomers use ‘little hurricanes’ to weigh and date planets around young stars

The protoplanetary disc surrounding the young star HL Tauri. These new ALMA observations reveal substructures within the disc that have never been seen before and even show the possible positions of planets forming in the dark patches within the system. 
Image Credit: ALMA (ESO/NAOJ/NRAO)

Researchers from the University of Cambridge and the Institute for Advanced Study have developed a technique, which uses observations of these ‘hurricanes’ by the Atacama Large Millimeter/submillimeter Array (ALMA) to place some limits on the mass and age of planets in a young star system.

Pancake-like clouds of gases, dust and ice surrounding young stars – known as protoplanetary discs - are where the process of planet formation begins. Through a process known as core accretion, gravity causes particles in the disc to stick to each other, eventually forming larger solid bodies such as asteroids or planets. As young planets form, they start to carve gaps in the protoplanetary disc, like grooves on a vinyl record.

Even a relatively small planet – as small as one-tenth the mass of Jupiter according to some recent calculations – may be capable of creating such gaps. As these ‘super-Neptune’ planets can orbit their star at a distance greater than Pluto orbits the Sun, traditional methods of exoplanet detection cannot be used.

In addition to the grooves, observations from ALMA have shown other distinct structures in protoplanetary discs, such as banana- or peanut-shaped arcs and clumps. It had been thought that at least some of these structures were also driven by planets.

Monkeypox viruses remain sensitive to the available drugs

Monkeypox Virus
Illustration Credit: Samuel F. Johanns

The three antiviral drugs commonly used to treat mpox viruses (monkeypox viruses) are also effective against the viruses from the current outbreak. This has been shown in cell culture experiments by scientists at Goethe University Frankfurt/University Hospital Frankfurt and the University of Kent in Canterbury, Great Britain.

The mpox virus is closely related to the smallpox virus (variola virus), which caused large, deadly outbreaks before it was eradicated by vaccination at the end of the 1970s. While the smallpox virus led to very severe disease progression with a death rate of about 30 percent, mpox is milder. Nevertheless, the mortality rate is still about three percent. Particularly at risk of a severe course of the disease are people with a weakened immune system, elderly persons, pregnant women, newborn babies and young children. Until recently, mpox outbreaks only occurred in certain parts of Africa when humans became infected through contact with wild animals, typically rodents such as the Gambian pouched rat and the rope squirrel.

However, in May 2022 a first large mpox outbreak outside Africa was detected; the virus spread solely through human-to-human transmission. This ongoing outbreak has so far reached more than 100 countries and been classified by the World Health Organization (WHO) as a "Public Health Emergency of International Concern".

How evolution works

Examples of phenotypic innovations across the eukaryotic tree of life, to which newly developed approaches can be applied.
Graphic Credit: Kenji Fukushima

What genetic changes are responsible for the evolution of phenotypic traits? This question is not always easy to answer. A newly developed method now makes the search much easier.

With its powerful digging shovels, the European mole can burrow through the soil with ease. The same applies to the Australian marsupial mole. Although the two animal species live far apart, they have developed similar organs in the course of evolution - in their case, extremities ideally adapted for digging in the soil.

Science speaks of "convergent evolution" in such cases, when animal, but also plant species independently develop features that have the same shape and function. There are many examples of this: Fish, for example, have fins, as do whales, although they are mammals. Birds and bats have wings, and when it comes to using poisonous substances to defend themselves against attackers, many creatures, from jellyfish to scorpions to insects, have all evolved the same instrument: the venomous sting.

Researchers Find that Wind Turbines Repel Bats in Finnish Forests

Northern bat (Eptesicus nilssonii) is the most common bat in Finland.
Photo Credit: Anna Blomberg

Wind turbines are built at an increasing pace but their effect on nature and animals is poorly known. Researchers from the Universities of Turku and Helsinki in Finland have investigated the impact of wind turbines on bat presence and activity in boreal forests. The results indicate clearly that bats don’t like wind turbines.

The researchers recorded bat acoustic activity for an entire summer at seven wind farms located in forests situated on the western coastline of Finland. By setting up recorders at varying distances from the wind turbines, they were able to see how bat activity and presence differed closer to the turbines as well as further away.

The researchers studied two groups of bats: the Northern bat, which is the most common species in Finland, and the Myotis, a group of five species, including the very common Daubenton’s bat.

“Our results showed that bat presence was impacted by the presence of wind turbines as both studied groups were found more often further away from the wind turbines. Northern bats were repelled up to 800 meters from the wind turbines, but for the Myotis species the negative impact of wind power was even greater than one kilometer, which was the maximum distance we studied”, summarizes lead author, Doctoral Researcher Simon Gaultier from the University of Turku.

A Theory of Rage

Left: Aditya Nair, Caltech graduate student and study's lead author. Photo Credit: J. Ehlert
Center: Ann Kennedy, Theoretical neuroscientist. Photo Credit: Ann Kennedy
Right: David Anderson, Professor of Biology Photo Credit: Courtesy of David Anderson

Have you ever been cut off while driving and found yourself swearing and laying on the horn? Or come home from a long day at work and lashed out at whoever left the dishes unwashed? From petty anger to the devastating violence we see in the news, acts of aggression can be difficult to comprehend. Research has yielded puzzling paradoxes about how rage works in the brain. But a new study from Caltech, pioneering a machine-learning research technique in the hypothalamus, reveals unexpected answers on the nature of aggression.

The hypothalamus is a brain region linked to many innate survival behaviors like mating, hunting, and the fight-or-flight response. Scientists have long believed that neurons in the hypothalamus are functionally specific—that is, certain groups of neurons correlate to certain specific behaviors. This seems to be the case in mating behavior, where neuron groups in the medial preoptic area (MPOA) of the hypothalamus, when stimulated, cause a male mouse to mount a female mouse. These same neurons are active when mounting behavior occurs naturally. The logical conclusion is that these neurons control mounting in mice.

Ludwig Cancer Research study uncovers novel aspect of tumor evolution and potential targets for therapy

 Ping-Chih Ho, Ludwig Lausanne Associate Member
Photo Credit: Ludwig Cancer Research

A Ludwig Cancer Research study has discovered that the immune system’s surveillance of cancer can itself induce metabolic adaptations in the cells of early-stage tumors that simultaneously promote their growth and equip them to suppress lethal immune responses.

Led by Ludwig Lausanne Associate Member Ping-Chih Ho and published in Cell Metabolism, the study details the precise mechanism by which this “immunometabolic editing” of emergent tumors occurs in mouse models of the skin cancer melanoma and identifies a novel biochemical signaling cascade and proteins that orchestrate its effects. Aside from illuminating a previously unknown dimension of tumor evolution, the findings hold significant promise for improving the efficacy of cancer immunotherapy.

“We have uncovered dozens of metabolic enzymes that contribute to immune evasion in melanoma tumors,” said Ho. “These enzymes, as well as some of the individual components of the signaling pathway we’ve identified, represent a rich trove of potential drug targets to undermine the defenses erected by immunometabolic editing. Such drugs could make tumors vulnerable to immune clearance and could also be used in combination with checkpoint blockade and other immunotherapies to overcome the resistance most cancers have to such treatments.”