Rare genetic disease: researchers discover new treatment for ADCY5-related dyskinesia

The movement disorder ADCY5-related dyskinesia can be treated with the asthma drug theophylline. This has been shown in a recent study by Martin Luther University Halle-Wittenberg (MLU), University Medicine Halle and University of Leipzig Medical Center. In the journal PLOS ONE, the researchers describe the case of a child with this disease whose symptoms improved significantly with the drug. ADCY5-related dyskinesia is an extremely rare disorder that causes dyskinesia and uncontrolled movements in affected individuals. Currently, there is no cure for this disease.

ADCY5-related dyskinesia is caused by defects in the ADCY5 gene. "Just one error in the genetic code of this gene can have devastating consequences," says Professor Andrea Sinz from the Institute of Pharmacy at MLU. In the case of ADCY5-related dyskinesia, the genetic defect causes a specific enzyme in the cells to become overactive. This enzyme is involved in the production of the second messenger "cAMP".

In those affected, too much "cAMP" tends to lead to uncontrolled movements, dyskinesia, and many other symptoms, such as speech deficiencies, starting in early infancy. The disease is considered very rare. According to estimates by the US National Institutes of Health, between one and 300 people are living with the disease in the United States; however, more precise numbers are not available. "Rare diseases like ADCY5-related dyskinesia are often not recognized and accurately diagnosed," says Sinz. The symptoms are easily confused with other medical conditions.

Red Deer Natural Habitat Recreated Over the Past 50,000 Years

During the period of global cooling (33,000 years ago), the range of the species declined and reached a minimum of around
Photo Credit: Alexis B

The natural habitat of the European Red deer over the last 50,000 years has been recreated and described by a team of scientists from Russia, Poland, Ukraine, the UK and Italy. An article summarizing the research has been published in The Journal of Archaeological Science.

The details of how reindeer ecology changed with climate warming during the Pleistocene to Holocene transition allow an assessment of the species' adaptive capacity. As reindeer have been widespread in Europe for tens of thousands of years, the data can be used for the study of human life and diet in this part of the world since the Late Pleistocene.

"At the beginning of the study period, the European Red deer tended to feed on plants inherent to open landscapes such as tundra, steppe, and meadows. During this stage, particularly with the maximum cold snap, 26-19 thousand years ago, the Red deer, as well as their ungulate neighbors (the reindeer and horses), were affected by prolonged low temperatures and lack of nutrients. The exception included some territories of modern Spain and Italy," says Pavel Kosintsev, Head Specialist of the UrFU Laboratory of Natural Science Methods in Humanities, Senior Researcher of the Institute of Plant and Animal Ecology of the Russian Academy of Sciences (Ural Branch), and co-author of the article.

Light-Induced Acceleration of Intracellular Delivery

Conceptual image of various cellular uptake processes accelerated by light irradiation
Illustration Credit: Courtesy of Osaka Metropolitan University

Light-induced accelerating system to increase the concentration of bio- functional molecules around targeted cells and their cytosolic delivery.

Cell membranes are barriers that maintain cellular homeostasis, and the intracellular delivery of biologically functional molecules, including peptides, proteins, and nucleic acids to manipulate cellular functions. Conventional intracellular uptake processes require high concentrations of bio functional molecules with low permeability to pass through the cell membrane. This results in low drug activity because the probability of the bio-functional molecules entering target cells and their organelles is low. In addition, many drugs damage healthy cells as well as the cells that are supposed to target due to poor selectivity, making it necessary to develop technology that can increase drugs’ selectivity so that they enter targeted cells with high efficiency.

A research group led by Professor Ikuhiko Nakase (Assistant Director) and Professor Takuya Iida (Director) of the Research Institute for Light-induced Acceleration System (RILACS) at Osaka Metropolitan University used light-induced convection with the aid of superradiance to achieve enhanced permeability of the cell membrane, by locally concentrating bio-functional molecules, including cell-penetrating peptides (CPPs). The light-induced system was capable of effective drug delivery, even at concentrations as low as 1 pmol/L.

Poverty is linked to increased dementia risk, regardless of genetics

Researchers looked at poverty and low socioeconomic status.
Photo Credit: Leroy Skalstad

People who live in poverty are significantly more likely to develop dementia compared to people of higher socioeconomic status, regardless of genetic risk, new research concludes.

A largescale study published in the American Journal of Preventative Medicine examined data from 196,368 UK Biobank participants whose genetic risk for developing dementia was assessed.

In the paper, researchers looked at poverty, or low socioeconomic status, on two levels. The researchers investigated the contribution of individual socioeconomic deprivation, including low income and low wealth. They also looked at area-level socioeconomic deprivation, including rates of employment, and the number of people who owned a car or home. They calculated risk of developing dementia, and compared these with genetic risk for dementia.

They found that deprivation, both linked to socioeconomic conditions of households and at area level, contributed to risk of dementia. The increased risk was particularly associated with people living in very disadvantaged neighborhoods.

23,000-year-old human genome from southern Spain decoded

Human tooth recovered Cueva de Malalmuerzo
Photo Credit: Pedro Cantalejo

A new study reports on genomic data from a 23,000-year-old individual who lived in what was probably the warmest place in Europe at the peak of the last Ice Age. The oldest human genome recovered from the southern tip of Spain adds an important piece of the puzzle to the genetic history of Europe.

An international team of researchers has analyzed ancient human DNA from several archaeological sites in Andalucía in southern Spain. The study, published in Nature Ecology and Evolution, reports on the oldest genome to date from Cueva del Malalmuerzo in southern Spain, as well as the 7,000 to 5,000-year-old genomes of early farmers from other well-known sites, such as Cueva de Ardales. The researchers describe their findings in the article ‘A 23,000-year-old southern-Iberian individual links human groups that lived in Western Europe before and after the Last Glacial Maximum’ in the Journal Nature Ecology and Evolution.

The Iberian Peninsula plays an important role in the reconstruction of human population history. As a geographic cul-de-sac in the southwest of Europe, it is on one hand considered a refuge during the last Ice Age with its drastic temperature fluctuations. On the other hand, it may have been one of the starting points for the recolonization of Europe after the glacial maximum. Indeed, previous studies had reported on the genomic profiles of 13,000 to 8,000-year-old hunter-gatherers from the Iberian Peninsula and provided evidence for the survival and continuation of a much older Paleolithic lineage that has been replaced in other parts of Europe and is no longer detectable. 

Fermilab completes the first-of-its-kind prototype of a superconducting accelerator module

The cavity string for the HB650 cryomodule after being assembled in April 2022. These cavities comprise the heart of the new cryomodule.
Photo Credit: Lynn Johnson, Fermilab

Technical staff at the U.S. Department of Energy’s Fermi National Accelerator Laboratory have completed a prototype of a special superconducting cryomodule, the first of its kind in the world. The national lab is home of the Proton Improvement Plan II, or PIP-II, a project to upgrade Fermilab’s particle accelerator complex.

The new high-beta 650-megahertz, or HB650, cryomodule is the longest and largest cryomodule in PIP-II. It will be responsible for accelerating protons to more than 80% of the speed of light. Ultimately, four of them will comprise the last section of the new linear accelerator, or linac, that will drive Fermilab’s accelerator complex.

In this final section of the linac, these superconducting cryomodules will power beams of protons to the final energy of 800 million electronvolts, or MeV, before the protons exit the linac. From there, the proton beam will transfer to the upgraded Booster and Main Injector accelerators, where it will gain more energy before being turned into a beam of neutrinos. These neutrinos will then be sent on a 1,300-kilometer journey through Earth to the Deep Underground Neutrino Experiment and the Long Baseline Neutrino Facility in Lead, South Dakota.

Wasps harness power of pitcher plants in first-ever observed defense strategy

This is a cynipid wasp, whose larvae were recently discovered to induce plant growths called galls containing acidity levels akin to lemons.
Photo Credit: Antoine Guiguet

As the saying goes, “When life gives you lemons, turn that tartness into little translucent balls in which to grow your young.” At least, that’s how the saying goes for a tiny insect called a cynipid wasp, whose larvae were recently discovered inducing plant growths called galls that contained acidity levels akin to lemons.

“This is exciting because it represents a novel defense system, one we haven’t seen before,” said Antoine Guiguet, an entomologist at Penn State and lead author on a paper about the discovery published today (March 1) in Biology Letters.

For decades, it has been known that most cynipid wasp species inject chemicals into leaves to induce oak trees to produce protective galls — or growths — around their larvae to ensure the safety of their developing offspring. The gall houses and feeds the insects during their larval development and serves a defensive function to ward off natural enemies. The galls eventually fall from the tree and the wasp larva eat their way out, leaving behind the little balls to decompose on the forest floor.

Could a Naturally Occurring Amino Acid Lead Us to a Cure for COVID-19?

An amino acid called 5-aminolevulinic acid (ALA) might be key to reduce the expression of ACE2, a cell membrane receptor that SARS-CoV-2 uses to infect cells. New insights gained by scientists at Tokyo Tech have clarified the relationship between ACE2, ALA, and the production of heme, which could pave the way to anti-viral drugs to cure COVID-19.

After more than two years since its discovery, six million deaths, and half a billion reported cases, there is still no effective cure for COVID-19. Even though vaccines have lowered the impact of outbreaks, patients that contract the disease can only receive supportive care while they wait for their own body to clear the infection.

A promising COVID-19 treatment strategy that has been gaining traction lately is targeting angiotensin-converting enzyme 2 (ACE2). This is a receptor found on the cell membrane that allows entry of the virus into the cell due to its high affinity for SARS-CoV-2’s spike protein. The idea is that reducing the levels of ACE2 on the membrane of cells could be a way to prevent the virus from entering them and replicating, thereby lowering its infectious capabilities.

Lipid nanoparticles highly effective in gene therapy

The RNP-ssODN is designed to ensure the CRISPR-Cas9 molecule is encapsulated by the LNP. Once inside the cells, the ssODN dissociates and CRISPR-Cas9 can carry out its effect.
Illustration Credits: Haruno Onuma, Yusuke Sato, Hideyoshi Harashima. Journal of Controlled Release. February 10, 2023.

Lipid nanoparticles have been used to encapsulate CRISPR-Cas9 and deliver it to cells in mice, where it was highly effective at knocking down expression of a target protein.

Gene therapy is a potential mode of treatment for a wide variety of diseases caused by genetic mutations. While it has been an area of diverse and intense research, historically, only a very few patients have been treated using gene therapy—and fewer still cured. The advent of the genetic modification technique called CRISPR-Cas9 in 2012 has revolutionized gene therapy—as well as biology as a whole—and it has recently entered clinical trials for the treatment of some diseases in humans.

Haruno Onuma, Yusuke Sato and Hideyoshi Harashima at Hokkaido University have developed a new delivery system for CRISPR-Cas9, based on lipid nanoparticles (LNPs), that could greatly increase the efficiency of in vivo gene therapy. Their findings were published in the Journal of Controlled Release.

Social bird species may be less competitive

Northern mockingbird
Photo Credit: Brian E. Kushner/Cornell Lab of Ornithology 

Using Cornell Lab of Ornithology data, a new study finds that birds that have evolved to be more social are less likely to kick other birds off a bird feeder or a perch.

Spend any time watching backyard bird feeders and it becomes clear that some species are more “dominant” than others. They evict other birds from a feeder or perch, usually based on their body size. Scientists wanted to learn if birds that have evolved to be more social have also evolved to be less aggressive.

Their findings published March 1 in the Proceedings of the Royal Society B, “The Effect of Sociality on Competitive Interactions Among Birds.”

“We found that species’ sociality was inversely related to dominance,” said lead author Ilias Berberi from Carleton University in Ottawa, Canada. “Using data collected from thousands of birdwatching volunteers, we measured the sociality of different species based on their typical group size when seen at bird feeders. Though some species are often found in groups, other tend to be loners. When we examined their dominance interactions, we found that more social species are weaker competitors. Overall, the more social bird species are less likely to evict competing species from the feeders.”