Biology Biochemistry

Scientists have found that extracellular calcium mediates the activation of a membrane protein that waves the flag signalling cell death

Anti-estrogenic therapies can suppress the growth of cancer that does not express estrogen receptors; when combined with immune checkpoint inhibitor therapies, they halt tumor progression in mice models.

The entire biosynthetic pathway of actinopyridazone has been unveiled, revealing that an unprecedented carrier protein-mediated ring-forming step is key to its synthesis.

Researchers at Kanazawa University report in Nano Letters how high-speed atomic force microscopy leads to insights into processes relevant to Alzheimer’s disease. Moreover, the technique is shown to be an excellent tool for studying the effect of drugs against the disease.

Researchers at Kanazawa University report in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) high-speed atomic force microscopy experiments that show how ligands associated with stimulating and suppressing activation of the TRPV1 protein increase and decrease the molecule’s structural variations. The observations provide insights into how these heat- and chilli-sensing proteins function.

A group including Osaka Metropolitan University researchers discovered that the rhodopsin—a protein in the eye that detects light—of whale sharks has changed to efficiently detect blue light, which penetrates deep-sea water easily. The amino acid substitutions–one of which is counterintuitively associated with congenital stationary night blindness in humans—aid in detecting the low levels of light in the deep-sea. Although these changes make the whale shark rhodopsin less thermally stable the deep-sea temperature, allows their rhodopsin to keep working. This suggests that the unique adaptation evolved to function in the low-light low-temperature environment where whale sharks live.

A research group at Osaka Metropolitan University has succeeded in simply creating an artificial metalloenzyme with the common metal-binding motif 2-his-1-carboxylate, which is found in natural non-heme metalloenzymes. They created a library of 12 different proteins and screened the library and found that the H52A/H58E variant had the best stereoselectivity. It is expected that this research can be expanded to produce a variety of biocatalysts that work under mild conditions.

Osaka Metropolitan University scientists successfully quantified the total reactive polysulfide content of 22 different types of vegetables, including onions and garlic. They also revealed that reactive polysulfides are not only found in the leek genus (Allium), such as onions and garlic but also in the cruciferous family of vegetables (Brassicaceae), such as broccoli and cabbage.

Osaka Metropolitan University researchers have used 100 seconds of laser irradiation to generate convection currents that selectively accelerate biochemical reactions—due to the photothermal effect—by concentrating biofunctional molecules at the cell surface. Using this method, useful molecules can be transported into cells at concentrations a hundred to a thousand times lower than with conventional methods. Furthermore, they also succeeded in selectively introducing small molecules into intracellular organelles usually impossible at low concentrations (hundreds of pmol/L) as well as inducing cell death in targeted cells by concentrating anticancer active peptides into them at concentrations so low that they would not be conventionally effective (several tens of nmol/L).

Osaka Metropolitan University scientists found that 2-oxo-imidazole-containing dipeptides (2-oxo-IDPs) exhibit very high antioxidant activity. Furthermore, they established a method to selectively and sensitively detect very small amounts of 2-oxo-IDPs and revealed for the first time that several types of 2-oxo-IDPs are contained in meat, including beef, pork, and chicken.

In hepatic steatosis, hepatocytes "die," resulting in liver damage. Severe steatosis increases hepatocellular deaths, thus aggravating liver damage. The mechanism is unclear. Using mice, we show that mild steatosis causes apoptosis whereas severe steatosis predominantly causes necroptosis leading to cell rupture. This induces strong inflammation and new cell death, producing further liver damage. We reveal the transcription factor ATF3 to be involved in this process. Our results are expected to contribute to therapeutic method development.

Osaka Metropolitan University scientists discovered the principle of light-induced acceleration of antigen–antibody reaction, allowing for simple, ultrafast, and highly sensitive detection of proteins. The researchers introduced target proteins and probe particles with modified antibodies selectively binding to the target proteins into a small channel and applied irradiation with infrared laser light. They achieved, for the first time, the rapid measurement of trace amounts of attogram-level target proteins after only 3 minutes of laser irradiation. These findings will potentially contribute to breakthroughs in the development of systems for ultra-early diagnosis of various diseases.

Using cryogenic electron microscopy, a research team from the Research Center for Artificial Photosynthesis (ReCAP) at Osaka Metropolitan University has revealed, for the first time, the structures and binding environments of pigments bound to a protein called a photosynthetic antenna of the marine green macroalga Codium fragile. The team’s results extend our knowledge about the molecular mechanism by which blue-green light—the only light available in deep seawater—is efficiently utilized for photosynthesis.

Revelations about the mechanisms of two key proteins which maintain the asymmetric distribution of cholesterol within the cell membrane could help understand and treat diseases linked to its imbalance

A research group at the Osaka Metropolitan University Graduate School of Science has revealed a new system that allows them to control the behavior of the nematode worm Caenorhabditis elegans, using two different animal opsins, a type of light-sensitive protein. The first opsin was expressed in the worms’ sensory cells responsible for triggering avoidance behavior, making the worms move. This opsin was found to be approximately 7,000 times more sensitive to white light than the commonly used optogenetic protein channelrhodopsin-2. Likewise, a UV-sensitive opsin was expressed in the worms’ motor neurons, causing the worms to stop when exposed to UV light and start moving again when exposed to green light. Both opsins tested can be switched on and off repeatedly without breaking down, making them robust tools for future research, including the field of drug discovery.

The research team investigated the role of D-amino acids in severe viral infection. Mouse models of influenza A and COVID-19 infection and patients with severe COVID-19 demonstrated reduced D-amino acid levels in the blood. Supplementation with D-alanine mitigated body weight reduction in IAV model mice and improved survival in COVID-19 model mice. D-amino acids may represent potential biomarkers and therapeutic agents for the treatment of severe viral infection.

Researchers led by Osaka University have shown that a molecule known as ATAD3A is essential for the movement of genetic material inside cellular substructures called mitochondria. Appropriate distribution of this DNA, organized into “nucleoid” structures, is key for the generation of energy by the “respiratory chain” protein complex. This study opens up opportunities for developing new methods to alter nucleoid movement and affect mitochondrial function, thereby providing potential therapies against mitochondrial diseases.

In a study recently published in the journal Nature Biomedical Engineering, researchers from Kanazawa University use a method called “lasso-grafting” to design therapeutics with enhanced longevity and brain penetration.

Investigations in Japan have uncovered some molecular mechanisms behind mitochondrial dysfunction in chronic heart failure.

An Osaka Metropolitan University researcher has provided a review article regarding INSL3, a circulating hormone secreted from the gonads, in domestic animals, in comparison to rodents and humans. In this review article, the author describes his research group’s work that (1) developed immunoassays, for the first time, that can measure circulating INSL3 in multiple domestic mammals, including cattle, goats, sheep, pigs, horses, and dogs, (2) provided evidence in studies with bulls and bucks that INSL3 offers more reliable and stable values by a single blood collection than testosterone, a conventional and well-known testicular hormone, and (3) suggested that blood INSL3 concentrations would be a good biomarker for testicular and reproductive functions in normal and abnormal male domestic animals. These findings suggest that the INSL3 assay might simplify the evaluation of reproductive functions in various male domestic animals. In particular, the assay method may facilitate earlier selection of valuable male animals such as beef sire bulls (Image) with higher reproductive performance, contributing to reductions in the labor and costs required for sire production.

Researchers from Hokkaido University and Toppan have developed a method to detect build-up of amyloid β in the brain, a characteristic of Alzheimer’s disease, from biomarkers in blood samples.

Two new approaches could help scientists use existing sequencing technology to better-distinguish RNA changes that affect how their genetic code is read.

The skin’s top layer contains a diverse set of hundreds of lipid molecules called ceramides with varying chain lengths that play a vital role in its barrier function.

In a global first, scientists have demonstrated that molecular robots are able to accomplish cargo delivery by employing a strategy of swarming, achieving a transport efficiency five times greater than that of single robots.

Researchers at Kanazawa University elucidate in Frontiers in Molecular Biosciences how small biocontainers enclosed by membranes are involved in a disease called ATTRv amyloidosis.

The molecule trimethylamine N-oxide (TMAO) can be used to reversibly modulate the rigidity of microtubules, a key component of molecular machines and molecular robots.

A soft hydrogel could help scientists find treatments for drug-resistant cancer stem cells.

A research team led by the National Institute for Physiological Sciences and joined by Hokkaido University explored the role of pain neurons in the regulation of endotoxic death. They found that peptide named Reg3γ acts as a pain neuron-enriched brain-targeted hormone that protects the host from endotoxic death.

Simulations have led to the fabrication of a polymer-DNA gel that could be used in tissue regeneration and robotics.

Giants in History: Eminent Filipina scientist and educator Clara Lim-Sylianco (18 August 1925 – 23 July 2013) is remembered for her extensive research on mutagens – often-carcinogenic agents that permanently alter genetic materials such as DNA – antimutagens and bioorganic mechanisms.