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A new study from Aarhus University demonstrates that a protein known for treating cardiovascular diseases also affects a mechanism in the kidney that reabsorbs proteins. This finding could lead to new treatment options for chronic kidney disease.

The new study is published in Kidney International in an article titled, “Proprotein convertase subtilisin/kexin type 9 targets megalin in the kidney proximal tubule and aggravates proteinuria in nephrotic syndrome.”

“Proteinuria is a prominent feature of chronic kidney disease,” wrote the researchers. “Interventions that reduce proteinuria slow the progression of chronic kidney disease and the associated risk of cardiovascular disease. Here, we propose a mechanistic coupling between proteinuria and proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of cholesterol and a therapeutic target in cardiovascular disease.”

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Genomic analyses, such as next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR), require pure nucleic acids and accurate analyte concentrations to perform successful reactions. The purification process to access this genetic material uses methods that rely on detergents, mechanical disruption, and heat to disrupt the cellular structures of nuclei, ribosomes, bacteria, and viruses. Nucleic acid is then purified by performing a solvent extraction, alcohol precipitation, and salting-out.

Contaminants can copurify with nucleic acids

Isolation of nucleic acids (including various forms of DNA and RNA) may be needed from cell harvest, PCR, restriction enzyme digest, agarose gel, and other sources. Several avenues in nucleic acid extraction protocols inadvertently allow the co-precipitation of contaminants owing to the type of starting material or the chosen extraction method (Table 1). In some cases, changing the method or adding another purification step can mitigate or eliminate the copurification issue. However, when contamination remains an issue, it is important to learn as much as possible about the impurities that can denature enzymes, block templates, or otherwise lead to failed chemical reactions necessary for downstream applications.

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Recently, a research team led by Professor Hongzhe SUN from the Department of Chemistry, Faculty of Science, The University of Hong Kong, has published a paper in Nature Communications.

The researchers found that, chromium(III) (Cr(III)), a nutritional supplement, can enhance cells’ ability to metabolise glucose by regulating ATP synthase activity. This process improves mitochondrial deformation caused by high glucose levels and significantly boosts glucose metabolism in type 2 diabetic mice. To uncover the protein targets of Cr(III) and elucidate the molecular mechanism, the team has developed a fluorescent probe for detecting transient metal-protein interactions, achieving a high spatiotemporal resolution tracking of the Cr(III) proteome in HepG2 cells. This led to the identification of Cr(III)-binding proteins within cells. The team then revealed that Cr(III) replaces magnesium ions (Mg2+) in ATP synthase, reduces ATP synthase activity, and activates the downstream AMPK pathway, resulting in improved glucose metabolism. This study provides a novel concept for hypoglycaemic research.

“Although Cr(III) compounds have long been used as a nutritional supplement for diabetes treatment, weight loss and muscle development, its protein target and mechanism of action remain concealed for over half a century. We used a novel fluorescent probe, along with other chemical biology approaches, to uncover the long-standing scientific problem of the biological chemistry of Cr(III) and discovered that Cr(III) targets ATP synthase to regulate glucose,” commented Professor Sun.

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Pump-probe spectroscopy is a versatile technique to explore ultrafast dynamics on the femtosecond timescale. Here the authors report a pump-probe experiment and quantum modeling combined study revealing dynamics of collective polaritonic states that are formed between a molecular photoswitch and plasmonic nanoantennas.

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A new technique produces perovskite nanocrystals right where they’re needed, so the exceedingly delicate materials can be integrated into nanoscale.

The nanoscale refers to a length scale that is extremely small, typically on the order of nanometers (nm), which is one billionth of a meter. At this scale, materials and systems exhibit unique properties and behaviors that are different from those observed at larger length scales. The prefix “nano-” is derived from the Greek word “nanos,” which means “dwarf” or “very small.” Nanoscale phenomena are relevant to many fields, including materials science, chemistry, biology, and physics.

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Scientists at Leipzig University, in collaboration with colleagues at Vilnius University in Lithuania, have developed a new method to measure the smallest twists and torques of molecules within milliseconds. The method makes it possible to track the gene recognition of CRISPR-Cas protein complexes, also known as “genetic scissors”, in real time and with the highest resolution. With the data obtained, the recognition process can be accurately characterised and modelled to improve the precision of the genetic scissors. The results obtained by the team led by Professor Ralf Seidel and Dominik Kauert from the Faculty of Physics and Earth Sciences have now been published in the prestigious journal Nature Structural and Molecular Biology.

When bacteria are attacked by a virus, they can defend themselves with a mechanism that fends off the genetic material introduced by the intruder. The key is CRISPR-Cas protein complexes. It is only in the last decade that their function for adaptive immunity in microorganisms has been discovered and elucidated. With the help of an embedded RNA, the CRISPR complexes recognize a short sequence in the attacker’s DNA. The mechanism of sequence recognition by RNA has since been used to selectively switch off and modify genes in any organism. This discovery revolutionized genetic engineering and was already honored in 2020 with the Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer A. Doudna.

Occasionally, however, CRISPR complexes also react to gene segments that differ slightly from the sequence specified by the RNA. This leads to undesirable side effects in medical applications. “The causes of this are not yet well understood, as the process could not be observed directly until now,” says Dominik Kauert, who worked on the project as a PhD student.

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Join top executives in San Francisco on July 11–12 and learn how business leaders are getting ahead of the generative AI revolution. Learn More

The messaging software company Slack sees massive potential in generative AI and large language models, allowing more automation to improve workplace productivity and efficiency, said Steve Wood, Slack’s SVP, product management at the VentureBeat Transform 2023 conference on Tuesday.

“For me, I think automation, integration and AI are going to have a profound impact on how we experience software going forward,” Wood said in his panel discussion with Brian Evergreen, founder and CEO of the Profitable Good Company, a leadership advisory firm.

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(NewsNation) — Flying cars are coming sooner than you think.

Companies are looking to turn a decades-old concept, reminiscent of “The Jetsons,” into reality in just a few short years. Morgan Stanley predicts “the urban air mobility market could be worth more than $1 trillion by 2040,” according to a report from Business Insider.

Start-ups all over the world are working to get their flying cars up and running.

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A newly discovered pathway for formaldehyde oxidation could be an important general mechanism in tropospheric chemistry. In the new route, absorption of sunlight allows organic molecules to react with atmospheric oxygen in a reaction that had not previously been observed. According to the researchers behind the findings, many compounds in the atmosphere are likely to undergo this process, particularly at low altitudes.

‘We discovered a new way molecules in the atmosphere can react,’ says Scott Kable at the University of New South Wales in Australia. He explains that in this process – called photophysical oxidation (PPO) – a molecule absorbs sunlight and before it breaks into fragments, it reacts with atmospheric oxygen to produce free radicals. In the common photochemical oxidation (PCO) reaction, which has been known for several decades, the molecules are first split by sunlight and then the fragments react with oxygen. ‘Importantly, the free radical fragments formed in the first step of PCO can be measured separately in the atmosphere or a lab,’ points out Kable.

The team demonstrated the PPO mechanism using formaldehyde as a model system. Meredith Jordan from the University of Sydney mentions that many organic compounds released to the environment turn into formaldehyde on their way to being oxidised to carbon dioxide. ‘But most importantly for our research, the spectroscopy and photochemistry of this compound are very well understood,’ she says. ‘Without this detailed pre-existing knowledge, we wouldn’t have been able to find the evidence of PPO.’

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