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Triplex Origami Method Suggests Potential Implications for Gene Therapy

With triplex origami, scientists can achieve a level of artificial control over the shape of double-stranded DNA that was previously unimaginable, thereby opening new avenues of exploration, according to the Aarhus University researchers. It has recently been suggested that triplex formation plays a role in the natural compaction of genetic DNA and the current study may offer insight into this fundamental biological process.

Potential in gene therapy and beyond

The work also demonstrates that the Hoogsteen-mediated triplex formation shields the DNA against enzymatic degradation. Thus, the ability to compact and protect DNA with the triplex origami method may have large implications for gene therapy, wherein diseased cells are repaired by encoding a function that they are missing into a deliverable piece of double-stranded DNA.

Study presents new database linking RNA editing and blood cell differentiation

The process of converting DNA to proteins through an RNA is far from straightforward. Of the several types of RNA involved in the process of protein synthesis, a few may be edited mid-way. In mammals, RNA editing mostly involves converting adenosine (A) to inosine (I) through deamination, which can result in a wide range of effects. For example, A-to-I conversion can regulate gene expression in different ways and significantly alter the final synthesized protein.

While RNA editing is an essential biological process, it is also a key underlying mechanism in some diseases, including cancer. Thus, scientists have created large-scale databases documenting RNA editing sites in various human tissues. These databases serve as useful platforms for identifying potential diagnostic or therapeutic targets from the RNA editome, which encompasses all edited RNA molecules in a given cell or tissue.

Unfortunately, there are currently no databases for RNA editing in hematopoietic cells. The hematopoietic cells are unique in that they can develop into all types of cells including , , and platelets.

DNA element with a murky past is borrowing cell’s repair machinery

Like its viral cousins, a somewhat parasitic DNA sequence called a retrotransposon has been found borrowing the cell’s own machinery to achieve its goals.

In a new work appearing online Wednesday in the journal Nature, a Duke University team has determined that retrotransposons hijack a little-known piece of the cell’s DNA repair function to close themselves into a ring-like shape and then create a matching double strand.

The finding upends 40 years of conventional wisdom saying these rings were just a useless by-product of bad gene copying. It may also offer new insights into cancer, viral infections and immune responses.

Potentially Unlimited Supply — Scientists Grow Meat From Immortal Stem Cells

For cellular agriculture—a technique that grows meat in bioreactors—to successfully feed millions, numerous technological hurdles must be conquered. The production of muscle cells from sources such as chicken, fish, cows, and more will need to increase to the point where millions of metric tons are yielded annually.

Researchers at the Tufts University Center for Cellular Agriculture (TUCCA) have made strides toward this objective by developing immortalized bovine muscle stem cells (iBSCs). These cells possess a rapid growth rate and the ability to divide hundreds of times, potentially even indefinitely, furthering the potential for large-scale meat production.

This advance, described in the journal ACS Synthetic Biology, means that researchers and companies around the globe can have access to and develop new products without having to source cells repeatedly from farm animal biopsies.

Role of AI in Spine Injuries in Sports

Sports teams spend millions of dollars on their players’ health and fitness and any injuries can be detrimental to their players’ careers. Artificial intelligence (AI) has the potential to significantly change the way that sports spine injuries are diagnosed, treated, and managed. Tools such as Spindle and SpindleX are making it easy to prevent long-term injuries or spinal issues by detecting even the minutest variations in time. However, AI has just begun its foray into the field of healthcare and more importantly radiology or spine imaging.

With AI-related radiology imaging, it is becoming easier to prevent and cure injuries we didn’t even know existed. AI-assisted reports are helping physicians and surgeons take better and more accurate decisions and treatment plans, saving millions of dollars in the healthcare industry. Here are a few examples of how AI is improving the treatment of sports-related spine injuries:

The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56–86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy.

6 Helpful Ways To Boost Immune Health

The innate immune system is able to identify foreign invaders and immediately respond to them. This system is important in order to protect the body from harmful substances.

The response to an infection triggers the arrival of cells called neutrophils, which attack the infection, followed by macrophages that attack bacteria and viruses.

Macrophages release cytokines in order to communicate with other cells when they encounter an enemy. Cytokines are small proteins that carry information. The immune system is activated by cytokines, which give the immune cells direction to fight.

Protein That Helps Treat Cardiovascular Disease May Also Aid in Kidney Disease

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.”

Failed NGS or qPCR? Spectrophotometry can tell why

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.

New insights into glucose metabolism: targeting ATP synthase with chromium (III) nutritional supplement for improved blood sugar control

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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