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Recombinant BjADAT2 and BjADAT3 were individually expressed in E. coli and purified, and their enzyme activities were tested by in vitro tRNA deamination assay (Supplementary Fig. 4). Neither BjADAT2 nor BjADAT3 showed any A-to-I editing activity, but BjADAT2, in complex with BjADAT3, could perform A-to-I editing of amphioxus tRNAVal(AAC), and the apparent first-order deamination rate constant (kapp) of tRNA deamination was 0.0287 ± 0.00219 min−1. Because the optimal RNA substrate for ADAT2 was the adenosines on the anticodon loop structure of tRNA, we wondered if BjADAT2 could mediate DNA deamination in a structure-specific fashion. Thus, we compared the deamination efficiency of BjADAT2 on DNA hairpin structure substrates (i.e., hpDNA-A and hpDNA-C, containing a single adenosine or cytidine in the loop region, respectively) and single-stranded linear structure substrates (i.e., ssDNA-A and ssDNA-C, containing a single adenosine or cytidine in the substrates, respectively). As shown in Fig. 3, both adenosine deamination of hpDNA-A and cytidine deamination of hpDNA-C were clearly observed under BjADAT2 treatment, and the change of the hairpin substrates to linear substrates resulted in about a threefold decrease in adenosine-and cytidine-deamination ratios. By contrast, no product band was seen in the lane of hpDNA-G or hpDNA-T treated with BjADAT2. Moreover, the BjADAT2-E58A protein purified in the same way as BjADAT2 showed no deamination activity (Supplementary Fig. 5f, g), ruling out the possibility that the observed deamination activity of BjADAT2 arose from a contaminant in the recombinant protein samples. In addition, BjADAT2-mediated adenosine-and cytidine deamination was inhibited by deoxycoformycin (DCF), an adenosine deaminase specific inhibitor, or tetrahydrouridine (THU), a cytidine deaminase specific inhibitor, or 1,10-o-phenanthroline, a zinc chelator. These indicated that BjADAT2 deaminated adenosine and cytidine in a zinc-dependent manner.

The kapp of BjADAT2-induced hpDNA-A deamination (0.00206 ± 0.00019 min−1) was comparable with that of ABE7.10-induced DNA adenosine deamination (0.0010 ± 0.00030 min−1)22. We compared the kinetics of BjADAT2-induced DNA deamination of the hairpin substrates and the linear substrates. The kapp was sixfold higher for the hpDNA-A substrate than for the ssDNA-A substrate (0.00032 ± 0.00004 min−1). Similarly, the kapp was 24-fold higher for hpDNA-C (0.00801 ± 0.00037 min−1) than for ssDNA-C (0.00033 ± 0.000026 min−1) (Fig. 3e). These data together indicated that BjADAT2 preferentially deaminates adenosines and cytidines in the hairpin loop of substrates.

It was known that ADAT3, as a non-catalytic subunit, served a structural role in the adenosine deamination of tRNA10,23. To date, only trypanosome ADAT2 was shown to be able to deaminate cytosines of DNA in the presence of ADAT3 in vitro6, but the specific role of the ADAT3 subunit in this DNA editing reaction was unclear. We demonstrated here that BjADAT3, though lacking catalytic function, could enhance the deamination activity of BjADAT2 toward hairpin structure substrates, including hpDNA-A and hpDNA-C (Fig. 3a, b). This was also supported by the results of kinetic analysis (Fig. 3e), which showed that the kapp of hpDNA-A deamination of BjADAT2/BjADAT3 complex (0.01092 ± 0.00062 min−1) was 5.3-fold higher than that of BjADAT2 alone, and the kapp of hpDNA-C deamination by the complex (0.01066 ± 0.00083 min−1) 1.3-fold higher than that of BjADAT2 alone. On the contrary, the kapp of ssDNA-A deamination of BjADAT2/BjADAT3 complex (0.00016 ± 0.

T cells are immune cells that fight off disease. The most common type of T cell, known as conventional T cells, maintains different functions, including activation of other T cells and killing pathogens. However, there is a less common type of T cell known as unconventional T cells. These cells regulate conventional T cells and often suppress conventional T cell function. How these cells develop and protect the body from infection and disease is unclear. Dr. Dan Pellicci and colleagues from Murdoch Children’s Research Institute and Federation University Australia reported on unconventional T cell development and their role in the immune system in a recent Science Immunology paper.

The researchers found that these unconventional T cells elicit an immune response. The discovery of an anti-pathogen role in these T cells has been unknown previously. Scientists can target these cells to prevent cancer and highly infectious diseases by understanding their role in immunity.

Dr. Pellicci and colleagues gathered samples from the Melbourne Children’s Heart Tissue Bank, where samples from children sixteen years old or younger who had heart surgery were kept. The researchers looked at the T cells from the thymus, a gland that further develops or matures T cells. After the T cells exit the thymus, they are ready to activate and target or kill infecting pathogens. Through T cell isolation, Dr. Pellicci and colleagues were able to determine the role of Unconventional T cells.

To understand the main determinants behind worldwide antibiotic resistance dynamics, scientists from the Institut Pasteur, Inserm, Université de Versailles Saint-Quentin-en-Yvelines and Université Paris-Saclay developed a statistical model based on a large-scale spatial-temporal analysis. Using the ATLAS antimicrobial resistance surveillance database, the model revealed significant differences in trends and associated factors depending on bacterial species and resistance to certain antibiotics.

For example, countries with high quality health systems were associated with low levels of among all the investigated, while high temperatures were associated with high levels of antibiotic in Enterobacteriaceae. Surprisingly, national antibiotic consumption levels were not correlated with resistance for the majority of the bacteria tested. The results suggest that antibiotic resistance control measures need to be adapted to the local context and to targeted bacteria-antibiotic combinations.

The results of the study were published in the journal The Lancet Planetary Health.

Ovarian cancer is the fourth-leading cause of cancer mortality among women and is characterized by late detection, extensive metastasis and poor prognosis.

One reason that treating this disease has been so challenging is that tumors often become resistant to chemotherapies, and generally respond poorly to immunotherapies.

While much of the research on overcoming resistance and efforts to develop new therapies have focused on the , it has often ignored the many other within the . Indeed, cells have the ability to reprogram the cells around them to nurture the tumor and help evade the patient’s .

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“The transplant was a success: The operation went smoothly, the new liver started working right away, and the patient recovered without any surgical complications.”

Doctors in the United States have successfully performed a robotic liver transplant procedure, marking a significant advancement in the field of medical surgery.

In May 2023, the inaugural transplantation of this kind was carried out by a surgical team from Washington University School of Medicine in St. Louis. The significant procedure occurred at Barnes-Jewish Hospital.

The story of a young science-writer at Memorial Sloan-Kettering Cancer Center, who risked everything by blowing the whistle on a massive cover-up involving a promising cancer therapy.

Cover-Up Of Promising Cancer Treatment (2014)
Director: Eric Merola.
Writers: Eric Merola.
Stars: Robert Good, Ben Moss, Martha Moss.
Genre: Documentary, Biography, Drama.
Country: United States.
Language: English.
Also Known As: Second Opinion — The Lie of America’s War on Cancer.
Release Date: March 1, 2014 (United States)

Reviews:
“This movie hits home since my dad died of cancer when I was 13 and it upsets me tremendously to think that our overall health care system has been corrupted due to the profit system. The Hippocratic oath seems to be more focused on maintaining the status quo of profit versus curing medical problems.

The Movie: An insider’s account from the 70’s at a well known NYC cancer research hospital exposing the truth (using the hospital’s own records) behind how the profit system has corrupted the search for finding a “cure” for cancer. A promising treatment was swept under the rug and the scientist who found it (co-founder of chemotherapy) was forced to lie about his treatment. The treatment was not the “cure”, but it worked remarkably well and very cheap. The problem was it was “very cheap”. Even though the movie is centered around 1 character and it’s almost entirely a narrative, the topic and the evidence is so damning, it’s exciting. It’s a knock-out punch guilty as charged for the hospital. Definitely recommended to all.“
- written by “ben-98–143433″ on IMDb.com.

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In a groundbreaking study, researchers have unlocked a new frontier in the fight against aging and age-related diseases. The study, conducted by a team of scientists at Harvard Medical School, has published the first chemical approach to reprogram cells to a younger state. Previously, this was only achievable using a powerful gene therapy.

The team’s findings build upon the discovery that the expression of specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs). This Nobel Prize-winning discovery raised the question of whether it might be possible to reverse cellular aging without causing cells to become too young and turn cancerous.

Reference:

Following the success of its first experiment.com campaign, which was raising money to identify therapeutics that reduce senescent cell accumulation and extend healthspan, the SENS Research Foundation has announced the next funding project.

Last month, we covered the fundraiser for Dr Abdelhadi Rebbaa’s research into the discovery and testing of novel senolytic molecules, which would back into his discovery of potential anti-senescence therapeutics. SRF has confirmed that this campaign is now fully funded.

Now SENS Research Foundation has launched its second experiment.com campaign for Dr Amutha Boominathan’s project Finding a cure for mitochondrial DNA diseases through COX2 variations to restore cell function, hoping to raise $8,000 over 45 days, with the campaign coming to an end next month, on 30th August. Dr Boominathan is head of the MitoSENS program at SENS Research Foundation.