Human brain organoids transplanted into rats could be used as an in vivo model for the study of neuropsychiatric diseases. Researchers at Stanford University managed to mature human organoid neurons in the somatosensory cortex of the animal's brain and incorporate them into its neural circuitry.The integration improved the morphological and physiological properties of the transplanted neurons. Compared to those of organoids in a Petri dish, human cells preserved their own identity, and they modified the rat's learned behavior through stimulation and reward experiments.
A germline change in a single nucleotide increased the risk by up to 6-fold of developing an isocitrate dehydrogenase (IDH) mutant low-grade glioma. The rs55705857 genotype could serve as a biomarker before surgery to identify an early glioma.
Researchers have gained new insights into both genetic and nongenetic factors affecting life span, and how they differ between males and females. Several genes were correlated with longevity, according to a study by the École Polytechnique Fédérale de Lausanne (EPFL). However, some did not affect life span until males reached a certain age. Early access to nutrients during growth also affected longevity, as they saw in their study of more than 3,000 mice and verified with human data. “This study is one of the biggest studies on mass longevity. We were looking for genetic determinants of longevity but there are non-genetic determinants affecting longevity,” the first author Maroun Bou Sleiman, researcher at EPFL, told Bioworld.
Arizona State University scientists have discovered an unprecedented pathway in a fungus to produce telomerase RNA (TER) from a protein-encoding messenger RNA (mRNA). Unlike in animals and other fungi, this fungal TER is transcribed by RNA polymerase III, lacks a protective 5′ cap and it is processed from the 3′-untranslated region of an mRNA transcript. This telomerase has two essential structural domains that keep it active. For now, scientists have only observed this process in the fungus Ustilago maydis, or Mexican truffle. “In animals, and even in Ascomycota, which is another fungal phylum, the telomerase RNA is transcribed by RNA polymerase II as an independent gene. This is the only case among all different kingdoms in eukaryotes that the telomerase RNA is processed from the mRNA molecule. It is a very unusual biogenesis pathway.” Julian Chen told BioWorld.
The 2022 Nobel Prize in chemistry was awarded to Carolyn Bertozzi of Stanford University, to Morten Meldal of the University of Copenhagen, and – for the second time – to Barry Sharpless of The Scripps Research Institute “for the development of click chemistry and bioorthogonal
chemistry.”
Click chemistry, the Nobel Committee’s Olof Ramström told reporters while announcing the prize, “is almost like it sounds – it’s all about linking different molecules.”
He likened click chemistry to a seatbelt buckle, whose interlocking parts can be attached to many different materials, linking them by snapping the two parts of the buckle together.
“The problem was to find good chemical buckles,” Ramström said – chemicals that “will easily snap together, and importantly, they won’t snap with anything else.”
Tumor mutational burden (TMB), a biomarker used to assess whether a patient will respond to immunotherapy, needs to be recalculated in order to be useful for patients of Asian or African descent. Scientists at the Dana-Farber Cancer Institute found a significant bias in the estimated TMB values affecting these populations and adjusted them for those patients.
The Nobel Prize in Physiology or Medicine 2022 was awarded to Svante Pääbo today "for his discoveries concerning the genomes of extinct hominins and human evolution." Pääbo, who is currently the director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues overcame extreme technical challenges to sequence the DNA of ancient hominids – because after tens of thousands of years, there is no such thing as aging well for DNA.
Cancer-associated fibroblasts (CAF) expressing the LRRC15 protein (leucine-rich repeat-containing protein 15) could be responsible for the suppression of antitumor immunity, according to a study using mouse models of pancreatic cancer. Scientists from Roche Holding AG subsidiary Genentech Inc. demonstrated in vivo that TGF-β type 2 receptor signaling in healthy universal fibroblasts produces cancer-associated LRRC15+ myofibroblasts.
A Mayo Clinic study demonstrated how the deficiency of the enzyme CDK12 or its regulation by cyclin K causes the expression of mutations related to resistance to endocrine therapy in prostate cancer. Prostate tumors with CDK12 deficiency are more aggressive, recurrent, produce metastases and are associated with castration-resistant prostate cancer (CRPC). CDK12 deficiency impairs DNA repair and increases genomic instability, causing an effect known as homologous recombination deficiency or BRCAness.
The coagulation factor XI (FXI) from the liver acts as an endocrine molecule in the heart, protecting it from heart failure. Scientists at the University of California, Los Angeles (UCLA) found that this communication between the two organs is mediated by the interaction between FXI and a heart protein. This interaction activated genes in cardiomyocytes that reduced inflammation, fibrosis and diastolic dysfunction, protecting the heart from a heart attack. That FXI participates in preventing heart failure suggests the possibility of using it as a therapeutic target.
