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The cerebral cortex forms early in development according to a series of heritable neurodevelopmental instructions. Despite deep evolutionary conservation of the cerebral cortex and its foundational six-layered architecture, significant variations in cortical size and folding can be found across mammals, including a disproportionate expansion of the prefrontal cortex in humans. Yet our mechanistic understanding of neurodevelopmental processes is derived overwhelmingly from rodent models, which fail to capture many human-enriched features of cortical development. With the advent of pluripotent stem cells and technologies for differentiating three-dimensional cultures of neural tissue in vitro, cerebral organoids have emerged as an experimental platform that recapitulates several hallmarks of human brain development.

A research team led by Professor Yuanliang ZHAI at the School of Biological Sciences, The University of Hong Kong (HKU) collaborating with Professor Ning GAO and Professor Qing LI from Peking University (PKU), as well as Professor Bik-Kwoon TYE from Cornell University, has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division. Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. Their findings have recently been published in Nature.

Background of the Research.

Our bodies are composed of many differentiated cell types. Genetic information is stored within our DNA which serves as a blueprint guiding the functions and development of our cells. However, not all parts of our DNA are active at all times. In fact, every cell type in our body contains the same DNA, but only specific portions are active, leading to distinct cellular functions. For example, identical twins share nearly identical genetic material but exhibit variations in physical characteristics, behaviours and disease susceptibility due to the influence of epigenetics. Epigenetics functions as a set of molecular switches that can turn genes on or off without altering the DNA sequence. These switches are influenced by various environmental factors, such as nutrition, stress, lifestyle, and environmental exposures.

For the first time, scientists have developed artificial nucleotides, the building blocks of DNA, with several additional properties in the laboratory. The DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory.

The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.

Artificial nucleic acids differ in structure from their originals.

Artificial human chromosomes that function within human cells hold the potential to revolutionize gene therapies, including treatments for certain cancers, and have numerous laboratory uses. However, significant technical challenges have impeded their progress.

Now a team led by researchers at the Perelman School of Medicine at the University of Pennsylvania has made a significant breakthrough in this field that effectively bypasses a common stumbling block.

In a study recently published in Science, the researchers explained how they devised an efficient technique for making HACs from single, long constructs of designer DNA. Prior methods for making HACs have been limited by the fact that the DNA constructs used to make them tend to join together—“multimerize”—in unpredictably long series and with unpredictable rearrangements. The new method allows HACs to be crafted more quickly and precisely, which, in turn, will directly speed up the rate at which DNA research can be done. In time, with an effective delivery system, this technique could lead to better-engineered cell therapies for diseases like cancer.

Gene therapy and correction can be used in almost all diseases and pathological conditions because of recent advancements, but some questions still have yet to be answered in this field of advancement. Based on the requirements and compatibility, gene therapy is divided into two parts: somatic gene therapy and germline gene therapy. If the transfer of DNA segments is done to cells that will affect the next generation, this is called somatic gene therapy. Somatic gene therapy is currently more efficient in research due to its less ethical issue and less complexity. The toughest task for curing diabetes with gene therapy is to have glucose responsiveness to insulin transgene expression. So studies were carried out to decrease obesity by gene therapy to decrease type 2 diabetes prevalence. Gene therapy using viral vectors remains risky and is still under scrutiny to ensure safety and efficacy during clinical trials.

Brain organoids are self-organizing tissue cultures grown from patient cell-derived induced pluripotent stem cells. They form tissue structures that resemble the brain in vivo in many ways. This makes brain organoids interesting for studying both normal brain development and for the development of neurological diseases. However, organoids have been poorly studied in terms of neuronal activity, as measured by electrical signals from the cells.

A team of scientists led by Dr. Thomas Rauen from the Max Planck Institute for Molecular Biomedicine in Münster, Germany, in collaboration with Dr. Peter Jones’ group at the NMI (Natural and Medical Sciences Institute at the University of Tübingen, Germany), has now developed a novel microelectrode array system (Mesh-MEA) that not only provides optimal growth conditions for human brain organoids, but also allows non-invasive electrophysiological measurements throughout the entire growth period. This opens up new perspectives for the study of various brain diseases and the development of new therapeutic approaches.

The study is published in the journal Biosensors and Bioelectronics.

Researchers at Rutgers and Emory University are gaining insights into how schizophrenia develops by studying the strongest-known genetic risk factor.

When a small portion of chromosome 3 is missing—known as 3q29 deletion syndrome—it increases the risk for schizophrenia by about 40-fold.

Researchers have now analyzed overlapping patterns of altered gene activity in two models of 3q29 deletion syndrome, including mice where the deletion has been engineered in using CRIPSR, and human brain organoids, or three-dimensional tissue cultures used to study disease. These two systems both exhibit impaired mitochondrial function. This dysfunction can cause energy shortfalls in the brain and result in psychiatric symptoms and disorders.

The tiny needle, called a nanopipette, allows researchers to take a biopsy of a living cell several times while it receives treatment without killing it — and could lead to new cancer cures.

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