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Category: genetics – Page 164

Genetic Modification of Brain Organoids

Brain organoids have become increasingly used systems allowing 3D-modeling of human brain development, evolution, and disease. To be able to make full use of these modeling systems, researchers have developed a growing toolkit of genetic modification techniques. These techniques can be applied to mature brain organoids or to the preceding embryoid bodies (EBs) and founding cells. This review will describe techniques used for transient and stable genetic modification of brain organoids and discuss their current use and respective advantages and disadvantages. Transient approaches include adeno-associated virus (AAV) and electroporation-based techniques, whereas stable genetic modification approaches make use of lentivirus (including viral stamping), transposon and CRISPR/Cas9 systems. Finally, an outlook as to likely future developments and applications regarding genetic modifications of brain organoids will be presented.

The development of brain organoids (Kadoshima et al., 2013; Lancaster et al., 2013) has opened up new ways to study brain development and evolution as well as neurodevelopmental disorders. Brain organoids are multicellular 3D structures that mimic certain aspects of the cytoarchitecture and cell-type composition of certain brain regions over a particular developmental time window (Heide et al., 2018). These structures are generated by differentiation of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) into embryoid bodies followed by, or combined, with neural induction (Kadoshima et al., 2013; Lancaster et al., 2013). In principle, two different classes of brain organoid protocols can be distinguished, namely: (i) the self-patterning protocols which produce whole-brain organoids; and (ii) the pre-patterning protocols which produce brain region-specific organoids (Heide et al., 2018).

The new science of optimism and longevity

Results of DNA studies also seem to confirm the idea that optimism is an effective tool for slowing down cellular aging, of which telomere shortening is a biomarker. (Telomeres are the protective caps at the end of our chromosomes.) This research is still in progress, but the early results are informative. In 2012, Elizabeth Blackburn, who three years earlier shared a Nobel Prize for her work in discovering the enzyme that replenishes the telomere, and Elissa Epel at the University of California at San Francisco, in collaboration with other institutions, identified a correlation between pessimism and accelerated telomere shortening in a group of postmenopausal women. A pessimistic attitude, they found, may indeed be associated with shorter telomeres. Studies are moving toward larger sample sizes, but it already seems apparent that optimism and pessimism play a significant role in our health as well as in the rate of cellular senescence. More recently, in 2021, Harvard University scientists, in collaboration with Boston University and the Ospedale Maggiore in Milan, Italy, observed the telomeres of 490 elderly men in the Normative Health Study on U.S. veterans. Subjects with strongly pessimistic attitudes were associated with shorter telomeres — a further encouraging finding in the study of those mechanisms that make optimism and pessimism biologically relevant.

Optimism is thought to be genetically determined for only 25 percent of the population. For the rest, it’s the result of our social relationships or deliberate efforts to learn more positive thinking. In an interview with Jane Brody for the New York Times, Rozanski explained that “our way of thinking is habitual, unaware, so the first step is to learn to control ourselves when negative thoughts assail us and commit ourselves to change the way we look at things. We must recognize that our way of thinking is not necessarily the only way of looking at a situation. This thought alone can lower the toxic effect of negativity.” For Rozanski, optimism, like a muscle, can be trained to become stronger through positivity and gratitude, in order to replace an irrational negative thought with a positive and more reasonable one.

While the exact mechanisms remain under investigation, a growing body of research suggests that optimism plays a significant role in promoting both physical and mental well-being. Cultivating a positive outlook, then, can be a powerful tool for fostering resilience, managing stress, and potentially even enhancing longevity. By adopting practices that nurture optimism, we can empower ourselves to navigate life’s challenges with greater strength and live healthier, happier lives.

Patient Walking Around Hospital After Transplant of Gene-Hacked Pig Kidney

In a world’s first, surgeons at the Massachusetts General Hospital in Boston have transplanted a kidney from a gene-hacked pig into a living 62-year-old man.

Researchers are hoping the procedure could reduce our reliance on both hard-to-come-by human donor kidneys, and the expensive dialysis machines that treat kidney disease and failure.

Fortunately, the surgeons’ efforts appear to have paid off — at least for now. The pig kidney started producing urine not long after the surgery last weekend, the New York Times reports. The patient’s condition also continues to improve, according to the report.

Astrocytes Remember: A New Layer of Immune Memory Uncovered

Researchers have made a pioneering discovery that astrocytes, cells within the central nervous system traditionally not associated with immune functions, are capable of developing what’s being called an “immune memory.” This capability…

Summary: Astrocytes, traditionally non-immune cells within the central nervous system, possess the ability to develop an immune memory, responding more vigorously to subsequent immune challenges. This groundbreaking study reveals that through an epigenetic mechanism involving the enzymes p300 and ATP-citrate lyase (ACLY), astrocytes enhance their pro-inflammatory responses, a trait similar to the immune memory seen in adaptive immunity.

The findings, which have been observed in both mouse models of multiple sclerosis (MS) and human cell samples, suggest that astrocyte immune memory may play a significant role in chronic neurological disorders, offering new insights into disease pathology and potential therapeutic targets to mitigate CNS inflammation.

Spatial study of lung cancer reveals immune markers of response to immunotherapy

Through Broad’s Scientists in the Classroom program, Broad researchers visit every 8th grade classroom in Cambridge each year to talk about genetics and evolution.

Every summer, 18 high school students spend six weeks at Broad working side-by-side with mentors on cutting-edge research.

In November 2022, Broad’s Genomics Platform sequenced its 500,000th whole human genome, a mere four years after sequencing its 100,000th.

Can epigenetic reprogramming reverse aging?

The field of aging research has made significant progress over the last three decades, reaching a stage where we now understand the underlying mechanisms of the aging process. Moreover, the knowledge has broadened to include techniques that quantify aging, decelerate its process, as well as sometimes reverse aging.

To date, twelve hallmarks of aging have been identified; these include reduced mitochondrial function, loss of stem cells, increased cellular senescence, telomere shortening, and impaired protein and energy homeostasis. Biomarkers of aging help to understand age-related changes, track the physiological aging process and predict age-related diseases [1].

Longevity. Technology: Biological information is stored in two main ways, the genomes consisting of nucleic acids, and the epigenome, consisting of chemical modifications to the DNA as well as histone proteins. However, biological information can be lost over time as well as disrupted due to cell damage. How can this loss be overcome? In the 1940s, American mathematician and communications engineer Claude Shannon came up with a neat solution to prevent the loss of information in communications, introducing an ‘observer’ that would help to ensure that the original information survives and is transmitted [2]. Can these ideas be applied to aging?

Essential tremor: MedlinePlus Genetics

Essential tremor is a movement disorder that causes involuntary, rhythmic shaking (tremor), especially in the hands. It is distinguished from tremor that results from other disorders or known causes, such as Parkinson’s disease or head trauma. Essential tremor usually occurs alone, without other neurological signs or symptoms. However, some experts think that essential tremor can include additional features, such as mild balance problems.

Essential tremor usually occurs with movements and can occur during many different types of activities, such as eating, drinking, or writing. Essential tremor can also occur when the muscles are opposing gravity, such as when the hands are extended. It is usually not evident at rest.

In addition to the hands and arms, muscles of the trunk, face, head, and neck may also exhibit tremor in this disorder; the legs and feet are less often involved. Head tremor may appear as a “yes-yes” or “no-no” movement while the affected individual is seated or standing. In some people with essential tremor, the tremor may affect the voice (vocal tremor).

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