Lifeboat Foundation

The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10¹² cells (95% CI 1.5–2.3 × 10¹²), weighing 1.2 kg (95% CI 0.8–1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their large size. The quantification of immune cells within the human body presented here can serve to understand the immune function better and facilitate quantitative modeling of this vital system.

In order to survive, organisms must control the pressure inside them, from the single-cell level to tissues and organs. Measuring these pressures in living cells and tissues in physiological conditions is a challenge.

In research that has its origin at UC Santa Barbara, scientists now at the Cluster of Excellence Physics of Life (PoL) at the Technical University in Dresden (TU Dresden), Germany, report in the journal Nature Communications a new technique to ‘visualize’ these pressures as organisms develop. These measurements can help understand how cells and tissues survive under pressure, and reveal how problems in regulating pressures lead to disease.

When molecules dissolved in water are separated into different compartments, water has the tendency to flow from one compartment to another to equilibrate their concentrations, a process known as osmosis. If some molecules cannot cross the membrane that separates them, a pressure imbalance—osmotic pressure—builds up between compartments.

Despite exciting advances in gene editing, the efficient delivery of genetic tools to extrahepatic tissues remains challenging. This holds particularly true for the skin, which poses a highly restrictive delivery barrier. In this study, we ran a head-to-head comparison between Cas9 mRNA or ribonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) to deliver gene editing tools into epidermal layers of human skin, aiming for in situ gene editing. We observed distinct LNP composition and cell-specific effects such as an extended presence of RNP in slow-cycling epithelial cells for up to 72 h. While obtaining similar gene editing rates using Cas9 RNP and mRNA with MC3-based LNPs (10–16%), mRNA-loaded LNPs proved to be more cytotoxic. Interestingly, ionizable lipids with a p K_a ∼ 7.1 yielded superior gene editing rates (55%–72%) in two-dimensional (2D) epithelial cells while no single guide RNA-dependent off-target effects were detectable. Unexpectedly, these high 2D editing efficacies did not translate to actual skin tissue where overall gene editing rates between 5%–12% were achieved after a single application and irrespective of the LNP composition. Finally, we successfully base-corrected a disease-causing mutation with an efficacy of ∼5% in autosomal recessive congenital ichthyosis patient cells, showcasing the potential of this strategy for the treatment of monogenic skin diseases. Taken together, this study demonstrates the feasibility of an in situ correction of disease-causing mutations in the skin that could provide effective treatment and potentially even a cure for rare, monogenic, and common skin diseases.

Link :- https://interestingengineering.com/science/blood-test-detect…tent=Nov03

Angelp/iStock.

Scientists are looking for specific DNA, cells, and molecules in our body which may be cancerous. They’ve made progress in finding some of these markers in the blood, but it’s still tricky to find them accurately and affordably for routine screening.

Harnessing and controlling light is vital for the development of technology, including energy harvesting, computation, communications, and biomedical sensing. Yet, in real-world scenarios, complexity in light’s behavior poses challenges for its efficient control. Physicist Andrea Alù likens the behavior of light in chaotic systems to the initial break shot in a game of billiards.

“In billiards, tiny variations in the way you launch the cue ball will lead to different patterns of the balls bouncing around the table,” said Alù, Einstein Professor of Physics at the CUNY Graduate Center, founding director of the Photonics Initiative at the CUNY Advanced Science Research Center and distinguished professor at CUNY.

“Light rays operate in a similar way in a chaotic cavity. It becomes difficult to model to predict what will happen because you could run an experiment many times with similar settings, and you’ll get a different response every time.”

In a paper published in the Journal of the International Society of Microbial Ecology, a UMBC team and colleagues from Washington University in St. Louis (WashU) describe the first observation of a satellite bacteriophage (a virus that infects bacterial cells) consistently attaching to a helper bacteriophage at its “neck”—where the capsid joins the tail of the virus.

In detailed electron microscopy images taken by Tagide deCarvalho, assistant director of the College of Natural and Mathematical Sciences core facilities and first author on the new paper, 80 percent (40 out of 50) helpers had a satellite bound at the neck. Some of those that did not had remnant satellite tendrils present at the neck. Erill, senior author on the paper, describes them as appearing like “bite marks.”

“When I saw it, I was like, ‘I can’t believe this,’” deCarvalho says. “No one has ever seen a bacteriophage—or any other virus—attach to another virus.”

Using nanoparticles administered directly into the cerebrospinal fluid (CSF), a research team has developed a treatment that may overcome significant challenges in treating a particularly deadly brain cancer.

The researchers, led by professors Mark Saltzman and Ranjit Bindra, administered to mice with medulloblastoma a treatment that features specially designed drug-carrying nanoparticles. The study, published in Science Translational Medicine, showed that mice who received this treatment lived significantly longer than mice in the control group.

Medulloblastoma, a brain cancer that predominantly affects children, often begins with a tumor deep inside the brain. The cancer is prone to spread along two protective membranes known as the leptomeninges throughout the central nervous system, particularly the surface of the brain and the CSF.

Identifying therapeutic targets for neurodegenerative conditions is often challenging due to the limited accessibility of reproducible, scalable in vitro cell models. Genome-level CRISPR screens are useful for these studies but performing screens that include the necessary replicates requires billions of cells. Human iPSC-derived cells can provide the needed scale, however, the complex process of directed differentiation is time-consuming, resource-intensive, and rarely feasible. Furthermore, delivering ribonucleases by transfection or transduction is inefficient in human iPSC-derived cells, especially delicate cell types like neurons. As a result, scientists often rely on immortalized cell lines, which do not accurately represent human biology or disease states, to run large-scale CRISPR screens.

In this GEN webinar, two experts will discuss solutions for running large-scale CRISPR screens to identify therapeutic targets for neurodegenerative diseases. They will present ioCRISPR-Ready Cells™: human iPSC-derived cells precision reprogrammed with opti-ox™, that constitutively express Cas9 nuclease, which are built for rapidly generating gene knockouts and CRISPR screens. During the webinar, you’ll learn about two peer-reviewed studies that performed large scale CRISPR knockout screens using opti-ox powered glutamatergic neurons with stable Cas9 expression. The first study demonstrates a loss-of-function genetic screen using a human druggable genome library. The second study investigated possible regulators of the RNA binding motif 3 protein, whose enhanced expression is highly neuroprotective both in vitro and in vivo.

In the summer of 2020, Keith Thomas dove into a swimming pool and became paralyzed from the chest down. He spent the next six months isolated in the hospital before joining a clinical medical trial that could make history for its use of groundbreaking Artificial Intelligence technology. Five chips were implanted into his brain which connects to a computer that can read his mind and send signals to parts of his body. Inside Edition Digital has more.