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Unexpected pathway for IgA antibody production may help improve vaccines

Scientists led by Stephanie Eisenbarth, MD, Ph.D., the Roy and Elaine Patterson Professor of Medicine and director of the Center for Human Immunobiology, have discovered how critical IgA antibodies are produced through unexpected cellular pathways, findings that may help inform the design of more effective vaccines to prevent infections, according to a recent study published in Immunity.

Immunoglobulin (Ig)A is an antibody that serves as the first line of defense for mucosal tissues that comprise the inner lining of organs in the respiratory system and digestive system. IgA antibodies play a role in humoral immunity, in which IgA and other antibodies produced by B-cells fight off and prevent the spread of infection.

However, inducing an IgA-specific immune response, particularly through vaccines, has remained unsuccessful, according to Eisenbarth.

HIE-ISOLDE: Ten years, ten highlights

The Isotope Separator On-Line facility (ISOLDE) directs a proton beam from the Proton Synchrotron Booster (PSB) onto specially developed thick targets, producing low-energy beams of radioactive nuclei—those with too many or too few neutrons to be stable. These beams can be further accelerated to energies of up to 10 MeV per nucleon using the HIE-ISOLDE linear accelerator, enabling a wide range of studies.

The HIE-ISOLDE beams are sent to three experimental stations: the Miniball array of high-purity germanium gamma-ray detectors, the ISOLDE solenoid spectrometer (ISS), which repurposed a former MRI magnet, and the scattering experimental chamber (SEC), used for a broad variety of physics experiments. Since its first experiment in October 2015, HIE-ISOLDE has been pushing back the boundaries of nuclear physics. To celebrate its 10th anniversary, we look back at 10 key achievements that have defined its first decade.

Switch Turns Brain’s Defenses Into Protectors Against Alzheimer’s

Specific immune cells in the brain may play a crucial role in preventing the onset of Alzheimer’s disease, according to a new study – a discovery that could lead to new therapies that try to coax cells into this protective state.

Earlier studies have shown that immune cells in the brain called microglia can effectively tackle the symptoms of Alzheimer’s, but also make them worse through inflammation.

Here, an international team of scientists took a detailed look at how microglia switch between those two helpful and harmful modes.

Leukemia mutations in nuclear droplets!

Leukemia starts when mutations in blood-forming cells disrupt the balance between growth and differentiation. Patients with entirely different genetic changes show strikingly similar patterns of gene activity and can respond to the same drugs. What invisible thread could make so many mutations behave the same way?

The authors looked into high-resolution microscope and saw something no one expected: leukemia cell nuclei shimmered with a dozen bright dots – tiny beacons missing from healthy cells.

Those dots weren’t random. They contained large amounts of mutant leukemia proteins and drew in many normal cell proteins to coordinate activation of the leukemia program. The dots were new nuclear compartments formed by phase separation, the same physical principle that describes why oil droplets form in water. The team named this new compartment, “coordinating bodies,” or C-bodies.

Inside the nucleus, these C-bodies act like miniature control rooms, pulling together the molecules that keep leukemia genes switched on. Like drops of oil collecting on the surface of soup, they appear when the cell’s molecular ingredients reach just the right balance.

Even more surprising, cells carrying entirely different leukemia mutations formed droplets with the same behavior. Although their chemistry differs, the resulting nuclear condensates perform the same function, using the same physical playbook.

A new quantitative assay confirmed it. These droplets are biophysically indistinguishable – like soups made from different ingredients that still simmer into the same consistency. No matter which mutation started the process, each leukemia formed the same kind of C-body.

The team confirmed the finding across human cell lines, mouse models and patient samples. When they tweaked the proteins so they could no longer form these droplets – or dissolved them with drugs, the leukemia cells stopped dividing and began to mature into healthy blood cells.

How statins harm muscles—and how to stop it

Statins have transformed heart health, saving millions of lives by lowering cholesterol and reducing the risk of heart attacks and strokes. But for many patients, these drugs come with a troubling downside: muscle pain, weakness and, in rare cases, severe muscle breakdown that can lead to kidney failure.

University of British Columbia researchers and their collaborators at the University of Wisconsin-Madison have now pinpointed the cause. Their findings, published last week in Nature Communications, could pave the way for a new generation of statins without these side effects.

New Breakthrough to Strengthen Bone Could Reverse Osteoporosis

A recent study points to a key bone-strengthening mechanism at work in the body, which could be targeted to treat the bone-weakening disease, osteoporosis.

Led by researchers from the University of Leipzig in Germany and Shandong University in China, the study identified the cell receptor GPR133 (also known as ADGRD1) as being crucial to bone density, via bone-building cells called osteoblasts.

Variations in the GPR133 gene had previously been linked to bone density, leading scientists to turn their attention to the protein it encoded.

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