A new study from the University of Colorado Anschutz Medical Campus has upended decades of neuroscience dogma, revealing that dopamine, a neurotransmitter critical for movement, motivation, learning and mood, communicates in the brain with extraordinary precision, not broad diffusion as previously believed

The annual number of heat-related deaths in England and Wales is set to rise up to fiftyfold over the next 50 years because of climate change, finds new research by UCL and the London School of Hygiene & Tropical Medicine.

Using newly developed mouse models and a microglia replacement strategy, researchers show that bone marrow transplantation could be used as an effective therapy for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare and fatal neurodegenerative disease, according to a new study. ALSP is caused by mutations in CSF1R, a gene expressed primarily in microglia, which are the brain’s resident immune cells. Currently, there is no cure for ALSP and a lack of suitable animal models has greatly limited research on this disease. To address this, Jingying Wu and colleagues developed a pair of mouse models carrying human disease-linked CSF1R mutations. These models exhibited hallmark ALSP symptoms, including widespread microglial loss, brain calcification, myelin abnormalities, axonal damage, motor dysfunction, and cognitive decline. To evaluate therapeutic strategies, Wu et al. used a bone marrow transplantation-based strategy called Mr BMT, which combines traditional bone marrow transplantation (tBMT) with pharmacological depletion of “resident” microglia. The authors found that gene correction via Mr BMT effectively improves ALSP symptoms in mouse models. While tBMT alone yields minimal microglia replacement under normal conditions due to cellular competition, the inherent CSF1R deficiency in ALSP mimics pharmacological inhibition, allowing tBMT to achieve high replacement efficiency. Wu et al. further evaluated these findings in a clinical cohort of 8 ALSP patients and found that tBMT successfully corrected CSF1R mutations and halted disease progression over a two-year follow-up, suggesting that microglia replacement could be a promising therapeutic strategy for ASLP and potentially other microglia-driven neurological disorders. “Although microglial replacement strategies hold therapeutic potential, several key questions remain,” write Siling Du and Jonathan Kipnis in a related Perspective. “Future strategies must strike a balance between replacement efficiency, systemic toxicity, and the functional competence of engrafted cells.”

A new bionic prosthesis that directly links to the body’s muscles and nerves enables above-knee amputees to move with greater agility, precision, and sensory awareness than traditional devices, researchers report. Prosthetic limbs are widely used to help restore mobility for individuals living with limb amputations. However, their design and use have remained largely unchanged for more than a century. While modern prostheses can be tailored to an individual's needs, they still fall short in enabling a dynamic range of movement and in providing users with sensory feedback. Advancements in traditional lower-limb prostheses have focused on mechanical enhancements that improve repetitive walking, overlooking the full range and complexity of natural leg movement, especially when there is a need to change gait or balance. As a result, amputees often struggle with tasks like navigating uneven terrain or climbing stairs. Here, Tony Shu et al. present a tissue-integrated prosthetic knee that uses implanted neural interfaces to directly connect the device to the body’s physiology. According to Shu et al., the system – called the osseointegrated mechanoneural prosthesis (OMP) – combines three core innovations: direct neuromuscular control that allows fluid and adaptive movement; (2) a bone-anchored implant; and (3) agonist-antagonist myoneural interfaces (AMI) that replicate natural muscle interactions to reestablish a sense of limb position and movement. Clinical trials involved 2 above-knee amputees.  For each, the OMP system enabled superior mobility across diverse, real-world leg movements, such as terrain navigation and sit-to-stand transitions. While some limitations remain, Shu et al. suggest that greater prosthetic embodiment and function can be achieved through biologically integrated systems like the OMP, potentially yielding transformative gains in rehabilitation, mobility, and user experience following limb loss. In a related Perspective, Lee Fisher discusses the study in greater detail.

Researchers present BioEmu – a new AI model that rapidly and accurately predicts the full range of shapes a protein can adopt, offering a faster, cheaper alternative to traditional molecular simulations. Proteins and their complexes are essential to nearly every biological process and are central to advances in medicine and biotechnology. While recent breakthroughs in sequencing and deep learning have made it easier to determine a protein’s sequence and structure, understanding how proteins function by shifting between different shapes in response to other molecules remains a central challenge. These dynamic shape changes underpin key biological activities. Current molecular dynamics (MD) simulation techniques provide detailed insights into protein behavior but are slow, costly, and resource-intensive. While generative machine learning models offer a faster alternative, they have yet to match experimental data reliably. Here, Sarah Lewis and colleagues developed BioEmu – a deep learning-based biomolecular emulator designed to sample the wide range of shapes a protein can adopt at equilibrium rapidly and accurately. According to Lewis et al., BioEmu can sample thousands of realistic protein conformations in just one GPU-hour, making it orders of magnitude faster and cheaper than traditional MD approaches. This is accomplished by combining training data from AlphaFold structural predictions, large-scale MD simulations, and extensive experimental measurements of protein stability, which were refined by a novel property-prediction fine-tuning (PFFT) algorithm that enables it to match experimental observations even in the absence of structural data. However, despite its efficiency and accuracy within its training domain, BioEmu has limitations. For example, it does not natively model molecular dynamics or interactions with membranes, ligands, or varying environmental conditions like temperature or pH. Nonetheless, the authors argue that BioEmu illustrates how deep learning can amortize the high cost of simulation and experimentation, paving the way toward large-scale, data-driven prediction of protein function.

MIT researchers developed a new type of bionic knee that can help people with above-the-knee amputations walk faster, climb stairs, and avoid obstacles more easily than they could with a traditional prosthesis.