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In vivo mapping of striatal neurodegeneration in Huntington's disease with Soma and Neurite Density Imaging
Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by progressive cognitive and motor decline driven by basal ganglia (BG) atrophy. Clinical trials of novel disease-modifying therapies are ongoing, creating a need for sensitive non-invasive imaging biomarkers. Soma and Neurite Density Imaging (SANDI) is a multi-shell diffusion MRI model that estimates intracellular signal fractions from sphere-shaped soma and shows promise as a marker of neurodegeneration. The...
Amenable Mortality Among Older Brazilians: Evidence From the Brazilian Longitudinal Study of Aging (ELSI-Brazil)
BackgroundAmenable mortality, deaths preventable through timely and effective healthcare, is a widely used indicator of health system performance, yet evidence is lacking on its individual-level determinants in Brazil.MethodsWe used data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a representative cohort of adults aged 50 and older. Deaths were classified as amenable using both the Brazilian and the Pan American Health Organization's definitions. Semi-parametric competing risks...
Why scientists should lead the shift away from AI mega data centres
A ‘super’ El Niño could transform the Amazon. Is the world’s biggest rainforest doomed?
Solar eclipse offers rare chance to solve Sun’s magnetic-field mysteries
When the best decision is no decision: the rise of randomization in grant funding
Seven tips for a graceful lab exit
Will AI make our dreams all look the same?
How escalating costs scuppered a radio telescope at Joddrell Bank
AI tools speed up analysis, but scientific truths must be grounded in reality
The case for responsible scientific activism
Funders should look beyond strict age criteria
Author Correction: Uncovering the role of LINE-1 in the evolution of lung adenocarcinoma
New GLP-1 pill delivers up to 12% weight loss in 36 weeks
An experimental GLP-1 pill helped people with obesity or overweight lose as much as 12.1% of their body weight in just 36 weeks. Unlike injectable drugs such as Wegovy and Ozempic, aleniglipron is a small molecule that can be taken once daily with or without food and could potentially be produced more easily at scale.
1 in 5 people may carry this hidden genetic heart risk
Very high levels of the inherited cholesterol-related particle Lp(a) were linked to a greater risk of major cardiovascular events, particularly stroke and cardiovascular death, in a study of more than 20,000 people. Since elevated Lp(a) often flies completely under the radar, a simple blood test could uncover hidden heart risk that standard cholesterol testing may miss.
How Europe can prevent a repeat of this year’s devastating wildfires
As climate change heats up the continent, experts say countries must shift focus toward preventing fires, rather than just suppressing them
The structural basis for LRRK2's activation and autoinhibition
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson's disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic PD, making LRRK2 a major actionable therapeutic target. LRRK2 is a 286-kDa multidomain enzyme containing a Ras-like GTPase (ROC) and a kinase domain. Using cryo-electron microscopy (cryo-EM), biochemical reconstitution, and cell-based assays, we show that the ROC GTPase governs switching between...
Chemical tools for inhibition and activity-based profiling of glucocerebrosidase in vitro and in vivo
Deficiencies in glucocerebrosidase (GCase) are associated with Parkinson's disease (PD). The mechanistic basis of this association is being intensively investigated, and new treatments are being developed aiming to boost brain GCase activity in patients. Despite the importance of GCase in PD, studies are hampered by the continued reliance on weak and non-selective inhibitors like conduritol B epoxide. Here, we report easily prepared and selective irreversible inhibitors and complementary...
Divergent somatic mutation patterns among human cerebellar neuron types
Neurons accumulate somatic mutations with age, but how mutation processes vary among neuronal types remains unclear. Characterizing this variability may elucidate the role of genome integrity in brain function and disease and reveal determinants of mutation rates and patterns. Using high-fidelity duplex DNA sequencing, we profiled somatic mutations across the lifespan in human cerebellar Purkinje and granule neurons, which differ markedly in size and physiology. Surprisingly, they exhibited...
Dioscin extends lifespan and ameliorates aging associated phenotypes in association with the endoplasmic reticulum unfolded protein response
Dioscin, a naturally occurring steroidal saponin isolated from various kinds of herbs with pleiotropic pharmacological properties, remains mechanistically undefined regarding its mammalian aging modulation. This study discovered that dioscin extended the lifespan of Caenorhabditis elegans. Concurrently, dioscin improved the motor function of C. elegans and reduced age pigment accumulation, while having no effect on the reproductive performance of the C. elegans. By pathway screening, we...