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The stop signal stepping task: how action cancellation commands disrupt step initiation in young and healthy older adults

2 weeks ago
Action cancellation - the ability to rapidly cancel an initiated movement in response to unexpected events - has been extensively studied in the upper limb using the stop signal task (SST). During gait, action cancellation is critical to stop and modify steps to avoid unexpected hazards and prevent falls. By adapting the SST to step initiation, this study investigated how the anticipatory postural adjustment (APA) and foot-lift phases of forward stepping were influenced by action-cancellation...
Rebecca Healey

Elucidation of a potent pro-resolving mediator of inflammation resolution via human neutrophil-vascular endothelial cell interactions

2 weeks ago
The acute inflammatory response is a highly coordinated programmed sequence that enables neutrophils to transmigrate from venules into tissues. Ideally self-limited, the active resolution phase produces specialized molecules that stimulate resolution and prevent collateral tissue damage from excessive neutrophil infiltration. The superfamily of pro-resolving molecules is termed specialized pro-resolving mediators including the essential polyunsaturated fatty acid-derived lipoxins, resolvins,...
Robert Nshimiyimana

The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models

2 weeks ago
Transglutaminase 2 (TG2) is implicated in synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies, as it promotes α-Synuclein (α-Syn) aggregation in vitro, and evidence for its activity is detected in Lewy bodies in human postmortem brains. Additionally, TG2 overexpression exacerbates α-Syn toxicity in double transgenic mice, while TG2 deletion mitigates the phenotype of α-Syn transgenic mice. Considering that TG2 is a multidomain and multifunctional protein, the...
Kambiz Hassanzadeh

Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models

2 weeks ago
Mitochondrial transplantation holds significant potential for the treatment of mitochondrial diseases. However, how to efficiently deliver exogenous mitochondria to somatic cells or tissues remains unresolved. We present a mitochondrial transplantation approach to deliver mitochondria into the cells and tissues of mice and monkeys with high efficiency, based on encapsulating mitochondria with vesicles derived from the plasma membrane of erythrocytes. Treatment with encapsulated mitochondria...
Shiwei Du

Tau phosphorylation homeostasis: Mechanisms, targets, and therapeutic implications in Alzheimer's disease

2 weeks ago
Neurofibrillary tangles, composed of excessively phosphorylated tau, are a core neuropathological hallmark of Alzheimer's disease (AD). However, therapeutic strategies aimed at directly clearing neurofibrillary tangles have demonstrated limited clinical efficacy, shifting the research focus towards the fundamental underlying mechanism- the dysregulation of tau phosphorylation. Evidence indicates that tau physiological phosphorylation is indispensable for microtubule stability and normal neuronal...
Shengwen Lu

From stiffness to automaticity: visuomotor training alters postural control strategies in older adults

2 weeks ago
Aging is often associated with a maladaptive "stiffness" strategy of postural control, which limits adaptability and increases fall risk. Complex visuomotor training (e.g., juggling) may counteract this decline, but the relationship between biomechanical reorganization and cognitive cost reduction remains unclear. We hypothesized that juggling would induce a shift from stiffness to "active monitoring" and reduce the dual-task cost. This exploratory secondary analysis of a randomized crossover...
Jakub Malik

Photoreceptor control of Platynereis growth and lifespan via evolutionarily conserved molecular pathways

2 weeks ago
Natural light is severely affected by human impact on Earth, yet little is known about the roles light receptors have outside vision and rhythmic processes, despite their tremendously wide abundance. Here we show that loss-of-function of the light-receptive cryptochrome (l-cry) in marine bristleworms significantly increases lifespan and adult size, similarly to wild-types reared in constant darkness. Quantitative transcriptomics revealed hormonal players crucial for invertebrate and vertebrate...
Gabriele Andreatta

Rescuing specific memories by rejuvenating engram cells

2 weeks ago
Partial cellular reprogramming can modulate aging-associated decline across multiple tissues. However, whether targeting memory-encoding ensembles within specific brain regions is sufficient to restore cognitive function has remained unknown. In this issue of Neuron, Berdugo-Vega et al. show that engram rejuvenation rescues memory deficits and restores epigenetic-transcriptional features and intrinsic excitability.
Louisa G Zielke

Divergent white matter metabolic signature patterns indicate impending cognitive decline in aging and dementia

2 weeks ago
White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition,...
Wen Zhang

Olfactory cleft biopsy analysis of Alzheimer's disease pathobiology across disease stages

2 weeks ago
Alzheimer's Disease (AD) is a neurodegenerative condition affecting millions worldwide. Defining early pathobiological events remains challenging, in part due to inaccessibility of neural tissue. Because olfactory neurons are accessible, and olfactory loss is prevalent in AD, we evaluated olfactory brush biopsies from controls, individuals with cerebrospinal fluid (CSF) biomarker-confirmed AD, and cognitively typical individuals whose positive CSF biomarkers signal a pre-clinical AD stage. Here...
Vincent M D'Anniballe

Divergent white matter metabolic signature patterns indicate impending cognitive decline in aging and dementia

2 weeks ago
White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition,...
Wen Zhang

The puzzling duality of mesenchymal stem cells and adipocytes in bone marrow and ageing

2 weeks ago
Mesenchymal stem cells (MSCs) in bone marrow (BM) play a role in the development of BM adipose tissue (BMAT). Here, we propose ways to restock the BM-MSC niche to meet the needs of BMAT in ageing, including the activation of pluripotent precursor cells, the breakdown of BM-MSC grafts and the mobilisation of extramedullary MSCs. It can be exploited to understand the BM-MSC-adipocyte axis in ageing and better target anti-ageing interventions.
Blanca Gonzalez-Garcia