Nat Rev Neurol

Genome-wide association studies (GWAS) have uncovered over two dozen candidate Alzheimer disease susceptibility genes; however, the results of these studies showed limited overlap. Two independently performed GWAS involving cohorts from europe and the US have now identified three additional putative Alzheimer disease genes that show modest but remarkably consistent effects across data sets

Observation of subdiffusion of a disordered interacting system

We study the transport dynamics of matter-waves in the presence of disorder and nonlinearity. An atomic Bose-Einstein condensate that is localized in a quasiperiodic lattice in the absence of atom-atom interaction shows instead a slow expansion with a subdiffusive behavior when a controlled repulsive interaction is added. The measured features of the subdiffusion are compared to numerical simulations and a heuristic model. The observations confirm the nature of subdiffusion as interaction-assisted hopping between localized states and highlight a role of the spatial correlation of the disorder.Comment: 8 pages, to be published on Physical Review Letter

Relationships among classifications of ayurvedic medicine diagnostics for imbalances and western measures of psychological states: An exploratory study.

BackgroundAccording to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest.ObjectiveThis study examined relationships among imbalances in the doshas (termed Vikruti) reported via questionnaire and Western measures of psychological states.Materials and methodsStudy participants were 101 women (n = 81) and men (n = 20), mean age 53.9 years (SD = 11.7; range 32-80). Participants completed questionnaires to categorize their Vikruti type and psychological states, which included depressed mood (CESD), anxiety (PROMIS), rumination & reflection (RRQ), mindfulness (MAAS), stress (PSS), and quality of life (Ryff).ResultsMultivariate general linear modeling, controlling for age, gender and body mass index (BMI), showed that Vata imbalance was associated with more anxiety (p ≤ 0.05), more rumination (p ≤ 0.01), less mindfulness (p ≤ 0.05), and lower overall quality of life (p ≤ 0.01). Pitta imbalance was associated with poorer mood (p ≤ 0.01) and less mindfulness (p ≤ 0.05), more anxiety (p ≤ 0.05) and stress (p ≤ 0.05). Kapha imbalance was associated with more stress (p ≤ 0.05), more rumination (p ≤ 0.05) and less reflection (p ≤ 0.05).ConclusionThese findings suggest that symptoms of mind-body imbalances in Ayurveda are differentially associated with western assessments of psychological states. Ayurvedic dosha assessment may be an effective way to assess physical as well as emotional wellbeing in research and clinical settings

Quantum liquid droplets in a mixture of Bose-Einstein condensates

Bose-Einstein condensatesquantum mixturesquantum liquidsquantum fluctuationsQuantum droplets are small clusters of atoms self-bound by the balance of attractive and repulsive forces. Here we report on the observation of a novel type of droplets, solely stabilized by contact interactions in a mixture of two Bose-Einstein condensates. We demonstrate that they are several orders of magnitude more dilute than liquid helium by directly measuring their size and density via in situ imaging. Moreover, by comparison to a single-component condensate, we show that quantum many-body effects stabilize them against collapse. We observe that droplets require a minimum atom number to be stable. Below, quantum pressure drives a liquid-to-gas transition that we map out as a function of interaction strength. These ultra-dilute isotropic liquids remain weakly interacting and constitute an ideal platform to benchmark quantum many-body theories.Peer ReviewedPreprin

A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP) and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs) and modulators (GSMs). GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative

Biochem Soc Trans

Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Abeta (amyloid beta-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration