Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and ...social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.
ABSTRACT
The growth of a longitudinal or quasi-longitudinal Langmuir mode in the outward-moving beam of ions and protons that forms the open sector of an ion-proton pulsar magnetosphere radiates as ...an analogue of an end-fed high-impedance horizontal straight-wire antenna an integral number of half-waves in length. The radiation has, broadly, the energy flux, linear polarization, and spectral index that are widely observed: also, the notch phenomenon seen in some integrated pulse profiles occurs naturally. The new field of pulsar observations below 100 MHz may lead to productive tests of the radio emission mechanism.
Prion-like, trans-neuronal spread of tau pathology in humans is controversial. By evaluating tau burden and functional connectivity in living patients, Cope et al. demonstrate relationships ...consistent with this in Alzheimer's disease but not progressive supranuclear palsy. Tau distribution in the latter is better explained by metabolic demand and trophic support.
Abstract
Alzheimer's disease and progressive supranuclear palsy (PSP) represent neurodegenerative tauopathies with predominantly cortical versus subcortical disease burden. In Alzheimer's disease, neuropathology and atrophy preferentially affect 'hub' brain regions that are densely connected. It was unclear whether hubs are differentially affected by neurodegeneration because they are more likely to receive pathological proteins that propagate trans-neuronally, in a prion-like manner, or whether they are selectively vulnerable due to a lack of local trophic factors, higher metabolic demands, or differential gene expression. We assessed the relationship between tau burden and brain functional connectivity, by combining in vivo PET imaging using the ligand AV-1451, and graph theoretic measures of resting state functional MRI in 17 patients with Alzheimer's disease, 17 patients with PSP, and 12 controls. Strongly connected nodes displayed more tau pathology in Alzheimer's disease, independently of intrinsic connectivity network, validating the predictions of theories of trans-neuronal spread but not supporting a role for metabolic demands or deficient trophic support in tau accumulation. This was not a compensatory phenomenon, as the functional consequence of increasing tau burden in Alzheimer's disease was a progressive weakening of the connectivity of these same nodes, reducing weighted degree and local efficiency and resulting in weaker 'small-world' properties. Conversely, in PSP, unlike in Alzheimer's disease, those nodes that accrued pathological tau were those that displayed graph metric properties associated with increased metabolic demand and a lack of trophic support rather than strong functional connectivity. Together, these findings go some way towards explaining why Alzheimer's disease affects large scale connectivity networks throughout cortex while neuropathology in PSP is concentrated in a small number of subcortical structures. Further, we demonstrate that in PSP increasing tau burden in midbrain and deep nuclei was associated with strengthened cortico-cortical functional connectivity. Disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer took less direct paths, passing through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality in PSP, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Our results have wide-ranging implications, from the validation of models of tau trafficking in humans to understanding the relationship between regional tau burden and brain functional reorganization.
Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model ...in which to test the specificity of in vivo binding of the putative tau ligand
FAV-1451, which is elevated in frontotemporal lobar degeneration tauopathies.
Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with
FAV-1451. Two independent preprocessing methods were used. For both methods, all patients had clearly elevated binding potential (BP
(non-displaceable binding potential)) in temporal lobes, lateralising according to their clinical syndrome and evident in raw images. Region of interest analyses confirmed that BP
was significantly increased in temporal regions, insula and fusiform gyrus, consistent with those areas known to be most affected in semantic dementia. Hierarchical cluster analysis, based on the distribution of
FAV-1451 binding potential, separated semantic dementia from controls with 86% sensitivity and 100% specificity.
FAV-1451 binds in vivo regions that are likely to contain TDP-43 and not significant tau pathology. While this suggests a non-tau target for
FAV-1451, the pathological regions in semantic dementia do not normally contain significant levels of recently proposed 'off target' binding sites for
FAV-1451, such as neuronal monoamine oxidase or neuromelanin. Postmortem and longitudinal data will be useful to assess the utility of
FAV-1451 to differentiate and track different types of frontotemporal lobar degeneration.
We present the next-to-leading-order QCD corrections to the production of a Higgs boson in association with one jet at the LHC including the full top-quark mass dependence. The mass of the bottom ...quark is neglected. The two-loop integrals appearing in the virtual contribution are calculated numerically using the method of sector decomposition. We study the Higgs boson transverse momentum distribution, focusing on the high p_{t,H} region, where the top-quark loop is resolved. We find that the next-to-leading-order QCD corrections are large but that the ratio of the next-to-leading-order to leading-order result is similar to that obtained by computing in the limit of large top-quark mass.
The electric field accelerating electrons in the Timokhin–Arons polar-cap model as applied to millisecond pulsars is so high that the electron Lorentz factors are limited either by radiation reaction ...or by the Breit–Wheeler process. In the former case, it is possible to obtain an upper limit for curvature-radiation momentum components perpendicular to the local magnetic field that is independent of the flux-line radius of curvature. The threshold value for single-photon conversion to pairs is high but is possibly reached in J0030+0451. However, owing to the high polar-cap temperature reported, direct pair production by the Breit–Wheeler process is probably more important. If the existence of coherent radio emission in millisecond pulsars is assumed to need a high-multiplicity pair plasma, then it follows that the primary electrons also produce gamma-rays in the Fermi-LAT energy band for which the magnetosphere is completely transparent. The absence of these, in phase with the radio emission, would be an immediate indication that ultra-high-energy electrons and an active Timokhin–Arons polar cap are not present in J0030+0451.
Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer's disease (AD). We tested the relationship between neuroinflammation and the disruption of functional connectivity in large-scale ...networks, and their joint influence on cognitive impairment. We combined
CPK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 patients (12 females/16 males) with clinical diagnosis of probable AD or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy controls (8 females/6 males). Source-based "inflammetry" was used to extract principal components of
CPK11195 PET signal variance across all participants. rs-fMRI data were preprocessed via independent component analyses to classify neuronal and non-neuronal signals. Multiple linear regression models identified sources of signal covariance between neuroinflammation and brain connectivity profiles, in relation to the diagnostic group (patients, controls) and cognitive status.Patients showed significantly higher
CPK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, frontal, and inferior temporal cortex. Patients with enhanced loading on this
CPK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits.Our study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer's disease. Neuroinflammation, and its association with functionally-relevant reorganization of brain networks, is proposed as a target for emerging immunotherapeutic strategies aimed at preventing or slowing the emergence of dementia.
Neuroinflammation is an important aspect of Alzheimer's disease (AD), but it was not known whether the influence of neuroinflammation on brain network function in humans was important for cognitive deficit. Our study provides clear evidence that
neuroinflammation in AD impairs large-scale network connectivity; and that the link between neuro inflammation and functional network connectivity is relevant to cognitive impairment. We suggest that future studies should address how neuroinflammation relates to network function as AD progresses, and whether the neuroinflammation in AD is reversible, as the basis of immunotherapeutic strategies to slow the progression of AD.
Anticancer effects of phytosterols Woyengo, T.A; Ramprasath, V.R; Jones, P.J.H
European journal of clinical nutrition,
07/2009, Letnik:
63, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Phytosterol and stanol (or phytosterols) consumption reduces intestinal cholesterol absorption, leading to decreased blood LDL-cholesterol levels and lowered cardiovascular disease risk. However, ...other biological roles for plant sterols and stanols have also been proposed. The objective of this review is to critically examine results from recent research regarding the potential effects and mechanisms of action of phytosterols on forms of cancer. Considerable emerging evidence supports the inhibitory actions of phytosterols on lung, stomach, as well as ovarian and breast cancer. Phytosterols seem to act through multiple mechanisms of action, including inhibition of carcinogen production, cancer-cell growth, angiogenesis, invasion and metastasis, and through the promotion of apoptosis of cancerous cells. Phytosterol consumption may also increase the activity of antioxidant enzymes and thereby reduce oxidative stress. In addition to altering cell-membrane structure and function, phytosterols probably promote apoptosis by lowering blood cholesterol levels. Moreover, consumption of phytosterols by healthy humans at the recommended level of 2 g per day does not cause any major health risks. In summary, mounting evidence supports a role for phytosterols in protecting against cancer development. Hence, phytosterols could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.
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