959 research outputs found
Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers
Objective:
Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. //
Methods:
As development of novel radiotracers and onâsite setup of existing radiotracers is highly timeâconsuming and expensive, we used dualâcentre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18Fâflumazenil (18FâFMZ; GABAA receptor), 18FâFPEB (metabotropic glutamate receptor 5; mGluR5), 18Fâflutriciclamide (translocator protein; TSPO, microglia activation) and 18Fâdeprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpineâinduced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12â14 weeks after SE) were normalized to a calibration curve, coâregistered to an MRIâbased 2D regionâofâinterest atlas, and activity concentration (Bq/mm2) was calculated. //
Results:
In epileptogenesisâassociated brain regions, 18FâFMZ and 18FâFPEB showed an early decrease after SE. 18FâFMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18FâFPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18Fâflutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5â15 days and decreasing during the chronic phase. On the other hand, 18Fâdeprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. //
Significance:
Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of interârelated targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments
What about if buildings respond to my mood?
This work analyzes the possibilities of interaction between the built environment and its users, focused on the responsiveness of the first to the emotions of the latter. Transforming the built environment according to the mood, feelings, and emotions of users, moment by moment, is discussed and analyzed. The main goal of this research is to define a responsive model by which the built environment can respond in a personalized way to the usersâ emotions. For such, computational technical issues, building construction elements and usersâ interaction are identified and analyzed. Case studies where occurs an interaction between the physical space and users are presented. We define a model for an architecture that is responsive to the userâs emotions assuming the individual at one end and the space at the other. The interaction between both ends takes place according to intermediate steps: the collection of data, the recognition of emotion, and the execution of the action that responds to the detected emotion. As this work focuses on an innovative and disruptive aspect of the built environment, the recognition of the new difficulties and related ethical issues are discussed.info:eu-repo/semantics/acceptedVersio
Tumor necrosis factor alpha, citrullination, and peptidylarginine deiminase 4 in lung and joint inflammation
BACKGROUND: The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung inflammation with resultant protein citrullination may trigger anti-citrullinated protein antibodies, inflammation, and arthritis. Alternatively, lung and joint inflammation may be two manifestations of a single underlying pathology. The lung has increased citrullination and TNF-alpha levels are high in rheumatoid arthritis; however, it is unknown if TNF-alpha can induce lung protein citrullination. The citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-alpha-induced arthritis, but a role for PAD4 in lung citrullination and TNF-alpha-induced lung inflammation has not been explored. Our aim was to use TNF-alpha-overexpressing mice to clarify the intersection of TNF-alpha, citrullination, PAD4, arthritis, and lung inflammation.
METHODS: Lung protein citrullination in wild-type mice, mice that overexpress TNF-alpha systemically (TNF(+)), TNF(+)PAD4(+/+), and TNF(+)PAD4(-/-) mice was quantified by both gel electrophoresis using a citrulline probe and western blot. Hematoxylin and eosin (HandE)-stained lung sections from TNF(+)PAD4(+/+) and TNF(+)PAD4(-/-) mice were scored for lung inflammation. HandE-stained ankle joint sections from mice that overexpress TNF-alpha only in the lungs were assessed for arthritis.
RESULTS: TNF(+) mice have increased lung protein citrullination. TNF(+)PAD4(-/-) mice do not have significantly reduced lung protein citrullination, but do have decreased lung inflammation compared to TNF(+)PAD4(+/+) mice. Mice that overexpress TNF-alpha only in the lungs do not develop arthritis.
CONCLUSIONS: PAD4 exacerbates lung inflammation downstream of TNF-alpha without having a major role in generalized protein citrullination in inflamed lungs. Also, TNF-alpha-induced lung inflammation is not sufficient to drive murine arthritis
Meta-analyses of whale-watching impact studies : Comparisons of cetacean responses to disturbance
Acknowledgements. The International Whaling Commission funded this study through a grant assigned to D.L. D.L. was also funded by the Scottish Funding Council for funding through grant HR09011 to the Marine Alliance for Science and Technology for Scotland. While writing the manuscript, V.S. was sponsored by a Fulbright scholarship. We thank the many people that replied to the 2 MAR - MAM calls and Dr. Stankowich for his previous comments on the manuscript.Peer reviewedPublisher PD
GRAVITY: getting to the event horizon of Sgr A*
We present the second-generation VLTI instrument GRAVITY, which currently is
in the preliminary design phase. GRAVITY is specifically designed to observe
highly relativistic motions of matter close to the event horizon of Sgr A*, the
massive black hole at center of the Milky Way. We have identified the key
design features needed to achieve this goal and present the resulting
instrument concept. It includes an integrated optics, 4-telescope, dual feed
beam combiner operated in a cryogenic vessel; near infrared wavefront sensing
adaptive optics; fringe tracking on secondary sources within the field of view
of the VLTI and a novel metrology concept. Simulations show that the planned
design matches the scientific needs; in particular that 10 microarcsecond
astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given
the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE
Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc
What is limiting near-infrared astrometry in the Galactic Center?
We systematically investigate the error sources for high-precision astrometry
from adaptive optics based near-infrared imaging data. We focus on the
application in the crowded stellar field in the Galactic Center. We show that
at the level of <=100 micro-arcseconds a number of effects are limiting the
accuracy. Most important are the imperfectly subtracted seeing halos of
neighboring stars, residual image distortions and unrecognized confusion of the
target source with fainter sources in the background. Further contributors to
the error budget are the uncertainty in estimating the point spread function,
the signal-to-noise ratio induced statistical uncertainty, coordinate
transformation errors, the chromaticity of refraction in Earth's atmosphere,
the post adaptive optics differential tilt jitter and anisoplanatism. For stars
as bright as mK=14, residual image distortions limit the astrometry, for
fainter stars the limitation is set by the seeing halos of the surrounding
stars. In order to improve the astrometry substantially at the current
generation of telescopes, an adaptive optics system with high performance and
weak seeing halos over a relatively small field (r<=3") is suited best.
Furthermore, techniques to estimate or reconstruct the seeing halo could be
promising.Comment: accepted by MNRAS, 13 pages, 14 figure
Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.
Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers
Interoceptive inference, emotion, and the embodied self
The concept of the brain as a prediction machine has enjoyed a resurgence in the context of the Bayesian brain and predictive coding approaches within cognitive science. To date, this perspective has been applied primarily to exteroceptive perception (e.g., vision, audition), and action. Here, I describe a predictive, inferential perspective on interoception: âinteroceptive inferenceâ conceives of subjective feeling states (emotions) as arising from actively-inferred generative (predictive) models of the causes of interoceptive afferents. The model generalizes âappraisalâ theories that view emotions as emerging from cognitive evaluations of physiological changes, and it sheds new light on the neurocognitive mechanisms that underlie the experience of body ownership and conscious selfhood in health and in neuropsychiatric illness
- âŠ