Brain-derived neurotrophic factor (BDNF) has recently been implicated as an anorexigenic factor in the central control of food intake. Previous studies focused on the hypothalamus as a probable site ...of action for this neurotrophin. It was demonstrated that BDNF is an important downstream effector of melanocortin signaling in the ventromedial hypothalamus. In this study, we addressed whether BDNF can modulate food intake in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). To this end, we used two complementary methodological approaches in adult rats. First, we measured the effects of intraparenchymal infusions of exogenous BDNF within the DVC on food intake and body weight. Second, we measured the endogenous BDNF protein content in the DVC and hypothalamus after food deprivation, refeeding, or peripheral treatments by the anorexigenic hormones leptin and cholecystokinin (CCK). BDNF infusion within the DVC induced anorexia and weight loss. In the DVC, BDNF protein content decreased after 48 h food deprivation and increased after refeeding. Acute and repetitive peripheral leptin injections induced an increase of the BDNF protein content within the DVC. Moreover, peripheral CCK treatment induced a transient increase of BDNF protein content first in the DVC (30 min after CCK) and later on in the hypothalamus (2 h after CCK). Taken together, these results strongly support the view that BDNF plays a role as an anorexigenic factor in the DVC. Our data also suggest that BDNF may constitute a common downstream effector of leptin and CCK, possibly involved in their synergistic action.
Non-invasive diagnosis of pulmonary hypertension (PH) relies on estimation of pulmonary arterial pressure (PAP) via Doppler echocardiographic measurement of tricuspid regurgitation pressure gradient ...(TRPG). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) recently has been described for the detection of pulmonary venous congestion. Whether this variable could be used to detect the presence of precapillary PH is unknown. The objective of the present study was to investigate the diagnostic value of PV/PA for prediction of TRPG, as a surrogate of PAP, in dogs with PH of precapillary origin.
Sixty-seven client-owned dogs were included in the study.
This was a retrospective study. Dogs with a measurable TRPG were included and classified into group 1 (TRPG < 30 mmHg), group 2 (TRPG 30–49 mmHg), group 3 (TRPG 50–80 mmHg), or group 4 (TRPG > 80 mmHg). The PV/PA, acceleration time-to-ejection time ratio of pulmonary artery flow, main pulmonary artery diameter-to-aortic diameter ratio, and right pulmonary artery distensibility index were measured retrospectively from cineloops in each dog.
The PV/PA measured by both two-dimensional (2D) and time-motion mode(MM) echocardiography decreased proportionally with PH severity. Using regression analysis, PV/PA (2D) was identified as the strongest predictor for TRPG (R2 = 0.70, p < 0.0001) among other variables studied, with a good diagnostic accuracy (area under the curve = 0.94) for moderate PH (TRPG > 50 mmHg) using a cutoff value of < 0.70 (sensitivity = 96%, specificity = 82%).
Results of the present study suggest that PV/PA can be useful as an additional, non-invasive, and indirect variable to identify precapillary PH in dogs.
The dorsal vagal complex (DVC) encompasses the nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve (DMX) and the area postrema (AP), that altogether provide the major ...integrative center for the mammalian autonomic nervous system. The adult rat DVC has been reported to contain afferent-dependent concentration of the plasticity-promoting polysialylated form of neural cell adhesion molecule J Neurosci 21 (2001) 4721; Eur J Neurosci 14 (2001) 1194. This prompted us to assess the occurrence of neurogenesis in the DVC of adult rats. Cumulative
in vivo labeling of cell proliferation with i.p. bromodeoxyuridine (BrdU) injections was combined with phenotypic markers and confocal microscopy on serial brainstem sections throughout the DVC extent. In basal condition, sparse BrdU+ nuclei were selectively detected in the DVC according to a discrete and reproducible pattern. Some of them were found to colocalize with the neuronal markers doublecortin, HuC/D, or neuronal-specific antigen (NeuN), demonstrating that neurogenesis does occur within the DVC of adult rat. In the NTS, 10% of the BrdU+ nuclei were also NeuN+. A comparable proportion of astrogliogenesis was found in the DVC. Nestin immunohistochemistry yielded a highly specific labeling pattern at the border between AP and NTS. These data may relate to the neural stem cells that have been reported in the floor of the IVth ventricle J Neurosci 16 (1996) 7599. In order to assess a possible modulation of neurogenesis by afferent input
in vivo, unilateral vagotomy was performed prior to cumulative BrdU treatment. Such DVC deafferentation triggered a large increase of BrdU incorporation in the ipsilateral DVC, which was associated with microglial proliferation in the DMX and with increased genesis of neurons and astrocytes in the NTS. These findings establish DVC as a novel model of adult neurogenesis that is reactive to deafferentation.
The mammalian olfactory epithelium (OE) is composed of primary olfactory sensory neurons (OSNs) that are renewed throughout adulthood by local, restricted neuronal progenitor cells. The molecular ...signals that control this neurogenesis in vivo are unknown. Using olfactory bulb ablation (OBX) in adult mice to trigger synchronous mitotic stimulation of neuronal progenitors in the OE, we show the in vivo involvement of a cytokine in the cellular events leading to the regeneration of the OE. We find that, of many potential mitogenic signals, only leukemia inhibitory factor (LIF) is induced before the onset of neuronal progenitor proliferation. The rise in LIF mRNA expression peaks at 8 hr after OBX, and in situ RT-PCR and immunocytochemistry indicate that LIF is upregulated, in part, in the injured neurons themselves. This rise in LIF is necessary for injury-induced neurogenesis, as OBX in the LIF knock-out mouse fails to stimulate cell proliferation in the OE. Moreover, delivery of exogenous LIF to the intact adult OE using an adenoviral vector stimulates BrdU labeling in the apical OE. Taken together, these results suggest that injured OSNs release LIF as a stimulus to initiate their own replacement.
In the last year ATLAS has radically updated its software development infrastructure hugely reducing the complexity of building releases and greatly improving build speed, flexibility and code ...testing. The first step in this transition was the adoption of CMake as the software build system over the older CMT. This required the development of an automated translation from the old system to the new, followed by extensive testing and improvements. This resulted in a far more standard build process that was married to the method of building ATLAS software as a series of 12 separate projects from Subversion. We then proceeded with a migration of the code base from Subversion to Git. As the Subversion repository had been structured to manage each package more or less independently there was no simple mapping that could be used to manage the migration into Git. Instead a specialist set of scripts that captured the software changes across official software releases was developed. With some clean up of the repository and the policy of only migrating packages in production releases, we managed to reduce the repository size from 62 GiB to 220 MiB. After moving to Git we took the opportunity to introduce continuous integration so that now each code change from developers is built and tested before being approved. With both CMake and Git in place we also dramatically simplified the build management of ATLAS software. Many heavyweight homegrown tools were dropped and the build procedure was reduced to a single bootstrap of some external packages, followed by a full build of the rest of the stack. This has reduced the time for a build by a factor of 2. It is now easy to build ATLAS software, freeing developers to test compile intrusive changes or new platform ports with ease. We have also developed a system to build lightweight ATLAS releases, for simulation, analysis or physics derivations which can be built from the same branch.
During the 2013-2014 shutdown of the Large Hadron Collider, ATLAS switched to a new event data model for analysis, called the xAOD. A key feature of this model is the separation of the object data ...from the objects themselves (the 'auxiliary store'). Rather than being stored as member variables of the analysis classes, all object data are stored separately, as vectors of simple values. Thus, the data are stored in a 'structure of arrays' format, while the user still can access it as an 'array of structures'. This organization allows for on-demand partial reading of objects, the selective removal of object properties, and the addition of arbitrary user- defined properties in a uniform manner. It also improves performance by increasing the locality of memory references in typical analysis code. The resulting data structures can be written to ROOT files with data properties represented as simple ROOT tree branches. This paper focuses on the design and implementation of the auxiliary store and its interaction with ROOT.
The dorsal vagal complex, located in the brainstem, is the major integrative center of the autonomic nervous system. By combining
in vivo bromodeoxyuridine incorporation and phenotypic ...immunolabeling, we have previously reported that neurogenesis occurs in the adult rat dorsal vagal complex Bauer S, Hay M, Amilhon B, Jean A, Moyse E (2005) In vivo neurogenesis in the dorsal vagal complex of the adult rat brainstem. Neuroscience 130:75–90.. In the present study we asked whether adult dorsal vagal complex contains proliferative and/or neural stem cells. Using Ki-67 immunolabeling and cyclin D1 Western blot, we showed intrinsic cell proliferation in the dorsal vagal complex and its stimulation by vagotomy. Detailed time-course analysis revealed that vagotomy-induced proliferation in the dorsal vagal complex peaked three days after lesion. In order to directly assess the presence of intrinsic stem cells, primary cell cultures from adult rat dorsal vagal complex were performed in the presence of epidermal growth factor and basic fibroblast growth factor (neurosphere assay). A discrete subpopulation of dorsal vagal complex cells proliferated as neurospheres, self-renewed when passaged, and differentiated into neurons, astrocytes and oligodendrocytes. Proliferation and neuron-differentiating potentials of dorsal vagal complex neurospheres were both lower than those of subventricular zone neurospheres from the same rats. The relationship between
in vitro neurosphere-forming cells of dorsal vagal complex and
in vivo dorsal vagal complex neurogenesis is discussed and remains to be directly addressed. The present data demonstrate the occurrence of neural stem cells in the dorsal vagal complex of adult rat brain.
Headache is usually considered a key symptom of intracranial hypertension (ICHT). However, there are no published experimental data to support the concept that increased intracranial pressure (ICP) ...is painful in humans.
This prospective study was performed in 16 patients with suspected normal-pressure hydrocephalus, necessitating a lumbar infusion test with measurement of cerebrospinal fluid (CSF) hydrodynamics. During the test, ICP was increased from baseline to a plateau. Headache was scored on a visual analog scale (VAS) (0 = no pain, 10 = very severe pain) at baseline ICP and when ICP plateaued.
At baseline, mean ICP was 11 ± 3.6 mmHg and VAS was 0. At plateau, mean ICP was 28 ± 9.5 mmHg and VAS was 0. There was a significant increase in ICP (p <0.001), but no increase in headache intensity (VAS). An acute (20-min) moderate increase in ICP was not accompanied by a headache.
We demonstrate that an acute, isolated increase in CSF pressure does not produce a headache. To occur, a headache needs activation of the pain-sensitive structures (dura and venous sinuses) or central activation of the cerebral nociceptive structures. This peripheral or central activation does not occur with an isolated increase in CSF pressure.
Event visualization in ATLAS Bianchi, R M; Boudreau, J; Konstantinidis, N ...
Journal of physics. Conference series,
10/2017, Letnik:
898, Številka:
7
Journal Article
Recenzirano
Odprti dostop
At the beginning, HEP experiments made use of photographical images both to record and store experimental data and to illustrate their findings. Then the experiments evolved and needed to find ways ...to visualize their data. With the availability of computer graphics, software packages to display event data and the detector geometry started to be developed. Here, an overview of the usage of event display tools in HEP is presented. Then the case of the ATLAS experiment is considered in more detail and two widely used event display packages are presented, Atlantis and VP1, focusing on the software technologies they employ, as well as their strengths, differences and their usage in the experiment: from physics analysis to detector development, and from online monitoring to outreach and communication. Towards the end, the other ATLAS visualization tools will be briefly presented as well. Future development plans and improvements in the ATLAS event display packages will also be discussed.
ATLAS fast physics monitoring: TADA Sabato, G; Elsing, M; Gumpert, C ...
Journal of physics. Conference series,
10/2017, Letnik:
898, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The ATLAS experiment at the LHC has been recording data from proton-proton collisions with 13 TeV center-of-mass energy since spring 2015. The collaboration is using a fast physics monitoring ...framework (TADA) to automatically perform a broad range of fast searches for early signs of new physics and to monitor the data quality across the year with the full analysis level calibrations applied to the rapidly growing data. TADA is designed to provide fast feedback directly after the collected data has been fully calibrated and processed at the Tier-0. The system can monitor a large range of physics channels, offline data quality and physics performance quantities. TADA output is available on a website accessible by the whole collaboration. It gets updated twice a day with the data from newly processed runs. Hints of potentially interesting physics signals or performance issues identified in this way are reported to be followed up by physics or combined performance groups. The note reports as well about the technical aspects of TADA: the software structure to obtain the input TAG files, the framework workflow and structure, the webpage and its implementation.
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