Characterization of 3 PET tracers for Quantification of Mitochondrial and Synaptic function in Healthy Human Brain: 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J

Mitochondrial complex 1 (MC1) is involved in maintaining brain bioenergetics, the sigma 1 receptor (σ1R) responds to neuronal stress and synaptic vesicle protein 2A (SV2A) reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here we characterise the kinetic behaviour of three positron emission tomography (PET) radioligands 18F-BCPP-EF, 11C-SA-4503 and 11CUCB- J, for the measurement of MC1, σ1R and SV2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. Methods: Twelve human subjects underwent dynamic PET scans including associated arterial blood sampling with each radioligand. A range of kinetic models were investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All three radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution (VT) were multilinear analysis 1 (MA1) and the 2-tissue compartment (2TC) model for 18F-BCPP-EF, MA1 for 11C-SA- 4503, and both MA1 and the 1-tissue compartment (1TC) model for 11C-UCB-J. Acquisition times of 70, 80 and 60 minutes for 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J, respectively, provided good estimates of regional VT values. An effect of age was observed on 18F-BCPP-EF and 11C-UCB-J signal in the caudate. Conclusion: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases

Characterization of 3 PET Tracers for Quantification of Mitochondrial and Synaptic Function in Healthy Human Brain: {18}^F-BCPP-EF, {11}^C-SA-4503, and {11}^C-UCB-J

Mitochondrial complex 1 is involved in maintaining brain bioenergetics; σ-1 receptor responds to neuronal stress; and synaptic vesicle protein 2A reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here, we characterize the kinetic behavior of 3 PET radioligands—{18}^F-BCPP-EF, {11}^C-SA-4503, and {11}^C-UCB-J for the measurement of mitochondrial complex 1, σ-1 receptor, and synaptic vesicle protein 2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. METHODS: Twelve human subjects underwent dynamic PET scans with each radioligand, including associated arterial blood sampling. A range of kinetic models was investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. RESULTS: All 3 radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution were multilinear analysis 1 (MA1) and the 2-tissue-compartment model for {18}^F-BCPP-EF, MA1 for 11}^C-SA-4503, and both MA1 and the 1-tissue-compartment model for {11}^C-UCB-J, respectively, provided good estimates of regional volume of distribution values. An effect of age was observed on {18}^F-BCPP-EF and {11}^C-UCB-J signal in the caudate. CONCLUSION: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases

Recent changes in drainage route and outburst magnitude of the Russell Glacier ice-dammed lake, West Greenland

Glacial lake outburst floods (GLOFs) or jökulhlaups from ice-dammed lakes are frequent in Greenland and can influence local ice dynamics and bedrock motion, cause geomorphological changes, and pose flooding hazards. Multidecadal time series of lake drainage dates, volumes, and flood outlets are extremely rare. However, they are essential for determining the scale and frequency of future GLOFs, for identifying drainage mechanisms, and for mitigating downstream flood effects. In this study, we use high-resolution digital elevation models (DEMs) and orthophotos (0.1 × 0.1 m) generated from uncrewed-aerial-vehicle (UAV) field surveys, in combination with optical satellite imagery. This allows us to reconstruct robust lake volume changes associated with 14 GLOFs between 2007 and 2021 at Russell Glacier, West Greenland. As a result, this is one of the most comprehensive and longest records of ice-dammed lake drainages in Greenland to date. Importantly, we find a mean difference of ∼ 10 % between our lake drainage volumes when compared with estimates derived from a gauged hydrograph 27 km downstream. Due to thinning of the local ice dam, the potential maximum drainage volume in 2021 is ∼ 60 % smaller than that estimated to have drained in 2007. Our time series also reveals variations in the drainage dates ranging from late May to mid-September and drainage volumes ranging between 0.9 and 37.7 Mm3. We attribute these fluctuations between short periods of relatively high and low drainage volumes to a weakening of the ice dam and an incomplete sealing of the englacial tunnel following the large GLOFs. This syphoning drainage mechanism is triggered by a reduction in englacial meltwater, likely driven by late-season drainage and sudden air temperature reductions, as well as annual variations in the glacial drainage system. Furthermore, we provide geomorphological evidence of an additional drainage route first observed following the 2021 GLOF, with a subglacial or englacial flow pathway, as well as supraglacial water flow across the ice margin. It seems probable that the new drainage route will become dominant in the future. This will drive changes in the downstream geomorphology and raise the risk of flooding-related hazards as the existing buffering outlet lakes will be bypassed.</p

Widespread cell stress and mitochondrial dysfunction in early Alzheimer’s Disease

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). We quantified the in vivo density of the endoplasmic reticulum stress marker, the sigma 1 receptor (S1R) using [11C]SA4503 PET, as well as that of mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and brain perfusion (CBF) measured with MRI arterial spin labelling. 8 AD patients were followed longitudinally to estimate rates of change with disease progression over 12-18 months. The AD patients showed widespread increases in S1R (≤ 27%) and regional decreases in MC1 (≥ -28%), SV2A (≥ -25%), brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 density (≥ -12%) and brain volumes (≥ -5%) were further reduced at follow up in brain regions consistent with the differences between AD patients and controls at baseline. Exploratory analyses showing associations of MC1, SV2A and S1R density with cognitive changes at baseline and longitudinally with AD, but not in controls, suggested a loss of metabolic functional reserve with disease. Our study thus provides novel in vivo evidence for widespread cellular stress and bioenergetic abnormalities in early AD and that they may be clinically meaningful

De l'urbain vers le rural : les transferts d'établissements de l'agro-alimentaire

A également fait l'objet d'une présentation au 38. Colloque de l'ASRDLF, les 21-23/08/2002 à Trois Rivières (CAN)National audienceLes événements démographiques attachés aux établissements (création, disparition...) jouent un rôle important mais mal connu en matière d'emploi. L'article est consacré à un type particulier d'évènement, le transfert d'un établissement, depuis une zone urbaine vers une zone rurale ou périurbaine. Les auteurs proposent d'abord un cadre théorique issu des modèles de la nouvelle économie géographique. Puis ils dressent un bilan du phénomène dans le cas des industries agro-alimentaires. Ce bilan est d'abord quantitatif et s'appuie sur une exploitation spécifique du fichier SIRENE de l'INSEE entre 1993 et 1998. L'ampleur du phénomène apparaît non négligeable, même s'il ne s'agit pas d'une tendance massive. Bon nombre de transferts sont caractérisés par un déplacement géographique limité, tandis que la variabilité intersectorielle du phénomène est très forte. Les auteurs proposent également un bilan qualitatif basé sur des études de cas approfondies. A l'origine du transfert se trouve d'abord la volonté de renouveler les équipements productifs et d'étendre leur capacité dans le cadre d'une localisation géographique moins contraignante, périurbaine ou rurale. L'accessibilité constitue un critère déterminant du choix de la zone d'accueil, aux côtés des caractéristiques de la main-d'oeuvre. Des qualités, telles que la stabilité ou la capacité à fournir des efforts importants, associées au milieu rural, voire à l'origine agricole des salariés, jouent ainsi un rôle important au moment des choix d'implantation