Ontogenetic variation in the marine foraging of Atlantic salmon functionally links genomic diversity with a major life history polymorphism.

The ecological role of heritable phenotypic variation in free-living populations remains largely unknown. Knowledge of the genetic basis of functional ecological processes can link genomic and phenotypic diversity, providing insight into polymorphism evolution and how populations respond to environmental changes. By quantifying the marine diet of Atlantic salmon, we assessed how foraging behaviour changes along the ontogeny, and in relation to genetic variation in two loci with major effects on age at maturity (six6 and vgll3).

Combined In Vivo Microdialysis and PET Studies to Validate [C]Yohimbine Binding as a Marker of Noradrenaline Release.

The noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device.

Atlantic herring () population structure in the Northeast Atlantic Ocean.

The Atlantic herring L has a vast geographical distribution and a complex population structure with a few very large migratory units and many small local populations. Each population has its own spawning ground and/or time, thereby maintaining their genetic integrity. Several herring populations migrate between common feeding grounds and over-wintering areas resulting in frequent mixing of populations.

[F]FEOBV positron emission tomography may not be a suitable method to measure parasympathetic denervation in patients with Parkinson's disease.

Introduction: The peripheral autonomic nervous system may be involved years before onset of motor symptoms in some patients with Parkinson's disease (PD). Specific imaging techniques to quantify the cholinergic nervous system in peripheral organs are an unmet need. We tested the hypothesis that patients with PD display decreased [F]FEOBV uptake in peripheral organs - a sign of parasympathetic denervation.

In vivo vesicular acetylcholine transporter density in human peripheral organs: an [F]FEOBV PET/CT study.

Background: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects.

Activated N-methyl-D-aspartate receptor ion channels detected in focal epilepsy with [ F]GE-179 positron emission tomography.

Objective: Imaging activated glutamate N-methyl-D-aspartate receptor ion channels (NMDAR-ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [ F]GE-179 is a known use-dependent marker of NMDAR-ICs. We studied whether interictal [ F]GE-179 PET would detect foci of abnormal NMDAR-IC activation in patients with refractory focal epilepsy.

NMDA receptor ion channel activation detected in vivo with [F]GE-179 PET after electrical stimulation of rat hippocampus.

The positron emission tomography (PET) tracer [F]GE-179 binds to the phencyclidine (PCP) site in the open -methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation.

In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET.

The number of functionally active synapses provides a measure of neural integrity, with reductions observed in neurodegenerative disorders. [11C]UCB-J binds to synaptic vesicle 2A (SV2A) transmembrane protein located in secretory vesicles. We aimed to assess [11C]UCB-J PET as an in vivo biomarker of regional cerebral synaptic SV2A density in rat lesion models of neurodegeneration.

Preclinical PET Studies of [C]UCB-J Binding in Minipig Brain.

Purpose: Loss of neuronal synapse function is associated with a number of brain disorders. The [C]UCB-J positron emission tomography (PET) tracer allows for in vivo examination of synaptic density, as it binds to synaptic vesicle glycoprotein 2A (SV2A) expressed in presynaptic terminals. Here, we characterise [C]UCB-J imaging in Göttingen minipigs.

Activation of NMDA receptor ion channels by deep brain stimulation in the pig visualised with [F]GE-179 PET.

Background: No PET radioligand has yet demonstrated the capacity to map glutamate N-methyl-d-aspartate receptor ion channel (NMDAR-IC) function. [F]GE-179 binds to the phencyclidine (PCP) site in open NMDAR-ICs and potentially provides a use-dependent PET biomarker of these ion channels.

Objective: To show [F]GE-179 PET can detect increased NMDAR-IC activation during electrical deep brain stimulation (DBS) of pig hippocampus.

Identification of male heterogametic sex-determining regions on the Atlantic herring Clupea harengus genome.

The sex determination system of Atlantic herring Clupea harengus L., a commercially important fish, was investigated. Low coverage whole-genome sequencing of 48 females and 55 males and a genome-wide association study revealed two regions on chromosomes 8 and 21 associated with sex.

Using long and linked reads to improve an Atlantic herring (Clupea harengus) genome assembly.

Atlantic herring (Clupea harengus) is one of the most abundant fish species in the world. It is an important economical and nutritional resource, as well as a crucial part of the North Atlantic ecosystem. In 2016, a draft herring genome assembly was published.

Acute in vivo effect of valproic acid on the GABAergic system in rat brain: A [C]Ro15-4513 microPET study.

γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system acting mainly through GABA receptors. In the presence of high levels of GABA, an allosteric shift in the GABA receptors can change the affinity of benzodiazepine (BZD) ligands. Valproic acid (VPA) is an anticonvulsant that enhances the level of endogenous GABA in the brain.

Noradrenergic Deficits in Parkinson Disease Imaged with C-MeNER.

Degeneration of noradrenergic neurons may underlie the disabling nonmotor symptoms in patients with Parkinson disease (PD). Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand ()-C-2-(α-(2-methoxyphenoxy)benzyl)morpholine (C-MeNER) is a highly selective inhibitor of noradrenaline transporters, and PET studies suggest that this radioligand is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo.

Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model.

Unlabelled: Increasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response in PD seems to involve, not only microglia, but also other immune cells infiltrated into the brain. Indeed, we observed here the infiltration of macrophages, specifically CD163+ macrophages, into the area of neurodegeneration in the 6-hydroxydopamine (6-OHDA) PD model.

SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia.

Balancing trophic and apoptotic cues is critical for development and regeneration of neuronal circuits. Here we identify SorCS2 as a proneurotrophin (proNT) receptor, mediating both trophic and apoptotic signals in conjunction with p75(NTR). CNS neurons, but not glia, express SorCS2 as a single-chain protein that is essential for proBDNF-induced growth cone collapse in developing dopaminergic processes.

The identification of AF38469: an orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin.

The identification of the novel, selective, orally bioavailable Sortilin inhibitor AF38469 is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.

Different vascular endothelial growth factor (VEGF), VEGF-receptor 1 and -2 mRNA expression profiles between clear cell and papillary renal cell carcinoma.

Objectives: To examine vascular endothelial growth factor (VEGF), VEGF-receptor-(R)1, and R2 mRNA levels in renal cell carcinoma (RCC), a tumour generally refractory to most medical therapy, but for which a potentially useful therapeutic alternative is inhibition of angiogenesis.

Patients And Methods: VEGF, VEGF-R1 and -R2 mRNA levels were analysed using the quantitative reverse transcription-polymerase chain reaction. RNA was extracted from 84 conventional (clear cell) RCCs (cRCC), 20 papillary (pRCC), six chromophobe (chRCC), and 27 corresponding kidney cortex tissues, obtained from 110 patients in whom high-quality RNA was available from the tumours (53 women and 57 men, mean age 64.

Different isoform patterns for vascular endothelial growth factor between clear cell and papillary renal cell carcinoma.

Objective: To investigate the protein expression of vascular endothelial growth factor (VEGF) isoforms in relation to the clinical course in patients with different renal cell carcinoma (RCC) types, as angiogenesis is essential for tumour growth and metastasis.

Patients And Methods: Western blots were assayed of protein extracts from tumour and concomitant kidney cortex samples from 96 patients. The levels of VEGF189, VEGF165, and VEGF121 isoforms were correlated with clinicopathological characteristics and survival.

Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma.

Obesity is associated with an increased risk of certain cancers, including renal cell carcinoma. A possible mediator of this risk is insulin-like growth factor-1 (IGF-1). The authors evaluated the prognostic information of IGF-1, IGFBP-3, leptin, and prealbumin in sera sampled at diagnosis from 256 consecutive patients with renal cell carcinoma.