Correction: Boiten et al. Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF. 2021, , 38.

The authors want to notify that they have made the following changes to the author list of the paper [...

Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF.

Dementia with Lewy bodies (DLB) is a neurodegenerative disease where synaptic loss and reduced synaptic integrity are important neuropathological substrates. Neuronal Pentraxin 2(NPTX2) is a synaptic protein that drives the GABAergic inhibitory circuit. Our aim was to examine if NPTX2 cerebral spinal fluid (CSF) levels in DLB patients were altered and how these levels related to other synaptic protein levels and to cognitive function and decline.

TLQP-21 changes in response to a glucose load.

Background: The TLQP-21 peptide potentiates glucose-stimulated insulin secretion, hence we investigated its endogenous response to glucose.

Methods: Fasted mice received intraperitoneal glucose (3 g/kg), or saline (controls), and were sacrificed 30 and 120 min later (4 groups, n = 6/group). We investigated TLQP-21 in pancreas and plasma using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography (HPLC), as well as TLQP-21 receptors (gC1q-R and C3a-R1) expression in pancreas by immunohistochemistry.

Dynamic of TLQP-peptides upon fasting.

Background: The VGF-derived TLQP peptides (TLQPp), a new potential drug target for obesity, are expressed in stomach, pancreas, adrenal gland as well as in adipose tissues, and, when exogenously injected, regulate energy expenditure and food intake. However, it is not clear if these peptides physiologically change in these organs in response to fasting.

Methods: Rats were subdivided into four groups: (A) fed ad libitum, (B) fed with restrictions (once a day) (C) fast for 48 h and (D) fast for 48 h and then fed 1 h before sacrifice.

Identification of novel cerebrospinal fluid biomarker candidates for dementia with Lewy bodies: a proteomic approach.

Background: Diagnosis of dementia with Lewy bodies (DLB) is challenging, largely due to a lack of diagnostic tools. Cerebrospinal fluid (CSF) biomarkers have been proven useful in Alzheimer's disease (AD) diagnosis. Here, we aimed to identify novel CSF biomarkers for DLB using a high-throughput proteomic approach.

VGF peptides as novel biomarkers in Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra (SN). At disease onset, a diagnosis is often difficult. VGF peptides are abundant in the SN and peripheral circulation; hence, we investigate whether their plasma profile may reflect the brain dopamine reduction.

VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies.

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer's disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM).

Photoperiodic changes in adiposity increase sensitivity of female Siberian hamsters to systemic VGF derived peptide TLQP-21.

TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural agonist for the complement 3a receptor 1 (C3aR1) has revived interest in this peptide as a potential drug target for obesity. We have investigated its function in Siberian hamsters (Phodopus sungorus), a rodent that displays natural seasonal changes in body weight and adiposity as an adaptation to survive winter.

Reduction of Total Brain and Cerebellum Volumes Associated With Neuronal Autoantibodies in Patients With APECED.

Context: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autoantibodies (AutoAbs) labeling brain neurons were reported; conversely, brain MRI alterations associated with these AutoAbs were never reported.

Objectives: To describe brain alterations in APECED and to correlate them with AutoAbs against glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), and 5-tryptophan hydroxylase (5-HT) neurons.

Design And Participants: Fourteen Sardinian patients with APECED and age-matched control subjects were recruited for MRI analysis and blood sampling to detect AutoAbs to GAD, TH, and 5-HT neurons by using rat brain sections.

TLQP Peptides in Amyotrophic Lateral Sclerosis: Possible Blood Biomarkers with a Neuroprotective Role.

While the VGF-derived TLQP peptides have been shown to prevent neuronal apoptosis, and to act on synaptic strengthening, their involvement in Amyotrophic Lateral Sclerosis (ALS) remains unclarified. We studied human ALS patients' plasma (taken at early to late disease stages) and primary fibroblast cultures (patients vs controls), in parallel with SOD1-G93A transgenic mice (taken at pre-, early- and late symptomatic stages) and the mouse motor neuron cell line (NSC-34) treated with Sodium Arsenite (SA) to induce oxidative stress. TLQP peptides were measured by enzyme-linked immunosorbent assay, in parallel with gel chromatography characterization, while their localization was studied by immunohistochemistry.

The Hypothalamic-Pituitary Axis and Autoantibody Related Disorders.

This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities.

Correction: Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

[This corrects the article DOI: 10.1371/journal.pone.

Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment.

From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia".

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice.

VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies.

VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model.

Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity.

VGF Peptide Profiles in Type 2 Diabetic Patients' Plasma and in Obese Mice.

To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry.

Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA) coupled with high-performance liquid (HPLC) or gel chromatography were carried out.

VGF changes during the estrous cycle: a novel endocrine role for TLQP peptides?

Although the VGF derived peptide TLQP-21 stimulates gonadotropin-releasing hormone (GnRH) and gonadotropin secretion, available data on VGF peptides and reproduction are limited. We used antibodies specific for the two ends of the VGF precursor, and for two VGF derived peptides namely TLQP and PGH, to be used in immunohistochemistry and enzyme-linked immunosorbent assay complemented with gel chromatography. In cycling female rats, VGF C-/N-terminus and PGH peptide antibodies selectively labelled neurones containing either GnRH, or kisspeptin (VGF N-terminus only), pituitary gonadotrophs and lactotrophs, or oocytes (PGH peptides only).

NPY and VGF immunoreactivity increased in the arcuate nucleus, but decreased in the nucleus of the Tractus Solitarius, of type-II diabetic patients.

Ample animal studies demonstrate that neuropeptides NPY and α-MSH expressed in Arcuate Nucleus and Nucleus of the Tractus Solitarius, modulate glucose homeostasis and food intake. In contrast is the absence of data validating these observations for human disease. Here we compare the post mortem immunoreactivity of the metabolic neuropeptides NPY, αMSH and VGF in the infundibular nucleus, and brainstem of 11 type-2 diabetic and 11 non-diabetic individuals.

VGF peptides upon osmotic stimuli: changes in neuroendocrine regulatory peptides 1 and 2 in the hypothalamic-pituitary-axis and plasma.

VGF or VGF nerve growth factor inducible is a protein that has been found to play a role in regulating energy homeostasis and metabolism. From VGF precursor derive two neuroendocrine regulatory peptides NERP-1 and NERP-2 that, intracerebroventricular (icv) injected, modulate the antidiuretic hormone (ADH) release. Thus, we investigated possible modulations of the NERPs and other VGF peptides (namely VGF C-terminus, TLQP and PGH) in the hypothalamic-pituitary-axis, adrenal gland and plasma upon osmotic stimuli.

Novel neuronal and endocrine autoantibody targets in Autoimmune Polyendocrine Syndrome type 1.

Context: Although pituitary autoantibodies have frequently been reported in Autoimmune Polyendocrine Syndrome type 1 (APS1), the autoimmune involvement of the hypothalamic-pituitary axis remains to be elucidated.

Objective: Our aim was to identify in APS1 patients novel autoantibodies, especially against hypothalamic-pituitary targets, and to correlate their presence with clinical features.

Patients: We analyzed 14 APS1 patients from Sardinia, compared to other diseases and healthy donors.

Computer-aided detection of lung nodules via 3D fast radial transform, scale space representation, and Zernike MIP classification.

Purpose: The authors presented a novel system for automated nodule detection in lung CT exams.

Methods: The approach is based on (1) a lung tissue segmentation preprocessing step, composed of histogram thresholding, seeded region growing, and mathematical morphology; (2) a filtering step, whose aim is the preliminary detection of candidate nodules (via 3D fast radial filtering) and estimation of their geometrical features (via scale space analysis); and (3) a false positive reduction (FPR) step, comprising a heuristic FPR, which applies thresholds based on geometrical features, and a supervised FPR, which is based on support vector machines classification, which in turn, is enhanced by a feature extraction algorithm based on maximum intensity projection processing and Zernike moments.

Results: The system was validated on 154 chest axial CT exams provided by the lung image database consortium public database.

VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers.

The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ∼20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity.