CRF serum levels differentiate PTSD from healthy controls and TBI in military veterans.

Background And Objective: Posttraumatic stress disorder (PTSD) is a serious and frequently debilitating psychiatric condition that can occur in people who have experienced traumatic stessors, such as war, violence, sexual assault and other life-threatening events. Treatment of PTSD and traumatic brain injury (TBI) in veterans is challenged by diagnostic complexity, partially due to PTSD and TBI symptom overlap and to the fact that subjective self-report assessments may be influenced by a patient's willingness to share their traumatic experiences and resulting symptoms. Corticotropin-releasing factor (CRF) is one of the main mediators of hypothalamic pituitary adrenal (HPA)-axis responses in stress and anxiety.

Ovarian cancer and KiSS-1 gene expression: A consideration of the use of Kisspeptin plus Kisspeptin aptamers in diagnostics and therapy.

Gynaecological cancers continue to present a significant health burden upon the health of the global female population. This deficit is most prominent with ovarian cancer which possesses the lowest survival rate compared to all other cancers occurring within this anatomical region, with an annual UK-mortality of 7,300. The poor tolerability and selectively of the treatment options that are currently available is likely to have contributed to this high mortality rate thus, demonstrating the need for the development of enhanced therapeutic approaches.

Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates.

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6-10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS).

Defining the mechanism of PDI interaction with disulfide-free amyloidogenic proteins: Implications for exogenous protein expression and neurodegenerative disease.

Protein disulfide isomerase (PDI) is an important molecular chaperone capable of facilitating protein folding in addition to catalyzing the formation of a disulfide bond. To better understand the distinct substrate-screening principles of Pichia pastoris PDI (Protein disulfide isomerase) and the protective role of PDI in amyloidogenic diseases, we investigated the expression abundance and intracellular retention levels of three archetypal amyloidogenic disulfide bond-free proteins (Aβ42, α-synuclein (α-Syn) and SAA1) in P. pastoris GS115 strain without and with the overexpression of PpPDI (P.

The -formyl peptide receptors: contemporary roles in neuronal function and dysfunction.

N-formyl peptide receptors (FPRs) were first identified upon phagocytic leukocytes, but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family. FPRs are expressed within neuronal tissues and markedly in the central nervous system, where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, as well as neurological cancers such as neuroblastoma. Whilst the homeostatic function of FPRs in the nervous system is currently undefined, a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.

The formyl peptide receptor agonist FPRa14 induces differentiation of Neuro2a mouse neuroblastoma cells into multiple distinct morphologies which can be specifically inhibited with FPR antagonists and FPR knockdown using siRNA.

The N-formyl peptide receptors (FPRs) have been identified within neuronal tissues and may serve as yet undetermined functions within the nervous system. The FPRs have been implicated in the progression and invasiveness of neuroblastoma and other cancers. In this study the effects of the synthetic FPR agonist FPRa14, FPR antagonists and FPR knockdown using siRNA on mouse neuroblastoma neuro2a (N2a) cell differentiation plus toxicity were examined.

Immunocytochemical staining of endogenous nuclear proteins with the HIS-1 anti-poly-histidine monoclonal antibody: a potential source of error in His-tagged protein detection.

Histidine-tagged proteins are widely used in biochemical studies and frequently detected with antibodies specific for the histidine tag. Immunocytochemistry is widely used in studies with overexpressed proteins to determine cellular localization and in the case of histidine-tagged proteins can be carried out with anti-polyhistidine antibodies. Recent studies have suggested that polyhistidine sequences are present within a small number of human proteins and may direct expression to the nucleus and nuclear speckles compartments of the cell.

Benzothiazole aniline tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro.

Alzheimer's disease, Familial British dementia, Familial Danish dementia, Type 2 diabetes mellitus, plus Creutzfeldt-Jakob disease are associated with amyloid fibril deposition and oxidative stress. The antioxidant enzyme catalase is a neuroprotective amyloid binding protein. Herein the effects of catalase overexpression in SH-SY5Y neuronal cells on the toxicity of amyloid-β (Aβ), amyloid-Bri (ABri), amyloid-Dan (ADan), amylin (IAPP), and prion protein (PrP) peptides were determined.

Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient.

The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits.

The Role of Neurotransmitters in Protection against Amyloid- β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons.

Recent studies have suggested that the kisspeptin (KP) and kissorphin (KSO) peptides have neuroprotective actions against the Alzheimer's amyloid- β (A β ) peptide. Overexpression of the human KiSS-1 gene that codes for KP and KSO peptides in SH-SY5Y neurons has also been shown to inhibit A β neurotoxicity. The in vivo actions of KP include activation of neuroendocrine and neurotransmitter systems.

Introduction and technical survey: protein aggregation and fibrillogenesis.

In this chapter we provided the overall background to the subject of protein aggregation and fibrillogenesis in amyloidogenesis, with introduction and brief discussion of the various topics that are included with the coming chapters. The division of the book into basic science and clinical science sections enables correlation of the topics to be made. The many proteins and peptides that have currently been found to undergo fibrillogenesis are tabulated.

Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro.

Alzheimer's disease (AD) onset is associated with changes in hypothalamic-pituitary-gonadal (HPG) function. The 54 amino acid kisspeptin (KP) peptide regulates the HPG axis and alters antioxidant enzyme expression. The Alzheimer's amyloid-β (Aβ) is neurotoxic, and this action can be prevented by the antioxidant enzyme catalase.

Fibril formation and toxicity of the non-amyloidogenic rat amylin peptide.

Full-length native rat amylin 1-37 has previously been widely shown to be unable to form fibrils and to lack the toxicity of the human amylin form leading to its use as a non-amyloidogenic control peptide. A recent study has suggested that rat amylin 1-37 forms amyloidogenic β-sheet structures in the presence of the human amylin form and suggested that this property could promote toxicity. Using TEM analysis we show here fibril formation by synthetic rat amylin 1-37 and 8-37 peptides when the lyophilized HPLC purified peptides are initially dissolved in 20 mM Tris-HCl.

In Vitro Activities of Kissorphin, a Novel Hexapeptide KiSS-1 Derivative, in Neuronal Cells.

The primary products of the metastasis-suppressor KiSS-1 gene are the kisspeptin (KP) peptides that stimulate gonadotrophin-releasing-hormone (GnRH) release via GPR-54 receptor activation. Recent studies have suggested that the KP-10 peptide also activates neuropeptide FF (NPFF) receptors. The aim of the current study was to determine the activities of the KiSS-1 derivative kissorphin (KSO), which contains the first six amino acids of the KP-10 peptide, is C-terminally amidated, and shares amino acid similarities with the biologically active NPFF 3-8 sequence.

A ground-layer adaptive optics system with multiple laser guide stars.

To determine the influence of the environment on star formation, we need to study the process in the extreme conditions of massive young star clusters ( approximately 10(4) solar masses) near the centre of our own Galaxy. Observations must be carried out in the near infrared because of very high extinction in visible light within the Galactic plane. We need high resolution to identify cluster members from their peculiar motions, and because most such clusters span more than 1', efficient observation demands a wide field of view.

Human islet amyloid polypeptide fibril binding to catalase: a transmission electron microscopy and microplate study.

The diabetes-associated human islet amyloid polypeptide (IAPP) is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-beta (A-beta) and prion protein (PrP) fibrils. Previous studies have shown that catalase binds to A-beta fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27.

Cholesterol in Alzheimer's disease and other amyloidogenic disorders.

The complex association of cholesterol metabolism and Alzheimer's disease is presented in depth, including the possible benefits to be gained from cholesterol-lowering statin therapy. Then follows a survey of the role of neuronal membrane cholesterol in Abeta pore formation and Abeta fibrillogenesis, together with the link with membrane raft domains and gangliosides. The contribution of structural studies to Abeta fibrillogenesis, using TEM and AFM, is given some emphasis.

Association of Group B Streptococcus colonization and bovine exposure: a prospective cross-sectional cohort study.

Background: While Group B Streptococcus (GBS) human colonization and infection has long been suspected as originating from cows, several investigators have suggested that ongoing interspecies GBS transmission is unlikely due to genotyping data demonstrating that human and bovine-derived GBS strains represent mostly distinct populations. The possibility of ongoing transmission between humans and their livestock has not been systematically examined.

Methodology/principal Findings: To examine ongoing interspecies transmission, we conducted a prospective cross-sectional cohort study of 68 families and their livestock.

Polymorphism of amyloid-beta fibrils and its effects on human erythrocyte catalase binding.

The Alzheimer's amyloid-beta (Abeta) peptide exists as a number of naturally occurring forms due to differential proteolytic processing of its precursor molecule. Many of the Abeta peptides of different lengths form fibrils in vitro, which often show polymorphisms in the fibril structure. This study presents a TEM based analysis of fibril formation by eighteen different Abeta peptides ranging in length from 5 to 43 amino acids.

Selection, recombination, and virulence gene diversity among group B streptococcal genotypes.

Transmission of group B Streptococcus (GBS) from mothers to neonates during childbirth is a leading cause of neonatal sepsis and meningitis. Although subtyping tools have identified specific GBS phylogenetic lineages that are important in neonatal disease, little is known about the genetic diversity of these lineages or the roles that recombination and selection play in the generation of emergent genotypes. Here, we examined genetic variation, selection, and recombination in seven multilocus sequence typing (MLST) loci from 94 invasive, colonizing, and bovine strains representing 38 GBS sequence types and performed DNA sequencing and PCR-based restriction fragment length polymorphism analysis of several putative virulence genes to identify gene content differences between genotypes.

Vial breakage during freeze-drying: crystallization of sodium chloride in sodium chloride-sucrose frozen aqueous solutions.

The purpose of this study was to evaluate sodium chloride-sucrose frozen solutions with regard to sodium chloride crystallization and vial strain. Sodium chloride-sucrose solutions were studied using Differential Scanning Calorimetry (DSC) and a strain gauge instrumented vial. The sodium chloride concentration was varied with a fixed concentration of sucrose to identify a composition where crystallization was observed during heating and this composition was examined using the strain-gauged vials.

Experimental results of ground-layer and tomographic wavefront reconstruction from multiple laser guide stars.

We describe results from the first multi-laser wavefront sensing system designed to support tomographic modes of adaptive optics (AO). The system, now operating at the 6.5 m MMT telescope in Arizona, creates five beacons by Rayleigh scattering of laser beams at 532 nm integrated over a range from 20 to 29 km by dynamic refocus of the telescope optics.

Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration.

Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils.