The Financial Health of the Pension Guaranty Benefit Corporation (PBGC)

[Excerpt] The Pension Benefit Guaranty Corporation (PBGC) is a federal government agency created by the Employee Retirement Income Security Act of 1974 (ERISA) to protect the pensions of participants covered by most private sector, defined benefit pension plans. The PBGC receives no appropriated funds. The agency’s costs are offset by the assets of the plans that the PBGC takes over and premiums paid by the sponsors of covered pension plans. The premiums are established by Congress. The PBGC’s single-employer program posted an all-time high deficit of $23 billion in 2004; as of September 30, 2006, the deficit was$18 billion. The PBGC discloses an additional, off-balance sheet liability for reasonably possible terminations; as of September 30, 2006, it was $73 billion

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q< 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

Functional Amyloid Formation within Mammalian Tissue

Amyloid is a generally insoluble, fibrous cross-β sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin—a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology

Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality

A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor Nuclear Matrix Protein 4 (Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared to wild type (WT) animals. Nmp4-/- mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyper-anabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4-/- MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that Nmp4 has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that Nmp4-/- MSPCs exhibited an enhanced capacity for glycolytic conversion- a key step in bone anabolism. Nmp4-/- cells showed elevated collagen translation and secretion. Expression of matrix genes that contribute to bone material-level mechanical properties were elevated in Nmp4-/- cells, an observation that was supported by biomechanical testing of bone samples from Nmp4-/- and WT mice. We conclude that loss of Nmp4 increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality

Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease

Purpose: The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson’s disease (PD) pathology, and be detectable with one or more imaging modalities. Procedure: A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson’s and Alzheimer’s disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood–brain barrier permeability using intravital microscopy. Results: Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer’s pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable. Conclusions: Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology

FDG-PET imaging, EEG and sleep phenotypes as translational biomarkers for research in Alzheimer's disease

Peer reviewedPublisher PD

Differenzierung neurodegenerativer Parkinsonsyndrome mittels vestibulär evozierter myogener Potentiale und Gleichgewichtsprüfung

Objective: Vestibular Evoked Myogenic Potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability. Methods: We assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson’s disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead. Results: Patients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A classifier using support vector machine was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires. Conclusions: Both oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment. Significance: OVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.:1. Einleitung 2. Publikationsmanuskript 3. Zusammenfassung 4. Literaturverzeichnis 5. Anlagen 6. Darstellung des eigenen Beitrages 7. Selbstständigkeitserklärung 8. Lebenslauf 9. Danksagun

Distress Disclosure and Personality in College Students

This study examined distress disclosure, the tendency to confide unpleasant feelings and experiences to others. Other factors under consideration were gender, personality factors (such as extraversion and one\u27s general tendency to disclose), and the identity of the person to whom individuals were asked to disclose. The subject pool included 22 male and 34 female volunteers from Bucknell University. Participants were asked to complete a measure of basic demographics, the Distress Disclosure Index, and the NEO-FFI measure of personality. They were then asked to disclose about an aspect of their lives that they personally found stressful, as if they were confiding in a best friend, a parent, or a professor, respectively. The transcriptions of those recordings were coded for length, depth, and breadth of the disclosure. The researcher hypothesized that greater length, depth, and breadth would be disclosed by females who scored highly on the Distress Disclosure Index, had high extraversion scores on the NEO-FFI, and had been asked to disclose to a best friend. The study found positive associations between openness and depth, neuroticism and depth, and gender with length, such that males were more likely to have longer disclosures. Negative associations were found between extraversion and depth, neuroticism and length, and openness and breadth. Personality factors, gender, and the disclosure target may act as better predictors of the tendency to disclose, rather than of the particular dimensions of disclosure, since every instance is unique

Parasite Variability in the Invasive Crayfish, Faxonius rusticus, in Northern New Jersey

The Northeast United States has been thoroughly invaded by the well-known invasive crayfish species Faxonius rusticus (rusty crayfish). Similar to the exploration of man to new regions, the spread of invasive species can cause the introduction of new diseases and parasites while conversely the invader has to deal with the already existing diseases and parasites. For crayfish, the most notable of these is a fungal plague, which has a poorly understood distribution in the United States. In this study, I collected rusty crayfish in Northern New Jersey to better understand the locations where they exist in the state. I also dissected a sample of collected individuals to look for various parasites or signs of parasitism. My results suggest that rusty crayfish are more likely to experience parasitism while in a cobble substratum compared to a mud substratum. In addition, most observed signs were primary indicators of the fungal plague. Although rusty crayfish and the fungal plague are well understood separately, these findings indicate that the two organisms need to be looked at more closely together to further clarify how impactful the plague truly is to the rusty crayfish population