The Impact of IT Structure and Firm Interdependency on Relational Rents in Innovation Collaboration Networks

This paper examines inter-organizational innovation collaboration networks (ICNs) using a relational view of the firm perspective. This study suggests that information technology (IT) structure and firm interdependencies can be significant predictors of relational rent generation for innovation collaboration networks. Furthermore, the authors argue that the alignment of these structural properties – IT structure and firm interdependency - will influence firm performance in terms of relational rents obtained by the innovation collaboration network. The relevant literature will be discussed and hypotheses proposed to empirically examine the relationship between IT structure and firm interdependencies on relational rent generation. Potential theoretical contributions to the relational view of the firm are identified and discussed. Limitations of the proposed study and discussion of the future research opportunities will also be provided

Randomized placebo controlled trials of n-acetyl cysteine as adjunct therapy for schizophrenia and bipolar disorder

Glutathione is the principal antioxidant of the brain. There is evidence of oxidative stress, lowered brain glutathione and genetic linkage involve glutathione metabolic genes in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a safe, orally bioavailable, precursor of glutathione. NAC has been shown to reverse animal models of oxidative stress, and raises brain glutathione levels.<br /

Employing the Precautionary Principle to Evaluate the Use of E-Cigarettes

Electronic cigarettes (e-cigarettes) have emerged onto the public market as an alternative to tobacco cigarettes; however, science is inconclusive as e-cigarettes have not been thoroughly investigated, including their short- and long-term risks and benefits (1, 2). The question arises of whether e-cigarettes will become the future tobacco crisis. This paper connects the precautionary principle to the use of e-cigarettes in an effort to guide decision-makers in the prevention of adverse health outcomes and societal costs

Missed Work Due to Occupational Illness Among Hispanic Horse Workers

Occupational illnesses are inadequately reported for agriculture, an industry dominated by a vulnerable Hispanic population and high fatal and nonfatal injury rates. Work-related illnesses can contribute to missed work, caused by a combination of personal and work factors, with costs to the individual, employer, and society. To better understand agricultural occupational illnesses, 225 Hispanic horse workers were interviewed via community-based convenience sampling. Descriptive statistics, bivariate analyses, and log binomial regression modeling were used to: (1) describe the prevalence of missed work due to work-related illnesses among Hispanic horse workers, (2) examine work-related and personal factors associated with missed work, and (3) identify health symptoms and work-related characteristics potentially associated with missed work. Key findings reveal that having at least one child (PR = 1.71, 95% CI = 1.03, 2.84), having poor self-reported general health (PR = 0.72, 95% CI = 0.48, 1.08), experiencing stress during a typical workday (PR = 2.58, 95% CI = 1.25, 5.32), or spending less time with horses (PR = 1.87, 95% CI = 1.15, 3.05) are significant predictors of missing work. Interventions can be designed to identify workers most susceptible to missing work and provide resources to reduce absenteeism. Future research should examine work-related illness in agricultural horse production, including personal and work-related factors, in order to diminish occupational health disparities among these workers, who are more likely to be employed in hazardous agricultural work

CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction

The linkages between neuroinflammation and Alzheimer's disease (AD) pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta) precursor protein mutant.We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP) mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion.We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain

HH Domain of Alzheimer’s Disease Aβ Provides Structural Basis for Neuronal Binding in PC12 and Mouse Cortical/Hippocampal Neurons

A key question in understanding AD is whether extracellular Aβ deposition of parenchymal amyloid plaques or intraneuronal Aβ accumulation initiates the AD process. Amyloid precursor protein (APP) is endocytosed from the cell surface into endosomes where it is cleaved to produce soluble Aβ which is then released into the brain interstitial fluid. Intraneuronal Aβ accumulation is hypothesized to predominate from the neuronal uptake of this soluble extracellular Aβ rather than from ER/Golgi processing of APP. We demonstrate that substitution of the two adjacent histidine residues of Aβ40 results in a significant decrease in its binding with PC12 cells and mouse cortical/hippocampal neurons. These substitutions also result in a dramatic enhancement of both thioflavin-T positive fibril formation and binding to preformed Aβ fibrils while maintaining its plaque-binding ability in AD transgenic mice. Hence, alteration of the histidine domain of Aβ prevented neuronal binding and drove Aβ to enhanced fibril formation and subsequent amyloid plaque deposition - a potential mechanism for removing toxic species of Aβ. Substitution or even masking of these Aβ histidine residues might provide a new therapeutic direction for minimizing neuronal uptake and subsequent neuronal degeneration and maximizing targeting to amyloid plaques

Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification

Background: The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results: In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion: Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

Background: The amyloid $\beta$-protein (A$\beta$) is believed to be the key mediator of Alzheimer's disease (AD) pathology. A$\beta$ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, A$\beta$ has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A$\beta$ as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of A$\beta$ and LL-37, an archetypical human AMP. Findings reveal that A$\beta$ exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A$\beta$ levels. Consistent with A$\beta$-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A$\beta$ antibodies. Conclusions/Significance: Our findings suggest A$\beta$ is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of A$\beta$-mediated pathology and has important implications for ongoing and future AD treatment strategies

Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal alzheimer\u27s disease: A preliminary study

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer\u27s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. Results: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401). Conclusions: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD