Best Practices in Managing Social Media for Business

The mixed results of social media impacting on businesses have motivated this research to understand the best practices affecting the brand equity of a company utilizing the social media in business. Literature review of relevant theories is conducted. The industry publications of companies doing well in social media are analyzed to distill the best practices implemented in their social media strategies. Multiple case studies are proposed to determine how these best practices explain the desired business outcome in brand equity. The social media strategy concepts, media richness theory and Hagel III and Armstrong’s framework of virtual member development are suggested in guiding our data collection, analysis and interpretation. This research in progress is expected to contribute to the existing knowledge by providing a prescriptive framework of best practices in utilizing Facebook social network, and integrating and extending existing theories to explain the use of social media for developing brand equity

Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice

Alzheimer’s disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research

Clarifying the translational potential of B-I09

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IFN-g Induces Histone 3 Lysine 27 Trimethylation in a Small Subset of Promoters to Stably Silence Gene Expression in Human Macrophages

The mechanisms by which IFN-g activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-g represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-g is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-g signaling was terminated, and these silenced genes were no longer responsive to glucocorticoids, IL-4, and M-CSF. These results identify cytokineinduced H3K27 trimethylation as a mechanism that stabilizes gene silencing in macrophages. IFN-ginduced macrophage activation is thus reinforced by a chromatin-based mechanism that blocks antiinflammatory and opposing pathways

Association between abdominal aortic calcification, bone mineral density and fracture in older women

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single‐energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10‐year study of 1,024 older predominantly Caucasian women (mean age 75.0±2.6 years) from the Perth Longitudinal Study of Aging cohort we evaluated the association between AAC, skeletal structure and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into; low AAC (score 0 and 1, n=459), moderate AAC (score 2‐5, n=373) and severe AAC (score \u3e 6, n=192). Prevalent vertebral fractures were calculated using the Genant semi‐quantitative method. AAC24 scores were inversely related to hip bone mineral density (BMD) (rs=‐0.077, p=0.013) and heel broadband ultrasound attenuation (rs=‐0.074, p=0.020) and stiffness index (rs=‐0.073, p=0.022). In cross‐sectional analyses women with moderate to severe AAC were more likely to have prevalent fracture and LSI detected lumbar spine but not thoracic spine fractures (Mantel‐Haentzel test of trend p \u3c 0.05). For 10‐year incident clinical fractures and fracture‐related hospitalizations women with moderate to severe AAC (AAC24 score \u3e1) had increased fracture risk (HR 1.48 [1.15‐1.91], p=0.002; HR 1.46 [1.07‐1.99], p=0.019, respectively) compared to women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40 [1.08‐1.81], p=0.010) but was attenuated for fracture‐related hospitalizations (HR 1.33 [0.98‐1.83], p=0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated

The Activation of DNA Damage Detection and Repair Responses in Cleavage-Stage Rat Embryos by a Damaged Paternal Genome

Male germ cell DNA damage, after exposure to radiation, exogenous chemicals, or chemotherapeutic agents, is a major cause of male infertility. DNA-damaged spermatozoa can fertilize oocytes; this is of concern because there is limited information on the capacity of early embryos to repair a damaged male genome or on the fate of these embryos if repair is inadequate. We hypothesized that the early activation of DNA damage response in the early embryo is a critical determinant of its fate. The objective of this study was to assess the DNA damage response and mitochondrial function as a measure of the energy supply for DNA repair and general health in cleavage-stage embryos sired by males chronically exposed to an anticancer alkylating agent, cyclophosphamide. Male rats were treated with saline or cyclophosphamide (6 mg/kg/day) for 4 weeks and mated to naturally cycling females. Pronuclear two- and eight-cell embryos were collected for immunofluorescence analysis of mitochondrial function and biomarkers of the DNA damage response: γH2AX foci, 53BP1 reactivity, and poly(ADP-ribose) polymer formation. Mitochondrial activities did not differ between embryos sired by control- and cyclophosphamide-exposed males. At the two-cell stage, there was no treatment-related increase in DNA double-strand breaks; by the eight-cell stage, a significant increase was noted, as indicated by increased medium and large γH2AX foci. This was accompanied by a dampened DNA repair response, detected as a decrease in the nuclear intensity of poly(ADP-ribose) polymers. The micronuclei formed in cyclophosphamide-sired embryos contained large γH2AX foci and enhanced poly(ADP-ribose) polymer and 53BP1 reactivity compared with their nuclear counterparts. Thus, paternal cyclophosphamide exposure activated a DNA damage response in cleavage-stage embryos. Furthermore, this damage response may be useful in assessing embryo quality and developmental competence

Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-B regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet\u27s disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-B signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IBα and nuclear translocation of the NF-B p65 subunit together with increased expression of NF-B-mediated proinflammatory cytokines. A20 restricts NF-B signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-B-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease

A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation

Highlights • We compared MRI and neuropsychological test data in twins discordant for VCP mutation. • Affected twin revealed rapid cognitive decline in a span of 1 year. • FTD related cognitive features may precede behavioral changes in VCP disease. • Cognitive-behavioral impairment may be missed on routine neurological exam and MMSE. • Need for a dedicated screening measure to recognize the neurological impairment. ARTICLE IN PRESS Please cite this article in press as: Abhilasha Surampalli, Brian T. Gold, Charles Smith, Rudy J. Abstract Inclusion body myopathy, Paget disease of bone and/or frontotemporal dementia is an autosomal dominant disease caused by mutations in the Valosin Containing Protein (VCP) gene. We compared clinical findings including MRI images and neuropsychological assessment data in affected and unaffected twin brothers aged 56 years from a family with the p.R155C VCP gene mutation. The affected twin presented with a 10 year history of progressive proximal muscle weakness, difficulty swallowing, gastroesophageal reflux, fecal incontinence, and peripheral neuropathy. Comprehensive neuropsychological testing revealed rapid cognitive decline in the absence of any behavioral changes in a span of 1 year. This case illustrates that frontotemporal dementia related cognitive impairment may precede behavioral changes in VCP disease as compared with predominance of behavioral impairment reported in previous studies. Our findings suggest that there is a need to establish VCP disease specific tools and normative rates of decline to detect pre-clinical cognitive impairment among affected individuals

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided