Unraveling the perceived overqualification puzzle: The role of distributive justice and leader political skill in influencing knowledge sharing.

Perceived overqualification is a prevalent phenomenon in any type of organization due to overeducation and worldwide economic downturn. Despite numerous empirical examinations of such phenomenon, the impact of perceived overqualification on individual behaviors is inconsistent and inconclusive. We draw on equity theory to examine the negative effect of perceived overqualification on knowledge sharing through distributive justice. In addition, we investigate a leader's political skill as a boundary condition that influences the impact of perceived overqualification on distributive justice and subsequent knowledge sharing. Using a sample of 339 team members in South Korea, we found that perceived overqualification negatively impacts distributive justice, subsequently deteriorating employees' knowledge-sharing behaviors. Furthermore, when team leader is politically skilled, the negative impact of perceived overqualification on knowledge sharing is weakened. Theoretical implications and directions for future research are discussed.

Altered expression of miR-202 in cerebellum of multiple-system atrophy.

Cerebellar degeneration is a devastating manifestation of cerebellar-type multiple-system atrophy (MSA), a rapidly progressive neurodegenerative disease, and the exact pathogenesis is unknown. Here, we examined the expression of micro-RNAs (miRNAs), which are short noncoding RNAs, in the cerebellum of MSA and the key target genes. miRNA microarray found 11 miRNAs with significantly different expression in MSA cerebellum compared to cerebellum from age-, sex-, and postmortem interval-matched controls. miR-202 was the most upregulated in the MSA samples. In silico analysis, followed by target gene luciferase assay, in vitro transfection, and Western blotting in human samples showed that miR-202 downregulates Oct1 (Pou2f1), a transcription factor expressed in cerebellar Purkinje cells. Transfection of Neuro-2a cells with miR-202 enhanced oxidative stress-induced cell death, and an antagomir to miR-202 inhibited this effect of miR-202. This study provides novel insight into the role of miRNA in cerebellar degeneration and suggests that miR-202 is a key miRNA mediating the pathogenesis of MSA.

Growth Hormone Deteriorates the Functional Outcome in an Experimental Model of Huntington's Disease Induced by 3-Nitropionic Acid.

BACKGROUND AND PURPOSE: Growth hormone (GH) has been frequently used to control the aging process in healthy individuals, probably due to its slowing effect on senescence-associated degeneration. Mitochondrial dysfunction is related to the aging process, and one of the chemical models of Huntington's disease is that it can be induced by mitochondrial toxin. To investigate the potential application of GH to modify the progression of Huntington's disease (HD), we examined whether GH can protect the functional deterioration by striatal damage induced by 3-nitropropionic acid (3NP). METHODS: 3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for five consecutive days, and the rats received intraperitoneal administration of GH or vehicle (saline) throughout the experiment. Neurological deficits and body weight were monitored. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to further determine the mitochondrial activity in cultured N18TG2 neuroblastoma cells in vitro. RESULTS: 3NP-treated rats showed progressive neurologic deficits with striatal damage. Application of GH accelerated behavioral deterioration, particularly between day 3 and day 5, resulting in reduced survival outcome. The body weights of rats given 3NP were decreased, but GH did not affect such decrease compared to the non-treated control group. The effect of GH on cultured neuronal cells was a decrease in the MTT absorbance, suggesting a lower number of cells in a dose dependent pattern. CONCLUSIONS: Those results suggest that application of GH to a 3NP-induced experimental model of HD deteriorates the progress of functional deficits, possibly disturbing mitochondrial activities.

Electroacupuncture enhances motor recovery performance with brain-derived neurotrophic factor expression in rats with cerebral infarction.

OBJECTIVE: Electroacupuncture (EA) is a traditional medicine in patients with post-stroke rehabilitation. Brain-derived neurotrophic factor (BDNF) is a potent growth factor involved in recovery following cerebral injury. The aim of the present study was to investigate whether EA increases BDNF levels and facilitates functional recovery. METHODS: Occlusion of the middle cerebral artery was performed in rats (N=12) followed by reperfusion. EA was applied at the GV20 (Baihui) acupoint. Motor and sensory functions were monitored on the Garcia scale for 2 weeks. Expressions of BDNF and receptor tyrosine kinase B (trkB) were determined by immunoblotting and immunohistochemistry. RESULTS: Improvement of Garcia scores, particularly in motor performance, were noted in the group with EA stimulation (p<0.05). With EA application, BDNF was elevated in the ischaemic hemisphere with increased numbers of BDNF(+) cells. Increased expression of trkB was also detected. CONCLUSION: These results indicate that EA at GV20 improves motor recovery and stimulates BDNF/trkB expression in rats with cerebral ischaemia.

Circulating CD62E+ microparticles and cardiovascular outcomes.

BACKGROUND: Activated endothelial cells release plasma membrane submicron vesicles expressing CD62E (E-selectin) into blood, known as endothelial microparticles (EMPs). We studied whether the levels of endothelial microparticles expressing CD62E(+), CD31(+)/Annexin-V(+), or CD31(+)/CD42(-) predict cardiovascular outcomes in patients with stroke history. METHODS/PRINCIPAL FINDINGS: Patients with stroke history at least 3 months prior to enrolment were recruited. Peripheral blood EMP levels were measured by flow cytometry. Major cardiovascular events and death were monitored for 36 months. Three hundred patients were enrolled, of which 298 completed the study according to protocol. Major cardiovascular events occurred in 29 patients (9.7%). Nine patients died, five from cardiovascular causes. Cumulative event-free survival rates were lower in patients with high levels of CD62E(+) microparticles. Multivariate Cox regression analysis adjusted for cardiovascular risk factors, medications and stroke etiologic groups showed an association between a high CD62E(+) microparticle level and a risk of major cardiovascular events and hospitalization. Levels of other kinds of EMPs expressing CD31(+)/Annexin-V(+) or CD31(+)/CD42(-) markers were not predictive of cardiovascular outcomes. CONCLUSION: A high level of CD62E(+) microparticles is associated with cardiovascular events in patients with stroke history, suggesting that the systemic endothelial activation increases the risk for cardiovascular morbidities.

Altered microRNA regulation in Huntington's disease models.

Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD. However, the profiles and regulation of miRNAs in HD are not fully understood. Here, we analyzed the miRNA expression and miRNA regulators in two transgenic models of HD, YAC128 and R6/2 mice, and in a 3-nitropropionic acid (3NP)-induced striatal degeneration rat model. After characterizing the phenotypes by behavioral tests and histological analyses, we profiled striatal miRNAs using a miRNA microarray and we measured the key molecules involved in miRNA biogenesis and function. YAC128 mice showed upregulation-dominant miRNA expressions at 5 months and downregulation-dominant expressions at 12 months. Concomitantly, the expressions of Drosha-DGCR8, Exportin-5, and Dcp1 were increased at 5months, and the expression of Dicer was decreased at 12 months. In 10-week-old R6/2 mice, downregulation was dominant in the miRNA expressions and the level of Drosha decreased concomitantly. Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice. Meanwhile, 3NP rats showed dynamic changes in the miRNA profiles during disease development and a few miRNAs with altered expression. Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD.

Let-7 microRNA inhibits the proliferation of human glioblastoma cells.

MicroRNAs (miRNAs) are small noncoding RNAs comprising 21-23 nucleotides that regulate gene expression by transcriptionally repressing their complementary mRNAs. In particular, let-7 miRNA has been postulated to function as a tumor suppressor in various cancer cells, but not yet in glioblastoma. In this study, we investigated the anti-tumorigenic effect of let-7 miRNA in glioblastoma cells. Human glioblastoma cells (U251 or U87 cells) were transfected with let-7 miRNA and assayed for in-vitro proliferation, migration, and in-vivo tumor formation. Transfection of let-7 miRNA reduced expression of pan-RAS, N-RAS, and K-RAS in the glioblastoma cells. Let-7 miRNA also reduced the in-vitro proliferation and migration of the cells, and reduced the sizes of the tumors produced after transplantation into nude mice. However, let-7 miRNA exerted no effect on the proliferation of normal human astrocytes. These results indicate that let-7 miRNA has an anti-tumorigenic effect on glioblastoma cells, and suggest possible use of let-7 miRNA for treating glioblastoma.

Slowed progression in models of Huntington disease by adipose stem cell transplantation.

OBJECTIVE: Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. METHODS: ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. RESULTS: In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1alpha expression. INTERPRETATION: Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors.

Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease.

The acetylcholinesterase inhibitor (AChEI) galantamine is currently used to treat mild to moderate Alzheimer's disease (AD), and it has been suggested to have several neuroprotective effects. To investigate the potential application of this drug to the treatment of Huntington's disease, we examined whether galantamine can reduce the striatal degeneration induced by the mitochondrial toxin, 3-nitropropionic acid (3NP). 3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for 5 consecutive days, and the rats received intraperitoneal administration of either different concentrations of galantamine (1mg/kg/day or 10 mg/kg/day, twice daily) or vehicle (saline) throughout the experiment. Galantamine attenuated the 3NP-induced neurologic deficits on days 2-5. Galantamine-treated rats showed smaller striatal lesion volumes measured by Nissl staining and lower numbers of TUNEL(+) apoptotic cells when compared to the vehicle-treated rats. Galantamine failed to reduce the striatal lesion volume when co-administered with mecamylamine, a nicotinic acetylcholine receptor antagonist. Our data indicate that galantamine can attenuate neurodegeneration in a Huntington's disease model by modulating nAChR.

The application of magnets directs the orientation of neurite outgrowth in cultured human neuronal cells.

Electric and magnetic fields have been known to influence cellular behavior. In the present study, we hypothesized that the application of static magnetic fields to neurons will cause neurites to grow in a specific direction. In cultured human neuronal SH-SY5Y cells or PC12 cells, neurite outgrowth was induced by forskolin, retinoic acid, or nerve growth factor (NGF). We applied static magnetic fields to the neurons and analyzed the direction and morphology of newly formed neuronal processes. In the presence of the magnetic field, neurites grew in a direction perpendicular to the direction of the magnetic field, as revealed by the higher orientation index of neurites grown under the magnetic field compared to that of the neurites grown in the absence of the magnetic field. The neurites parallel to the magnetic field appeared to be dystrophic, beaded or thickened, suggesting that they would hinder further elongation processes. The co-localized areas of microtubules and actin filaments were arranged into the vertical axis to the magnetic field, while the levels of neurofilament and synaptotagmin were not altered. Our results suggest that the application of magnetic field can be used to modulate the orientation and direction of neurite formation in cultured human neuronal cells.

Neuroprotective effect of neural stem cell-conditioned media in in vitro model of Huntington's disease.

Although neural stem cell (NSC) transplantation has been investigated as a promising tool for reconstituting damaged brains, recent evidences suggest that NSCs may rescue the brain via paracrine effects rather than by direct cell replacements. In this study, we attempted to determine the neuroprotective effect of NSC-conditioned media (NSC-CM) in in vitro model of Huntington's disease. Cerebral hybrid neurons (A1) were transfected with either wild-type huntingtin (18 CAG repeats) or mutant huntingtin (100 CAG repeats). At 24h after the transfection, immunocytochemical patterns of the huntingtin aggregations, as well as the level of N-terminal proteolytic cleavages of huntingtin were analyzed. Neuronal apoptosis was evaluated with flowcytometry after Annexin-V and propidium iodide (PI) staining. Cerebral hybrid neurons transfected with mutant huntingtin showed five aggregates patterns, including diffuse cytoplasmic, dispered vacuoles, perinuclear vacuoles, nuclear inclusions (NI), and cytoplasmic inclusions (CI). NSC-CM reduced the levels of nuclear and cytoplasmic inclusions. The transfection with mutant huntingtin increased the level of N-terminal cleavages, which was reduced by the NSC-CM treatment. In addition, NSC-CM reduced the Annexin-V(+)PI(+) and Annexin-V(+)PI(-) neurons which were induced by the mutant huntingtin transfection. In summary, NSC-CM was neuroprotective in in vitro model of Huntington's disease with modulating mutant huntingtin-induced cytotoxicity.

Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease.

Huntington's disease (HD) has a mitochondrial dysfunction causing the vulnerability to the excitotoxicity and activations of multiple cell death pathways. Recent evidences suggest that the hematopoietic cytokine, granulocyte-colony stimulating factor (G-CSF), exerts pleiotropic neuroprotection in acute neural injury with activating various survival pathways. Thus, we investigated whether G-CSF can modulate neurodegeneration in an HD animal model induced by 3-nitropropionic acid (3NP), which inhibits mitochondrial succinate dehydrogenase complex II. Either G-CSF (50 microg/kg/day) or saline (as vehicle) was administered intraperitoneally for 5 days with 3NP (63 mg/kg/day) continuous osmotic pump infusion into male Lewis rats. We measured motor scales (0-8) daily and sacrificed rats at 5 days. We observed that G-CSF receptors were expressed in 3NP-induced degenerating striatum. Rats treated with G-CSF showed less degree of neurologic deficits. In the G-CSF-treated rats, the striatal lesion volume measured by Nissl staining, TUNEL+ apoptotic cells, Fluorojade C+ degenerating neurons, and c-Jun+ cells were all decreased. In western blotting, G-CSF activated survival pathways including p-ERK, p-eNOS, p-STAT3, and p-Akt. In summary, G-CSF was found to have neuroprotective effects and save striatal cells through activations of survival pathways in the 3NP-induced striatal degeneration model for HD.

Atorvastatin attenuates mitochondrial toxin-induced striatal degeneration, with decreasing iNOS/c-Jun levels and activating ERK/Akt pathways.

Mitochondrial dysfunction is a major contributor to neurodegeneration, and causes vulnerability to oxidative stress and the activations of downstream cell death pathways. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, statins, were originally developed as cholesterol lowering agents, and have cholesterol-independent anti-excitotoxic and anti-oxidative properties. We investigated whether atorvastatin can prevent the neurodegeneration induced by a mitochondrial toxin, 3-nitropropionic acid (3NP), which inhibits succinate dehydrogenase complex II. Male Lewis rats were administered 3NP (63 mg/kg/day) using osmotic pumps for 5 days to induce striatal degeneration, and were also treated with either atorvastatin (1 or 10 mg/kg/day, orally) or vehicle (control) on five consecutive days. Atorvastatin-treated rats showed fewer neurologic deficits than control animals as measured at day 3-5. Atorvastatin-treated animals showed reduced striatal lesion volumes by Nissl staining, and decreased numbers of TUNEL-positive apoptosis and Fluoro-Jade C-positive degenerating neurons at 5 days. Atorvastatin reduced the numbers of c-Jun-positive and p-c-Jun-positive cells, as well as 3-nitrotyrosin-positive cells. In addition, atorvastatin increased p-extracellular signal-regulated kinase and p-Akt levels, and attenuated the up-regulation of inducible nitric oxide synthase by 3NP. When N(omega)-nitro-l-arginine methyl ester hydrochloride was administered concomitantly with the 3NP infusion, atorvastatin failed to further reduce the striatal lesion volume and c-Jun levels compared to the vehicle treatment. In summary, atorvastatin decreased striatal neurodegeneration induced by 3NP, with attenuating inducible nitric oxide synthase and c-Jun levels as well as activating extracellular signal-regulated kinase and Akt.