Major Neurotransmitters in the Brain

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review is to examine the roles of four of the major neurotransmitters (dopamine, acetylcholine, serotonin, and glutamate) and the interactions that lead to the formation of Parkinson’s Disease and long-term potentiation

Quantum phase transition in ultrahigh mobility SiGe/Si/SiGe two-dimensional electron system

The metal-insulator transition (MIT) is an exceptional test bed for studying strong electron correlations in two dimensions in the presence of disorder. In the present study, it is found that in contrast to previous experiments on lower-mobility samples, in ultra-high mobility SiGe/Si/SiGe quantum wells the critical electron density, $n_{\text{c}}$, of the MIT becomes smaller than the density, $n_{\text{m}}$, where the effective mass at the Fermi level tends to diverge. Near the topological phase transition expected at $n_{\text{m}}$, the metallic temperature dependence of the resistance should be strengthened, which is consistent with the experimental observation of more than an order of magnitude resistance drop with decreasing temperature below $\sim1$ K.Comment: Misprints corrected. As publishe

"Taking Care of a Fruit Tree": Nurturing as a Layer of Concern in Online Community Moderation

Care in communities has a powerful influence on potentially disruptive social encounters. Practising care in moderation means exposing a group's core values, which, in turn, has the potential to strengthen identity and relationships in communities. Dissent is as inevitable in online communities as it is in their offline counterparts. However, dissent can be productive by sparking discussions that drive the evolution of community norms and boundaries, and there is value in understanding the role of moderation in this process. Our work draws on an exploratory analysis of moderation practices in the MetaFilter community, focusing on cases of intervention and response. We identify and analyse MetaFilter moderation with the metaphor: ``taking care of a fruit tree'', which is quoted from an interview with moderators on MetaFilter. We address the relevance of care as it is evidenced in these MetaFilter exchanges, and discuss what it might mean to approach an analysis of online moderation practices with a focus on nurturing care. We consider how HCI researchers might make use of care-as-nurture as a frame to identify multi-faceted and nuanced concepts characterising dissent and to develop tools for the sustainable support of online communities and their moderators

IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

Cadherin-4 plays a role in the development of zebrafish cranial ganglia and lateral line system

We previously reported that cadherin-4 (also called R-cadherin) was expressed by the majority of the developing zebrafish cranial and lateral line ganglia. Cadherin-4 (Cdh4) function in the formation of these structures in zebrafish was studied using morpholino antisense technology. Differentiation of the cranial and lateral line ganglia and lateral line nerve and neuromasts of the cdh4 morphants was analyzed using multiple neural markers. We found that a subset of the morphant cranial and lateral line ganglia were disorganized, smaller, with reduced staining, and/or with altered shape compared to control embryos. Increased cell death in the morphant ganglia likely contributed to these defects. Moreover, cdh4 morphants had shorter lateral line nerves and a reduced number of neuromasts, which was likely caused by disrupted migration of the lateral line primordia. These results indicate that Cdh4 plays a role in the normal formation of the zebrafish lateral line system and a subset of the cranial ganglia. Developmental Dynamics 236:893–902, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55963/1/21085_ftp.pd

OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.

Pathogenic OPA1 mutations cause autosomal dominant optic atrophy (DOA), a condition characterized by the preferential loss of retinal ganglion cells and progressive optic nerve degeneration. Approximately 20% of affected patients will also develop more severe neuromuscular complications, an important disease subgroup known as DOA(+). Cytochrome c oxidase (COX)-negative fibres and multiple mitochondrial DNA (mtDNA) deletions have been identified in skeletal muscle biopsies from patients manifesting both the pure and syndromal variants, raising the possibility that the accumulation of somatic mtDNA defects contribute to the disease process. In this study, we investigated the mtDNA changes induced by OPA1 mutations in skeletal muscle biopsies from 15 patients with both pure DOA and DOA(+) phenotypes. We observed a 2- to 4-fold increase in mtDNA copy number at the single-fibre level, and patients with DOA(+) features had significantly greater mtDNA proliferation in their COX-negative skeletal muscle fibres compared with patients with isolated optic neuropathy. Low levels of wild-type mtDNA molecules were present in COX-deficient muscle fibres from both pure DOA and DOA(+) patients, implicating haplo-insufficiency as the mechanism responsible for the biochemical defect. Our findings are consistent with the 'maintenance of wild-type' hypothesis, the secondary mtDNA deletions induced by OPA1 mutations triggering a compensatory mitochondrial proliferative response in order to maintain an optimal level of wild-type mtDNA genomes. However, when deletion levels reach a critical level, further mitochondrial proliferation leads to replication of the mutant species at the expense of wild-type mtDNA, resulting in the loss of respiratory chain COX activity

Neuropsychological Predictors of Safety in Urban Left-Turn Scenarios

Left turns at urban intersections can be dangerous, especially when views are obstructed or pedestrians are present. Impairments in driver vision, motor, and cognition functions may further increase left-turn risk. We examined this problem in a simulated environment that included left-turn scenarios to study the driving behaviors of 28 drivers, ages 37 to 88 years, six of whom had “Useful Field of View” (UFOV) impairments. Subjects also completed a battery of neuropsychological tests. The simulated drive included an urban section with six left turns in three types of scenarios: 1) a semi truck blocking the view of oncoming traffic, 2) a lead vehicle obstruction, and 3) a pedestrian crossing ahead of the turning driver. Results showed a mean (SD) of 1.46 (1.60) collisions per driver (range 0 to 7), 83% of which occurred at intersections with semi trucks. Far visual acuity, contrast sensitivity, UFOV, Mini Mental State Examination, TrailMaking Test Part B, the Wisconsin Card Sort task, and age were all associated with the total number of collisions (Pearson correlation magnitudes between 0.37 to 0.77; p-values\u3c0.05). Spearman correlations were less significant. Findings indicate that visual obstruction by on oncoming semi-truck is a particularly dangerous left-turn situation

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority