Economic Sustainability of Inner City Streets: A Collaborative Sustainable Asset Management Transportation System Model

The research team developed and created a sustainable asset management transportation system model, focusing on inner-city road conditions related to municipal asset allocation within three St. Louis, Missouri wards. To facilitate the research objectives, the team collaborated with Missouri constituents including the Missouri Department of Transportation (MoDOT), the City of St. Louis Street Department, local government officials, universities, and stakeholders. Selection criteria for roadways included roads, traffic, location, safety, utility, and demographics. A 45-block area was divided into six sections and roads were surveyed, photographed, and evaluated using The Transportation Engineers Association of Missouri’s Pavement Surface Evaluation and Rating (PASER). Necessary street repairs and costs of each repair were calculated using global mapping technology and historical cost data. Since aldermen decide street asset allocations, costs were allocated to each city ward district. These assessments, which were based on a technology-driven model, should assist in the construction of future financial models based on a need projection to dollars spent ratio per fiscal year. It is expected that this economic model will be implemented in the St. Louis Metropolitan Region and replicated by similar municipalities

Microglia-Astrocyte Communication in Alzheimer's Disease

Microglia and astrocytes are regarded as active participants in the central nervous system under various neuropathological conditions, including Alzheimer's disease (AD). Both microglia and astrocyte activation have been reported to occur with a spatially and temporarily distinct pattern. Acting as a double-edged sword, glia-mediated neuroinflammation may be both detrimental and beneficial to the brain. In a variety of neuropathologies, microglia are activated before astrocytes, which facilitates astrocyte activation. Yet reactive astrocytes can also prevent the activation of adjacent microglia in addition to helping them become activated. Studies describe changes in the genetic profile as well as cellular and molecular responses of these two types of glial cells that contribute to dysfunctional immune crosstalk in AD. In this paper, we construct current knowledge of microglia-astrocyte communication, highlighting the multifaceted functions of microglia and astrocytes and their role in AD. A thorough comprehension of microglia-astrocyte communication could hasten the creation of novel AD treatment approaches.</p

The State of the Art in Smart City Research – A Literature Analysis on Green IS Solutions to Foster Environmental Sustainability

Environmental sustainability is one of the most critical issues worldwide, concerning every individual. The main objective in this area is to preserve scarce resources and reduce CO2 emissions in order to prevent environmental degradation. In recent years the potential of information systems (IS) as a driver for environmental sustainability has emerged under the term “Green IS”. Given that cities represent a huge share of environmental degradation due to factors such as mobility, energy and water consumption, and waste production, the municipal domain offers huge potentials in terms of sustainability. The advent of smart cites is an attempt to address this concern. In this paper we aim to provide an overview of current publications on environmental sustainability in smart cities, as research in this field is still unstructured. This paper focuses on structuring the research field by providing a research framework to achieve a more holistic view on the application of Green IS. We distinguish between research performed by the IS community and that of related fields, such as urban development, and perform a cross-sectional, exhaustive literature analysis with almost 1,500 articles to uncover the differences and commonalities between the domains

The old second messenger cAMP teams up with novel cell death mechanisms:Potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease

Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent neurodegenerative disorders severely impacting life expectancy and quality of life of millions of people worldwide. AD and PD exhibit both a very distinct pathophysiological disease pattern. Intriguingly, recent researches, however, implicate that overlapping mechanisms may underlie AD and PD. In AD and PD, novel cell death mechanisms, encompassing parthanatos, netosis, lysosome-dependent cell death, senescence and ferroptosis, apparently rely on the production of reactive oxygen species, and seem to be modulated by the well-known, "old" second messenger cAMP. Signaling of cAMP via PKA and Epac promotes parthanatos and induces lysosomal cell death, while signaling of cAMP via PKA inhibits netosis and cellular senescence. Additionally, PKA protects against ferroptosis, whereas Epac1 promotes ferroptosis. Here we review the most recent insights into the overlapping mechanisms between AD and PD, with a special focus on cAMP signaling and the pharmacology of cAMP signaling pathways.</p

Reductive chain separation of botulinum A toxin — a prerequisite to its inhibitory action on exocytosis in chromaffin cells

Cleavage of the disulfide bond linking the heavy and the light chains of tetanus toxin is necessary for its inhibitory action on exocytotic release ofcatecholamines from permeabi1ized chromaffin cells [(1989) FEBS Lett. 242, 245-248; (1989) J. Neurochern., in press]. The related botulinum A toxin also consists of a heavy and a light chain linked by a disulfide bond. The actions ofboth neurotoxins on exocytosis were presently compared using streptolysin O-permeabilized bovine adrenal chromaffin cells. Botulinum A toxin inhibited Ca2 +-stimulated catecholamine release from these cells. Addition of dithiothreitollowered the effective doses to values below 5 nM. Under the same conditions, the effective doses of tetanus toxin were decreased by a factor of five. This indicates that the interchain S-S bond of botulinum A toxin must also be split before the neurotoxin can exert its effect on exocytosis

Vaccination prevented short-term memory loss, but deteriorated long-term spatial memory in Alzheimer's disease mice, independent of amyloid-β pathology

Background: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer's disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed.Objective: Study the therapeutic potential of this new vaccine in a mouse model for AD.Methods: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests.Results: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter.Conclusion: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.</p

Iron chelators inhibit amyloid-beta-induced production of lipocalin 2 in cultured astrocytes

Lipocalin 2 (Lcn2) has been implicated to play a role in various neurodegenerative diseases, and normalizing its overexpression may be of therapeutic potential. Iron chelators were found to reduce Lcn2 levels in certain animal models of CNS injury. Focusing on Alzheimer's disease (AD), we found that the iron chelators deferoxamine and deferiprone inhibited amyloid-β (Aβ)-induced Lcn2 production in cultured primary astrocytes. Accordingly, Aβ-exposure increased astrocytic ferritin production, indicating the possibility that Aβ induces iron accumulation in astrocytes. This effect was not significantly modulated by Lcn2. Known neuroprotective effects of iron chelators may rely in part on normalization of Lcn2 levels