Environmental Racism: Nuclear Waste as an Agent of Oppression?

This research seeks to analyze the decision-making processes of managing nuclear waste for countries dealing with this problem, as well as the interplay between national and local governments, private companies, the populace, and native nations. The long-term storage of nuclear waste is a serious global problem, and despite the millions of people enjoying the benefits of nuclear power, most refuse to accept the burdens associated with its waste. The driving question for this research largely ties to how governments attempt to designate who will bear the burden of these wastes. When a problem needs to be solved, yet there are no clear, easy solutions, the weight is often placed on those who are either politically, economically, socially, or geographically disadvantaged. Through a deeper investigation into the global community, Australia, the United States, and the Skull Valley Goshute Tribe, we can see how these issues unfold and how affected communities attempt to fight back

The Effectiveness of Co-Teaching in the Elementary School

In 1994, the Individuals with Disabilities Education Act (IDEA) determined that students with disabilities should receive their education in the least restrictive environment (LRE) and should be integrated with their nondisabled peers in the general education classroom to the greatest extent possible (Murawaski & Dieker, 2008). The guiding principle was that being in a general education setting helps students learn what their peers are learning in the classroom. To fulfill the placement goals of IDEA, co-teaching has been promulgated as a teaching model that can ensure students with disabilities have access to the same core curriculum as their peers. Co-teaching is an approach that allows students with disabilities to receive the necessary support to meet their individual needs in the general education setting

The Potential of iPS Cells in Synucleinopathy Research

α-synuclein is a protein involved in the pathogenesis of several so-called synucleinopathies including Parkinson's disease. A variety of models have been so far assessed. Human induced pluripotent stem cells provide a patient- and disease-specific model for in vitro studies, pharmacotoxicological screens, and hope for future cell-based therapies. Initial experimental procedures include the harvest of patients' material for the reprogramming process, the investigation of the patients genetic background in the cultured cells, and the evaluation of disease-relevant factors/proteins under various cell culture conditions

The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells

Shank proteins, initially also described as ProSAP proteins, are scaffolding adaptors that have been previously shown to integrate neurotransmitter receptors into the cortical cytoskeleton at postsynaptic densities. We show here that Shank proteins are also crucial in receptor tyrosine kinase signaling. The PDZ domain–containing Shank3 protein was found to represent a novel interaction partner of the receptor tyrosine kinase Ret, which binds specifically to a PDZ-binding motif present in the Ret9 but not in the Ret51 isoform. Furthermore, we show that Ret9 but not Ret51 induces epithelial cells to form branched tubular structures in three-dimensional cultures in a Shank3-dependent manner. Ret9 but not Ret51 has been previously shown to be required for kidney development. Shank3 protein mediates sustained Erk–MAPK and PI3K signaling, which is crucial for tubule formation, through recruitment of the adaptor protein Grb2. These results demonstrate that the Shank3 adaptor protein can mediate cellular signaling, and provide a molecular mechanism for the biological divergence between the Ret9 and Ret51 isoform

Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation

ProSAP/Shank are scaffolding proteins that localize to the postsynaptic density (PSD). This study shows that Zn2+ ions directly regulate the localization and recruitment of Shank/ProSAP1/2 to PSDs to facilitate synapse formation and maturation

Development of Novel Zn2+ Loaded Nanoparticles Designed for Cell-Type Targeted Drug Release in CNS Neurons: In Vitro Evidences

Intact synaptic function and plasticity are fundamental prerequisites to a healthy brain. Therefore, synaptic proteins are one of the major targets for drugs used as neuro-chemical therapeutics. Unfortunately, the majority of drugs is not able to cross the blood–brain barrier (BBB) and is therefore distributed within the CNS parenchyma. Here, we report the development of novel biodegradable Nanoparticles (NPs), made of poly-lactide-co-glycolide (PLGA) conjugated with glycopeptides that are able to cross the BBB and deliver for example Zn2+ ions. We also provide a thorough characterization of loaded and unloaded NPs for their stability, cellular uptake, release properties, toxicity, and impact on cell trafficking. Our data reveal that these NPs are biocompatible, and can be used to elevate intracellular levels of Zn2+. Importantly, by engineering the surface of NPs with antibodies against NCAM1 and CD44, we were able to selectively target neurons or glial cells, respectively. Our results indicate that these biodegradable NPs provide a potential new venue for the delivery Zn2+ to the CNS and thus a means to explore the influence of altered zinc levels linked to neuropsychological disorders such as depression

Shank3 related muscular hypotonia is accompanied by increased intracellular calcium concentrations and ion channel dysregulation in striated muscle tissue

Phelan-McDermid syndrome (PMS) is a syndromic form of Autism Spectrum Disorders (ASD) classified as a rare genetic neurodevelopmental disorder featuring global developmental delay, absent or delayed speech, ASD-like behaviour and neonatal skeletal muscle hypotonia. PMS is caused by a heterozygous deletion of the distal end of chromosome 22q13.3 or SHANK3 mutations. We analyzed striated muscles of newborn Shank3Δ11(−/−) animals and found a significant enlargement of the sarcoplasmic reticulum as previously seen in adult Shank3Δ11(−/−) mice, indicative of a Shank3-dependent and not compensatory mechanism for this structural alteration. We analyzed transcriptional differences by RNA-sequencing of muscle tissue of neonatal Shank3Δ11(−/−) mice and compared those to Shank3(+/+) controls. We found significant differences in gene expression of ion channels crucial for muscle contraction and for molecules involved in calcium ion regulation. In addition, calcium storage- [i.e., Calsequestrin (CSQ)], calcium secretion- and calcium-related signaling-proteins were found to be affected. By immunostainings and Western blot analyses we could confirm these findings both in Shank3Δ11(−/−) mice and PMS patient muscle tissue. Moreover, alterations could be induced in vitro by the selective downregulation of Shank3 in C2C12 myotubes. Our results emphasize that SHANK3 levels directly or indirectly regulate calcium homeostasis in a cell autonomous manner that might contribute to muscular hypotonia especially seen in the newborn

An Inducible Expression System of the Calcium-Activated Potassium Channel 4 to Study the Differential Impact on Embryonic Stem Cells

Rationale. The family of calcium-activated potassium channels consists of four members with varying biological functions and conductances. Besides membrane potential modulation, SK channels have been found to be involved in cardiac pacemaker cell development from ES cells and morphological shaping of neural stem cells. Objective. Distinct SK channel subtype expression in ES cells might elucidate their precise impact during cardiac development. We chose SK channel subtype 4 as a potential candidate influencing embryonic stem cell differentiation. Methods. We generated a doxycycline inducible mouse ES cell line via targeted homologous recombination of a cassette expressing a bicistronic construct encoding SK4 and a fluorophore from the murine HPRT locus. Conclusion. We characterized the mouse ES cell line iSK4-AcGFP. The cassette is readily expressed under the control of doxycycline, and the overexpression of SK4 led to an increase in cardiac and pacemaker cell differentiation thereby serving as a unique tool to characterize the cell biological variances due to specific SK channel overexpression