Partnering to Enhance Education and Public Engagement Programs

Collaborating with partners is a fundamental aspect of the Lunar and Planetary Institute's (LPI) educational and public engagement efforts. Such partnerships enable scientists and educators to include members of the audience in program planning and execution. Ultimately, partnerships strengthen programs by providing diverse resources, expertise, and expanding the potential audience

Selenium Status in Paediatric Patients with Neurodevelopmental Diseases

Neurodevelopmental diseases are often associated with other comorbidities, especially inflammatory processes. The disease may affect the trace element (TE) status, which in turn may affect disease severity and progression. Selenium (Se) is an essential TE required for the biosynthesis of selenoproteins including the transporter selenoprotein P (SELENOP) and extracellular glutathione peroxidase (GPX3). SELENOP deficiency in transgenic mice resulted in a Se status-dependent phenotype characterized by impaired growth and disturbed neuronal development, with epileptic seizures on a Se-deficient diet. Therefore, we hypothesized that Se and SELENOP deficiencies may be prevalent in paediatric patients with a neurodevelopmental disease. In an exploratory cross-sectional study, serum samples from children with neurodevelopmental diseases (n = 147) were analysed for total serum Se, copper (Cu), and zinc (Zn) concentrations as well as for the TE biomarkers SELENOP, ceruloplasmin (CP), and GPX3 activity. Children with epilepsy displayed elevated Cu and Zn concentrations but no dysregulation of serum Se status. Significantly reduced SELENOP concentrations were found in association with intellectual disability (mean +/- SD (standard deviation); 3.9 +/- 0.9 mg/L vs. 4.4 +/- 1.2 mg/L, p = 0.015). A particularly low GPX3 activity (mean +/- SD; 172.4 +/- 36.5 vs. 192.6 +/- 46.8 U/L, p = 0.012) was observed in phacomatoses. Autoantibodies to SELENOP, known to impair Se transport, were not detected in any of the children. In conclusion, there was no general association between Se deficiency and epilepsy in this observational analysis, which does not exclude its relevance to individual cases. Sufficiently high SELENOP concentrations seem to be of relevance to the support of normal mental development. Decreased GPX3 activity in phacomatoses may be relevant to the characteristic skin lesions and merits further analysis. Longitudinal studies are needed to determine whether the observed differences are relevant to disease progression and whether correcting a diagnosed TE deficiency may confer health benefits to affected children

Perceived Mental Illness Stigma Among Youth in Psychiatric Outpatient Treatment

This research explores the experiences of mental illness stigma in 24 youth (58.3% male, 13–24 years, 75% Latino) in psychiatric outpatient treatment. Using Link and Phelan’s (2001) model of stigmatization, we conducted thematic analysis of the interview texts, examining experiences of stigma at individual and structural levels, in addition to the youths’ social-psychological processes. Youth in psychiatric treatment acknowledged that their larger cultural context holds pejorative viewpoints toward those with mental illness and reported experiences of stigma within their families and social networks. Our results also offer insight into the social-psychological processes of stigma, highlighting how labeling may influence their self-concept and the strategies in which youth engage to manage a stigmatized identity. We discuss differences in stigma experiences by gender, age, and diagnosis. Findings provide new information on the stigma experiences of youth in psychiatric treatment and suggest that a multilevel approach to reduce stigma is warranted

Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations

L

Q134R: Small Chemical Compound with NFAT Inhibitory Properties Improves Behavioral Performance and Synapse Function in Mouse Models of Amyloid Pathology

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer\u27s disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. Q134R partially inhibited NFAT activity in primary rat astrocytes, but did not prevent CN-mediated dephosphorylation of a non-NFAT target, either in vivo, or in vitro. Acute (≤1 week) oral delivery of Q134R to APP/PS1 (12 months old) or wild-type mice (3–4 months old) infused with oligomeric Aβ peptides led to improved Y maze performance. Chronic (≥3 months) oral delivery of Q134R appeared to be safe, and, in fact, promoted survival in wild-type (WT) mice when given for many months beyond middle age. Finally, chronic delivery of Q134R to APP/PS1 mice during the early stages of amyloid pathology (i.e., between 6 and 9 months) tended to reduce signs of glial reactivity, prevented the upregulation of astrocytic NFAT4, and ameliorated deficits in synaptic strength and plasticity, without noticeably altering parenchymal Aβ plaque pathology. The results suggest that Q134R is a promising drug for treating AD and aging-related disorders

Historische Anthropologie

Im Schnittfeld von Europäischer Ethnologie / Volkskunde und Geschichtswissenschaften hat sich die Historische Anthropologie in den letzten drei Jahrzehnten international etabliert. Dabei orientiert sie sich an einem breiten Kulturbegriff und widmet sich der wissenschaftlichen Rekonstruktion wie Analyse von Lebenswelten und Alltagspraktiken. Gegenwärtig ist das ausdifferenzierte Feld von Debatten um Epistemologien und Methoden geprägt. Daher scheint es an der Zeit, ein Diskussionsforum zum state of the art in der Historischen Anthropologie zu veröffentlichen und auf H-Soz-u-Kult einen Diskussionsrahmen für aktuelle Forschungsfragen und Standortbestimmungen zu schaffen. Dieser Band aus der Reihe "Historisches Forum" versammelt Essays zu den aktuellen Debatten und liefert Anregungen zu Methoden- wie Theoriediskussionen

Cell-Specific DNA Methylation Patterns of Retina-Specific Genes

Many studies have demonstrated that epigenetic mechanisms are important in the regulation of gene expression during embryogenesis, gametogenesis, and other forms of tissue-specific gene regulation. We sought to explore the possible role of epigenetics, specifically DNA methylation, in the establishment and maintenance of cell type-restricted gene expression in the retina. To assess the relationship between DNA methylation status and expression level of retinal genes, bisulfite sequence analysis of the 1000 bp region around the transcription start sites (TSS) of representative rod and cone photoreceptor-specific genes and gene expression analysis were performed in the WERI and Y79 human retinoblastoma cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the retina and in non-expressing tissues. Finally, bisulfite sequencing was performed on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser capture microdissection. Differential methylation of rhodopsin (RHO), retinal binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated with gene expression levels. Similarly, we found tissue-specific hypomethylation of the promoter region of Rho and Rbp3 in mouse retina as compared to non-expressing tissues, and also observed hypomethylation of retinal-expressed microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing photoreceptor cells and methylated in non-expressing, non-photoreceptor cells from the inner nuclear layer. A third regional hypomethylation pattern of photoreceptor-specific genes was seen in a subpopulation of non-expressing photoreceptors (Rho in cones from the Nrl −/− mouse and Opn1sw in rods). These results demonstrate that a number of photoreceptor-specific genes have cell-specific differential DNA methylation that correlates inversely with their expression level. Furthermore, these cell-specific patterns suggest that DNA methylation may play an important role in modulating photoreceptor gene expression in the developing mammalian retina

Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations

The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms

Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson's and Huntington's diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging