Adult neurogenesis in the orexin/ataxin-3 mouse

Introduction: The adult mammalian brain retains neural stem cells (NSCs) that continually generate new neurons within two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus (HC). This process is called adult neurogenesis. Controlled stimulation of endogenous neurogenesis might be an elegant way to treat neurodegenerative diseases. It is therefore important to understand the molecular signals, which govern the proliferation, migration, and differentiation of endogenous NSCs in the neurogenic niches. Regulatory mechanisms in the so-called neurogenic niches have already been shown by in vivo studies for various factors, including numerous neurotransmitters, and behavioral and environmental factors. However, our knowledge is still insufficient to exploit adult neurogenesis for controlled brain repair or for stimulation of its physiological function. The sleep disorder narcolepsy is considered to be a neurodegenerative disease because there is a massive progressive loss of neurons containing the neuropeptide orexin. Consequently narcoleptic patients have very low cerebrospinal fluid levels of orexin. Narcolepsy is defined as a sleep-wake disorder with REM and non-REM sleep associated symptoms existing longer than 6 months, such as daytime sleepiness, cataplexy, fractionated sleep at night and automatic behaviors. The postulated pathophysiology of human narcolepsy is mimicked very closely in a transgenic mouse model called orexin/ataxin-3 mouse, in which orexin-containing neurons are ablated progressively by specific overexpression of a truncated cytotoxic ataxin-3 gene product under the orexin-promoter. Aim: We aimed to study the possible role of the protein orexin in the regulation of adult neurogenesis in the orexin/ataxin-3 mouse. Study design: Adult neurogenesis in the SGZ, SVZ and rostral migratory stream (RMS), where the cells migrate from the SVZ to the olfactory bulb (OB), was studied by immunohistology. For the evaluation of the stem cell proliferation in SVZ and SGZ and migration in the RMS, orexin/ataxin-3 mice (n = 8) and wild type (WT) mice (n = 8) received a single intraperitoneal injection of 100 mg BrdU (bromodeoxyuridine)/kg body weight 2 hour prior to sacrifice. For the analysis of differentiation and survival of newly built cells, BrdU was administered intraperitoneally on 5 consecutive days once per day to orexin/ataxin-3 mice (n = 8) and WT mice (n = 8) and they were sacrificed 30 days after the last injection. Results: We found a significantly higher proliferation of stem/precursor cells in the orexin/ataxin-3 mice in both neurogenic regions, the SGZ and the SVZ. Also in the RMS, higher levels of newly built cells in the orexin/ataxin group were found, but these differences were not significant. We were able to demonstrate a significantly higher survival of newly built cells in the granular zone, but not for the periglomerular zone of the OB in the orexin/ataxin group. A tendency for higher survival rates could be shown for the HC of the orexin/ataxin-3 mice (not significant). By triple staining we could show that the proportion of newly born neurons relative to the total number of newly built cells in the HC was significantly higher with 90 % in the orexin-ataxin group compared to 83 % in the control group. In both the granular zone and the periglomerular zone of the OB, over 90 % of the total amount of new built cells differentiated into neurons in both groups. Also the rate of differentiation into a dopaminergic phenotype of the newly born neurons in the periglomerular zone of the OB was not significantly changed with 93 % in the orexin/ataxin-3 mice compared to 91 % in the WT mice. Conclusion: In the absence of orexin in the adult mouse brain, the proliferation of adult neural stem/precursor cells was increased, the survival rate was significantly increased in the granular zone of the OB and a consistent not significant trend was seen in the HC. The proportion of newborn neurons among all newly born cells was higher in the HC, however, no significant differences in the differentiation of newly built cells could be found in the OB. Together, these observations lead to the assumption that orexin suppresses the proliferation of adult NSC, affects the survival rate in the OB negatively and hinders the differentiation of newly built cells into neurons in the HC

Just Immigration with Allison Wolf

Overview & Shownotes When the philosopher Allison Wolf heard a news story in 2014 about Central American children migrating to the United States, she was angry. She wasn’t upset about the minors coming in the first place, she was furious about the heartlessness of her fellow Americans reacting to the crisis. It wasn’t until she started writing about immigration that she discovered what was at the heart of the issue. By examining the stories at the center of dehumanizing policies, she realized that feminism, and its focus on oppression, could shed light on the problem of justice and immigration. For the episode transcript, download a copy or read it below. Contact us at [email protected] Links to people and ideas mentioned in the show Just Immigration in the Americas: A Feminist Account by Allison Wolf 2014 Central American migrant crisis Some of the philosophical and ethics issues related to immigration Marilyn Frye, “The Systemic Birdcage of Sexism“ “Remain in Mexico” policy Ann Cahill and derivatization José Jorge Mendoza Grant Silva Carlos Alberto Sánchez Credits Thanks to Evelyn Brosius for our logo. Music featured in the show: Insatiable Toad by Blue Dot Session

Die erste Preisverleihung am 1. Dezember 2007 von The Missing Link. Der Preis für Psychoanalyse und …: Eine Anerkennung des Psychoanalytischen Seminars Zürich

Kein Abstract vorhanden

Transportschein für eine Bronzefigur - Empfangsstation Weimar. Ein Versuch zu "Eva gehört zu uns"

Vortrag über die Restaurierung der Bronzeplastik zur feierlichen Wiederaufstellung der von Auguste Rodin gestalteten Plastik "Eva" auf ihren angestammten Platz im Foyer des Hauptgebäudes der Bauhaus-Universität Weimar am 12. Dezember 201

The Challenges of Developing an Instrument to Assess Health Provider Motivation at Primary Care Level in Rural Burkina Faso, Ghana and Tanzania.

The quality of health care depends on the competence and motivation of the health workers that provide it. In the West, several tools exist to measure worker motivation, and some have been applied to the health sector. However, none have been validated for use in sub-Saharan Africa. The complexity of such tools has also led to concerns about their application at primary care level. To develop a common instrument to monitor any changes in maternal and neonatal health (MNH) care provider motivation resulting from the introduction of pilot interventions in rural, primary level facilities in Ghana, Burkina Faso, and Tanzania. Initially, a conceptual framework was developed. Based upon this, a literature review and preliminary qualitative research, an English-language instrument was developed and validated in an iterative process with experts from the three countries involved. The instrument was then piloted in Ghana. Reliability testing and exploratory factor analysis were used to produce a final, parsimonious version. This paper describes the actual process of developing the instrument. Consequently, the concepts and items that did not perform well psychometrically at pre-test are first presented and discussed. The final version of the instrument, which comprises 42 items for self-assessment and eight for peer-assessment, is then shown. This is followed by a presentation and discussion of the findings from first use of the instrument with MNH providers from 12 rural, primary level facilities in each of the three countries. It is possible to undertake work of this nature at primary health care level, particularly if the instruments are kept as straightforward as possible and well introduced. However, their development requires very lengthy preparatory periods. The effort needed to adapt such instruments for use in different countries within the region of sub-Saharan Africa should not be underestimated

Mitochondrial haplogroup U is associated with a reduced risk to develop exfoliation glaucoma in the German population

<p>Abstract</p> <p>Background</p> <p>Various lines of evidence demonstrate the involvement of mitochondrial dysfunction in the pathogenesis of glaucoma. Therefore, mitochondrial DNA is a promising candidate for genetic susceptibility studies on glaucoma. To test the hypothesis that mitochondrial haplogroups influence the risk to develop glaucoma, we genotyped 12 single-nucleotide polymorphisms that define the European mitochondrial DNA haplogroups in healthy controls and two German patient cohorts with either exfoliation glaucoma or the normal tension subgroup of primary open angle glaucoma.</p> <p>Results</p> <p>Mitochondrial haplogroup U was significantly under-represented in patients with exfoliation glaucoma (8.3% compared with 18.9% in controls; p = 0.004).</p> <p>Conclusions</p> <p>People with haplogroup U have a lower risk to develop exfoliation glaucoma. Our results substantiate the suggestion that mitochondrial alterations have an impact on the etiology of glaucoma.</p

Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019

This paper studies the features of metabolic parameters, diabetic complications and drug therapy of a single-centre cohort of patients with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) in secondary care and tertiary care over a 15-year period. Methods: Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care ( n = 5571) or tertiary care ( n = 2001) were included. Statistical analyses were performed using linear mixed models. Results: Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care ( p < 0.001). Patients in secondary care consistently showed good glycaemic control, while patients in tertiary care showed inadequate glycaemic control. All four cross-sectional cohorts showed a significant increase in the prevalence of nephropathy over time and three out of four cohorts (T1DM and T2DM in secondary care and T2DM in tertiary care) showed an increase in the prevalence of neuropathy (all p < 0.001). The incidence of severe hypoglycaemia was consistently low. The use of insulin pumps and insulin analogues in the therapy of T1DM increased significantly. Conclusions: The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care

PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-κB and XBP1 binding sites.

Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility