A Pointing Solution for the Medium Size Telescopes for the Cherenkov Telescope Array

An important aspect of the calibration of the Cherenkov Telescope Array is the pointing, which enables an exact alignment of each telescope and therefore allows to transform a position in the sky to a point in the plane of the Cherenkov camera and vice versa. The favoured approach for the pointing calibration of the medium size telescopes (MST) is the installation of an optical CCD-camera in the dish of the telescope that captures the position of the Cherenkov camera and of the stars in the night sky simultaneously during data taking. The adaption of this approach is presented in this proceeding.Comment: 6 pages, 9 figures, Proceedings of the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma2016

Deletion of p38α MAPK in Microglia Blunts Trauma-Induced Inflammatory Responses in Mice

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the USA and other developed countries worldwide. Following the initial mechanical insult, the brain’s primary innate immune effector, microglia, initiate inflammatory signaling cascades and pathophysiological responses that can lead to chronic neuroinflammation and neurodegenerative sequelae. The p38α MAPK signaling pathway in microglia is a key contributor to inflammatory responses to diverse disease-relevant stressors and injury conditions. Therefore, we tested here whether microglia p38α contributes to acute and persistent inflammatory responses induced by a focal TBI. We generated conditional cell-specific knockout of p38α in microglia using a CX3CR1 Cre-lox system, subjected the p38α knockout and wild-type mice to a controlled cortical impact TBI, and measured inflammatory responses at acute (1-day) and subacute (7-day) post-injury time points. We found that deletion of p38α in microglia only was sufficient to attenuate multiple pro-inflammatory responses following TBI, notably reducing pro-inflammatory cytokine/chemokine production and recruitment of inflammatory monocytes into the brain and preventing the persistent microglial morphological activation. These data provide strong evidence supporting a role for microglial p38α in propagation of a chronic and potentially neurotoxic pro-inflammatory environment in the brain following TBI

Observations of the Crab Nebula with H.E.S.S. Phase II

The High Energy Stereoscopic System (H.E.S.S.) phase I instrument was an array of four $100\,\mathrm{m}^2$ mirror area Imaging Atmospheric Cherenkov Telescopes (IACTs) that has very successfully mapped the sky at photon energies above $\sim 100\,$GeV. Recently, a $600\,\mathrm{m}^2$ telescope was added to the centre of the existing array, which can be operated either in standalone mode or jointly with the four smaller telescopes. The large telescope lowers the energy threshold for gamma-ray observations to several tens of GeV, making the array sensitive at energies where the Fermi-LAT instrument runs out of statistics. At the same time, the new telescope makes the H.E.S.S. phase II instrument. This is the first hybrid IACT array, as it operates telescopes of different size (and hence different trigger rates) and different field of view. In this contribution we present results of H.E.S.S. phase II observations of the Crab Nebula, compare them to earlier observations, and evaluate the performance of the new instrument with Monte Carlo simulations.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherland

Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid

BACKGROUND: Interleukin 1 (IL-1) is a key mediator of immune responses in health and disease. Although classically the function of IL-1 has been studied in the systemic immune system, research in the past decade has revealed analogous roles in the CNS where the cytokine can contribute to the neuroinflammation and neuropathology seen in a number of neurodegenerative diseases. In Alzheimer's disease (AD), for example, pre-clinical and clinical studies have implicated IL-1 in the progression of a pathologic, glia-mediated pro-inflammatory state in the CNS. The glia-driven neuroinflammation can lead to neuronal damage, which, in turn, stimulates further glia activation, potentially propagating a detrimental cycle that contributes to progression of pathology. A prediction of this neuroinflammation hypothesis is that increased IL-1 signaling in vivo would correlate with increased severity of AD-relevant neuroinflammation and neuronal damage. METHODS: To test the hypothesis that increased IL-1 signaling predisposes animals to beta-amyloid (Aβ)-induced damage, we used IL-1 receptor antagonist Knock-Out (IL1raKO) and wild-type (WT) littermate mice in a model that involves intracerebroventricular infusion of human oligomeric Aβ1–42. This model mimics many features of AD, including robust neuroinflammation, Aβ plaques, synaptic damage and neuronal loss in the hippocampus. IL1raKO and WT mice were infused with Aβ for 28 days, sacrificed at 42 days, and hippocampal endpoints analyzed. RESULTS: IL1raKO mice showed increased vulnerability to Aβ-induced neuropathology relative to their WT counterparts. Specifically, IL1raKO mice exhibited increased mortality, enhanced microglial activation and neuroinflammation, and more pronounced loss of synaptic markers. Interestingly, Aβ-induced astrocyte responses were not significantly different between WT and IL1raKO mice, suggesting that enhanced IL-1 signaling predominately affects microglia. CONCLUSION: Our data are consistent with the neuroinflammation hypothesis whereby increased IL-1 signaling in AD enhances glia activation and leads to an augmented neuroinflammatory process that increases the severity of neuropathologic sequelae

Microglial-Associated Responses to Comorbid Amyloid Pathology and Hyperhomocysteinemia in an Aged Knock-in Mouse Model of Alzheimer\u27s Disease

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer\u27s disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies. METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of B-vitamin deficiency-induced HHcy to better understand how microglia are affected in this comorbidity context. RESULTS: We found that HHcy-inducing diet increased amyloid plaque burden, altered the neuroinflammatory milieu, and upregulated the expression of multiple damage-associated and homeostatic microglial genes. CONCLUSIONS: Taken together, these data indicate complex effects of comorbid pathologies on microglial function that are not driven solely by increased amyloid burden. Given the highly dynamic nature of microglia, their central role in AD pathology, and the frequent occurrence of various comorbidities in AD patients, it is increasingly important to understand how microglia respond to mixed pathological processes

Personality, depressive symptoms, the interparental relationship and parenting: Prospective associations of an actor-partner interdependency model.

Grounded on Belsky's process model and family systems theories and using an actor-partner interdependency modeling (APIM) approach (Belsky & Jaffee, 2006; Cox & Paley, 2003), the current study was the first to examine whether Big Five personality characteristics and depressive symptoms of parents and their partners are related to adolescent-perceived parenting behavior directly and indirectly via interparental stress experienced by both parents. Longitudinal data (Time 1: 2001; Time 2: 2007; and Time 3: 2009) from a large community sample of Flemish families was used (N = 455; Time 1 children: Mage = 7.10 years). Results revealed that, for both parents, more agreeableness and autonomy predicted more parental warmth, and more depressive symptoms and lower agreeableness predicted more overreactive discipline (i.e., actor effects). Both parents' depressive symptoms predicted their own interparental stress (i.e., actor effects). Regarding partner-effects, paternal overreactive discipline was shaped by mother's extraversion and experienced interparental stress, and paternal warmth was affected by mother's experienced interparental stress in addition to fathers' own psychological resources. In contrast, maternal parenting was affected by their own psychological resources only. Although no consistent mediating role of interparental stress was found, one small dyadic indirect effect indicated that maternal depressive symptoms were related to more paternal overreactive discipline via heightened levels of interparental stress experienced by both parents. These results provide new support for the idea of interdependency between parents and specifically support the fathering vulnerability hypothesis. Tentatively, this study informs clinical practice by showing that family interventions aiming to improve parenting should pay attention to specific personality characteristics affecting parenting behavior and adopt a dyadic approach including both parents, especially when targeting paternal parenting. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Factors Associated with Unmet Needs among African-American Dementia Care Providers

Racial and ethnic minorities currently comprise 20% of the U.S. population; in 2050, this figure is expected to rise to 42%. As a result, Alzheimer’s disease (AD), the 5th leading cause of death for people aged 65 and older, is likely to increase in these groups. Most dementia caregiving for these populations comes from family and friends, especially among families with lower socioeconomic status. A convenience sample of 30 African-American dementia caregivers was interviewed to determine unmet needs. Participants expressed a limited desire for formal services, such as support groups, legal advice, case management, and homemaker services. Instead, commonly expressed needs were daytime respite care and especially a desire for family and social support. Many caregivers expressed a need for other family members to share responsibility in the process; therefore, methods for caregiver support that address multiple family members in care provision may be beneficial for this group

Therapeutic Treatment with the Anti-Inflammatory Drug Candidate MW151 May Partially Reduce Memory Impairment and Normalizes Hippocampal Metabolic Markers in a Mouse Model of Comorbid Amyloid and Vascular Pathology

Alzheimer\u27s disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop small molecule, anti-inflammatory therapeutics for neurological injury and disease, we have recently been exploring potentially promising treatments in preclinical multi-morbidity contexts. In the present study, we generated a mouse model of mixed amyloid and hyperhomocysteinemia (HHcy) pathology in which to test the efficacy of one of our anti-inflammatory compounds, MW151. HHcy can cause cerebrovascular damage and is an independent risk factor for both AD dementia and vascular contributions to cognitive impairment and dementia. We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context, and further, that the benefit is associated with a normalization of hippocampal metabolites detectable via magnetic resonance spectroscopy. These findings provide evidence that MW151 in particular, and potentially anti-inflammatory treatment more generally, may be beneficial in AD patients with comorbid vascular pathology