Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding of AD pathogenesis, and are useful tools in the development of potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system to study the biochemical, genetic, environmental, and behavioral aspects of complex human diseases, including AD. In an effort to model AD, we over-expressed human APP and BACE genes in the Drosophila central nervous system. Biochemical, neuroanatomical, and behavioral analyses indicate that these flies exhibit aspects of clinical AD neuropathology and symptomology. These include the generation of Aβ40 and Aβ42, the presence of amyloid aggregates, dramatic neuroanatomical changes, defects in motor reflex behavior, and defects in memory. In addition, these flies exhibit external morphological abnormalities. Treatment with a γ-secretase inhibitor suppressed these phenotypes. Further, all of these phenotypes are present within the first few days of adult fly life. Taken together these data demonstrate that this transgenic AD model can serve as a powerful tool for the identification of AD therapeutic interventions

CO2-brine flow-through on an Utsira Sand core sample: Experimental and modelling. Implications for the Sleipner storage field

Sleipner (North Sea) is the world’s first commercial-scale carbon capture and storage (CCS) project, active since 1996, with ∼17 million tonnes of CO2 stored. The main reservoir, Utsira Sand, constitutes an ideal host formation of exceptionally high porosity-permeability and large lateral extent. However, the extensive seismic time-lapse, gravity and electromagnetic monitoring surveys deployed at Sleipner have not been well-supported by laboratory measurements. Here, we investigate the geophysical and geomechanical response of an Utsira core sample for the first time, using controlled inflation/depletion cycles at variable CO2-to-brine fractional flow rates. Ultrasonic P-wave velocities and attenuations are measured together with electrical resistivity (converted into CO2-saturation), along with continuous axial and radial strain monitoring. Ultrasonic velocity and attenuation data were simultaneously inverted and results extrapolated to field-scale seismic-frequencies using a new rock physics theory, which combines patchy fluid distribution and squirt flow effects. It provides a velocity-saturation relationship of practical importance to CO2 plume monitoring. Furthermore, by combining ultrasonic and deformation data, we report empirical relations between pore pressure changes and geomechanical effects in the reservoir, for different saturation ranges. Our dataset complements and constrains existing geophysical monitoring surveys at Sleipner and, more generally, improves the understanding of shallow weakly-cemented sand reservoirs

An analysis of school wide supports and barriers to collaborative problem solving teams

While there is preliminary evidence supporting the use of collaborative problem solving teams in schools (e.g., Telzrow, McNamara, & Hollinger, 2000) only a few outcome measures have been explored in relation to these procedures, and the results have been inconsistently demonstrated across projects (Burns & Symington, 2002). Additionally, it has been found that many school teams are inconsistent in their implementation of quality consultation procedures (e.g., Doll et al., 2005). Unfortunately the positive outcomes that have been associated with collaborative problem solving teams cannot be implied in practice until there is evidence that these procedures can be incorporated into real life situations (Telzrow et al., 2000). This research utilized an explanatory case study design to investigate the factors that contribute to quality team consultation procedures in applied settings. The analysis of the permanent products of cases seen by three Instructional Support Teams (IST) during the 2006-2007 school year, revealed that on average IST’s were able to implement five out of seven problem solving steps with fidelity. There was little evidence to confirm that teams provided detailed information on interventions that were implemented, or that treatment integrity data were collected regularly. Higher rates of implementation were found to be weakly associated with both greater goal attainment (r=.203, p=.044) and fewer referrals to special education (r=.230, p=.025). A comparison of mean implementation rates between academic and behavioral problems also indicated that teams implemented the process with greater fidelity when working on academic concerns (t (97) =3.387, p=.001). Focus group discussions revealed that team members and teaching staff considered the IST process to be more effective in addressing academic rather than behavioral problems. IST members identified the following factors as contributing to the success of their teams: administrative support, intervention support provided by specialists and Title 1 staff, participation of experts on teams, and teachers’ attitudes. Teachers and IST members identified time and scheduling to be the most significant barrier associated with the IST process. The supports and barriers to the IST process were interpreted in the context of the studies limitations, and presented with implications for practice and future research

Genotoxic effects of 60Co gamma-rays on Chinese hamster ovary (CHO) cells

The aim of the present study was to evaluate the cellular radiosensitivity and radiation-induced DNA damage and repair in Chinese hamster ovary (CHO) cells. Cell survival after irradiation was assessed using the clonogenic assay. The initial, radio-induced and residual DNA damage in Chinese hamster ovary (CHO) cells exposed to 60Co gamma-rays were determined using the alkaline comet assay. A linear-quadratic (LQ) survival curve was observed in CHO line. Data obtained by comet assay demonstrated a linear dose-response correlation in the range of tested doses (0.3-4 Gy). The process of DNA repair was modeled by exponential equation. In addition, we found a good correlation (R2 = 0.995) between clonogenic cell survival and radio-induced DNA damage

COVID-19 outbreak in a state prison: a case study on the implementation of key public health recommendations for containment and prevention.

BackgroundPeople incarcerated in US prisons have been disproportionately harmed by the COVID-19 pandemic. That prisons are such efficient superspreading environments can be attributed to several known factors: small, communal facilities where people are confined for prolonged periods of time; poor ventilation; a lack of non-punitive areas for quarantine/medical isolation; and staggeringly high numbers of people experiencing incarceration, among others. While health organizations have issued guidance on preventing and mitigating COVID-19 infection in carceral settings, little is known about if, when, and how recommendations have been implemented. We examined factors contributing to containment of one of the first California prison COVID-19 outbreaks and remaining vulnerabilities using an adapted multi-level determinants framework to systematically assess infectious disease risk in carceral settings.MethodsCase study employing administrative data; observation; and informal discussions with: people incarcerated at the prison, staff, and county public health officials.ResultsOutbreak mitigation efforts were characterized by pre-planning (e.g., designation of ventilated, single-occupancy quarantine) and a quickly mobilized inter-institutional response that facilitated systematic, voluntary rapid testing. However, several systemic- and institutional-level vulnerabilities were unaddressed hindering efforts and posing significant risk for future outbreaks, including insufficient decarceration, continued inter-facility transfers, incomplete staff cohorting, and incompatibility between built environment features (e.g., dense living conditions) and public health recommendations.ConclusionsOur adapted framework facilitates systematically assessing prison-based infectious disease outbreaks and multi-level interventions. We find implementing some recommended public health strategies may have contributed to outbreak containment. However, even with a rapidly mobilized, inter-institutional response, failure to decarcerate created an overreliance on chance conditions. This left the facility vulnerable to future catastrophic outbreaks and may render standard public health strategies - including the introduction of effective vaccines - insufficient to prevent or contain those outbreaks