Removal of Giα1 Constraints on Adenylyl Cyclase in the Hippocampus Enhances LTP and Impairs Memory Formation

AbstractStimulation of adenylyl cyclase in the hippocampus is critical for memory formation. However, generation of cAMP signals within an optimal range for memory may require a balance between stimulatory and inhibitory mechanisms. The role of adenylyl cyclase inhibitory mechanisms for memory has not been addressed. One of the mechanisms for inhibition of adenylyl cyclase is through activation of Gi-coupled receptors, a mechanism that could serve as a constraint on memory formation. Here we report that ablation of Giα1 by gene disruption increases hippocampal adenylyl cyclase activity and enhances LTP in area CA1. Furthermore, gene ablation of Giα1 or antisense oligonucleotide-mediated depletion of Giα1 disrupted hippocampus-dependent memory. We conclude that Giα1 provides a critical mechanism for tonic inhibition of adenylyl cyclase activity in the hippocampus. We hypothesize that loss of Giα1 amplifies the responsiveness of CA1 postsynaptic neurons to stimuli that strengthen synaptic efficacy, thereby diminishing synapse-specific plasticity required for new memory formation

Daptomycin exposure precedes infection and/or colonization with daptomycin non-susceptible enterococcus

<p>Abstract</p> <p>Background</p> <p>Daptomycin non-susceptible enterococci (DNSE) are emerging as an important cause of healthcare-associated infection, however little is known about the epidemiology of DNSE. At the University of Iowa Hospitals and Clinics (UIHC) an increase in the frequency of patients infected and/or colonized with DNSE has occurred. The goals of this study were to evaluate potential factors associated with the development of DNSE colonization and/or infection and to compare the characteristics of patients with prior daptomycin exposure to those without prior daptomycin exposure.</p> <p>Methods</p> <p>The study is a retrospective case-series involving all patients with DNSE infection and/or colonization at UIHC, a 734-bed academic referral center, from June 1, 2005 to June 1, 2011.</p> <p>Results</p> <p>The majority of patients with DNSE colonization and/or infection had prior daptomycin exposure (15 of 25; 60%), a concomitant gastrointestinal process (19 of 25; 76%), or were immunosuppressed (21 of 25; 84%). DNSE infection was confirmed in 17 of 25 (68%) patients, including 9 patients with bacteremia. Twelve of 17 (71%) patients with DNSE infection had prior daptomycin exposure, including 7 of 9 (78%) patients with bacteremia. Compared to patients without prior daptomycin exposure, patients with prior daptomycin exposure were less likely to harbor <it>E. faecalis</it> (0% vs. 33%; p = 0.019). A high proportion of patients (10 of 25; 40%) died during their hospitalizations. Most enterococcal isolates were <it>E. faecium</it> (86%), and were vancomycin-resistant (72%). Molecular typing revealed a diverse population of DNSE.</p> <p>Conclusions</p> <p>Prior daptomycin exposure, immunosuppression, and/or a concomitant gastrointestinal process, may be associated with the development of DNSE. PFGE revealed a diverse population of DNSE, which along with both increasing numbers of DNSE detected yearly and increasing annual rates of daptomycin usage, suggests the emergence of DNSE under antimicrobial pressure.</p

Cubesat Laser Communications Transceiver for Multi-Gbps Downlink

Fibertek is developing a cubesat laser communications (lasercom) downlink terminal that supports direct optical data downlink from cubesats to modest optical ground stations with 30 to 50 cm diameter telescopes. This paper describes the design, development, and lab testing of the optical transceiver portion of a compact cubesat space lasercom terminal. The design uses a relatively large aperture, low divergence, and accurate pointing approach to minimize the required laser power as well as the overall electrical power of the system. The optical transceiver has a shared transmit/receive optical path that uses a 1 um laser beacon to ensure high pointing accuracy, control the pointing stability, and ensure a strong optical signal-to-noise ratio (SNR) during link operation. The fundamental terminal optical design has been manufactured and tested providing high accuracy pointing and low jitter. The systems design is completed by adding a cubesat form-factor 1.5-um fiber-amplifier with 2 W optical power, high-data-rate optical transceiver card, and digital-modem/bus-interface card to lasercom terminal capable of supporting \u3e5 Gbit/sec optical downlink

Increased Mortality Rates Associated with Staphylococcus aureus and Influenza Co-infection, Maryland and Iowa, USA

We retrospectively analyzed data for 195 respiratory infection patients who had positive Staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in Iowa and Maryland, USA, during 2003–2009. Odds for death for patients who also had influenza-positive test results were >4 times higher than for those who had negative influenza test results

The Role of Cognitive Functioning in Medication Adherence of Children and Adolescents with HIV Infection

Objective To evaluate the relationship between cognitive functioning and medication adherence in children and adolescents with perinatally acquired HIV infection. Methods Children and adolescents, ages 3–18 (N = 1,429), received a cognitive evaluation and adherence assessment. Multiple logistic regression models were used to identify associations between adherence and cognitive status, adjusting for potential confounding factors. Results Children's average cognitive performance was within the low-average range; 16% of children were cognitively impaired (MDI/FSIQ <70). Cognitive status was not associated with adherence to full medication regimens; however, children with borderline/low average cognitive functioning (IQ 70–84) had increased odds of nonadherence to the protease inhibitor class of antiretroviral therapy. Recent stressful life events and child health characteristics, such as HIV RNA detectability, were significantly associated with nonadherence. Conclusion Cognitive status plays a limited role in medication adherence. Child and caregiver psychosocial and health characteristics should inform interventions to support adherence