Cholinergic suppression: A postsynaptic mechanism of long-term associative learning

Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscariniclike receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-ß -methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning -- namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species

HST/NICMOS Observations of Massive Stellar Clusters Near the Galactic Center

We report Hubble Space Telescope (HST) Near-infrared Camera and Multi-object Spectrometer (NICMOS) observations of the Arches and Quintuplet clusters, two extraordinary young clusters near the Galactic Center. For the first time, we have identified main sequence stars in the Galactic Center with initial masses well below 10 Msun. We present the first determination of the initial mass function (IMF) for any population in the Galactic Center, finding an IMF slope which is significantly more positive (Gamma approx -0.65) than the average for young clusters elsewhere in the Galaxy (Gamma approx -1.4). The apparent turnoffs in the color-magnitude diagrams suggest cluster ages which are consistent with the ages implied by the mixture of spectral types in the clusters; we find tau(age) approx 2+/-1 Myr for the Arches cluster, and tau(age) approx 4+/-1 Myr for the Quintuplet. We estimate total cluster masses by adding the masses of observed stars down to the 50% completeness limit, and then extrapolating down to a lower mass cutoff of 1 Msun. Using this method, we find > 10^4 Msun for the total mass of the Arches cluster. Such a determination for the Quintuplet cluster is complicated by the double-valued mass-magnitude relationship for clusters with ages > 3 Myr. We find a lower limit of 6300 Msun for the total cluster mass, and suggest a best estimate of twice this value which accounts for the outlying members of the cluster. Both clusters have masses which place them as the two most massive clusters in the Galaxy.Comment: accepted by ApJ higher resolution versions of figures 1 and 2 can be found at: ftp://quintup.astro.ucla.edu/nicmos1

Lead-associated endocarditis: the important role of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Infection is a potentially life-threatening complication of cardiac device implantation. Lead-associated endocarditis (LAE) may be the most serious complication since it is associated with a high mortality. METHODS: The medical records of patients referred to our institution for the treatment of LAE between 1999 and 2007 were reviewed. RESULTS: A total of 51 of 107 patients referred for device-related infections met the criteria for LAE. Of these, 19 occurred within 6 months of their most recent procedure (early), while the remaining 32 occurred more than 6 months later (mean = 31.9 months post procedure). Devices included pacemakers in 33 patients and ICDs in 18 patients. The most common organism responsible for infection was Staphylococcus aureus (S. aureus) followed by coagulase-negative staphylocci (22%) and streptococci (12%). Methicillin-resistant S. aureus (MRSA) accounted for 67% of the S. aureus infections. Coagulase-negative staphylococci were responsible for only 26% of early and 19% of late cases. A distant site of infection was common (26/51 = 51%), particularly in patients with MRSA LAE. The device and leads were removed percutaneously in all patients. Only one patient failed to respond to intravenous antibiotics. CONCLUSIONS: Our data suggest that methicillin-resistant S. aureus is an important pathogen in LAE. Since many infections occur months after the last device procedure, hematogenous spread of organisms from a distant site may be an important contributing factor. These data suggest that strategies to prevent hematogenous infection, particularly with S. aureus, are critical in patients with implantable cardiac devices

Comparison of type 2 diabetes prevalence estimates in Saudi Arabia from a validated Markov model against the International Diabetes Federation and other modelling studies

AbstractAimsTo compare the estimates and projections of type 2 diabetes mellitus (T2DM) prevalence in Saudi Arabia from a validated Markov model against other modelling estimates, such as those produced by the International Diabetes Federation (IDF) Diabetes Atlas and the Global Burden of Disease (GBD) project.MethodsA discrete-state Markov model was developed and validated that integrates data on population, obesity and smoking prevalence trends in adult Saudis aged ≥25 years to estimate the trends in T2DM prevalence (annually from 1992 to 2022). The model was validated by comparing the age- and sex-specific prevalence estimates against a national survey conducted in 2005.ResultsPrevalence estimates from this new Markov model were consistent with the 2005 national survey and very similar to the GBD study estimates. Prevalence in men and women in 2000 was estimated by the GBD model respectively at 17.5% and 17.7%, compared to 17.7% and 16.4% in this study. The IDF estimates of the total diabetes prevalence were considerably lower at 16.7% in 2011 and 20.8% in 2030, compared with 29.2% in 2011 and 44.1% in 2022 in this study.ConclusionIn contrast to other modelling studies, both the Saudi IMPACT Diabetes Forecast Model and the GBD model directly incorporated the trends in obesity prevalence and/or body mass index (BMI) to inform T2DM prevalence estimates. It appears that such a direct incorporation of obesity trends in modelling studies results in higher estimates of the future prevalence of T2DM, at least in countries where obesity has been rapidly increasing

Bcl-2 Can Rescue T Lymphocyte Development in Interleukin-7 Receptor–Deficient Mice but Not in Mutant rag-1−/− Mice

AbstractSignals from cytokine and antigen receptors play crucial roles during lymphocyte development. Mice lacking interleukin-7 receptor are lymphopenic, due to a defect in cell expansion at an early stage of differentiation, and the few mature T cells that develop in IL-7R−/− animals are functionally impaired. Both defects were rescued completely by overexpression of the anti- apoptosis protein Bcl-2. T cell progenitors lacking antigen receptor molecules are also blocked in differentiation and die, presumably because they fail to receive a positive signal via their pre-T cell receptor. Surprisingly, Bcl-2 did not promote survival or differentiation of T cells in rag-1−/− mice. These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2

Target Selection for the LBTI Exozodi Key Science Program

The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ~300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.Comment: accepted to ApJ