Functional characterization of a glutamate/aspartate transporter from the mosquito Aedes aegypti

Glutamate elicits a variety of effects in insects, including inhibitory and excitatory signals at both neuromuscular junctions and brain. Insect glutamatergic neurotransmission has been studied in great depth especially from the standpoint of the receptor-mediated effects, but the molecular mechanisms involved in the termination of the numerous glutamatergic signals have only recently begun to receive attention. In vertebrates, glutamatergic signals are terminated by Na^+/K^+-dependent high-affinity excitatory amino acid transporters (EAAT), which have been cloned and characterized extensively. Cloning and characterization of a few insect homologues have followed, but functional information for these homologues is still limited. Here we report a study conducted on a cloned mosquito EAAT homologue isolated from the vector of the dengue virus, Aedes aegypti. The deduced amino acid sequence of the protein, AeaEAAT, exhibits 40–50% identity with mammalian EAATs, and 45–50% identity to other insect EAATs characterized thus far. It transports l-glutamate as well as l- and d-aspartate with high affinity in the micromolar range, and demonstrates a substrate-elicited anion conductance when heterologously expressed in Xenopus laevis oocytes, as found with mammalian homologues. Analysis of the spatial distribution of the protein demonstrates high expression levels in the adult thorax, which is mostly observed in the thoracic ganglia. Together, the work presented here provides a thorough examination of the role played by glutamate transport in Ae. aegypti

The transporter-like protein inebriated mediates hyperosmotic stimuli through intracellular signaling

We cloned the inebriated homologue MasIne from Manduca sexta and expressed it in Xenopus laevis oocytes. MasIne is homologous to neurotransmitter transporters but no transport was observed with a number of putative substrates. Oocytes expressing MasIne respond to hyperosmotic stimulation by releasing intracellular Ca(2+), as revealed by activation of the endogenous Ca(2+)-activated Cl(-) current. This Ca(2+) release requires the N-terminal 108 amino acid residues of MasIne and occurs via the inositol trisphosphate pathway. Fusion of the N terminus to the rat gamma-aminobutyric acid transporter (rGAT1) also renders rGAT1 responsive to hyperosmotic stimulation. Immunohistochemical analyses show that MasIne and Drosophila Ine have similar tissue distribution patterns, suggesting functional identity. Inebriated is expressed in tissues and cells actively involved in K(+) transport, which suggests that it may have a role in ion transport, particularly of K(+). We propose that stimulation of MasIne releases intracellular Ca(2+) in native tissues, activating Ca(2+)-dependent K(+) channels, and leading to K(+) transport

The Design of Pumpjets for Hydrodynamic Propulsion

A procedure for use in the design of a wake adapted pumpjet mounted on the aft end of a body of revolution is presented. To this end, a pumpjet is designed for the Akron airship. The propulsor mass flow is selected to minimize kinetic energy losses through the duct and in the discharge jet. The shaft speed and disk size are selected to satisfy specified limits of cavitation performance and to provide acceptable blade loading. The streamtubes which pass through a propulsor mounted on a tapered afterbody follow essentially conical surfaces. A method is provided for defining these surfaces as a function of shroud geometry, rotor head distribution, and the energy distribution of the ingested mass flow. The three-dimensional effects to which the conical flow subjects the cylindrical blade design sections are described and a technique is presented which permits incorporation of these effects in the blade design procedure

Chimpanzee communities differ in their inter- and intrasexual social relationships

Male and female human social bonding strategies are culturally shaped, in addition to being genetically rooted. Investigating nonhuman primate bonding strategies across sex groups allows researchers to assess whether, as with humans, they are shaped by the social environment or whether they are genetically predisposed. Studies of wild chimpanzees show that in some communities males have strong bonds with other males, whereas in others, females form particularly strong intrasex bonds, potentially indicative of cultural differences across populations. However, excluding genetic or ecological explanations when comparing different wild populations is difficult. Here, we applied social network analysis to examine male and female social bonds in two neighbouring semiwild chimpanzee groups of comparable ecological conditions and subspecies compositions, but that differ in demographic makeup. Results showed differences in bonding strategies across the two groups. While female–female party co-residence patterns were significantly stronger in Group 1 (which had an even distribution of males and females) than in Group 2 (which had a higher proportion of females than males), there were no such differences for male–male or male–female associations. Conversely, female–female grooming bonds were stronger in Group 2 than in Group 1. We also found that, in line with captive studies but contrasting research with wild chimpanzees, maternal kinship strongly predicted proximity and grooming patterns across the groups. Our findings suggest that, as with humans, male and female chimpanzee social bonds are influenced by the specific social group they live in, rather than predisposed sex-based bonding strategies

Biological Markers of Auditory Gap Detection in Young, Middle-Aged, and Older Adults

The capability of processing rapid fluctuations in the temporal envelope of sound declines with age and this contributes to older adults' difficulties in understanding speech. Although, changes in central auditory processing during aging have been proposed as cause for communication deficits, an open question remains which stage of processing is mostly affected by age related changes. We investigated auditory temporal resolution in young, middle-aged, and older listeners with neuromagnetic evoked responses to gap stimuli with different leading marker and gap durations. Signal components specific for processing the physical details of sound stimuli as well as the auditory objects as a whole were derived from the evoked activity and served as biological markers for temporal processing at different cortical levels. Early oscillatory 40-Hz responses were elicited by the onsets of leading and lagging markers and indicated central registration of the gap with similar amplitude in all three age groups. High-gamma responses were predominantly related to the duration of no-gap stimuli or to the duration of gaps when present, and decreased in amplitude and phase locking with increasing age. Correspondingly, low-frequency activity around 200 ms and later was reduced in middle aged and older participants. High-gamma band, and long-latency low-frequency responses were interpreted as reflecting higher order processes related to the grouping of sound items into auditory objects and updating of memory for these objects. The observed effects indicate that age-related changes in auditory acuity have more to do with higher-order brain functions than previously thought

Interpersonal prosodic correlation in frontotemporal dementia.

Communication accommodation describes how individuals adjust their communicative style to that of their conversational partner. We predicted that interpersonal prosodic correlation related to pitch and timing would be decreased in behavioral variant frontotemporal dementia (bvFTD). We predicted that the interpersonal correlation in a timing measure and a pitch measure would be increased in right temporal FTD (rtFTD) due to sparing of the neural substrate for speech timing and pitch modulation but loss of social semantics. We found no significant effects in bvFTD, but conversations including rtFTD demonstrated higher interpersonal correlations in speech rate than healthy controls

Information scraps: how and why information eludes our personal information management tools

In this paper we describe information scraps -- a class of personal information whose content is scribbled on Post-it notes, scrawled on corners of random sheets of paper, buried inside the bodies of e-mail messages sent to ourselves, or typed haphazardly into text files. Information scraps hold our great ideas, sketches, notes, reminders, driving directions, and even our poetry. We define information scraps to be the body of personal information that is held outside of its natural or We have much still to learn about these loose forms of information capture. Why are they so often held outside of our traditional PIM locations and instead on Post-its or in text files? Why must we sometimes go around our traditional PIM applications to hold on to our scraps, such as by e-mailing ourselves? What are information scraps' role in the larger space of personal information management, and what do they uniquely offer that we find so appealing? If these unorganized bits truly indicate the failure of our PIM tools, how might we begin to build better tools? We have pursued these questions by undertaking a study of 27 knowledge workers. In our findings we describe information scraps from several angles: their content, their location, and the factors that lead to their use, which we identify as ease of capture, flexibility of content and organization, and avilability at the time of need. We also consider the personal emotive responses around scrap management. We present a set of design considerations that we have derived from the analysis of our study results. We present our work on an application platform, jourknow, to test some of these design and usability findings

Novel Iron-Chelator DIBI Inhibits Staphylococcus aureus Growth, Suppresses Experimental MRSA Infection in Mice and Enhances the Activities of Diverse Antibiotics in vitro

DIBI, a purpose-designed hydroxypyridinone-containing iron-chelating antimicrobial polymer was studied for its anti-staphylococcal activities in vitro in comparison to deferiprone, the chemically related, small molecule hydroxypyridinone chelator. The sensitivities of 18 clinical isolates of Staphylococcus aureus from human, canine and bovine infections were determined. DIBI was strongly inhibitory to all isolates, displaying approximately 100-fold more inhibitory activity than deferiprone when compared on their molar iron-binding capacities. Sensitivity to DIBI was similar for both antibiotic-resistant and -sensitive isolates, including hospital- and community-acquired (United States 300) MRSA. DIBI inhibition was primarily bacteriostatic in nature at low concentration and was reversible by addition of Fe. DIBI also exhibited in vivo anti-infective activity in two distinct MRSA ATCC43300 infection and colonization models in mice. In a superficial skin wound infection model, topical application of DIBI provided a dose-dependent suppression of infection along with reduced wound inflammation. Intranasal DIBI reduced staphylococcal burden by >2 log in a MRSA nares carriage model. DIBI was also examined for its influence on antibiotic activities with a reference isolate ATCC6538, typically utilized to assess new antimicrobials. Sub-bacteriostatic concentrations of DIBI resulted in Fe-restricted growth and this physiological condition displayed increased sensitivity to GEN, CIP, and VAN. DIBI did not impair antibiotic activity but rather it enhanced overall killing. Importantly, recovery growth of survivors that typically followed an initial sub-MIC antibiotic killing phase was substantially suppressed by DIBI for each of the antibiotics examined. DIBI has promise for restricting staphylococcal infection on its own, regardless of the isolate’s animal source or antibiotic resistance profile. DIBI also has potential for use in combination with various classes of currently available antibiotics to improve their responses

Mediastinal abscess after endobronchial ultrasound with transbronchial needle aspiration: a case report

Endobronchial ultrasound (EBUS) with transbronchial needle aspiration is now becoming widely accepted as a preferred staging technique. It has been perceived as a non-invasive and well tolerated procedure with minimal complications. We report the development and treatment of a severe complication that developed 2 weeks after the initial procedure in the form of a complex mediastinal abscess. EBUS although useful in its non-invasive application for diagnosing mediastinal or hilar disease, must be regarded with caution since the potential exists to develop severe complications