[Beta]-amyloid-mediated nitric oxide release from rat microglia by ligation of the integrin Mac-1

Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder characterized histopathologically by a loss of neurons and an accumulation of [beta]-amyloid plaques, neurofibrillary tangles, dystrophic neurites, and reactive glial cells. While most previous studies on the neurodegeneration of AD have focused on neuronal cells and direct [beta]-amyloid-mediated neurotoxicity, few have focused on the role of reactive glial cells in [beta]-amyloid-mediated neurotoxicity. In the present study nitric oxide release from cultured rat microglia was examined by exposing the cells to synthetic [beta]-amyloid peptides ([beta]25-35 and [beta]1-40) alone and in combination with cytokines. Assessment of microglial release of nitric oxide was based on the colorimetric assay for nitrite in the culture medium and histochemistry for nitric oxide synthase. Of the cytokines tested, only IFN-[gamma] (1000 U/ml) induced nitric oxide release from microglia. [beta]25-35 did not stimulate nitric oxide release by itself, but it did induce nitric oxide release when co-exposed with IFN-[gamma]. In contrast, [beta]1-40 did induce microglial release of nitric oxide by itself, and this effect was enhanced significantly by co-exposure with IFN-[beta] (100 U/ml). To elucidate the mechanisms involved in [beta]-amyloid mediated nitric oxide release, the binding of [beta]25-35 with the leukocyte integrin Mac-1, a cell surface receptor on microglia, was studied by observing (1) [beta]-amyloid ([beta]25-35)-mediated release of nitric oxide from cultured microglial cells following exposure to monoclonal antibodies against each subunit of Mac-1 (anti-CD18 and anti-CD11b) and (2) competitive binding assay of fluorochrome-labeled [beta]25-35 with anti-CD18 or anti-CD11b by fluorescent flow cytometry. The results demonstrate that binding of CD18 and CD11b on microglial cells are individually sufficient to elicit release of nitric oxide and that a combination of CD18 and CD11b elicit a maximal NO release. [beta]25-35 significantly reduced nitric oxide release mediated by Wt.3. In contrast, [beta]25-35 significantly increased nitric oxide release by OX42. The binding study further suggested that Wt.3 and [beta]25-35 share a common site of action on the CD18 of Mac-1. These findings warrant a further investigation into the role of microglia in the neurodegeneration of Alzheimer\u27s disease via nitric oxide toxicity induced by the synergistic action of [beta]-amyloid (with a costimulatory factor) and mediated by the microglial surface receptor Mac-1

Surviving gas expulsion with substructure

We investigate the reaction of clumpy stellar distributions to gas expulsion. We show that regions containing highly unbound substructures/subclusters after gas expulsion can produce a significant final bound cluster. The key quantity in determining if a region is able to form a bound cluster is the global virial ratio, and so regions must be looked at as a whole rather than by individual substructure/subclusters when determining if they might survive as a bound cluster

Discovery of A Binary System in IRAM 04191+1522

We present high angular resolution observations of the Class 0 protostar IRAM04191+1522, using the Submillimeter Array (SMA). The SMA 1.3 mm continuum images reveal within IRAM04191+1522 two distinct sources with an angular separation of 7.8\,$\pm$\,0.2$"$. The two continuum sources are located in the southeast-northwest direction, with total gas masses of about 0.011 M_sun and about 0.005 M_sun, respectively. The southeastern source, associated with an infrared source seen in the Spitzer images, is the well-known Class 0 protostar with a bolometric luminosity of about 0.08 L_sun. The newly-discovered northwestern continuum source is not visible in the Spitzer images at wavelengths from 3.6 to 70 micron, and has an extremely low bolometric luminosity (< 0.03 L_sun). Complementary IRAM N2H+(1-0) data that probe the dense gas in the common envelope suggest that the two sources were formed through the rotational fragmentation of an elongated dense core. Furthermore, comparisons between IRAM04191+1522 and other protostars suggest that most cores with binary systems formed therein have ratios of rotational energy to gravitational energy $\beta_{\rm rot}$ > 1%. This is consistent with theoretical simulations and indicates that the level of rotational energy in a dense core plays an important role in the fragmentation process.Comment: 15 pages, 4 figures, to be published by ApJ Letter

Variable number of tandem repeat markers in the genome sequence of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana (Musa spp)

ABSTRACT. We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas (Musa spp). Recently, the entire genome sequence of M. fijiensis became available. We screened this database for VNTR markers. Forty-two primer pairs were selected for validation, based on repeat type and length and the number of repeat units. Five VNTR markers showing multiple alleles were validated with a reference set of isolates from different parts of the world and a population from a banana plantation in Costa Rica. Polymorphism information content values varied from 0.6414 to 0.7544 for the reference set and from 0.0400 and 0.7373 for the population set. Eighty percent of the polymorphism information content values were above 0.60, indicating that the markers are highly informative. These markers allowed robust scoring of agarose gels and proved to be useful for variability and population genetics studies. In conclusion, the strategy we developed to identify and validate VNTR markers is an efficient means to incorporate markers that can be used for fungicide resistance management and to develop breeding strategies to control banana black leaf streak disease. This is the first report of VNTR-minisatellites from the M. fijiensis genome sequence. Key words: Molecular markers; VNTRs; Genetic diversity; Population genetics; Black Sigatok

Star cluster evolution in the Magellanic Clouds revisited

The evolution of star clusters in the Magellanic Clouds has been the subject of significant recent controversy, particularly regarding the importance and length of the earliest, largely mass-independent disruption phase (referred to as “infant mortality”). Here, we take a fresh approach to the problem, using a large, independent, and homogeneous data set of UBVR imaging observations, from which we obtain the cluster age and mass distributions in both the Large and Small Magellanic Clouds (LMC, SMC) in a self-consistent manner. We conclude that the (optically selected) SMC star cluster population has undergone at most ~30% (1σ) infant mortality between the age range from about 3–10 Myr, to that of approximately 40–160 Myr. We rule out a 90% cluster mortality rate per decade of age (for the full age range up to 109 yr) at a > 6σ level. Using a simple approach, we derive a “characteristic” cluster disruption time-scale for the cluster population in the LMC that implies that we are observing the initial cluster mass function (CMF). Preliminary results suggest that the LMC cluster population may be affected by <10% infant mortality

Using VR for Training how to Conduct A Tire Change on an Aircraft

Virtual Reality (VR) is becoming an affordable and increasingly common tool for training. Twenty-four Aviation Maintenance Science students were randomly assigned to a VR group or a Traditional Training (Demonstration) group for a Cessna tire change module. The VR group spent about 5 minutes interacting with the VR application where they completed several actions to replace a tire. The Traditional group watched the course instructor change a tire in the maintenance hangar. One week later, students from both groups changed a tire in a real-world environment. Time to complete tasks were measured for locating the procedure in the manual, jacking the airplane up, removing the cotter pin, removing the wheel, replacing the wheel, and jacking the airplane down. Participants self-reported on a scale of 1(Not helpful at all) to 10 (Extremely helpful) how beneficial they felt their training session was. The Traditional group was significantly faster than the VR group in locating the procedure in the manual (a task not conducted in the VR application). No other difference in time to complete tasks were found. The Traditional group rated their training as significantly more helpful for changing the tire than the VR group did. Except for downjacking the aircraft, a significant correlation was found between the more helpful students found their respective training and the faster they completed each task. Although the VR application was not better than the Traditional Training for the real-world task, finding VR training not worse than Traditional training for transfer of task warrants further study

Affiliation, Aggression, and Selectivity of Peer Relationships in Meadow and Prairie Voles

Relationships between adult peers are central to the structure of social groups. In some species, selective preferences for specific peers provide a foundation for consistent group composition. These preferences may be shaped by affiliation toward familiar individuals, and/or by aversion to unfamiliar individuals. We compared peer interactions in two vole species that form selective preferences for familiar same-sex individuals but differ in mating system. Prairie voles (Microtus ochrogaster) form pair bonds with mates and may reside in family groups. Meadow voles (Microtus pennsylvanicus) are promiscuous breeders that form communal winter groups in the wild, and exhibit greater social behavior in short day (SD) lengths in the laboratory. We characterized affiliative, anxiety-like, and aggressive interactions with familiar and novel same-sex conspecifics in meadow and prairie voles housed in summer- or winter-like photoperiods. Species differences in affective behaviors were pronounced, with prairie voles exhibiting more aggressive behavior and less anxiety-like behavior relative to meadow voles. Meadow voles housed in short (vs. long) day lengths were more affiliative and more interactive with strangers; prosocial behavior was also facilitated by a history of social housing. Prairie voles exhibited partner preferences regardless of sex or day length, indicating that selective peer preferences are the norm in prairie voles. Prairie vole females formed preferences for new same-sex social partners following re-pairing; males were often aggressive upon re-pairing. These data suggest that preferences for familiar peers in prairie voles are maintained in part by aggression toward unfamiliar individuals, as in mate partnerships. In contrast, social tolerance is an important feature of meadow vole peer affiliation, demonstrated by low aggression toward unfamiliar conspecifics, and consistent with field data on winter tolerance

Spiky oscillations in NF-kB signalling

The NF-kB signalling system is involved in a variety of cellular processes including immune response, inflammation, and apoptosis. Recent experiments have found oscillations in the nuclear-cytoplasmic translocation of the NF-kB transcription factor. How the cell uses the oscillations to differentiate input conditions and send specific signals to downstream genes is an open problem. We shed light on this issue by examining the small core network driving the oscillations, which, we show, is designed to produce periodic spikes in nuclear NF-kB concentration. The oscillations can be used to regulate downstream genes in a variety of ways. In particular, we show that genes to whose operator sites NF-kB binds and dissociates fast can respond very sensitively to changes in the input signal, with effective Hill coefficients in excess of 20.Comment: 11 pages, 13 figure

Pattern speed of main spiral arms in NGC 2997: Estimate based on very young stellar complexes

Deep JHK-Brg photometry of the southern arm of the grand-design spiral galaxy NGC 2997 was obtained by ISAAC/VLT. All sources in the field brighter than K=19 mag were located. Color-color diagrams were used to identify young stellar complexes among the extended sources. Ages can be estimated for the youngest complexes and correlated with azimuthal distances from the spiral arms defined by the K-band intensity variation. The extended sources with Mk <-12 mag display a diffuse appearance and are more concentrated inside the arm region than fainter ones, which are compact and uniformly distributed in the disk. The NIR colors of the bright diffuse objects are consistent with them being young starforming complexes with ages <10 Myr and reddened by up to 8 mag of visual extinction. They show a color gradient as a function of their azimuthal distance from the spiral arms. Interpreting this gradient as an age variation, the pattern speed Op = 16 km/s/kpc of the main spiral was derived assuming circular motion. The alignment and color gradient of the bright, diffuse complexes strongly support a density wave scenario for NGC 2997. Only the brightest complexes with Mk <-12 mag show a well aligned structure along the arm, suggesting that a strong compression in the gas due to the spiral potential is required to form these most massive aggregates, while smaller starforming regions are formed more randomly in the disk. The sharp transition between the two groups at Mk = -12 mag may be associated with expulsion of gas when the first supernovae explode in the complex.Comment: 4 pages, 5 figures. Accepted for publication as A&A Lette

Initial psychological responses to influenza A, H1N1 ("Swine flu")

Background The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. Methods 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption Results 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. Conclusion Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation