Observation of thundercloud-related gamma rays and neutrons in Tibet

During the 2010 rainy season in Yangbajing (4300 m above sea level) in Tibet, China, a long-duration count enhancement associated with thunderclouds was detected by a solar-neutron telescope and neutron monitors installed at the Yangbajing Comic Ray Observatory. The event, lasting for ∼40  min, was observed on July 22, 2010. The solar-neutron telescope detected significant γ-ray signals with energies >40  MeV in the event. Such a prolonged high-energy event has never been observed in association with thunderclouds, clearly suggesting that electron acceleration lasts for 40 min in thunderclouds. In addition, Monte Carlo simulations showed that >10  MeV γ rays largely contribute to the neutron monitor signals, while >1  keV neutrons produced via a photonuclear reaction contribute relatively less to the signals. This result suggests that enhancements of neutron monitors during thunderstorms are not necessarily clear evidence for neutron production, as previously thought

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

ALMA Observations of a Gap and a Ring in the Protoplanetary Disk around TW Hya

We report the first detection of a gap and a ring in 336 GHz dust continuum emission from the protoplanetary disk around TW Hya, using the Atacama Large Millimeter/Submillimeter Array (ALMA). The gap and ring are located at around 25 and 41 au from the central star, respectively, and are associated with the CO snow line at ∼30 au. The gap has a radial width of less than 15 au and a mass deficit of more than 23%, taking into account that the observations are limited to an angular resolution of ∼15 au. In addition, the 13CO and C18O J=3-2 lines show a decrement in CO line emission throughout the disk, down to ∼10 au, indicating a freeze-out of gas-phase CO onto grain surfaces and possible subsequent surface reactions to form larger molecules. The observed gap could be caused by gravitational interaction between the disk gas and a planet with a mass less than super-Neptune (2{M}{{Neptune}}), or could be the result of the destruction of large dust aggregates due to the sintering of CO ice

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

An initial event in insect innate immune response: structural and biological studies of interactions between β-1,3-glucan and the N-terminal domain of β-1,3-glucan recognition protein

In response to invading microorganisms, insect β-1,3-glucan recognition protein (βGRP), a soluble receptor in the hemolymph, binds to the surfaces of bacteria and fungi and activates serine protease cascades that promote destruction of pathogens by means of melanization or expression of antimicrobial peptides. Here we report on the NMR solution structure of the N-terminal domain of βGRP (N-βGRP) from Indian meal moth (Plodia interpunctella), which is sufficient to activate the prophenoloxidase (proPO) pathway resulting in melanin formation. NMR and isothermal calorimetric titrations of N-βGRP with laminarihexaose, a glucose hexamer containing β-1,3 links, suggest a weak binding of the ligand. However, addition of laminarin, a glucose polysaccharide (~ 6 kDa) containing β-1,3 and β-1,6 links that activates the proPO pathway, to N-βGRP results in the loss of NMR cross-peaks from the backbone 15N-1H groups of the protein, suggesting the formation of a large complex. Analytical ultra centrifugation (AUC) studies of formation of N-βGRP:laminarin complex show that ligand-binding induces sel-fassociation of the protein:carbohydrate complex into a macro structure, likely containing six protein and three laminarin molecules (~ 102 kDa). The macro complex is quite stable, as it does not undergo dissociation upon dilution to sub-micromolar concentrations. The structural model thus derived from the present studies for N-βGRP:laminarin complex in solution differs from the one in which a single N-βGRP molecule has been proposed to bind to a triple helical form of laminarin on the basis of an X-ray crystallographic structure of N-βGRP:laminarihexaose complex [Kanagawa, M., Satoh, T., Ikeda, A., Adachi, Y., Ohno, N., and Yamaguchi, Y. (2011) J. Biol. Chem. 286, 29158-29165]. AUC studies and phenoloxidase activation measurements carried out with the designed mutants of N-βGRP indicate that electrostatic interactions involving Asp45, Arg54, and Asp68 between the ligand-bound protein molecules contribute in part to the stability of N-βGRP:laminarin macro complex and that a decreased stability is accompanied by a reduced activation of the proPO pathway. Increased β-1,6 branching in laminarin also results in destabilization of the macro complex. These novel findings suggest that ligand-induced self-association of βGRP:β-1,3-glucan complex may form a platform on a microbial surface for recruitment of downstream proteases, as a means of amplification of the initial signal of pathogen recognition for the activation of the proPO pathway

A Gap with a Deficit of Large Grains in the Protoplanetary Disk around TW Hya

We report ∼3 au resolution imaging observations of the protoplanetary disk around TW Hya at 145 and 233 GHz with the Atacama Large Millimeter/submillimeter Array. Our observations revealed two deep gaps (∼25%-50%) at 22 and 37 au and shallower gaps (a few percent) at 6, 28, and 44 au, as recently reported by Andrews et al. The central hole with a radius of ∼3 au was also marginally resolved. The most remarkable finding is that the spectral index α(R) between bands 4 and 6 peaks at the 22 au gap. The derived power-law index of the dust opacity β(R) is ∼1.7 at the 22 au gap and decreases toward the disk center to ∼0. The most prominent gap at 22 au could be caused by the gravitational interaction between the disk and an unseen planet with a mass of ≲1.5 M Neptune, although other origins may be possible. The planet-induced gap is supported by the fact that β(R) is enhanced at the 22 au gap, indicating a deficit of ∼millimeter-sized grains within the gap due to dust filtration by a planet

Heterosexual interactions of pairs of laboratory-housed stumptail macaques (Macaca arctoides) under continuous observation with closed-circuit video recording

Female-male interaction of heterosexual pairs of stumptail macaques, housed together continuously, was studied 24 hr per day using closed-circuit video recording. Two pairs were studied for approximately 2 months each. Although no generalizations can be made from such a small sample, no aspect of behavioral interaction varied significantly with the stage of the menstrual cycle of the female partner. Copulation occurred regularly but only during the daylight hours. Both pairs showed several peak ejaculation days (5-21 ejaculations/day), which were distributed throughout the entire menstrual cycle. In general, the highest number of ejaculations was observed to occur when the animals were put together either for the first time or following a separation of a few days. In one pair the female became pregnant, and from the fifth week of pregnancy onward there was a gradual increase in male aggression, coinciding with a decrease in male sexual and grooming behavior. In a second study eight different pairs were observed during the first day together and male copulatory behavior was studied. Two patterns of copulatory behavior could be discerned: pairs displaying a high number of ejaculations (19-38) and pairs displaying a low number of ejaculations (4-8). With regard to the interejaculatory interval (IEI), the male stumptail appeared to be unique. In contrast to what has been reported for other mammals, i.e., a steady increase in IEI with subsequent ejaculations, the stumptail showed increasing IEIs only during the first three to four, as well as between the last, ejaculations; in between, the IEI remained relatively constant. The maximum number of consecutive ejaculations observed was 38, displayed during a 10-hr time period (mean (± SEM)IEI, 12.9 ± 3.5 min)

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window