Effects of Ethanol Exposure and Withdrawal on Neuronal Morphology in the Agranular Insular and Prelimbic Cortices: Relationship with Withdrawal-Related Structural Plasticity in the Nucleus Accumbens

peer-reviewedThe present study investigated the effects of chronic intermittent ethanol exposure and withdrawal on dendritic morphology and spine density in the agranular insular and prelimbic cortices. Adult male Sprague–Dawley rats were passively exposed to vaporized ethanol (~37 mg/L; 12 h/day) or air (control) for ten consecutive days. Dendritic length, branching, and spine density were quantified in layer II/III pyramidal neurons 24 hours or seven days following the final ethanol exposure. Compared to unexposed control animals there were structural alterations on neurons in the prelimbic cortex, and to a lesser extent the agranular insular cortex. The most prominent ethanol-related differences were the transient increases in dendritic length and branching in prelimbic neurons at 24 h post-cessation, and increased mushroom-shaped spines at seven days post-cessation. The results obtained in the prelimbic cortex are the opposite of those previously reported in the nucleus accumbens core (Peterson, et al. 2015), suggesting that these regions undergo distinct functional adaptations following ethanol exposure and withdrawal

A third red supergiant rich cluster in the Scutum-Crux arm

Aims. We aim to characterise the properties of a third massive, red supergiant dominated galactic cluster. Methods. To accomplish this we utilised a combination of near/mid-IR photometry and spectroscopy to identify and classify the properties of cluster members, and statistical arguments to determine the mass of the cluster. Results. We found a total of 16 strong candidates for cluster membership, for which formal classification of a subset yields spectral types from K3-M4 Ia and luminosities between log(L/L-circle dot) similar to 4.5-4.8 for an adopted distance of 6 +/- 1 kpc. For an age in the range of 16-20 Myr, the implied mass is 2-4 x 10(4) M-circle dot, making it one of the most massive young clusters in the Galaxy. This discovery supports the hypothesis that a significant burst of star formation occurred at the base of Scutum-Crux arm between 10-20 Myr ago, yielding a stellar complex comprising at least similar to 10(5) M-circle dot of stars (noting that since the cluster identification criteria rely on the presence of RSGs, we suspect that the true stellar yield will be significantly higher). We highlight the apparent absence of X-ray binaries within the star formation complex and finally, given the physical association of at least two pulsars with this region, discuss the implications of this finding for stellar evolution and the production and properties of neutron stars

The VLT-FLAMES Tarantula survey XX. The nature of the X-ray bright emission-line star VFTS 399

Context. The stellar population of the 30 Doradus star-forming region in the Large Magellanic Cloud contains a subset of apparently single, rapidly rotating O-type stars. The physical processes leading to the formation of this cohort are currently uncertain. Aims. One member of this group, the late O-type star VFTS 399, is found to be unexpectedly X-ray bright for its bolometric luminosity − in this study we aim to determine its physical nature and the cause of this behaviour. Methods. To accomplish this we performed a time-resolved analysis of optical, infrared and X-ray observations. Results. We found VFTS 399 to be an aperiodic photometric variable with an apparent near-IR excess. Its optical spectrum demonstrates complex emission profiles in the lower Balmer series and select He i lines − taken together these suggest an OeBe classification. The highly variable X-ray luminosity is too great to be produced by a single star, while the hard, non-thermal nature suggests the presence of an accreting relativistic companion. Finally, the detection of periodic modulation of the X-ray lightcurve is most naturally explained under the assumption that the accretor is a neutron star. Conclusions. VFTS 399 appears to be the first high-mass X-ray binary identified within 30 Dor, sharing many observational characteristics with classical Be X-ray binaries. Comparison of the current properties of VFTS 399 to binary-evolution models suggests a progenitor mass ≳25 M⊙ for the putative neutron star, which may host a magnetic field comparable in strength to those of magnetars. VFTS 399 is now the second member of the cohort of rapidly rotating “single” O-type stars in 30 Dor to show evidence of binary interaction resulting in spin-up, suggesting that this may be a viable evolutionary pathway for the formation of a subset of this stellar population

Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: Involvement of src family protein kinases

The increased production of amyloid beta -peptide (A beta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to A beta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to A beta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar A beta (25-35) and A beta (1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-( 4-chlorophenyl)- 7(t-butyl) pyrazol(3,4-D) pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from A beta (25-35)-treated neurons showed an increased association of Fyn with FAK. A beta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in A beta -treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to A beta exposure and may be critical for subsequent neurodegenerative changes

Limits on models of the ultrahigh energy cosmic rays based on topological defects

An erratum exists for this article. Please see the description link below for details.Using the propagation of ultrahigh energy nucleons, photons, and electrons in the universal radiation backgrounds, we obtain limits on the luminosity of topological defect scenarios for the origin of the highest energy cosmic rays. The limits are set as a function of the mass of the X particles emitted by the cosmic strings or other defects, the cosmological evolution of the topological defects, and the strength of the extragalactic magnetic fields. The existing data on the cosmic ray spectrum and on the isotropic 100 MeV gamma-ray background limit significantly the parameter space in which topological defects can generate the flux of the highest energy cosmic rays, and rule out models with the standard X-particle mass of 10¹⁶GeV and higher.R. J. Protheroe and Todor Stane

Probing Grand Unified Theories with Cosmic Ray, Gamma-Ray and Neutrino Astrophysics

We explore scenarios where the highest energy cosmic rays are produced by new particle physics near the grand unification scale. Using detailed numerical simulations of extragalactic nucleon, gamma-ray, and neutrino propagation, we show the existence of an interesting parameter range for which such scenarios may explain part of the data and are consistent with all observational constraints. A combination of proposed observatories for ultra-high energy cosmic rays, neutrino telescopes of a few kilometer scale, and gamma-ray astrophysics instruments should be able to test these scenarios. In particular, for neutrino masses in the eV range, exclusive neutrino decay modes of superheavy particles can give rise to neutrino fluxes comparable to those predicted in models of active galactic nuclei.Comment: 15 latex pages, 5 postscript figures included, uses revtex.sty and psfig.sty. Submitted to Physical Review

Errors in the bisulfite conversion of DNA: modulating inappropriate- and failed-conversion frequencies

Bisulfite treatment can be used to ascertain the methylation states of individual cytosines in DNA. Ideally, bisulfite treatment deaminates unmethylated cytosines to uracils, and leaves 5-methylcytosines unchanged. Two types of bisulfite-conversion error occur: inappropriate conversion of 5-methylcytosine to thymine, and failure to convert unmethylated cytosine to uracil. Conventional bisulfite treatment requires hours of exposure to low-molarity, low-temperature bisulfite (‘LowMT’) and, sometimes, thermal denaturation. An alternate, high-molarity, high-temperature (‘HighMT’) protocol has been reported to accelerate conversion and to reduce inappropriate conversion. We used molecular encoding to obtain validated, individual-molecule data on failed- and inappropriate-conversion frequencies for LowMT and HighMT treatments of both single-stranded and hairpin-linked oligonucleotides. After accounting for bisulfite-independent error, we found that: (i) inappropriate-conversion events accrue predominantly on molecules exposed to bisulfite after they have attained complete or near-complete conversion; (ii) the HighMT treatment is preferable because it yields greater homogeneity among sites and among molecules in conversion rates, and thus yields more reliable data; (iii) different durations of bisulfite treatment will yield data appropriate to address different experimental questions; and (iv) conversion errors can be used to assess the validity of methylation data collected without the benefit of molecular encoding

Persistent elastic behavior above a megathrust rupture patch: Nias island, West Sumatra

We quantify fore-arc deformation using fossil reefs to test the assumption commonly made in seismic cycle models that anelastic deformation of the fore arc is negligible. Elevated coral microatolls, paleoreef flats, and chenier plains show that the Sumatran outer arc island of Nias has experienced a complex pattern of relatively slow long-term uplift and subsidence during the Holocene epoch. This same island rose up to 2.9 m during the Mw 8.7 Sunda megathrust rupture in 2005. The mismatch between the 2005 and Holocene uplift patterns, along with the overall low rates of Holocene deformation, reflects the dominance of elastic strain accumulation and release along this section of the Sunda outer arc high and the relatively subordinate role of upper plate deformation in accommodating long-term plate convergence. The fraction of 2005 uplift that will be retained permanently is generally <4% for sites that experienced more than 0.25 m of coseismic uplift. Average uplift rates since the mid-Holocene range from 1.5 to −0.2 mm/a and are highest on the eastern coast of Nias, where coseismic uplift was nearly zero in 2005. The pattern of long-term uplift and subsidence is consistent with slow deformation of Nias along closely spaced folds in the north and trenchward dipping back thrusts in the southeast. Low Holocene tectonic uplift rates provide for excellent geomorphic and stratigraphic preservation of the mid-Holocene relative sea level high, which was under way by ∼7.3 ka and persisted until ∼2 ka

'It's small steps, but that leads to bigger changes': evaluation of a nurture group intervention

This article presents the results of a small-scale research project that aimed to evaluate the effectiveness of a part-time nurture group recently established in one primary school. Qualitative interviews were used to gather staff, pupil and parental perceptions about the nurture group. These focused on what difference the nurture group was making to the pupils concerned but also on views about what factors contributed to noted changes. All stakeholder groups identified areas of development for nurture group pupils. These included improved social skills, growth in personal confidence, greater engagement with academic tasks, and fewer incidences of undesirable behaviour. The evidence gathered so far suggests that the nurture group offered an effective way of supporting the social, emotional and behavioural skills of a group of 'at-risk' pupils. A range of factors thought to be important in achieving these outcomes are highlighted. These align broadly with the theoretical underpinnings of nurture groups

Activity loss is associated with cognitive decline in age-related macular degeneration.

BACKGROUND/METHODS: The objective of this study was to determine whether relinquishing cognitive, physical, and social activities is associated with an increased risk of cognitive decline in patients with age-related macular degeneration (AMD). We conducted a 3-year longitudinal study of 206 nondemented patients with AMD. RESULTS: Twenty-three subjects (14.4%) declined cognitively. Age, sex, education, decline in visual acuity, and number of dropped activities were associated with cognitive decline; each additional dropped activity increased the risk by 58%. Subjects who relinquished three activities were 3.87 times (95% confidence interval, 1.95-7.76) more likely to become demented than subjects who relinquished no activities; those who relinquished five activities were 9.54 times (95% confidence interval, 3.05-30.43) more likely. A multivariate model demonstrated that number of dropped activities was a powerful predictor of cognitive decline after controlling for relevant risk factors, particularly for subjects younger than 80 years of age. CONCLUSIONS: Relinquishing valued activities is associated with an increased risk of cognitive decline in older patients with vision loss caused by AMD. These data suggest the importance of promoting optimal cognitive and physical health in patients with AMD and perhaps other chronic diseases