Agonist-Specific Calcium Signaling and Phosphoinositide Hydrolysis in Human SK-N-MCIXC Neuroepithelioma Cells

Fura-2 digital imaging microfluorimetry was used to evaluate the Ca 2+ signals generated in single clonal human neuroepithelioma cells (SK-N-MCIXC) in response to agonists that stimulate phosphoinositide hydrolysis. Addition of optimal concentrations of either endothelin-1 (ET-1), ATP, oxotremorine-M (Oxo-M), or norepinephrine (NE) all resulted in an increase in the concentration of cytosolic calcium (Ca 2+ i ) but of different magnitudes (ET-1 = ATP> NE). The Ca 2+ signals elicited by the individual agonists also differed from each other in terms of their latency of onset, rate of rise and decay, and prevalence of a sustained phase of Ca 2+ influx. The Ca 2+ signals that occurred in response to ATP had a shorter latency and more rapid rates of rise and decay than those observed for the other three agonists. Furthermore, a sustained plateau phase of the Ca 2+ signal, which was characteristic of the response to Oxo-M, was observed in 94% of cells responded to ET-1 or ATP, whereas corresponding values for Oxo-M and NE were ∼74 and ∼48%. Sequential addition of agonists to cells maintained in a Ca 2+ -free buffer indicated that each ligand mobilized Ca 2+ from a common intracellular pool. When monitored as a release of a total inositol phosphate fraction, all four agonists elicited similar (four- to sixfold) increases in phosphoinositide hydrolysis. However, the addition of ET-1 or ATP resulted in larger increases in the net formation of inositol 1,4,5-trisphosphate than did either Oxo-M or NE. These results indicate that, in SK-N-MCIXC cells, the characteristics of both Ca 2+ signaling and inositol phosphate production are agonist specific.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66414/1/j.1471-4159.1994.63062099.x.pd

Depositional and structural history of the Pennsylvanian system of the Illinois Basin : field trip 9, Ninth International Congress of Carboniferous Stratigraphy and Geology

Field trip held May 26 to June 1, 1979.Includes bibliographies.Pt. 1. Road log and descriptions of stops.--Pt. 2. Invited papers

Mapping the Galactic Halo. V. Sgr dSph Tidal Debris 60 degrees from the Main Body

As part of the Spaghetti Project Survey (SPS) we have detected a concentration of giant stars well above expectations for a smooth halo model. The position (l~350, b~50) and distance (~50 kpc) of this concentration match those of the Northern over-density detected by SDSS (Yanny et al. 2000, Ivezic et al. 2000). We find additional evidence for structure at ~80 kpc in the same direction. We present radial velocities for many of these stars, including the first published results from the 6.5m Magellan telescope. The radial velocities for stars in these structures are in excellent agreement with models of the dynamical evolution of the Sgr dwarf tidal debris, whose center is 60 degrees away. The metallicity of stars in these streams is lower than that of the main body of the Sgr dwarf, which may indicate a radial metallicity gradient prior to disruption.Comment: 10 pages, 3 figures accepted in Astrophysical Journal Letter

The Relation Between Ocular Dominance, Handidness, and Visual Acuity

It is of certain theoretical and academic interest to learn whether persons who are right handed also tend to be right-eyed or visa versa. The question often comes up as to whether one who has marked ocular dominance tends to use the better eye or whether the eye being used most gets weaker or stronger. Data were available that could be analyzed to throw light on these problems which might be formulated into the following questions: 1. Is there a tendency for right-handed persons to be right-eyed and left-handed persons to be left-eyed? 2. Is the dominant eye the strongest eye

Potential for tree rings to reveal spatial patterns of past drought variability across western Australia

Proxy records have provided major insights into the variability of past climates over long timescales. However, for much of the Southern Hemisphere, the ability to identify spatial patterns of past climatic variability is constrained by the sparse distribution of proxy records. This is particularly true for mainland Australia, where relatively few proxy records are located. Here, we (1) assess the potential to use existing proxy records in the Australasian region—starting with the only two multi-century tree-ring proxies from mainland Australia—to reveal spatial patterns of past hydroclimatic variability across the western third of the continent, and (2) identify strategic locations to target for the development of new proxy records. We show that the two existing tree-ring records allow robust reconstructions of past hydroclimatic variability over spatially broad areas (i.e. > 3° × 3°) in inland north- and south-western Australia. Our results reveal synchronous periods of drought and wet conditions between the inland northern and southern regions of western Australia as well as a generally anti-phase relationship with hydroclimate in eastern Australia over the last two centuries. The inclusion of 174 tree-ring proxy records from Tasmania, New Zealand and Indonesia and a coral record from Queensland did not improve the reconstruction potential over western Australia. However, our findings suggest that the addition of relatively few new proxy records from key locations in western Australia that currently have low reconstruction skill will enable the development of a comprehensive drought atlas for the region, and provide a critical link to the drought atlases of monsoonal Asia and eastern Australia and New Zealand

Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood

IMPORTANCE: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes.OBJECTIVES: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood.DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024.EXPOSURES: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation.MAIN OUTCOMES AND MEASURES: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score.RESULTS: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years.CONCLUSIONS AND RELEVANCE: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.</p

Five centuries of Upper Indus River flow from tree rings

Water wars are a prospect in coming years as nations struggle with the effects of climate change, growing water demand, and declining resources. The Indus River supplies water to the world’s largest contiguous irrigation system generating 90% of the food production in Pakistan as well as 13 gigawatts of hydroelectricity. Because any gap between water supply and demand has major and far-reaching ramifications, an understanding of natural flow variability is vital – especially when only 47 years of instrumental record is available. A network of tree-ring sites from the Upper Indus Basin (UIB) was used to reconstruct river discharge levels covering the period AD 1452–2008. Novel methods tree-ring detrending based on the ‘signal free’ method and estimation of reconstruction uncertainty based on the ‘maximum entropy bootstrap’ are used. This 557-year record displays strong inter-decadal fluctuations that could not have been deduced from the short gauged record. Recent discharge levels are high but not statistically unprecedented and are likely to be associated with increased meltwater from unusually heavy prior winter snowfall. A period of prolonged below-average discharge is indicated during AD 1572–1683. This unprecedented low-flow period may have been a time of persistently below-average winter snowfall and provides a warning for future water resource planning. Our reconstruction thus helps fill the hydrological information vacuum for modeling the Hindu Kush–Karakoram–Himalayan region and is useful for planning future development of UIB water resources in an effort to close Pakistan’s “water gap”. Finally, the river discharge reconstruction provides the basis for comparing past, present, and future hydrologic changes, which will be crucial for detection and attribution of hydroclimate change in the Upper Indus Basin

Mapping the Galactic Halo I. The `Spaghetti' Survey

We describe a major survey of the Milky Way halo designed to test for kinematic substructure caused by destruction of accreted satellites. We use the Washington photometric system to identify halo stars efficiently for spectroscopic followup. Tracers include halo giants (detectable out to more than 100 kpc), blue horizontal branch stars, halo stars near the main sequence turnoff, and the ``blue metal-poor stars'' of Preston et al (1994). We demonstrate the success of our survey by showing spectra of stars we have identified in all these categories, including giants as distant as 75 kpc. We discuss the problem of identifying the most distant halo giants. In particular, extremely metal-poor halo K dwarfs are present in approximately equal numbers to the distant giants for V fainter than 18, and we show that our method will distinguish reliably between these two groups of metal-poor stars. We plan to survey 100 square degrees at high galactic latitude, and expect to increase the numbers of known halo giants, BHB stars and turnoff stars by more than an order of magnitude. In addition to the strong test that this large sample will provide for the question `was the Milky Way halo accreted from satellite galaxies?', we will improve the accuracy of mass measurements of the Milky Way beyond 50 kpc via the kinematics of the many distant giants and BHB stars we will find. We show that one of our first datasets constrains the halo density law over galactocentric radii of 5-20 kpc and z heights of 2-15 kpc. The data support a flattened power-law halo with b/a of 0.6 and exponent -3.0. More complex models with a varying axial ratio may be needed with a larger dataset.Comment: 55 pages, 22 figures, to appear in the Astronomical Journa