Ceramic composition at Chalcolithic Shiqmim, northern Negev desert, Israel: investigating technology and provenance using thin section petrography, instrumental geochemistry and calcareous nannofossils

Technological innovations in ceramic production and other crafts are hallmarks of the Chalcolithic period (4500–3600 BCE) in the southern Levant, but details of manufacturing traditions have not been fully investigated using the range of analytical methods currently available. This paper presents results of a compositional study of 51 sherds of ceramic churns and other pottery types from the Chalcolithic site of Shiqmim in the northern Negev desert. By applying complementary thin section petrography, instrumental geochemistry and calcareous nannofossil analyses, connections between the raw materials, clay paste recipes and vessel forms of the selected ceramic samples are explored and documented. The study indicates that steps in ceramic manufacturing can be related to both technological choices and local geology. Detailed reporting of the resulting data facilitates future comparative ceramic compositional research that is needed as a basis for testable regional syntheses and to better resolve networks of trade/exchange and social group movement

AMPK regulates basal skeletal muscle capillarization and VEGF expression, but is not necessary for the angiogenic response to exercise

5 -AMP-activated protein kinase(AMPK)is a metabolic fuel sensor that monitors cellular energy charge, while the vasculature is important for maintaining cellular energy homeostasis. Mice with muscle-specific inactive AMPK (AMPK DN) were used to investigate if AMPK regulates skeletal muscle capillarization and the angiogenic responses to exercise. Two hours of the AMP analogueAICAR(1.0 g kg - 1)or systemichypoxia (6%O2) increased vascular endothelial growth factor (VEGF) mRNA in wild-type (WT), but not in AMPK DN mice. In contrast, the increase in VEGF mRNA with acute exercise (1 h at 20m min - 1, 10% gradient) was greater in AMPK DN compared to WT mice. Nuclear run-on assay demonstrated that exercise increased VEGF transcription, while hypoxia decreased VEGF transcription. There was no difference in VEGF transcription between WT and AMPK DN. There was a strong correlation between VEGF transcription and VEGF mRNA at rest and with exercise. Resting capillarization was lower in AMPK DN compared to WT. Wheel running (28 days) increased capillarization and this response was AMPK independent. Significant correlations between VEGF protein and muscle capillarization are consistent with VEGF being an important determinant of skeletal muscle capillarization. These data are to our knowledge the first to demonstrate in skeletal muscle in vivo that: (1) AMPK is necessary for hypoxia-induced VEGF mRNA stabilization, (2) acute exercise increases VEGF transcription, (3) inhibition of AMPK augments the VEGF mRNA response to acute exercise, and (4) AMPK regulates basal VEGF expression and capillarization, but is not necessary for exercise-induced angiogenesis. Originally published Journal of Physiology, Vol. 586, No. 24, Dec 200

miRNAs that associate with conjunctival inflammation and ocular Chlamydia trachomatis infection do not predict progressive disease.

We previously showed that conjunctival miR-147b and miR-1285 were upregulated in Gambian adults with inflammatory scarring trachoma, and miR-155 and miR-184 expression was strongly associated with conjunctival inflammation and ocular Chlamydia trachomatis infection in children from Guinea-Bissau. We investigated whether the single or combined expression of miR-147b, miR-1285, miR-155 and miR-184 was able to identify individuals with increased risk of incident or progressive scarring trachoma. Conjunctival swab samples were collected from 506 children between the ages of 4 and 12 living in northern Tanzania. These 506 samples formed the baseline sample set of a 4-year longitudinal study. Chlamydia trachomatis infection was diagnosed by droplet digital PCR and expression of miR-155, miR-184, miR-1285 and miR-147b was tested by qPCR. Individuals were assessed for incidence and progression of conjunctival scarring by comparison of conjunctival photographs taken at baseline and 4 years later. miR-184 and miR-155 were strongly associated with inflammation and infection at baseline; however, no miR was associated with 4-year scarring incidence or progression. miR-184 expression was more strongly downregulated during inflammation in non-progressors relative to progressors, suggesting that a disequilibrium in the efficiency of wound healing is a significant determinant of progressive conjunctival fibrosis

The cnidarian-bilaterian ancestor possessed at least 56 homeoboxes: evidence from the starlet sea anemone, Nematostella vectensis

BACKGROUND: Homeodomain transcription factors are key components in the developmental toolkits of animals. While this gene superclass predates the evolutionary split between animals, plants, and fungi, many homeobox genes appear unique to animals. The origin of particular homeobox genes may, therefore, be associated with the evolution of particular animal traits. Here we report the first near-complete set of homeodomains from a basal (diploblastic) animal. RESULTS: Phylogenetic analyses were performed on 130 homeodomains from the sequenced genome of the sea anemone Nematostella vectensis along with 228 homeodomains from human and 97 homeodomains from Drosophila. The Nematostella homeodomains appear to be distributed among established homeodomain classes in the following fashion: 72 ANTP class; one HNF class; four LIM class; five POU class; 33 PRD class; five SINE class; and six TALE class. For four of the Nematostella homeodomains, there is disagreement between neighbor-joining and Bayesian trees regarding their class membership. A putative Nematostella CUT class gene is also identified. CONCLUSION: The homeodomain superclass underwent extensive radiations prior to the evolutionary split between Cnidaria and Bilateria. Fifty-six homeodomain families found in human and/or fruit fly are also found in Nematostella, though seventeen families shared by human and fly appear absent in Nematostella. Homeodomain loss is also apparent in the bilaterian taxa: eight homeodomain families shared by Drosophila and Nematostella appear absent from human (CG13424, EMXLX, HOMEOBRAIN, MSXLX, NK7, REPO, ROUGH, and UNC4), and six homeodomain families shared by human and Nematostella appear absent from fruit fly (ALX, DMBX, DUX, HNF, POU1, and VAX)

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

Kinematics of the Galactic Globular Cluster System: New Radial Velocities for Clusters in the Direction of the Inner Galaxy

HIRES on the Keck I telescope has been used to measure the first radial velocities for stars belonging to eleven, heavily-reddened globular clusters in the direction of the inner Galaxy. The question of kinematic substructuring among the Galactic globular cluster system is investigated using an updated catalog of globular cluster distances, metallicities and velocities. It is found that the population of metal-rich globular clusters shows significant rotation at all Galactocentric radii. For the metal-rich clusters within 4 kpc of the Galactic center, the measured rotation velocity and line-of-sight velocity dispersion are similar to those of bulge field stars. We investigate claims that the metal-rich clusters are associated with the central Galactic bar by comparing the kinematics of the innermost clusters to that of the atomic hydrogen in the inner Galaxy. The longitude-velocity diagram of both metal-rich and metal-poor clusters bears a remarkable similarity to that of the gas, including the same non-circular motions which have traditionally been interpreted as evidence for a Galactic bar, or, alternatively, a non-axisymmetric bulge. However, uncertainties in the existing three-dimensional Galactocentric positions for most of the clusters do not yet allow an unambiguous discrimination between the competing scenarios of membership in a rigidly rotating bar, or in a bulge which is an oblate isotropic rotator. We conclude that the majority of metal-rich clusters within the central 4 kpc of the Galaxy are probably associated with the bulge/bar, and not the thick disk. (ABRIDGED)Comment: 18 pages, including 7 of 13 postscript figures. Figures 1-6 available at http://astro.caltech.edu/~pc. Accepted for publication in the Astronomical Journa

Elemental Abundance Ratios in Stars of the Outer Galactic Disk. II. Field Red Giants

We summarize a selection process to identify red giants in the direction of the southern warp of the Galactic disk, employing VI_C photometry and multi-object spectroscopy. We also present results from follow-up high-resolution, high-S/N echelle spectroscopy of three field red giants, finding [Fe/H] values of about -0.5. The field stars, with Galactocentric distances estimated at 10 to 15 kpc, support the conclusion of Yong, Carney, & de Almeida (2005) that the Galactic metallicity gradient disappears beyond R_GC values of 10 to 12 kpc for the older stars and clusters of the outer disk. The field and cluster stars at such large distances show very similar abundance patterns, and, in particular, all show enhancements of the "alpha" elements O, Mg, Si, Ca, and Ti and the r-process element Eu. These results suggest that Type II supernovae have been significant contributors to star formation in the outer disk relative to Type Ia supernovae within the past few Gyrs. We also compare our results with those available for much younger objects. The limited results for the H II regions and B stars in the outer disk also suggest that the radial metallicity gradient in the outer disk is shallow or absent. The much more extensive results for Cepheids confirm these trends, and that the change in slope of the metallicity gradient may occur at a larger Galactocentric distance than for the older stars and clusters. However, the younger stars also show rising alpha element enhancements with increasing R_GC, at least beyond 12 kpc. These trends are consistent with the idea of a progressive growth in the size of the Galactic disk with time, and episodic enrichment by Type II supernovae as part of the disk's growth. [Abridged]Comment: Accepted for publication in A

Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy with heterogeneous clinical presentation and genetic background. The axonal form (CMT2) is characterised by decreased action potentials indicating primary axonal damage. The underlying pathology involves axonal degeneration which is supposed to be related to axonal protein dysfunction caused by various gene mutations. The overlapping clinical manifestation of CMT2 with distal hereditary motor neuropathy (dHMN) and intermediate CMT causes further diagnostic difficulties. Aminoacyl-tRNA synthetases have been implicated in the pathomechanism of CMT2. They have an essential role in protein translation by attaching amino acids to their cognate tRNAs. To date six families have been reported worldwide with dominant missense alanyl-tRNA synthetase (AARS) mutations leading to clinically heterogeneous axonal neuropathies. The pathomechanism of some variants could be explained by impaired amino acylation activity while other variants implicating an editing defect need to be further investigated. Here, we report a cohort of six additional families originating from the United Kingdom and Ireland with dominant AARS-related neuropathies. The phenotypic manifestation was distal lower limb predominant sensorimotor neuropathy but upper limb impairment with split hand deformity occasionally associated. Nerve conduction studies revealed significant demyelination accompanying the axonal lesion in motor and sensory nerves. Five families have the c.986G>A, p.(Arg329His) variant, further supporting that this is a recurrent loss of function variant. The sixth family, of Irish origin, had a novel missense variant, c.2063A>G, p.(Glu688Gly). We discuss our findings and the associated phenotypic heterogeneity in these families, which expands the clinical spectrum of AARS-related neuropathies

Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR

Study of the Composite Supernova Remnant MSH 11-62

We present the analysis of the X-ray data collected during an observation of the supernova remnant (SNR) MSH 11-62 by the Advanced Satellite for Cosmology and Astrophysics (ASCA). We show that MSH 11-62 is a composite remnant whose X-ray emission comes from two distinct contributions. Nonthermal, synchrotron emission, localized to a region of radius (~~)3' (consistent with a point source) dominates the total flux above 2 keV. A second contribution comes from a thermal component, extended up to a radius of (~~)6' and detected only at energies below 2keV. The spatial and spectral analysis imply the presence of a neutron star losing energy at a rate of about (10**36 - 10**37) ergs/s. No pulsed emission is detected and we set a limit on the pulsed fraction of 10%. This is consistent with the lack of a radio pulsar in the remnant, which may indicate that the pulsed emission from the rapidly rotating compact object that should be powering the synchrotron nebula is beamed and our viewing direction is unfavorable. In either event, the central neutron star deposits much of its spin-down energy into the surrounding synchrotron nebula where, through direct imaging with broadband satellites such as ASCA, it is possible to study the energetics and evolution of the compact remnant.Comment: 30 pages, including 5 figures, Latex. To appear in ApJ (May 20, 1998 issue, Vol. 499.