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Objective; To determine whether the same relationships between early life risk factors and socioeconomic status with childhood BMI are observed in a modern cohort (2000) compared with an historic cohort (1947). Study design; The relationships between early life factors and SES with childhood BMI were examined in two prospective birth cohorts from the same region, born 50 years apart: 711 children in the 1947 Newcastle Thousand Families Study (NTFS) and 475 from the 2000 Gateshead Millennium Study (GMS). The associations between birthweight, breastfeeding, rapid infancy growth (0-12 months), early life adversity (0-12 months) and parental SES (birth and childhood) with childhood BMI z-scores, and whether overweight/obese (BMI >91 st centile using UK 1990) aged 9 were examined using linear regression, path analyses and logistic regression. Results; In the NTFS, the most advantaged children were taller than the least (+0.91 height z-score, P = .001), whereas in GMS they had lower odds of overweight/obese than the least (0.35 (0.14, 0.86)). Rapid infancy growth was associated with increased BMIz in both cohorts, and with increased likelihood of overweight/obese in GMS. Conclusions; This suggests that children exposed to socioeconomic disadvantage or who have rapid infancy growth in modern environments are now at lower risk of growth restriction, but greater risk of overweight.

Synthetic promoters are an attractive alternative for use in mammalian hosts such as CHO cells as they can be designed de novo with user-defined functionalities. In this study, we describe and validate a method for bioprocess-directed design of synthetic promoters utilizing CHO genomic sequence information. We designed promoters with two objective features, (i) constitutive high-level recombinant gene transcription, and (ii) upregulated transcription under mild hypothermia or late-stage culture. CHO genes varying in transcriptional activity were selected based on a comparative analysis of RNA-Seq transcript levels in normal and biphasic cultures in combination with estimates of mRNA half-life from published genome scale datasets. Discrete transcription factor regulatory elements (TFREs) upstream of these genes were informatically identified and functionally screened in vitro to identify a subset of TFREs with the potential to support high activity recombinant gene transcription during biphasic cell culture processes. Two libraries of heterotypic synthetic promoters with varying TFRE combinations were then designed in silico that exhibited a maximal 2.5-fold increase in transcriptional strength over the CMV-IE promoter after transient transfection into host CHO-K1 cells. A subset of synthetic promoters was then used to create stable transfectant pools using CHO-K1 cells under glutamine synthetase selection. Whilst not achieving the maximal 2.5-fold increase in productivity over stable pools harboring the CMV promoter, all stably transfected cells utilizing synthetic promoters exhibited increased reporter production - up to 1.6-fold that of cells employing CMV, both in the presence or absence of intron A immediately downstream of the promoter. The increased productivity of stably transfected cells harboring synthetic promoters was maintained during fed-batch culture, with or without a transition to mild hypothermia at the onset of stationary phase. Our data exemplify that it is important to consider both host cell and intended bioprocess contexts as design criteria in the de novo construction of synthetic genetic parts for mammalian cell engineering.

Objectives:\ud To investigate whether high weight in infancy predicts obesity in childhood.\ud \ud Method:\ud Data from two UK cohorts (Newcastle Growth and Development N = 795, Gateshead Millennium N = 393) and one Finnish (Tampere N = 1262) were combined. Z scores of weight at 3 and 12 months and body mass index (BMI) at 5 and 8 years were categorized as raised/overweight (1 to

In this paper we set out to explore the prevalence of child undernutrition found in community studies in affluent societies, but a preliminary literature review revealed that, in the absence of a gold standard method of diagnosis, the prevalence largely depends on the measure, threshold and the growth reference used, as well as age. We thus go on to explore describe the common clinical ‘syndromes’ of child undernutrition: wasting, stunting and failure to thrive (weight faltering) and how we have used data from two population-based cohort studies, this paper to explore how much these different ‘syndromes’ overlap and the extent to which they reflect true undernutrition. This analysis revealed that when more than one definition is applied to the same children, a majority are below the lower threshold for only one measure. However, those with both weight faltering and low BMI in infancy, go on in later childhood to show growth and body composition patterns suggestive of previous undernutrition. In older children there is even less overlap and most children with either wasting or low fat seem to be simply growing at one extreme of the normal range. We conclude that in affluent societies the diagnosis of undernutrition is only robust when it relies on a combination of both, that is decline in weight or BMI centile and wasting.

Context. Young stars are formed with dusty discs around them. The dust grains in the disc are originally of the same size as interstellar dust, i.e., of the order of 0.1 μm. Models predict that these grains will grow in size through coagulation. Observations of the silicate features around 10 and 20 μm are consistent with growth from submicron to micron sizes in selected sources whereas the slope of the spectral energy distribution (SED) at mm and cm wavelengths traces growth up to mm sizes and larger. Aims. We here look for a correlation between these two grain growth indicators. Methods. A large sample of T-Tauri and Herbig-Ae/Be stars, spread over the star-forming regions in Chamaeleon, Lupus, Serpens, Corona Australis, and the Gum nebula in Vela, was observed with the Spitzer Space Telescope at 5–13 μm, and a subsample was observed with the SMA, ATCA, CARMA, and VLA at mm wavelengths. We complement this subsample with data from the literature to maximise the overlap between μm and mm observations and search for correlations in the grain-growth signatures. Synthetic spectra are produced to determine which processes may produce the dust evolution observed in protoplanetary discs. Results. Dust disc masses in the range

Observations with the Short Wavelength Spectrometer (SWS) onboard the {\it Infrared Space Observatory} (ISO) have led to the first detection of the methyl radical ${\rm CH_3}$ in the interstellar medium. The $\nu_2$ $Q-$branch at 16.5 $\mu$m and the $R$(0) line at 16.0 $\mu$m have been unambiguously detected toward the Galactic center SgrA$^*$. The analysis of the measured bands gives a column density of (8.0$\pm$2.4)$\times10^{14}$ cm$^{-2}$ and an excitation temperature of $(17\pm 2)$ K. Gaseous ${\rm CO}$ at a similarly low excitation temperature and ${\rm C_2H_2}$ are detected for the same line of sight. Using constraints on the ${\rm H_2}$ column density obtained from ${\rm C^{18}O}$ and visual extinction, the inferred ${\rm CH_3}$ abundance is $(1.3{{+2.2}\atop{-0.7}}) \times 10^{-8}$. The chemically related ${\rm CH_4}$ molecule is not detected, but the pure rotational lines of ${\rm CH}$ are seen with the Long Wavelength Spectrometer (LWS). The absolute abundances and the ${\rm CH_3/CH_4}$ and ${\rm CH_3/CH}$ ratios are inconsistent with published pure gas-phase models of dense clouds. The data require a mix of diffuse and translucent clouds with different densities and extinctions, and/or the development of translucent models in which gas-grain chemistry, freeze-out and reactions of ${\rm H}$ with polycyclic aromatic hydrocarbons and solid aliphatic material are included., Comment: 2 figures. ApJL, Accepted

We report a detection in the interstellar medium of an infrared transition within the electronic ground state of the deuterated hydrogen molecule, HD. Through a deep integration with the Short-Wavelength-Spectrometer on ISO, the pure rotational v=0-0 R(5) line at 19.43um was detected toward the Orion (OMC-1) outflow at its brightest H_2 emission region, Peak 1. The ~20" beam-averaged observed flux of the line is (1.84 +- 0.4) 10^-5 erg cm^-2 s^-1 sr^-1. Upper flux limits were derived for sixteen other rotational and ro-vibrational HD lines in the wavelength range 2.5 to 38 um. We utilize the rich spectrum of H_2 lines observed at the same position to correct for extinction, and to derive a total warm HD column density under the assumption that similar excitation conditions apply to H_2 and HD. Accounting for non-LTE HD level populations in a partially dissociated gas, our best estimate for the total warm HD column density is N(HD)=(2.0+-0.75)10^16 cm^-2. The warm molecular hydrogen column density is (2.21+-0.24)10^21 cm^-2, so that the relative abundance is [HD]/[H_2]=(9.0+-3.5)10^-6. Accounting for HD depletion relative to H_2 in partially dissociative shocks we derive a deuterium abundance in the warm shocked gas, [D]/[H]= (7.6+-2.9)10^-6. Our implied deuterium abundance is low compared to previous determinations in the local interstellar medium, but it is consistent with two other recent observations toward Orion, suggesting that deuterium may be significantly depleted there., Comment: 12 pages, 9 figures, to appear in A&A, vol 346 (1999)