Differential effects of thyroid hormone manipulation and ß adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T(3)) in on the first day of life. T(3) and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective beta3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T(3) (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T(3) administration raised plasma T(3) concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T(3) administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets.

Validation of a FFQ for estimating whole-grain cereal food intake

Estimation of whole-grain (WG) food intake in epidemiological and nutritional studies is normally based on general diet FFQ, which are not designed to specifically capture WG intake. To estimate WG cereal intake, we developed a forty-three-item FFQ focused on cereal product intake over the past month. We validated this questionnaire against a 3-d-weighed food record (3DWFR) in thirty-one subjects living in the French-speaking part of Switzerland (nineteen female and twelve male). Subjects completed the FFQ on day 1 (FFQ1), the 3DWFR between days 2 and 13 and the FFQ again on day 14 (FFQ2). The subjects provided a fasting blood sample within 1 week of FFQ2. Total cereal intake, total WG intake, intake of individual cereals, intake of different groups of cereal products and alkylresorcinol (AR) intake were calculated from both FFQ and the 3DWFR. Plasma AR, possible biomarkers for WG wheat and rye intake were also analysed. The total WG intake for the 3DWFR, FFQ1, FFQ2 was 26 (sd 22), 28 (sd 25) and 21 (sd 16) g/d, respectively. Mean plasma AR concentration was 55.8 (sd 26.8) nmol/l. FFQ1, FFQ2 and plasma AR were correlated with the 3DWFR (r 0.72, 0.81 and 0.57, respectively). Adjustment for age, sex, BMI and total energy intake did not affect the results. This FFQ appears to give a rapid and adequate estimate of WG cereal intake in free-living subjects.

Characterization of a gamma-aminobutyric acid transport system of rhizobium leguminosarum bv. viciae 3841

Spontaneous mutants of Rhizobium leguminosarum bv. viciae 3841 were isolated that grow faster than the wild type on gamma-aminobutyric acid (GABA) as the sole carbon and nitrogen source. These strains (RU1736 and RU1816) have frameshift mutations (gtsR101 and gtsR102, respectively) in a GntR-type regulator (GtsR) that result in a high rate of constitutive GABA transport. Tn5 mutagenesis and quantitative reverse transcription-PCR showed that GstR regulates expression of a large operon (pRL100242 to pRL100252) on the Sym plasmid that is required for GABA uptake. An ABC transport system, GtsABCD (for GABA transport system) (pRL100248-51), of the spermidine/putrescine family is part of this operon. GtsA is a periplasmic binding protein, GtsB and GtsC are integral membrane proteins, and GtsD is an ATP-binding subunit. Expression of gtsABCD from a lacZ promoter confirmed that it alone is responsible for high rates of GABA transport, enabling rapid growth of strain 3841 on GABA. Gts transports open-chain compounds with four or five carbon atoms with carboxyl and amino groups at, or close to, opposite termini. However, aromatic compounds with similar spacing between carboxyl and amino groups are excellent inhibitors of GABA uptake so they may also be transported. In addition to the ABC transporter, the operon contains two putative mono-oxygenases, a putative hydrolase, a putative aldehyde dehydrogenase, and a succinate semialdehyde dehydrogenase. This suggests the operon may be involved in the transport and breakdown of a more complex precursor to GABA. Gts is not expressed in pea bacteroids, and gtsB mutants are unaltered in their symbiotic phenotype, suggesting that Bra is the only GABA transport system available for amino acid cycling.

Crops and cultures in the Pacific: new data and new techniques for the investigation of old questions

Fifty years ago Carl Sauer suggested, controversially and on the basis of theory rather than evidence, that Southeast Asia was the source area for agriculture throughout the Old World, including the Pacific. Since then, the archaeobotanical record (macroscopic and microscopic) from the Pacific islands has increased, leading to suggestions, also still controversial, that Melanesia was a center of origin of agriculture independent of South-east Asia, based on tree fruits and nuts and vegetatively propagated starchy staples. Such crops generally lack morphological markers of domestication, so exploitation, cultivation and domestication cannot easily be distinguished in the archaeological record. Molecular studies involving techniques such as chromosome painting, DNA fingerprinting and DNA sequencing, can potentially complement the archaeological record by suggesting where species which were spread through the Pacific by man originated and by what routes they attained their present distributions. A combination of archaeobotanical and molecular studies should therefore eventually enable the rival claims of Melanesia versus South-east Asia as independent centers of invention of agriculture to be assessed.

Designs for an adaptive tuned vibration absorber with variable shape stiffness element

An adaptive tuned vibration absorber (ATVA) with a smart variable stiffness element is capable of retuning itself in response to a time-varying excitation frequency., enabling effective vibration control over a range of frequencies. This paper discusses novel methods of achieving variable stiffness in an ATVA by changing shape, as inspired by biological paradigms. It is shown that considerable variation in the tuned frequency can be achieved by actuating a shape change, provided that this is within the limits of the actuator. A feasible design for such an ATVA is one in which the device offers low resistance to the required shape change actuation while not being restricted to low values of the effective stiffness of the vibration absorber. Three such original designs are identified: (i) A pinned-pinned arch beam with fixed profile of slight curvature and variable preload through an adjustable natural curvature; (ii) a vibration absorber with a stiffness element formed from parallel curved beams of adjustable curvature vibrating longitudinally; (iii) a vibration absorber with a variable geometry linkage as stiffness element. The experimental results from demonstrators based on two of these designs show good correlation with the theory.

Actinomyces canis sp. nov., isolated from dogs

Three strains of a previously undescribed catalase-positive Actinomyces-like bacterium were isolated from dogs. Biochemical testing and PAGE analysis of whole-cell proteins indicated that the strains were phenotypically highly related to each other but different from previously described Actinomyces and Arcanobacterium species. Sequencing of 16S rRNA showed that the unknown bacterium represents a new subline within a cluster of species which includes Actinomyces hyovaginalis, Actinomyces georgiae, Actinomyces meyeri, Actinomyces odontolyticus, Actinomyces radingae and Actinomyces turicensis. On the basis of phenotypic evidence and 16S rRNA sequence divergence levels (greater than 5% with recognized Actinomyces species) it is proposed that the unknown strains from canine sources be classified as a new species with the name Actinomyces canis sp. nov. The type strain of Actinomyces canis is CCUG 41706T (= CIP 106351T).

High leverage interventions: three cases of defensive action and their lessons for OR/MS today.

This paper has two aims. First, to present cases in which scientists developed a defensive system for their homeland: Blackett and the air defense of Britain in WWII, Forrester and the SAGE system for North America in the Cold War, and Archimedes’ work defending Syracuse during the Second Punic War. In each case the historical context and the individual’s other achievements are outlined, and a description of the contribution’s relationship to OR/MS is given. The second aim is to consider some of the features the cases share and examine them in terms of contemporary OR/MS methodology. Particular reference is made to a recent analysis of the field’s strengths and weaknesses. This allows both a critical appraisal of the field and a set of potential responses for strengthening it. Although a mixed set of lessons arise, the overall conclusion is that the cases are examples to build on and that OR/MS retains the ability to do high stakes work.

Quarrels with the Quarrels with History

This essay is about my intellectual formation.

Technical note: a simple procedure for removing temporal discontinuities in ERA-Interim upper stratospheric temperatures for use in nudged chemistry-climate model simulations

This note describes a simple procedure for removing unphysical temporal discontinuities in ERA-Interim upper stratospheric global mean temperatures in March 1985 and August 1998 that have arisen due to changes in satellite radiance data used in the assimilation. The derived temperature adjustments (offsets) are suitable for use in stratosphere-resolving chemistry-climate models that are nudged (relaxed) to ERA-Interim winds and temperatures. Simulations using a nudged version of the Canadian Middle Atmosphere Model (CMAM) show that the inclusion of the temperature adjustments produces temperature time series that are devoid of the large jumps in 1985 and 1998. Due to its strong temperature dependence, the simulated upper stratospheric ozone is also shown to vary smoothly in time, unlike in a nudged simulation without the adjustments where abrupt changes in ozone occur at the times of the temperature jumps. While the adjustments to the ERA-Interim temperatures remove significant artefacts in the nudged CMAM simulation, spurious transient effects that arise due to water vapour and persist for about 5 yr after the 1979 switch to ERA-Interim data are identified, underlining the need for caution when analysing trends in runs nudged to reanalyses.

Youth unemployment and vocational training

This paper focuses on the determinants of the labor market situation of young people in developed countries and the developing world, with a particular emphasis on the role of vocational training and education policies. We highlight the role of demographic factors, economic growth and labor market institutions in explaining young people's transition into work. Subsequently, we assess differences between the setup and functioning of the vocational education and training policies across major world regions as an important driver of differential labor market situation of youth. Based on our analysis, we argue in favor of vocational education and training systems combining work experience and general education and provide some policy recommendations regarding the implementation of education and training systems adapted to a country's economic and institutional context.

Highly efficient neural differentiation of human somatic stem cells, isolated by minimally invasive periodontal surgery

Neural stem cells (NSCs) are potential sources for cell therapy of neurodegenerative diseases and for drug screening. Despite their potential benefits, ethical and practical considerations limit the application of NSCs derived from human embryonic stem cells (ES) or adult brain tissue. Thus, alternative sources are required to satisfy the criteria of ready accessibility, rapid expansion in chemically defined media and reliable induction to a neuronal fate. We isolated somatic stem cells from the human periodontium that were collected during minimally invasive periodontal access flap surgery as part of guided tissue regeneration therapy. These cells could be propagated as neurospheres in serum-free medium, which underscores their cranial neural crest cell origin. Culture in the presence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) under serum-free conditions resulted in large numbers of nestin-positive/Sox-2-positive NSCs. These periodontium-derived (pd) NSCs are highly proliferative and migrate in response to chemokines that have been described as inducing NSC migration. We used immunocytochemical techniques and RT-PCR analysis to assess neural differentiation after treatment of the expanded cells with a novel induction medium. Adherence to substrate, growth factor deprivation, and retinoic acid treatment led to the acquisition of neuronal morphology and stable expression of markers of neuronal differentiation by more than 90% of the cells. Thus, our novel method might provide nearly limitless numbers of neuronal precursors from a readily accessible autologous adult human source, which could be used as a platform for further experimental studies and has potential therapeutic implications.

Neural stem cells adopt tumorigenic properties by constitutively activated NF-kappaB and subsequent VEGF up-regulation

One of the challenges in stem cell research is to avoid transformation during cultivation. We studied high passage subventricular zone derived neural stem cells (NSCs) cultures of adult rats in the absence of growth factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). We termed this culture exogenous growth factor independent neural stem cells (GiNSCs). GiNSCs expressed stemness markers, displayed a high constitutive NF-kappaB activity and an increased, aberrant, polyploid DNA content. GiNSCs showed a tumorigenic phenotype and formed colonies in a soft agar assay. Microarray analysis showed the up-regulation of the NF-kappaB target gene vascular endothelial growth factor (VEGF). In contrast, proneuronal genes were down-regulated. Under neuronal differentiation conditions GiNSCs adopted a glioma-like phenotype, with nuclear p53, preserving high amounts of Nestin positive cells and prolonged proliferation. Neutralization of VEGF strongly inhibited proliferation and induced differentiation. In a gain of function approach, the transfection of NSCs with constitutively active upstream kinase IKK-2 led to constitutively activated NF-kappaB, proliferation in absence of growth factors and augmented VEGF secretion. In a rescue experiment a reduction of NF-kappaB activity by overexpression of IkappaB-AA1 was able to shift the morphology toward an elongated cell form, increased cell death, and decreased proliferation. Thus GiNSCs may provide a potent tool in cancer research, as their exogenous cytokine independent proliferation and their constitutively high NF-kappaB expression presumes cancerous properties observed in gliomas. In addition, this study might add a novel mechanism for detecting oncogenic transformation in therapeutic stem cell cultures.