5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

<p><b>Background:</b> Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).</p> <p><b>Methods:</b> The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.</p> <p><b>Results:</b> Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.</p> <p><b>Conclusion:</b> Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.</p&gt

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory

Target-site resistance mutations (kdr and RDL), but not metabolic resistance, negatively impact male mating competiveness in the malaria vector Anopheles gambiae

The implementation of successful insecticide resistance management strategies for malaria control is currently hampered by poor understanding of the fitness cost of resistance on mosquito populations, including their mating competiveness. To fill this knowledge gap, coupled and uncoupled Anopheles gambiae s.l. males (all M form (Anopheles coluzzii)) were collected from mating swarms in Burkina Faso. This multiple insecticide resistant population exhibited high 1014F kdrR allele frequencies (460%) and RDLR (480%) in contrast to the Ace-1R allele (o6%). Kdr heterozygote males were more likely to mate than homozygote resistant (OR=2.36; Po0.001), suggesting a negative impact of kdr on An. coluzzii mating ability. Interestingly, heterozygote males were also more competitive than homozygote susceptible (OR=3.26; P=0.006), suggesting a heterozygote advantage effect. Similarly, heterozygote RDLR/RDLS were also more likely to mate than homozygote-resistant males (OR=2.58; P=0.007). Furthermore, an additive mating disadvantage was detected in male homozygotes for both kdr/RDL-resistant alleles. In contrast, no fitness difference was observed for the Ace-1 mutation. Comparative microarray-based genome-wide transcription analysis revealed that metabolic resistance did not significantly alter the mating competitiveness of male An. coluzzii mosquitoes. Indeed, no significant difference of expression levels was observed for the main metabolic resistance genes, suggesting that metabolic resistance has a limited impact on male mating competiveness. In addition, specific gene classes/GO terms associated with mating process were detected including sensory perception and peroxidase activity. The detrimental impact of insecticide resistance on mating competiveness observed here suggests that resistance management strategies such as insecticide rotation could help reverse the resistance, if implemented early

The prevention of type 2 diabetes

Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the US and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action—potential targets of preventive interventions—are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level

Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic response

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic respons

Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor eIF-4A1

Control of translation initiation was recognised as a critical checkpoint for cell proliferation and tumorigenesis. In human melanoma cells, we have previously reported consistent overexpression of translation initiation factor eIF-4A1. Here, we investigated by transfection of antisense constructs its significance for the control of melanoma cell growth. The tetracycline-inducible expression system was established in melanoma cells, and three fragments of the 5′-, central-, and 3′-portion of the eIF-4A1 cDNA were subcloned in antisense and in sense orientation after a tetracycline inducible promoter. Significant proliferation decrease was obtained after transient transfection and induction of antisense RNA directed against the 5′- and the central portion (up to 10%), whereas, no effects were seen after induction of the 3′-fragment and the sense controls. Cell clones stably transfected with the central antisense fragment revealed after doxycycline induction reduced expression of endogeneous eIF-4A1 mRNA correlated with decreased proliferation rates (up to 6%). These data demonstrate the applicability of antisense strategies against translation factors in melanoma cells. Translation initiation factor eIF-4A1 contributes to the control of melanoma cell proliferation and may be taken into consideration when scheduling new therapeutic approaches targeting the translational control