Exercise, Appetite Control, and Body Weight Regulation

Exercise has many health benefits and should be an effective weight loss strategy because it increases energy expenditure. However, the success of exercise in producing and sustaining weight loss is influenced by compensatory changes in energy intake and non-exercise activity, among other factors (see King et al. Obesity 15(6):1373–1383, 2007 for a detailed review). The aim of this chapter is to discuss the evidence describing the relationship between exercise and body weight regulation, with a particular focus on appetite control. Evidence is discussed which demonstrates that weight loss responses to exercise are highly variable between individuals. The mechanisms underlying the relationship between exercise, appetite and energy intake, and hence body weight are also discussed. Some people experience an increase in fasting hunger in response to 12 weeks of supervised exercise. However, this is offset by an increase in meal-related satiety in overweight and obese individuals. It is worth noting that weight loss should not be considered as the only successful outcome of an exercise program. Indeed, exercise, even in the absence of weight loss, is associated with numerous health benefits. Nevertheless, an improved understanding of compensatory responses to exercise is vital so that exercise can be more effectively used in weight management; such an understanding may assist us to devise strategies to sustain greater long-term participation in physical activity.

Altered immunoglobulin E diversity and regulation of allergic inflammation in asthma

The clinical efficacy of anti-immunoglobulin E (IgE) therapy indicates a central role for IgE in perpetuation of allergic inflammatory diseases. Omalizumab is now uti- lized in treatment of a wide variety of allergic conditions including severe asthma, allergic rhinitis, atopic dermati- tis, food allergy and urticaria either alone or adjunct with other therapies such as steroid administration or allergen- specific immunotherapy [1, 2]. Current research activity is focused on the cellular and molecular mechanisms by which IgE influences the immunopathogenesis of allergic disease [3]. Increased knowledge of how IgE exerts its effects will underpin effective clinical use of anti-IgE treatment. In this issue Kerzel et al. [4] investigate the effects of altered antibo dy repertoire on the outcomes of an experimental model of allergic asthma.

Territoriality and the regulation of public space in Favela Morro da Formiga, Rio de Janeiro

Public space in many communities around the world has been identified as over-regulated and devoid of social vibrancy. This research contributed new knowledge regarding the way local residents territorialise and take ownership of streets and open areas in a favela, or informal settlement, in Rio De Janeiro, Brazil. Findings showed that public spaces were only partly activated by spatial pattern or structure. User agency also played a significant role, despite recent regulatory and policing interventions in the favela. This may have important implications for new communities where design could allow for more flexible usage and thereby enhance social vibrancy.

Post-transcriptional regulation in the nucleus and cytoplasm: study of mean time to threshold (MTT) and narrow escape problem

Messenger RNAs (mRNAs) can be repressed and degraded by small non-coding RNA molecules. In this paper, we formulate a coarsegrained Markov-chain description of the post-transcriptional regulation of mRNAs by either small interfering RNAs (siRNAs) or microRNAs (miRNAs). We calculate the probability of an mRNA escaping from its domain before it is repressed by siRNAs/miRNAs via cal- culation of the mean time to threshold: when the number of bound siRNAs/miRNAs exceeds a certain threshold value, the mRNA is irreversibly repressed. In some cases,the analysis can be reduced to counting certain paths in a reduced Markov model. We obtain explicit expressions when the small RNA bind irreversibly to the mRNA and we also discuss the reversible binding case. We apply our models to the study of RNA interference in the nucleus, examining the probability of mRNAs escaping via small nuclear pores before being degraded by siRNAs. Using the same modelling framework, we further investigate the effect of small, decoy RNAs (decoys) on the process of post-transcriptional regulation, by studying regulation of the tumor suppressor gene, PTEN : decoys are able to block binding sites on PTEN mRNAs, thereby educing the number of sites available to siRNAs/miRNAs and helping to protect it from repression. We calculate the probability of a cytoplasmic PTEN mRNA translocating to the endoplasmic reticulum before being repressed by miRNAs. We support our results with stochastic simulations

Threat of resource loss: The role of self-regulation in adaptive task performance

Changes at work are often accompanied with the threat of, or actual, resource loss. Through an experiment, we investigated the detrimental effect of the threat of resource loss on adaptive task performance. Self-regulation (i.e., task focus and emotion control) was hypothesized to buffer the negative relationship between the threat of resource loss and adaptive task performance. Adaptation was conceptualized as relearning after a change in task execution rules. Threat of resource loss was manipulated for 100 participants undertaking an air traffic control task. Using discontinuous growth curve modeling, 2 kinds of adaptation—transition adaptation and reacquisition adaptation—were differentiated. The results showed that individuals who experienced the threat of resource loss had a stronger drop in performance (less transition adaptation) and a subsequent slower recovery (less reacquisition adaptation) compared with the control group who experienced no threat. Emotion control (but not task focus) moderated the relationship between the threat of resource loss and transition adaptation. In this respect, individuals who felt threatened but regulated their emotions performed better immediately after the task change (but not later on) compared with those individuals who felt threatened and did not regulate their emotions as well. However, later on, relearning (reacquisition adaptation) under the threat of resource loss was facilitated when individuals concentrated on the task at hand.

MicroRNA regulation of epithelial-to-mesenchymal transition during re-epithelialisation: Assessing an open wound

It is becoming increasing clear that microRNAs contribute to the regulation of many biological processes, including wound healing. After injury, keratinocytes need to undergo what is known as an epithelial-to-mesenchymal transition (EMT) to initiate re-epithelialisation. During this process, keratinocytes reduce their attachment to the underlying matrix, extend membrane protrusions, become motile and migrate over the wound bed, affecting wound closure. MicroRNAs that regulate EMT are aberrantly upregulated in keratinocytes at the edge of non-healing wounds and potentially play a role in the chronicity of these wounds. In vitro and in vivo, downregulation of these microRNAs promotes EMT and migration, facilitating re-epithelialisation in wound models. This review will focus on the role of microRNAs that regulate or have potential to regulate EMT and re-epithelialisation during wound healing

Temporal trend of pesticide concentrations in the Chikugo River (Japan) with changes in environmental regulation and field infrastructure

Contamination of pesticides, which are applied to rice paddy fields, in river water has been a major problem in Japan for decades. A prolonged water holding period after pesticide application in paddy fields is expected to reduce the concentration of rice pesticides in river water. Therefore, a long monitoring campaign was conducted from 2004 to 2010 to measure the concentrations of pesticides in water samples collected from several points along the Chikugo River (Japan) including tributaries and the main stream to see if there was any reduction in the level of pesticide contamination after the extension of the water holding period (from 3–4 days to 7 days) was introduced in 2007 by the new water management regulation. No significant difference (p > 0.05) was found in pesticide concentrations between the periods before and after 2007 in all monitoring points, except in one tributary where the pesticide concentrations after 2007 were even higher than that of the previous period. A detailed study in one of the tributaries also revealed that the renovated infrastructure did not reduce the pesticide concentrations in the drainage canals. Neither the introduction of the new regulation nor the improved infrastructure had any significant effect on reducing the contamination of pesticides in water of the Chikugo River. It is probably because most farmers did not properly implement the new requirement of holding paddy water within the field for 7 days after the application of pesticides. Only tightening the regulation would not be sufficient and more actions should be taken to enforce/provide extension support for the new water management regulation in order to reduce the level of residual pesticides in river water in Japan.

Degradability of creatinine under sewer conditions affects its potential to be used as biomarker in sewage epidemiology

Creatinine was proposed to be used as a population normalising factor in sewage epidemiology but its stability in the sewer system has not been assessed. This study thus aimed to evaluate the fate of creatinine under different sewer conditions using laboratory sewer reactors. The results showed that while creatinine was stable in wastewater only, it degraded quickly in reactors with the presence of sewer biofilms. The degradation followed first order kinetics with significantly higher rate in rising main condition than in gravity sewer condition. Additionally, daily loads of creatinine were determined in wastewater samples collected on Census day from 10 wastewater treatment plants around Australia. The measured loads of creatinine from those samples were much lower than expected and did not correlate with the populations across the sampled treatment plants. The results suggested that creatinine may not be a suitable biomarker for population normalisation purpose in sewage epidemiology, especially in sewer catchment with high percentage of rising mains.

Saviour Siblings and the Regulation of Assisted Reproductive Technology: Harm, Ethics and Law

Advances in the field of Assisted Reproductive Technology (ART) have been revolutionary. This book focuses on the use of ARTs in the context of families who seek to conceive a matching sibling donor as a source of tissue to treat an existing sick child. Such children have been referred to as ‘saviour siblings’. Considering the legal and regulatory frameworks that impact on the accessibility of this technology in Australia and the UK, the work analyses the ethical and moral issues that arise from the use of the technology for this specific purpose. The author claims the only justification for limiting a family’s reproductive liberty in this context is where the exercise of reproductive decision-making results in harm to others. It is argued that the harm principle is the underlying feature of legislative action in Western democratic society, and as such, this principle provides the grounds upon which a strong and persuasive argument is made for a less-restrictive regulatory approach in the context of ‘saviour siblings’.

Mycobacterium tuberculosis groE promoter controls the expression of the bicistronic groESL1 operon and shows differential regulation under stress conditions

Heat shock promoters of mycobacteria are strong promoters that become rapidly upregulated during macrophage infection and thus serve as valuable candidates for expressing foreign antigens in recombinant BCG vaccine. In the present study, a new heat shock promoter controlling the expression of the groESL1 operon was identified and characterized. Mycobacterium tuberculosis groESL1 operon codes for the immunodominant 10 kDa (Rv3418c, GroES/Cpn10/Hsp10) and 60 kDa (Rv3417c, GroEL1/Cpn60.1/Hsp60) heat shock proteins. The basal promoter region was 115 bp, while enhanced activity was seen only with a 277-bp fragment. No promoter element was seen in the groES-groEL1 intergenic region. This operon codes for a bicistronic mRNA transcript as determined by reverse transcriptase-PCR and Northern blot analysis. Primer extension analysis identified two transcriptional start sites (TSSs) TSS1 (-236) and TSS2 (-171), out of which one (TSS2) was heat inducible. The groE promoter was more active than the groEL2 promoter in Mycobacterium smegmatis. Further, it was found to be differentially regulated under stress conditions, while the groEL2 promoter was constitutive.

Role of TATATAA element in the regulation of tRNA(1)(Gly) gene expression in Bombyx mori is position dependent

Transcription of tRNA genes by RNA polymerase III is controlled by the internal conserved sequences within the coding region and the immediate upstream flanking sequences. A highly transcribed copy of glycyl tRNA gene tRNA1(Gly)-1 from Bombyx mori is down regulated by sequences located much farther upstream in the region -150 to -300 nucleotides (nt), with respect to the +1 nt of tRNA. The negative regulatory effect has been narrowed down to a sequence motif 'TATATAA', a perfect consensus recognised by the TATA binding protein, TBP. This sequence element, when brought closer to the transcription start point, on the other hand, exerts a positive effect by promoting transcription of the gene devoid of other cis regulatory elements. The identity of the nuclear protein interacting with this 'TATATAA' element to TBP has been established by antibody and mutagenesis studies. The 'TATATAA' element thus influences the transcription of tRNA genes positively or negatively in a position-dependent manner either by recruitment or sequestration of TBP from the transcription machinery.

Genome-Wide Gene Expression Analysis Reveals a Dynamic Interplay between Luteotropic and Luteolytic Factors in the Regulation of Corpus Luteum Function in the Bonnet Monkey (Macaca radiata)

Although LH is essential for survival and function of the corpus luteum (CL) in higher primates, luteolysis occurs during nonfertile cycles without a discernible decrease in circulating LH levels. Using genome-wide expression analysis, several experiments were performed to examine the processes of luteolysis and rescue of luteal function in monkeys. Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted in differential regulation of 3949 genes, whereas replacement with exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes (1563 down-regulation and 2871 up-regulation). A model system for prostaglandin (PG) F-2 alpha-induced luteolysis in the monkey was standardized and demonstrated that PGF(2 alpha) regulated expression of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome revealed that 120 genes were regulated in an antagonistic fashion by PGF(2 alpha). Based on the microarray data, 25 genes were selected for validation by real-time RT-PCR analysis, and expression of these genes was also examined in the CL throughout the luteal phase and from monkeys treated with human chorionic gonadotropin (hCG) to mimic early pregnancy. The results indicated changes in expression of genes favorable to PGF(2 alpha) action during the late to very late luteal phase, and expressions of many of these genes were regulated in an opposite manner by exogenous hCG treatment. Collectively, the findings suggest that curtailment of expression of downstream LH-target genes possibly through PGF(2 alpha) action on the CL is among the mechanisms underlying cross talk between the luteotropic and luteolytic signaling pathways that result in the cessation of luteal function, but hCG is likely to abrogate the PGF(2 alpha)-responsive gene expression changes resulting in luteal rescue crucial for the maintenance of early pregnancy. (Endocrinology 150: 1473-1484, 2009)

Guanylyl Cyclase C Receptor: Regulation of Catalytic Activity by ATP

Guanylyl cyclase C (GCC), a member of the family of membrane bound guanylyl cyclases is the receptor for the heat-stable enterotoxin (ST) peptides and the guanylin family of endogenous peptides. GCC is activated upon ligand binding to increase intracellular cGMP levels, which in turn activates other downstream signalling events in the cell. GCC is also activated in vitro by nonionic detergents. We have used the T84 cell line as a model system to investigate the regulation of GCC activity by ATP. Ligand-stimulated GCC activity is potentiated in the presence of ATP, whereas detergent-stimulated activity is inhibited. The potentiation of GCC activity by ATP is dependent on the presence of Mg2+ ions, and is probably brought about by a direct binding of Mg-ATP to GCC. The protein kinase-like domain of GCC, which has earlier been shown to play a critical role in the regulation of GCC activity, may be a possible site for the binding of Mg-ATP to GCC.