Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females

Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR. A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT prevalence and activity measured by other modalities. Consistent assessment of this uniquely metabolic tissue is fundamental to the discovery of potential therapeutic strategies against metabolic disease

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains.</p> <p>Methods</p> <p>This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the <it>APOE </it>gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (<it>LIPC </it>-514C>T, LIPC -250G>A) were considered.</p> <p>Results</p> <p>At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the <it>APOE </it>E3/E3 genotype, LDL-cholesterol (<it>P </it>= 0.02) increased in the NGI group (n = 7), and TAG (<it>P </it>= 0.03) and TAG:HDL-cholesterol (<it>P </it>= 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread.</p> <p>Conclusions</p> <p>In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the <it>APOE </it>E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.</p

Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli

Ventral midbrain dopamine (DA) is unambiguously involved in motivation and behavioral arousal, yet the contributions of other DA populations to these processes are poorly understood. Here, we demonstrate that the dorsal raphe nucleus DA neurons are critical modulators of behavioral arousal and sleep-wake patterning. Using simultaneous fiber photometry and polysomnography, we observed time-delineated dorsal raphe nucleus dopaminergic (DRNDA) activity upon exposure to arousal-evoking salient cues, irrespective of their hedonic valence. We also observed broader fluctuations of DRNDA activity across sleep-wake cycles with highest activity during wakefulness. Both endogenous DRNDA activity and optogenetically driven DRNDA activity were associated with waking from sleep, with DA signal strength predictive of wake duration. Conversely, chemogenetic inhibition opposed wakefulness and promoted NREM sleep, even in the face of salient stimuli. Therefore, the DRNDA population is a critical contributor to wake-promoting pathways and is capable of modulating sleep-wake states according to the outside environment, wherein the perception of salient stimuli prompts vigilance and arousal

Sexual dimorphism of brown adipose tissue function

ObjectiveTo determine whether brown adipose tissue (BAT) activity in school-age children differs between the sexes and to explore the impact of dietary intake, sedentary behavior, and picky/fussy eating.Study designChildren aged 8.5-11.8 years of age (n = 36) underwent infrared thermography to determine the temperature of the skin overlying the main superficial BAT depot in the supraclavicular region before and after 5 minutes of mild cold exposure (single-hand immersion in cool tap water at about 20°C). The relationships between the supraclavicular region temperature and parental reports of food consumption, eating behavior, and inactivity were explored.ResultsThe supraclavicular region temperature was higher in boys (n = 16) at baseline, and after cold exposure. Boys displayed a greater thermogenic response to cold. Strong negative correlations were observed between the supraclavicular region temperature and body mass index percentile, and differences in supraclavicular region temperature between girls and boys persisted after adjustment for body mass index percentile. A negative linear relationship was observed between protein and vegetable intake and supraclavicular region temperature in girls only, but did not persist after adjustment for multiple comparisons. There was no difference in the adjusted supraclavicular region temperature between active or inactive children, or picky and nonpicky eaters.ConclusionsThese findings indicate sexual dimorphism in BAT thermogenic activity and a sex-specific impact of diet. Future studies should aim to quantify the contribution of BAT to childhood energy expenditure, energy imbalance, and any role in the origins of childhood obesity

The end of the beginning? Taking forward local democratic renewal in the post-referendum North East.

This article draws upon the author’s commissioned research on the nature of regional governance following the 2004 Referendum in the North East on elected regional assemblies. The article aimed to both capture these views and to assess how the ‘No vote in the referendum has impacted on subsequent developments in sub-national governance. The article provides both an empirical overview of recent developments and engages with the wider conceptual debates on democratic renewal. The arguments covered in this output are aimed at both academic and practitioner audiences, and have been also disseminated at regional and national conferences

A Microfluidic Device for Whole-Animal Drug Screening Using Electrophysiological Measures in the Nematode C. Elegans

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.Chemistry and Chemical Biolog

Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species

Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes

CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9- sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. MiSeq-based sequence analysis of targeted loci in individual embryos using CrispRVariants, a customized software tool for mutagenesis quantification and visualization, reveals efficient biallelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis exposes loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show that targeting of non-coding elements in gene regulatory regions using saturating mutagenesis uncovers functional control elements in transgenic reporters and endogenous genes in injected embryos. Our results establish that optimally solubilized, in vitro assembled fluorescent Cas9-sgRNA RNPs provide a reproducible reagent for direct and scalable loss-of-function studies and applications beyond zebrafish experiments that require maximal DNA cutting efficiency in vivo