Acute effects of exercise on appetite, appetite regulatory hormones and energy intake in lean and overweight men and women

The acute effects of exercise on appetite, ad libitum energy intake and gut hormone responses have received much attention over the past two decades. The experiments in this thesis have contributed to this research by examining appetite, acylated ghrelin, peptide-YY (PYY), leptin and ad libitum energy intake responses to two consecutive days of moderate-high intensity running. To achieve this 15 individuals aged 21 (2) y, with a BMI of 23.0 (1.9) kg·m-2 were recruited. Additionally, appetite, acylated ghrelin, PYY, glucagon-like peptide-1 (GLP-1), and ad libitum energy intake responses to an acute bout of moderate intensity treadmill exercise were compared in lean and overweight/obese (ow/ob) males and females. Two separate cohorts of individuals were recruited; 22 lean individuals and 25 ow/ob individuals (aged 38 (15) and 45 (12) y, with a BMI of 22 (2) and 29 (3) kg·m 2, for lean and ow/ob individuals, respectively). In Chapter 4, two consecutive days of 60 min treadmill running at 70% V̇O2 peak did not produce compensatory changes in appetite or energy intake over two days. There were no main effects of trial for acylated ghrelin or leptin. However a main effect of trial for PYY indicated higher concentrations on the exercise than control trial. A meta-analysis was completed in Chapter 5, suggesting further research in the effects of acute exercise on appetite regulatory hormones in individuals who are ow/ob was necessary. In Chapter 6, 60 min of treadmill exercise at 60% V̇O2 peak did not alter appetite sensations or energy intake in the 7 h after exercise in lean and ow/ob males and females. There were no main effects of sex, BMI or trial for acylated ghrelin; however, PYY and GLP-1 concentrations were higher in exercise than control trials. This thesis has demonstrated that over two days, high volume exercise does not stimulate compensatory appetite regulatory changes, in lean healthy males. In the short term, lean and ow/ob males and females respond similarly to acute exercise, showing no alterations in appetite or food intake responses, whilst PYY and GLP-1 concentrations are higher in exercise than control trials

Quantification of three-dimensional folding using fluvial terraces: A case study from the Mushi anticline, northern margin of the Chinese Pamir

Fold deformation in three dimensions involves shortening, uplift, and lateral growth. Fluvial terraces represent strain markers that have been widely applied to constrain a fold's shortening and uplift. For the lateral growth, however, the utility of fluvial terraces has been commonly ignored. Situated along northern margin of Chinese Pamir, the Mushi anticline preserves, along its northern flank, flights of passively deformed fluvial terraces that can be used to constrain three-dimensional folding history, especially lateral growth. The Mushi anticline is a geometrically simple fault-tip fold with a total shortening of 740?±?110?m and rock uplift of ~1300?m. Geologic and geomorphic mapping and dGPS surveys reveal that terrace surfaces perpendicular to the fold's strike display increased rotation with age, implying the fold grows by progressive limb rotation. We use a pure-shear fault-tip fold model to estimate a uniform shortening rate of 1.5?+?1.3/?0.5?mm/a and a rock-uplift rate of 2.3?+?2.1/?0.8?mm/a. Parallel to the fold's strike, longitudinal profiles of terrace surfaces also display age-dependent increases in slopes. We present a new model to distinguish lateral growth mechanisms (lateral lengthening and/or rotation above a fixed tip). This model indicates that eastward lengthening of the Mushi anticline ceased by at least ~134?ka and its lateral growth has been dominated by rotation. Our study confirms that terrace deformation along a fold's strike not only can constrain the lateral lengthening rate but can serve to quantify the magnitude and rate of lateral rotation: attributes that are commonly difficult to define when relying on other geomorphic criteria

Lynx X-Ray Observatory: Response to the First Astro 2020 Decadal Survey Request for Information

This document serves as the Lynx Teams response to the first Request For Information (RFI) from the 2020 Decadal Survey in Astronomy and Astrophysics. Detailed answers to all of the questions asked in this RFI can be found in the Lynx Concept Study Report, Supplementary Technology Roadmaps, and the Lynx Cost Book

A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection

The transduction of sound in the auditory periphery, the cochlea, is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells. One fundamental question in auditory neuroscience is what role(s) this feedback plays in our ability to hear. In the present study, we have engineered a genetically modified mouse model in which the magnitude and duration of efferent cholinergic effects are increased, and we assess the consequences of this manipulation on cochlear function. We generated the Chrna9L9′T of knockin mice with a threonine for leucine change (L9′T) at position 9′ of the second transmembrane domain of the α9 nicotinic cholinergic subunit, rendering α9-containing receptors that were hypersensitive to acetylcholine and had slower desensitization kinetics. The Chrna9L9′T allele produced a 3-fold prolongation of efferent synaptic currents in vitro. In vivo, Chrna9L9′T mice had baseline elevation of cochlear thresholds and efferent-mediated inhibition of cochlear responses was dramatically enhanced and lengthened: both effects were reversed by strychnine blockade of the α9α10 hair cell nicotinic receptor. Importantly, relative to their wild-type littermates, Chrna9L9′T/L9′T mice showed less permanent hearing loss following exposure to intense noise. Thus, a point mutation designed to alter α9α10 receptor gating has provided an animal model in which not only is efferent inhibition more powerful, but also one in which sound-induced hearing loss can be restrained, indicating the ability of efferent feedback to ameliorate sound trauma.Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School of Medicine; Estados UnidosFil: Maison, Stéphane F.. Massachusetts Eye and Ear Infirmary; Estados UnidosFil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Savino, Jessica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vetter, Douglas E.. Tufts University School of Medicine; Estados UnidosFil: Boulter, Jim. University of California at Los Angeles; Estados UnidosFil: Liberman, M. Charles. Massachusetts Eye and Ear Infirmary; Estados UnidosFil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentin

Network analysis of differential Ras isoform mutation effects on intestinal epithelial responses to TNF-α

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine that can elicit distinct cellular behaviors under different molecular contexts. Mitogen activated protein kinase (MAPK) pathways, especially the extracellular signal-regulated kinase (Erk) pathway, help to integrate influences from the environmental context, and therefore modulate the phenotypic effect of TNF-α exposure. To test how variations in flux through the Erk pathway modulate TNF-α-elicited phenotypes in a complex physiological environment, we exposed mice with different Ras mutations (K-Ras activation, N-Ras activation, and N-Ras ablation) to TNF-α and observed phenotypic and signaling changes in the intestinal epithelium. Hyperactivation of Mek1, an Erk kinase, was observed in the intestine of mice with K-Ras activation and, surprisingly, in N-Ras null mice. Nevertheless, these similar Mek1 outputs did not give rise to the same phenotype, as N-Ras null intestine was hypersensitive to TNF-α-induced intestinal cell death while K-Ras mutant intestine was not. A systems biology approach applied to sample the network state revealed that the signaling contexts presented by these two Ras isoform mutations were different. Consistent with our experimental data, N-Ras ablation induced a signaling network state that was mathematically predicted to be pro-death, while K-Ras activation did not. Further modeling by constrained Fuzzy Logic (cFL) revealed that N-Ras and K-Ras activate the signaling network with different downstream distributions and dynamics, with N-Ras effects being more transient and diverted more towards PI3K-Akt signaling and K-Ras effects being more sustained and broadly activating many pathways. Our study highlights the necessity to consider both environmental and genomic contexts of signaling pathway activation in dictating phenotypic responses, and demonstrates how modeling can provide insight into complex in vivo biological mechanisms, such as the complex interplay between K-Ras and N-Ras in their downstream effects.National Institute of General Medical Sciences (U.S.) (Grant R01-GM088827)National Cancer Institute (U.S.) (U54-CA112967)United States. Army Research Office (Institute for Collaborative Biotechnologies Grant W911NF-09-D-000

Phytoplankton blooms weakly influence the cloud forming ability of sea spray aerosol

After many field studies, the establishment of connections between marine microbiological processes, sea spray aerosol (SSA) composition, and cloud condensation nuclei (CCN) has remained an elusive challenge. In this study, we induced algae blooms to probe how complex changes in seawater composition impact the ability of nascent SSA to act as CCN, quantified by using the apparent hygroscopicity parameter (κapp). Throughout all blooms, κapp ranged between 0.7 and 1.4 (average 0.95 ± 0.15), consistent with laboratory investigations using algae‐produced organic matter, but differing from climate model parameterizations and in situ SSA generation studies. The size distribution of nascent SSA dictates that changes in κapp associated with biological processing induce less than 3% change in expected CCN concentrations for typical marine cloud supersaturations. The insignificant effect of hygroscopicity on CCN concentrations suggests that the SSA production flux and/or secondary aerosol chemistry may be more important factors linking ocean biogeochemistry and marine clouds.Key PointsChanges in seawater and sea spray composition did not strongly affect expected CCN concentrationsBlooms may impact clouds more strongly through changes in aerosol flux or secondary chemistryModel parameterizations likely overestimate changes in cloud nuclei due to primary marine organicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/1/grl54978_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/2/grl54978-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134444/3/grl54978.pd

Temporal aspects of polar bear occurrences at field camps in Wapusk National Park, Canada

Wapusk National Park, University of Manitoba, University of Saskatchewan, the Social Sciences and Humanities Research Council of Canada, Hudson Bay Helicopters, the Churchill Northern Studies Centre, and EarthRangers.Interaction between polar bears (Ursus maritimus) and people is a growing concern for both bear conservation and human safety in a warming Arctic climate. Consequently, the importance of monitoring temporal trends in the proximity of polar bears to people has become critical in managing human-polar bear conflicts. Such concerns are acute in Wapusk National Park in Manitoba, Canada on the Western Hudson Bay coast, where we deployed 18 camera traps at three remote field camps from 2010–2014 (~22,100 camera-days) to monitor the frequency and timing of bears’ visits to those facilities. Following seasonal breakup of Hudson Bay’s sea ice polar bear occurrences at these camps increased throughout the summer and into fall (low in May–July and increasing sharply through August–November and then approaching zero in December when Hudson Bay freezes). We quantified age and sex class and estimated body condition of bears visiting the camps: adult males were most prevalent at Nester One camp close to where adult males congregate at Cape Churchill, whereas the two camps farther south were visited more frequently by females with dependent young, likely traveling to and from a known maternal denning area. Few subadults were observed. As expected, body condition scores declined throughout the on-shore season. Our method of monitoring polar bear occurrence on shore is robust, cost-effective, and non-invasive, and so may provide an economical complement to data gathered through more conventional techniques

Destruction of Opportunistic Pathogens Via Polymer Nanoparticle-Mediated Release of Plant-Based Antimicrobial Payloads

The synthesis of antimicrobial thymol/carvacrol‐loaded polythioether nanoparticles (NPs) via a one‐pot, solvent‐free miniemulsion thiol‐ene photopolymerization process is reported. The active antimicrobial agents, thymol and carvacrol, are employed as “solvents” for the thiol‐ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (\u3e95%), and elimination of all postpolymerization purification processes. The NPs serve as high capacity reservoirs for slow‐release and delivery of thymol/carvacrol‐combination payloads that exhibit inhibitory and bactericidal activity (\u3e99.9% kill efficiency at 24 h) against gram‐positive and gram‐negative bacteria, including both saprophytic (Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 25922) and pathogenic species (E. coli ATCC 43895, Staphylococcus aureus RN6390, and Burkholderia cenocepacia K56‐2). This report is among the first to demonstrate antimicrobial efficacy of essential oil‐loaded nanoparticles against B. cenocepacia – an innately resistant opportunistic pathogen commonly associated with debilitating respiratory infections in cystic fibrosis. Although a model platform, these results point to promising pathways to particle‐based delivery of plant‐derived extracts for a range of antimicrobial applications, including active packaging materials, topical antiseptics, and innovative therapeutics

A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck

Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUV(max)) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUV(max) of target lesions after cycle 1 was −21% (range: +72% to −81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN