12/15-Lipoxygenase Is Required for the Early Onset of High Fat Diet-Induced Adipose Tissue Inflammation and Insulin Resistance in Mice

Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance.Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT) and 12/15LO knockout (KO) mice after 2-4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b(+), F4/80(+) macrophages and elevated protein levels of the inflammatory markers IL-1beta, IL-6, IL-10, IL-12, IFNgamma, Cxcl1 and TNFalpha. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle) insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice.These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding

Household water insecurity experiences and their perceived determinants in a low-income community of Cartagena, Colombia, during a water service expansion project

Traditional water indicators primarily focus on water quantity and quality, but emergent research demonstrates that measurement of lived experiences with water availability, accessibility, and use is important for understanding how household water insecurity impacts health and well-being. Few empirical studies have explored which household water insecurity experiences are most salient, or their potential causes, in Latin American cities. We analyzed data from 266 households in a low-income settlement of Cartagena, Colombia, to identify correlates and perceived determinants of water insecurity. The most prevalent household water insecurity experiences were water supply interruptions (96%), water worry (94%), and anger about the water situation (90%). Unexpected water interruptions and use of non-piped primary drinking water sources were associated with greater household water insecurity scores, water worry subscores, and hygiene subscores. Respondents perceived water issues in their community to be caused by deficiencies in gray infrastructure (49%), which included deficiencies in water distribution, treatment, or storage technologies. Social infrastructure (36%), including issues with political, economic, or administrative systems, was also cited as a barrier to water security. We did not detect significant relationships between water insecurity scores and the attribution of these problems to gray or social infrastructure, but there may be relationships between these factors and duration of residency and using a non-piped water source. These findings underscore the importance of socio-political factors and community engagement for improving urban water insecurity through slum-upgrade projects

Acute Ingestion Of L-Arginine Alpha-Ketoglutarate Fails To Improve Muscular Strength And Endurance In ROTC Cadets

International Journal of Exercise Science 6(2) : 91-97, 2013. L-Arginine Alpha-Ketoglutarate (AAKG) is purported to stimulate the release of nitric oxide, and is suggested to facilitate muscular performance by increasing blood flow and increase oxygen and nutrient delivery to the working muscle. However, the ergogenic benefit of AAKG during resistance exercise has not been established. Therefore the purpose of this study was to investigate the effects of acute AAKG ingestion in active ROTC Cadets on measures of one-repetition maximal strength (1RM) and muscular endurance. Nineteen apparently healthy males ingested either AAKG (3 g) or a placebo 45 minutes prior to resistance testing in a randomized, double-blind crossover design. Initially, blood lactate (BLA) was obtained followed by 1RM testing on the barbell bench press and leg press. Upon determination of 1RM, participants completed repetitions to failure at 60% of 1RM. Blood lactate measures were immediately taken following the final repetition. Analysis revealed no significant differences between the conditions for bench press 1RM. Additionally, there were no differences between conditions for 1RM leg press, or for number of repetitions performed for the bench press or leg press. Blood lactate values did increase significantly from baseline to post-bench press in both the AAKG (t33 = 7.56, p \u3c 0.01) and placebo conditions (t33 = 8.45, p \u3c 0.01). Further, BLA lactate levels were also significantly greater post leg-press in the AAKG (t33 = 9.23, p \u3c 0.01) and placebo (t33 = 8.10, p \u3c 0.01). The results indicate that acute AAKG supplementation provides no ergogenic benefit in this study

Complications of Open Approaches to the Skull Base in the Endoscopic Era

Objective It is important to characterize the developing complication profile of the open approach as it becomes reserved for more complex disease during the endoscopic era. Our objective was to characterize complication rates of current open skull base surgery

Serotonin 5-HT\u3csub\u3e2\u3c/sub\u3e receptor activation prevents allergic asthma in a mouse model

© 2015 the American Physiological Society. Asthma is an inflammatory disease of the lung characterized by airways hyper-responsiveness (AHR), inflammation, and mucus hyperproduction. Current main-stream therapies include bronchodilators that relieve bronchoconstriction and inhaled glucocorticoids to reduce inflammation. The small molecule hormone and neurotransmitter serotonin has long been known to be involved in inflammatory processes; however, its precise role in asthma is unknown. We have previously established that activation of serotonin 5-hydroxytryptamine (5-HT)2A receptors has potent anti-inflammatory activity in primary cultures of vascular tissues and in the whole animal in vasculature and gut tissues. The 5-HT2A receptor agonist, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] is especially potent. In this work, we have examined the effect of (R)-DOI in an established mouse model of allergic asthma. In the ovalbumin mouse model of allergic inflammation, we demonstrate that inhalation of (R)-DOI prevents the development of many key features of allergic asthma, including AHR, mucus hyperproduction, airways inflammation, and pulmonary eosinophil recruitment. Our results highlight a likely role of the 5-HT2 receptors in allergic airways disease and suggest that 5-HT2 receptor agonists may represent an effective and novel small molecule-based therapy for asthma

A Phase Glass is a Bose Metal: New Conducting State in 2D

In the quantum rotor model with random exchange interactions having a non-zero mean, three phases, a 1) phase (Bose) glass, 2) superfluid, and 3) Mott insulator, meet at a bi-critical point. We demonstrate that proximity to the bi-critical point and the coupling between the energy landscape and the dissipative degrees of freedom of the phase glass lead to a metallic state at T=0. Consequently, the phase glass is unique in that it represents a concrete example of a metallic state that is mediated by disorder, even in 2D. We propose that the experimentally observed metallic phase which intervenes between the insulator and the superconductor in a wide range of thin films is in actuality a phase glass.Comment: 4 pages, 1 .eps figure, final version to appear in Phys. Rev. Let

Laboratory Testing of a Lyot Coronagraph Equipped with an Eighth-Order Notch Filter Image Mask

We have built a series of notch filter image masks that make the Lyot coronagraph less susceptible to low-spatial-frequency optical aberrations. In this paper, we present experimental results of their performance in the lab using monochromatic light. Our tests show that these ``eighth-order'' masks are resistant to tilt and focus alignment errors, and can generate contrast levels of 2 x 10^-6 at 3 lambda/D and 6 x 10^-7 at 10 lambda/D without the use of corrective optics such as deformable mirrors. This work supports recent theoretical studies suggesting that eighth-order masks can provide the Terrestrial Planet Finder Coronagraph with a large search area, high off-axis throughput, and a practical requisite pointing accuracy.Comment: Accepted to ApJ. 16 pages, 7 figures, Contact [email protected] for high resolution image

The Environment as an Unrecognized Reservoir for Community-Associated Methicillin Resistant Staphylococcus aureus USA300: A Case-Control Study

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are spreading, but the source of infections in non-epidemic settings remains poorly defined. METHODS: We carried out a community-based, case-control study investigating socio-demographic risk factors and infectious reservoirs associated with MRSA infections. Case patients presented with CA-MRSA infections to a New York hospital. Age-matched controls without infections were randomly selected from the hospital's Dental Clinic patient population. During a home visit, case and control subjects completed a questionnaire, nasal swabs were collected from index respondents and household members and standardized environmental surfaces were swabbed. Genotyping was performed on S. aureus isolates. RESULTS: We enrolled 95 case and 95 control subjects. Cases more frequently reported diabetes mellitus and a higher number of skin infections among household members. Among case households, 53 (56%) were environmentally contaminated with S. aureus, compared to 36 (38%) control households (p = .02). MRSA was detected on fomites in 30 (32%) case households and 5 (5%; p<.001) control households. More case patients, 20 (21%) were nasally colonized with MRSA than were control indexes, 2 (2%; p<.001). In a subgroup analysis, the clinical isolate (predominantly USA300), was more commonly detected on environmental surfaces in case households with recurrent MRSA infections (16/36, 44%) than those without (14/58, 24%, p = .04). CONCLUSIONS: The higher frequency of environmental contamination of case households with S. aureus in general and MRSA in particular implicates this as a potential reservoir for recolonization and increased risk of infection. Environmental colonization may contribute to the community spread of epidemic strains such as USA300

Antilocalization in a 2D Electron Gas in a Random Magnetic Field

We construct a supersymmetric field theory for the problem of a two-dimensional electron gas in a random, static magnetic field. We find a new term in the free energy, additional to those present in the conventional unitary sigma-model, whose presence relies on the long-range nature of the disorder correlations. Under a perturbative renormalization group analysis of the free energy, the new term contributes to the scaling function at one-loop order and leads to antilocalization.Comment: 4 pages, RevTe

Impact Shocking of a Zircon-Sanidine Mixture and Investigations of Pb Mobility

The purpose of this project is to explore the mobility, mixing, and possible clumping of Pb isotopes during laboratory impact shock experiments. Impact events are a common planetary occurrence and their effect on istotope systematics and subsequent geochronology is not fully understood. By artificially shocking mixtures of zircon and sanidine and investigating the sample products, it may be possible to understand if and how Pb is mobilized during impact shock. Isotopes of Pb are the final daughter products of the decay chains of 238U, 235U and 232Th and therefore understanding how mobile the daughter product is during impact events could have consequences for dating impact events. These investigations will also reveal if Pb isotopes can be mixed between mineral