150 research outputs found

    Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

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    The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/ 0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6

    Exploiting Pan Influenza A and Pan Influenza B Pseudotype Libraries for Efficient Vaccine Antigen Selection.

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    We developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18 and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for detecting virus-specific neutralizing antibodies against influenza viruses and can be used to assess antibody functionality in vitro. Here we show the production of these viral HA pseudotypes and their employment as substitutes for wildtype viruses in influenza neutralization assays. We demonstrate their utility in detecting serum responses to vaccination with the ability to evaluate cross-subtype neutralizing responses elicited by specific vaccinating antigens. Our findings may inform further preclinical studies involving immunization dosing regimens in mice and may help in the creation and selection of better antigens for vaccine design. These HA pseudotypes can be harnessed to meet strategic objectives that contribute to the strengthening of global influenza surveillance, expansion of seasonal influenza prevention and control policies, and strengthening pandemic preparedness and response

    Climatically driven changes in the supply of terrigenous sediment to the East China Sea

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    Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 19 (2018): 2463-2477, doi:10.1029/2017GC007339.We examine the paleoceanographic record over the last ∼400 kyr derived from major, trace, and rare earth elements in bulk sediment from two sites in the East China Sea drilled during Integrated Ocean Drilling Program Expedition 346. We use multivariate statistical partitioning techniques (Q‐mode factor analysis, multiple linear regression) to identify and quantify five crustal source components (Upper Continental Crust (UCC), Luochuan Loess, Xiashu Loess, Southern Japanese Islands, Kyushu Volcanics), and model their mass accumulation rates (MARs). UCC (35–79% of terrigenous contribution) and Luochuan Loess (16–55% contribution) are the most abundant end‐members through time, while Xiashu Loess, Southern Japanese Islands, and Kyushu Volcanics (1–22% contribution) are the lowest in abundance when present. Cycles in UCC and Luochuan Loess MARs may indicate continental and loess‐like material transported by major rivers into the Okinawa Trough. Increases in sea level and grain size proxy (e.g., SiO2/Al2O3) are coincident with increased flux of Southern Japanese Islands, indicating localized sediment supply from Japan. Increases in total terrigenous MAR precede minimum relative sea levels by several thousand years and may indicate remobilization of continental shelf material. Changes in the relative contribution of these end‐members are decoupled from total MAR, indicating compositional changes in the sediment are distinct from accumulation rate changes but may be linked to variations in sea level, riverine and eolian fluxes, and shelf‐bypass processes over glacial‐interglacials, complicating accurate monsoon reconstructions from fluvial dominated sediment.U.S. National Science Foundation Grant Numbers: NSF‐EAR1434175, NSF‐EAR1433665, NSF‐EAR143413

    Psychosocial issues of women with type 1 diabetes transitioning to motherhood: a structured literature review

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    BACKGROUND: Life transitions often involve complex decisions, challenges and changes that affect diabetes management. Transition to motherhood is a major life event accompanied by increased risk that the pregnancy will lead to or accelerate existing diabetes-related complications, as well as risk of adverse pregnancy outcomes, all of which inevitably increase anxiety. The frequency of hyperglycaemia and hypoglycaemia often increases during pregnancy, which causes concern for the health and physical well-being of the mother and unborn child. This review aimed to examine the experiences of women with T1DM focusing on the pregnancy and postnatal phases of their transition to motherhood. METHODS: The structured literature review comprised a comprehensive search strategy identifying primary studies published in English between 1990-2012. Standard literature databases were searched along with the contents of diabetes-specific journals. Reference lists of included studies were checked. Search terms included: 'diabetes', 'type 1', 'pregnancy', 'motherhood', 'transition', 'social support', 'quality of life' and 'psychological well-being'. RESULT: Of 112 abstracts returned, 62 articles were reviewed in full-text, and 16 met the inclusion criteria. There was a high level of diversity among these studies but three common key themes were identified. They related to physical (maternal and fetal) well-being, psychological well-being and social environment. The results were synthesized narratively. CONCLUSION: Women with type 1 diabetes experience a variety of psychosocial issues in their transition to motherhood: increased levels of anxiety, diabetes-related distress, guilt, a sense of disconnectedness from health professionals, and a focus on medicalisation of pregnancy rather than the positive transition to motherhood. A trusting relationship with health professionals, sharing experiences with other women with diabetes, active social support, shared decision and responsibilities for diabetes management assisted the women to make a positive transition. Health professionals can promote a positive transition to motherhood by proactively supporting women with T1DM in informed decision-making, by facilitating communication within the healthcare team and co-ordinating care for women with type 1 diabetes transitioning to motherhood

    Exploiting Pan Influenza A and Pan Influenza B pseudotype libraries for efficient vaccine antigen selection

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    We developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18 and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for detecting virus-specific neutralizing antibodies against influenza viruses and can be used to assess antibody functionality in vitro. Here we show the production of these viral HA pseudotypes and their employment as substitutes for wildtype viruses in influenza neutralization assays. We demonstrate their utility in detecting serum responses to vaccination with the ability to evaluate cross-subtype neutralizing responses elicited by specific vaccinating antigens. Our findings may inform further preclinical studies involving immunization dosing regimens in mice and may help in the creation and selection of better antigens for vaccine design. These HA pseudotypes can be harnessed to meet strategic objectives that contribute to the strengthening of global influenza surveillance, expansion of seasonal influenza prevention and control policies, and strengthening pandemic preparedness and response.Bill and Melinda Gates Foundation: Grand Challenges Universal Influenza Vaccines Award; UK Research and Innovation (UKRI); EC FETopen (Virofight, Grant 899619); Department of Science and Technology of South Africa; UK Department for the Environment, Food and Rural Affairs (Defra); Scottish and Welsh governments.http://www.mdpi.com/journal/vaccinespm2022Veterinary Tropical Disease

    A Place to Rest Your (Burnt) Bones? Mortuary Houses in Early Anglo-Saxon England

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    This is an Accepted Manuscript of an article published by Taylor & Francis in Archaeological Journal on 5th October 2017, available online: doi: 10.1080/00665983.2017.1366704This article presents a fresh interpretation of square and rectangular mortuary structures found in association with deposits of cremated material and cremation burials in a range of early Anglo-Saxon (fifth-/sixth-century AD) cemeteries across southern and eastern England. Responding to a recent argument that they could be traces of pyre structures, a range of ethnographic analogies are drawn upon, and the full-range of archaeological evidence is synthesized, to re-affirm and extend their interpretation as unburned mortuary structures. Three interleaving significances are proposed: (i) demarcating the burial place of specific individuals or groups from the rest of the cemetery population, (ii) operating as ‘columbaria’ for the above-ground storage of the cremated dead (i.e. not just to demarcate cremation burials), and (iii) providing key nodes of commemoration between funerals as the structures were built, used, repaired and eventually decayed within cemeteries. The article proposes that timber ‘mortuary houses’ reveal that groups in early Anglo-Saxon England perceived their cemeteries in relation to contemporary settlement architectures, with some groups constructing and maintaining miniaturized canopied buildings to store and display the cremated remains of the dead
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