The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection.

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi\u27s sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are needed to better characterize the oral microbiome in children and those with poorly-controlled HIV infections

The argument of the broken pane: Suffragette consumerism and newspapers

Within the cut-throat world of newspaper advertising the newspapers of Britain's Women's Social and Political Union (WSPU) Votes for Women and the Suffragette managed to achieve a balance that has often proved to be an impossible challenge for social movement press—namely the maintenance of a highly political stance whilst simultaneously exploiting the market system with advertising and merchandising. When the militant papers advocated window smashing of West End stores in 1912–1913, the companies who were the target still took advertisements. Why? What was the relationship between news values, militant violence and advertising income? ‘Do-it-yourself’ journalism operated within a context of ethical consumerism and promotionally orientated militancy. This resulted in newspaper connections between politics, commerce and a distinct market profile, evident in the customisation of advertising, retailer dialogue with militants and longer-term loyalty—symptomatic of a wider trend towards newspaper commercialism during this period

Tracing river chemistry in space and time : dissolved inorganic constituents of the Fraser River, Canada

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 124 (2014): 283-308, doi:10.1016/j.gca.2013.09.006.The Fraser River basin in southwestern Canada bears unique geologic and climatic features which make it an ideal setting for investigating the origins, transformations and delivery to the coast of dissolved riverine loads under relatively pristine conditions. We present results from sampling campaigns over three years which demonstrate the lithologic and hydrologic controls on fluxes and isotope compositions of major dissolved inorganic runoff constituents (dissolved nutrients, major and trace elements, 87Sr/86Sr, δD). A time series record near the Fraser mouth allows us to generate new estimates of discharge-weighted concentrations and fluxes, and an overall chemical weathering rate of 32 t km-2 y-1. The seasonal variations in dissolved inorganic species are driven by changes in hydrology, which vary in timing across the basin. The time series record of dissolved 87Sr/86Sr is of particular interest, as a consistent shift between higher (“more radiogenic”) values during spring and summer and less radiogenic values in fall and winter demonstrates the seasonal variability in source contributions throughout the basin. This seasonal shift is also quite large (0.709 – 0.714), with a discharge-weighted annual average of 0.7120 (2 s.d. = 0.0003). We present a mixing model which predicts the seasonal evolution of dissolved 87Sr/86Sr based on tributary compositions and water discharge. This model highlights the importance of chemical weathering fluxes from the old sedimentary bedrock of headwater drainage regions, despite their relatively small contribution to the total water flux.This work was supported by the WHOI Academic Programs Office and MIT PAOC Houghton Fund to BMV, a WHOI Arctic Research Initiative grant to ZAW, NSF-ETBC grant OCE-0851015 to BPE and TIE, and NSF grant EAR-1226818 to BPE

Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo.

BACKGROUND: Recent reports suggest that latrepirdine (Dimebon, dimebolin), a retired Russian antihistamine, improves cognitive function in aged rodents and in patients with mild to moderate Alzheimer's disease (AD). However, the mechanism(s) underlying this benefit remain elusive. AD is characterized by extracellular accumulation of the amyloid-beta (Abeta) peptide in the brain, and Abeta-lowering drugs are currently among the most popular anti-amyloid agents under development for the treatment of AD. In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Abeta using in vitro and in vivo experimental systems. RESULTS: We evaluated extracellular levels of Abeta in three experimental systems, under basal conditions and after treatment with latrepirdine. Mouse N2a neuroblastoma cells overexpressing Swedish APP were incubated for 6 hr in the presence of either vehicle or vehicle + latrepirdine (500pM-5 muM). Synaptoneurosomes were isolated from TgCRND8 mutant APP-overexpressing transgenic mice and incubated for 0 to 10 min in the absence or presence of latrepirdine (1 muM or 10 muM). Drug-naïve Tg2576 Swedish mutant APP overexpressing transgenic mice received a single intraperitoneal injection of either vehicle or vehicle + latrepirdine (3.5 mg/kg). Picomolar to nanomolar concentrations of acutely administered latrepirdine increased the extracellular concentration of Abeta in the conditioned media from Swedish mutant APP-overexpressing N2a cells by up to 64% (p = 0.01), while a clinically relevant acute dose of latrepirdine administered i.p. led to an increase in the interstitial fluid of freely moving APP transgenic mice by up to 40% (p = 0.01). Reconstitution of membrane protein trafficking and processing is frequently inefficient, and, consistent with this interpretation, latrepirdine treatment of isolated TgCRND8 synaptoneurosomes involved higher concentrations of drug (1-10 muM) and led to more modest increases in extracellular Abeta(x-42 )levels (+10%; p = 0.001); of note, however, was the observation that extracellular Abeta(x-40 )levels did not change. CONCLUSIONS: Here, we report the surprising association of acute latrepirdine dosing with elevated levels of extracellular Abeta as measured in three independent neuron-related or neuron-derived systems, including the hippocampus of freely moving Tg2576 mice. Given the reported association of chronic latrepirdine treatment with improvement in cognitive function, the effects of chronic latrepirdine treatment on extracellular Abeta levels must now be determined.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Migratory shorebird adheres to Bergmann’s Rule by responding to environmental conditions through the annual lifecycle

The inverse relationship between body size and environmental temperature is a widespread ecogeographic pattern. However, the underlying forces that produce this pattern are unclear in many taxa. Expectations are particularly unclear for migratory species, as individuals may escape environmental extremes and reorient themselves along the environmental gradient. In addition, some aspects of body size are largely fixed while others are environmentally flexible and may vary seasonally. Here, we used a long-term dataset that tracked multiple populations of the migratory piping plover Charadrius melodus across their breeding and non-breeding ranges to investigate ecogeographic patterns of phenotypically flexible (body mass) and fixed (wing length) size traits in relation to latitude (Bergmann’s Rule), environmental temperature (heat conservation hypothesis), and migratory distance. We found that body mass was correlated with both latitude and temperature across the breeding and non-breeding ranges, which is consistent with predictions of Bergmann’s Rule and heat conservation. However, wing length was correlated with latitude and temperature only on the breeding range. This discrepancy resulted from low migratory connectivity across seasons and the tendency for individuals with longer wings to migrate farther than those with shorter wings. Ultimately, these results suggest that wing length may be driven more by conditions experienced during the breeding season or tradeoffs related to migration, whereas body mass is modified by environmental conditions experienced throughout the annual lifecycle

Migratory shorebird adheres to Bergmann’s Rule by responding to environmental conditions through the annual lifecycle

The inverse relationship between body size and environmental temperature is a widespread ecogeographic pattern. However, the underlying forces that produce this pattern are unclear in many taxa. Expectations are particularly unclear for migratory species, as individuals may escape environmental extremes and reorient themselves along the environmental gradient. In addition, some aspects of body size are largely fixed while others are environmentally flexible and may vary seasonally. Here, we used a long-term dataset that tracked multiple populations of the migratory piping plover Charadrius melodus across their breeding and non-breeding ranges to investigate ecogeographic patterns of phenotypically flexible (body mass) and fixed (wing length) size traits in relation to latitude (Bergmann’s Rule), environmental temperature (heat conservation hypothesis), and migratory distance. We found that body mass was correlated with both latitude and temperature across the breeding and non-breeding ranges, which is consistent with predictions of Bergmann’s Rule and heat conservation. However, wing length was correlated with latitude and temperature only on the breeding range. This discrepancy resulted from low migratory connectivity across seasons and the tendency for individuals with longer wings to migrate farther than those with shorter wings. Ultimately, these results suggest that wing length may be driven more by conditions experienced during the breeding season or tradeoffs related to migration, whereas body mass is modified by environmental conditions experienced throughout the annual lifecycle

Dietary composition modulates brain mass and solubilizable Aβ levels in a mouse model of aggressive Alzheimer's amyloid pathology

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Objective Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Aβ content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions. Results Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.Published versio

The Lantern Vol. 53, No. 1, Fall 1986

• Living In-Sanity • Sentence of Dawn • Addict • Where Do They Come From? • Midnight Hags Astride • Escape • Here I Sit • A Minor Key • To Picasso\u27s Old Guitarist • Nothing More • Love or Futility • A Few Inches • My Only Gift • Reserved • A Message to a Disillusioned Friend • Doing it the Hard Way • The Wall • A Look Ahead at a Look Behind • Fantasy Secret • Lisa • Caesar\u27s Last Words • There\u27s a Grouse in My House • If You Want Me • The Education of a Samaritan • Death of Illusion • I Walked and Pondered • A Woman Walked Past Him and He Smiled • Betrayal • Blindness • Innocence Unveiled • Amandahttps://digitalcommons.ursinus.edu/lantern/1129/thumbnail.jp

Examining the validity and utility of two secondary sources of food environment data against street audits in England

Background: Secondary data containing the locations of food outlets is increasingly used in nutrition and obesity research and policy. However, evidence evaluating these data is limited. This study validates two sources of secondary food environment data: Ordnance Survey Points of Interest data (POI) and food hygiene data from the Food Standards Agency (FSA), against street audits in England and appraises the utility of these data. Methods: Audits were conducted across 52 Lower Super Output Areas in England. All streets within each Lower Super Output Area were covered to identify the name and street address of all food outlets therein. Audit-identified outlets were matched to outlets in the POI and FSA data to identify true positives (TP: outlets in both the audits and the POI/FSA data), false positives (FP: outlets in the POI/FSA data only) and false negatives (FN: outlets in the audits only). Agreement was assessed using positive predictive values (PPV: TP/(TP+FP)) and sensitivities (TP/(TP+FN)). Variations in sensitivities and PPVs across environment and outlet types were assessed using multi-level logistic regression. Proprietary classifications within the POI data were additionally used to classify outlets, and agreement between audit-derived and POI-derived classifications was assessed. Results: Street audits identified 1172 outlets, compared to 1100 and 1082 for POI and FSA respectively. PPVs were statistically significantly higher for FSA (0.91, CI: 0.89-0.93) than for POI (0.86, CI: 0.84-0.88). However, sensitivity values were not different between the two datasets. Sensitivity and PPVs varied across outlet types for both datasets. Without accounting for this, POI had statistically significantly better PPVs in rural and affluent areas. After accounting for variability across outlet types, FSA had statistically significantly better sensitivity in rural areas and worse sensitivity in rural middle affluence areas (relative to deprived). Audit-derived and POI-derived classifications exhibited substantial agreement (p < 0.001; Kappa = 0.66, CI: 0.63 - 0.70). Conclusions: POI and FSA data have good agreement with street audits; although both datasets had geographic biases which may need to be accounted for in analyses. Use of POI proprietary classifications is an accurate method for classifying outlets, providing time savings compared to manual classification of outlets

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis