The light of other days : the first twenty years of the Center for Research on Vermont

Occasional paper (University of Vermont. Center for Research on Vermont) ; no. 18

A large-scale proteogenomics study of apicomplexan pathogens-Toxoplasma gondii and Neospora caninum

Proteomics data can supplement genome annotation efforts, for example being used to confirm gene models or correct gene annotation errors. Here, we present a large‐scale proteogenomics study of two important apicomplexan pathogens: Toxoplasma gondii and Neospora caninum. We queried proteomics data against a panel of official and alternate gene models generated directly from RNASeq data, using several newly generated and some previously published MS datasets for this meta‐analysis. We identified a total of 201 996 and 39 953 peptide‐spectrum matches for T. gondii and N. caninum, respectively, at a 1% peptide FDR threshold. This equated to the identification of 30 494 distinct peptide sequences and 2921 proteins (matches to official gene models) for T. gondii, and 8911 peptides/1273 proteins for N. caninum following stringent protein‐level thresholding. We have also identified 289 and 140 loci for T. gondii and N. caninum, respectively, which mapped to RNA‐Seq‐derived gene models used in our analysis and apparently absent from the official annotation (release 10 from EuPathDB) of these species. We present several examples in our study where the RNA‐Seq evidence can help in correction of the current gene model and can help in discovery of potential new genes

BG-4, a novel anticancer peptide from bitter gourd (Momordica charantia), promotes apoptosis in human colon cancer cells

Momordica charantia is a perennial plant with reported health benefits. BG-4, a novel peptide from Momordica charantia, was isolated, purified and characterized. The trypsin inhibitory activity of BG-4 is 8.6 times higher than purified soybean trypsin inhibitor. The high trypsin inhibitory activity of BG-4 may be responsible for its capability to cause cytotoxicity to HCT-116 and HT-29 human colon cancer cells with ED50values of 134.4 and 217.0 μg/mL after 48 h of treatment, respectively. The mechanism involved in the cytotoxic effect may be associated with induction of apoptosis as evidenced by increased percentage of HCT-116 and HT-29 colon cancer cells undergoing apoptosis from 5.4% (untreated) to 24.8% (BG-4 treated, 125 μg/mL for 16 h) and 8.5% (untreated) to 31.9% (BG-4 treated, 125 μg/mL for 16 h), respectively. The molecular mechanistic explanation in the apoptosis inducing property of BG-4 is due to reduced expression of Bcl-2 and increased expression of Bax leading to increased expression of caspase-3 and affecting the expression of cell cycle proteins p21 and CDK2. This is the first report on the anti-cancer potential of a novel bioactive peptide isolated from Momordica charantia in vitro supporting the potential therapeutic property of BG-4 against colon cancer that must be addressed using in vivo models of colon carcinogenesis

The relationship between inhibition of bacterial adhesion to a solid surface by sub-MICs of antibiotics and subsequent development of a biofilm

Many studies have demonstrated that subminimal inhibitory concentrations (sub-MICs) of antibiotics can inhibit initial microbial adherence to medical device surfaces. It has been suggested that, by inhibiting initial adhesion, biofilm formation might be prevented. However, since initial adherence and subsequent biofilm formation may be two distinct phenomena, conclusions regarding the effects of sub-MIC antibiotics on initial adhesion cannot be extrapolated to biofilm formation. In this study, we evaluated the adherence of several clinical isolates of coagulase-negative staphylococci (CoNS) to acrylic and the effect of sub-MICs of vancomycin, cefazolin, dicloxacillin and combinations of these antibiotics on adherence and biofilm formation. Most of the antibiotics used resulted in effective reduction of bacterial adherence to acrylic, in some cases reaching over 70% inhibition of adherence. When strains with a high biofilm-forming capacity were grown in sub-MICs of those antibiotics, there existed combinations of the drugs that significantly inhibited biofilm formation. However, most of the antibiotic combinations that inhibited adherence did not have a profound effect on biofilm formation. When comparing the results of the effect of sub-MIC amounts of antibiotics in inhibiting adherence with their effect on the inhibition of biofilm formation, significant differences were found, mainly when using combinations of antibiotics. In general, the effect on the inhibition of adherence was greater than the effect on inhibiting biofilm formation. These results demonstrate that assays evaluating the inhibition of initial adherence to medical surfaces cannot fully predict the effect on inhibition of biofilm formation.NIH - grant AI 46706.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/ESP/42688/2001, SFRH/BD/8676/2002

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

BG-4 from Bitter Gourd (Momordica charantia) Differentially Affects Inflammation In Vitro and In Vivo

BG-4 isolated from bitter gourd has been reported for anti-cancer properties. The objective was to evaluate the anti-inflammatory properties of BG-4 in vitro and in vivo. Comparative study of the anti-inflammatory properties of BG-4 in vitro and in vivo was conducted on lipopolysaccharide (LPS)-activated mouse macrophages, and on dextran sodium sulfate (DSS)-induced colitis in mice. BG-4 reduced the production of pro-inflammatory markers in LPS-activated macrophages. On the other hand, intraperitoneal administration of BG-4 in DSS-induced colitis led to colon shortening, elevated neutrophils infiltration and myeloperoxidase activity, presence of blood in the stool, and loss of body weight, with differential systemic and local effects on pro-inflammatory cytokines in vivo. The results demonstrated that BG-4 differentially affected inflammation in vitro and in vivo

Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making

Quantitative analysis of adhesion and biofilm formation on hydrophilic and hydrophobic surfaces of clinical isolates of Staphylococcus epidermidis

Staphylococcus epidermidis is now well established as a major nosocomial pathogen associated with infections of indwelling medical devices. The major virulence factor of these organisms is their ability to adhere to devices and form biofilms. However, it has not been established that adherence and biofilm formation are closely linked phenotypes for clinical isolates. In this study, the initial adhesion to different materials (acrylic and glass) of 9 clinical isolates of S. epidermidis, along with biofilm-positive and biofilm-negative control strains, was assayed using physico-chemical interactions to analyze the basis for bacterial adherence to the substratum. X-ray photo electron spectroscopy (XPS) analysis of the cell surface elemental composition was also performed in an attempt to find a relationship between chemical composition and adhesion capabilities. Biofilm formation on the two surfaces was evaluated by dry weight measurements. Human erythrocytes were used to evaluate the ability of S. epidermidis strains to cause hemagglutination, an indicator of the production of a poly-N-acetyl glucosamine cell surface polysaccharide also involved in biofilm formation. The clinical isolates exhibited different cell wall physico-chemical properties, resulting in differing abilities to adhere to surfaces. Adhesion to hydrophobic substrata for all strains occurred to a greater extent than that to hydrophilic surfaces. Bacterial cell hydrophobicity seemed to have little or no influence on adhesion. X-ray photoelectron spectroscopy analysis showed a high ratio of oxygen/carbon for all strains, which is a common characteristic of S. epidermidis species. No relevant relationship was found between XPS data and adhesion values. All strains forming biofilms were able to agglutinate erythrocytes. However, no direct relationship was found between the amount of biofilm formed and the initial adhesion extent. These results indicate that high levels of initial adherence do not necessarily lead to thick biofilm formation. These two aspects of the pathogenesis of medical device related-infection may need to be evaluated independently to ascertain the contribution of each to the virulence of S. epidermidis causing device-related infections.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/ESP/42688/2001, grant SFRH/BD/8676/2002.NIH - grant AI 46706

Eye-tracking for longitudinal assessment of social cognition in children born preterm

Background and objectives: Preterm birth is associated with atypical social cognition in infancy, and cognitive impairment and social difficulties in childhood. Little is known about the stability of social cognition through childhood, and its relationship with neurodevelopment. We used eye‐tracking in preterm and term‐born infants to investigate social attentional preference in infancy and at 5 years, its relationship with neurodevelopment and the influence of socioeconomic deprivation.Methods: A cohort of 81 preterm and 66 term infants with mean (range) gestational age at birth 28+5 (23+2–33+0) and 40+0 (37+0–42+1) respectively, completed eye‐tracking at 7–9 months, with a subset re‐assessed at 5 years. Three free‐viewing social tasks of increasing stimulus complexity were presented, and a social preference score was derived from looking time to socially informative areas. Socioeconomic data and the Mullen Scales of Early Learning at 5 years were collected.Results: Preterm children had lower social preference scores at 7–9 months compared with term‐born controls. Term‐born children’s scores were stable between time points, whereas preterm children showed a significant increase, reaching equivalent scores by 5 years. Low gestational age and socioeconomic deprivation were associated with reduced social preference scores at 7–9 months. At 5 years, preterm infants had lower Early Learning Composite scores than controls, but this was not associated with social attentional preference in infancy or at 5 years.Conclusions: Preterm children have reduced social attentional preference at 7–9 months compared with term‐born controls, but catch up by 5 years. Infant social cognition is influenced by socioeconomic deprivation and gestational age. Social cognition and neurodevelopment have different trajectories following preterm birth