Novel Anti-Campylobacter Compounds Identified Using High Throughput Screening of a Pre-selected Enriched Small Molecules Library

Campylobacter is a leading cause of foodborne bacterial gastroenteritis worldwide and infections can be fatal. The emergence of antibiotic-resistant Campylobacter spp. necessitates the development of new antimicrobials. We identified novel anti-Campylobacter small molecule inhibitors using a high throughput growth inhibition assay. To expedite screening, we made use of a “bioactive” library of 4,182 compounds that we have previously shown to be active against diverse microbes. Screening for growth inhibition of Campylobacter jejuni, identified 781 compounds that were either bactericidal or bacteriostatic at a concentration of 200 µM. Seventy nine of the bactericidal compounds were prioritized for secondary screening based on their physico-chemical properties. Based on the minimum inhibitory concentration against a diverse range of C. jejuni and a lack of effect on gut microbes, we selected 12 compounds. No resistance was observed to any of these 12 lead compounds when C. jejuni was cultured with lethal or sub-lethal concentrations suggesting that C. jejuni is less likely to develop resistance to these compounds. Top 12 compounds also possessed low cytotoxicity to human intestinal epithelial cells (Caco-2 cells) and no hemolytic activity against sheep red blood cells. Next, these 12 compounds were evaluated for ability to clear C. jejuni in vitro. A total of 10 compounds had an anti-C. jejuni effect in Caco-2 cells with some effective even at 25 µM concentrations. These novel 12 compounds belong to five established antimicrobial chemical classes; piperazines, aryl amines, piperidines, sulfonamide and pyridazinone. Exploitation of analogues of these chemical classes may provide Campylobacter specific drugs that can be applied in both human and animal medicine.

Legalities of treating wildlife in UK veterinary practice.

Many different species of wildlife will be presented to veterinary practices. In addition to providing care for these patients, veterinary nurses need to be aware of the legal aspects that apply. Legislation relating to wildlife species is particularly relevant to taking animals from the wild, keeping wild animals and birds in care, releasing them back into the wild and notifiable diseases. Following devolution, there are some differences in legislation in different parts of the UK. Specific species, particularly endangered species, have more detailed legislation which also needs to be adhered to. While lay people may have the best of intentions, they need to be aware that all veterinary care needs to follow Schedule 3 of the Veterinary Surgeon's Act 1966, and the best interests of the animals must be central to all care that is given.

Granulomatosis with Polyangiitis (Wegener Granulomatosis) Mimicking Infective Endocarditis

Introduction Infective endocarditis (IE) has been reported to mimic granulomatosis with polyangiitis (GPA) and to test positive to antineutrophil cytoplasmic antibodies (ANCA), which may lead to a misdiagnosis and inappropriate treatment. Case presentation We report a case of a 59-year-old man admitted for purpura, gangrenous digital infarcts and glomerulonephritis. The diagnosis of IE was initially considered on the basis of heart murmur and two positive haemocultures to corynebacterium. Ineffectiveness of antimicrobial therapy and further neurological and nasal manifestations supported the diagnosis of GPA. Conclusions IE should be ruled out before initiation of immunosuppressive treatment. If the disease progresses despite antimicrobial treatment, vascular diseases should be rapidly taken into account in differential diagnosis and treated early to avoid fatal complications.

Analyse comparative du cadre de gestion des fonds verts du Canada et des États-Unis en vue d'améliorer le fonds vert du Québec

Créé en 2006, le Fonds vert du Québec a été établi dans le but de financer les mesures et les activités favorisant le développement durable. Au fil des années, ce fonds a permis d’amasser d’importantes sommes, notamment grâce aux redevances, à la tarification ou à la compensation. Les changements climatiques ont amené le Ministère du Développement durable, de l’Environnement et de la Lutte contre les changements climatiques à consacrer la majeure partie des revenus du Fonds vert pour cet enjeu. Avec un bilan positif dans les revenus, on peut penser que le Fonds vert a aidé à réaliser les objectifs du Québec en matière de changements climatiques. Or, dans les dernières années, plusieurs parties prenantes, dont le Commissaire au développement durable, ont relevé des problèmes importants dans la gestion du fonds. Ces problèmes se situent notamment dans la gestion stratégique, dans la gestion des programmes et des projets ainsi que dans la diffusion de l’information. La gouvernance actuelle du Fonds vert du Québec n’a donc pas apporté les résultats souhaités en matière d’adaptation aux changements climatiques et en réduction des émissions de gaz à effet de serre. L’objectif de l’essai est d’analyser le cadre de gestion des fonds verts existants du Canada et des États-Unis afin de relever des solutions qui permettraient d’améliorer le Fonds vert du Québec en matière de changements climatiques au Québec. Pour atteindre cet objectif, divers fonds verts existants partageant des traits similaires à celui du Québec ont été analysés. Le choix s’est arrêté au Fonds municipal vert, au Climate Change and Emissions Management Fund et au California Climate Investments. Ces derniers ont été analysés en fonction d’un tableau comparatif comprenant des critères comme l’établissement d’objectifs visant l’atteinte de résultats, l’élaboration d’un processus de sélection de projets, la mise en œuvre d’un mécanisme de surveillance ou de suivi et la diffusion des informations relatives aux programmes. L’analyse comparative a permis de constater quelques tendances dans la gestion des fonds verts. D’abord, les fonds verts ont adopté leur propre approche dans la formulation des objectifs du fonds. Le Fonds municipal vert se démarque en établissant des objectifs de nature budgétaire et stratégique. De plus, ces objectifs sont énoncés de façon spécifique, mesurable, appropriée, réaliste et délimitée dans le temps. Les fonds verts analysés présentent également un processus de sélection de projets plus élaborés que celui du Fonds vert du Québec, en ce qu’il prévoit des critères d’admissibilités bien définis, une multitude d’étapes de sélection et la participation de plusieurs acteurs, notamment des acteurs externes. Le Climate Change and Emissions Management Fund se distingue des autres fonds, en ce qu’il introduit un comité, le Fairness monitor, pour surveiller le processus de sélection. Pour tous les fonds verts de cette analyse, le mécanisme de surveillance ou de suivi se traduit par des livrables, comme des rapports annuels, exécutés par des auditeurs indépendants. Enfin, les fonds verts utilisent divers moyens de communication pour faciliter la compréhension du fonctionnement du fonds en question. Le Fonds municipal vert offre des activités, telles que du réseautage, du mentorat, des conférences afin d’encourager le partage des connaissances et l’apprentissage par les pairs. Le California Climate Investments a mis sur pied une plateforme sur Internet qui permet de voir en continu l’évolution et les résultats des projets financés. Aux termes de cette analyse, quatre recommandations ont été formulées en fonction des éléments de gestion qui sont le plus ressortis des trois fonds verts.

O Litoral e a metrópole dinâmica imobiliária, turismo e expansão urbana na região metropolitana de Natal-RN

The metropolitan regions of Northeast Brazil are being gradually included in a scenario of international investments, which are motivated by the restructuring of both touristic and real-estate sectors. The new capital, real-estate developers and space configurations that result from this process indicate the need for the creation and implementation of public tools which should, at least, allow the mitigation of the urban impacts and environmental losses resulting from this situation. The effects on landscape and on the socio-spatial configuration result from the intensification caused by the dynamism of the "real estate-tourism" sector. There is a regional integration as an expression of the urban expansion of the metropolitan area of Natal. This study investigates the uniqueness of the restructuring and territorial integration of coastal areas and the strategies of the circuit of capital accumulation formed by linking the real estate to tourism. It is intended to increase the understanding about the strategies of tourism, real estate and public policy agents involved in this territorial reconfiguration and in the fund-raising needed for the investments, to understand the existing social and environmental effects and their future trends and also to understand the forms of spatial production as results from the practices of approaching the land transformation and the tourism valorization of the landscape, in a synchronous manner, first in the Northeast region and, as a focal study, in the Metropolitan Area of Natal. Likewise, it is intended to apprehend the current processes of metropolization of the eastern coast of Rio Grande do Norte, in addition to indicate its physical-territorial transformation and the types of projects/developments promoted by the market in the recent period. Based upon analysis undertaken for the Metropolitan Region of Natal RN, this piece of work presents some considerations on possible legal instruments that can be adjusted to the municipalities which are experiencing the impact of this peculiar and recent phenomenon in the region, caused by the arrival of the real estate-touristic capital. It is also intended to point out basic proposals to the forms of public intervention, in a speculative way, starting from a Metropolitan Planning project within a medium and long term

The Early Intestinal Microbiota of Healthy Korean Newborns

Background: The microflora hypothesis may be the underlying explanation for the growth of inflammatory disease. In addition to many known affecting factors, knowing the gut microbiota of healthy newborns can help to understand the gut immunity and modulate it. Objectives: This study examined the microbiota of healthy newborns from urban regions. Patients and Methods: We enrolled 128 full-term newborns, born at Seoul St. Mary and St. Paul hospital from January 2009 to February 2010. All 143 samples of feces were cultivated in six culture plates to determine the amounts of total bacteria, anaerobes, gram-positive bacteria, coliforms, lactobacilli, and bifidobacteria. The samples were evaluated with a bivariate correlation between coliforms and lactobacilli. Terminal restriction fragment length polymorphism (T-RFLP) analysis with HhaI and MspI and a clustering analysis were performed for determination of diversity. Results: Bacteria were cultured in 61.5% of feces in the following order: anaerobes, gram-positive bacteria, lactobacilli, coliform, and bifidobacteria. The growth of total bacteria and lactobacilli increased in feces defecated after 24 hours of birth (P < 0.001, P = 0.008) and anaerobes decreased (P = 0.003). A negative correlation between the growth of lactobacilli and coliforms was found (r = -463, P < 0.001). Conclusions: This study confirms that bacterial colonization of healthy newborns born in cities is non-sterile, but has early diversification and inter-individuality.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Letters to Ebenezer Hancock from his mother, Mary Perkins, and his stepfather, Daniel Perkins, 1758 June 27 and 1758 November 16

These two letters were written to Ebenezer Hancock while he was an undergraduate at Harvard College. His stepfather, Daniel Perkins, wrote on June 27, 1758 and his mother, Mary Perkins, wrote on November 16, 1758. Both letters were sent from Bridgewater, Massachusetts, where the Perkins lived. The letters contain general greetings and wishes for Hancock's well being, as well as parental advice regarding his behavior and comportment.

The Laughing philosopher : being the entire works of Momus, jester of Olympus; Democritus, the merry philosopher of Greece, and their illustrious disciples, Ben Jonson, Butler, Swift, Gay, Joseph Miller, Esq. Churchill, Voltaire, Foote, Steevens, Wolcot, Sheridan, Curran, Colman, and others. /

Gathering E unsigned; page 65 misnumbered 5.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.