Genome Sequence of SN1, a Bacteriophage That Infects \u3ci\u3eSphaerotilus natans\u3c/i\u3e and \u3ci\u3ePseudomonas aeruginosa\u3c/i\u3e

Phage SN1 infects Sphaerotilus natans and Pseudomonas aeruginosa strains. Its genome consists of 61,858 bp (64.3% GC) and 89 genes, including 32 with predicted functions. SN1 genome is very similar to Pseudomonas phage M6, which contains hypermodified thymidines. Genome analyses revealed similar base-modifying genes as those found in M6

Farnesol restores wild-type colony morphology to 96% of \u3ci\u3eCandida albicans\u3c/i\u3e colony morphology variants recovered following treatment with mutagens

Candida albicans is a diploid fungus that undergoes a morphological transition between budding yeast, hyphal, and pseudohyphal forms. The morphological transition is strongly correlated with virulence and is regulated in part by quorum sensing. Candida albicans produces and secretes farnesol that regulates the yeast to mycelia morphological transition. Mutants that fail to synthesize or respond to farnesol could be locked in the filamentous mode. To test this hypothesis, a collection of C. albicans mutants were isolated that have altered colony morphologies indicative of the presence of hyphal cells under environmental conditions where C. albicans normally grows only as yeasts. All mutants were characterized for their ability to respond to farnesol. Of these, 95.9% fully or partially reverted to wildtype morphology on yeast malt (YM) agar plates supplemented with farnesol. All mutants that respond to farnesol regained their hyphal morphology when restreaked on YM plates without farnesol. The observation that farnesol remedial mutants are so common (95.9%) relative to mutants that fail to respond to farnesol (4.1%) suggests that farnesol activates and (or) induces a pathway that can override many of the morphogenesis defects in these mutants. Additionally, 9 mutants chosen at random were screened for farnesol production. Two mutants failed to produce detectable levels of farnesol. Candida albicans est un champignon diploïde qui subit une transition morphologique entre les levures en herbe, les hyphes et les formes pseudohyphales. La transition morphologique est fortement corrélée à la virulence et est régulée en partie par la détection du quorum. Candida albicans produit et sécrète du farnésol qui régule la transition morphologique levure-mycélium. Les mutants qui ne parviennent pas à synthétiser ou à répondre au farnésol pourraient être verrouillés en mode filamenteux. Pour tester cette hypothèse, une collection de mutants de C. albicans a été isolée qui ont modifié les morphologies des colonies, indiquant la présence de cellules hyphales dans des conditions environnementales où C. albicans ne pousse normalement que sous forme de levures. Tous les mutants ont été caractérisés pour leur capacité à répondre au farnésol. Parmi ceux-ci, 95,9% sont entièrement ou partiellement revenus à la morphologie de type sauvage sur des plaques de gélose au levure de malt (YM) complétées par du farnésol. Tous les mutants qui répondent au farnésol ont retrouvé leur morphologie hyphale lorsqu\u27ils ont été recréés sur des plaques YM sans farnésol. L\u27observation selon laquelle les mutants curatifs du farnésol sont si communs (95,9%) par rapport aux mutants qui ne répondent pas au farnésol (4,1%) suggère que le farnésol s\u27active et (ou) induit une voie qui peut supplanter bon nombre des défauts de morphogenèse de ces mutants. De plus, 9 mutants choisis au hasard ont été testés pour la production de farnésol. Deux mutants n\u27ont pas réussi à produire des niveaux détectables de farnésol

Inoculum Size Effect in Dimorphic Fungi: Extracellular Control of Yeast-Mycelium Dimorphism in \u3ci\u3eCeratocystis ulmi\u3c/i\u3e

We studied the inoculum size effect in Ceratocystis ulmi, the dimorphic fungus that causes Dutch elm disease. In a defined glucose-proline-salts medium, cells develop as budding yeasts when inoculated at \u3e106 spores per ml and as mycelia when inoculated at type, age of the spores, temperature, pH, oxygen availability, trace metals, sulfur source, phosphorous source, or the concentration of glucose or proline. Similarly, it was not influenced by added adenosine, reducing agents, methyl donors, amino sugars, fatty acids, or carbon dioxide. Instead, growing cells excreted an unknown quorum-sensing factor that caused a morphological shift from mycelia to budding yeasts. This yeast-promoting effect is abolished if it is extracted with an organic solvent such as ethyl acetate. The quorum-sensing activity acquired by the organic solvent could be added back to fresh medium in a dosedependent fashion. The quorum-sensing activity in C. ulmi spent medium was specific for C. ulmi and had no effect on the dimorphic fungus Candida albicans or the photomorphogenic fungus Penicillium isariaeforme. In addition, farnesol, the quorum-sensing molecule produced by C. albicans, did not inhibit mycelial development of C. ulmi when present at concentrations of up to 100 μM. We conclude that the inoculum size effect is a manifestation of a quorum-sensing system that is mediated by an excreted extracellular molecule, and we suggest that quorum sensing is a general phenomenon in dimorphic fungi

Comparison of estimated energy intake in children using a Web-based Dietary Assessment Software with accelerometer-estimated energy expenditure in children

Background: The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) project carried out a school meal study to assess the impact of a New Nordic Diet (NND). The random controlled trial involved 834 children aged 8–11 in nine local authority schools in Denmark. Dietary assessment was carried out using a program known as WebDASC (Web-based Dietary Assessment Software for Children) to collect data from the children. Objective: To compare the energy intake (EI) of schoolchildren aged 8–11 estimated using the WebDASC system against the total energy expenditure (TEE) as derived from accelerometers worn by the children during the same period. A second objective was to evaluate the WebDASC's usability. Design: Eighty-one schoolchildren took part in what was the pilot study for the OPUS project, and they recorded their total diet using WebDASC and wore an accelerometer for two periods of seven consecutive days: at baseline, when they ate their usual packed lunches and at intervention when they were served the NND. EI was estimated using WebDASC, and TEE was calculated from accelerometer-derived activity energy expenditure, basal metabolic rate, and diet-induced thermogenesis. WebDASC's usability was assessed using a questionnaire. Parents could help their children record their diet and answer the questionnaire. Results: Evaluated against TEE as derived from the accelerometers worn at the same time, the WebDASC performed just as well as other traditional methods of collecting dietary data and proved both effective and acceptable with children aged 8–11, even with perhaps less familiar foods of the NND. Conclusions: WebDASC is a useful method that provided a reasonably accurate measure of EI at group level when compared to TEE derived from accelerometer-determined physical activity in children. WebDASC will benefit future research in this area

Growth rate, health and welfare in a dairy herd with natural suckling until 6–8 weeks of age: a case report

Over a period of two years, growth rate and health were measured for dairy calves allowed to suckle their mothers up to 6–8 weeks of age. Thirty-one calves were weighted weekly, and the mean daily growth rate was 1.2 ± 0.03 kg from birth up to 13 weeks of age. Illness in calves and young stock was not observed. In the cows, the mean incidences of ketosis, displaced abomasum, puerperal paresis, mastitis, teat injury and retained placenta were 0, 0, 8, 22, 1 and 1%, respectively, during a 6-year period. The mean daily gain of 56 growing bulls was 1.4 kg when slaughtered at 15 months of age, which is higher than the mean daily gain of 0.95 kg in the population. Probiotics, hormones and vaccines were not used, and antibiotics were only used for treating illness. The present study indicates many advantages and few problems when dairy calves are penned together with the cows and allowed natural feeding up to 6–8 weeks of age. This production system was easy to manage, preferred by the farmer, and may satisfy the public concern regarding the practice of immediate separation of cow and calf in commercial milk production

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis