Innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. The intracellular pathogen recognition receptors RIG-I and MDA5 are essential for interferon induction by viral RNAs containing 5′ triphosphates or double-stranded structures, respectively. Viruses with a negative-stranded RNA genome are an important group of pathogens causing emerging and re-emerging diseases. We investigated the ability of genomic RNAs from substantial representatives of this virus group to induce interferon via RIG-I or MDA5. RNAs isolated from particles of Ebola virus, Nipah virus, Lassa virus, and Rift Valley fever virus strongly activated the interferon-beta promoter. Knockdown experiments demonstrated that interferon induction depended on RIG-I, but not MDA5, and phosphatase treatment revealed a requirement for the RNA 5′ triphosphate group. In contrast, genomic RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus did not trigger interferon induction. Sensitivity of these RNAs to a 5′ monophosphate-specific exonuclease indicates that the RIG-I-activating 5′ triphosphate group was removed post-transcriptionally by a viral function. Consequently, RIG-I is unable to bind the RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus. These results establish RIG-I as a major intracellular recognition receptor for the genome of most negative-strand RNA viruses and define the cleavage of triphosphates at the RNA 5′ end as a strategy of viruses to evade the innate immune response.

The prerequisites for evidence-based practice were assessed as good, but ways to make evidence-based practice time efficient, easy to access and relevant to clinical practice need to be continuously supported at the management level, so that research evidence becomes linked to work-flow in a way that does not adversely affect productivity and the flow of patients.

Little is known about common factors (e.g., macronutrients and energy supply) regulating the protein secretory function of adipose tissue. We therefore compared the effects of randomly assigned 10-week hypoenergetic (؊600 kcal/day) diets with moderate-fat/moderate-carbohydrate or low-fat/high-carbohydrate content on circulating levels and production of proteins (using radioimmunoassays and enzyme-linked immunosorbent assays) from subcutaneous adipose tissue in 40 obese but otherwise healthy women. Similar results were obtained by the two diets. Body weight decreased by ϳ7.5%. The secretion rate of leptin decreased by ϳ40%, as did that of tumor necrosis factor-␣ (TNF-␣), and interleukin (IL)-6 and -8 decreased by 25-30%, whereas the secretion of plasminogen activator inhibitor 1 (PAI-1) and adiponectin did not show any changes. Regarding mRNA expression (by real-time PCR), only that of leptin and IL-6 decreased significantly. Circulating levels of leptin and PAI-1 decreased by 30 and 40%, respectively, but there were only minor changes in circulating TNF-␣, IL-6, or adiponectin. In conclusion, moderate caloric restriction but not macronutrient composition influences the production and secretion of adipose tissue-derived proteins during weight reduction, leptin being the most sensitive and adiponectin and PAI-1 the least sensitive. Diabetes 53: 1966 -1971, 2004 A dipose tissue secretes a number of proteins with auto-, para-, and endocrine actions, such as tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-6 and -8, plasminogen activator inhibitor 1 (PAI-1), leptin, and adiponectin (1,2). Little is known about the regulation of the protein secretory function of human adipose tissue except for leptin (3). The effect of energy restriction is of particular importance for obesity treatment (4). Dietary-induced weight loss normalizes plasma levels and adipose tissue gene expression of several adipocyte-derived proteins (5-12). Whether the same is true for protein secretion is unknown, except for TNF-␣ (5,10). Furthermore, the relative roles of loss of body fat, energy restriction per se, and changes in macronutrient supply are not known. It is also unknown which proteins are more or less sensitive to nutritional changes regarding their production by adipose tissue. These questions were investigated by studying the release of leptin, adiponectin, IL-6 and -8, TNF-␣, and PAI-1 in subcutaneous adipose tissue of 40 obese women before and after 10 weeks on moderate hypoenergetic diets with either low-fat/highcarbohydrate content or moderate-fat/moderate-carbohydrate content. RESEARCH DESIGN AND METHODSAll subjects participated in a European multicenter study termed NutrientGene Interactions in Human Obesity: Implications for Dietary Guidelines (NUGENOB, www.nugenob.com), which examines the interaction between hypoenergetic diets and genes. Our Swedish center included 40 obese women aged 21-49 years with a BMI of 30.9 -47.7 kg/m 2 who were otherwise healthy and free of regular medication, except 1 woman who was treated wit...

Macronutrients have a secondary role in changes in adipocyte gene expression after energy-restricted diets. The most striking alteration after energy restriction is a coordinated reduction in the expression of genes regulating the production of polyunsaturated fatty acids.

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Nairovirus within the family Bunyaviridae and is the causative agent of severe hemorrhagic fever. Despite increasing knowledge about hemorrhagic fever viruses, the factors determining their pathogenicity are still poorly understood. The interferoninduced MxA protein has been shown to have an inhibitory effect on several members of the Bunyaviridae family, but the effect of MxA against CCHFV has not previously been studied. Here, we report that human MxA has antiviral activity against CCHFV. The yield of progeny virus in cells constitutively expressing MxA was reduced up to 1,000-fold compared with control cells, and accumulation of viral genomes was blocked. Confocal microscopy revealed that MxA colocalizes with the nucleocapsid protein (NP) of CCHFV in the perinuclear regions of infected cells. Furthermore, we found that MxA interacted with NP by using a coimmunoprecipitation assay. We also found that an amino acid substitution (E645R) within the C-terminal domain of MxA resulted in a loss of MxA antiviral activity and, concomitantly, in the capacity to interact with CCHFV NP. These results suggest that MxA, by interacting with a component of the nucleocapsid, prevents replication of CCHFV viral RNA and thereby inhibits the production of new infectious virus particles.

OBJECTIVE:The main aim of this study was to identify subjects with (1) night eating syndrome (de®ned as morning anorexia, evening hyperphagia and insomnia) and (2) nocturnal eating syndrome (de®ned as eating at night after having gone to bed). In the literature the differences and similarities between these two syndromes are not clear. SUBJECTS: One-hundred and ninety-four obese patients from an academic, clinical obesity unit. Mean BMI ( AE s.d.) was 40 AE 5 kgam 2 , age 44 AE 12 y and 76% were women. MEASUREMENTS: Questionnaires with multiple choices and open questions along with the Binge Eating Scale. RESULTS: Fourteen percent of the patients met the criteria for night eating andaor nocturnal eating syndrome. Night eating syndrome was manifest in 6% of the patients and nocturnal eating syndrome in 10%. Both the night eaters and the nocturnal eaters had more trouble getting to sleep than the patients without nightanocturnal eating problems (P`0.001 and P`0.01). The nocturnal eaters also had more trouble staying asleep (P`0.001). Morning anorexia was not typically found in nocturnal eaters. Being on long-term sick leave was more common among the nocturnal eaters (P`0.01). CONCLUSION: Fourteen percent of the patients at our obesity unit met the criteria for night eating andaor nocturnal eating syndrome. There are clear similarities between night eating syndrome and nocturnal eating syndrome, but also differences.

Adipose tissue hyperplasia (too many small fat cells) and low leptin production resulting in relative hypoleptinemia in the fasting (basal) state are common features of the postobese state in women.

1. A cross-sectional observational study was carried out to investigate spatial, temporal and management aspects of foot-pad dermatitis in Swedish broilers. The efficacy of a control programme was evaluated. 2. Flock information on producer, breed, foodstuff manufacturer, region, abattoir, date of slaughter, age at slaughter, planned and actual stocking density was recorded. A total of 6988 flocks, representing approximately 110 million broilers was examined. A total of 175 broiler producers from 15 geographical regions is represented. 3. The total foot-pad score per flock ranged from 0 to 200, with a mean of 34.7 and a standard deviation of 40.9. 4. Simple linear regression analysis showed that the mean total score on a weekly basis decreased (P < 0.001) over time, mainly because of a decrease in the prevalence of severe foot-pad lesions. 5. There was an association (P < 0.05) between slaughterhouse, foodstuff supplier and geographic region respectively and the mean total foot pad score of the flocks slaughtered.