Identification of a multidrug efflux pump in Flavobacterium johnsoniae

In this study, the mechanism conferring multiple drug resistance in several strains of flavobacteria isolated from the ovarian fluids of hatchery reared 3-year old brook trout Salvelinus fontinalis was investigated. Metabolic fingerprinting and 16S rRNA gene sequences identified the isolates as Flavobacterium johnsoniae. The isolates exhibited multiple resistances to a wide range of antimicrobial classes including penicillin, cephem, monobactam, aminoglycoside, and phenicol. Although plasmids and other transposable elements containing antimicrobial resistance genes were not detected, the isolates did contain a genomic sequence for a chloramphenicol-inducible resistance-nodulation-division family multidrug efflux pump system. Efflux pumps are non-specific multidrug efflux systems. They are also a component of cell-cell communication systems, and respond specifically to cell membrane stressors such as oxidative or nitrosative stress. Understanding of efflux pump mediated antibiotic resistances will affect efficacy of clinical treatments of fishes associated with F. johnsoniae epizootics

Spearmint (\u3cem\u3el\u3c/em\u3e-carvone) Oil and Wintergreen (methyl salicylate) Oil Emulsion is an Effective Immersion Anesthetic of Fishes

This study evaluates the effects of a spearmint (/-carvone) and wintergreen oil (methyl salicylate) emulsion (CMSE) on age 1 landlocked Atlantic salmon Salmo salar sebago (hereafter salmon). Salmon were immersed in either 257 µl/L CMSE or 75 mg/L tricaine methanesulfonate (MS-222) to induce anesthesia (stage 4), useful for emersion and noninvasive husbandry procedures, and then salmon were recovered in fresh water. Induction was quicker in the CMSE group; however, recovery was quicker in the MS-222 group. A second experiment was conducted in which salmon were immersed in 257 µl/L CMSE for 8.5 min, or 75 mg/L MS-222 for 8.5 min in order to compare electrocardiographs during deeper anesthesia (stage 5) between salmon continuously immersed in CMSE to those continuously immersed in MS-222. Because salmon remained sedated longer after CMSE exposure than after MS-222 exposure, a third group of salmon was immersed in 257 µl/L CMSE for just 2.5 min before undergoing the 6-min electrocardiograph procedure. Anesthesia induction rates, recovery rates, and electrocardiographs of salmon anesthetized with CMSE were comparable to salmon anesthetized with MS-222. Salmon anesthetized with CMSE and then transferred immediately to fresh water had more stable heart rates than salmon anesthetized with either MS-222 or CMSE continuously. Salmon bathed continuously in CMSE showed clinical signs of increasing anesthetic depth including decreasing heart rate, decreasing respiration rate and electrocardiograph abnormalities. The CMSE, with its mint and wintergreen concentrations less than in household products such as chewing gum, toothpaste, and mouthwash, is a potent, rapid-acting immersion fish anesthetic comparable to MS-222 for stages 4 and 5 anesthesia

C-reactive protein haplotypes and dispositional optimism in obese and nonobese elderly subjects

Background Chronic low-grade inflammation, characterized by elevated plasma levels of C-reactive protein (CRP), has been inversely associated with dispositional optimism. Using a Mendelian randomization design, this study explores whether CRP haplotypes that determine CRP plasma levels are also associated with dispositional optimism. Methods In a sample of 1,084 community-dwelling subjects (aged 60–85 years) from three cohort studies (Arnhem Elderly Study, n = 426; Leiden Longevity Study, n = 355; Zutphen Elderly Study, n = 303), six CRP polymorphisms (rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) coding for five common haplotypes were genotyped. The association of CRP haplotypes with CRP plasma levels and dispositional optimism was analyzed using multivariable linear regression models. Subanalyses were stratified by body mass index (BMI =25 kg/m2). Results CRP haplotypes determined CRP plasma levels (adjusted ß = 0.094, p <0.001). In the whole group, no association was found between CRP haplotypes and dispositional optimism scores (adjusted ß = -0.02, p = 0.45). In BMI strata, CRP haplotypes were associated with increasing levels of plasma CRP levels (adjusted ß = 0.112; p = 0.002) and lower dispositional optimism levels (adjusted ß = -0.068; p = 0.03) in the obese group only. Conclusions These results suggest that genetically increased CRP levels are involved in low dispositional optimism, but only in case of obesit

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

The advice of the wise

Advice, Buddhism, Confucianism, Epicurus, Happiness, New Age, Schopenhauer, Self-help, Taoism,