ABSTRACT
Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs. In the current study, we have analyzed circadian rhythms in daily activity and sleep, and the circadian gene expression in a cohort of healthy controls (N = 22), ADHD participants not using ADHD-medication (N = 17), and participants with ADHD and current use of ADHD medication (N = 17). Rhythms of sleep/wake behavior were assessed via wrist-worn actigraphy, whilst rhythms of circadian gene expression were assessed ex-vivo in primary human-derived dermal fibroblast cultures. Behavioral data indicate that patients with ADHD using ADHD-medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency, more nocturnal activity but not more nocturnal wakenings than both controls and ADHD participants without medication. At the molecular level, there were alterations in the expression of PER2 and CRY1 between ADHD individuals with no medication compared to medicated ADHD patients or controls, whilst CLOCK expression was altered in patients with ADHD and current medication. Analysis of fibroblasts transfected with a BMAL1:luc reporter showed changes in the timing of the peak expression across the three groups. Taken together, these data support the contention that both ADHD and medication status impact on circadian processes.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/physiopathology , Circadian Rhythm Signaling Peptides and Proteins/genetics , Circadian Rhythm , Sleep/physiology , Actigraphy , Adult , Attention Deficit Disorder with Hyperactivity/drug therapy , CLOCK Proteins/genetics , Cells, Cultured , Circadian Clocks/genetics , Cryptochromes/genetics , Female , Fibroblasts/metabolism , Gene Expression , Humans , Male , Middle Aged , Period Circadian Proteins/geneticsABSTRACT
Temperate coliphages were recovered from sewage, mammalian feces, and lysogenic strains of Escherichia coli. A total of 32 phages of independent origin were divided into six groups by applying the criteria of host range, antigenic homology, and the ultraviolet inducibility of the prophage. The demonstration of genetic interactions in some cases has confirmed the classification scheme. Nine phages were assigned to the P2 family and 19 to the lambda family. The remaining four isolates may represent some novel phylogenetic types. Phages recovered from the lysogenic strains of E. coli were all found to be P2 related, whereas a majority of the phages recovered as cell-free plaque-forming units were assignable to the lambda family. It is proposed that the biological attributes of the phages belonging to the two principal families are reflected in the distribution patterns observed. The virions of phage HK256 show multiple tail fibers and may thus represent a "new" virion form among the temperate coliphages.
Subject(s)
Coliphages/classification , Bacteriophage lambda/classification , Coliphages/ultrastructure , Escherichia coli , Feces/microbiology , Lysogeny , Serotyping , Sewage , Ultraviolet Rays , Viral Plaque Assay , Virus Activation/radiation effectsABSTRACT
Freshly voided samples of the feces of cows, pigs, and humans were analyzed for the enumeration of cell-free plaque-forming units (PFU) of coliphages and Salmonella phages. Coliphage PFU counts per gram (wet weight) of feces were found to range from less than 10(1) to greater than 10(7). Salmonella phages were found in three out of five porcine samples, but none were found in the four bovine samples analyzed. Virulent coliphages related to the phiX174/S13 serological group showed some "habitat preference" in that the S13 type of phages was found only in pig feces, whereas the phiX174 type of phages was found only in cow dung. Temperate coliphages were detectable in a majority of samples of both human and porcine origin but were infrequently found in bovine samples. About 80% of the temperate coliphages of fecal origin have been found to be serologically related to phage HK022 (Dhillon and Dhillon, 1973), and all are efficiently inducible by ultraviolet light irradiation. However, considerable diversity with the group was found when the prophage immunity pattern of 10 randomly selected isolates was examined.
