Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.

The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification.

Idiopathic intracranial hypertension, hormones, and 11ß-hydroxysteroid dehydrogenases.

Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11ß-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH.

Head lice infestation in schoolchildren and related factors in Mafraq governorate, Jordan.

BACKGROUND: Little is known about the effect of socioeconomic status on the infestation by head lice in schoolchildren in Jordan. MATERIALS AND METHODS: A cross-sectional school-based study was conducted from December 2009 to February 2010. A list of all primary schools in Mafraq governorate was obtained (394 primary schools). Eight primary schools were randomly selected (four male schools and four female schools). Data were collected by five well-trained nurses. Hair was examined for head lice as well as for eggs/nits. Analysis of data was conducted by using SPSS software version 16. The chi-square test was used to assess statistical significance of subgroup differences in the prevalence of infestation, and multivariate logistic regression was used to control for potential confounding. RESULTS: Out of 1550 primary schoolchildren screened, 412 (26.6%) were infected with lice, 163 (19.6%) boys and 249 (34.7%) girls. The results showed significant variations in head lice infestation by factors such as gender, age, and socioeconomic variables (family income, father's education, mother's education, number of rooms, number of siblings younger than 15 years, frequency of hair washing per week, and bathing per week). There was no significant variation in lice infestation with parents' occupation (P > 0.05). CONCLUSIONS: Socioeconomic status is a major factor influencing the occurrence of pediculosis capitis among schoolchildren in both sexes. Improving standards of living and personal hygiene might significantly reduce pediculosis capitis in schoolchildren in Jordan.

Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.

Two experiments were performed to assess the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. The NA depletions were achieved through two different pharmacological means: systemic N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine. Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Experiment 1, DSP4, and in Experiment 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the two stimuli (a taste cue, i.e., saccharin presented in bottles with nozzles that do not have ball bearings, "silent bottles," or a tongue-tactile cue, i.e., water in bottles with nozzles that had ball bearings "noisy bottles") initially was used as the conditioned stimulus (CS1, i.e., the stimulus first followed by contingent administration of lithium chloride, and later, in Phase 2, followed by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed.