Interactions of inorganic oxide nanoparticles with sewage biosolids.

The use of nanoparticles (NPs) in manufacturing continues to increase despite the growing concern over their potential environmental and health effects. Understanding the interaction of NPs and sewage sludge is crucial for determining the ultimate fate of NPs released to municipal wastewater treatment plants (WWTPs) as those interactions will determine whether the bulk of the material is retained in the sludge or released in the effluent stream. Analyzing the affinity of aluminum oxide, cerium oxide, and silicon oxide NPs, which are commonly used in semiconductor manufacturing processes, for biosolids used in municipal WWTPs provides a basis for estimating their removal efficiency. Batch studies were performed and the NPs were shown to partition onto the cellular surface. At the maximum equilibrium values tested (75-92 mg nanoparticles/L), the concentration of Al(2)O(3), CeO(2) and SiO(2) associated with the sludge was 137, 238, and 28 mg/g-sludge VSS, respectively. These results suggest that electrostatic interactions play a major role in determining NP association with biosolids.

Triggering of nocturnal arrhythmias by sleep-disordered breathing events.

OBJECTIVES: This study sought to evaluate respiratory disturbances as potential triggers for arrhythmia in patients with sleep-disordered breathing (SDB). BACKGROUND: SDB is associated with an increased risk of atrial fibrillation and nonsustained ventricular tachycardia (NSVT) as well as a predilection for sudden cardiac death during nocturnal sleeping hours. However, prior research has not established whether respiratory disturbances operate as triggers for nocturnal arrhythmias. METHODS: Overnight polysomnograms from the Sleep Heart Health Study (n = 2,816) were screened for paroxysmal atrial fibrillation and NSVT. We used the case-crossover design to determine whether apneas and/or hypopneas are temporally associated with episodes of paroxysmal atrial fibrillation or NSVT. For each arrhythmia, 3 periods of sinus rhythm were identified as control intervals. Polysomnograms were examined for the presence of respiratory disturbances, oxygen desaturations, and cortical arousals within a 90-s hazard period preceding each arrhythmia or control period. RESULTS: Fifty-seven participants with a wide range of SDB contributed 62 arrhythmias (76% NSVT). The odds of an arrhythmia after a respiratory disturbance were nearly 18 times (odds ratio: 17.5; 95% confidence interval: 5.3 to 58.4) the odds of an arrhythmia occurring after normal breathing. The absolute rate of arrhythmia associated with respiratory disturbances was low (1 excess arrhythmia per 40,000 respiratory disturbances). Neither hypoxia nor electroencephalogram-defined arousals alone increased arrhythmia risk. CONCLUSIONS: Although the absolute arrhythmia rate is low, the relative risk of paroxysmal atrial fibrillation and NSVT during sleep is markedly increased shortly after a respiratory disturbance. These results support a direct temporal link between SDB events and the development of these arrhythmias.

Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.

Emery-Dreifuss muscular dystrophy (EDMD1) is caused by mutations in either the X-linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene. Here, we describe the derivation of mice lacking emerin in an attempt to derive a mouse model for EDMD1. Although mice lacking emerin show no overt pathology, muscle regeneration in these mice revealed defects. A bioinformatic array analysis of regenerating Emd null muscle revealed abnormalities in cell-cycle parameters and delayed myogenic differentiation, which were associated with perturbations to transcriptional pathways regulated by the retinoblastoma (Rb1) and MyoD genes. Temporal activation of MyoD transcriptional targets was significantly delayed, whereas targets of the Rb1/E2F transcriptional repressor complex remained inappropriately active. The inappropriate modulation of Rb1/MyoD transcriptional targets was associated with up-regulation of Rb1, MyoD and their co-activators/repressors transcripts, suggesting a compensatory effort to overcome a molecular block to differentiation at the myoblast/myotube transition during regeneration. This compensation appeared to be effective for MyoD transcriptional targets, although was less effective for Rb1 targets. Analysis of Rb1 phosphorylation states showed prolonged hyper-phosphorylation at key developmental stages in Emd null myogenic cells, both in vivo and in vitro. We also analyzed the same pathways in Lmna null muscle, which shows extensive dystrophy. Surprisingly, Lmna null muscle did not show the same perturbations to Rb- and MyoD-dependent pathways. We did observe increased transcriptional expression of Lap2alpha and delayed expression of Rb1, which may regulate alternative transcriptional pathways in the Lmna null myoblasts. We suggest that the dominant LMNA mutations seen in many clinically disparate laminopathies may similarly alter Rb function, with regard to either the timing of exit from the cell cycle or terminal differentiation programs or both.

Mutations in the mouse Lmna gene causing progeria, muscular dystrophy and cardiomyopathy.

At least ten different diseases have been linked to mutations in proteins associated with the nuclear envelope (NE). Eight of these diseases are associated with mutations in the lamin A gene (LMNA). These diseases include the premature ageing or progeric diseases Hutchinson-Gilford progeria and atypical Werner's syndrome, diseases affecting striated and cardiac muscle including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting white fat deposition and skeletal development and a peripheral neuropathy resulting in motor neuron demyelination. To understand how these diseases arise from different mutations in the same protein, we established mouse lines carrying some of the same mutations found in the human LMNA gene, as both mouse and human lamin genes show a very high degree of sequence conservation. We have generated mice with different mutations resulting in progeria, muscular dystrophy and dilated cardiomyopathy. Our mouse lines are providing novel insights into how changes to the nuclear lamina affect the mechanical integrity of the nucleus and in turn intracellular signalling, such as the NF-kappaB pathway, as well as cell proliferation and survival, cellular functions that, when disrupted, may be the basis for the origin of such diseases.