Lead exposure in adult males in urban Transvaal Province, South Africa during the apartheid era

Human exposure to lead is a substantial public health hazard worldwide and is particularly problematic in the Republic of South Africa given the country’s late cessation of leaded petrol. Lead exposure is associated with a number of serious health issues and diseases including developmental and cognitive deficiency, hypertension and heart disease. Understanding the distribution of lifetime lead burden within a given population is critical for reducing exposure rates. Femoral bone from 101 deceased adult males living in urban Transvaal Province (now Gauteng Province), South Africa between 1960 and 1998 were analyzed for lead concentration by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Of the 72 black and 29 white individuals sampled, chronic lead exposure was apparent in nearly all individuals. White males showed significantly higher median bone lead concentration (ME = 10.04 µg·g−1), than black males (ME = 3.80 µg·g−1) despite higher socioeconomic status. Bone lead concentration covaries significantly, though weakly, with individual age. There was no significant temporal trend in bone lead concentration. These results indicate that long-term low to moderate lead exposure is the historical norm among South African males. Unexpectedly, this research indicates that white males in the sample population were more highly exposed to lead

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts

Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain

Contains fulltext : 125235.pdf (publisher's version ) (Open Access)BACKGROUND: Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon. METHODS: For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants. RESULTS: We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression. CONCLUSIONS: We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function

Bearbeitungen

Intermediale Bearbeitungen der Texte Elfriede Jelineks: Dramatisierungen, Hörspiele, Musiktheater, Hörstücke, Tanzperformance, Michael Hanekes Film La pianiste (=Bearbeitungen von anderen

Spatial distribution of parasitism on Phyllocnistis citrella Stainton, 1856 (Lepidoptera: Gracillariidae) in citrus orchards

Many species of microhymenopterous parasitoids have been registered on Phyllocnistis citrella, the citrus leafminer. The present study aimed to identify the spatial distribution pattern of the native and introduced parasitoids of P. citrella in two citrus orchards in Montenegro, RS. The new shoots from 24 randomly selected trees in each orchard were inspected at the bottom (0-1.5 m) and top (1.5-2.5 m) stratum and had their position relative to the quadrants (North, South, East and West) registered at every 15 days from July/2002 to June/2003. The leaves with pupae were collected and kept isolated until the emergence of parasitoids or of the leaf miner; so, the sampling was biased towards parasitoids that emerge in the host pupal phase. The horizontal spatial distribution was evaluated testing the fitness of data to the Poisson and negative binomial distributions. In Montenegrina, there was no significant difference in the number of parasitoids and in the mean number of pupae found in the top and bottom strata (χ2 = 0.66; df = 1; P > 0.05) (χ2 = 0.27; df =1; P > 0.05), respectively. In relation to the quadrants, the highest average numbers of the leafminer pupae and of parasitoids were registered at the East quadrant (χ2 = 11.81; df = 3; P < 0.05), (χ2 = 10.36; df = 3; P < 0.05). In the Murcott orchard, a higher number of parasitoids was found at the top stratum (63.5%) (χ2 = 7.24; df =1 P < 0.05), the same occurring with the average number of P. citrella pupae (62.9%) (χ2 = 6.66; df = 1; P < 0.05). The highest number of parasitoids and of miners was registered at the North quadrant (χ2 = 19. 29; df = 3; P < 0.05), (χ2 = 4.39; df = 3; P < 0.05). In both orchards, there was no difference between the numbers of shoots either relative to the strata as well as to the quadrants. As the number of shoots did not varied much relative to the quadrants, it is possible that the higher number of miners and parasitoids in the East and West quadrants would be influenced by the higher solar exposure of these quadrants. The data of the horizontal spatial distribution of the parasitism fit to the negative binomial distribution in all sampling occasions, indicating an aggregated pattern