Subregional Hippocampal Thickness Abnormalities in Older Adults with a History of Heavy Cannabis Use.

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology. Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB- group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use. Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p<0.0001], and in the entire HC averaged over all subregions [F(1,42)=8.49, p=0.006]. Conclusions: Negative effects of chronic adolescent CB use on hippocampal structure are maintained well into late life. Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage. Clinical Trial Registration: ClinicalTrials.gov # NCT01874886

HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia

Preeclampsia is a multi-system disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 weeks of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 236 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. Whilst general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30 ± 0.9 fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88 ± 2.24 fold change). We have identified that HLA-A is up-regulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is up-regulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia

Differential expression of microRNA-206 and its target genes in pre-eclampsia

Objectives: Pre-eclampsia is a multi-system disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with pre-eclampsia. Methods: Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed pre-eclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with pre-eclampsia matched with 19 women with normotensive pregnancies. Results: From the microarray, we identified 1 miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and 6 miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation only one, miR-206, was found to be significantly increased in 28 week samples in women who later developed pre-eclampsia (1.4 fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with pre-eclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be down-regulated (0.41 ± 0.04) in placental tissue from women with pre-eclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. Conclusions: Our pilot study has identified miRNA-206 as a novel factor up-regulated in pre-eclampsia within the maternal circulation and in placental tissue

Mulat-estetiek: ’n Analise van Adam Small se dramas

Opsomming In hierdie artikel word die dramakonvensies van Adam Small ondersoek met besondere aandag aan perspektiewe op die mulat as ’n sosiale gegewe. Hierdie element bied ’n gepaste invalshoek omdat dit enersyds ‘n verskynsel is wat Small in sy dramas en ander skryfwerk aansny en daar andersyds ’n uitgebreide literatuur bestaan waarin oor die dramatiese, lewensbeskoulike en literêr-teoretiese inkleding daarvan besin word. Die werk van onder andere Langston Hughes en Derek Walcott word ondersoek om ’n leesstrategie te ontwikkel waarmee die Small-teks geanaliseer kan word.Web of Scienc

In Vivo Calcium Imaging of Cardiomyocytes in the Beating Mouse Heart With Multiphoton Microscopy

Background: Understanding the microscopic dynamics of the beating heart has been challenging due to the technical nature of imaging with micrometer resolution while the heart moves. The development of multiphoton microscopy has made in vivo, cell-resolved measurements of calcium dynamics and vascular function possible in motionless organs such as the brain. In heart, however, studies of in vivo interactions between cells and the native microenvironment are behind other organ systems. Our goal was to develop methods for intravital imaging of cardiac structural and calcium dynamics with microscopic resolution.Methods: Ventilated mice expressing GCaMP6f, a genetically encoded calcium indicator, received a thoracotomy to provide optical access to the heart. Vasculature was labeled with an injection of dextran-labeled dye. The heart was partially stabilized by a titanium probe with a glass window. Images were acquired at 30 frames per second with spontaneous heartbeat and continuously running, ventilated breathing. The data were reconstructed into three-dimensional volumes showing tissue structure, vasculature, and GCaMP6f signal in cardiomyocytes as a function of both the cardiac and respiratory cycle.Results: We demonstrated the capability to simultaneously measure calcium transients, vessel size, and tissue displacement in three dimensions with micrometer resolution. Reconstruction at various combinations of cardiac and respiratory phase enabled measurement of regional and single-cell cardiomyocyte calcium transients (GCaMP6f fluorescence). GCaMP6f fluorescence transients in individual, aberrantly firing cardiomyocytes were also quantified. Comparisons of calcium dynamics (rise-time and tau) at varying positions within the ventricle wall showed no significant depth dependence.Conclusion: This method enables studies of coupling between contraction and excitation during physiological blood perfusion and breathing at high spatiotemporal resolution. These capabilities could lead to a new understanding of normal and disease function of cardiac cells

Mitigation of atmospheric perturbations and solid Earth movements in a TerraSAR-X time-series

The TerraSAR-X (TSX) synthetic aperture radar (SAR) marks the recent emergence of a new generation of spaceborne radar sensors that can for the first time lay claim to localization accuracies in the sub-meter range. The TSX platform’s extremely high orbital stability and the sensor’s hardware timing accuracy combine to enable direct measurements of atmospheric refraction and solid Earth movements. By modeling these effects for individual TSX acquisitions, absolute pixel geolocation accuracy on the order of several centimeters can be achieved without need for even a single tiepoint. A 16-month time series of images was obtained over a fixed test site, making it possible to validate both an atmospheric refraction and a solid Earth tide model, while at the same time establishing the instrument’s long-term stability. These related goals were achieved by placing trihedral corner reflectors (CRs) at the test site and estimating their phase centers with centimeter-level accuracy using differential GPS (DGPS). Oriented in pairs toward a given satellite track, the CRs could be seen as bright “points” in the images, providing a geometric reference set. SAR images from the high-resolution spotlight (HS) mode were obtained in alternating ascending and descending orbit configurations. The highest-resolution products were selected for their small sample dimensions, as positions can be more precisely determined. Based on the delivered product annotations, the CR image positions were predicted, and these predictions were compared with their measured image positions both before and after compensation for atmospheric refraction and systematic solid Earth deviations. It was possible to show that when the atmospheric distortion and Earth tides are taken into account, the TSX HS products have geolocation accuracies far exceeding the specified requirements. Furthermore, this accuracy was maintained for the duration of the 16-month test period. It could be demonstrated that with a correctly calibrated sensor, and after accounting for atmospheric and tidal effects, tiepoint-free geolocation is possible with TSX with an absolute product accuracy of about 5 cm