Structured inquiry-based learning: Drosophila GAL4 enhancer trap characterization in an undergraduate laboratory course.

We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)

Left ventricular pseudoaneurysm following atrioventricular groove rupture after mitral valve replacement

Left ventricular pseudoaneurysm is a partial cardiac rupture, contained by the surrounding pericardium that maintains communication with the left ventricular lumen. Whereas most cases of left ventricular pseudoaneurysms are related to myocardial infarction (loss of myocardial integrity), only a handful are associated with valve surgery. We present a female patient, who was admitted for elective mitral valve replacement. After the implantation of the mechanical valve, we encountered a rupture of the atrioventricular groove. After 3 months, a left ventricular pseudoaneurysm was found and the patient was reoperated. The valve was explanted and the inspection of the annulus and previously implanted pericardial patch revealed a loosened stitch on the inferior (ventricular) side. The defect was reinforced with additional stitches and the valve was reimplanted. In conclusion, we report an unusual case with two serious complications after mitral valve replacement – atrioventricular groove rupture and left ventricular pseudoaneurysm

Veno-arterial extracorporeal membrane oxygenation for post-infarction ventricular septal defect in a low-volume center

Managing patients with post-ischaemic ventricular septal defects (VSD) and postcardiotomy cardiogenic shock can be extremely challenging in a low-volume cardiac surgery unit. We present a case of a 68-year-old patient who received veno-arterial extracorporeal membrane oxygenation support due to cardiogenic shock after VSD repair. The patient was successfully weaned off support after 86 h. In the postoperative period, mediastinitis occurred, and negative pressure wound therapy was instituted

Veno-arterial extracorporeal membrane oxygenation for post-infarction ventricular septal defect in a low-volume center

Managing patients with post-ischaemic ventricular septal defects (VSD) and postcardiotomy cardiogenic shock can be extremely challenging in a low-volume cardiac surgery unit. We present a case of a 68-year-old patient who received veno-arterial extracorporeal membrane oxygenation support due to cardiogenic shock after VSD repair. The patient was successfully weaned off support after 86 h. In the postoperative period, mediastinitis occurred, and negative pressure wound therapy was instituted

Soft-x-ray-induced ionization and fragmentation dynamics of Sc3N@C80 investigated using an ion-ion-coincidence momentum-imaging technique

Citation: Xiong, H., Obaid, R., Fang, L., Bomme, C., Kling, N. G., Ablikim, U., … Berrah, N. (2017). Soft-x-ray-induced ionization and fragmentation dynamics of ${\mathrm{Sc}}_{3}\mathrm{N}@{\mathrm{C}}_{80}$ investigated using an ion-ion-coincidence momentum-imaging technique. Physical Review A, 96(3), 033408. https://doi.org/10.1103/PhysRevA.96.033408The fragmentation dynamics of an endohedral fullerene, Sc3N@C80, after absorption of a soft-x-ray photon, has been studied with an ion-ion-coincidence momentum-imaging technique. Molecular inner-shell ionization at 406.5 eV, targeting the Sc (2p) shell of the encapsulated Sc3N moiety and the C (1s) shell of the C80 cage, leads to the cage fragmentation through evaporation of C2, emission of small molecular carbon ions (Cn+, n≤24), and release of Sc and Sc-containing ions associated with the carbon cage opening or fragmentation. The predominant charge states of Sc and Sc-containing ionic fragments are +1 despite an effective Sc valence of 2.4, indicating that charge transfer or redistribution plays an important role in the fragmentation of the encaged Sc3N. Sequential emission of two out of the three Sc atoms of the encaged moiety, via Coulomb explosion in the form of Sc+ or Sc-containing ions, is significant. We also find that the resonant excitation of the Sc (2p) shell electrons significantly increased the yield of the parent Sc3N@C80 and its fragment ions, partially attributed to the collision of the energetic Auger electrons from the Sc site with the carbon cage

Reactivity of Aromatic Radical Cations. Rate Constants for Reactions of 9-Phenyl- and 9,10-Diphenylanthracene Radical Cations with Acyclic Amines

Peer reviewed: YesNRC publication: Ye

Odanacatib in the Treatment of Postmenopausal Women With Low Bone Mineral Density: Three-Year Continued Therapy and Resolution of Effect

The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased bone-resorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1-year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T-scores between −2.0 and −3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n = 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross-linked N-telopeptide of type I collagen (NTx) remained suppressed at year 3 (−50.5%), but bone-specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse-event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone-resorption markers remained suppressed, whereas bone-formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation

Structured Inquiry-Based Learning: Drosophila GAL4 Enhancer Trap Characterization in an Undergraduate Laboratory Course

We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community