β-arrestin regulates estradiol membrane-initiated signaling in hypothalamic neurons.

Estradiol (E2) action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS). E2 regulates membrane estrogen receptor-α (ERα) levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH), membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2) in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN) into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001). These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity

Case report: Metaplastic carcinoma presenting as a breast abscess

Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of epithelial and mesenchymal elements. The epithelial component is usually ductal carcinoma but may include other variants of breast carcinomas including squamous carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of comparable ductal carcinoma. This is the case of a 57 year old patient with MBC presenting with a breast abscess. A thorough literature search has not revealed any previous reports of MBC presenting as a breast abscess

A Comparison of Perceptions of Knowledge and Skills Held by Primary and Secondary Teachers: From the Entry to Exit of Their Preservice Programme

The purpose of this study was to investigate if there were differences in the levels of pedagogical knowledge and skills as perceived by the student teachers who were enrolled in the Primary and the Secondary Post Graduate Diploma in Education programme at the National Institute of Education in Singapore. 170 Primary and 426 Secondary student teachers participated in the study. The results showed that there were no significant differences at the beginning of the programme between the two cohorts. However, there were significant differences between the two groups at the end of programme, with the Primary student teachers tending to perceive themselves as gaining more pedagogical knowledge and skills by the end of their initial teacher preparation programme than the Secondary student teachers

Career decision making in undergraduate medical education

Background: It is unclear how medical students prioritize different factors when selecting a specialty. With rising under and unemployment rates a novel approach to career counselling is becoming increasingly important.  A better understanding of specialty selection could lead to improved career satisfaction amongst graduates while also meeting the health care needs of Canadians.  Methods: Medical students from the University of Toronto participated in a two-phase study looking at factors impacting specialty selection. Phase I consisted of focus groups, conducted independently for each year, and Phase II was a 21-question electronic survey sent to all students.  Results: Twenty-one students participated in the focus group phase and 95 in the survey phase.  Primary themes related to career selection identified in Phase I in order of frequency included personal life factors (36), professional life factors (36), passion/interest (20), changing interests (19) and hidden curriculum (15). The survey phase had similar results with passion (83), lifestyle (79), flexibility (75), employment opportunities (60) and family (50) being ranked as the factors most important in specialty selection. Conclusion: Personal factors, professional factors and passion/interest may be key themes for medical students when deciding which specialty to pursue. Targeting career counselling around these areas may be important.&nbsp

A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 A resolution.

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like ('Johnson') for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001

PATIENT SATISFACTION AND DIETARY OUTCOMES FROM ATTENDING A MULTIDISCIPLINARY CYSTINURIA CLINIC

Cystinuria is a genetic disease that leads to frequent cystine stone formation. A reduced methionine (precursor to cystine) diet has been recommended for cystinuria patients, involving maintenance of healthy weight, limiting intake of animal protein and salt whilst increasing vegetable protein, fruit, vegetables and fluid intake. The ability of patients to adhere to these dietary regimes has been questioned. We evaluated the dietetic service and dietary changes within our multidisciplinary cystinuria clinic using food frequency questionnaires (ffqs), dietary change questionnaires (dcqs) and diet histories. Most patients were seen by the dietitian 6–12 monthly.100% of patients felt they benefited from dietetic input. There was a move away from ffqs due to them being difficult and cumbersome to complete. Dcqs and diet histories revealed 23/28 increased fruit and vegetable intake, 20/28 decreased salt intake, 20/28 decreased animal protein intake, 14/28 increased vegetable protein intake and 9/28 increased fluid intake. There were a few discrepancies in reported change between dcqs and diet histories, supporting the use of multi-source feedback for diet analysis.Patients had varying degrees of success with making changes to each dietary parameter. Multi-source diet analysis allowed us to develop tailored consultations. All patients made some positive dietary changes which may help prevent stone formation. The areas of least change were fluid (due to changes made prior to clinic attendance) and vegetable protein. Our results support the need for continued dietetic input. These results should be re-audited to check that patients are maintaining the changes made