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Abstract Background Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients. Methods To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro. Results FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls. Conclusions Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.

Introduction: The UK General Dental Council (GDC) requires dental graduates to competently identify, manage and refer patients with dental pain and anxiety. This study aimed to explore sedation training experience quantitatively and qualitatively through individual reflective logs. Materials & Methods: A single-centred mixed-methods evaluation of teaching, within a UK university conscious sedation department. Fourth-year dental students undertook lectures and supervised clinical sessions following the undergraduate curriculum. Patient attendance patterns, individual experience and group experience were analysed descriptively. Reflective log sheets were analysed by Thematic Framework Analysis. Results: Seventy-two students participated. Of 153 booked patients, 79 (51.6%) attended of which 74 (48.4%) were treated by undergraduates. The mean performed inhalation sedation and intravenous sedation cases per student were 1 and 0.8, respectively. Three students (4%) assisted only. Group experience varied. Three themes arose from reflections: consolidation of theory and learning; confidence through experience; and responding to challenges. Discussion: Whilst experience quotas were not met, GDC requirements for increasing students' knowledge and confidence within CS were met. Practical experience enhanced learning. "Hands-on" experience was most valuable for self-reported confidence but learning by proxy also aided development. Students recognised challenges, but not the implications for themselves or their career. Strategies to reduce barriers to experience require research. Conclusion: Whilst variable, all students were provided learning opportunities. Physical experience gave the greatest confidence. Opportunities afforded by the undergraduate curriculum allowed students to learn and develop through consolidation of theory, response to challenges and ultimately the gaining of confidence. [ABSTRACT FROM AUTHOR]

Modeling has proposed that the amount of neural tissue folding is set by the level of differential-expansion between tissue layers and that the wavelength is set by the thickness of the outer layer. Here we used inbred mouse strains with distinct amounts of cerebellar folding to investigate these predictions. We identified a critical period where the folding amount diverges between the strains. In this period, regional changes in the level of differential-expansion between the external granule layer (EGL) and underlying core correlate with the folding amount in each strain. Additionally, the thickness of the EGL is regionally adjusted during the critical period alongside corresponding changes in wavelength. While the number of SHH-expressing Purkinje cells predicts the folding amount, the proliferation rate in the EGL is the same between the strains. However, regional changes in the cell division angle within the EGL predicts both the tangential-expansion and thickness of the EGL. Cell division angle is likely a tunable mechanism whereby both the level of differential-expansion and thickness of the EGL are regionally tuned to set the amount and wavelength of folding., Competing Interests: Competing Interests: The authors no competing or financial interests.