Didactic lessons are only one part of the multimodal teaching strategies used in gross anatomy courses today. Increased emphasis is placed on providing more opportunities for students to develop lifelong learning and critical thinking skills during medical training. In a pilot program designed to promote more engaged and independent learning in anatomy, self‐study modules were introduced to supplement human gross anatomy instruction at Joan C. Edwards School of Medicine at Marshall University. Modules use three‐dimensional constructs to help students understand complex anatomical regions. Resources are self‐contained in portable bins and are accessible at any time. Students use modules individually or in groups in a structured self‐study format that augments material presented in lecture and laboratory. Pilot outcome data, measured by feedback surveys and examination performance statistics, suggest that the activity may be improving learning in gross anatomy. Positive feedback on both pre‐ and post‐examination surveys showed that students felt the activity helped to increase their understanding of the topic. In concordance with student perception, average examination scores on module‐related laboratory and lecture questions were higher in the two years of the pilot program compared with the year before its initiation. Modules can be fabricated on a modest budget using minimal resources, making implementation practical for smaller institutions. Upper level medical students assist in module design and upkeep, enabling continuous opportunities for vertical integration across the curriculum. This resource offers a feasible mechanism for enhancing independent and lifelong learning competencies, which could be a valuable complement to any gross anatomy curriculum. Anat Sci Educ 7: 406–416. © 2014 American Association of Anatomists.

Testicular cancer is the most common malignancy affecting young men ages 15 to 35. Although highly treatable if detected at an early stage, patients with metastases at the time of initial diagnosis have a poor prognosis for survival. Our previous studies of the role of the SKI gene in testicular cancer indicate that loss of SKI function promotes a metastatic phenotype in cell lines derived from testicular germ cell tumors. Germ cell tumors commonly metastasize to the retroperitonal lymph nodes and lung. Metastases can also occur in liver, brain and bone, and more rarely in kidney. In this study we hypothesized that cells in tissues associated with metastatic disease produce factors that promote the migration of testicular cancer cells to these sites. We used the Matigel invasion assay to determine whether the migration of our previously established SKI knockdown NCCIT cells (sh-SKI NCCIT) and control NCCIT cells (sh-NC NCCIT) is enhanced by factors secreted by cell lines of brain and kidney origin. C8D1A cells, derived from mouse cerebellum and exhibiting properties of astrocytes, normal rat kidney epithelial cells (NRK), and NIH-3T3 mouse fibroblasts were grown in six well culture dishes in low serum medium for 48 hours. Matrigel coated invasion chambers containing the sh-SKI NCCIT or sh-NC NCCIT cells were then placed in the wells. Wells containing only low serum medium were used as a control. After 24 hours, the numbers of NCCIT cells migrating through the Matrigel coated membrane were counted. SKI knockdown cells exhibited significantly increased migration when grown in the presence of C8D1A, NRK, and NIH-3T3 compared to medium alone. The migration of the control sh-NC NCCIT cell line was not significantly increased by the presence of any of the other cell lines. These data suggest that cells derived from brain and kidney, as well as fibroblasts, produce chemokines that can attract cancer cells to metastasize to these sites and that in the absence of SKI function, testicular cancer cells have an increased ability to respond to these signaling molecules. One candidate chemokine that has been shown to play a role in germ cell migration is stromal derived factor 1 (SDF1/CXCL12). We investigated whether SDF1 could increase sh-SKI NCCIT cell migration using the Matrigel invasion assay. SDF1 was added to the low serum medium in the lower chamber and migration of sh-SKI NCCITand sh-NC NCCIT cells was measured after 24 h. The migration of sh-SKI NCCIT cells increased slightly, but significantly, in the presence of SDF1 compared to cells not treated with SDF1. This effect was blocked by the simultaneous addition of AMD 3100, a specific inhibitor of CXCR4--the receptor for SDF1. The migration of the sh-NC NCCIT cells was not affected by either treatment. The data support the hypothesis that cells at sites distant from the primary tumors secrete factors that promote the metastasis of germ cell tumors to specific organs and suggest that SDF1 is at least one such factor. (This work supported by COBRE grant 1P20 RR020180 and a WV EPSCoR NASA Space Grant Consortium Graduate Student Fellowship to ANN.) (poster)

Mammalian spermatogenesis is precisely regulated by many germ cell-specific factors. In search for such a germ cell-specific factor, we have identified a novel mouse gene testis-specific factor 1 (TESF-1). Messenger RNA of TESF-1 was found only in the testis and its expression appeared to be regulated in a developmental manner. Further analysis demonstrated that the expression of TESF-1 was specifically in male germ cells, supported by the observation that we were not able to detect the TESF-1 mRNA from at/at homozygous mutant testes, which lack germ cells. The deduced amino acid sequence of TESF-1 contains a leucine-zipper motif, a potential nuclear localization signal, and two cAMP- and cGMP-dependent protein kinase phosphorylation sites. The green fluorescent protein (GFP)-tagged TESF-1 fusion protein was expressed in COS-7 cells and localized primarily in the nucleus. Taken together, these results indicate that TESF-1 is a novel male germ cell-specific gene, and its protein product may function as a nuclear factor involved in the regulation of spermatogenesis.

The Niemann-Pick C1 (NPC1) gene encodes for a multiple membrane spanning protein, which regulates the trafficking of low-density lipoprotein-mediated endocytosed cholesterol. Mutation of the human NPC1 gene causes Niemann-Pick type C (NPC) disease. The Npc1(NIH) mice, a model of human NPC disease, bear a spontaneous mutation of the Npc1 gene, and are infertile. In this study, we have performed sperm analysis to search for the cause of male infertility in the Npc1(NIH) mouse. The number of cauda sperms in Npc1(-/-) mice was decreased roughly three-and-half-fold of that in wild-type mice. The decreased sperm number in Npc1(-/-) mice is due, at least in part, to partial arrest of spermatogenesis in the testes, as revealed by histological analysis. Compared to wild-type sperm, Npc1(-/-) sperm displayed a high frequency of morphological abnormalities, including tailless heads and aberrant heads. In the in vitro fertilization (IVF) assay using cumulus-intact eggs, Npc1(-/-) sperm failed to produce two-cell embryos. In the IVF assay where zona-free eggs were used, Npc1(-/-) sperm bound normally but could not fuse with the egg. Further analysis indicated that Npc1(-/-) sperms are drastically impaired in the binding to the egg zona pellucida, only 14% of the level of wildtype sperm. Moreover, on Npc1(-/-) cauda sperm, one-third of the total cyritestin protein was not proteolytically processed, while fertilin beta was processed normally. Taken together, these results demonstrate that there are multiple defects in sperms from mice lacking a functional NPC1 protein, and these observed sperm defects may result in sterility.

While a first-year doctoral student in Instructional Technology and Distance Education at Nova Southeastern University, the writer chose to analyse, redesign and implement the redesign of her school's website page in partial fulfilment of requirements for ITDE 7005, Multimedia and Technology. The writer found the multimedia assignment an opportunity to learn how to begin to transform the static, mainly public relations school website, into a lively medium with current school information that could revolutionize and greatly improve school communications. The desired by-product of this improved communications was time-savings through a better-informed school community.

As the initiator of DNA double-strand breaks during meiosis in Saccharomyces cerevisiae, the SPO11 protein is essential for recombination. Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialization of a DNA cleavage function for meiotic recombination, To determine whether this extends to mammals, we isolated and characterized mouse and human SPO11 cDNAs, Mammalian SPO11 genes were found to be expressed at high levels only in testis, wherein mouse Spell transcript is restricted primarily to meiotic germ cells and is maximally expressed at mid-pachynema, Mouse Spell is located near the distal end of chromosome 2, while human SPO11 is found in the homologous position of chromosome 20q13.2-13.3, a region that is amplified in some breast cancers. Sequence homology and differential expression together support a highly conserved role for SPO11 in the enzymatic cleavage of DNA that accompanies meiotic recombination, (C) 1999 Federation of European Biochemical Societies.

As the initiator of DNA double-strand breaks during meiosis in Saccharomyces cerevisiae, the SPO11 protein is essential for recombination. Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialization of a DNA cleavage function for meiotic recombination. To determine whether this extends to mammals, we isolated and characterized mouse and human SPO11 cDNAs. Mammalian SPO11 genes were found to be expressed at high levels only in testis, wherein mouse Spo11 transcript is restricted primarily to meiotic germ cells and is maximally expressed at midpachynema. Mouse Spo11 is located near the distal end of chromosome 2, while human SPO11 is found in the homologous position of chromosome 20q13.2-13.3, a region that is amplified in some breast cancers. Sequence homology and differential expression together support a highly conserved role for SPO11 in the enzymatic cleavage of DNA that accompanies meiotic recombination.

As the initiator of DNA double‐strand breaks during meiosis in Saccharomyces cerevisiae, the SPO11 protein is essential for recombination. Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialization of a DNA cleavage function for meiotic recombination. To determine whether this extends to mammals, we isolated and characterized mouse and human SPO11 cDNAs. Mammalian SPO11 genes were found to be expressed at high levels only in testis, wherein mouse Spo11 transcript is restricted primarily to meiotic germ cells and is maximally expressed at mid‐pachynema. Mouse Spo11 is located near the distal end of chromosome 2, while human SPO11 is found in the homologous position of chromosome 20q13.2–13.3, a region that is amplified in some breast cancers. Sequence homology and differential expression together support a highly conserved role for SPO11 in the enzymatic cleavage of DNA that accompanies meiotic recombination.

The human XPF protein, an endonuclease subunit essential for DNA excision repair, may also function in homologous recombination. To investigate a possible link between mammalian XPF and recombination that occurs during meiosis, we isolated, characterized, and determined an expression profile for the mouse Xpf gene. The predicted mouse XPF protein, encoded by a 3.4-kb cDNA, contains 917 amino acids and is 86% identical to human XPF. Appreciable similarity also exists between mouse XPF and homologous proteins in budding yeast (Rad1), fission yeast (Rad16), and fruit fly (Mei-9), all of which have dual functions in excision repair and recombination. Sequence analysis of the 38.3-kb Xpf gene, localized to a region in proximal mouse chromosome 16, revealed greater than 72% identity to human XPF in 16 regions. Of these conserved elements, 11 were exons and 5 were noncoding sequence within introns. Xpf transcript and protein levels were specifically elevated in adult mouse testis. Moreover, increased levels of Xpf and Ercc1 mRNAs correlated with meiotic and early postmeiotic spermatogenic cells. These results support a distinct role for the XPF/ERCC1 junction-specific endonuclease during meiosis, most likely in the resolution of heteroduplex intermediates that arise during recombination.