Expression-Based Cell Lineage Analysis in Drosophila Through a Course-Based Research Experience for Early Undergraduates.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Predictive value of current imaging modalities for the detection of urolithiasis during pregnancy: a multicenter, longitudinal study.

PURPOSE: We determined the optimal imaging study by which to diagnose and treat pregnant patients with suspected urolithiasis. MATERIALS AND METHODS: A retrospective, multicenter study was performed to determine the comparative accuracy of imaging modalities used before the surgical management of suspected urolithiasis in pregnant patients. Patients with a clinical suspicion of urolithiasis were evaluated with directed imaging including renal ultrasound alone, renal ultrasound and low dose computerized tomography, or renal ultrasound and magnetic resonance urography. When indicated, patients underwent therapeutic ureteroscopy. The rate of negative ureteroscopy was determined and the positive predictive values of the imaging modalities were calculated. RESULTS: A total of 51 pregnant patients underwent ureteroscopy. The mean age of the cohort was 27 years. Mean gestational age was 24.4 weeks. Of the women 24 (47%) underwent renal ultrasound and low dose computerized tomography, 22 (43%) underwent ultrasound alone, and 5 (10%) underwent renal ultrasound and magnetic resonance urography. Negative ureteroscopy occurred in 7 of the 51 patients (14%). The rate of negative ureteroscopy among patients who underwent renal ultrasound alone, renal ultrasound and low dose computerized tomography, and renal ultrasound and magnetic resonance urography was 23%, 4.2% and 20%, respectively. The positive predictive value of computerized tomography, magnetic resonance and ultrasound was 95.8%, 80% and 77%, respectively. CONCLUSIONS: The rate of negative ureteroscopy was 14% among pregnant women undergoing intervention in our series. Of the group treated surgically after imaging with ultrasound alone, 23% had no ureteral stone, resulting in the lowest positive predictive value of the modalities used. Alternative imaging techniques, particularly low dose computerized tomography, offer improved diagnostic information that can optimize management and obviate unnecessary intervention.

Obstetric complications of ureteroscopy during pregnancy.

PURPOSE: During pregnancy a ureteral stone and its management may pose risks for the mother and fetus. Definitive ureteroscopic management of an obstructing stone during pregnancy has been increasingly used without a reported increased incidence of urological complications. However, the rate of obstetric complications of ureteroscopy during pregnancy remains undefined. MATERIALS AND METHODS: Charts of pregnant women who had undergone ureteroscopy at 5 tertiary centers were reviewed. Patient and procedure characteristics were collected. Records were evaluated for the occurrence of obstetric complications in the postoperative period. RESULTS: A total of 46 procedures were performed in 45 patients at 5 institutions. There were 2 obstetric complications (4.3%), including 1 preterm labor managed conservatively and 1 preterm labor resulting in preterm delivery. There was no fetal loss. No statistically significant characteristics were identified differentiating those patients having obstetric complications. CONCLUSIONS: Ureteroscopy performed during pregnancy has been previously reported to be urologically safe and effective for addressing ureteral stones. In our multi-institutional series a 4% rate of obstetric complications was observed. Based on this risk a multidisciplinary approach is prudent for the pregnant patient undergoing ureteroscopy.

Effects of Exogenous and Endogenous Distracters on Immediate and Long-Term Recall in Toddlers.

We explored the role that exogenous and endogenous competitors for attention play in infants' abilities to encode and retain information over a 6-month period. Sixty-six children visited the laboratory at 15 months, and 32 returned for a second visit at 21 months. Children observed models of conventional- relation and enabling-relation action sequences. Half the children were distracted by a "Mister Monkey" mechanical toy during the conventional-relation sequence, while the other half was distracted during the enabling-relation sequence. The Early Childhood Behavior Questionnaire indexed endogenous factors at both ages. Immediate postmodel production of target actions indexed encoding efficiency, and 6-month production of target actions indexed long-term recall. The exogenous distracter impacted encoding efficiency (i.e., immediate recall), but not long-term recall. Endogenous factors (i.e., temperament) were primarily associated with long-term recall. Of special interest was our finding that endogenous factors, especially surgency, moderated the effect of the exogenous distracter. It appears that when learning conventional-relation sequences in the presence of exogenous distracters, surgency mobilizes attentional resources toward the learning objective; however, when learning enabling-relation sequences under the same conditions, surgency either boosts the saliency of the distracters or boosts children's susceptibility to them.

Emergency room management of ureteral calculi: current practices.

OBJECTIVE: To evaluate current practice patterns in U.S. emergency departments (EDs) for the diagnosis, treatment, and counseling of patients with ureteral calculi. METHODS: Hospital-based ED physicians were invited by e-mail to participate in a Survey-Monkey survey. E-mails were delivered in March 2008 by Direct Medical Data using a listserv provided by the American Medical Association. Of the e-mails sent, 173 e-mails were opened, and 135 physicians responded. Physicians were compensated with a $10 Amazon.com gift card. RESULTS: Ninety percent of ED physicians use noncontrast CT as their initial imaging modality, and 63% use alpha-blockers for medical expulsive therapy. Only 13% of evaluated EDs have guidelines for the management of renal colic, and only 58% of these guidelines that recommend the use of an alpha-blocker. Alpha-blocker use was more common with physicians who have been practicing fewer than 5 years (81%) compared with those with more than 10 years of experience (56%). The majority of physicians used ketorolac and morphine to achieve effective analgesia. Although the average responses concerning the chance of spontaneous stone passage for stones 4 mm (44%) were close to evidence-based values, great variation in the answers was noted (standard deviations: 12% and 22%, respectively). Indeed, 38% of respondents stated that stones 95% chance of passage. Twenty-eight percent of ED physicians would arrange follow-up with a primary care physician, while the remainder would arrange follow-up with a urologist. CONCLUSIONS: This study establishes a need for educational opportunities for ED physicians in the management of renal colic. The development of collaborative practice guidelines between urology and emergency medicine associations may be warranted.

Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in large-cell medulloblastoma.

The growth factor hepatocyte growth factor (HGF), also known as scatter factor, and its tyrosine kinase receptor c-Met play important roles in medulloblastoma malignancy. The transcription factor c-Myc is another contributor to the malignancy of these most common pediatric brain tumors. In the present study, we observed strong morphological similarities between medulloblastoma xenografts overexpressing HGF and medulloblastoma xenografts overexpressing c-Myc. We therefore hypothesized a biologically significant link between HGF/c-Met and c-Myc in medulloblastoma malignancy and studied the molecular and functional interactions between them. We found that HGF induces c-Myc mRNA and protein in established and primary medulloblastoma cells. HGF regulated c-Myc levels via transcriptional and post-transcriptional mechanisms as evidenced by HGF induction of c-Myc promoter activity and induction of c-Myc protein levels in the setting of inhibited transcription and translation. We also found that HGF induces cell cycle progression, cell proliferation, apoptosis and increase in cell size in a c-Myc-dependent manner. Activation of MAPK and PI3K, inhibition of GSK-3beta and translocation of beta-catenin to the nucleus as well as Tcf/Lef transcriptional activity were involved in mediating c-Myc induction by HGF. Induction of Cdk2 kinase activity was involved in mediating the cell cycle progression effects, and downregulation of Bcl-XL was involved in mediating the proapoptotic effects of HGF downstream of c-Myc. All molecules that mediated the effects of HGF on c-Myc expression, cell proliferation and apoptosis were expressed in human large-cell medulloblastoma tissues. We therefore established for the first time a functional cooperation between HGF/c-Met and c-Myc in human medulloblastoma and elucidated the molecular mechanisms of this cooperation. The findings provide a potential explanation for the high frequency of c-Myc overexpression in medulloblastoma and suggest a cooperative role for c-Met and c-Myc in large-cell anaplastic medulloblastoma formation.