An SVD-based comparison of nine whole eukaryotic genomes supports a coelomate rather than ecdysozoan lineage

BACKGROUND: Eukaryotic whole genome sequences are accumulating at an impressive rate. Effective methods for comparing multiple whole eukaryotic genomes on a large scale are needed. Most attempted solutions involve the production of large scale alignments, and many of these require a high stringency pre-screen for putative orthologs in order to reduce the effective size of the dataset and provide a reasonably high but unknown fraction of correctly aligned homologous sites for comparison. As an alternative, highly efficient methods that do not require the pre-alignment of operationally defined orthologs are also being explored. RESULTS: A non-alignment method based on the Singular Value Decomposition (SVD) was used to compare the predicted protein complement of nine whole eukaryotic genomes ranging from yeast to man. This analysis resulted in the simultaneous identification and definition of a large number of well conserved motifs and gene families, and produced a species tree supporting one of two conflicting hypotheses of metazoan relationships. CONCLUSIONS: Our SVD-based analysis of the entire protein complement of nine whole eukaryotic genomes suggests that highly conserved motifs and gene families can be identified and effectively compared in a single coherent definition space for the easy extraction of gene and species trees. While this occurs without the explicit definition of orthologs or homologous sites, the analysis can provide a basis for these definitions

Putting Teaching to the Test to the Test: Is This Really a Problem in Arkansas?

Arkansas’s state standardized tests have changed over the past few years. Since the ACTAAP legislation of 1999, Arkansas students have taken criterion-referenced Benchmark Tests based on the state’s curricular standards along with national norm-referenced exams each year. Prior to 2004, students in grades 4, 6, and 8 were administered the Benchmark tests in Mathematics and in English Language Arts. Starting in 2005, the odd-numbered grades were added so that students in grades 3-8 took the week-long Benchmark tests, in accordance with the requirements of the federal No Child Left Behind act

A survey of well conserved families of C2H2 zinc-finger genes in Daphnia

BACKGROUND: A recent comparative genomic analysis tentatively identified roughly 40 orthologous groups of C2H2 Zinc-finger proteins that are well conserved in "bilaterians" (i.e. worms, flies, and humans). Here we extend that analysis to include a second arthropod genome from the crustacean, Daphnia pulex. RESULTS: Most of the 40 orthologous groups of C2H2 zinc-finger proteins are represented by just one or two proteins within each of the previously surveyed species. Likewise, Daphnia were found to possess a similar number of orthologs for all of these small orthology groups. In contrast, the number of Sp/KLF homologs tends to be greater and to vary between species. Like the corresponding mammalian Sp/KLF proteins, most of the Drosophila and Daphnia homologs can be placed into one of three sub-groups: Class I-III. Daphnia were found to have three Class I proteins that roughly correspond to their Drosophila counterparts, dSP1, btd, CG5669, and three Class II proteins that roughly correspond to Luna, CG12029, CG9895. However, Daphnia have four additional KLF-Class II proteins that are most similar to the vertebrate KLF1/2/4 proteins, a subset not found in Drosophila. Two of these four proteins are encoded by genes linked in tandem. Daphnia also have three KLF-Class III members, one more than Drosophila. One of these is a likely Bteb2 homolog, while the other two correspond to Cabot and KLF13, a vertebrate homolog of Cabot. CONCLUSION: Consistent with their likely roles as fundamental determinants of bilaterian form and function, most of the 40 groups of C2H2 zinc-finger proteins are conserved in kind and number in Daphnia. However, the KLF family includes several additional genes that are most similar to genes present in vertebrates but missing in Drosophila

Authors' Response to Letter to the Editor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98450/1/end%2E2012%2E1527.pd

Long-term Outcomes of Immediate Versus Delayed Nephroureterectomy for Upper Tract Urothelial Carcinoma

Purpose: To compare immediate nephroureterectomy with delayed nephroureterectomy after a trial of nephron-sparing endoscopic surgery in patients who were treated initially at our institution from 1996 to 2004 for upper tract urothelial carcinoma. Patients were monitored for upper tract recurrences, metastases, cancer-specific and overall survival. Survival outcomes and perioperative measurements were compared between treatment groups. Results: Of 73 patients, 62 underwent immediate nephroureterectomy and 11 proceeded to nephroureterectomy after failed endoscopic management. Mean follow-up for all patients was 58 months and 75 months for patients who were alive at last follow-up. Patients treated initially with endoscopy averaged a surveillance procedure every 3.7 months and had a median delay to nephroureterectomy of 10 months. Perioperative measurements at time of nephroureterectomy did not differ between groups. Overall survival 5 years from initial resection in the delayed group and from nephroureterectomy in the immediate group was 64% and 59%, respectively; the corresponding 5-year cancer-specific and metastasis-free survival estimates were 91% vs 80% and 77% vs 73%, respectively (P>0.05). Pathologic progression from low to high-grade occurred in three of seven patients from the delayed group. Conclusions: Failure of endoscopic management necessitating nephroureterectomy does not appear to affect survival outcomes compared with immediate nephroureterectomy in patients with upper tract urothelial carcinoma. A trial of endoscopic management can be considered in patients with low-grade disease and a normal contralateral kidney. Endoscopy is a viable option when there are imperative indications for nephron sparing in the setting of high-grade disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90447/1/end-2E2011-2E0220.pd

Ureteral Stents for Impassable Ureteroscopy

Background: For the narrow ureter that will not accommodate a ureteroscope, it is common practice to place a ureteral stent, to allow subsequent ureteroscopy in the passively dilated ureter. Surprisingly, there are limited data on the effectiveness or safety of these maneuvers. Methods: We retrospectively analyzed patients managed with ureteral stent placement followed by another attempt at ureteroscopy after an initial attempt of flexible ureteroscopy failed because the ureteroscope would not pass up an otherwise normal ureter. Results: Of 41 patients with follow-up who underwent ureteral stenting for this reason, the ureteroscope passed with ease poststenting in 29 (71%) and there was continued resistance in 12. Of these 12 patients, the ureteroscopy was continued despite resistance in 9, while another stent was placed in the remaining 3. Of these three patients, the third attempt at ureteroscopy was successful in two, and further attempts at ureteroscopy were not made after the third attempt failed in one. With a mean overall follow-up of 32 months, two patients (5%) developed ureteral strictures. Both were among nine patients in whom repeat ureteroscopy was performed despite resistance, with a rate of obstruction of 22% in this subgroup. Overall, ureteral stenting allowed successful ureteroscopy in 98% of patients. Conclusions: Ureteral stenting with subsequent ureteroscopy is a successful and safe method of addressing a narrow ureter that initially does not allow passage of a flexible ureteroscope, as long as persistent subsequent attempts to insert the ureteroscope are made only if it passes easily.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140373/1/end.2012.0414.pd

Determination of aortic valve area in valvular aortic stenosis by direct measurement using intracardiac echocardiography: A comparison with the gorlin and continuity equations

AbstractObjectives. This study sought to 1) show that intracardiac echocardiography can allow direct measurement of the aortic valve area, and 2) compare the directly measured aortic valve area from intracardiac echocardiography with the calculated aortic valve area from the Gorlin and continuity equations.Background. Intracardiac echocardiography has been used in the descriptive evaluation of the aortic valve; however, direct measurement of the aortic valve area using this technique in a clinical setting has not been documented. Despite their theoretical and practical limitations, the Gorlin and continuity equations remain the current standard methods for determining the aortic valve orifice area.Methods. Seventeen patients underwent intracardiac echocardiography for direct measurement of the aortic valve area, including four patients studied both before and after valvuloplasty, for a total of 21 studies. Immediately after intracardiac echocardiography, hemodynamic data were obtained from transthoracic echocardiography and cardiac catheterization.Results. Adequate intracardiac echocardiographic images were obtained in 17 (81%) of 21 studies. The average aortic valve area (mean ± SD) determined by intracardiac echocardiography for the 13 studies in the Gorlin analysis group was 0.59 ± 0.18 cm2(range 0.37 to 1.01), and the average aortic valve area determined by the Gorlin equation was 0.62 ± 0.18 cm2(range 0.31 to 0.88). The average aortic valve area determined by intracardiac echocardiography for the 17 studies in the continuity analysis group was 0.66 ± 0.23 cm2(range 0.37 to 1.01), and that for the continuity equation was 0.62 ± 0.22 cm2(range 0.34 to 1.06). There was a significant correlation between the aortic valve area determined by intracardiac echocardiography and the aortic valve area calculated by the Gorlin (r = 0.78, p = 0.002) and continuity equations (r = 0.82, p < 0.0001).Conclusions. In the clinical setting, intracardiac echocardiography can directly measure the aortic valve area with an accuracy similar to the invasive and noninvasive methods currently used. This study demonstrates a new, quantitative use for intracardiac echocardiographic imaging with many potential clinical applications

Symptomatic Subcapsular and Perinephric Hematoma Following Ureteroscopic Lithotripsy for Renal Calculi

Objective: Ureteroscopic lithotripsy (URSL) is believed to be associated with less risk of symptomatic renal hematoma than extracorporeal shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL). We sought to document the rate of and risk factors for this rare complication following URSL for renal calculi. Methods: With Institutional Review Board approval, we reviewed 1087 cases of URSL performed between July 2009 and October 2012 for four surgeons. We identified cases for renal calculi complicated by symptomatic ?hematoma? by searching electronic medical records of patients undergoing URSL with a web-based search tool and cross-referencing with a departmental quality improvement database for postoperative complications. Chi-squared tests were used to assess risk factors. Results: Among 877 renal units exposed to URSL for renal calculi, 4 were complicated by symptomatic subcapsular hematomas (SH) and 3 by symptomatic perinephric hematomas (PH), yielding a 0.5% and 0.3% rate for each complication, respectively. Pain was the primary presenting symptom. Almost all cases presented within 24 to 48 hours postop. Two PH patients required postoperative blood transfusion. Four patients (two SH, two PH) were hospitalized for observation. Ureteral sheaths were used in two cases (one PH and one SH). There was no association with age, diabetes, body mass index (BMI), or operative duration (p-values all>0.05). However, hematoma did correlate with female gender, preoperative hypertension, preoperative ureteral stenting, intraoperative ureteral sheath use, and postoperative ureteral stenting (all p-values<0.0001). Conclusions: While symptomatic hematoma is a complication of URSL, the rate of such outcome (0.8%) is far less than that reported by prior series with SWL and PCNL. This may partially be attributable to collection biases, where subclinical cases are not imaged, or anchoring biases, where clinicians attribute symptoms to another possible etiology. This outcome can be morbid, but can often be conservatively managed with observation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140379/1/end.2014.0176.pd

Success of Ureteral Stents for Intrinsic Ureteral Obstruction

Purpose: Previous reports suggest a high success rate for retrograde ureteral stenting for intrinsic ureteral obstruction, but few preoperative predictors of success have been offered. We reviewed our experience to look for factors that suggest failure of stents for intrinsic ureteral obstruction. Materials and Methods: We retrospectively reviewed the outcome of retrograde ureteral stent placement for intrinsic ureteral obstruction without concurrent or intended definitive management of the obstruction. Results: Thirty-eight patients treated for intrinsic ureteral obstruction, representing 41 ureteral units (UUs), were monitored for an average of 25.5 months. The overall success rate was 88%. Of the successes, 13 UUs had definitive therapy to permanently remove the cause of obstruction, obstruction resolved in 12 UUs after stent placement, and 11 UUs were managed with indwelling stents. Therapy failed in five UUs, with a median time to failure of 1.9 months. Of the UUs in which failure occurred, three failures were caused by misdiagnosis; in the remaining two, the stent did not correct the obstruction. On univariate analysis, male sex (P = 0.006), increased creatinine level as a presenting symptom (P = 0.002), and more severe preoperative hydronephrosis (P = 0.042) were predictive of failure. Adverse events were low, with complications from stenting occurring on only four of 41 UUs. Conclusion: If initial stent placement was possible, intrinsic ureteral obstruction was managed successfully in 88% of patients. Given high success and minimal complications, retrograde placement of ureteral stents can be performed to treat patients with intrinsic ureteral obstruction. Treatment failure is more likely to occur in men and patients with severe hydronephrosis or an elevated creatinine level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63109/1/end.2007.0201.pd

Parasites lacking the micronemal protein MIC2 are deficient in surface attachment and host cell egress, but remain virulent in vivo

Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence. Results: We verified the role of MIC2 in efficient surface attachment, but were unable to identify any direct function of MIC2 in sustaining gliding motility or host cell invasion once initiated. Furthermore, we find that deletion of mic2 causes a slightly delayed infection in vivo, leading only to mild attenuation of virulence; like with wildtype parasites, inoculation with even low numbers of mic2 KO parasites causes lethal disease in mice. However, deletion of mic2 causes delayed host cell egress in vitro, possibly via disrupted signal transduction pathways. Conclusions: We confirm a critical role of MIC2 in parasite attachment to the surface, leading to reduced parasite motility and host cell invasion. However, MIC2 appears to not be critical for gliding motility or host cell invasion, since parasite speed during these processes is unaffected. Furthermore, deletion of MIC2 leads only to slight attenuation of the parasite