The quadruplex structures formed by guanine-rich nucleic acid sequences have received significant attention recently because of growing evidence for their role in important biological processes and ...as therapeutic targets. G-quadruplex DNA has been suggested to regulate DNA replication and may control cellular proliferation. Sequences capable of forming G-quadruplexes in the RNA have been shown to play significant roles in regulation of polyadenylation and splicing events in mammalian transcripts. Whether quadruplex structure directly plays a role in regulating RNA processing requires investigation. Computational approaches to study G-quadruplexes allow detailed analysis of mammalian genomes. There are no known easily accessible user-friendly tools that can compute G-quadruplexes in the nucleotide sequences. We have developed a web-based server, QGRS Mapper, that predicts quadruplex forming G-rich sequences (QGRS) in nucleotide sequences. It is a user-friendly application that provides many options for defining and studying G-quadruplexes. It performs analysis of the user provided genomic sequences, e.g. promoter and telomeric regions, as well as RNA sequences. It is also useful for predicting G-quadruplex structures in oligonucleotides. The program provides options to search and retrieve desired gene/nucleotide sequence entries from NCBI databases for mapping G-quadruplexes in the context of RNA processing sites. This feature is very useful for investigating the functional relevance of G-quadruplex structure, in particular its role in regulating the gene expression by alternative processing. In addition to providing data on composition and locations of QGRS relative to the processing sites in the pre-mRNA sequence, QGRS Mapper features interactive graphic representation of the data. The user can also use the graphics module to visualize QGRS distribution patterns among all the alternative RNA products of a gene simultaneously on a single screen. QGRS Mapper can be accessed at http://bioinformatics.ramapo.edu/QGRS/.
Purpose We assessed the effects of prostate size on long-term health related quality of life and functional outcomes after laparoscopic radical prostatectomy. Materials and Methods A total of 729 ...consecutive patients who underwent laparoscopic radical prostatectomy for localized prostate cancer were stratified by pathological prostate gland weight, including group 1—less than 35 gm, group 2—35 to 70 gm and group 3—greater than 70 gm. Urinary health related quality of life was assessed preoperatively and at regular intervals following laparoscopic radical prostatectomy using the validated Expanded Prostate Cancer Index Composite questionnaire. Results A total of 613 evaluable patients were studied with a mean age of 57.7 years, a preoperative prostate specific antigen of 6.0 ng/ml, a median preoperative and postoperative Gleason score of 6, and a mean pathological gland weight of 51.3 gm (range 13.4 to 145.7). Patients with the largest glands had significantly worse baseline urinary function, as demonstrated by Expanded Prostate Cancer Index Composite urinary domain summary (p <0.001) and subscale scores, including scores for urinary bother (p <0.001), urinary irritative/obstructive (p = 0.001) and urinary incontinence (p = 0.03). Patients in group 3 also had significantly older age, a higher body mass index, longer operative time and more blood loss (each p <0.05). Despite preoperative differences and possible confounders all groups approached similar urinary health related quality of life outcomes at all time points postoperatively. At 12 months patients with the largest glands had improved Expanded Prostate Cancer Index Composite urinary irritative/obstructive and urinary bother subscale scores compared to their baseline scores (p <0.05). Conclusions In laparoscopic radical prostatectomy despite preoperative differences increasing prostatic size is not associated with delayed or worse postoperative urinary health related quality of life. Furthermore, in patients with large glands an improvement in urinary irritative/obstructive and bother symptoms from baseline may be seen 12 months postoperatively.
Nucleic acids containing guanine tracts can form quadruplex structures via non-Watson-Crick base pairing. Formation of G-quadruplexes is associated with the regulation of important biological ...functions such as transcription, genetic instability, DNA repair, DNA replication, epigenetic mechanisms, regulation of translation, and alternative splicing. G-quadruplexes play important roles in human diseases and are being considered as targets for a variety of therapies. Identification of functional G-quadruplexes and the study of their overall distribution in genomes and transcriptomes is an important pursuit. Traditional computational methods map sequence motifs capable of forming G-quadruplexes but have difficulty in distinguishing motifs that occur by chance from ones which fold into G-quadruplexes.
We present Quadruplex forming 'G'-rich sequences (QGRS)-Conserve, a computational method for calculating motif conservation across exomes and supports filtering to provide researchers with more precise methods of studying G-quadruplex distribution patterns. Our method quantitatively evaluates conservation between quadruplexes found in homologous nucleotide sequences based on several motif structural characteristics. QGRS-Conserve also efficiently manages overlapping G-quadruplex sequences such that the resulting datasets can be analyzed effectively.
We have applied QGRS-Conserve to identify a large number of G-quadruplex motifs in the human exome conserved across several mammalian and non-mammalian species. We have successfully identified multiple homologs of many previously published G-quadruplexes that play post-transcriptional regulatory roles in human genes. Preliminary large-scale analysis identified many homologous G-quadruplexes in the 5'- and 3'-untranslated regions of mammalian species. An expectedly smaller set of G-quadruplex motifs was found to be conserved across larger phylogenetic distances. QGRS-Conserve provides means to build datasets that can be filtered and categorized in a variety of biological dimensions for more targeted studies in order to better understand the roles that G-quadruplexes play.
DSEF-1 protein selectively binds to a G-rich auxiliary sequence element which influences the efficiency of processing of the SV40 late polyadenylation signal. We have obtained cDNA clones of DSEF-1 ...using sequence information from tryptic peptides isolated from DSEF-1 protein purified from HeLa cells. DSEF-1 protein contains three RNA-binding motifs and is a member of the hnRNP H family of RNA-binding proteins. Recombinant DSEF-1 protein stimulated the efficiency of cleavage and polyadenylation in an AAUAAA-dependent manner in in vitro reconstitution assays. DSEF-1 protein was shown to be able to interact with several poly(A) signals that lacked a G-rich binding site using a less stringent, low ionic strength gel band shift assay. Recombinant DSEF-1 protein specifically stimulated the processing of all of the poly(A) signals tested that contained a high affinity G-rich or low affinity binding site. DSEF-1 specifically increased the level of crosslinking of the 64 kDa protein of CstF to polyadenylation substrate RNAs. These observations suggest that DSEF-1 is an auxiliary factor that assists in the assembly of the general 3′-end processing factors onto the core elements of the polyadenylation signal.
The codesign of an impulse generator and miniaturized antennas for ultra-wideband impulse radio is described. The impulse generator, discussed by Bragga in 2004, is designed with differential outputs ...that are fed to the antenna, producing an optimum match of the generator to the antenna, an improved magnitude response, and reduced ringing of the radiated pulse. The impulse generator is preceded by a programmable pulse-position modulator and consists of a triangular pulse generator and a cascade of complex first-order systems, which, in turn, are made up of differential pairs employing partial positive feedback to approximate a Gaussian monocycle waveform. The complete pulse generator is fabricated in IBM 0.18-/spl mu/m Bi-CMOS IC technology. Measurements show the correct operation of the circuit for supply voltages of 1.8 V and a power consumption of 45 mW. The output pulse approximates the Gaussian monocycle having a pulse duration of about 375 ps. Proper modulation of the pulse in time is confirmed. A number of antennas with differentially fed baluns and input impedances of 100 /spl Omega/ have been designed. From measurements, it can be seen that ringing is considerably smaller as compared to conventionally fed antennas.
Purpose Improved bladder and renal management benefit patients with congenital uropathy and congenital pediatric kidney disease. This may translate to delayed initial renal transplantation in these ...patients, and improved graft and patient survival. Our primary study purpose was to determine whether patients with congenital uropathy and congenital pediatric kidney disease have demonstrated later time to first transplantation and/or graft survival. Materials and Methods SRTR (Scientific Registry of Transplant Recipients) was analyzed for first renal transplant and survival data in patients with congenital uropathy and congenital pediatric kidney disease from 1996 to 2012. Congenital uropathy included chronic pyelonephritis/reflux, prune belly syndrome and congenital obstructive uropathy. Congenital pediatric kidney disease included polycystic kidney disease, hypoplasia, dysplasia, dysgenesis, agenesis and familial nephropathy. Results A total of 7,088 patients with congenital uropathy and 24,315 with congenital pediatric kidney disease received a first renal transplant from 1996 to 2012. A significant shift was seen in both groups toward older age at initial renal transplantation in those 18 through 64 years old. In the congenital uropathy group this effect was most facilitated by decreased renal transplantion in patients between 18 and 35 years old (38% in 1996 vs 26% in 2012). The congenital pediatric kidney disease group showed a substantial decrease in patients who were 35 to 49 years old (from 39% to 29%). At 10-year followup the congenital uropathy group showed better graft and patient survival than the congenital pediatric kidney disease group. However, aged matched comparison revealed comparable survival rates in the 2 groups. Conclusions Analysis of trends in the last 14 years demonstrated that patients with both lower and upper tract congenital anomalies experienced delayed time to the first renal transplant. Furthermore, patients had similar age matched graft and patient survival whether the primary source of renal demise was the congenital lower or upper tract. These findings may indicate that improved urological and nephrological care are promoting renal preservation in both groups.
We retrospectively compared the oncological adequacy of laparoscopic partial nephrectomy to that of open partial nephrectomy in the treatment of patients with pathological stage T1N0M0 renal cell ...carcinoma.
A total of 143 patients with stage T1N0M0 renal tumors confirmed by pathological examination of the surgical specimen underwent partial nephrectomy between January 1996 and June 2004 with a followup of at least 1.5 years. Of these patients 85 were treated laparoscopically and the remaining 58 underwent open surgery. Medical and operative records were retrospectively reviewed with emphasis on tumor recurrence and survival. Statistical analysis was performed using Kaplan-Meier analysis.
The mean followup for the laparoscopy group was 40.4 +/- 18.0 months. A total of 83 patients survived. Of these patients 2 patients experienced disease recurrence within 18 to 46.2 months, 1 patient died of cancer metastasis to brain within 29.7 months and 1 died of an unrelated cause. Seeding of the port sites did not develop in any of the patients. The 5-year disease-free and actuarial survival rates for this group were 91.4%, and 93.8%, respectively. The 58 patients who underwent open surgery had a mean followup of 49.68 +/- 28.84 months. A total of 53 patients survived without any disease recurrence, 1 survived with recurrence within 8 months, 1 survived with metastasis within 49 months and 3 died of unrelated causes. The 5-year disease-free and patient survival rates for this group were 97.6% and 95.8%, respectively. Kaplan-Meier disease-free survival and patient survival analysis revealed no significant differences between the laparoscopic and open partial nephrectomy groups.
Laparoscopic partial nephrectomy is an alternative technique with mid-range oncological results comparable to open partial nephrectomy in patients with localized pathological stage T1N0M0 renal cell carcinoma.