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Biomedical subjects

David Lee

Publications and source records attributed to David Lee.

At least 73 records · Page 4Linked to original sources

Needle-based ablation of renal parenchyma using microwave, cryoablation, impedance- and temperature-based monopolar and bipolar radiofrequency, and liquid and gel chemoablation: laboratory studies and review of the literature.

BACKGROUND AND PURPOSE: Small renal tumors are often serendipitously detected during the screening of patients for renal or other disease entities. Rather than perform a radical or partial nephrectomy for these diminutive lesions, several centers have begun to explore a variety of ablative energy sources that could be applied directly via a percutaneously placed needle-like probe. To evaluate the utility of such treatment for small renal tumors/masses, we compared the feasibility, regularity (consistency in size and shape), and reproducibility of necrosis produced in normal porcine kidneys by different modes of tissue ablation: microwaves, cold impedance-based and temperature-based radiofrequency (RF) energy (monopolar and bipolar), and chemical. Chemoablation was accomplished using ethanol gel, hypertonic saline gel, and acetic acid gel either alone or with simultaneous application of monopolar or bipolar RF energy. MATERIALS AND METHODS: A total of 107 renal lesions were created laparoscopically in 33 domestic pigs. Microwave thermoablation (N=12) was done using a Targis T3 (Urologix) 10F antenna. Cryoablation (N=16) was done using a single 1.5-mm probe or three 17F microprobes (17F SeedNet system; Galil Medical) (N=10 single probe and N=6 three probes); a double freeze cycle with a passive thaw was employed under ultrasound guidance. Dry RF lesions were created using custom-made 18-gauge single-needle monopolar probe with two or three exposed metal tips (GelTx) (N=12) or a single-needle bipolar probe (N=6) at 50 W of 510 kHz RF energy for 5 minutes. In addition, a multitine RF probe (RITA Medical Systems) was used in one set of studies (N=6). Both impedance- and temperature-based RF were evaluated. Chemoablation was performed with 95% ethanol (4 mL), 24% hypertonic saline (4 mL), and 50% acetic acid (4 mL) as single injections. In addition, chemoablation was tested with monopolar and bipolar RF (wet RF). Tissues were harvested 1 week after ablation for light microscopy. RESULTS: In 11 of the 15 ablation techniques, there was complete necrosis in all lesions; however, three ethanol gel lesions had skip areas, three hypertonic saline gel lesions showed no necrosis or injury, and one monopolar RF and one bipolar RF lesion showed skip areas. In contrast to impedance-based RF, heat-based RF (RITA) caused complete necrosis without skip areas. All cryolesions resulted in complete tissue necrosis, and cryotherapy was the only modality for which lesion size could be effectively monitored using ultrasound imaging. CONCLUSIONS: Cryoablation and thermotherapy produce well-delineated, completely necrotic renal lesions. The single-probe monopolar and bipolar RF produce limited areas of tissue necrosis; however, both are enhanced by using hypertonic saline, acetic acid, or ethanol gel. Hypertonic saline gel with RF consistently provided the largest lesions. Ethanol and hypertonic saline gels tested alone failed to produce consistent cellular necrosis at 1 week. In contrast, RITA using the Starburst XL probe produced consistent necrosis, while impedance-based RF left skip areas of viable tissue. Renal cryotherapy under ultrasound surveillance produced hypoechoic lesions, which could be reasonably monitored, while all other modalities yielded hyperechoic lesions the margins of which could not be properly monitored with ultrasound imaging.

Acetic Acid↗

Laparoscopic radical prostatectomy: Washington University initial experience and prospective evaluation of quality of life.

BACKGROUND AND PURPOSE: The laparoscopic approach to radical prostatectomy offers an alternative to the open surgical procedure with less morbidity. We prospectively collected data including a validated quality-of-life questionnaires on our first 38 laparoscopic radical prostatectomies (LRPs). The first 10 patients (group 1), second 10 patients (group II), and the most recent 18 patients (group III) were examined separately to study the learning curve for this procedure. In addition, we determined the pattern of recovery of urinary continence, potency, and quality of life. PATIENTS AND METHODS: Between July 1999 and July 2002, 38 consecutive transperitoneal laparoscopic radical prostatectomies were performed for clinically localized prostate carcinoma. Patients completed quality-of-life questionnaires (Rand 36 Health Survey) before surgery as well as at 1, 3, 6, and 12 months and every 6 months thereafter. The patients were also interviewed by an individual not directly involved in patient care. RESULTS: One patient (the second in our experience) was converted to the open approach because of failure to progress. The average operating time for the whole series was 423 +/- 137.6 minutes (range 215-825 minutes), the last 10 procedures taking 305 +/- 63 minutes (range 215-420 minutes). Complications consisted of one case each of intraoperative bladder injury, transient superficial peroneal nerve palsy, pulmonary embolism, and bladder neck obstruction. The bladder injury was closed laparoscopically without further complication. Bladder neck obstruction was secondary to a bladder wall fold that was treated with transurethral resection 14 months after surgery with good results. Four patients in group 1 had minor anastomotic leaks, while only one patient after that had a leak (group III). Four patients required transfusion, two intraoperatively and two postoperatively. In group III, the urethral catheter remained in place for an average of 8 days (range 6-10 days). With a mean follow-up of 22.8 months (range 9-43 months), 84.8% of the patients had perfect urinary control. Postoperatively, 9 patients (27%) were fully continent on removal of the Foley catheter. At 1, 3, 6, and 9 months postoperatively, diurnal urinary control was reported by 30.3%, 48%, 72.7%, and 84.8% of the patients, respectively. One patient needed an artificial urinary sphincter. Among the incontinent patients, 24.2% had urinary urgency, and one third of these patients reported urge incontinence. CONCLUSIONS: Laparoscopic prostatectomy is a reproducible technique with a steep learning curve. Operating times and the incidence of anastomotic leaks and urinary incontinence decrease significantly after the initial 10 patients.

Erectile Dysfunction↗

Overexpression of phytochelatin synthase in Arabidopsis leads to enhanced arsenic tolerance and cadmium hypersensitivity.

Phytochelatin synthase (PCS) catalyzes the final step in the biosynthesis of phytochelatins, which are a family of cysteine-rich thiol-reactive peptides believed to play important roles in processing many thiol-reactive toxicants. A modified Arabidopsis thaliana PCS sequence (AtPCS1) was active in Escherichia coli. When AtPCS1 was overexpressed in Arabidopsis from a strong constitutive Arabidopsis actin regulatory sequence (A2), the A2::AtPCS1 plants were highly resistant to arsenic, accumulating 20-100 times more biomass on 250 and 300 microM arsenate than wild type (WT); however, they were hypersensitive to Cd(II). After exposure to cadmium and arsenic, the overall accumulation of thiol-peptides increased to 10-fold higher levels in the A2::AtPCS1 plants compared with WT, as determined by fluorescent HPLC. Whereas cadmium induced greater increases in traditional PCs (PC2, PC3, PC4), arsenic exposure resulted in the expression of many unknown thiol products. Unexpectedly, after arsenate or cadmium exposure, levels of the dipeptide substrate for PC synthesis, gamma-glutamyl cysteine (gamma-EC), were also dramatically increased. Despite these high thiol-peptide concentrations, there were no significant increases in concentrations of arsenic and cadmium in above-ground tissues in the AtPCS1 plants relative to WT plants. The potential for AtPCS1 overexpression to be useful in strategies for phytoremediating arsenic and to compound the negative effects of cadmium are discussed.

Aminoacyltransferases↗

Comprehensive evaluation of ureteral healing after electrosurgical endopyelotomy in a porcine model: original report and review of the literature.

PURPOSE: Endopyelotomy (EP) has yet to equal the success achieved with open dismembered pyeloplasty. To understand better the ureteral response to EP we performed a timed histopathological evaluation of the porcine ureter after Acucise (Applied Medical, Rancho Santa Margarita, California) EP. MATERIALS AND METHODS: In 28 domestic pigs bilateral Acucise EPs were performed and bilateral 7Fr stents were placed. The kidneys, ureters and bladder were harvested after EP at 0, 1, 2, 3, 6, 12 and 18 hours, 1, 3 and 5 days, and 1, 2, 4 and 8 weeks. The stents were removed after 4 weeks. The healing area of the ureter was sectioned. Half was fixed in formalin 10%, stained and evaluated by light microscopy. The other half was frozen and reverse transcriptase-polymerase chain reaction was performed to measure steady state levels of epidermal growth factor, transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, keratinocyte growth factor, vascular endothelial growth factor, insulin-like growth factor, platelet derived growth factor, collagen type 1, integrin and fibronectin transcript expression. Immunohistochemistry for actin, desmin and myosin expression was completed. The same studies were applied to the mid portion of the unoperated ureter. RESULTS: Initial sealing of the ureterotomy defect was by blood clot and periureteral fat. Complete healing of the mucosa was observed at 2 weeks in animals without an associated urinoma. However, in no case did the muscle layer bridge the whole circumference of the ureter despite followup out to 8 weeks. In the operated ureter elevated expression of keratinocyte growth factor, vascular endothelial growth factor, TGF-alpha, TGF-beta 1, TGF-beta 3 and integrin was detected 2 hours after the operation and sustained for 7 to 14 days after the procedure. Immunohistochemistry revealed that most presumed myocytes seen in the defect were actually myofibroblasts. Persistent urinoma formation beyond the first few days appeared to slow the healing process. CONCLUSIONS: Urothelium regenerated rapidly over an iatrogenic ureteral defect despite the absence of a lamina propria. Muscle cell coverage failed to occur completely at 8 weeks. In the initial 8 weeks of the healing process myofibroblasts appear to be prevalent. A persistent urinoma negatively impacts the healing process.

Animals↗

Tubulin-based polymorphism (TBP): a new tool, based on functionally relevant sequences, to assess genetic diversity in plant species.

TBP (tubulin-based polymorphism) is a new molecular marker based tool that relies on the presence of intron-specific DNA polymorphisms of the plant beta-tubulin gene family. The multifunctional and essential role of the tubulin proteins is reflected in the conservation of regions within their primary amino acid sequence. The ubiquitous nature of this gene family can be exploited using primers that amplify the first intron of different beta-tubulin isotypes, revealing specific fingerprints. The method is rapid, simple, and reliable and does not require preliminary sequence information of the plant genome of interest. The ability of TBP to discriminate between accessions and species in oilseed rape, coffee, and lotus is shown. In all cases, TBP was able to detect specific genetic polymorphisms in the context of a simplified and readily appreciable pattern of DNA amplification. The application of TBP for assessing genetic diversity and genome origins in disseminated plant landraces rather than in highly inbred cultivated species is also discussed.

Brassica napus↗

Gypsy-like retrotransposons in Pyrenophora: an abundant and informative class of molecular markers.

This paper describes the development of S-SAP (sequence-specific amplified polymorphism) using a primer derived from the LTR (long terminal repeat) of the Pyggy retrotransposon isolated from Pyrenophora graminea. Fragments were amplified by S-SAP from different Pyrenophora spp., indicating the presence of Pyggy-like sequences in these genomes. The bands were highly polymorphic between isolates and the number of bands differed by as much as 10-fold between species, demonstrating the potential of this method for genetic analysis in fungi. The phylogenetic relationship among the isolates as deduced using S-SAP data is presented, and shows evidence of genetic exchange between P. graminea and P. teres.

Ascomycota↗

Efficacy of oxymorphone extended release in postsurgical pain: a randomized clinical trial in knee arthroplasty.

Patients with moderate or severe pain following knee arthroplasty and washout from standard patient-controlled analgesia (PCA) were randomized to receive 20 mg of an extended-release (ER) oxymorphone formulation (n = 65) or placebo (n = 61) q12h for 1 day. Oxymorphone PCA was used as rescue analgesic. Oxymorphone ER provided significant improvements over placebo for most standard single-dose analgesic parameters, including mean total pain relief (TOTPAR) over 0 to 12 hours (19.30 vs. 13.72; p = 0.0056), as well as for all multiple-dose (24-h) efficacy assessments. Oxymorphone-treated patients used significantly less rescue PCA than those who received placebo (p < 0.02). Adverse events such as nausea and constipation were typical of opioids, and laboratory and physical findings were similar between groups. Oxymorphone ER was effective and generally well tolerated. A single dose was active from 2 hours until > or = 12 hours after administration. Comparisons with other oral opioids are warranted, especially in the setting of outpatient and day surgery.

Adult↗

The rate, pattern, and cost of use of antiparkinsonian agents among patients treated for schizophrenia in a managed care setting.

OBJECTIVE: To examine the use and economic cost of antiparkinsonian agents during the medication management of patients diagnosed with schizophrenic disorders in a naturalistic healthcare setting. DESIGN: Cross-sectional retrospective analysis of 1-year (1999) administrative data from a large managed care organization. PATIENTS AND METHODS: Patients were 1938 adults who were treated for a schizophrenic disorder. Monthly per patient utilization rate and cost of antiparkinsonian agents, and the proportion of the total psychiatric medication costs attributed to the antiparkinsonian agents, were compared across antipsychotic medications (typical, atypical, olanzapine, risperidone), age, sex, and diagnostic subtype. RESULTS: About one third (39%) of the patients were treated with typical antipsychotics only, and half of them (51%) received antiparkinsonian agents. Those treated with atypical antipsychotics only (41%) were considerably less likely to receive antiparkinsonian agents (25%), and the rate of use differed by atypical type such that risperidone-treated patients were more likely to receive antiparkinsonian agents than those treated with olanzapine. Lower utilization rates of antiparkinsonian agents were also found among patients age 75 years or older, and among those diagnosed with a schizoaffective disorder. Average monthly per patient cost of antiparkinsonian agents was 3.0 dollars, constituting 2.6% of the monthly expenditure on all psychiatric medications. CONCLUSIONS: Adjunctive use of antiparkinsonian agents differs widely among patients who are treated with typical or atypical antipsychotic drugs, and differs between types of atypical antipsychotics. The choice of atypical antipsychotics that have a lower liability for extrapyramidal symptoms may assist in optimizing the long-term functional outcomes of schizophrenia patients.

Adolescent↗

Gene3D: structural assignments for the biologist and bioinformaticist alike.

The Gene3D database (http://www.biochem.ucl.ac.uk/bsm/cath_new/Gene3D/) provides structural assignments for genes within complete genomes. These are available via the internet from either the World Wide Web or FTP. Assignments are made using PSI-BLAST and subsequently processed using the DRange protocol. The DRange protocol is an empirically benchmarked method for assessing the validity of structural assignments made using sequence searching methods where appropriate assignment statistics are collected and made available. Gene3D links assignments to their appropriate entries in relevent structural and classification resources (PDBsum, CATH database and the Dictionary of Homologous Superfamilies). Release 2.0 of Gene3D includes 62 genomes, 2 eukaryotes, 10 archaea and 40 bacteria. Currently, structural assignments can be made for between 30 and 40 percent of any given genome. In any genome, around half of those genes assigned a structural domain are assigned a single domain and the other half of the genes are assigned multiple structural domains. Gene3D is linked to the CATH database and is updated with each new update of CATH.

Animals↗

National Health Interview Survey mortality among US farmers and pesticide applicators.

BACKGROUND: The mortality experience of pesticide-exposed workers across the US has not been thoroughly studied. METHODS: Cox regression mortality analyses adjusted for the complex sample survey design were performed on mortality-linked 1986-1994 National Health Interview Survey (NHIS) data. RESULTS: Nine thousand four hundred seventy-one farmers and pesticide applicators with 571 deaths were compared to 438,228 other US workers with 11,992 deaths. Age-adjusted risk of accidental death, as well as cancers of the nervous and lymphatic/hematopoietic systems, was significantly elevated in male and female pesticide-exposed workers; breast, prostate, and testicular cancer mortality risks were not elevated. CONCLUSIONS: Compared to all other workers, farmers and pesticide applicators were at greater risk of accidental mortality. These pesticide-exposed workers were not at an increased risk of cancers possibly associated with exposure to estrogen analogue compounds, but were at an increased risk of hematopoietic and nervous system cancers. NHIS mortality follow-up represents an important occupational health surveillance instrument.

Accidents↗

Trimethylaminuria and a human FMO3 mutation database.

Trimethylaminuria (TMAuria), or fish-odor syndrome, is due to defective flavin-containing monooxygenase 3 (FMO3). In the liver, this protein catalyzes the NADPH-dependent oxidative metabolism of odorous trimethylamine (TMA), derived in the gut from dietary sources, to nonodorous trimethylamine N-oxide (TMA N-oxide). Affected individuals are unable to carry out this reaction and consequently exude a fishy body odor, due to the secretion of TMA in their breath and sweat and its excretion in their urine. This leads to a variety of psychosocial problems, including disruption of schooling, clinical depression, and attempted suicide. Twelve missense, three nonsense, and one gross deletion mutation are known to cause TMAuria. FMO3 is also a drug-metabolizing enzyme and compromised activity is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions both in TMAuric patients and in the general population. To date eight polymorphic variants, not associated with TMAuria, have been reported. A human FMO3 mutation database was created using MuStar, a locus-specific database system for maintaining data about allelic variants and distributing these via the World Wide Web. The database currently contains 24 entries and is accessible on the World Wide Web via the URL http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3. Additional entries can be submitted via the curator of the database or via a web-based form.

Alleles↗

Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial.

BACKGROUND: Neurologic and clinical morbidity after coronary artery bypass grafting (CABG) can be significant. By avoiding cardiopulmonary bypass, off-pump CABG (OPCAB) may reduce morbidity. METHODS: Sixty patients (30 CABG and 30 OPCAB) were prospectively randomized. Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation. Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward. Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli. All examiners were blinded to treatment group. Clinical morbidity and costs were compared. RESULTS: Coronary artery bypass grafting was associated with more cerebral microemboli (575 +/- 278.5 CABG versus 16.0 +/- 19.5 OPCAB (median +/- semiinterquartile range) and significantly reduced cerebral perfusion after the operation to the bilateral occipital, cerebellar, precunei, thalami, and left temporal lobes (p < or = 0.01). Cerebral perfusion with OPCAB was unchanged. Compared with base line, OPCAB patients performed better on the Rey Auditory Verbal Learning Test (total and recognition scores) at both 2 weeks and at 1 year (p < or = 0.05), whereas CABG performance was statistically unchanged for all cognitive measures. Patients who underwent CABG had more chest tube drainage (1389 +/- 1256 mL CABG versus 789 +/- 586 mL OPCAB, p = 0.02) and required more blood (3.9 +/- 5.8 U CABG versus 1.2 +/- 2.2 U OPCAB, p = 0.02), fresh frozen plasma (3.0 +/- 6.0 U CABG versus 0.5 +/- 2.2 U OPCAB, p = 0.03), and hours of postoperative use of dopamine (16.3 +/- 21.2 hours CABG versus 7.3 +/- 9.7 hours OPCAB, p = 0.04). These differences culminated in higher costs for CABG ($23,053 +/- $5,320 CABG versus $17,780 +/- $4,390 OPCAB, p < 0.0001). One stroke occurred with CABG, compared with none with OPCAB (p = NS). One OPCAB patient died because of a pulmonary embolus (p = NS). CONCLUSIONS: Compared with CABG, OPCAB may reduce neurologic and clinical morbidity as well as cost.

Aged↗

Hemostatic laparoscopic partial nephrectomy assisted by a water-cooled, high-density, monopolar device without renal vascular control.

OBJECTIVES: To evaluate the feasibility of laparoscopic partial nephrectomy assisted by a water-cooled, high-density, monopolar device (TissueLink Floating Ball). METHODS: Transperitoneal laparoscopic partial nephrectomy was performed without vascular control for four renal tumors in 3 patients. A flexible ultrasound probe was used to confirm tumor location and depth. Gerota's fascia was opened distant from the tumor site. Renal fat was dissected from the renal parenchyma except for the fat overlying the tumor. The tumor resection area was marked 1 cm outside the boundaries of the tumor. After application of the TissueLink Floating Ball at the planned surgical margin, the tumor was resected with cold laparoscopic scissors. Bleeding from the vessels of the divided renal parenchyma was controlled with the Floating Ball if necessary. The specimen was sent for frozen section to confirm margin status. RESULTS: Mean estimated blood loss per tumor was 275 mL. The dissection extended to the collecting system in 2 of 4 cases. In 1 patient, a minor postoperative urine leak resolved spontaneously. CONCLUSIONS: Use of the TissueLink Floating Ball facilitated resection of small renal tumors without renal vascular control. Although further study is necessary, water-cooled, high-density monopolar energy may have a role in laparoscopic partial nephrectomy.

Aged↗

Renal hypothermia achieved by retrograde endoscopic cold saline perfusion: technique and initial clinical application.

We describe the technique and initial clinical results with application of a novel method to achieve renal parenchymal hypothermia using retrograde ureteral access. A 38-year-old man was scheduled to undergo an open right partial nephrectomy for renal cell carcinoma. Before the open procedure, a ureteral access sheath was advanced to the ureteropelvic junction under fluoroscopic guidance; through the access sheath, a 7.1F pigtail catheter was also advanced. After clamping the renal artery and vein, ice-cold saline (-1.7 degrees C) was circulated through the access sheath and drained via the 7.1F pigtail catheter; renal cortical and medullary parenchymal temperatures were measured using thermocouples. This technique of intrarenal cooling achieved a renal cortical temperature of 24 degrees C and a medullary temperature of 21 degrees C. The endoscopic procedure required an additional 35 minutes of operation time to complete. Histopathologic investigation of the specimen revealed no associated damage to the ureteral urothelium from access sheath placement or to the collecting system urothelium from exposure to ice-cold saline irrigation. Retrograde endoscopic renal hypothermia is feasible and effective. The technique requires no novel equipment or special surgical skills. This method can be applied to patients undergoing open or laparoscopic complex renal ablative and reconstructive procedures that require renal hypothermia.

Adult↗

Evaluation of synchronous twin pulse technique for shock wave lithotripsy: in vivo tissue effects.

OBJECTIVES: To study the in vivo tissue effects of synchronous twin pulse technology. Recently, the concept of a synchronous twin pulse technique for shock wave therapy has been introduced with the development of the Twinheads' unit. METHODS: In 10 pigs (20 kidneys), one of three sites was targeted: the renal pelvis (2 pigs), the mid-zone parenchyma (5 pigs), or the lower pole parenchyma (3 pigs). The treatment parameters were 1000 twin shock waves at 14 kV with a 90 degrees angle between the shock wave reflectors using a rate of 60 shock waves/min in 17 kidneys and 120 shock waves/min in 3 kidneys. To study the effect of an increasing number of twin shock waves, 4 animals (8 kidneys) were used; the mid-zone parenchyma was subjected to 2000 and 3000 twin shock waves in 4 kidneys each, using a rate of 60 shock waves/min at 14 kV and a 90 degrees angle in all of them. For comparison with the use of a single head, another 3 animals (6 kidneys) were treated with the use of the single under-table head; all of them received 2000 single shock waves at 14 kV focused on the mid zone of the kidney parenchyma. Within 1 hour of treatment, the treated kidneys were harvested, inspected, and sectioned at the focal site, as well as at 1 and 2 cm distant to the focal site. RESULTS: No gross lesions of the surrounding organs, subcapsular hemorrhage, or parenchymal damage were found at the outer surfaces of the kidneys undergoing twin head shock wave lithotripsy even after 3000 twin shocks. The coronal section revealed minimal gross lesions in 4 of 28 kidneys. Microscopically, the parenchymal changes were minimal. In vivo study of the use of the single under-table head revealed that 5 of 6 kidneys had large subcapsular hematomas at both anterior and posterior surfaces and on coronal section extending into the parenchyma. Microscopically, the changes were significant. CONCLUSIONS: Synchronous twin pulse shock waves induced minimal damage compared with single pulse standard shock waves. Of note, even after 3000 twin pulses (ie, a total of 6000 shock waves), the renal damage remained minimal.

Animals↗

A structural perspective on genome evolution.

Protein translations of over 100 complete genomes are now available. About half of these sequences can be provided with structural annotation, thereby enabling some profound insights into protein and pathway evolution. Whereas the major domain structure families are common to all kingdoms of life, these are combined in different ways in multidomain proteins to give various domain architectures that are specific to kingdoms or individual genomes, and contribute to the diverse phenotypes observed. These data argue for more targets in structural genomics initiatives and particularly for the selection of different domain architectures to gain better insights into protein functions.

Evolution, Molecular↗