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PubMed2002

Integrating biosystematic data into conservation planning: perspectives from southern Africa's Succulent Karoo.

In this paper we explore the role that biosystematists can play in conservation planning. Conservation planning concerns the location and design of reserves that both represent the biodiversity of a region and enable the persistence of that biodiversity by maintaining key ecological and evolutionary processes. For conservation planning to be effective, quantitative targets are needed for the spatial components of a region that reflect evolutionary processes. Using examples from southern Africa's Succulent Karoo, we demonstrate how spatially explicit data on morphological variation within taxa provide essential information for conservation planning in that such variation represents an important surrogate for the spatial component of lineage diversification. We also provide an example of how the spatial components of evolutionary processes can be identified and targeted for conservation action. Key to this understanding are the recognition and description of taxonomic units at all spatial scales. Without the recognition of subspecific variation, it is difficult to formulate evolutionary hypotheses, let alone set quantitative targets for the conservation of this variation. Given the escalating threats to biodiversity, and the importance of planning for persistence by incorporating ecological and evolutionary processes into conservation plans, it is essential that systematists develop hypotheses on the spatial surrogates for these processes for a wide range of lineages. The important questions for systematists to be asking are (1) how is variation distributed in the landscape, and (2) how did it come about? Conservation planners too need to highlight these spatial components for conservation action.

Africa↗

PubMed2004

Breast conservation in breast cancer: surgical and adjuvant considerations.

PURPOSE OF REVIEW: Breast-conserving surgery is accepted as an alternative to mastectomy for the treatment of early breast cancer. This paper reviews the recent contributions to the literature, with special emphasis on breast-conserving surgery in the management of invasive breast cancer. RECENT FINDINGS: Long-term follow-up of randomized trials confirms that in women with early stage breast cancer, breast-conserving surgery achieves similar survival compared with mastectomy. Increase in early breast cancer detection, and efforts in patient and physician education are likely to enhance breast-conserving surgery use. Patients with locally advanced tumors may also become eligible for breast-conserving surgery after tumor downsizing with preoperative chemotherapy, with acceptable rates of ipsilateral breast tumor recurrence. Efforts should be made to minimize the risk of ipsilateral breast tumor recurrences after breast-conserving surgery as they have been associated with worse distant-disease-free and breast cancer-specific survival rates. One of the most effective strategies to minimize ipsilateral breast tumor recurrence risk is to ensure negative surgical margins. This necessitates careful surgical planning, tumor localization, precise surgical technique and careful pathological processing. Radiation therapy is also a critical therapeutic tool to minimize the risk. Although the standard of care has been whole-breast irradiation, preliminary results with accelerated partial breast irradiation are promising. Adjuvant systemic therapy can further reduce the risk of ipsilateral breast tumor recurrence, but it cannot replace adequate surgery and radiation therapy for achieving local control after breast-conserving surgery. SUMMARY: Breast-conserving surgery is confirmed to be appropriate therapy for patients with early stage breast cancer. Increasing numbers of patients are likely to be eligible for surgery in the future. Strategies to minimize the risk of ipsilateral breast tumor recurrence while enhancing the convenience of breast-conserving surgery need to be pursued.

Breast Neoplasms↗

PubMed1992

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.

Adult↗

PubMed2000

Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study.

STUDY DESIGN: A cohort of 100 patients with symptomatic lumbar spinal stenosis, characterized in a previous article, were given surgical or conservative treatment and followed for 10 years. OBJECTIVES: To identify the short- and long-term results after surgical and conservative treatment, and to determine whether clinical or radiologic predictors for the treatment result can be defined. SUMMARY OF BACKGROUND DATA: Surgical decompression has been considered the rational treatment. However, clinical experience indicates that many patients do well with conservative treatment. METHODS: In this study, 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment, whereas 31 patients were randomized between the conservative (n = 18) and surgical (n = 13) treatment groups. Pain was decisive for the choice of treatment group. All patients were observed for 10 years by clinical evaluation and questionnaires. The results, evaluated by patient and physician, were rated as excellent, fair, unchanged, or worse. RESULTS: After a period of 3 months, relief of pain had occurred in most patients. Some had relief earlier, whereas for others it took 1 year. After a period of 4 years, excellent or fair results were found in half of the patients selected for conservative treatment, and in four fifths of the patients selected for surgery. Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months (median, 3.5 months). The treatment result of delayed surgery was essentially similar to that of the initial group. The treatment result for the patients randomized for surgical treatment was considerably better than for the patients randomized for conservative treatment. Clinically significant deterioration of symptoms during the final 6 years of the follow-up period was not observed. Patients with multilevel afflictions, surgically treated or not, did not have a poorer outcome than those with single-level afflictions. Clinical or radiologic predictors for the final outcome were not found. There were no dropouts, except for 14 deaths. CONCLUSIONS: The outcome was most favorable for surgical treatment. However, an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome.

Activities of Daily Living↗

PubMed1997

Is conservative surgery for tubal pregnancy preferable to salpingectomy? An economic analysis.

OBJECTIVE: The traditional treatment of ectopic pregnancy is salpingectomy, while conservative surgery aims to save the function of the uterine tube. This study compares the effectiveness and the economic costs of salpingectomy and conservative tubal surgery in women with a tubal pregnancy. METHODS: Salpingectomy and conservative tubal surgery were compared economically, based on a combined retrospective and prospective cohort study and a review of the literature. A model was developed in which conservative surgery and salpingectomy with in vitro fertilisation and embryo-transfer (IVF-ET) were compared with salpingectomy alone. PARTICIPANTS: One hundred and fifteen consecutive women treated laparoscopically for tubal pregnancy. MAIN OUTCOME MEASURES: Complete removal of the tubal pregnancy; subsequent intrauterine pregnancy rate; economic analysis. RESULTS: Tubal pregnancy was always treated successfully by both methods, sometimes with additional treatment for persistent trophoblast. In the short term costs per patient were 1554 pounds (95% confidence interval [CI] 1501 pounds-1656 pounds) for salpingectomy and 1787 pounds (95% CI 1683 pounds-1930 pounds) for conservative surgery. The mean difference between costs of salpingectomy and costs of conservative surgery was 233 pounds (95% CI 80 pounds-371 pounds). Concerning subsequent intrauterine pregnancy, conservative surgery is slightly more effective than salpingectomy but is more expensive. Costs per subsequent intrauterine pregnancy are 4063 pounds. If IVF-ET is performed in all women who are not pregnant within three years after salpingectomy, costs per subsequent intrauterine pregnancy are 15,629 pounds. CONCLUSIONS: Salpingectomy is the treatment of choice in women not desiring future pregnancy. Salpingectomy seems less effective than conservative surgery when future pregnancy is desired, but is less costly. Conservative surgery seems more cost effective than salpingectomy with additional IVF-ET.

Cohort Studies↗

PubMed1979

Oligoribonucleotide map and protein of CMII: detection of conserved and nonconserved genetic elements in avian acute leukemia viruses CMII, MC29, and MH2.

RNA and protein of the defective avian acute leukemia virus CMII, which causes myelocytomas in chickens, and of CMII-associated helper virus (CMIIAV) were investigated. The RNA of CMII measured 6 kilobases (kb) and that of CMIIAV measured 8.5 kb. By comparing more than 20 mapped oligonucleotides of CMII RNA with mapped and nonmapped oligonucleotides of acute leukemia viruses MC29 and MH2 and with mapped oligonucleotides of CMIIAV and other nondefective avian tumor viruses, three segments were distinguished in the oligonucleotide map of CMII RNA: (i) a 5' group-specific segment of 1.5 kb which was conserved among CMII, MC29, and MH2 and also homologous with gag-related oligonucleotides of CMIIAV and other helper viruses (hence, group specific); (ii) an internal segment of 2 kb which was conserved specifically among CMII, MC29, and MH2 and whose presence in CMII lends new support to the view that this class of genetic elements is essential for oncogenicity, because it was absent from an otherwise isogenic, nontransforming helper, CMIIAV; and (iii) a 3' group-specific segment of 2.5 kb which shared 13 of 14 oligonucleotides with CMIIAV and included env oligonucleotides of other nondefective viruses of the avian tumor virus group (hence, group specific). This segment and analogous map segments of MC29 and MH2 were not conserved at the level of shared oligonucleotides. CMII-transformed cells contained a nonstructural, gag gene-related protein of 90,000 daltons, distinguished by its size from 110,000-daltom MC29 and 100,000-dalton MH2 counterparts. The gag relatedness and similarity to the 110,000-dalton MC29 counterpart indicated that the 90,000-dalton CMII protein is translated from the 5' and internal segments of CMII RNA. The existence of conserved 5' and internal RNA segments and conserved nonstructural protein products in CMII, MC29, and MH2 indicates that these viruses belong to a related group, termed here the MC29 group. Viruses of the MC29 group differ from one another mainly in their 3' RNA segments and in minor variations of their conserved RNA segments as well as by strain-specific size markers of their gag-related proteins. Because (i) the conserved 5' gag-related and internal RNA segments and their gag-related, nonvirion protein products correlate with the conserved oncogenic spectra of the MC29 group of viruses and because (ii) the internal RNA sequences and nonvirion proteins are not found in nondefective viruses, we propose that the conserved RNA and protein elements are necessary for oncogenicity and probably are the onc gene products of the MC29 group of viruses.

Animals↗

PubMed1998

Use of breast-conserving surgery for treatment of stage I and stage II breast cancer.

PURPOSE: To assess the use of breast-conserving surgery in two states reported to differ with respect to surgical treatment of breast cancer. METHODS: A retrospective cohort study based on data collected from medical records and patients was performed among 1,514 patients diagnosed with early-stage breast cancer in Massachusetts and 1,061 patients in Minnesota. Patients were identified at 18 randomly selected hospitals in Massachusetts and at 30 hospitals in Minnesota. The rate of breast-conserving surgery in both states and the correlates of breast-conserving surgery among women eligible for the procedure were determined. RESULTS: The rate of breast-conserving surgery in both states was much higher than previously reported. Among those eligible for the procedure, nearly 75% underwent breast-conserving surgery in Massachusetts and nearly half did so in Minnesota. Significantly (P < .003) more women who underwent mastectomy in Minnesota (27%) than in Massachusetts (15%) reported that their surgeon did not discuss breast-conserving surgery with them. Among women who underwent mastectomy and who reported being informed of both surgical alternatives, more women (P < .001) in Minnesota (74%) than in Massachusetts (62%) said they ultimately chose mastectomy because their surgeon recommended it. In Massachusetts, women treated at teaching hospitals were twice as likely as other women to undergo breast-conserving surgery. In Minnesota, women over age 70 and those who lived in rural areas were less likely than other women to undergo breast-conserving surgery. CONCLUSION: Although the rate of breast-conserving surgery in each state was higher than expected based on earlier reports, the rates differed considerably between states. Additional studies are needed to determine whether variation in practice between geographic areas is due to differences in patients' preferences and values or to surgeons' propensity for one type of surgery based on where they practice.

Aged↗

PubMed2004

Statistical methods for identifying conserved residues in multiple sequence alignment.

The assessment of residue conservation in a multiple sequence alignment is a central issue in bioinformatics. Conserved residues and regions are used to determine structural and functional motifs or evolutionary relationships between the sequences of a multiple sequence alignment. For this reason, residue conservation is a valuable measure for database and motif search or for estimating the quality of alignments. In this paper, we present statistical methods for identifying conserved residues in multiple sequence alignments. While most earlier studies examine the positional conservation of the alignment, we focus on the detection of individual conserved residues at a position. The major advantages of multiple comparison methods originate from their ability to select conserved residues simultaneously and to consider the variability of the residue estimates. Large-scale simulations were used for the comparative analysis of the methods. Practical performance was studied by comparing the structurally and functionally important residues of Src homology 2 (SH2) domains to the assignments of the conservation indices. The applicability of the indices was also compared in three additional protein families comprising different degrees of entropy and variability in alignment positions. The results indicate that statistical multiple comparison methods are sensitive and reliable in identifying conserved residues.

Journal Article↗

PubMed2001

[Tumors of the upper urinary tract: results of conservative surgery].

OBJECTIVE: To determine the results of conservative surgery for upper urinary tract urothelial tumours. PATIENTS AND METHODS: From 1986 to 1997, 352 patients were treated in the Belgrade urology clinic for upper urinary tract urothelial tumour. 54 patients (15.3%) were treated by conservative surgery. The sex ratio was 1.3 men for 1 woman. The mean age was 63 years. In most cases, the tumour was situated in the ureter. Conservative surgery was performed on principle in 60% of patients for a small isolated lesion (solitary low-stage, low-grade tumour). In contrast, in about 40% of cases, conservative surgery was performed by necessity due to the presence of bilateral tumours, a solitary kidney or renal failure related to Balkan nephropathy. The median follow-up was 67.3 months (range: 6 months-14 years). RESULTS: 15.8% of patients developed a local recurrence during the follow-up period. The risk of recurrence was higher when conservative surgery was performed for indications of necessity than when it was performed on principle (21.7% versus 11.8%), but the difference was not statistically significant (c2 test, t test). The stage and grade of differentiation were identified as the most significant predictive factors for the risk of local recurrence. The overall 5-year survival rate was 67% with more favourable results in the case of conservative surgery performed on principle compared conservative surgery by necessity (72% versus 60%). The difference between these results was not statistically significant, but a statistically significant difference was observed for tumour stage and grade (grade III versus grade I and II, pT3 versus pT1, pT2). The 5-year survival probability was 68.5%. Recurrence was most likely to occur during the early postoperative course, as 81.56% occurred during the first 18 months. CONCLUSION: Urothelial tumours can be managed conservatively. However, the risk of recurrence is directly correlated with the tumour stage and grade, with a high level of statistical significance, and with the type of indication for conservative surgery performed, but with no statistically significant difference.

Female↗

PubMed1992

Efficacy, complications, and cost of a comprehensive blood conservation program for cardiac operations.

We reviewed blood use in 118 consecutive patients who underwent primary, elective cardiac operations in 1989. In June 1989 we initiated a blood conservation program that included attempts to limit preoperative aspirin use, intraoperative phlebotomy and hemodilution, use of a cell conservation device (Electromedics, Inc., Englewood, Colo.) to concentrate residual oxygenator contents, reinfusion of chest drainage, and acceptance of a minimum hemoglobin level of 8.0 gm/dl in stable patients. Patient characteristics were similar for patients operated on both before (n = 58) and after (n = 60) initiation of the blood conservation program, except for age and preoperative aspirin use (both greater in postconservation patients). Fewer blood products were transfused (5.8 +/- 5.7 units per patient before conservation versus 4.0 +/- 7.4 units per patient after conservation; p = 0.005). More complete data were available for 82 patients (40 patients before conservation and 42 after conservation). In the postconservation patients, 20 of 42 had 575 +/- 140 ml of blood withdrawn before cardiopulmonary bypass and reinfused afterward, 26 of 42 had 806 +/- 376 ml of blood processed with the cell conservation device returned, and 21 of 42 patients had an average of 287 +/- 127 ml of chest drainage reinfused. Chest tube drainage, postoperative hematologic parameters, and the prevalence of complications were not significantly different between groups. Stepwise linear regression analysis identified intraoperative withdrawal of blood before cardiopulmonary bypass, bypass duration, and preoperative hematocrit value as predictors of blood use. Intraoperative withdrawal of blood before cardiopulmonary bypass is an important conservation measure, and its use should be expanded.

Aspirin↗

PubMed2005

[Trends and variation in breast conserving surgery in the southeast and east of the Netherlands over the period 1990-2002].

OBJECTIVE: To give an overview of the trends and variation in breast-conserving surgery in patients with a breast tumour < or = 2 cm (pT1) or > 2 and < or = 5 cm (pT2), treated in general hospitals in the southeast and east of the Netherlands. DESIGN: Descriptive. METHOD: Data from the regional cancer registries of the Comprehensive Cancer Centre South (CS) and the Comprehensive Cancer Centre Stedendriehoek Twente (CST) were used to study trends and variations in the use of breast-conserving surgery in 12,985 pT1 tumours and 8,893 pT2 tumours in the period 1990-2002. RESULTS: The mean percentage of patients that underwent breast-conserving surgery from 1990-2002 was 54 in the CS region and 43 in the CST region. In patients < 50 years old with a pT1 tumour a decrease in the percentage of breast-conserving surgery from 73 to 64 was seen in the CS region, and in the CST region this percentage decreased from 72 to 51. In pT2 tumours a decrease from 47 to 37 was seen in the CS region and from 34 to 31 in the CST region. In patients of 50 to 69 years of age with a pT1 tumour, the percentage of breast-conserving surgery increased in the CS region from 67 to 74 and in the CST region from 54 to 61. In pT2 tumours it increased from 40 to 44 and from 25 to 37. In patients > or = 70 years the percentage of breast-conserving surgery in pT1 tumours increased from 37 to 59 in the CS region and in the CST region from 42 to 50. In pT2 tumours it increased from 20 to 31 in the CS region whereas it remained 17 in the CST region. The variation in breast-conserving surgery between hospitals in the period 1999-2002 was large. The percentage of breast-conserving surgery in patients with pT1 tumours varied between 47 and 86 in the hospitals in the CS region and between 54 and 71 in the CST region. In patients with a pT2 tumour the percentages varied between 25 and 43 in the CST region and between 16 and 64 in the CS region. CONCLUSION: More than 20 years after the introduction of breast-conserving surgery a large regional variation still exists in the use of this treatment, in the CS region in particular. There is also wide inter-hospital variation.

Age Factors↗

PubMed2005

Phenotypic & genotypic conservation of ompL1 & lipL41 among leptospiral isolates of Andaman Islands.

BACKGROUND & OBJECTIVES: The leptospiral antigens that are conserved among the diverse pathogenic leptospires have potential importance in the development of new serodiagnostic and immunoprotective strategies. The present study was therefore carried out to find out the phenotypic conservation of the leptospiral proteins OmpL1 and LipL41, and the genetic conservation of ompL1 and lipL41 genes among the leptospiral isolates of Andaman Islands and among the reference strains. METHODS: In one dimensional SDS-PAGE the leptospiral samples prepared from strains of various leptospiral serovars were run and transferred on to nitrocellulose paper and probed with pooled convalescent phase human sera to find out the phenotypic conservation of the protein fragments at 31 and 41 kDa. Further, the proteins were indirectly confirmed as OmpL1 and LipL41 by using specific rabbit hyperimmune sera. Specific primers were utilized to amplify the fragments to study the genetic conservation of ompL1 and lipL41. Further, these two fragments were sequenced and BLAST analysis was done with the whole genome of Leptospira interrogans serovar Lai for comparison. RESULTS: Analysis of individual immunoblots using patient sera showed that the OmpL1 and LipL41 were conserved among all the isolates used in the study. Further, these two proteins were probed with specific rabbit hyperimmune sera of OmpL1 and LipL41 for confirming the fragments and it was found to be conserved among all the isolates. The PCR based amplification further showed that the genes ompL1 and lipL41 were conserved among the leptospiral isolates studied. Sequencing followed by BLAST analysis of these showed 97 per cent similarity with the whole genome sequence and low score values in comparison with other bacterial species. INTERPRETATION & CONCLUSION: The antigenic and genetic conservation of the two proteins, OmpL1 and LipL41, indicated that these could be potential candidates for development of diagnostic test systems for leptospirosis.

Animals↗

PubMed1976

Accelerated conservation acquisition and IQ gains by blind children.

Because blind chidlren are retarded in the attainment of substance conservation and other Piagetial concepts, it was hypothesized that a learning set training procedure which incorporated both substance conservation and subordinate concepts might accelerate the acquisition of substance conservation itself and promote generalization to weight conservation scores and IQ. To test the hypotheses, 28 blind children aged 8 to 13 (IQ range 62 to 131) were divided into two groups. Their visual capacities ranged from 20/500 in the best eye to total congenital blindness and etiologies were varied, but consisted primarily of cataracts and glaucoma. All children were pretested and posttested on Slosson's Intelligence Test, 40 substance conservation tasks, and 20 weight conservation tasks, which involved both continuous and discontinuous substance and included almost all those found in the literature prior to 1970. A lengthy learning set procedure employing everyday household objects was then used to teach the experimental children conceptual skills that are prerequisites to substance conservation. Finally the learning set procedure was used to teach the concept of substance conservation itself to the children. The trained group exhibited significantly increased substance and weight conservation scores and IQs (all ps less than .005). The control group, which had spent matched periods of time in intellectual enrichment activities failed to improve significantly on any of the dependent variables. The research suggests that acceleration of the development of Piagetian concepts may be profitable enterprise in the case of blind children.

Adolescent↗

PubMed2002

Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction.

CONTEXT: In the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-Thrombolysis in Myocardial Infarction (TIMI) 18 trial, patients with either unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) treated with the platelet glycoprotein (Gp IIb/IIIa) inhibitor tirofiban had a significantly reduced rate of major cardiac events at 6 months with an early invasive vs a conservative strategy. OBJECTIVE: To examine total 6-month costs and long-term cost-effectiveness of an invasive vs a conservative strategy. DESIGN: Randomized controlled trial including a priori economic end points. SETTING: Hospitalization for UA/NSTEMI with 6-month follow-up period. PATIENTS: A total of 2220 patients with UA/NSTEMI; economic data from 1722 patients at US-non-VA hospitals. INTERVENTION: Early invasive strategy with routine catheterization and revascularization as appropriate vs a conservative strategy with catheterization performed only for recurrent ischemia or a positive stress test. MAIN OUTCOME MEASURE: Total 6-month costs and incremental cost-effectiveness ratio. RESULTS: The average initial hospitalization costs among those in the invasive strategy group were $15714 vs $14047 among those in the conservative strategy group, a difference of $1667 (95% confidence interval [CI], $387-3091). The in-hospital costs were offset significantly at the 6-month follow-up, with an average cost in the invasive group of $6098 vs $7180 in the conservative group, a difference of $1082 (95% CI, -$2051 to $76). The average total costs at 6 months, including productivity costs, for the invasive group was $21 813 vs $21 227 for the conservative group, a $586 difference (95% CI, -$1087 to $2486). The average 6-month costs excluding productivity costs in the invasive group was $19 780 vs $19 111 in the conservative group, a difference of $670, 95% CI; (-$1035 to $2321). Estimated cost per year of life gained for the invasive strategy, based on projected life expectancy, was $12739 for the base case, and ranged from $8371 to $25769, based on model assumptions. CONCLUSIONS: In patients with UA/NSTEMI treated with the Gp IIb/IIIa inhibitor tirofiban, the clinical benefit of an early invasive strategy was achieved with a small increase in cost, yielding favorable projected estimates of cost per year of life gained. These results support the broader use of an early invasive strategy in these patients.

Aged↗

PubMed2000

An integrated approach to the analysis and modeling of protein sequences and structures. III. A comparative study of sequence conservation in protein structural families using multiple structural alignments.

The information required to generate a protein structure is contained in its amino acid sequence, but how three-dimensional information is mapped onto a linear sequence is still incompletely understood. Multiple structure alignments of similar protein structures have been used to investigate conserved sequence features but contradictory results have been obtained, due, in large part, to the absence of subjective criteria to be used in the construction of sequence profiles and in the quantitative comparison of alignment results. Here, we report a new procedure for multiple structure alignment and use it to construct structure-based sequence profiles for similar proteins. The definition of "similar" is based on the structural alignment procedure and on the protein structural distance (PSD) described in paper I of this series, which offers an objective measure for protein structure relationships. Our approach is tested in two well-studied groups of proteins; serine proteases and Ig-like proteins. It is demonstrated that the quality of a sequence profile generated by a multiple structure alignment is quite sensitive to the PSD used as a threshold for the inclusion of proteins in the alignment. Specifically, if the proteins included in the aligned set are too distant in structure from one another, there will be a dilution of information and patterns that are relevant to a subset of the proteins are likely to be lost. In order to understand better how the same three-dimensional information can be encoded in seemingly unrelated sequences, structure-based sequence profiles are constructed for subsets of proteins belonging to nine superfolds. We identify patterns of relatively conserved residues in each subset of proteins. It is demonstrated that the most conserved residues are generally located in the regions where tertiary interactions occur and that are relatively conserved in structure. Nevertheless, the conservation patterns are relatively weak in all cases studied, indicating that structure-determining factors that do not require a particular sequential arrangement of amino acids, such as secondary structure propensities and hydrophobic interactions, are important in encoding protein fold information. In general, we find that similar structures can fold without having a set of highly conserved residue clusters or a well-conserved sequence profile; indeed, in some cases there is no apparent conservation pattern common to structures with the same fold. Thus, when a group of proteins exhibits a common and well-defined sequence pattern, it is more likely that these sequences have a close evolutionary relationship rather than the similarities having arisen from the structural requirements of a given fold.

Algorithms↗

PubMed2001

Role of conserved nucleotides in building the 16 S rRNA binding site for ribosomal protein S15.

Ribosomal protein S15 recognizes a highly conserved target on 16 S rRNA, which consists of two distinct binding regions. Here, we used extensive site-directed mutagenesis on a Escherichia coli 16 S rRNA fragment containing the S15 binding site, to investigate the role of conserved nucleotides in protein recognition and to evaluate the relative contribution of the two sites. The effect of mutations on S15 recognition was studied by measuring the relative binding affinity, RNA probing and footprinting. The crystallographic structure of the Thermus thermophilus complex allowed molecular modelling of the E. coli complex and facilitated interpretation of biochemical data. Binding is essentially driven by site 1, which includes a three-way junction constrained by a conserved base triple and cross-strand stacking. Recognition is based mainly on shape complementarity, and the role of conserved nucleotides is to maintain a unique backbone geometry. The wild-type base triple is absolutely required for protein interaction, while changes in the conserved surrounding nucleotides are partially tolerated. Site 2, which provides functional groups in a conserved G-U/G-C motif, contributes only modestly to the stability of the interaction. Binding to this motif is dependent on binding at site 1 and is allowed only if the two sites are in the correct relative orientation. Non-conserved bulged nucleotides as well as a conserved purine interior loop, although not directly involved in recognition, are used to provide an appropriate flexibility between the two sites. In addition, correct binding at the two sites triggers conformational adjustments in the purine interior loop and in a distal region, which are known to be involved for subsequent binding of proteins S6 and S18. Thus, the role of site 1 is to anchor S15 to the rRNA, while binding at site 2 is aimed to induce a cascade of events required for subunit assembly.

Amino Acid Sequence↗

PubMed2002

Identifying a folding nucleus for the lysozyme/alpha-lactalbumin family from sequence conservation clusters.

Four subfamilies of c-type lysozyme and one subfamily of alpha-lactalbumin are defined from 78 sequences, and their folding nucleus is identified with a method based on conserved residues and native structural contacts between pairs of conserved residues. One large cluster of 19 conserved residues is found which is mostly nonpolar, buried, and nonfunctional. It can be subdivided into three subclusters: (1) conserved residues in four helices; (2) conserved residues that stabilize the connector between the alpha and the beta domains; and (3) a beta-turn, sitting in the middle of a bowl of alpha-helix residues. It is proposed that this folding nucleus initiates four helices, A, B, C, and D, three beta sheets, and the connector, which corresponds closely to the nucleation of the so-called fast folding track pathway. As the secondary structures propagate, nonconserved residues and functionally conserved residues would form additional contacts. The conserved residues are selected with a phylogenetic scheme in which single members of subfamilies are selected. Subfamilies are then equally weighted to obtain the consensus conservation.

Amino Acid Sequence↗

PubMed2002

Conservation and development projects in the Brazilian Amazon: lessons from the Community Initiative Program in Rondônia.

Community-based conservation and development has become the prevailing programmatic paradigm of conservation organizations and development donors over the last 20 years, spawning a myriad of integrated conservation and development projects (ICDP) around the world. Appealing for its ambitious aspiration to harmonize sustainable economic development at the local level with the conservation of legally established protected areas (e.g., parks and reserves), the ICDP approach recently has drawn criticism from conservation biologists for failing to ensure adequate protection of biodiversity. Development planners and economists have also raised questions about the financial sustainability of ICDPs in practice and the replicability of the model from highly local contexts to larger regional scales. This paper briefly reviews the central elements of the concept of integrated conservation and development and the emerging debate over its effectiveness. A description of the Community Initiative Program (CIP), a pilot program of the Rondônia Natural Resources Management project (PLANAFLORO) in the western Brazilian Amazon state of Rondônia, follows. The CIP is a significant experiment because it boldly attempted to apply the principles of ICDP to the regional scale involving numerous different communities in one program simultaneously. Based on the author's mid-term review of the CIP in 1999, the development and conservation impacts of the program are considered. While the CIP has not significantly curbed the degradation of protected areas in Rondônia as intended, the evidence suggests lower rates of deforestation in municipios (i.e. counties) with the highest concentrations of CIP projects. Although the economic development impacts are mixed, approximately 50% of the projects delivered tangible benefits to local communities. Lessons learned from the CIP are presented in the final section. Among the lessons learned from the CIP, detailed in the final section, are several that will be familiar to other ICDP evaluators: the importance of thematic coherence in initial project design, the need for explicit attention on environmental conservation objectives, deficient institutional capacity of implementing organizations, inadequate attention to women's concerns and roles in community projects, and lack of technical criteria for measuring project sustainability.

Agriculture↗