Biomedical subjects

C Zeng

Publications and source records attributed to C Zeng.

At least 19 recordsLinked to original sources

PubMed2006

Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.

The molecular mechanisms controlling beta-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.

Adrenergic beta-Agonists↗

PubMed2006

Treatment of early mixed cellular and humoral renal allograft rejection with tacrolimus and mycophenolate mofetil.

This prospective study investigated the efficiency of the tacrolimus (Tac) combined with mycophenolate mofetil (MMF) alone without immunoadsorption (IA) or plasmapheresis (PPH) as treatment for early (within 2 weeks) acute humoral rejection (AHR) in non-sensitized renal allograft recipients. Of 160 patients enrolled in this prospective study, 11 patients had histologically and clinically confirmed early steroid-resistant acute rejection with an antibody response and received Tac-MMF therapy. No other aggressive rescue methods such as IA, PPH were used, according to the study design. Patients (n=11) were followed for 13.8+/-3.5 months; nine were females. The complement-dependent cytotoxicity crossmatch was negative before transplantation in all patients and only positive for panel-reactive antibody in one patient. Most of the rejection episodes were mixed with cellular rejection (four patients met Banff IIA criteria, five patients met Banff IIB, one patient met Banff IB, and one patient met Banff borderline). After 16.19+/-6.16 days of treatment, all rejection episodes were successfully reversed and all graft functions were stable, with a mean serum creatinine level of 1.12+/-0.32 mg/dl during follow-up. No patient suffered from severe infectious complications (except one case of urinary infection). Our investigation suggests that Tac combined with MMF alone is adequate to reverse early mixed cellular and humoral C4d-positive rejection in non-sensitized renal allograft recipients.

Acute Disease↗

PubMed2006

Late and early C4d-positive acute rejection: different clinico-histopathological subentities in renal transplantation.

This study was performed to investigate the clinical and pathologic features of C4d-positive steroid-resistant acute rejection (AR) at different phases after renal transplantation. Fifty-six kidney allograft recipients with C4d-positive AR were divided into three groups, very early rejection (VER, occurring < or =14 days following transplantation, n=28), early rejection (ER, occurring 15-180 days following transplantation, n=5), and late rejection (LR, occurring >180 days following transplantation, n=23). Clinical and pathological features were evaluated. Significantly more patients in the ER and LR groups were associated with a reduction or withdrawal of immunosuppressants. More patients in the ER and LR groups experienced a significant (>3 g/l) decrease in serum albumin (80% ER, 91.3% LR, 7.1% VER, P<0.001) and a decrease in hemoglobin (>1 g/dl) (80, 100 vs 17.9%, P<0.001). Most VER patients reported a fever and had very rapid graft dysfunction requiring dialysis. Significantly more patients (87%) had interstitial fibrosis and tubular atrophy in the LR group compared with the other groups and 13% had transplant glomerulopathy. Most cases of VER were reversed with tacrolimus and mycophenolate mofetil treatment, with or without immunoadsorption, with a 1-year survival rate of 96.4%, compared with only 60 and 52.2% in the ER and LR groups. In conclusion, C4d-positive steroid-resistant AR at different time points is associated with unique clinico-histopathological manifestations requiring distinct treatment strategies. Late episodes are usually associated with significantly reduced serum albumin and hemoglobin levels and a poorer outcome. A more specialized treatment protocol should be established for these patients.

Acute Disease↗

PubMed2006

Value of B-type natriuretic peptide in diagnosing left ventricular dysfunction in dialysis-dependent patients.

BACKGROUND: B-type natriuretic peptide (BNP) is elevated in patients with end-stage renal failure. The reported accuracy of BNP in diagnosing left ventricular dysfunction in these patients has been inconsistent. AIM: To investigate the diagnostic values of BNP for left ventricular dysfunction in patients undergoing haemodialysis for chronic renal failure. METHODS: We measured plasma BNP before and at 10 min and 3, 6 and 24 h after haemodialysis in 56 patients. RESULTS: The average plasma BNP before haemodialysis was 284 +/- 369 pg/mL, which was higher than that of healthy subjects (37 +/- 37 pg/mL; n = 32, P < 0.01). The average plasma BNP in patients with left ventricular dysfunction (n = 21) was substantially higher than that in those with normal ventricular function before and at 10 min and 3, 6 and 24 h after haemodialysis (P < 0.001). The area under the receiver operating characteristic curves was greater than 0.895 before and at the four time points after haemodialysis (P < 0.01). Using 152 pg/mL as a cut-off value, predialysis BNP has 81% sensitivity and 83% specificity in diagnosing left ventricular dysfunction in these patients. CONCLUSION: We concluded that plasma BNP offers a good sensitivity and specificity in diagnosing left ventricular dysfunction in patients with dialysis-dependent renal failure.

Adolescent↗

PubMed2005

B-type natriuretic peptide in patients with clinical hyperthyroidism.

AIMS: To investigate the level and clinical significance of plasma B-type natriuretic peptide (BNP) in patients with hyperthyroidism. METHODS: Plasma BNP was measured in 32 healthy subjects and 67 patients with clinical hyperthyroidism. Left ventricular anatomy and function was assessed with echocardiography. RESULTS: The average BNP in hyperthyroid patients was higher than that in healthy subjects (186+/-140 vs 34+/-17 ng/l, p =0.001). The increase in BNP was mainly found in hyperthyroid patients who had clinical and echocardiographic evidence of left ventricular dysfunction (250+/-190 ng/l). The BNP level in patients with hyperthyroidism, but with normal left ventricular function, was similar to that of the controls (37+/-17 vs 34+/-17, ng/l, p>0.05). Multi-regression analysis showed that left atrial diameter and left ventricular ejection fraction were independently associated with the plasma levels of BNP. CONCLUSIONS: there is a significant elevation in plasma BNP in patients with hyperthyroidism; the increase is largely due to hyperthyroidism-induced left ventricular dysfunction. Measurements of plasma BNP may help to detect heart failure in patients with clinical hyperthyroidism.

Adult↗

PubMed2005

Autologous transplantation followed closely by reduced-intensity allogeneic transplantation as consolidative immunotherapy in advanced lymphoma patients: a feasibility study.

We report outcomes in advanced lymphoma patients (n = 32) who enrolled in a trial of prospectively planned combined autologous/reduced-intensity transplantation (RIT) (n = 25) or who received RIT shortly after prior autografting because of high relapse risk or progressive disease (n = 7). Nine patients on the autologous/RIT transplant protocol did not proceed to planned RIT because of patient choice (n = 4), disease progression (n = 3), toxicity (n = 1), or no adequate donor (n = 1). Among the 23 other patients, RIT was started a median of 59 days (range 31-123) after autologous transplant. Fifteen patients had related donors, five patients had unrelated donors, and three patients had cord blood donors. Among all patients completing RIT, the median overall survival time was 385 days (95% CI 272-792), and the median relapse-free survival time was 157 days (95% CI 119-385). At the time of reporting, six patients (26%) remain alive and three patients (13%) remain alive without relapse. The 100-day transplant-related mortality (TRM) was 9% among all patients and was 0% among matched sibling donors. Overall TRM was 43%. Tandem transplant is feasible in advanced lymphoma with low early TRM. However, practical challenges associated with the strategy were significant and high levels of late TRM due to graft-versus-host disease and infections suggest that modifications of the procedure will be needed to improve outcomes and patient retention.

Adult↗

PubMed2005

Relationship between the regulatory region polymorphism of human tissue kallikrein gene and essential hypertension.

Ten alleles with length and nucleotide sequence variations were identified in the regulatory region of human tissue kallikrein gene. This present study aimed to study the polymorphisms of the regulatory region of human tissue kallikrein gene of the Chinese and investigate the relationship of the polymorphisms with essential hypertension. A case-control study was conducted in 200 hypertensive and 200 normotensive subjects of unrelated Chinese Han origin. All subjects were aged from 30 to 70 years and had no history of diabetes mellitus, kidney failure, or thyroid gland disease. The alleles were detected by polymerase chain reaction (PCR) and genotyping was performed with allele-specific oligonucleotide analysis (ASO). Data from the essential hypertensive and control subjects were statistically analysed by the Student's t-test and chi2-test. The age- and gender-matching of the groups were accurate. The case group and the control group were in Hardy-Weinberg equilibrium at this locus (cases, P=0.313; control subjects, P=0.457). There were nine alleles among the case and control groups, and the allele frequencies were found to be significantly different between cases and controls (chi2=25.701, P<0.001). The genotype frequencies were also significantly different (chi2=70.100, P<0.001) between these two groups. In conclusion, there are polymorphisms in the regulatory region of human tissue kallikrein gene in the Chinese Han people. Differences in both allele frequencies and genotype frequencies between these two groups have provided evidence towards the association of hypertension with the polymorphisms in this studied site.

Asian People↗

PubMed2005

Systolic and diastolic heart failure are associated with different plasma levels of B-type natriuretic peptide.

Previous studies have found that plasma B-type natriuretic peptide (BNP) is elevated during left ventricular systolic or diastolic dysfunction. It is unclear whether the ventricular systolic and diastolic function is associated with different levels of plasma BNP. Plasma BNP was measured in 149 heart failure patients by a rapid point-of-care assay. The patients were divided into left ventricular diastolic dysfunction (n = 48), left ventricular systolic dysfunction (n = 62) and right ventricular systolic dysfunction group (n = 39). The mean BNP level in the left ventricular diastolic dysfunction, left ventricular systolic dysfunction and right ventricular systolic dysfunction was 115 +/- 80 pg/ml, 516 +/- 445 pg/ml and 345 +/- 184 pg/ml, respectively (p < 0.05). We concluded that ventricular systolic and diastolic dysfunction increases plasma BNP levels to a different extent. Left and right ventricular systolic dysfunction is associated with a higher level of plasma BNP than left ventricular diastolic dysfunction.

Adult↗

PubMed2005

Amyloid-beta peptide enhances tumor necrosis factor-alpha-induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes.

Although accumulating evidence demonstrates that white matter degeneration contributes to pathology in Alzheimer's disease (AD), the underlying mechanisms are unknown. In order to study the roles of the amyloid-beta peptide in inducing oxidative stress damage in white matter of AD, we investigated the effects of amyloid-beta peptide 25-35 (Abeta) on proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)-induced inducible nitric oxide synthase (iNOS) in cultured oligodendrocytes (OLGs). Although Abeta 25-35 by itself had little effect on iNOS mRNA, protein, and nitrite production, it enhanced TNF-alpha-induced iNOS expression and nitrite generation in OLGs. Abeta, TNF-alpha, or the combination of both, increased neutral sphingomyelinase (nSMase) activity, but not acidic sphingomyelinase (aSMase) activity, leading to ceramide accumulation. Cell permeable C2-ceramide enhanced TNF-alpha-induced iNOS expression and nitrite generation. Moreover, the specific nSMase inhibitor, 3-O-methyl-sphingomyelin (3-OMS), inhibited iNOS expression and nitrite production induced by TNF-alpha or by the combination of TNF-alpha and Abeta. Overexpression of a truncated mutant of nSMase with a dominant negative function inhibited iNOS mRNA production. 3-OMS also inhibited nuclear factor kappaB (NF-kappaB) binding activity induced by TNF-alpha or by the combination of TNF-alpha and Abeta. These results suggest that neutral sphingomyelinase/ceramide pathway is required but may not be sufficient for iNOS expression induced by TNF-alpha and the combination of TNF-alpha and Abeta.

Amyloid beta-Peptides↗

PubMed2005

Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM crescentic glomerulonephritis.

OBJECTIVE: To study the prevalence of ANCA and their target antigen in Chinese patients with anti-GBM crescentic glomerulonephritis (CGN), and to evaluate the possible role of ANCA in Chinese anti-GBM CGN patients with coexisting serum ANCA by studying clinicopathologic features of this disease. MATERIAL AND METHODS: Twenty-three sera were collected from 23 renal biopsy-proven anti-GBM CGN patients. According to the standardized procedures, all of the sera were determined by both, indirect immunofluorescence (IIF) ANCA, and enzyme-linked immunosorbent assay (ELISA) MPO-ANCA, PR3-ANCA and BPI-ANCA. The patients were divided into two groups according to serum ANCA positivity (Group A) or negativity (Group B). Thirty-three ANCA-associated pauci-immune CGN patients were regarded as control group (Group C). Their clinicopathologic features were compared to reveal whether ANCA correlated with disease activity. RESULTS: There were 11 (47.8%) cases with positive serum ANCA in 23 anti-GBM glomerulonephritis patients. There were 4/11 MPO-ANCA (one with positive PR3-ANCA and C-ANCA, three with negative IIF-ANCA), 1/11 PR3-ANCA (with positive MPO-ANCA and C-ANCA), 3/11 P-ANCA (with negative ELISA-ANCA) and 5/11 C-ANCA (one with positive PR3-ANCA and MPO-ANCA, and the other four with negative ELISA-ANCA). No BPI-ANCA was detected. No different clinicopathologic features were found between Groups A and B. Both were different from Group C in age, sex ratio, frequence of anuria and ESRD, variety of crescents, glomerular sclerosis, vessel lesion and prognosis. CONCLUSION: Our data demonstrate that ANCA in Chinese patients with anti-GBM CGN is not rare. The major target antigen of ANCA is MPO. ANCA seems not to be correlated with disease activity.

Adolescent↗

PubMed2004

Hox expression in AML identifies a distinct subset of patients with intermediate cytogenetics.

We previously reported that favorable and poor prognostic chromosomal rearrangements in acute myeloid leukemia (AML) were associated with distinct levels of HOX expression. We have now analyzed HOX expression in 50 independent adult AML patients (median age=62 years), together with FLT3 and FLT3-ligand mRNA levels, and FLT3 mutation determination. By cluster analysis, we could divide AMLs into cases with low, intermediate and high HOX expression. Cases with high expression were uniquely restricted to a subset of AMLs with intermediate cytogenetics (P=0.0174). This subset has significantly higher levels of FLT3 expression and appears to have an increase of FLT3 mutations (44%), while CEBPalpha mutations were infrequent (6%). FLT3 mRNA levels were correlated with the expression of multiple HOX genes, whereas FLT3 mutations were correlated with HOXB3. In some cases, FLT3 was expressed at levels equivalent to GAPDH in the absence of genomic amplification. We propose that high HOX expression may be characteristically associated with a distinct biologic subset of AML. The apparent global upregulation of HOX expression could be due to growth-factor signaling or, alternatively, these patterns may reflect a particular stage of differentiation of the leukemic cells.

Acute Disease↗

PubMed2002

Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas.

HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials.

Aged↗

PubMed2002

Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia.

We used a degenerate RT-PCR screen and subsequent real-time quantitative RT-PCR assays to examine the expression of HOX and TALE-family genes in 34 cases of chromosomally defined AML for which outcome data were available. AMLs with favorable cytogenetic features were associated with low overall HOX gene expression whereas poor prognostic cases had high levels. Characteristically, multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed in conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression were also observed in the FAB subtype, AML-M1. Spearmann correlation coefficients indicated that the expression levels for many of these genes were highly inter-related. While we did not detect any significant correlations between HOX expression and complete response rates or age in this limited set of patients, there was a significant correlation between event-free survival and HOXA7 with a trend toward significance for HoxA9, HoxA4 and HoxA5. While patients with elevated HOX expression did worse, there were notable exceptions. Thus, although HOX overexpression and clinical resistance to chemotherapy often coincide, they are not inextricably linked. Our results indicate that quantitative HOX analysis has the potential to add new information to the management of patients with AML, especially where characteristic chromosomal alterations are lacking.

Acute Disease↗

PubMed2002

The effect of hepatocyte growth factor on turkey satellite cell proliferation and differentiation.

The effect of hepatocyte growth factor (HGF) on turkey satellite cell proliferation and differentiation was examined in cell culture. Satellite cell clones were established from one muscle of an individual turkey. The results showed that HGF is a potent activator and mitogen of turkey satellite cells and embryonic myoblasts with maximal stimulation at 1 ng/mL. HGF is also an inhibitor of differentiation of turkey satellite cells. Heterogeneity in the responsiveness to HGF in the turkey satellite cell population was observed between clones selected for fast (Early) or slow (Late) rates of proliferation. However, two other Early clones exhibited responses similar to those of two other Late clones. When combined with insulin-like growth factor (IGF) and fibroblast growth factor (FGF), singularly or in combination, HGF did not exert any additive or synergistic effects on Early or Late clone proliferation. Whereas when combined with IGF, FGF, and platelet-derived growth factor (PDGF), HGF significantly stimulated proliferation of the Late clone but not the Early clone. Addition of anti-HGF antibody to culture media diminished proliferation and provided evidence of autocrine production of HGF by turkey satellite cell cultures. Heterogeneity also exists in the turkey satellite cell population with respect to autocrine production of HGF.

Animals↗

PubMed2001

Biochemical analysis of retroviral structural proteins to identify and quantify retrovirus expressed by an NS0 murine myeloma cell line.

A subclone of the NS0 murine myeloma cell line, frequently used to produce recombinant monoclonal antibodies, was found by a transmission electron microscopy method to express a surprisingly high titer of 10(11) retroviral particles per ml of culture supernatant. Infectivity assays showed a very low infectious titer with the restricted host range expected for a murine amphotropic retrovirus. A Western blot assay for the viral capsid protein was developed to confirm the high titer values and provide a means for monitoring batch consistency and virus removal during the purification process. Mass spectrometry of several of the viral Gag proteins demonstrated that the cell line appeared to produce at least two closely related retroviruses. N-terminal sequencing of three of the Gag proteins demonstrated that these retroviruses were members of the murine leukemia retroviral family. Western blot detection with an antibody for the capsid protein gave a linear standard curve over the range of 0.1-3 ng per lane. This allows the detection of viral titers as low as 6x10(7) virions per ml without the need to concentrate the sample. The Western blot method has higher throughput and less variability than transmission electron microscopy methods and has potential for monitoring viral titer and clearance during development of manufacturing processes.

Amino Acid Sequence↗

PubMed2001

Membrane interactions of a novel viral enterotoxin: rotavirus nonstructural glycoprotein NSP4.

The rotavirus enterotoxin, NSP4, is a novel secretory agonist that also plays a role in the unique rotavirus morphogenesis that involves a transient budding of newly made immature viral particles into the endoplasmic reticulum. NSP4 and an active peptide corresponding to NSP4 residues 114 to 135 (NSP4(114-135)) mobilize intracellular calcium and induce secretory chloride currents when added exogenously to intestinal cells or mucosa. Membrane-NSP4 interactions may contribute to these alterations; however, details of a lipid-binding domain are unresolved. Therefore, circular dichroism was used to determine (i) the interaction(s) of NSP4 and NSP4(114-135) with model membranes, (ii) the conformational changes elicited in NSP4 upon interacting with membranes, (iii) if NSP4(114-135) is a membrane interacting domain, and (iv) the molar dissociation constant (K(d)) of NSP4(114-135) with defined lipid vesicles. Circular dichroism revealed for the first time that NSP4 and NSP4(114-135) undergo secondary structural changes upon interaction with membrane vesicles. This interaction was highly dependent on both the membrane surface curvature and the lipid composition. NSP4 and NSP4(114-135) preferentially interacted with highly curved, small unilamellar vesicle membranes (SUV), but significantly less with low-curvature, large unilamellar vesicle membranes (LUV). Binding to SUV, but not LUV, was greatly enhanced by negatively charged phospholipids. Increasing the SUV cholesterol content, concomitant with the presence of negatively charged phospholipids, further potentiated the interaction of NSP4(114-135) with the SUV membrane. The K(d) of NSP4(114-135) was determined as well as partitioning of NSP4(114-135) with SUVs in a filtration-binding assay. These data confirmed NSP4 and its active peptide interact with model membranes that mimic caveolae.

Amino Acid Sequence↗

PubMed2001

Large-insert BAC/YAC libraries for selective re-isolation of genomic regions by homologous recombination in yeast.

We constructed representative large-insert bacterial artificial chromosome (BAC) libraries of two human pathogens (Trypanosoma brucei and Giardia lamblia) using a new hybrid vector, pTARBAC1, containing a yeast artificial chromosome (YAC) cassette (a yeast selectable marker and a centromere). The cassette allows transferring of BACs into yeast for their further modification. Furthermore, the new hybrid vector provides the opportunity to re-isolate each DNA insert without construction of a new library of random clones. Digestion of a BAC DNA by an endonuclease that has no recognition site in the vector, but which deletes most of the internal insert sequence and leaves the unique flanking sequences, converts a BAC into a TAR vector, thus allowing direct gene isolation. Cotransformation of a TAR vector and genomic DNA into yeast spheroplasts, and subsequent recombination between the TAR vector's flanking ends and a specific genomic fragment, allows rescue of the fragment as a circular YAC/BAC molecule. Here we prove a new cloning strategy by re-isolation of randomly chosen genomic fragments of different size from T. brucei cloned in BACs. We conclude that genomic regions of unicellular eukaryotes can be easily re-isolated using this technique, which provides an opportunity to study evolution of these genomes and the role of genome instability in pathogenicity.

Animals↗

PubMed2001

The designability of protein structures.

It has been noted that natural proteins adapt only a limited number of folds. Several researchers have investigated why and how nature has selected this small number of folds. Using simple models of protein folding, we demonstrate systematically that there is a "designability principle" behind nature's selection of protein folds. The designability of a structure (fold) is measured by the number of sequences that can design the structure--that is, sequences that possess the structure as their unique ground state. Structures differ drastically in terms of their designability. A small number of highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess proteinlike secondary structures, motifs, and even tertiary symmetries. In addition, they are thermodynamically more stable and fold faster than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.

Amino Acid Motifs↗