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PubMed2006

Functional stability of microbial communities from long-term stressed soils to additional disturbance.

Functional stability, measured in terms of resistance and resilience of soil respiration rate and bacterial growth rate, was studied in soils from field plots that have been exposed to copper contamination and low pH for more than two decades. We tested whether functional stability follows patterns predicted by either the "low stress-high stability" or the "high stress-high stability" theory. Treatments consisting of soils with no or high copper load (0 or 750 kg/ha) and with low or neutral pH (4.0 or 6.1) were used. Stability was examined by applying an additional disturbance by heat (50 degrees C for 18 h) or drying-rewetting cycles. After heating, the respiration rate indicated that the soils without copper were less stable (more affected) than the soils with 750 kg/ha. Bacterial growth rate was more stable (resistant) to heat in the pH 6.1 than in the pH 4.0 soils. Growth rate was stimulated rather than inhibited by heating and was highly resilient in all soils. The respiration rate was less affected by drying-rewetting cycles in the pH 4.0 soils than in the pH 6.1 soils. Bacterial growth rate after drying-rewetting disturbance showed no distinct pattern of stability. We found that the stability of a particular process could vary significantly, depending on the kind of disturbance; therefore, neither of the two theories could adequately predict the response of the microbial community to disturbance.

Bacteria↗
PubMed1996

Effect of a chondral-labral defect on glenoid concavity and glenohumeral stability. A cadaveric model.

One of the primary stabilizing mechanisms of the glenohumeral joint is concavity-compression, the maintenance of the humeral head in the concave glenoid fossa by the compressive force generated by the surrounding muscles. This mechanism is active in all glenohumeral positions but it is particularly important in the functional mid-range, in which the capsule and ligaments are slack. The effectiveness of concavity-compression in the stabilization of a joint can be characterized in terms of the ratio between the maximum dislocating force that can be stabilized in a given direction and the load compressing the head into the glenoid (the stability ratio). Glenoid concavity can be described by the lateral humeral displacement during translation across the glenoid. The purpose of the present investigation was to characterize the concavity and stability ratios of normal cadaveric glenoids, to measure the effect of an anteroinferior chondral-labral defect on these parameters, and to measure the effectiveness of a simulated operative reconstruction on the restoration of glenoid concavity and the stability ratio. The chondral-labral defect created in this study reduced the height of the glenoid by approximately 80 per cent and the stability ratio by approximately 65 per cent for translation in the direction of the defect. Reconstruction of the anteroinferior aspect of the glenoid concavity with use of an autogenous biceps-tendon graft restored normal values for these variables.

Aged↗
PubMed1996

A tapered titanium femoral stem inserted without cement in a total hip arthroplasty. Radiographic evaluation and stability.

The results of 416 total hip arthroplasties performed in 372 patients with insertion of a Mallory-Head titanium femoral component without cement were reviewed retrospectively, to determine the stability and the radiographic parameters of stability for this type of stem. The average duration of clinical and radiographic follow-up was 3.7 years (range, 2.0 to 6.5 years). No revisions were performed to treat instability of the stem, pain, or osteolysis by the time of the latest follow-up examination. Although the clinical results were excellent, the radiographic signs of fixation that have been well described for chromium-cobalt stems were frequently absent. So-called endosteal spot welds, commonly seen in association with long, extensively coated stems, were seen infrequently. Resorptive bone-remodeling rarely extended beyond zones 1 and 7 of Gruen et al. Both endosteal and periosteal distal cortical hypertrophy was common, but the cause was unknown. Osteolysis of the distal aspect of the femur, shedding of the porous coating, and breakage of the stem were not seen. Forty-four stems (11 per cent) had initial subsidence; however, it nearly always stabilized within six months postoperatively and did not affect the eventual stability at the time of the short-term follow-up. The short-term clinical outcome confirmed the stability of these stems that had been determined from the radiographic findings and the lack of revisions. At the latest follow-up examination, 323 (87 per cent) of the patients (362 [87 per cent] of the hips) had no or slight pain in the lower limb over-all and only twenty-two (6 per cent) of the patients (twenty-seven [6 per cent] of the hips) had pain in the thigh. This tapered titanium femoral component appears to provide excellent short-term stability, without resorptive bone-remodeling, osteolysis, or a high prevalence of pain in the thigh. Radiographic evaluation of stability of this stem is clearly different from that of chromium-cobalt stems-particularly extensively coated anatomic medullary locking stems-in that so-called spot welds and severe resorptive bone changes were uncommon and distal cortical hypertrophy was common.

Adolescent↗
PubMed2000

Early ADME in support of drug discovery: the role of metabolic stability studies.

The area of Drug Discovery has undergone an amazing evolution in the past decade. This evolution is typified by the development of automated combinatorial synthesis and high throughput pharmacological testing. This, in turn, has lead to the ability to create and mine extensive databases and then model this new information. The overall result is a substantial increase in the rate of target identification, generation of new leads, and finally, optimization of those leads into clinical candidates. ADME studies have always played a critical role in helping to optimize the pharmacokinetic (PK) properties of new drugs thereby increasing their success rate. As a consequence of the increased throughput of drug discovery, ADME studies have evolved to keep pace. These so-called "early ADME" studies, are characterized by parallel processing and higher throughput than before. A primary concern of medicinal chemists is to design molecules that will have not only the desired activity, but also suitable potency and duration of action, which is influenced by pharmacokinetic properties such as bioavailability and half-life. This article focuses on a particular subset of eADME studies known as "metabolic stability", which can be an important contributor for a good pharmacokinetic profile. Metabolic stability studies represent the adaptation of more complex metabolism rate studies to a minimized system suitable for parallel processing of large numbers of compounds. The theoretical basis for metabolic stability lies in its relationship to the concept of metabolic intrinsic clearance. Typical metabolic stability protocols are discussed with respect to their relation to drug design. How metabolic stability studies have evolved to keep pace with advances in drug discovery is also discussed. Several case studies of the role of metabolic stability in drug design over the past few years are summarized to exemplify the utility of this kind of study. Finally, future trends in drug metabolism and analytical chemistry and how they may influence metabolic stability studies are reviewed.

Animals↗
PubMed2004

Microbial counts, fermentation products, and aerobic stability of whole crop corn and a total mixed ration ensiled with and without inoculation of Lactobacillus casei or Lactobacillus buchneri.

Whole crop corn (DM 29.2%) and a total mixed ration (TMR, DM 56.8%) containing wet brewers grains, alfalfa hay, dried beet pulp, cracked corn, soybean meal, and molasses at a ratio of 5:1:1:1:1:1 on fresh weight basis, were ensiled with and without Lactobacillus casei or Lactobacillus buchneri in laboratory silos. The effects of inoculation on microbial counts, fermentation products, and aerobic stability were determined after 10 and 60 d. Untreated corn silage was well preserved with high lactic acid content, whereas large numbers of remaining yeasts resulted in low stability on exposure to air. Inoculation with L. casei suppressed heterolactic fermentation, but no improvements were found in aerobic stability. The addition of L. buchneri markedly enhanced the aerobic stability, while not affecting the DM loss and NH3-N production. Large amounts of ethanol were found when the TMR was ensiled, and the content of ethanol overwhelmed that of lactic acid in untreated silage. This fermentation was related to high yeast populations and accounted for a large loss of DM found in the initial 10 d. The ethanol production decreased when inoculated with L. casei and L. buchneri, but the effects diminished at 60 d of ensiling. Inoculation with L. buchneri lowered the yeasts in TMR silage from the beginning of storage; however, the populations decreased to undetectable levels when stored for 60 d, regardless of inoculation. No heating was observed in TMR silage during aerobic deterioration test for 7 d. This stability was achieved even when a high population of yeasts remained and was not affected by either inoculation or ensiling period. The results indicate that inoculation with L. buchneri can inhibit yeast growth and improve aerobic stability of corn and TMR silage; however, high stability of TMR silage can be obtained even when no treatments were made and high population (>10(5) cfu/g) of yeasts were detected.

Aerobiosis↗
PubMed2005

Biomechanical comparison: stability of lateral-approach anterior lumbar interbody fusion and lateral fixation compared with anterior-approach anterior lumbar interbody fusion and posterior fixation in the lower lumbar spine.

OBJECT: The stability of lateral lumbar interbody graft-augmented fusion and supplementary lateral plate fixation in human cadavers has not been determined. The purpose of this study was to investigate the immediate biomechanical stabilities of the following: 1) femoral ring allograft (FRA)-augmented anterior lumbar interbody fusion (ALIF) after left lateral discectomy combined with additional lateral MACS HMA plate and screw fixation; and 2) ALIF combined with posterior transpedicular fixation after anterior discectomy. METHODS: Sixteen human lumbosacral spines were loaded with six modes of motion. The intervertebral motion was measured using a video-based motion-capturing system. The range of motion (ROM) and the neutral zone (NZ) in each loading mode were compared with a maximum of 7.5 Nm. The ROM values for both stand-alone ALIF approaches were similar to those of the intact spine, whereas NZ measurements were higher in most loading modes. No significant intergroup differences were found. The ROM and NZ values for lateral fixation in all modes were significantly lower than those of intact spine, except when NZ was measured in lateral bending. All ROM and NZ values for transpedicular fixation were significantly lower than those for stand-alone anterior ALIF. Transpedicular fixation conferred better stabilization than lateral fixation in flexion, extension, and lateral bending modes. CONCLUSIONS: Neither approach to stand-alone FRA-augmented ALIF provided sufficient stabilization, but supplementary instrumentation conferred significant stabilization. The MACS HMA plate and screw fixation system, although inferior to posterior transpedicular fixation, provided adequate stability compared with the intact spine and can serve as a sound alternative to supplementary spinal stabilization.

Aged↗
PubMed2002

Features associated with the delayed initiation of mood stabilizers at illness onset in bipolar disorder.

BACKGROUND: Whether delays in the initiation of appropriate pharmacotherapy for bipolar illness negatively affect course, outcome, or lifetime suicide risk remains at issue. METHOD: Lifetime affective syndromes and the initial emergence of affective symptoms were assessed by lifecharting in 56 DSM-IV bipolar patients. Lifetime treatment interventions were recorded by clinical interview with corroboration via record reviews. Lag times to the initiation of a mood stabilizer (after initial symptom onset and/or first lifetime affective episode) were assessed relative to functional outcome and lifetime suicide attempts. RESULTS: Mean +/- SD lag time from initial affective symptoms until first mood stabilizer treatment was 9.8 +/- 9.4 years. A greater number of years from symptom onset to first mood stabilizer was associated with poorer past year social functioning (r = -0.35, p =.008), more annual hospitalizations (r = 0.38, p =.004), and a greater likelihood for making a lifetime suicide attempt (odds ratio = 7.26, 95% confidence interval = 1.62 to 32.59; Wald chi2 = 6.69, df = 1, p =.010). Delayed mood stabilizer initiation was linked with poorer outcomes in these domains regardless of initial index episode polarities of mania versus depression. Prolonged delays to bipolar diagnoses and mood stabilizer initiation were associated with earlier ages at affective symptom onset (p <.03) and milder severity of initial symptoms (p =.003). Psychotherapy initiation often preceded mood stabilizer introduction by >/= 8 years. CONCLUSION: Delays in the initiation of mood stabilizer pharmacotherapy at illness onset, even for relatively mild symptoms at illness onset and regardless of index episode polarity, may confer an elevated risk for suicidal behavior, poorer social adjustment, and more hospitalizations in bipolar disorder. Greater surveillance screening for bipolar illness in patients who first present for psychotherapy may help to diminish these adverse outcomes.

Adolescent↗
PubMed2004

Risperidone in combination with mood stabilizers: a 10-week continuation phase study in bipolar I disorder.

BACKGROUND: Combination therapy (risperidone and a mood stabilizer) for patients with a history of bipolar disorder (DSM-IV) and hospitalized for treatment of a manic episode was assessed in a 13-week study. METHOD: Subjects received flexible doses of a mood stabilizer (lithium or divalproex) plus placebo, risperidone, or haloperidol in a 3-week double-blind study. They could then enter a 10-week open-label study during which they received risperidone combined with a mood stabilizer. RESULTS: Of the 156 patients enrolled in the 3-week study, 85 entered the 10-week open-label extension, of whom 48 completed 10 weeks of treatment. The mean +/- SE doses of risperidone were 3.8 +/- 0.3 mg/day during the 3-week study and 3.1 +/- 0.2 mg/day during the 10-week study. At double-blind endpoint, mean reductions in Young Mania Rating Scale (YMRS) scores were significantly greater in patients receiving risperidone plus mood stabilizer than in those receiving placebo plus mood stabilizer (-14.3 vs. -8.2, p <.001). Further significant (p <.001) reductions were seen during the 10 weeks of treatment with risperidone plus mood stabilizer. Symptom remission (YMRS score <or= 12) was seen in 38 patients (79%) at the end of the 10-week study. Scores on the Brief Psychiatric Rating Scale, Hamilton Rating Scale for Depression, and Clinical Global Impressions scale improved significantly (p <.05) during both the 3-week and 10-week studies. Treatment was well tolerated, and modest weight gain was observed during the 13-week study period. CONCLUSION: The combination of risperidone and a mood stabilizer was efficacious and well tolerated in the continuation treatment of patients initially hospitalized for the management of an acute manic episode.

Adult↗
PubMed1999

[Clinical benefits of stabilization after second-line chemotherapy in patients with metastatic colorectal cancer].

New innovative cytotoxic agents have proven active for treating patients with metastatic cancer who have failed first line 5FU based therapy, with sizeable objective response rates and a much higher rate of stabilization. The benefit of stabilization has not yet been well evaluated. A prospective multicentric study was carried out with 80 patients treated by second line chemotherapy for metastatic colorectal cancer. Tumor assessment and symptomatic status were reported at each cycle with a 4-month follow-up, allowing dynamic patient categorization per health state associated with the treatment. It appears that patients who are stabilized by chemotherapy have a quality of life profile comparable to that of responders, as opposed to patients with progressive disease. More patients experience improvement or stabilization of their quality of life, while they are stabilized versus progressive patients. Average number of days in hospital and hospital costs are cut down by three during stabilization as opposed to progressive disease. These results provide evidence that disease stabilization brings benefit to patients and reduces hospitalization.

Activities of Daily Living↗
PubMed1996

[Study on the stability of Japanese encephalitis vaccine--development of freeze-dry dosage form].

In order to prolong shelf-life and improve the quality of the vaccine product, not only an effective stabilizer but also a more proper dosage form has been sought. The stability of a Japanese encephalitis (JE) vaccine produced from mouse brain along with a variety of stabilizers and lyophilization protocols was evaluated. Without any stabilizers added, almost 90% of the antigenicity would vanish after freeze-drying process. Comparative studies of various compounds, including carbohydrates, amino acids, peptides and medium 199, on both antigenicity preservation and thermostability of the vaccine were carried out. The results indicated that the best reconstituted vaccines were prepared with two stabilizer formulations, sucrose and sucrose/gelatin. They were further examined by accelerated stability test at room and higher temperatures. The sucrose-added lyophilized vaccine can retain its original antigenicity for more than 60 days both at 37 degrees C and 45 degrees C. We conclude the thermostability efficiency of each of the stabilizers tested is as that follows: sucrose > sucrose/gelatin > gelatin/medium > gelatin.

Animals↗
PubMed2000

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

UNLABELLED: Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.

Adult↗
PubMed2001

The effect of hand-grip stabilization on isokinetic torque at the knee.

Isokinetic dynamometers commonly measure muscle strength during conditioning and rehabilitation. Previous studies have shown that stabilization can affect isokinetic torque production. However, the effect of stabilization with hand-grip use has not been examined, and there are inconsistencies in the literature regarding its use. Fifteen men (mean age +/- SD = 24 +/- 3 years, height = 187 +/- 6 cm, mass = 84 +/- 10 kg) and 15 women (age = 25 +/- 4 years, height = 167 +/- 8 cm, mass = 62 +/- 6 kg) were tested on a Cybex 6000 dynamometer. Torque and joint angle signals, as well as quadriceps and hamstrings electromyographic (EMG) signals, were recorded during maximal knee flexion/extension at speeds of 60, 180, and 300 degrees x s(-1). Subjects performed the testing both with (stabilized) and without (nonstabilized with arms folded across the chest) hand-grip use. Repeated-measures analysis of variance (ANOVA) revealed a significant-motion (flexion, extension), X-condition (stabilized, non-stabilized) interaction in the data from the men in which hand-grip stabilization resulted in an 8.4% increase in knee extensor torque vs. a 0.2% increase in knee flexor torque. Stabilization did not significantly affect torque in women. The EMG analyses did not indicate a significant change in either agonist drive or antagonist cocontraction that accounted for the enhanced torque output with hand-grip use. This study found that hand-grip use enhanced knee extension maximal torque in men, but did not affect torque in women. The EMG data did not account for the changes in the torque data. Differences between men and women may have been due to mechanical factors and grip strength. These results indicate that hand-grip use needs to be considered when examining gender differences in knee strength and when studying knee flexion-extension ratios.

Adult↗
PubMedDate not supplied

[Ontogenesis and population: evaluation of developmental stability in natural populations].

Ontogenetic and population studies traditionally develop independently. At the same time, the relevance of specific analysis of a specimen as ontogenesis for both correct assessment of populations and their dynamics in time and space and understanding the mechanisms underlying population processes is becoming more and more clear. Developmental stability serves as the most general description of the developing organism status. The level of developmental noise commonly evaluated by fluctuating asymmetry is the main index of developmental stability. High developmental stability is maintained on the basis of genetic coadaptation under optimal developmental conditions. Coordinated changes in developmental stability and other homeostatic indices, including genetic, physiological, biochemical, and immune indices suggest that we consider the general status of the organism by evaluating its developmental stability. Evaluation of developmental stability as a measure of environmental stress, apparently, is the most promising. In practical terms, this allows us to evaluate and monitor environmental health under both natural and various anthropogenic conditions. Outlooks of this approach as relates to studies of developmental stability are discussed.

Adaptation, Physiological↗
PubMed1992

[Rotational stability of angiography catheters].

Rotatory stability is a parameter that reflects the ability of a catheter to transmit a rotation applied at the outer end to the catheter tip for the purpose of selective probing. A method for measuring the rotatory stability is described, and the results of rotatory stability measurements of 70 different commercially available catheters are reported. There is an almost linear correlation between the rotatory stability and the difference between the respective fourth power of the external and internal diameter or, approximately, to the fourth power of the external diameter for catheters without wire reinforcement. With the same cross-sectional dimensions, the rotatory stability of teflon, polyethylene, and nylon catheters has an approximate ratio of 1:2:4. Wire reinforcement increases rotatory stability by an average factor of about 3. For catheters of calibers 5 F and 6 F, a correlation between the rotatory stability and the weight of the reinforcing wire mesh is apparent.

Biomechanical Phenomena↗
PubMed2004

Variational and genetic properties of developmental stability in Dalechampia scandens.

Because low developmental stability may compromise the precision with which adaptations can be reached, the variability and genetic basis of developmental stability are important evolutionary parameters. Developmental stability is also an important clue to understanding how traits are regulated to achieve their phenotypic target value. However, developmental stability must be studied indirectly through proxy variables, such as fluctuating asymmetry, that are suggested to have noisy and often nonlinear relationships to the underlying variable of interest. In this paper we first show that mean-standardized measures of variance and covariance in fluctuating asymmetry, unlike heritabilities, repeatabilities, and correlations, are linearly related to corresponding measures of variation in underlying developmental stability. We then examine the variational properties of developmental stability in a population of the Neotropical vine, Dalechampia scandens (Euphorbiaceae). By studying fluctuating asymmetry in a large number of floral characters in both selfed and outcrossed individuals in a diallel design, we assemble strong evidence that both additive genetic and individual variation and covariation in developmental stability are virtually absent in this population.

Analysis of Variance↗
PubMed2005

[Heavy metal stabilization in municipal solid waste incineration fly ash using soluble phosphate].

The physico-chemical characteristics of municipal solid waste incineration fly ashes was analyzed. It indicated that the main elements of fly ashes are Ca, Cl, K, S and Si, and many heavy metals such as Pb, Zn, Cu, Mn and Cr can be found in fly ashes, and the heavy metal leaching toxicity such as Pb, Cu, Zn and Cd is much higher than the standards. A new kind of stabilization agent-soluble phosphate is chosen to treat with fly ash, different influence factors including agent dosage, curing time and pH are taken into consideration to test its stabilization for the stabilized fly ash. The experimental results indicate that fly ash treated with soluble phosphate can have excellent stabilization effect, and the leaching toxicity for Pb, Cd and Zn can be reduced by 97.5%, 91.6% and 95.5% at a phosphate dosage of 3%; curing time can not influence its stabilization; and, stabilized fly ash using soluble phosphate can keep long-term stabilization at a broad pH value.

Carbon↗
PubMed1992

The protein-protein complex between pp60v-src and hsp90 is stabilized by molybdate, vanadate, tungstate, and an endogenous cytosolic metal.

In a recent study demonstrating the cell-free reconstitution of the pp60v-src-hsp90 complex, we found that the tyrosine kinase-hsp90 complex is stabilized by molybdate (Hutchison, K. A., Brott, B. K., De Leon, J. H., Perdew, G. H., Jove, R., and Pratt, W. B. (1992) J. Biol. Chem. 267, 2902-2908). In this paper, we examine in detail the stabilization of this protein-protein interaction by transition metal oxyanions. The pp60v-src-hsp90 complex is stabilized by sodium molybdate with the same concentration dependence as the glucocorticoid receptor-hsp90 complex. As with the steroid receptor heterocomplexes, vanadate and tungstate also stabilize the pp60v-src-hsp90 interaction. Passage of cytosol through a Chelex-100 metal-chelating resin destabilizes the native pp60v-src-hsp90 complex, suggesting that the complex is normally stabilized by an endogenous metal factor. Readdition of either the heat-stable components of cytosol or a partially purified endogenous metal factor stabilizes the metal-depleted complex. Molybdate also stabilizes the presence of p50, a known hsp90-associated protein, in the pp60v-src heterocomplex. Given the identical effects of transition metal oxyanions on both pp60v-src- and steroid receptor-hsp90 complexes and the lack of any sequence homology between pp60v-src and the receptors, it seems very likely that it is the common component, hsp90, that contains the site of the metal interaction.

Animals↗
PubMed1992

Evidence that a salt bridge in the light chain contributes to the physical stability difference between heavy and light human ferritins.

Human ferritin, a multimeric iron storage protein, is composed by various proportions of two subunit types: the H- and L-chains. The biological functions of these two genic products have not been clarified, although differences in reactivity with iron have been shown. Starting from the hypothesis that the high stability typical of ferritin is an important property which may be relevant for its iron storage function, we studied ferritin homopolymers of H- and L-chains in different denaturing conditions. In addition we analyzed 13 H-chain variants with alterations in regions conserved within mammalian H-chains. In all the denaturation experiments H-chain ferritin showed lower stability than L-chain ferritin. The difference was greater in guanidine HCl denaturation experiments, where the end products are fully unfolded peptides, than in acidic denaturation experiments, where the end products are peptides with properties analogous to "molten globule." The study on H-chain variants showed: (i) ferritin stability was not affected by alterations of regions exposed to the inner or outer surface of the shell and not involved in intra- or inter-chain interactions; (ii) stability was reduced by alterations of sequences involved in inter-subunit interactions such as the deletion of the N-terminal extension or substitutions along the hydrophobic and hydrophilic channels; (iii) stability was increased by the substitution of 2 amino acids inside the four-helix bundle with those of the homologous L-chain. One of the residues is involved in a salt bridge in the L-chain, and we concluded that the stability difference between H- and L-ferritins is to a large extent due to the stabilizing effect of this salt bridge on the L-subunit fold.

Amino Acid Sequence↗