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Fifty subjects who were followed longitudinally between 13 and 18 years showed an average increase in lower arch crowding of 2.36 mm. This increase in crowding was examined in relation to tooth width, arch width and jaw width, actual and relative, and to changes in these dimensions with correlation and multiple regression analyses. No relationship was found between width dimensions and late crowding in the lower arch.
The purpose of this study was to determine the manner in which mandibular arch crowding was resolved in Class I growing patients who were treated nonextraction. A retrospective study was completed with 30 patients from a postgraduate orthodontic clinic, treated with a variety of treatment modalities. Eight study models and six cephalometric parameters were examined before treatment and at the end of active treatment (posttreatment). The results showed that statistically significant increases in arch width occurred at the canine (0.9 mm), first premolar (1.6 mm), second premolar (1.8 mm), and first molar (1.2 mm). The incisors were advanced an average of 2.1 mm and proclined 6.1 degrees. The molars showed no anteroposterior movement. Arch perimeter increased 2.3 mm and arch depth increased 1.6 mm. Multiple linear regression analysis revealed that 52% of the variance in crowding resolution was accounted for by an increase in arch perimeter. It was concluded that the resolution of crowding, in this group of patients with Class I malocclusions, was achieved by generalized expansion of the buccal segments, along with advancement of the lower incisors. In some cases, these changes may be consistent with treatment objectives; in others, they may be undesirable. It is therefore important for practitioners to carefully evaluate treatment outcome irrespective of the treatment modality, to determine whether treatment objectives are being met.
PURPOSE: To compare the testability and threshold acuity levels for very young children on the crowded HOTV logMAR distance visual acuity test presented on the BVAT apparatus and the Lea Symbols logMAR distance visual acuity chart. METHODS: Subjects were 87 Head Start children from age 3 to 3.5 years. Testing consisted of binocular pretraining at near using a lap card as needed, binocular pretraining at 3 m, and threshold testing for each eye. The testing procedure, adapted from the Amblyopia Treatment Study, presented optotypes until the child was unable to correctly name or match three of three or three of four optotypes of a given size. Threshold acuity was the smallest size for which at least three optotypes were correctly identified. RESULTS: Both near and distance pretraining were completed by 71% of children for HOTV and by 75% for Lea Symbols (P =.39). The distribution of threshold acuities differed between the two tests. For the 69 eyes of 53 children who were successfully tested with both optotypes, results from the crowded HOTV acuity test were on average 0.25 logMar (2.5 lines) better than those from the Lea Symbols acuity test (P <.001). CONCLUSIONS: The proportion of children between 3 and 3.5 years of age whose monocular visual acuity could be assessed was high and was similar for the two charts tested. Crowded HOTV acuity results were better on average than results using Lea symbols. The different formats of the two tests may explain the observed differences in threshold acuity level.
The concept of excluded volume and the theory of effects of excluded volume on the equilibria and rates of macromolecular reactions in fluid media containing high total concentrations of macromolecules ('crowded' media) are summarized. Reports of experimental studies of crowding effects published during the last year are tabulated. Limitations of current excluded volume theory are discussed, and a determination is made of conditions under which this theory may and may not be validly applied. Recently suggested novel approaches to quantitative analysis of crowding phenomena, which may help to overcome some of the limitations of current theory, are summarized.
Parkinson's disease (PD) is one of many neurodegenerative diseases that are characterized by amyloid fibril formation. Alpha-synuclein is a primary component of the fibrillar neuronal inclusions, known as Lewy bodies, that are diagnostic of PD. In addition, the alpha-synuclein gene is linked to familial PD. Fibril formation by alpha-synuclein proceeds via discrete beta-sheet-rich oligomers, or protofibrils, that are consumed as fibrils grow. Both FPD mutations accelerate formation of protofibrils, suggesting that these intermediates, rather than the fibril product, trigger neuronal loss. In idiopathic PD, other factors may be responsible for accelerating protofibril formation by wild-type alpha-synuclein. One possible factor could be molecular crowding in the neuronal cytoplasm. We demonstrate here that crowding using inert polymers significantly reduced the lag time for protofibril formation and the conversion of the protofibril to the fibril, but did not affect the morphology of either species. Physiologically realistic changes in the degree of in vitro crowding have significant kinetic consequences. Thus, nonspecific changes in the total cytoplasmic protein concentration, induced by cell volume changes and/or altered protein degradation, could promote formation of and stabilize the alpha-synuclein protofibril.
Crowded triarylphosphines possessing ferrocenyl groups [(4-ferrocenyl-2,6-diisopropylphenyl)(n)(2,4,6-triisopropylphenyl)(3-n)P (5a, n = 1; 5b, n = 2; 5c, n = 3)] were synthesized by the reaction of the corresponding arylcopper(I) reagents with the diarylchlorophosphines. Structures of the triarylphosphines were studied by 1H, 13C, and 31P NMR spectroscopies, and the characteristic patterns of the proton signals of the 2,6-isopropyl groups and upfielded 31P chemical shifts suggest structural similarities of the triarylphosphine moiety to the previously reported tris(2,4,6-triisopropylphenyl)phosphine (2). X-ray crystallography of 5c also revealed that the structure around the phosphorus is similar to that of 1, where the average bond angle and length around the phosphorus atom are 110.8 degrees and 1.854 A, respectively. According to the electrochemical measurements, phosphines 5a, 5b, and 5c are reversibly oxidized in two, three, and four steps, respectively, which suggests significant electronic interaction among the triarylphosphine and the ferrocene redox centers as well as weak interaction among the ferrocene redox centers. The EPR spectra obtained at cryogenic temperature after oxidation of phosphines 5a, 5b, and 5c are superpositions of those for the cation radicals of the crowded triarylphosphine and ferricinium. The solution spectra obtained at 293 K, which consist of two lines typical of the cation radical of the crowded triarylphosphines, become weaker as the number of the ferrocenyl groups increases and the cation radical of 5c does not show EPR signals. These findings suggest not only instability of the tetra(cation radical) of 5c but also the course of oxidation where the ferrocenyl groups in the periphery of the molecules are oxidized at first.
The effects of macromolecular crowding on protein stability and folding kinetics have been studied using the recently developed 15N spin relaxation dispersion technique. By applying this method to a redesigned apocytochrome b562, the kinetics and thermodynamics of the protein folding processes in both the presence and the absence of crowding agents have been characterized. The result indicates that, even under the mild crowded environments (in the presence of 85 mg/mL of PEG 20K), the folding rate of the protein can speed up significantly while the unfolded rate remains unchanged within experimental error.
The sterically crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was synthesized by dehydrohalogenation of the corresponding 3,4-dibromophospholane, in order to probe the possibility that the steric congestion would cause some flattening of the phosphorus pyramid and an increase in electron delocalization. The phosphole was a recrystallizable solid with (31)P NMR delta 1.8. Semiempirical calculations indicated that the pyramidal shape was retained but was noticeably flatter than in 1-phenylphosphole. In the low energy conformation, the phosphole and phenyl ring planes are approximately orthogonal, with the 2-tert-butyl group in the less crowded position that is syn to the lone pair on phosphorus. The 6-methyl group is positioned under the phosphole ring. This conformational prediction was amply confirmed by several chemical shift and coupling effects in the (13)C NMR spectrum. The (1)H NMR spectrum displayed an unusually large four-bond coupling (6 Hz) of (31)P to the m-phenyl proton syn to the lone pair (and none to the anti-meta proton), consistent with the orthogonal conformation. The oxide of the phosphole showed more stability than that of less crowded phospholes and gave a (31)P NMR signal that was detectable over a several hour period at room temperature. The oxide proceeded to give the usual Diels-Alder dimer and also formed a cycloadduct with N-phenylmaleimide. The phosphoryl group of the latter was reduced with trichlorosilane to give the phosphine. This new 7-phosphanorbornene derivative gave the most downfield (31)P NMR shift (delta 153.3) of any member of this family, all of which are characterized by remarkable deshielding in the syn isomer.
Small proteins move in crowded cell compartments by anomalous diffusion. In many of them, e.g., the endoplasmic reticulum, the proteins move between lipid membranes in the aqueous lumen. Molecular crowding in vitro offers a systematic way to study anomalous and normal diffusion in a well controlled environment not accessible in vivo. We prepared a crowded environment in vitro consisting of hexaethylene glycol monododecyl ether (C(12)E(6)) nonionic surfactant and water and observed lysozyme diffusion between elongated micelles. We have fitted the data obtained in fluorescence correlation spectroscopy using an anomalous diffusion model and a two-component normal diffusion model. For a small concentration of surfactant (below 4 wt %) the data can be fitted by single-component normal diffusion. For larger concentrations the normal diffusion fit gave two components: one very slow and one fast. The amplitude of the slow component grows with C(12)E(6) concentration. The ratio of diffusion coefficients (slow to fast) is on the order of 0.1 for all concentrations of surfactant in the solution. The fast diffusion is due to free proteins while the slow one is due to the protein-micelle complexes. The protein-micelle interaction is weak since even in a highly concentrated solution (35% of C(12)E(6)) the amplitude of the slow mode is only 10%, despite the fact that the average distance between the micelles is the same as the size of the protein. The anomalous diffusion model gave the anomaly index (r(2)(t) approximately t(alpha)), alpha monotonically decreasing from alpha = 1 (at 4% surfactant) to alpha = 0.88 (at 37% surfactant). The fits for two-component normal diffusion and anomalous diffusion were of equally good quality, but the physical interpretation was only straightforward for the former.
DNA:Au nanosphere bioconjugates have applications in biosensing and in the bottom-up assembly of materials. These bioconjugates can be selectively assembled into three-dimensional aggregates upon addition of complementary DNA oligonucleotides and can be dissociated by heating above a melting transition temperature at which the DNA duplexes are denatured. Herein we describe the impact of polymeric solutes on the thermal denaturation behavior of DNA:Au nanoparticle bioconjugate assemblies. Polymeric solutes can dramatically impact biochemical reactions via macromolecular crowding. Poly(ethylene glycol)s (PEGs) and dextrans of varying molecular weights were used as crowding reagents. While both PEG and dextran increased the stability of DNA:Au aggregates, melting transition temperatures in the presence of PEG were impacted more significantly. Polymer molecular weight was less important than polymer chemistry and weight percent in solution. For a high (15%) weight percent of PEG, aggregation was observed even in the absence of complementary oligonucleotides. These results underscore the importance of polymer chemistry in addition to physical volume exclusion in macromolecular crowding and point to the importance of understanding these effects when designing biorecognition-based nanoparticle assembly schemes in complex matrixes (i.e., any involving polymeric solutes).
The effects of crowding agents, polyethylene glycol (PEG 20K), Dextran 70, and bovine serum albumin, on the denaturation of homotetrameric D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) in 0.5 M guanidine hydrochloride and the reactivation of the fully denatured enzyme have been examined quantitatively. Increasing the concentration of PEG 20K to 225 mg/ml decreases the rate constant of slow phase of GAPDH inactivation to 5% but with no change for the fast phase. Chaperone GroEL assists GAPDH refolding greatly and shows even higher efficiency under crowding condition. Crowding mainly affects refolding steps after the formation of the dimeric folding intermediate.
This study examines 21 cases in which crowds were present when a disturbed person threatened to jump off a building, bridge, or tower. Baiting or jeering occurred in 10 of the cases. Analysis of newspaper accounts of the episodes suggests several deindividuation factors that might contribute to the baiting phenomenon: membership in a large crowd, the cover of nighttime, and physical distance between crowd and victim (all factors associated with anonymity). The baiting phenomenon was also associated with warm temperatures and long duration of episode. These factors suggest leads for more systematic investigation.
A shape can be more difficult to identify when other shapes are near it. For example, when several grating patches are viewed parafoveally, observers are unable to report the orientation of the central patch. This phenomenon, known as 'crowding,' has historically been confused with lateral masking, in which one stimulus attenuates signals generated by another stimulus. Here we show that despite their inability to report the orientation of an individual patch, observers can reliably estimate the average orientation, demonstrating that the local orientation signals are combined rather than lost. Our results imply that crowding is distinct from ordinary masking, and is perhaps related to texture perception. Under crowded conditions, the orientation signals in primary visual cortex are pooled before they reach consciousness.
The purpose of this study was to (1) describe the prevalence of mandibular incisor irregularity (II) among untreated adults in the United States and (2) evaluate the factors explaining individual differences in II. Data were derived for a random sample of 9044 individuals (49% male and 51% female; 35% Mexican American, 34% black, and 31% white) between 15 and 50 years of age collected as part of the Third National Health and Nutrition Examination Survey. Although the differences were small (0.5 mm), males had significantly greater II than did females; blacks showed less II than did whites (0.9 mm) and Mexican Americans (1.1 mm). Family income was negatively related with II. Incisor irregularity increased in a curvilinear fashion with age, with the greatest increases occurring during early adulthood. Although the number of premolars and molars (first and second) were positively related with II, the presence of third molars had a negative effect on II. Multivariate Poisson regression analyses showed that the ethnicity, the number of first and second molars, sex, and age combined to explain differences in II. Odds ratios were relatively low, indicating that these factors explained relatively small amounts of between-subject variation. We conclude that (1) approximately 50% of individuals in the United States who were 15-50 years of age have little or no II, 23% have moderate II, and 17% have severe irregularity, (2) erupted third molars are not associated with increased crowding, (3) crowding increases most during early adulthood, and (4) although individual differences in crowding are multifactorial, the primary determinants remain unidentified.
This study reports the treatment of an adolescent patient with dilacerated maxillary incisor. She complained of severe crowding with a high-positioned left upper canine. Her left central incisor had been impacted and moved to proper position at the age of eight years, resulting in a severe root dilaceration. To avoid any progression of root dilacerations and resorption in the maxillary incisor, maxillary lateral expansion and molar distalization plus multibracket appliance were selected as the best nonextraction treatment plan. The maxillary expansion and molar distalization should provide adequate space for the correction of the severe crowding, and treatment with a multibracket appliance was initiated. After a 17-month treatment with a multibracket appliance, an acceptable occlusion was achieved with a Class I molar relationship. An acceptable occlusion was maintained without recurrence of the crowding and impairment of the dilacerated root in the maxillary incisor during three years of retention. It is emphasized that careful planning is required to avoid any progression of the root dilaceration and resorption through orthodontic treatment. A shortening of the period of applying orthodontic force on the dilacerated incisor and avoidance of tooth extraction will minimize the risk factors.
An innovative technique that involves a nickel-titanium mandibular bonded lingual 3-3 retainer was used to treat relapse of mandibular anterior crowding. The purpose of this study was to demonstrate clinical procedures and to study the effects of a new mandibular bonded lingual 3-3 retainer on the mandibular dental arch. In 18 patients, changes in the irregularity index and in arch dimensions (intercanine width, arch length, and arch depth) were measured against the patients' mandibular dental casts, which were obtained at completion of the previous orthodontic treatment (T(0)). These measurements were taken at the beginning of retreatment (T(1)), and 2 (T(2)), 4 (T(3)), and 6 (T(4)) months after initiation of retreatment. During the period of relapse (T(0)-T(1)), the irregularity index increased from 1.3 to 3.5 mm and the mandibular arch dimensions decreased. Four months after a segment of.018-in nickel-titanium archwire was bonded lingually from canine to canine, the irregularity index decreased from 3.5 to 1.0 mm and the arch dimensions increased and recovered their original posttreatment dimensions. The nickel-titanium archwire was left in place for permanent retention after the period of retreatment. This simple technique effectively solved relapse of mandibular anterior crowding in 4 months. This mandibular bonded lingual 3-3 retainer could be used both actively, to re-treat mandibular anterior crowding without the use of lingual brackets, and passively, for maintenance as a bonded lingual retainer.
The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-beta-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, phi(c), of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at phi(c) = 0, increase nonmonotonically as phi(c) increases, reaching a maximum at phi(c)=phi(c)(*). At high values of phi(c), the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes in native state stability and folding kinetics at phi(c) can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius R(s) approximately (4pi/3phi(c))(1/3) R(c) (R(c) is the radius of the crowding particles) as long as phi(c)< or =phi(c)(*). We show that the extent of native state stabilization at finite phi(c) is comparable with that in a spherical pore. In both situations, rate enhancement is due to destabilization of the denatured states with respect to phi(c) = 0.
Parasite transmission generally exhibits some form of positive density dependence. Thus, as population density increases, so too does the per capita risk of becoming infected. Under such circumstances, natural selection should favor individuals that use cues associated with population density to determine the optimal allocation of resources to disease resistance mechanisms. As a consequence, individuals experiencing crowded conditions are predicted to be more resistant to parasites and pathogens than those experiencing low-density conditions. This phenomenon (termed "density-dependent prophylaxis") [Wilson, K. & Reeson, A. F. (1998) Ecol. Entomol. 23, 100-101] is predicted to be particularly prevalent in outbreak pest species and in species exhibiting density-dependent phase polyphenism, such as the desert locust, Schistocerca gregaria. Here we show that, as predicted, desert locusts reared under crowded conditions are significantly more resistant than solitary locusts to the entomopathogenic fungus, Metarhizium anisopliae var. acridum, a key natural disease of acridids and an important agent in locust and grasshopper biocontrol. Moreover, enhanced pathogen resistance in crowded locusts is associated with elevated antimicrobial activity, but not with any difference in thermal preferences or behavioral fever response. These results have implications for understanding the development and biocontrol of locust plagues.