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PubMed1984

Domain structure of flagellin.

The chemotaxis of bacteria such as Salmonella and Escherichia coli involves smooth swimming punctuated by periods of tumbling. In smooth swimming the flagellar filaments are left-handed, in tumbling they are right-handed with a different wavelength. The filaments are constructed from a globular protein, flagellin, by a process of self-assembly. The existing models assume that the flagellin molecule is bistable and longitudinal rows of subunits take one of the two possible conformations. Such a model explains the observed different morphology of the flagellum. We have studied Salmonella and E. coli flagellins in polymeric and monomeric forms by scanning microcalorimetry and circular dichroism. We have inferred that a flagellin molecule consists of several domains, two of which are structured at physiological temperatures and are in the monomeric form, while the others acquire a regular form only in the process of polymerization. This phenomenon may be the basis of a process during which the flagellin molecule, fitting into the flagellum, acquires a conformation analogous to that of the neighbouring molecule in the longitudinal row.

Bacterial Proteins↗

PubMed1988

Multi-site binding of human nuclear protein to the Alu-family repeated DNA.

Nuclear protein which selectively binds to the Alu-family DNA repeat (AFR, Blur8) is partially purified from human HeLa cells using a gel retention assay. At low protein concentrations only a single complex of the protein with AFR is formed (CII). Increasing protein concentrations lead to the gradual disappearance of CII, being replaced by complexes with higher (CI) and lower (CIII, CIV) electrophoretic mobilities. Differential binding of AFR restriction subfragments indicates that multiple protein-binding sites are present within AFR. We discuss two models explaining the anomalous electrophoretic mobility of CII by DNA bending or looping upon cooperative multi-site binding of the protein to AFR.

Antigens, Polyomavirus Transforming↗

PubMed1983

Effects of surrounding sequence on the suppression of nonsense codons.

Using a lacI-Z fusion system, we have determined the efficiency of suppression of nonsense codons in the I gene of Escherichia coli by assaying beta-galactosidase activity. We examined the efficiency of four amber suppressors acting on 42 different amber (UAG) codons at known positions in the I gene, and the efficiency of a UAG suppressor at 14 different UGA codons. The largest effects were found with the amber suppressor supE (Su2), which displayed efficiencies that varied over a 35-fold range, and with the UGA suppressor, which displayed a 170-fold variation in efficiency. Certain UGA sites were so poorly suppressed (less than 0.2%) by the UGA suppressor that they were not originally detected as nonsense mutations. Suppression efficiency can be correlated with the sequence on the 3' side of the codon being suppressed, and in many cases with the first base on the 3' side. In general, codons followed by A or G are well suppressed, and codons followed by U or C are poorly suppressed. There are exceptions, however, since codons followed by CUG or CUC are well suppressed. Models explaining the effect of the surrounding sequence on suppression efficiency are considered in the Discussion and in the accompanying paper.

Base Sequence↗

PubMed1989

Association between craniomandibular disorders and occlusal interferences.

No theoretical model explaining craniomandibular disorders has been generally accepted, despite the large number of studies on its etiology. This article suggests that one reason for the lack of a well-structured causal explanation could be associated with the study design most often used: cross-sectional studies of samples representative of a base population. Variation in the number of interferences was increased among the subjects by eliminating occlusal interferences annually in the treatment group (n = 53). The control group (n = 46) underwent placebo treatment. A double-blind design was used throughout the 3-year study. A cross-sectional analysis in the third year disclosed a significant association between the number of interferences and the signs of craniomandibular disorders. The results suggest that the absence of interference-free subjects in nonselected samples can be one explanation for the lack of association reported in most studies.

Adolescent↗

PubMed1976

Stress at the pleural surface.

The transmission of forces between the visceral and parietal pleural is modelled as being mediated by two distinct pathways: (a) a contact pressure (Pcon) acting on an area of contact (Acon) and (2) a pleural liquid pressure (Pliq) acting on the area of liquid anfractuosities (Aliq). Summation of the forces yields a new equation relating pleural surface pressure (Ppl) to Pcon, Acon, Pliq, and Aliq. A complete solution of the equation is restricted by present limitations on measurement technology. However, assuming that the volume of pleural liquid is constant during tidal breathing, analysis of the model explains the findings that tidal swings in Pliq (deltaPliq) are sometimes greater than tidal swings in Ppl (deltaPpl). It also predicts that the influence of a change of lung elastic recoil on Pliq may be different in magnitude than its effect on Ppl. Therefore deltaPliq is not necessarily equivalent to deltaPpl.

Airway Resistance↗

PubMed1993

Modelling the dependence of contrast sensitivity on grating area and spatial frequency.

We modelled the human foveal visual system in a detection task as a simple image processor comprising (i) low-pass filtering due to the optical transfer function of the eye, (ii) high-pass filtering of neural origin, (iii) addition of internal neural noise, and (iv) detection by a local matched filter. Its detection efficiency for gratings was constant up to a critical area but then decreased with increasing area. To test the model we measured Michelson contrast sensitivity as a function of grating area at spatial frequencies of 0.125-32 c/deg for simple vertical and circular cosine gratings. In circular gratings luminance was sinusoidally modulated as a function of the radius of the grating field. In agreement with the model, contrast sensitivity at all spatial frequencies increased in proportion to the square-root of grating area at small areas. When grating area exceeded critical area, the increase saturated and contrast sensitivity became independent of area at large grating areas. Spatial integration thus obeyed Piper's law at small grating areas. The critical area of spatial integration, marking the cessation of Piper's law, was constant in solid degrees at low spatial frequencies but inversely proportional to spatial frequency squared at medium and high spatial frequencies. At low spatial frequencies the maximum contrast sensitivity obtainable by spatial integration increased in proportion to spatial frequency but at high spatial frequencies it decreased in proportion to the cube of the increasing spatial frequency. The increase was due to high-pass filtering of neural origin (lateral inhibition) and the decrease was mainly due to the optical transfer function of the eye. Our model explained 95% of the total variance of the contrast sensitivity data.

Computer Simulation↗

PubMed1984

Occupational stress, health-related behavior, and blood pressure: a 5-year follow-up.

The association of occupational stress factors and health-related habits with blood pressure and blood pressure change over a 5-year follow-up was studied in 388 Finnish white-collar and blue-collar workers. The occupational stress factors consisted of noise level, discomfort due to noise, monotony, and self-suppression of opinion. Behavioral variables included the frequency of mild intoxication, leisure-time physical activity, cigarette smoking, relative weight, and change in weight. In the cross-sectional study, only relative weight was positively associated with both the systolic and diastolic blood pressure. For the prediction of blood pressure change, multiple linear regression showed that in the total sample none of the nine variables was a statistically significant predictor of systolic blood pressure change over the follow-up period. The change in weight was the most significant predictor (P less than 0.001) of diastolic blood pressure change, followed by intoxication (P less than 0.01). Further analyses by sex and occupational status showed that among female white-collar workers, intoxication was the strongest predictor of both systolic and diastolic blood pressure changes. In this group, the total model explained 34% of the variability in systolic and 27.7% in diastolic blood pressure change. In other groups and in the total sample, the proportions explained were markedly smaller. Also, in some subgroups, self-suppression, noise, and physical activity were significant predictors of blood pressure change. It is concluded that in comparison with reduction of weight, the other behavioral and stress factors studied seem to be of minor importance in the prevention of high blood pressure in normal populations, even if these factors may be relevant in some susceptible subpopulations or in populations whose exposure levels are extreme.

Adult↗

PubMed1994

The A. thaliana disease resistance gene RPS2 encodes a protein containing a nucleotide-binding site and leucine-rich repeats.

In plants, resistance to a pathogen is frequently correlated with a genetically defined interaction between a plant resistance gene and a corresponding pathogen avirulence gene. A simple model explains these gene-for-gene interactions: avirulence gene products generate signals (ligands), and resistance genes encode cognate receptors. The A. thaliana RPS2 gene confers resistance to the bacterial pathogen P. syringae carrying the avirulence gene avrRpt2. A map-based positional cloning strategy was used to identify RPS2. The identification of RPS2 was verified using a newly developed transient assay for RPS2 function and by genetic complementation in transgenic plants. RPS2 encodes a novel 105 kDa protein containing a leucine zipper, a nucleotide-binding site, and 14 imperfect leucine-rich repeats.

Amino Acid Sequence↗

PubMed1982

Determinants of foster care placement for the maltreated child.

This study examined the records of the North Carolina Central Registry of Child Abuse and Neglect to determine which social, family, and child characteristics were most influential in the decision to place a child in foster care. These records contained all theoretically relevant factors as well as demographic data. Analysis included the computation of odds ratios for foster care for each of 250 variables. A maximum likelihood logistic regression model was constructed to obtain the independent and cumulative contribution of each factor. Some expected variables such as parental stress factors (substance abuse) and types of abuse (burns and scalds) placed a child at a significant risk for placement in foster care (p less than 0.01). However, less obvious factors such as referral source (law enforcement agencies) or geographic area also placed children at risk. Overall, the model explained little of the variance of these decisions (R2 = 0.168) and poorly predicted placement (sensitivity 66.3 per cent, specificity 74.6 per cent). Using existing data, we were unable to adequately describe the decision process in selecting foster care.

Adolescent↗

PubMed1987

(A)GGG(A), (A)CCC(A) and other potential 3' splice signals in primate nuclear pre-mRNA sequences.

Several 3' splice signals in nuclear precursor mRNAs have already been known for some time: the AG doublet on the left-hand side of the splice and a run of pyrimidines just upstream of it. More recently it has been noted that the YNYTRAY sequence (where Y is a pyrimidine, R a purine and N any base) is a branching-sequence participating in formation of a lariat structure. Keller and Noon have shown the existence of several putative consensus sequences at this site. In this work, extensive computations of the distributions of 256 quartets in all primate nuclear pre-mRNA intron sequences present in GenBank have been carried out. Several putative signals upstream and downstream of the 3' splice have been detected. These have been compared with the results obtained in analogous computations carried out on all nuclear pre-mRNA introns present in a combined eukaryotic file containing mammal, non-mammalian vertebrate, invertebrate and plant sequences. The distributions of the more interesting oligomers are shown here. Of particular interest are the putative (A)GGG(A) signal 60 nucleotides upstream of the 3' splice site and (A)CCC(A) 3-40 nucleotides downstream of it. A possible splicing model explaining these data and involving formation of alternative hairpin loop structures is proposed.

Animals↗

PubMed1990

Ontogeny of the endorphinergic and dopaminergic modulation on the immobility reflex elicited by clamping in rats.

The effects of some dopaminergic and endorphinergic agonists and antagonists on the immobility reflex (IR) elicited by clamping the neck of the rat were investigated. We found that both morphine and haloperidol produce a significant increase in the duration of this IR at all ages tested (10, 20 and 300 days). The effect of apomorphine depends on the age of the rat, showing an increase in the duration of the immobility reflex only at the age of 10 days which was not counteracted by haloperidol. Naloxone alone showed a slight non-significant tendency to increase the duration of the IR but blocked morphine effects at all ages tested. When naloxone was added to apomorphine there was a peculiar effect: the duration of the immobility reflex was increased significantly in rats of 20 days and adults, but not in 10-day-old rats. The combination of morphine plus haloperidol showed the most marked potentiation of the immobility reflex at all ages tested. These results are discussed with respect to the development of dopaminergic and endorphinergic systems to control posture and movement during the IR, and its possible relation to the catatonia of schizophrenics. A hypothetical model explaining an interaction between the dopaminergic and endorphinergic systems in developing and adult rats is presented.

Aging↗

PubMed1983

Prostaglandins and gene action: possible relevance to the effect of PG system on leukocyte alkaline phosphatase enzyme activity.

Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) synthesis respectively and chloroquine, a PGE1 synthesis enhancer and PGE2 antagonist can alter the leukocyte alkaline phosphatase (LAP) enzyme activity. Thromboxane A2 and other related prostaglandins (PGs) are known to bind to DNA and thus possibly regulate DNA action. It is proposed here that prostaglandins are able to modify LAP activity by their action on the DNA and thus the Gene that codes for LAP. This hypothesis envisages that normally there are specific receptors on the genes for PGs. Taking LAP enzyme system as the model, it is proposed that the affinity of TxA1, TxA2, PGE2 and PGE1 to the operator is more than to that of the repressor. But when the levels of TxA2, PGE2 and PGE1 are in excess, all the receptors on the operator are not only completely occupied but they are also able to bind to repressor in sufficient amounts to transiently switch off the LAP synthesis by the structural gene. It is further envisaged that the affinity of the PG receptors on the operator and repressor systems of the operon is greatest for TxA1 and least for PGE2 (TxA1 greater than TxA2 greater than PGE1 greater than PGE2). This hypothesis though simply in its model explains all the variables obtained in our studies on the effect of PGs on the LAP activity. This concept by itself or a suitable modification, may explain the role of PGs in the pathogenesis of cancer. It will be interesting to study, in the light of this hypothesis, the role of the PG system on DNA repair mechanism, m-RNA and t-RNA synthesis and gene action in several systems.

Alkaline Phosphatase↗

PubMed1992

An explanation for the rarity of extraaxial metastases in brain tumors.

Primary brain tumors invade and metastasize within the central nervous system (CNS), but rarely extraaxially. A model explaining this behavior is presented. In non-CNS tumors metastases occur since subpopulations of cells capable of invasion and metastases are selected by the tissular environment, and in particular by the connective stroma, which opposes invasion. The CNS lacks a connective stroma, therefore a primary tumor can grow easily in it, but subpopulations capable of metastasization are not selected. Implications of the explanation are: 1) metastasization is largely based on the ability to invade the connective stroma, 2) paradoxically, a less favourable host tissue environment can result in a more aggressive tumoral behavior.

Brain Neoplasms↗

PubMed1995

Neuronal circuitry controlling the near response.

Experiments in primates have contributed greatly to our understanding of the neural mechanisms involved in the eye movements required to view objects at different distances. Early work focused on the circuitry for generating horizontal vergence eye movements alone. However, vergence eye movements are associated with lens accommodation and are usually accompanied by saccadic eye movements, so more recent work has been directed at understanding the interactions between vergence and accommodation, and between vergence and saccades. A new model explains the neural basis for interactions between vergence and accommodation by a neural network in which pre-motor elements are shared by these two systems. The effects of saccades on vergence eye movements appear to be the result of shared pre-motor circuits as well. Current evidence suggests that pontine omnipause neurons, known to be crucial for the generation of saccades, play an important role in the vergence pre-motor circuitry.

Accommodation, Ocular↗

PubMed1994

Concentrations of Lp(a) in black and white young adults: relations to risk factors for cardiovascular disease.

The purpose of this report is to compare the distribution of total lipoprotein(a) [Lp(a)] mass in a population-based sample of blacks and whites, and to investigate the association of Lp(a) with other cardiovascular risk factors. A cross-sectional study design was used. Black and white men and women (n = 4125), aged 23-35 from the Coronary Artery Risk Development in Young Adults Study had the following data collected: Lp(a), lipids and lipoproteins, other metabolic parameters, anthropometry, physical activity, dietary intake, cigarette use, and alcohol use. Blacks had concentrations of Lp(a) approximately three-fold higher than whites. Medians were: black men 21.5 mg/dL, black women 23.9 mg/dL, white men 6.1 mg/dL, and white women 6.4 mg/dL. Lp(a) concentrations were higher in women than in men. Lp(a) was not consistently associated with smoking, alcohol consumption, physical activity, dietary fat, or obesity. In stepwise regression analyses in both blacks and whites, Lp(a) was consistently associated with low-density lipoprotein (LDL) cholesterol, fibrinogen, and apoB; regression models explained about 7% of the variance in Lp(a). In whites, Lp(a) tended to be higher in those with a positive family history of myocardial infarction. The large differences in Lp(a) between blacks and whites, and the absence of association with many other variables are consistent with previous suggestions that Lp(a) concentration is in large part genetically determined. The association of Lp(a) with LDL and fibrinogen, two strong risk factors for cardiovascular disease (CVD), could represent part of the mechanism of the CVD risk associated with Lp(a) in other studies. Longitudinal data are needed to determine the extent to which Lp(a) will independently predict disease, especially in diverse ethnic groups.

Adult↗

PubMed1996

Gravity sensing in tip-growing cells.

In addition to the statocytes of roots and shoots, a number of tip-growing cells also sense gravity, which influences the cells' growth and development. Since these tip-growing cells are highly suitable for observations in vivo, the movement and sedimentation of their statoliths can be studied in detail. Experimental manipulation by centrifugation, drug application, optical tweezers or microgravity can be monitored by light microscopy. The statoliths are localized in distinct cytoplasmic areas by interactions with actin filaments or microtubules, and their sedimentation seems to be narrowly confined. Since gravisensing and the graviresponse take place within the same cell, the gravitropic signal transduction chain is not complicated by signal transmission between sensing and responding cells. Studies on tip-growing cells have now enabled the formulation of models explaining positive and negative gravitropism.

Actins↗

PubMed1996

Adaptation of bone to altered loading environment: a biomechanical approach using X-ray absorptiometric data from the patella of a young woman.

Loading induced changes in the bone mineral apparent density (BMAD) and average strain magnitude (strain index) of the patella were estimated using a novel analytic method of dual energy X-ray absorptiometric (DXA) and isometric strength data obtained from repeated measurements of a 26-year-old woman. The strain index was used as a major determinant of bone adaptation to physical loading. The subject's lower limb skeleton was measured 12 times during a 3-year period including a 1-year unilateral strength training intervention, an accidental knee ligament rupture, and a 2-year rehabilitation period. Instead of standard DXA analysis, the patella, a bone practically affected by quadriceps activity only, was analyzed in terms of estimated loading induced stresses and strains. The mechanical stress is directly proportional to the effective force and inversely proportional to the area over which the given force is applied. The strain, in turn, is proportional to the given stress divided by the bone stiffness, which was assumed to be proportional to BMAD. The effective force, the contact area, and the BMAD were estimated from the muscle strength and DXA data, respectively. In addition, post-traumatic bone loss and subsequent recovery with time were assessed using an exponential model. The loading during the 1-year training period increased the average patellar strain index by 47% and did not affect the patellar BMAD. Immediately after the injury, the apparent inability to do muscle work drastically reduced the strain index and likely initiated the patellar bone loss, a loss which continued for about 4 months. During rehabilitation, the imbalance between the patellar stiffness and increased functional stress (muscular performance) became sufficiently large to level off the bone loss and stimulate bone gain. At that time, the strain index indicated that the patellar deformation more than doubled (135%) as compared to baseline level. Accordingly, the BMAD increased until an apparent balance between BMAD and the muscular strength was achieved by the 3-year end point. The exponential models explained well both the post-traumatic bone loss (R2 = 0.89) and bone gain during recovery (R2 = 0.98). In conclusion, the present observations support the concept of the nonlinear nature of the skeletal response to mechanical loading and suggest a potential utility of muscle strength measurements and DXA information for improved understanding of the effects of training, immobilization and remobilization on bone tissue.

Absorptiometry, Photon↗

PubMed2006

Factors influencing treatment time in orthodontic patients.

INTRODUCTION: The purpose of this retrospective study was to identify (and quantify the effect of) factors that influence orthodontic treatment time. METHOD: The sample consisted of 366 consecutive orthodontic patients (220 female, 146 male, aged 10-20 years, treated by 1 orthodontist) who completed treatment in a single stage with fixed appliances. Four categories of data (sociodemographic characteristics, malocclusion characteristics, treatment methods, and patient cooperation) were collected from treatment records and analyzed. RESULTS: Average treatment time was 23.5 months (range, 12-37; SD, 4.7). A multiple regression model explained 38% of the variance and identified 9 significant variables. Five were pretreatment characteristics: male sex, maxillary crowding of 3 mm or more, Class II molar relationships, proposed treatment plan involving extractions, and delayed extractions. The remaining variables (3 of which were associated with patient cooperation) were poor oral hygiene, poor elastic wear, bracket breakages, and brackets rebonded for repositioning. CONCLUSIONS: Orthodontic treatment time is influenced by a number of patient characteristics and clinical decisions. It is possible to predict estimated treatment time for a patient by using a small number of personal characteristics and treatment decisions.

Adolescent↗