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At least 1,243 records · Page 69Linked to original sources
PubMed1999

Increased expression of matrix metalloproteinase-1 in osteocytes precedes bone resorption as stimulated by disuse: evidence for autoregulation of the cell's mechanical environment?

An in vivo animal model of bone adaptation was used to examine a possible role for matrix metalloproteinase-1 in the local mediation of bone remodeling: to corrode the coupling of osteocytes to the matrix in an attempt to autoregulate the cell's perception of its mechanical environment. Twelve young (12-16 months old) skeletally mature turkeys were separated into groups to be studied for stimulus periods of either 3 or 30 days. In each animal, the left ulna was functionally isolated and subjected to either disuse or 3,000 microstrain at 1 Hz for 10 minutes per day. The right ulna remained intact and served as an intra-animal control. No significant differences in bone area were detected at 3 days; however, ulnae subjected to disuse lost 8 +/- 4% (+/-SD) of bone area by 30 days. Over the same period, ulnae subjected to the mechanical stimulus gained 21 +/- 9% of bone area. With use of in situ reverse transcription-polymerase chain reaction, less than 2% of the osteocytes examined from the intact control ulnae stained positively for matrix metalloproteinase-1 mRNA. An antibody raised against matrix metalloproteinase-1 revealed no positively labeled osteocytes in the intact ulnae. This low percentage of osteocytes expressing matrix metalloproteinase-1 mRNA was similar to that seen in ulnae subjected to the osteogenic mechanical stimuli. In contrast, ulnae subjected to either 3 or 30 days of disuse showed evidence of matrix metalloproteinase-1 mRNA activity in a high percentage of osteocytes (89 +/- 5 and 66 +/- 8%, respectively; each time point significantly different from intact ulnae, as well as from each other, p < 0.05). The percentage of osteocytes labeled with the anti-matrix metalloproteinase-1 antibody was also highly elevated following 3 days of disuse (74 +/- 17%). These data demonstrate that an early response of bone to disuse is the upregulation of matrix metalloproteinase-1 activity in osteocytes. It is proposed that this upregulation of collagenase activity is indicative of the cell's degradation of coupling to the matrix, and it thus reflects the osteocyte's regulation of its own mechanical environment. We believe that such autoregulation of the osteocyte's physical environment will accommodate subtle changes in the bone's functional environment without the need to add or resorb bone tissue.

Animals↗
PubMed2006

Regenerative properties of fetal sheep tendon are not adversely affected by transplantation into an adult environment.

Tendon injuries account for a significant number of musculoskeletal afflictions each year. While new surgical techniques and rehabilitation protocols have led to improved clinical outcomes, postsurgical scarring remains the most problematic aspect of tendon repair. In contrast to this typical pattern of fibrosis, recent studies have shown that fetal tendon is capable of healing without scar. However, whether this regenerative healing pattern is intrinsic to the fetal tissue itself or the result of its environment is not known. Thus, the objective of this study is to examine the influence of an adult environment on healing in adult and fetal tendons. We hypothesized that injured fetal tendon tissue transplanted into an adult environment would retain a regenerative healing pattern after injury, demonstrating normal histological and mechanical properties. Our results support this hypothesis. Histological analyses revealed considerable alterations in adult tendon transplants after injury while fetal transplants showed no abnormalities. The injured adult tendons also demonstrated elevated levels of TGF-beta1, bFGF, and CD44 at the wound site, whereas the fetal specimens showed little or no such changes in response to injury. The data from our biomechanical studies further corroborate these observations, with significant decreases in the stiffness, modulus, and almost all viscoelastic properties in wounded versus unwounded adult tendons, and fetal specimens showing no differences in mechanical properties between the wounded and unwounded groups. Thus, the results of our investigation demonstrate that the adult environment is not an impediment to scarless repair and that this capability is intrinsic to the fetal tendon itself. Our study also begins to provide insight into the mechanisms controlling this regenerative response.

Age Factors↗
PubMedDate not supplied

Clinical study of paramyotonia congenita with and without myotonia in a warm environment.

Fourteen patients with paramyotonia congenita were examined clinically. Patients of 3 families had no myotonia in a warm environment while in a cold environment they developed paradoxical myotonia (myotonia aggravated by repeated muscle contraction). Patients of a 4th family had myotonia associated with after-activity in a warm environment which was not paradoxical. This myotonia was aggravated by cooling. In a warm environment the resting muscles of all patients showed no spontaneous electromyographic activity except for occasional myotonic runs. On cooling, spontaneous fibrillations developed. This was most intense at 32 degrees C-28 degrees C (muscle temperature). On deeper cooling it ceased. In contrast, 5 patients with myotonia congenita did not show such activity during cooling. In all paramyotonic patients cooling (30 degrees C-25 degrees C) produced muscle paralysis, which outlasted rewarming by several hours. At 32 degrees C-30 degrees C muscle relaxation was slowed. Recording of electromyographic activity and isometric contractions of the long finger flexors during cooling revealed that the slowing of muscle relaxation in paramyotonia is not as closely linked to after-activity as is the slowing of muscle relaxation in myotonia congenita.

Adolescent↗
PubMed2005

Structural characterization of proteins using residue environments.

A primary challenge for structural genomics is the automated functional characterization of protein structures. We have developed a sequence-independent method called S-BLEST (Structure-Based Local Environment Search Tool) for the annotation of previously uncharacterized protein structures. S-BLEST encodes the local environment of an amino acid as a vector of structural property values. It has been applied to all amino acids in a nonredundant database of protein structures to generate a searchable structural resource. Given a query amino acid from an experimentally determined or modeled structure, S-BLEST quickly identifies similar amino acid environments using a K-nearest neighbor search. In addition, the method gives an estimation of the statistical significance of each result. We validated S-BLEST on X-ray crystal structures from the ASTRAL 40 nonredundant dataset. We then applied it to 86 crystallographically determined proteins in the protein data bank (PDB) with unknown function and with no significant sequence neighbors in the PDB. S-BLEST was able to associate 20 proteins with at least one local structural neighbor and identify the amino acid environments that are most similar between those neighbors.

Amino Acids↗
PubMed1994

Polar and nonpolar atomic environments in the protein core: implications for folding and binding.

Hydrophobic interactions are believed to play an important role in protein folding and stability. Semi-empirical attempts to estimate these interactions are usually based on a model of solvation, whose contribution to the stability of proteins is assumed to be proportional to the surface area buried upon folding. Here we propose an extension of this idea by defining an environment free energy that characterizes the environment of each atom of the protein, including solvent, polar or nonpolar atoms of the same protein or of another molecule that interacts with the protein. In our model, the difference of this environment free energy between the folded state and the unfolded (extended) state of a protein is shown to be proportional to the area buried by nonpolar atoms upon folding. General properties of this environment free energy are derived from statistical studies on a database of 82 well-refined protein structures. This free energy is shown to be able to discriminate misfolded from correct structural models, to provide an estimate of the stabilization due to oligomerization, and to predict the stability of mutants in which hydrophobic residues have been substituted by site-directed mutagenesis, provided that no large structural modifications occur.

Chemical Phenomena↗
PubMed2002

Investigation of penetratin peptides. Part 1. The environment dependent conformational properties of penetratin and two of its derivatives.

The homeodomain, the DNA-binding domain of Antennapedia homeoprotein, is composed of three alpha-helices and one beta-turn between helices II and III. Its third helix from the N-terminal (helix III) can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. To the best of our knowledge, this helix III, called penetratin, which consists of 16 amino acids, is internalized by cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, the structure of penetratin was examined in both extracellular matrix-mimetic and membrane-mimetic environments: 1H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. The molecular conformations of two analogue peptides [(6,14-Phe)-penetratin and a 12 amino acid penetratin derivative (peptide 3)] were also studied. An atomic level comprehensive analysis of penetratin and its two analogues was performed. In a membrane-mimetic solvent system (TFEd2/water = 9: 1), on the basis of 553 distance restraints, the 4-12 region of penetratin exhibits a bent, irregular helical structure on NMR examination. Interactions between hydrophobic amino acid residues in conjunction with H-bonds stabilize the secondary structure of the molecule. Thus, both derivatives adopt a helix-like conformation. However, while (6,14-Phe)-penetratin displays both alpha-helical and 310-helical features, the structure of peptide 3 is predominantly a 310-helix. Of the three peptides, surprisingly (6,14-Phe)-penetratin has the largest helical content. An increase in the polarity of the molecular environment gradually disintegrates these helix-like secondary structures. In a highly aqueous molecular system (TFEd2/water = 1 : 9), the fast exchange of multiple conformers leads to too few distance restraints being extracted, therefore the NMR structures can no longer be determined. The NMR data show that only short-range order can be traced in these peptides. Under these conditions, the molecules adopt nascent helix-like structures. On the other hand, CD spectra could be recorded at any TFE/water ratio and the conformational interconversion could therefore be monitored as a function of the polarity of the molecular environment. The CD data were analysed comprehensively by the quantitative deconvolution method (CCA+). All three penetratin peptides display helical conformational features in a low dielectric medium, with significant differences as a function of their amino acid composition. However, these conformational features are gradually lost during the shift from an apolar to a polar molecular environment.

Amino Acid Sequence↗
PubMed1995

Effects of local environment on the circular dichroism spectra of polypeptides.

The secondary structures of proteins may be estimated by analysis of their circular dichroism spectra using techniques which empirically fit component spectra derived from water-soluble protein databases. However, local environment effects red- or blue-shift peptide energy transitions primarily through solvent polarization effects and may be an especially important factor for proteins in nonaqueous environments. In this study the reference basis spectra were deconvoluted into three component Gaussian curves corresponding to each of the peptide absorbances in the wavelength range from 190 to 240 nm. These Gaussians were then systematically shifted and utilized in the analyses of the spectra of crambin solubilized in a variety of nonaqueous solvents, including that of the polypeptide associated with small unilamellar phospholipid vesicles. Crambin was selected since its well-characterized structure was found to retain native structure in a variety of nonaqueous environments. This method was more successful in estimating the helical content of this protein than conventional methodologies. This type of analysis may prove to be appropriate for estimating the secondary structure of proteins found in nonaqueous environments, such as membrane proteins.

Alcohols↗
PubMed1994

The use of composite crystal-field environments in molecular recognition and the de novo design of protein ligands.

Small molecule crystal data have been retrieved from the Cambridge Crystallographic Database to compile composite crystal-field environments about different functional groups, which also occur in proteins and nucleotides. Their spatial distribution can be used to map-out putative interaction sites, e.g. about amino acid residues oriented towards the binding site of a given protein. Although influenced by packing forces, these composite environments show systematic patterns which reflect preferred interaction geometries of the functional groups under consideration with neighboring groups, e.g. hydrogen bonding partners. Similar but substantially less detailed distributions have been obtained from crystallographically determined ligand/protein complexes, which demonstrate that the properties observed in low-molecular weight structures are representative also for the sought after spatial orientation of interactions between ligands and their receptor proteins. The crystallographically determined binding geometries of three inhibitor/enzyme complexes are compared with the distributions of putative interaction sites predicted from corresponding composite field environments. In some cases, the observed positions of ligand atoms interacting with the proteins coincide with a region which is also frequently occupied by similar bonding partners in organic crystal structures, however, interaction geometries are also found which fall close to the limits of the ranges observed in the small molecule reference data. The information contained in the different composite crystal-field environments can be translated into rules which serve as guide-lines for automatic docking of small molecule fragments into the active site of proteins.

Binding Sites↗
PubMed1998

Optimal dispersal range and seed size in a stable environment

The evolutionary stable (ESS) dispersal range for annual plants is studied in a stable environment when there is a trade -off between seed survivability and dispersal range via seed size. Larger seed size is more beneficial in the competition for safe sites, but likely to be dispersed a shorter distance and to suffer competition among siblings. Previously Hamilton & May found that dispersal can be adaptive in a stable environment to reduce competition among sibs, but they assumed that dispersers were likely to enter all the patches equally-this is not suitable for many terrestrial plants with limited dispersal range. In this article I discuss the evolution of dispersal range for wind dispersed seeds when dispersal range is tightly coupled with seed size. I assume that the density of dispersed seed follows a two-dimensional normal distribution function, with variance decreasing with seed size. Due to the trade-off between the seed number and the survivability of a seedling offspring, there is a seed size &wtilde; that maximizes the product of the two quantities. This is the optimal seed size when size-dependent dispersal is neglected. The ESS seed size considering the size-dependent dispersal w* is also calculated by neglecting the effect of spatial clumping of relatives. Under the environment unfavorable for seed dispersal, the ESS seed size w* can be much smaller than the optimal seed size &wtilde;, but there is a lower limit for the ESS dispersal range even in the extremely sticky environment. Even if the dependency of seed survivability on the seed size is so weak that the cost of long-range dispersal is small, the ESS seed dispersal range cannot become very large. These results are confirmed by individual-based computer simulations with more realistic assumptions considering spatial clumping of non-sib relatives.Copyright 1998 Academic Press Limited

Journal Article↗
PubMed1996

Potential health risks related to carcinogens in the atmospheric environment in India.

In India, rapid urbanization and industrialization have contributed positively toward meeting the materialistic needs of the citizens, but have also resulted in contamination of the atmospheric environment. This paper deals with the assessment of potential health risks posed by carcinogenic substances, namely cadmium, chromium, and nickel, present in certain atmospheric environments in India. Average air concentrations of these carcinogenic metals have been assessed for different states and regions of India (C. R. Krishnamurti and P. Vishwanathan, Toxic Metals in the Indian Environment, Tata/McGraw-Hill, New Delhi, 1991). Based on these assessments, both individual and societal risks have been estimated in different states of the country, and comparisons were made. Reported concentration, release sources, potential health risks including cancer risk estimates, and ambient air interim guidelines are discussed. The reported environmental releases and cancer risk from cadmium are minimal. There is a potential for increased respiratory cancer risk from exposure to chromium and nickel in some northern Indian states. These metals are irritants to nasal passages and the respiratory tract. Chromium is also corrosive to mucus membranes. They have the potential to cause chronic respiratory problems. Since it appears that these metals may cause some adverse health effects in humans, exposure to these ambient air pollutants should be minimized by managing the release of these contaminants to the environment. There is a need for the development and strict enforcement of national and state regulatory standards.

Air Pollutants↗
PubMed1996

Chlorophenols in the terrestrial environment.

Chlorophenols are presently widespread in the environment. Even in the most remote natural environments, the presence of chlorophenols in both aquatic and terrestrial food chains has been recorded. These pervasive compounds have been used for a wide range of domestic, agricultural, and industrial purposes for more than 50 years. In addition to industrial production and usage, chlorophenols are produced from naturally occurring phenols as a result of chlorine bleaching of wood pulp in the paper industry and through the chlorination of domestic water supplies and swimming pools. It must be emphasized that chlorophenols, although a local problem in some areas, generally cannot be considered a major environmental problem today because their use is prohibited or restricted in many countries. Future reduction in the use of the herbicidal phenoxy acids will further minimize their levels in the terrestrial environment. Because of the long persistence and high toxicity of pentachlorophenol in particular, however, it is important that the discharge of chlorophenols to the terrestrial environment by way of sewage sludge or pulp mill effluents be maintained at their current levels or even reduced to lower levels.

Animals↗
PubMed1997

Phenotypic and evolutionary adaptation of a model bacterial system to stressful thermal environments.

We studied both phenotypic and evolutionary adaptation to various thermal environments using the bacterium Escherichia coli as an experimental model system. We determined that 42 degrees C was stressful to a bacterial clone adapted to 37 degrees C, based on reductions in both absolute and competitive fitness, as well as induction of a heat stress response. This clone was also used to found replicated populations that were propagated for thousands of generations under several different thermal regimes, including 42 degrees C. Evolutionary adaptation of the populations to 42 degrees C resulted in an increase in both absolute and relative fitness at that temperature, measured respectively as an increase in the number of descendants (and their biovolume) and in competitive ability relative to the ancestral clone. The replicated experimental lineages achieved their evolutionary improvement by several distinct pathways, which produced differential preadaptation to a non-stressful nutrient environment. Adaptation to this stressful temperature entailed neither a change in the ancestral thermal niche nor any pronounced trade-offs in fitness within the thermal niche, contrary to a priori predictions. This study system was several important advantages for evaluating hypotheses concerning the effects of stress on phenotypic and evolutionary adaptation, including the ability to obtain lineages that have evolved in controlled and defined environments, to make direct measurements of fitness and to quantify the degree of stress imposed by different environments.

Adaptation, Physiological↗
PubMed1996

Detection of the merA gene and its expression in the environment

Bacterial transformation of mercury in the environment has received much attention owing to the toxicity of both the ionic form and organomercurial compounds. Bacterial resistance to mercury and the role of bacteria in mercury cycling have been widely studied. The genes specifying the required functions for resistance to mercury are organized on the mer operon. Gene probing methodologies have been used for several years to detect specific gene sequences in the environment that are homologous to cloned mer genes. While mer genes have been detected in a wide variety of environments, less is known about the expression of these genes under environmental conditions. We combined new methodologies for recovering specific gene mRNA transcripts and mercury detection with a previously described method for determining biological potential for mercury volatilization to examine the effect of mercury concentrations and nutrient availability on rates of mercury volatilization and merA transcription. Levels of merA-specific transcripts and Hg(II) volatilization were influenced more by microbial activity (as manipulated by nutrient additions) than by the concentration of total mercury. The detection of merA-specific transcripts in some samples that did not reduce Hg(II) suggests that rates of mercury volatilization in the environment may not always be proportional to merA transcription.

Journal Article↗
PubMed1996

Characteristics of voluntary visual sampling of the environment for safe locomotion over different terrains.

The characteristics of visual sampling required for successful locomotion over various terrains is the focus of this work. In the first experiment we directly address the role of continuous visual monitoring of the environment in guiding locomotion by allowing the subjects to choose when and where to take a visual sample of the terrain and examine the effects of different terrains on characteristics of visual sampling. Young subjects walked over travel paths of varying difficulties while wearing opaque liquid crystal eyeglasses and pressed a hand-held switch to make the glasses transparent when they needed to sample the environment. Travel time and visual sampling characteristics were recorded. Results show that intermittent sampling (less than 50%) of the environment is adequate for safe locomotion, even over a novel travel path. The frequency, duration and timing of visual samples are dependent on terrain characteristics. Visual sampling of the environment is unaffected by preview restriction of the travel path and is increased when specific foot placement is required and there is a potential hazard in the travel path. In the second experiment we dissociated steering control and obstacle avoidance from specific foot placement and examined visual sampling demands prior to the initiation of the swing phase and during the swing phase. The results show that steering control and obstacle avoidance do influence the visual sampling time, which is scaled to the magnitude of change. Vision was used in a feedforward control mode to plan for and initiate appropriate changes in the swing limb trajectory: its use during the swing phase to provide on-line control was minimal.

Adult↗
PubMed1989

The use of getting up and lying down movements in the evaluation of cattle environments.

The aim of this review is to find out if getting up and lying down movements can be used as one of several parameters when evaluating different cattle environments. Getting up and lying down movements are performed according to innate movement patterns. An unsuitable environment can cause these movements to become incomplete or abnormal and so lead to injuries. Physiological measurements at lying down show a greater change in tethered cattle than in cattle kept on deep litter. In short stalls the use of certain types of tethers and the height of the manager edge affect the normal getting up and lying down movements. Unsuitably designed cubicles in loose housing systems can lead to changed movement patterns. Calves and fattening bulls have fewer lying down and getting up movements and longer lying intervals on slatted floors than on deep litter. Calves kept in small individual crates carry out a large percentage of their lying down and getting up procedures abnormally. In this review it is shown that it is possible to make improvements in the environment of cattle by using results from studies of these behaviour patterns. The conclusion is that getting up and lying down movements can be used as one of several parameters when evaluating different cattle environments.

Animals↗
PubMed1987

Skin blood flow during incremental exercise in a thermoneutral and a hot dry environment.

Eight physically fit men performed two incremental bicycle ergometer tests, one in an ambient temperature of 25 degrees C and the other at 40 degrees C. Oesophageal temperature (Tes) increased continuously throughout the tests up to 38.0 and 38.3 degrees C, respectively. In both environments, forearm blood flow (plethysmography) was linearly related to Tes above the Tes threshold for vasodilation, but at the heaviest work loads this relationship was clearly attenuated and therefore indicated skin vasoconstriction, which tended to be more pronounced at 25 degrees C. During recovery at 25 degrees C, in some subjects the forearm blood flow increased above the levels observed at the end of the graded exercise in spite of a decreasing Tes. Skin blood flow, measured by laser Doppler flow meter at the shoulder, was quantitatively different but, on average, seemed to reveal the same response pattern as the forearm blood flow. In spite of the higher level of skin blood flow in the heat, blood lactate accumulation did not differ between the two environments. The present results suggest that there is competition between skin vasoconstriction and vasodilation at heavy work rates, the former having precedence in a thermoneutral environment to increase muscle perfusion. During short-term graded exercise in a hot environment, skin vasoconstriction with other circulatory adjustments seems to be able to maintain adequate muscle perfusion at heavy work levels, but probably not during maximum exercise.

Adult↗
PubMed1993

Work environment and schizophrenia: an extension of the arousal hypothesis to occupational self-selection.

The present study investigated a possible mechanism underlying the occupational self-selection of future schizophrenic patients prior to their first admission. More precisely, we explored whether schizophrenic patients are more likely than other psychotic patients to work in environments with a low potential for arousal (low complexity environments) in the last full-time job that preceded their hospitalization. All first admissions with psychotic symptoms to 15 hospitals providing inpatient psychiatric services in the Baltimore-Washington area were surveyed during a 6-year period. Patients diagnosed with schizophrenia were compared to patients diagnosed with bipolar disorder and other psychotic disorders to evaluate the suspected association. Study participants were assessed with a modified version of the Diagnostic Interview Schedule. Standard survey questions were used to assess occupational background. A measure based on the dictionary of occupational titles (DOT) was used to estimate the degree of complexity to which patients had been exposed in their last full-time occupation. Data were analyzed using multinomial logistic regression. After adjustment for age, gender, marital status, unemployment, socioeconomic status, hospital type, and physical demands and hazards on the job, patients with schizophrenia were more likely to have been working in low complexity environments in their last full-time jobs (e.g., janitors, gardeners, guards) than patients with bipolar disorder or with other psychotic disorders. Alternative explanations and potential implications regarding which work environments might be best suited to the social behavior of patients with schizophrenia are examined.

Adolescent↗
PubMed1993

The reconstruction of an astrocytic environment in glia-deficient areas of white matter.

Injection of ethidium bromide into X-irradiated spinal cord white matter produces a lesion in which demyelinated axons reside in an environment that is permanently depleted of glial cells. By transplanting defined populations of glial cells into this lesion it is possible to recreate normal or novel glial environments. In this study we have transplanted cultures of astrocytes into the X-irradiated ethidium bromide lesion in order to (1) assess the ability of these cells to relate to components within the lesion environment and thereby contribute to tissue reconstruction and (2) establish an astrocytic environment around demyelinated axons that resembles pathological states such as the chronic demyelinated plaques of multiple sclerosis. In order to focus attention on the interactions between astrocytes and demyelinated axons we developed a protocol for depleting astrocyte cultures of oligodendrocyte lineage cells and Schwann cells based on complement-mediated immunocytolysis and in vitro X-irradiation. In addition to establishing the ability of transplanted astrocytes to form an astrocytic matrix around demyelinated axons, this study has also revealed the diversity of cell types present within neonatal forebrain cultures.

Animals↗