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At least 73 records · Page 4Linked to original sources

Influence of substrate conformation on the deglycosylation of ribonuclease B by recombinant yeast peptide:N-glycanase.

Peptide:N-glycanase has been thought to be responsible for proteasome-dependent degradation of misfolded glycoproteins translocated from the endoplasmic reticulum (ER) to the cytosol. Therefore, the enzyme was supposed to be able to distinguish between native and non-native glycoproteins. In the present study, a recombinant, yeast peptide:N-glycanase, Png1p, was expressed in Escherichia coli as inclusion bodies and was purified, refolded and characterized. The results showed that the recombinant enzyme has a broad pH range adaptation, from pH 4.0 to pH 10.0, and has an optimum temperature of 30 degrees C. This enzyme is a zinc metalloenzyme. Its activity was abolished with the addition of EDTA and not restored by adding metal ions. Furthermore, the deglycosylation efficiency of recombinant Png1p from E. coli was investigated with respect to the substrate conformation in vitro. When ribonuclease B (RNase B) was denatured at 60-65 degrees C or by 40-60 mM dithiothreitol, indicated by its obvious structural change and sharpest activity change, its deglycosylation by Png1p was most prominent. The deglycosylation efficiency of RNase B by Png1p was found to be related to its structural conformation and enzymatic activity.

Glycosylation↗

Induction of primary virus-cross-reactive human immunodeficiency virus type 1-neutralizing antibodies in small animals by using an alphavirus-derived in vivo expression system.

We have studied the induction of neutralizing antibodies by in vivo expression of the human immunodeficiency virus type 1 (HIV-1) envelope by using a Venezuelan equine encephalitis virus (VEE) replicon system with mice and rabbits. The HIV-1 envelope, clone R2, has broad sensitivity to cross-reactive neutralization and was obtained from a donor with broadly cross-reactive, primary virus-neutralizing antibodies (donor of reference serum, HIV-1-neutralizing serum 2 [HNS2]). It was expressed as gp160, as secreted gp140, and as gp160deltaCT with the cytoplasmic tail deleted. gp140 was expressed in vitro at a high level and was predominantly uncleaved oligomer. gp160deltaCT was released by cells in the form of membrane-bound vesicles. gp160deltaCT induced stronger neutralizing responses than the other forms. Use of a helper plasmid for replicon particle packaging, in which the VEE envelope gene comprised a wild-type rather than a host range-adapted sequence, also enhanced immunogenicity. Neutralizing activity fractionated with immunoglobulin G. This activity was cross-reactive among a panel of five nonhomologous primary clade B strains and a Chinese clade C strain and minimally reactive against a Chinese clade E (circulating recombinant form 1) strain. The comparative neutralization of these strains by immune mouse sera was similar to the relative neutralizing effects of HNS2, and responses induced in rabbits were similar to those induced in mice. Together, these results demonstrate that neutralizing antibody responses can be induced in mice within 2 to 3 months that are similar in potency and cross-reactivity to those found in the chronically infected, long-term nonprogressive donor of HNS2. These findings support the expectation that induction of highly cross-reactive HIV-1 primary virus-neutralizing activity by vaccination may be realized.

AIDS Vaccines↗

Hereditary dominance of fast-twitch fibers in skeletal muscles and relation of thyroid hormone under physiological conditions in rats.

To investigate whether muscle fiber compositions of various skeletal muscles were correlated with each other and whether muscle fiber type composition was related to the serum thyroid hormone level, fast-twitch fiber dominant rats (FFDR), which had a higher percentage of fast-twitch (FT) fibers in the deep portion of the lateral head of the gastrocnemius muscle (GAS), were compared to a control group. The FFDR group was obtained by the selective breeding for high-percentage FT fibers in the GAS, and the control group was obtained by random breeding from the same base population. The percentages of FT fibers of the GAS, soleus (SOL), vastus intermedius (VI), biceps brachii (BB), rectus abdominis (RA) and extensor digitorum longus (EDL) muscles were analyzed. The percentages of FT fibers of the GAS, SOL, VI and BB in the FFDR group were significantly higher than in the control group (p<0.05), and percent FT fibers of the GAS were significantly correlated with those of the SOL (r = 0.62, p<0.01), VI (r = 0.45, p <0.05) and BB (r = 0.43, p<0.05). On the other hand, no significant differences between FFDR and the control group and no significant correlations with the GAS were observed in percent FT fibers of the RA and EDL. The total 3,3',5-triiodo-L-thyronine (T3) level in FFDR was not significantly different from the control group and was not significantly correlated with the percentage of FT fibers. These data suggest that the percentages of FT fibers of various skeletal muscles are genetically correlated with each other, but some FT muscles are not because they might be close to the upper limits of the genetic adaptive range. In addition, percentages of FT fibers are independent of the total T3 level under physiological conditions.

Animals↗

Utility of specific locus systems in higher plants to monitor for mutagens.

Plants possess biological and operational attributes that have encouraged geneticists to use them extensively in the development of fundamental genetic concepts. Attributes such as regenerative plasticity, high fecundity, cultural adaptability, range of ploidy, economics of culture and maintenance of specific populations, and versatility make plant genetic systems prime candidates with which to monitor the environment for mutagens. A specific locus (equivalent to a classical Mendelian gene) controls the development of a phenotypic characteristic. It can also mutate to a new allelic form with a consequentially altered phenotypic characteristic and can be separated by crossing over from adjacent loci that govern other specific phenotypic characteristics. Since various plant species have numerous specific loci, one has a rich array of potential systems from which to select. Specific locus systems in higher plants could be used to assess the mutagenicity of single chemical compounds or combinations of chemical compounds. Depending on the circumstances, seeds and/or seedlings could be used; plants could be grown in situ in either containers or plots to assess the immediate environment for one or more mutagens over an extended period. Since plants are eucaryotes, data from such experiments could serve as one more source of information along with that obtained from a battery of other tests used in the tier system.

Biological Assay↗

Application of a programmable dual-channel adaptive electrical stimulation system for the control and analysis of gait.

A dual-channel electrical stimulation system with a stimulator and a programmer/stride analyzer was designed for clinical rehabilitation of gait and for subsequent daily use as an orthotic aid. The stimulator, with controls to adjust amplitude only (50 mA), adapts chosen stimulation sequences to the walking rate of a patient. Pulse duration (50-500 microseconds), frequency (5-120 Hz), shape (symmetrical biphasic, monophasic), stimulation sequences (16 stride segments) and their cycle (2-12 sec), and right/left foot-switch choices are selected for each patient and programmed into a separate unit. The programming unit also statistically processes the foot-switch data collected by the stimulator. The device was evaluated with regard to the programmable parameters, effectiveness during gait, and feasibility in clinical use. It was applied to 11 stroke patients and 10 brain injury patients during gait, stimulating 22 combinations of peroneal nerve and hamstring, quadriceps, triceps brachii, and gluteus maximus muscles. Forces on both feet, equinovarus, knee extension and hyperextension, elbow flexion, and hip extension were corrected. Selection of the stimulation sequences, their adaptation, range of pulse duration, and valid statistics were verified. Improved forces and joint angles were recorded together with significant changes in the stride time, length, and velocity by the stimulation.

Adult↗

TMD: it's our responsibility! Part Two.

Dentists modify and construct occlusions. This occurs on a daily basis in the disciplines of restorative, fixed and removable prosthetics and orthodontics. These procedures influence the TMJ, the muscles of mastication, the supporting structure of the teeth and the teeth as well. Dentists have an opportunity to not only objectively analyze how they all interrelate, but to create a physiological harmonious relationship. This will reduce a traumatic occlusion to one that is within the histological adaptive range for the tissue to accommodate. This knowledge can be applied to not only help patientsí pain and dysfunction, but to ensure confidence that dentists are not going to be responsible for iatrogenic results. The future of dentistry is not only being able to effectively deal with TMD but to prevent the problems. Management of mandibular whiplash and migraine headaches are also becoming our responsibility. Dentists are the specialists of occlusion. With the technology available to render this quality of care, they must fulfill their obligation to the public, take responsibility and continue to increase their capability. This approach to dentistry provides a new "window of opportunity" as its many applications have yet to be explored.

Electromyography↗

Unsupervised classification of Space Acceleration Measurement System (SAMS) data using ART2-A.

The Space Acceleration Measurement System (SAMS) has been developed by NASA to monitor the microgravity acceleration environment aboard the space shuttle. The amount of data collected by a SAMS unit during a shuttle mission is in the several gigabytes range. Adaptive Resonance Theory 2-A (ART2-A), an unsupervised neural network, has been used to cluster these data and to develop cause and effect relationships among disturbances and the acceleration environment. Using input patterns formed on the basis of power spectral densities (psd), data collected from two missions, STS-050 and STS-057, have been clustered.

Acceleration↗

[Current status of gene test market].

The technological innovation of the gene analysis makes the adaptation range of the gene test in clinical diagnosis expand. Then, gene test has popularized increasingly around the infection disease for clinical inspection. Also in the field of clinical inspection, the increase of the importance of clinical application and the inspection item new year by year have appeared with the functional analysis of a gene. Moreover, the new test method and automation analysis equipment tend to be developed by progress of gene-analysis technology, and it is going to be introduced. The spread of gene test and development of a gene test market have an important possibility of activating the present clinical inspection field.

Clinical Laboratory Techniques↗

Transcriptional regulation of heat shock genes. A paradigm for inducible genomic responses.

The heat shock response offers an ideal paradigm to understand how the cell recognizes and responds to acute and chronic exposures to environmental and physiological stress. Of the numerous inducible genomic responses, the heat shock response has contributed fascinating insights into the molecular and cellular mechanisms of adaptation, ranging from the regulation of heat shock gene expression to the function of stress proteins. The recent cloning of multiple heat shock transcription factor (HSF) genes in higher eukaryotes and studies on the biochemical and cellular properties of HSFs have revealed several novel features of the transcriptional response.

Animals↗

[Recent medication to renal osteodystrophy].

P control according to phosphorus (P) adsorbent by the medication to renalosteodystrophy (ROD) and the medical treatment by active vitamin D are main. Although the present calcium carbonate is used as P adsorbent, sufficient quantity to control P for hypercalcemia may be unable to be prescribed for the patient. The near future use of sevelamer hydrochloride under development which does not cause hypercalcemia will be attained at such a case. Although alphacalcidol and calcitriol are used for some time, the present clinical use of the vitamin derivatives which made calcitriol basic structure and made the action powerful, such as maxacalcitol and falecalcitriol, is developed and carried out. Thus, although the choice of vitamin D medical treatment increased by clinical use of much active vitamin D or its derivative having been attained and the adaptation range also spread, there is no view which now unified how such a medicine would be used properly. The validity to ROD, such as calcitonin, vitamin K, and bisphosphonates, is examined in addition to P adsorbent, or vitamin D and its derivative, and calcimimetics is developed as a new medicine.

English Abstract↗

Range shifts and adaptive responses to Quaternary climate change.

Tree taxa shifted latitude or elevation range in response to changes in Quaternary climate. Because many modern trees display adaptive differentiation in relation to latitude or elevation, it is likely that ancient trees were also so differentiated, with environmental sensitivities of populations throughout the range evolving in conjunction with migrations. Rapid climate changes challenge this process by imposing stronger selection and by distancing populations from environments to which they are adapted. The unprecedented rates of climate changes anticipated to occur in the future, coupled with land use changes that impede gene flow, can be expected to disrupt the interplay of adaptation and migration, likely affecting productivity and threatening the persistence of many species.

Adaptation, Physiological↗

Toward a middle-range theory of adaptation to chronic pain.

Merton postulated that to significantly advance disciplinary knowledge, scholarship must include the development of middle-range theories that derive hypotheses, can be empirically investigated, and are linked to extant theories. The purpose of this paper is to present the strategies used to develop a middle-range nursing theory of adaptation to chronic pain based on Merton's description. Analysis and synthesis of the theoretical and research literature provided the foundational, theory-building strategies used to develop the adaptation to chronic pain model. Theoretical substruction was then used to deduce the adaptation to chronic pain model from Roy's adaptation model.

Adaptation, Psychological↗

Adaptation and species range.

Phase III of Sewall Wright's shifting-balance process involves the spread of a superior genotype throughout a structured population. However, a number of authors have suggested that this sort of adaptive change is unlikely under biologically plausible conditions. We studied relevant mathematical models, and the results suggest that the concerns about phase III of the shifting-balance process are justified, but only if environmental conditions are stable. If environmental conditions change in a way that alters species range, then phase III can be effective, leading to an enhancement of adaptedness throughout a structured population.

Adaptation, Biological↗

Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions.

Maternal nutrient restriction from early to midgestation can lead to fetal growth retardation, with long-term impacts on offspring growth, physiology, and metabolism. We hypothesized that ewes from flocks managed under markedly different environmental conditions and levels of nutrition might differ in their ability to protect their own fetus from a bout of maternal nutrient restriction. We utilized multiparous ewes of similar breeding, age, and parity from 2 flocks managed as 1) ewes adapted to a nomadic existence and year-long, limited nutrition near Baggs, WY (Baggs ewes), and 2) University of Wyoming ewes with a sedentary lifestyle and continuous provision of more than adequate nutrition (UW ewes). Groups of Baggs ewes and UW ewes were fed 50 (nutrient restricted) or 100% (control fed) of National Research Council recommendations from d 28 to 78 of gestation, then necropsied, and fetal and placental data were obtained. Although there was a marked decrease (P < 0.05) in fetal weight and blood glucose concentrations in nutrient-restricted vs. control fed UW ewes, there was no difference in these fetal measurements between nutrient-restricted and control-fed Baggs ewes. Nutrient-restricted and control-fed UW ewes exhibited predominantly type A placentomes on d 78, but there were fewer (P c0.05) type A and greater (P < 0.05) numbers of type B, C, and D placentomes in nutrient-restricted than control-fed Baggs ewes. Placental efficiency (fetal weight/placentomal weight) was reduced (P = 0.04) in d 78 nutrient-restricted UW ewes when compared with control-fed UW ewes. In contrast, nutrient-restricted and control-fed Baggs ewes exhibited similar placental efficiencies on d 78. This is the first report of different placental responses to a nutritional challenge during pregnancy when ewes were selected under different management systems. These data are consistent with the concept that Baggs ewes or their conceptuses, which were adapted to both harsh environments and limited nutrition, initiated conversion of type A placentomes to other placentomal types when subjected to an early to mid-gestational nutrient restriction, whereas this conversion failed to occur in UW ewes. This early placentomal conversion in the Baggs ewes may function to maintain normal nutrient delivery to their developing fetuses during maternal nutrient restriction.

Animal Husbandry↗

A homogeneous fluorescence polarization assay adaptable for a range of protein serine/threonine and tyrosine kinases.

Recently, a new technology for high-throughput screening has been developed, called IMAP(patent pending). IMAP technology has previously been implemented in an assay for cyclic nucleotide phosphodiesterases (PDE). The authors describe the development of a homogeneous, non-antibody-based fluorescence polarization (FP) assay for a variety of protein kinases. In this assay, fluorescently labeled peptide substrate phosphorylated by the kinase is captured on modified nanoparticles through interactions with immobilized metal (M(III)) coordination complexes, resulting in a change from low to high polarization values. This assay is applicable to protein kinases that phosphorylate serine, threonine, or tyrosine residues. The IMAP platform is very compatible with high-throughput robotics and can be applied to the 1536-well format. As there are hundreds of different kinases coded for in the human genome, the assay platform described in this report is a valuable new tool in drug discovery.

Biological Assay↗

[Two-stimulus--two choice paradigm for psychophysics: range-frequency model and adaptation level theory in comparison].

The predictions provided by the range-frequency model and the adaptation-level theory were compared in respect of size judgments in an averbal two-category experiment. Squares of different sizes were presented in two different frequency distributions. After a two stimulus-two choice training, in which the subjects (N = 64) learned to which of the two response categories a relative small or large square belonged, a generalization context-series test followed. The two test series represented the two different frequency distributions used (the arithmetic mean was either smaller or larger than the median or midpoint). The percentage of large responses was registered. Furthermore, to investigate which experimental design would be appropriate for this research paradigm, the study was carried out using both a between-subjects and a within-subjects design. For the two experimental designs, the results pointed to a confirmation of the predictions provided by the adaptation-level theory (D. R. Thomas, 1993) but not the range-frequency model (Parducci, 1983, 1995).

Adult↗

Geographical patterns of adaptation within a species' range: interactions between drift and gene flow.

We use individual-based stochastic simulations and analytical deterministic predictions to investigate the interaction between drift, natural selection and gene flow on the patterns of local adaptation across a fragmented species' range under clinally varying selection. Migration between populations follows a stepping-stone pattern and density decreases from the centre to the periphery of the range. Increased migration worsens gene swamping in small marginal populations but mitigates the effect of drift by replenishing genetic variance and helping purge deleterious mutations. Contrary to the deterministic prediction that increased connectivity within the range always inhibits local adaptation, simulations show that low intermediate migration rates improve fitness in marginal populations and attenuate fitness heterogeneity across the range. Such migration rates are optimal in that they maximize the total mean fitness at the scale of the range. Optimal migration rates increase with shallower environmental gradients, smaller marginal populations and higher mutation rates affecting fitness.

Adaptation, Biological↗