Alpha Components Research Articles

Changes in synaptic integration during the growth of the lateral giant neuron of crayfish.

1. The effect of growth on the electrotonic structure and synaptic integrative properties of the lateral giant (LG) interneuron was assessed from anatomic and electrophysiological measurements of LGs in small (1-2.4 cm) and large (9-11.2 cm) crayfish and from calculated responses of mathematical models of these neurons. Postsynaptic responses of small and large LGs were compared with model responses to determine whether the differences in the neurons' responses result from growth-related changes in their physical characteristics. 2. LG neurons in the terminal abdominal ganglia of small and large crayfish are similar in shape but differ in size according to an approximately isometric pattern of growth. The soma diameter of the large LG is 2.2 times larger than the small LG, the major ipsilateral dendrite is 2.8 times longer and 3.6 times greater in diameter, and the axon is 7.6 times longer and 4.5 times greater in diameter. The projected area of the major ipsilateral dendrite of LG in the horizontal plane of the terminal abdominal ganglion is 27 times larger in the large than in the small crayfish. 3. LG's input resistance was nearly 80% smaller in the large (167 K omega) than in the small (742 K omega) crayfish when measured at or near the initial axon segment. The cell's membrane time constant displayed an opposite relationship, with the value in the large crayfish (20.9 ms) nearly two-and-a-half times larger than the value in the small crayfish (8.6 ms). 4. Simultaneous recordings were made from the distal portion of the ipsilateral dendrite and the initial axon segment of small and large LGs to determine how excitatory postsynaptic potentials (EPSPs) are attenuated or filtered by the electrotonic properties of the different sized cells. In the small LG, the fast alpha and the slower beta components of compound EPSPs evoked by sensory nerve stimulation were similarly attenuated. In the large LG, the alpha component of the compound EPSP was much more attenuated and smoothed than the slower beta component. 5. Multicompartment models of small and large LGs were constructed and used to test whether differences in the two neurons' physical properties could account for the differences in their passive response properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Tyrosine phosphorylation of the alpha and beta subunits of the type I interferon receptor. Interferon-beta selectively induces tyrosine phosphorylation of an alpha subunit-associated protein.

We studied the phosphorylation of the alpha and beta subunits of the Type I interferon (IFN) receptor induced by Type I IFNs in the human U-266 and MOLT-4 cell lines. Both IFN-alpha and IFN-beta induced tyrosine phosphorylation of the beta subunit of the receptor. The Type I IFN-induced tyrosine phosphorylation of the beta subunit was rapid and transient, being detectable within 1 min of Type I IFN treatment and gradually diminishing to almost base-line levels by 60 min. All Type I IFNs studied were found to induce tyrosine phosphorylation of the alpha subunit of the Type I IFN receptor, the p135tyk2 and JAK-1 tyrosine kinases, and the ISGF3 alpha components. Interestingly, IFN-beta, but not IFN-alpha or IFN-omega, induced tyrosine phosphorylation of an alpha subunit-associated protein with an apparent molecular mass of approximately 100 kDa (p100). These data suggest the existence of a common signaling pathway(s) for Type I IFNs involving the alpha and beta subunits of the receptor, the tyrosine kinases p135tyk2 and JAK-1, and the ISGF3 alpha components. However, differences between the signaling pathways of different Type I IFNs exist, as suggested by tyrosine phosphorylation of an alpha subunit-associated protein only in response to IFN-beta.

Assessing the Effects of Standardized Testing on Schools

This study brings empirical data to the debate about the efficacy of standardized tests. A teacher questionnaire containing 81 Likert-type items was mailed to 450 upper elementary school teachers in 48 schools. Questions of interest included (a) What are the effects of these tests on the teaching and learning process in schools? (b) What is the meaning of test score gains? and (c) Does such testing have differential effects in schools serving students at different socioeconomic status (SES) levels? Approximately 75% of the teachers (n = 341) completed the questionnaires. Results of Cronbach's alpha and principal components analyses indicated that items within specified subscales were internally consistent. Results of a confirmatory factor analysis showed that the interitem correlations within subscales were stronger than those across subscales. The results of multiple discriminant analysis (DA) using categories of TREND (schools with increasing vs. stable or decreasing test scores) as the grouping variable indicated that only two subscales were significantly different across TREND categories. However, the results of a second multiple DA showed that many subscale scores significantly discriminated groups formed by student SES levels. The DA by SES findings suggest that teachers of lower SES students are under greater pressure to improve test scores and focus more on test content in their classroom instruction than teachers of higher SES students.

Alpha/beta separation in liquid scintillation gel samples

The pulse shape analysis commonly used in liquid scintillation alpha/beta separations is satisfactory for moderate quench levels. However, for gel samples, the alpha particle counting efficiency is never greater than 10%, and an optimum separation of the alpha component cannot be achieved when beta to alpha counting rate ratios are greater than 100. In such cases, it is better to use a spectrum analysis method for alpha/beta separation.

Event-related desynchronization (ERD) during visual processing

Event-related desynchronization (ERD) is the short-lasting attenuation or blocking of rhythms within the alpha (beta) band. ERD is found during but also before visual stimulation. Two different types of ERD can be differentiated: one short-lasting, localized to occipital areas and involving upper alpha components; the other longer lasting, more widespread, most prominent over parietal areas and maximal for lower alpha components. The former most likely reflects primary visual processing and feature extraction, the latter is more related to cognitive processing and mechanisms of attention.

The effect of uremia on tumor necrosis factor-alpha release after an in vitro whole-blood endotoxin challenge.

Uremia has been associated with immunologic aberrations, including anergy, increased susceptibility to infections, and reduced phagocytic activity of polymorphonuclear leukocytes. In this study, cytokine release in uremic and nonuremic blood after in vitro endotoxin stimulation was studied. Blood from nonuremic controls, chronic renal failure patients not on dialysis, and chronic hemodialysis patients predialysis and postdialysis was spiked with 10 ng/mL of Escherichia coli endotoxin and incubated for 2 and 26 h. Plasma tumor necrosis factor-alpha (TNF alpha) concentrations were determined by ELISA after each incubation period. To further study which uremic blood component may be responsible for enhanced release of TNF alpha, plasma and cellular components of chronic renal failure patients and controls were switched and then given an in vitro endotoxin stimulation (1 ng/mL). It was found that (1) TNF alpha release is enhanced by uremia and is exacerbated with progressive declines in renal function, (2) enhanced TNF alpha release is related to a blood cellular phenomenon induced by uremia, and (3) enhanced TNF alpha release in hemodialysis patients is associated with a prolonged stimulation and/or reduced plasma elimination of TNF alpha.

Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes.

Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFR alpha) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte.

Estimation of the Initial Slope of the Cell Survival Curve after Irradiation from Micronucleus Frequency in Cytokinesis-Blocked Cells

We have already reported that the alpha/beta ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the alpha value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the alpha component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondingly decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -ln NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the alpha value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: alpha = 1.01 a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the alpha value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens.

Mutant cell lines unresponsive to alpha/beta and gamma interferon are defective in tyrosine phosphorylation of ISGF-3 alpha components.

The 84-, 91-, and 113-kDa proteins of the ISGF-3 alpha complex are phosphorylated on tyrosine residues upon alpha interferon (IFN-alpha) treatment and subsequently translocate to the nucleus together with a 48-kDa subunit. In this study, we investigated the presence and the functional status of ISGF-3 alpha subunits and Tyk-2 and JAK1 tyrosine kinases in mutant HeLa cells defective in the IFN-alpha/beta and -gamma response. Stable cell fusion analysis revealed a single complementation group among one class (class B) of mutants. The class B mutants contain detectable level of mRNA and proteins of the 84-, 91-, and 113-kDa proteins, but neither the protein nor mRNA is inducible by IFN-alpha or -gamma. The 91-kDa protein IFN-gamma-activated factor fails to be activated into a DNA-binding state after IFN-alpha or -gamma treatment. In addition, the 91-kDa protein is unable to localize in the nucleus after IFN-alpha and -gamma treatment, and the 113-kDa protein fails to translocate after IFN-alpha treatment. Immunoprecipitation studies document a failure of phosphorylation of the 84- or 91-kDa proteins after IFN-alpha or -gamma treatment. Similarly, no tyrosine-phosphorylated 113-kDa protein was detected after IFN-alpha treatment. The inability of class B mutants to phosphorylate the 84-, 91-, or 113-kDa protein on tyrosine residues correlated with the loss of biological response to IFN-alpha and -gamma. The genetic defect appears to be the absence of the tyrosine kinase JAK1. Our data therefore confirm a recent report that JAK1 plays a critical early signaling role for both IFN-alpha/beta and IFN-gamma systems.

Concerted action of RAS and G proteins in the sexual response pathways of Schizosaccharomyces pombe.

We have shown that the expression of mam2, the gene encoding the Schizosaccharomyces pombe P-factor pheromone receptor, is dependent upon components of the pheromone signal transduction pathway, including Ras1, Gpa1, Byr1 and Byr2, each of which is required for both conjugation and sporulation. Studies of the expression of mam2 in mutant S. pombe cells confirm previous conclusions, based on the ability of cells to sporulate, that the Byr1 protein kinase acts downstream of the Byr2 protein kinase and that both act downstream of Ras1, the S. pombe RAS homolog, and Gpa1, the G alpha component that mediates the occupancy of the mam2 receptor. In addition, our present studies show that Ras1 and Gpa1 each act downstream from the other and hence act in concert. The Spk1 kinase, which is required for conjugation and sporulation and which is a structural and functional homolog of the vertebrate MAP kinases, is not required for mam2 expression.

Concerted action of RAS and G proteins in the sexual response pathways of Schizosaccharomyces pombe.

We have shown that the expression of mam2, the gene encoding the Schizosaccharomyces pombe P-factor pheromone receptor, is dependent upon components of the pheromone signal transduction pathway, including Ras1, Gpa1, Byr1 and Byr2, each of which is required for both conjugation and sporulation. Studies of the expression of mam2 in mutant S. pombe cells confirm previous conclusions, based on the ability of cells to sporulate, that the Byr1 protein kinase acts downstream of the Byr2 protein kinase and that both act downstream of Ras1, the S. pombe RAS homolog, and Gpa1, the G alpha component that mediates the occupancy of the mam2 receptor. In addition, our present studies show that Ras1 and Gpa1 each act downstream from the other and hence act in concert. The Spk1 kinase, which is required for conjugation and sporulation and which is a structural and functional homolog of the vertebrate MAP kinases, is not required for mam2 expression.

Heterogeneity of chromosome damage in beta-thalassaemia traits. An evaluation of spontaneous and gamma-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G0 and G2 phase irradiation.

This study is an attempt to evaluate the chromosomal radiosensitivity of beta-thalassaemia traits compared with healthy individuals from the general population, necessitated by the fact that beta-thalassaemia trait is present in 1-17% of different population groups in India and the chances of encountering them in radiation and chemical related industries do exist. Spontaneous chromosome aberration frequencies in peripheral blood lymphocytes from beta-thalassaemia traits were found to be in the normal range, whereas significantly higher frequencies of micronuclei (MN) were observed in thalassaemia traits. Based on MN frequency at 2 Gy, beta-thalassaemia traits fall into two distinct categories. A hypersensitive group with significant increase in radiation-induced MN over the control group, and a second group with MN frequency slightly above normal individuals. Even when compared with the fitted data at 2 Gy obtained from the pooled results of extensive dose-response investigations from 0.5-5 Gy gamma-rays with normal donors for MN, dicentrics and total aberrations, the difference between the means of MN frequencies in beta-thalassaemia traits and normals is significant. MN have a higher control level, a higher value for the alpha component, and much lower value for the beta component, when compared with total aberrations. Both in 2-Gy irradiated G0 lymphocytes as well as 0.5 and 1-Gy irradiated G2 lymphocytes, there is a certain degree of hypersensitivity when the results are meaned over a number of individuals, but some individuals overlap within the normal range. In G0 irradiated lymphocytes from beta-thalassaemia traits, the dicentric chromosome is the only aberration category in which the yield is seen to rise. The heterogeneity in chromosomal radiosensitivity observed in beta-thalassaemia traits is discussed in terms of the oxidative damage consequent to the genetic and biochemical features peculiar to the beta-thalassaemia trait cell. The data presented herein may have wider implications in radiation protection.

Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells.

Ciliary neurotrophic factor was discovered based on its ability to support the survival of ciliary neurons, and is now known to act on a variety of neuronal and glial populations. Two distant relatives of ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M, mimic ciliary neurotrophic factor with respect to its actions on cells of the nervous system. In contrast to ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M also display a broad array of actions on cells outside of the nervous system. The overlapping activities of leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor can be attributed to shared receptor components. The specificity of ciliary neurotrophic factor for cells of the nervous system results from the restricted expression of the alpha component of the ciliary neurotrophic factor receptor complex, which is required to convert a functional leukemia inhibitory factor/oncostatin M receptor complex into a ciliary neurotrophic factor receptor complex. The recent observation that the alpha component of the ciliary neurotrophic factor receptor complex is expressed by very early neuronal precursors suggested that ciliary neurotrophic factor may act on even earlier precursors, particularly on cells previously thought to be targets for leukemia inhibitory factor action. Here we show the first example of ciliary neurotrophic factor responsiveness in cells residing outside of the nervous system by demonstrating that embryonic stem cells express a functional ciliary neurotrophic factor receptor complex, and that ciliary neurotrophic factor is similar to leukemia inhibitory factor in its ability to maintain the pluripotentiality of these cells.

Suppression of a dominant G protein β‐subunit mutation in yeast by Gα protein expression

SCG1/GPA1, STE4 and STE18 encode the alpha, beta and gamma components of the G protein involved in mating pheromone signal transduction in Saccharomyces cerevisiae. Responses, including G1 arrest and expression of genes such as FUS1, are activated by beta gamma, which is negatively controlled by alpha(GDP). We previously demonstrated that overexpression of Scg1 suppresses responses to alpha factor and that expression of certain hybrids between Scg1 and mammalian G alpha proteins has the same effect and also suppresses growth arrest in an scg1-null mutant. Effects were attributed to sequestration of beta gamma. We now show that effects on growth rate, morphology and FUS1 expression are consistent with this model. The STE4HPL allele causes dominant activation of the response pathway, and is presumed to encode a beta subunit insensitive to control by alpha(GDP). Scg1 overexpression suppresses the growth arrest due to STE4HPL; normal alpha-factor responses and fertility are restored. A model based on sequestration of beta gamma reconciles this result with the apparent paradox that the same level of Scg1 overexpression inhibits responses and mating in wild-type cells. A G alpha i hybrid also restores growth and allows inefficient mating in the STE4HPL strain.

Effect of aging on the spatio-temporal pattern of event-related desynchronization during a voluntary movement

Event-related desynchronization (ERD) of alpha components was studied in young and elderly subjects during planning of voluntary movement. ERD was quantified from 11 source derivations covering regions of the scalp corresponding to the supplementary motor area, the left and right primary sensorimotor areas, the vertex, and the medial posterior parietal cortex. Spatio-temporal display of ERD showed a very different pattern in elderly subjects, with mainly a spatial diffusion of ERD over the parietal and frontal regions. On the contrary, ERD in young subjects was limited to the central regions. ERD was also more lasting in elderly subjects. Changes of the ERD pattern in elderly subjects could indicate a change of cortical activation during voluntary movement. The data also confirm that ERD study is a useful electrophysiological exploration to observe the changes of cortical activation during cerebral aging.

Neonatal group B streptococcal infection in Mallorca, Spain.

Early onset infection in neonates caused by group B Streptococcus and the prevalence of colonization by this microorganism in a group of 1,003 pregnant women and their neonates were studied. The capsular serotypes of the colonizing and infecting bacterial isolates and the components of C protein expressed were determined. Except for serotype IV, all the currently recognized capsular serotypes (including serotype V) were found. Among the colonizing strains, serotypes III, Ia, and Ib were almost equally represented and accounted for 82% of the isolates. Serotype III was predominantly found in cases of infection (55%), and serotypes Ia and V were also found in such cases. C protein was not detected in serotype III isolates, but alpha and/or beta components of this protein were found in isolates of all other serotypes. Neonatal infection and colonization due to this microorganism were observed in 1.2 cases per 1,000 live births and in 7.1% of pregnant women. Host factors for infection, such as low birth weight, premature delivery, and prolonged rupture of membranes, were uncommon. The level of specific antibodies to serotype III was also quantitated; lower levels were found in infected children and their mothers than in healthy infants and pregnant women. Further similar studies in Spain are necessary so that preventive measures can be planned.

Released Form of CNTF Receptor α Component as a Soluble Mediator of CNTF Responses

The alpha component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF alpha receptor component. These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.

Role of the γ component of preprotoxin in expression of the yeast K1 killer phenotype

K1 killer strains of Saccharomyces cerevisiae secrete a polypeptide toxin to which they are themselves immune. The alpha and beta components of toxin comprise residues 45-147 and 234-316 of the 316-residue K1 preprotoxin. The intervening 86-residue segment is called gamma. A 26-residue signal peptide is removed on entry into the endoplasmic reticulum. The Kex2 protease excises the toxin components from the 290-residue glycosylated protoxin in a late Golgi compartment. Expression of a cDNA copy of the preprotoxin gene confers the complete K1 killer phenotype on sensitive cells. We now show that expression of immunity requires the alpha component and the N-terminal 31 residues of gamma. An additional C-terminal extension, either eight residues of gamma or three of four unrelated peptides, is also required. Expression of preprotoxin terminating at the alpha C-terminus, or lacking the gamma N-terminal half of gamma causes profound but reversible growth inhibition. Inhibition is suppressed in cis by the same 31 residues of gamma required for immunity to exocellular toxin in trans, but not by the presence of beta. Both immunity and growth inhibition are alleviated by insertions in alpha that inactivate toxin. Inhibition is not suppressed by kex2, chc1 or kre1 mutations, by growth at higher pH or temperature, or by normal K1 immunity. Inhibition, therefore, probably does not involve processing of the alpha toxin component at its N-terminus or release from the cell and binding to glucan receptors. Some insertion and substitution mutations in gamma severely reduce toxin secretion without affecting immunity. They are presumed to affect protoxin folding in the endoplasmic reticulum and translocation to the Golgi.

IL-4 attenuates the transcriptional activation of both IFN-alpha and IFN-gamma-induced cellular gene expression in monocytes and monocytic cell lines.

The interaction of IFN-alpha and IFN-gamma with monocytes results in several actions that significantly influence the course of an immune response. Many of these effects are proinflammatory and can contribute to the degree of tissue injury at a site of inflammation. Whereas recent investigations target IL-4 as a T cell product that can antagonize some of the responses induced by IFN, little is known regarding the mechanisms involved. We have taken advantage of two well defined systems: the transcriptional activation of the cellular genes ISG-54 by IFN-alpha and IP-10 by IFN-gamma. IL-4 treatment of both the monocytic leukemia cell line, THP-1, and normal peripheral blood monocytes resulted in inhibition of IFN-induced RNA levels for both genes. Nuclear run-on assays in THP-1 cells indicated that the effects of IL-4 were due to the inhibition of the transcriptional activation of these genes by both IFN-alpha and IFN-gamma. This inhibition was not due to alteration in the binding characteristics of IFN-alpha or IFN-gamma to the cell. In the IFN-alpha system, we were able to show that IL-4 treatment resulted in reduced formation of the transcriptional activator, IFN-stimulated gene factor 3. This reduction appears to be the result of a defect in the ability of IFN alpha to activate the IFN-stimulated gene factor 3 alpha component of IFN-stimulated gene factor 3.

EEG power spectrum changes due to listening to pleasant music and their relation to relaxation effects.

Electroencephalogram (EEG) power spectrum changes induced by pleasant music (2-min. fractions of 6 samples of music [famous classical and commercially available "alpha music" at 10-sec. intervals]) were investigated in relation to changes in 16 kinds of psychosomatic feelings. Subjects were 42 healthy young people aged 18-25 yrs. Two major components, "pleasant & relaxed" and "calm", were extracted through principal component analysis of the feeling changes, both of which were related to the "relaxation effects" of the music. These component scores were not related to the changes of EEG powers in the delta, theta, alpha and beta frequency components in 6 regions (frontal, parietal and occipital regions of the left and right hemispheres), when examined separately. However, the change of the total delta power for all the regions was significantly associated with both the "pleasant & relaxed" and "calm" component scores. The association between the total theta power change and "calm" score was found to be insignificant if the type-A personality variable was added to their regression model. On the other hand, the alpha-peak frequency was inversely related to the decrease of the "calm" score in the left occipital region (LO). The reduction of the alpha-peak power in the LO was also significant, and was associated not with the alpha-peak frequency changes but inversely with the "calm" score, although these alpha-component changes were not shown to be modified by the personality. Thus, the present study suggests, as a preliminary finding, that the "relaxation effects" of pleasant music can be associated with the EEG power spectrum component changes, especially with the change in the total theta power and possibly with that in the alpha power in the occipital, and the frequency shift of the peak in the alpha-range. Some of the associations were also shown to vary for the type-A personality, suggesting a clue to relating the personality to a differential stress-related psychosomatic trait, although the physiological significance of the changes in the low-frequency component range as well as those in the alpha-frequency component, which are obtained through FFT, should be further clarified.