Contribution Of Different Classes Research Articles

Emerging Role of Non-Coding RNAs in Senescence.

Senescence is defined as a gradual weakening of functional features of a living organism. Cellular senescence is a process that is principally aimed to remove undesirable cells by prompting tissue remodeling. This process is also regarded as a defense mechanism induced by cellular damage. In the course of oncogenesis, senescence can limit tumor progression. However, senescence participates in the pathoetiology of several disorders such as fibrotic disorders, vascular disorders, diabetes, renal disorders and sarcopenia. Recent studies have revealed contribution of different classes of non-coding RNAs in the cellular senescence. Long non-coding RNAs, microRNAs and circular RNAs are three classes of these transcripts whose contributions in this process have been more investigated. In the current review, we summarize the available literature on the impact of these transcripts in the cellular senescence.

PO-629-03 IN-DEPTH ANALYSIS OF THE SCN5A LOCUS HIGHLIGHTS DISTINCT GENETIC ARCHITECTURES FOR BRUGADA SYNDROME IN DIFFERENT ANCESTRIES AND IDENTIFIES A NOVEL RARE ENHANCER VARIANT ASSOCIATED WITH DISEASE IN SOUTHEAST ASIAN PATIENTS

Brugada syndrome (BrS) is a cardiac arrhythmia disorder that can cause sudden death in young adults. Genetic variation in the Nav1.5 cardiac sodium channel encoding SCN5A gene is robustly associated with BrS, across both rare coding and common non-coding variants. Despite a markedly higher prevalence of BrS, the diagnostic yield from SCN5A genetic testing in east and southeast Asia has been reported to be much lower than other regions. To compare the contribution of different classes of SCN5A variants (by variant type and rarity) to BrS between northwest European and Thai populations in order to investigate the apparent paradox between high disease prevalence and low diagnostic yield in southeast Asia. Genome sequencing data from European (412 cases, 769 controls) and Thai (202 cases, 410 controls) samples was analysed. SCN5A coding variants were binned by gnomAD exomes (v2.1) filtering allele frequency (FAF) and case-control odds ratios (OR) were calculated for each bin and ancestry. Rare non-coding variants in promoter and enhancer regions of SCN5A and SCN10A were assessed for enrichment or depletion in BrS cohorts. Ultra-rare (FAF<0.00001) SCN5A coding variants are more prevalent and enriched in European (22.6% of cases, OR=22.1, 11.4-43.0) compared to Thai (5.9% of cases, OR=4.3, 1.6-11.5) BrS patients. In contrast, low frequency variants (FAF 0.00005-0.001) that are expected to have intermediate effect sizes are uniquely enriched in Thai samples, occurring in 9.9% of patients. 3/6 of these variants (p.R965C, p.A1428S, p.V2016M) are known to affect Nav1.5 function. A rare non-coding variant in the SCN5A RE5 enhancer region (GRCh37:3-38621871-A-C), affecting a base conserved across species, was highly and uniquely enriched in Thai BrS cases (4.5% vs 0.2%, OR=19.1, p=3e-04). Distinct SCN5A genetic architectures are observed in European and southeast Asian BrS patients. The increased prevalence of BrS in southeast Asia is not due to an increased population burden of ultra-rare and highly deleterious SCN5A coding variants (which are relatively depleted in case cohorts). Our data suggest that other SCN5A variant classes, including coding variants of intermediate effect size and rare non-coding enhancer variants, are genetic risk factors in Thai BrS cases.

Competitive binding and molecular crowding regulate the cytoplasmic interactome of non-viral polymeric gene delivery vectors

In contrast to the processes controlling the complexation, targeting and uptake of polycationic gene delivery vectors, the molecular mechanisms regulating their cytoplasmic dissociation remains poorly understood. Upon cytosolic entry, vectors become exposed to a complex, concentrated mixture of molecules and biomacromolecules. In this report, we characterise the cytoplasmic interactome associated with polycationic vectors based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) and poly(2-methacrylolyloxyethyltrimethylammonium chloride) (PMETAC) brushes. To quantify the contribution of different classes of low molar mass molecules and biomacromolecules to RNA release, we develop a kinetics model based on competitive binding. Our results identify the importance of competition from highly charged biomacromolecules, such as cytosolic RNA, as a primary regulator of RNA release. Importantly, our data indicate the presence of ribosome associated proteins, proteins associated with translation and transcription factors that may underly a broader impact of polycationic vectors on translation. In addition, we bring evidence that molecular crowding modulates competitive binding and demonstrate how the modulation of such interactions, for example via quaternisation or the design of charge-shifting moieties, impacts on the long-term transfection efficiency of polycationic vectors. Understanding the mechanism regulating cytosolic dissociation will enable the improved design of cationic vectors for long term gene release and therapeutic efficacy.

Infrared action spectroscopy of doubly charged PAHs and their contribution to the aromatic infrared bands

The so-called aromatic infrared bands (AIBs) are attributed to emission of polycyclic aromatic hydrocarbons (PAHs). The observed variations toward different regions in space are believed to be caused by contributions of different classes of PAH molecules, that is to say with respect to their size, structure, and charge state. Laboratory spectra of members of these classes are needed to compare them to observations and to benchmark quantum-chemically computed spectra of these species. In this paper we present the experimental infrared (IR) spectra of three different PAH dications, naphthalene2+, anthracene2+, and phenanthrene2+, in the vibrational fingerprint region 500–1700 cm−1. The dications were produced by electron impact ionization of the vapours with 70 eV electrons, and they remained stable against dissociation and Coulomb explosion. The vibrational spectra were obtained by IR predissociation of the PAH2+ complexed with neon in a 22-pole cryogenic ion trap setup coupled to a free-electron infrared laser at the Free-Electron Lasers for Infrared eXperiments (FELIX) Laboratory. We performed anharmonic density-functional theory calculations for both singly and doubly charged states of the three molecules. The experimental band positions showed excellent agreement with the calculated band positions of the singlet electronic ground state for all three doubly charged species, indicating its higher stability over the triplet state. The presence of several strong combination bands and additional weaker features in the recorded spectra, especially in the 10–15 μm region of the mid-IR spectrum, required anharmonic calculations to understand their effects on the total integrated intensity for the different charge states. These measurements, in tandem with theoretical calculations, will help in the identification of this specific class of doubly-charged PAHs as carriers of AIBs.

Application of the metabolomics approach to the discovery of active compounds from Brazilian trees against resistant human melanoma cells

The chemical diversity of plants plays an essential role in the development of new drugs. However, new bioactive compound identification and isolation are challenging due to the complexity and time-consuming nature of the traditional process. Recently, alternative strategies have become popular, such as the statistical approach to correlate compounds with biological activities, overcoming bottlenecks in bioactive natural product research. We aimed to determine bioactive compounds against resistant human melanoma cells from leaves of Aspidosperma subincanum, Copaifera langsdorffii, Coussarea hydrangeifolia, Guarea guidonea and Tapirira guianensis, using a metabolomics approach. The extracts and fractions were obtained by accelerated solvent extraction (ASE) and tested against resistant melanoma cells SK-MEL-28 and SK-MEL-103. Chemical analysis was performed by high-performance diode array detector tandem mass spectrometry (HPLC-DAD-MS/MS). Chemical and biological data were analysed through univariate and multivariate analysis. The species present high chemical diversity, including indole alkaloids, glycosylated flavonoids, galloylquinic acid derivatives, cinnamic acid derivatives, and terpenes. The ASE fractionation separated the compounds according to the physicochemical properties; only C. langsdorffii and T. guianensis extracts were active. Both results from the chemical profile and the biological assay were treated using a metabolomics approach to identify the contribution of different classes of secondary metabolites in the viability of human melanoma cells. The analyses showed the metabolites from C. langsdorffii and T. guianensis, such as polyphenols and terpenes, were the main compounds correlated with the biological response. These findings afford alternative pathways that are trustworthy and less time-consuming to identify new bioactive compounds against multidrug-resistant human melanoma cells.

Hemagglutinin-Specific Non-neutralizing Antibody Is Essential for Protection Provided by Inactivated and Viral-Vectored H7N9 Avian Influenza Vaccines in Chickens.

Hemagglutination inhibition (HI) and virus neutralization antibody (nAb) do not always correlate with the protection of H7 avian influenza vaccines in mammals and humans. The contribution of different classes of antibodies induced by H7N9 vaccines to protection is poorly characterized in chickens. In this study, antibody responses induced by both inactivated and viral-vectored H7N9 vaccines in chickens were dissected. Chickens immunized with inactivated H7N9 vaccine showed 50% seroconversion rate and low HI and nAb titers at week 3 post immunization. However, inactivated H7N9 vaccine elicited 100% seroconversion rate in terms of high levels of HA-binding IgG antibody determined by ELISA. Despite inducing low levels of nAb, inactivated H7N9 vaccine conferred full protection against H7N9 challenge in chickens and markedly inhibited virus shedding. Similarly, Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and nAb titers but high level of IgG antibody against H7N9 virus. In addition, NDV-H7N9 vaccine also provided complete protection against H7N9 challenge. Chicken antisera had a high IgG/VN ratio, indicating that a larger proportion of serum antibodies were non-neutralizing antibody (non-nAb). More importantly, passive transfer challenge experiment showed that non-neutralizing antisera provided partial protection (37.5%) of chickens against H7N9 challenge, without significant difference from that provided by neutralizing antisera. In conclusion, our results suggest that antibodies measured by the traditional HI and virus neutralization assays do not correlate with the protection of inactivated and viral-vectored H7N9 vaccines in chickens, and HA-binding non-nAb also contributes to the protection against H7N9 infection. Total binding antibody can be used as a key correlate to the protection of H7N9 vaccine.

Effect of Stove Technology and Combustion Conditions on Gas and Particulate Emissions from Residential Biomass Combustion.

We have systematically examined the gas and particle phase emissions from seven wood combustion devices. Among total carbon mass emitted (excluding CO2), CO emissions were dominant, together with nonmethane volatile organic compounds (NMVOCs) (10-40%). Automated devices emitted 1-3 orders of magnitude lower CH4 (0.002-0.60 g kg-1 of wood) and NMVOCs (0.01-1 g kg-1 of wood) compared to batch-operated devices (CH4: 0.25-2.80 g kg-1 of wood; NMVOCs: 2.5-19 g kg-1 of wood). 60-90% of the total NMVOCs were emitted in the starting phase of batch-operated devices, except for the first load cycles. Partial-load conditions or deviations from the normal recommended operating conditions, such as use of wet wood/wheat pellets, oxygen rich or deficit conditions, significantly enhanced the emissions. NMVOCs were largely dominated by small carboxylic acids and alcohols, and furans. Despite the large variability in NMVOCs emission strengths, the relative contribution of different classes showed large similarities among different devices and combustion phases. We show that specific improper operating conditions may even for advanced technology not result in the emission reduction of secondary organic aerosol (SOA) forming compounds and thus not reduce the impact of wood combustion on climate and health.

Old Trade, New Tricks: Insights into the Spontaneous Mutation Process from the Partnering of Classical Mutation Accumulation Experiments with High-Throughput Genomic Approaches.

Mutations spawn genetic variation which, in turn, fuels evolution. Hence, experimental investigations into the rate and fitness effects of spontaneous mutations are central to the study of evolution. Mutation accumulation (MA) experiments have served as a cornerstone for furthering our understanding of spontaneous mutations for four decades. In the pregenomic era, phenotypic measurements of fitness-related traits in MA lines were used to indirectly estimate key mutational parameters, such as the genomic mutation rate, new mutational variance per generation, and the average fitness effect of mutations. Rapidly emerging next-generating sequencing technology has supplanted this phenotype-dependent approach, enabling direct empirical estimates of the mutation rate and a more nuanced understanding of the relative contributions of different classes of mutations to the standing genetic variation. Whole-genome sequencing of MA lines bears immense potential to provide a unified account of the evolutionary process at multiple levels—the genetic basis of variation, and the evolutionary dynamics of mutations under the forces of selection and drift. In this review, we have attempted to synthesize key insights into the spontaneous mutation process that are rapidly emerging from the partnering of classical MA experiments with high-throughput sequencing, with particular emphasis on the spontaneous rates and molecular properties of different mutational classes in nuclear and mitochondrial genomes of diverse taxa, the contribution of mutations to the evolution of gene expression, and the rate and stability of transgenerational epigenetic modifications. Future advances in sequencing technologies will enable greater species representation to further refine our understanding of mutational parameters and their functional consequences.

Electron correlation trends in the permanent electric dipole moments of alkaline-earth-metal monohydrides

We report the results of our theoretical studies of the permanent electric dipole moments (PDMs) of alkaline-earth-metal monohydride (AEMH) molecules, in their $X{\phantom{\rule{0.16em}{0ex}}}^{2}{\mathrm{\ensuremath{\Sigma}}}^{+}$ state, using a variant of the relativistic coupled-cluster theory in the singles and doubles approximation. It is the most detailed evaluation to date of the correlation effects associated with this property for this class of molecules. The molecules that have been considered in the present work are BeH, MgH, CaH, SrH, and BaH. We find that for SrH and BaH, the correlation contributions to the PDM are significant, about 18% and 21%, respectively, at the coupled-cluster singles and doubles level. All the core electrons have been excited in our calculations. We highlight the details of the individual contributions of different classes of correlation effects. For all the above molecular candidates, we have also made a comprehensive analysis of the possible sources of error in our calculations.

Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis.

Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only inhibit growth and proliferation of cancer cells, but also control invasion and metastasis. One class of targets gaining international attention is the aquaporins, a family of membrane-spanning water channels with diverse physiological functions and extensive tissue-specific distributions in humans. Aquaporins−1,−2,−3,−4,−5,−8, and−9 have been linked to roles in cancer invasion, and metastasis, but their mechanisms of action remain to be fully defined. Aquaporins are implicated in the metastatic cascade in processes of angiogenesis, cellular dissociation, migration, and invasion. Cancer invasion and metastasis are proposed to be potentiated by aquaporins in boosting tumor angiogenesis, enhancing cell volume regulation, regulating cell-cell and cell-matrix adhesions, interacting with actin cytoskeleton, regulating proteases and extracellular-matrix degrading molecules, contributing to the regulation of epithelial-mesenchymal transitions, and interacting with signaling pathways enabling motility and invasion. Pharmacological modulators of aquaporin channels are being identified and tested for therapeutic potential, including compounds derived from loop diuretics, metal-containing organic compounds, plant natural products, and other small molecules. Further studies on aquaporin-dependent functions in cancer metastasis are needed to define the differential contributions of different classes of aquaporin channels to regulation of fluid balance, cell volume, small solute transport, signal transduction, their possible relevance as rate limiting steps, and potential values as therapeutic targets for invasion and metastasis.

The effect of solids residence time on phosphorus adsorption to hydrous ferric oxide floc

The impact of solids residence time (SRT) on phosphate adsorption to hydrous ferric oxide (HFO) floc when striving for ultra-low P concentrations was characterized and an equilibrium model that describes the adsorption of P onto HFO floc of different ages was developed. The results showed that fresh HFO had a higher adsorption capacity in comparison to aged (2.8, 7.4, 10.8 and 22.8 days) HFO and contributed substantially to P removal at steady state. P adsorption onto HFO solids was determined to be best described by the Freundlich isotherm. P desorption from HFO solids was negligible supporting the hypothesis that chemisorption is the mechanism of P adsorption on HFO solids. A model that included the contribution of different classes of HFO solids (i.e. High, Low or Old, containing high concentration, low concentration or no active surface sites, respectively) to adsorption onto HFO from a sequencing batch reactor (SBR) system was found to adequately describe P adsorption onto HFO solids of different ages. From the model it was determined that the fractions of High and Low HFO decreased with SRT while the fraction of Old HFO increased with SRT. The transformation of High HFO to Low HFO did not limit the overall production of Old HFO and the fresh HFO solids contributed more to P removal at steady state than the aged solids.

How Sensitive is the Analysis of Firm and Employment Dynamics to Longitudinal Linkage Problems?

Empirical measures of firm and employment dynamics based on administrative datasets are biased due to missing links in the longitudinal observation of firms. This paper quantifies the bias in a set of widely used measures and evaluates the performance of two linkage methods in reducing bias. We find that a linkage method that builds on the continuity of the firm’s workforce is more effective for producing reliable estimates of these measures than a traditional record linking method commonly applied by statistical agencies.Using improved linkages considerably modifies results regarding the contribution of different classes of firms to employment growth. It almost completely shifts the mass of employment at entry and exit towards the smallest firms. It reduces job creation by entrants and job destruction due to exit by half and reveals a greater importance of established firms for employment growth.

Contribution of different classes of glutamate receptors in the corticostriatal polysynaptic responses from striatal direct and indirect projection neurons

BackgroundPrevious work showed differences in the polysynaptic activation of GABAergic synapses during corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (dSPNs and iSPNs). Here, we now show differences and similarities in the polysynaptic activation of cortical glutamatergic synapses on the same responses. Corticostriatal contacts have been extensively studied. However, several questions remain unanswered, e.g.: what are the differences and similarities in the responses to glutamate in dSPNs and iSPNs? Does glutamatergic synaptic activation exhibits a distribution of latencies over time in vitro? That would be a strong suggestion of polysynaptic cortical convergence. What is the role of kainate receptors in corticostriatal transmission? Current-clamp recordings were used to answer these questions. One hypothesis was: if prolonged synaptic activation distributed along time was present, then it would be mainly generated from the cortex, and not from the striatum.ResultsBy isolating responses from AMPA-receptors out of the complex suprathreshold response of SPNs, it is shown that a single cortical stimulus induces early and late synaptic activation lasting hundreds of milliseconds. Prolonged responses depended on cortical stimulation because they could not be elicited using intrastriatal stimulation, even if GABAergic transmission was blocked. Thus, the results are not explained by differences in evoked inhibition. Moreover, inhibitory participation was larger after cortical than after intrastriatal stimulation. A strong activation of interneurons was obtained from the cortex, demonstrating that polysynaptic activation includes the striatum. Prolonged kainate (KA) receptor responses were also elicited from the cortex. Responses of dSPNs and iSPNs did not depend on the cortical area stimulated. In contrast to AMPA-receptors, responses from NMDA- and KA-receptors do not exhibit early and late responses, but generate slow responses that contribute to plateau depolarizations.ConclusionsAs it has been established in previous physiological studies in vivo, synaptic invasion over different latencies, spanning hundreds of milliseconds after a single stimulus strongly indicates convergent polysynaptic activation. Interconnected cortical neurons converging on the same SPNs may explain prolonged corticostriatal responses. Glutamate receptors participation in these responses is described as well as differences and similarities between dSPNs and iSPNs.

Spectrum simulation and decomposition with nuclear ensemble: formal derivation and application to benzene, furan and 2-phenylfuran

A formal derivation of the nuclear-ensemble method for absorption and emission spectrum simulations is presented. It includes discussions of the main approximations employed in the method and derivations of new features aiming at further developments. Additionally, a method for spectrum decomposition is proposed and implemented. The method is designed to provide absolute contributions of different classes of states (localized, diffuse, charge-transfer, delocalized) to each spectral band. The methods for spectrum simulation and decomposition are applied to the investigation of UV absorption of benzene, furan, and 2-phenylfuran, and of fluorescence of 2-phenylfuran.

THE EFFECT OF BLAZAR SPECTRAL BREAKS ON THE BLAZAR CONTRIBUTION TO THE EXTRAGALACTIC GAMMA-RAY BACKGROUND

The spectral shapes of the contributions of different classes of unresolved gamma-ray emitters can provide insight into their relative contributions to the extragalactic gamma-ray background (EGB) and the natures of their spectra at GeV energies. We calculate the spectral shapes of the contributions to the EGB arising from BL Lacertae type objects (BL Lacs) and flat-spectrum radio quasars (FSRQs) assuming blazar spectra can be described as broken power laws. We fit the resulting total blazar spectral shape to the Fermi Large Area Telescope measurements of the EGB, finding that the best-fit shape reproduces well the shape of the Fermi EGB for various break scenarios. We conclude that a scenario in which the contribution of blazars is dominant cannot be excluded on spectral grounds alone, even if spectral breaks are shown to be common among Fermi blazars. We also find that while the observation of a featureless (within uncertainties) power-law EGB spectrum by Fermi does not necessarily imply a single class of contributing unresolved sources with featureless individual spectra, such an observation and the collective spectra of the separate contributing populations determine the ratios of their contributions. As such, a comparison with studies including blazar gamma-ray luminosity functions could have profound implications for the blazar contribution to the EGB, blazar evolution, and blazar gamma-ray spectra and emission.

Characterization of digestive proteolytic activity in Lygus hesperus Knight (Hemiptera: Miridae)

The tarnished plant bug, Lygus hesperus Knight, is a pest that causes considerable economic losses to vegetables, cotton, canola, and alfalfa. Detailed knowledge of its digestive physiology will provide new opportunities for a sustainable pest management approach to control this insect. Little is known about the different protease class contributions to the overall digestion of a specific protein. To this end, the proteolytic activities in female adult L. hesperus salivary gland and midgut homogenates were quantified over a range of pH's and time points, and the contribution of different classes of proteases to the degradation of FITC-casein was determined. In the salivary gland, serine proteases were the predominant class responsible for caseinolytic activity, with the rate of activity increasing with increasing pH. In contrast, both aspartic and serine proteases contributed to caseinolytic activity in the midgut. Aspartic protease activity predominated at pH 5.0 and occurred immediately after incubation, whereas serine protease activity predominated at pH 7.5 after a 9 h delay and was resistant to aprotinin. The salivary serine proteases were distinctly different from midgut serine proteases, based on the tissue-specific differential susceptibility to aprotinin and differing pH optima. Collectively, the caseinolytic activities complement one another, expanding the location and pH range over which digestion can occur.

Upstate Channel Switch

Medium spiny neurons (MSNs) of the striatum are key regulators of voluntary movement, and loss or deregulation of these neurons causes movement disorders, such as Huntington's or Parkinson's disease. These GABAergic neurons are activated by glutamatergic input to their dendritic spines. MSNs exist in a resting (—80 mV membrane potential) and an "upstate" (—50 mV membrane potential). Carter and Sabatini used 2-photon laser-scanning microscopy (2PLSM) and 2-photon laser uncaging of glutamate to investigate the calcium signals generated in resting or upstate MSNs in rat striatal slices. Calcium signals were larger and longer lasting in upstate cells, with the largest increase detected in the dendritic spine head. Using pharmacological inhibitors of different classes of voltage-gated calcium channels (VGCCs), the authors determined that stimulation of resting cells activates T-type and R-type VGCCs, and stimulation of upstate cells activates L-type and R-type VGCCs. Resting cells also respond to localized uncaging of glutamate with a fast Ca 2+ transient mediated by AMPA receptors and a slower, prolonged Ca 2+ transient mediated by N -methyl D aspartate (NMDA) receptors. Comparing responses in resting and upstate cells indicated a strong AMPA receptor contribution in resting cells and a dominant NMDA receptor contribution in upstate cells. These results indicate that differences in calcium signaling observed in resting and upstate MSNs arise from changes in the contributions of different classes of VGCCs and glutamate receptors. A. G. Carter, B. L. Sabatini, State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44 , 483-493 (2004). [Online Journal]

C(a2+)-dependent glutamate release involves two classes of endoplasmic reticulum Ca(2+) stores in astrocytes.

Astrocytes can modulate synaptic transmission by releasing glutamate in a Ca(2+)-dependent manner. Although the internal Ca(2+) stores have been implicated as the predominant source of Ca(2+) necessary for this glutamate release, the contribution of different classes of these stores is still not well defined. To address this issue, we cultured purified solitary cortical astrocytes and monitored changes in their internal Ca(2+) levels and glutamate release into the extracellular space. Ca(2+) levels were monitored by using the Ca(2+) indicator fluo-3 and quantitative fluorescence microscopy. Glutamate release was monitored by an L-glutamate dehydrogenase-linked detection system. Astrocytes were mechanically stimulated with a glass pipette, which reliably caused an increase in internal Ca(2+) levels and glutamate release into the extracellular space. Although we find that the presence of extracellular Cd(2+), a Ca(2+) channel blocker, significantly reduces mechanically induced glutamate release from astrocytes, we confirm that internal Ca(2+) stores are the predominant source of Ca(2+) necessary for this glutamate release. To test the involvement of different classes of internal Ca(2+) stores, we used a pharmacological approach. We found that diphenylboric acid 2-aminoethyl ester, a cell-permeable inositol 1,4,5-trisphosphate (IP(3)) receptor antagonist, greatly reduced mechanically induced glutamate release. Additionally, the preincubation of astrocytes with caffeine or ryanodine also reduced glutamate release. Taken together, our data are consistent with dual IP(3)- and caffeine/ryanodine-sensitive Ca(2+) stores functioning in the control of glutamate release from astrocytes.

The significance of A-δ and C fibres for the perception of synthetic heat

Synthetic heat is a perception of strong, but not painful, heat arising when skin is stimulated by an alternating pattern of adjacent cold and warmth. This study examines the contribution of different classes of nerve fibres to this perception. In 40 subjects changes in synthetic heat and thermal perceptions were studied during a 30-min ischaemic nerve block in one reaction time, and one threshold determination task. Synthetic heat stimuli were described as hot or warm, but not as painful, and were preceded by a transient cold. Reaction times for synthetic heat stimuli did not differ from those for cold stimuli. Thresholds for synthetic heat and thermal stimuli were similar. During A fibre nerve block the perception of synthetic heat lost the cold component whereas the frequency of hot and warm descriptors did not change. The perception of cold stimuli changed, such that pure cold was replaced by dysaesthetic descriptors. Reaction times and thresholds for thermal and synthetic heat stimuli increased equally during the nerve block. It is concluded that the perception of synthetic heat most likely arises from the fusion of signals dependent on unmyelinated low threshold cold and warm receptors. It is not dependent on A-δ cold fibres, and a contribution of nociceptors is quite unlikely. The possibility of a psychological contribution at the perceptual level is discussed.

The Role of Familial Factors in Bulimia Nervosa

This research investigated three levels of family variables--general family dysfunction, family eating attitudes and behaviors, and negative familial communication regarding physical appearance and encouragement to diet--as predictors of the severity of bulimic symptomatology in a sample of 345 undergraduate women. Participants completed The Bulimia Test--Revised (Thelen, Farmer, Wonderlich, & Smith, 1991), the Family Environment Scale (Moos & Moos, 1984), and the Family Eating Attitude and Behavior Scale (Hogen, 1988) and rated the frequency with which family members made negative statements regarding their physical appearance and the need to diet. A hierarchical multiple regression analysis indicated that all three levels of family variables accounted for significant proportions of the variance in bulimic symptomatology. When the contribution of other variables to the regression equation was controlled, negative family communications, external control of food intake, and rules related to family mealtimes remained as significant predictors. These results illustrate the importance of investigating the relative contribution of different classes of familial variables to our understanding of bulimia nervosa and suggest important foci for the prevention of eating problems and eating disorders among young women.