Temporal integration in auditory sensory memory: neuromagnetic evidence

The cortical mechanisms of auditory sensory memory were investigated by analysis of neuromagnetic evoked responses. The major deflection of the auditory evoked field (N100m) appears to comprise an early posterior component (N100m^P) and a late anterior component (N100m^A) which is sensitive to temporal factors. When pairs of identical sounds are presented at intervals less than about 250 msec, the second sound evokes N100m^A with enhanced amplitude at a latency of about 150 msec. We suggest that N100m^A may index the activity of two distinct processes in auditory sensory memory. Its recovery cycle may reflect the activity of a memory trace which, according to previous studies, can retain processed information about an auditory sequence for about 10 sec. The enhancement effect may reflect the activity of a temporal integration process, whose time constant is such that sensation persists for 200–300 msec after stimulus offset, and so serves as a short memory store. Sound sequences falling within this window of integration seem to be coded holistically as unitary events.     

Towards habitat-oriented systems biology of “Aromatoleum aromaticum” EbN1

The denitrifying betaproteobacterium “Aromatoleum aromaticum” EbN1 is a well-studied model organism for anaerobic degradation of aromatic compounds. Following publication of its genome in 2005, comprehensive physiological–proteomic studies were conducted to deduce functional understanding from the genomic blueprint. A catabolic network (85 predicted, 65 identified proteins) for anaerobic degradation of 24 aromatic growth substrates (including 11 newly recognized) was established. Newly elucidated pathways include those for 4-ethylphenol and plant-derived 3-phenylpropanoids, involving functional assignment of several paralogous genes. The substrate-specific regulation of individual peripheral degradation pathways is probably initiated by highly specific chemical sensing via dedicated sensory/regulatory proteins, e.g. three different σ⁵⁴-dependent one-component sensory/regulatory proteins are predicted to discriminate between three phenolic substrates (phenol, p-cresol and 4-ethylphenol) and two different two-component systems are assumed to differentiate between two alkylbenzenes (toluene, ethylbenzene). Investigations under in situ relevant growth conditions revealed (a) preferred utilization of benzoate from a mixture with succinate results from repressed synthesis of a C₄-dicarboxylate TRAP transporter; (b) response to alkylbenzene-induced solvent stress comprises metabolic re-routing of acetyl-CoA and reducing equivalents to poly(3-hydroxybutyrate) synthesis, alteration of cellular membrane composition and formation of putative solvent efflux systems; and (c) multifaceted adaptation to slow growth includes adjustment of energy demand for maintenance and preparedness for future nutritional opportunities, i.e. provision of uptake systems and catabolic enzymes for multiple aromatic substrates despite their absence. This broad knowledge base taken together with the recent development of a genetic system will facilitate future functional, biotechnological (stereospecific dehydrogenases) and habitat re-enacting (“eco-”systems biology) studies with “A. aromaticum” EbN1.     

Parallel processing in the honeybee olfactory pathway: structure, function, and evolution

Animals face highly complex and dynamic olfactory stimuli in their natural environments, which require fast and reliable olfactory processing. Parallel processing is a common principle of sensory systems supporting this task, for example in visual and auditory systems, but its role in olfaction remained unclear. Studies in the honeybee focused on a dual olfactory pathway. Two sets of projection neurons connect glomeruli in two antennal-lobe hemilobes via lateral and medial tracts in opposite sequence with the mushroom bodies and lateral horn. Comparative studies suggest that this dual-tract circuit represents a unique adaptation in Hymenoptera. Imaging studies indicate that glomeruli in both hemilobes receive redundant sensory input. Recent simultaneous multi-unit recordings from projection neurons of both tracts revealed widely overlapping response profiles strongly indicating parallel olfactory processing. Whereas lateral-tract neurons respond fast with broad (generalistic) profiles, medial-tract neurons are odorant specific and respond slower. In analogy to “what-” and “where” subsystems in visual pathways, this suggests two parallel olfactory subsystems providing “what-” (quality) and “when” (temporal) information. Temporal response properties may support across-tract coincidence coding in higher centers. Parallel olfactory processing likely enhances perception of complex odorant mixtures to decode the diverse and dynamic olfactory world of a social insect.     

TRP channels in disease

“Transient receptor potential” cation channels (TRP channels) play a unique role as cell sensors, are involved in a plethora of Ca²⁺-mediated cell functions, and play a role as “gate-keepers” in many homeostatic processes such as Ca²⁺ and Mg²⁺ reabsorption. The variety of functions to which TRP channels contribute and the polymodal character of their activation predict that failures in correct channel gating or permeation will likely contribute to complex pathophysiological mechanisms. Dysfunctions of TRPs cause human diseases but are also involved in a complex manner to contribute and determine the progress of several diseases. Contributions to this special issue discuss channelopathias for which mutations in TRP channels that induce “loss-“ or “gain-of-function” of the channel and can be considered “disease-causing” have been identified. The role of TRPs will be further elucidated in complex diseases of the intestinal, renal, urogenital, respiratory, and cardiovascular systems. Finally, the role of TRPs will be discussed in neuronal diseases and neurodegenerative disorders.     

Human nonshivering thermogenesis

Metabolic responses, skin temperatures and changes in heart rate and blood pressure were measured in a control group and in “polar swimmers” after infusion of different doses of epinephrine, norepinephrine and isoprenaline. In controls the highest infusion dose of isoprenaline (0.1 μg min⁻¹ kg⁻¹) increased metabolic rate in normal humans by 36%, while the highest infusion doses of epinephrine and norepinephrine (0.45 μg min⁻¹ kg⁻¹) increased metabolic rate by 24%, only. In “polar swimmers” the epinephrine thermogenesis was potentiated significantly, reaching about 45% of the basal metabolic rate. The norepinephrine and isoprenaline thermogenesis were not different from that of the control group. It is concluded that in humans the epinephrine thermogenesis is probably located in muscles and in the white fat (Simonsen et al., 1992), and may be the principal mechanism of metabolic adaptation to cold. It was calculated that the increased capacity of epinephrine thermogenesis in cold exposed “polar swimmers” could theoretically shift the survival limit downwards to lower environmental temperatures by about 5°C.     

Multiple roles for Hox genes in segment-specific shaping of CNS lineages

In this “Extra View” article we highlight some of the recently accumulating evidence showing that Hox genes are involved at different steps during the development of neural cell lineages to control segmental patterning of the CNS. In addition to their well-known early role in establishing segmental identities, Hox genes act on neural stem cells and their progeny at various stages during embryonic and postembryonic development to control proliferation, cell fate and/or apoptosis in a segment-specific manner. This leads to differential shaping of serially homologous lineages and thus to structural diversification of segmental CNS units (neuromeres) in adaptation to their specific functional tasks in processing sensory information and generation of motor patterns.     

Microwave irradiation affects radial-arm maze performance in the rat

After 45 min of exposure to pulsed 2450 MHz microwaves (2 μsec pulses, 500 pps, 1 mW/cm², average whole body SAR 0.6 W/kg), rats showed retarded learning while performing in the radial-arm maze to obtain food rewards, indicating a deficit in spatial “working memory” function. This behavioral deficit was reversed by pretreatment before exposure with the cholinergic agonist physostigmine or the opiate antagonist naltrexone, whereas pretreatment with the peripheral opiate antagonist naloxone methiodide showed no reversal of effect. These data indicate that both cholinergic and endogenous opioid neurotransmitter systems in the brain are involved in the microwave-induced spatial memory deficit. © 1994 Wiley-Liss, Inc.     

Cerebral Evoked Potential Correlates in Forced-paced Tasks

CEREBRAL evoked potentials can be monitored by averaging scalp records in subjects performing psychological tasks. The waveform is affected not only by the physical features of the sensory stimulus but also by cognitive and motivational parameters^1–7. These can be manipulated through verbal instructions given to the subject and several studies have shown that a slow positive component of about 300 ms peak latency (P₃₀₀) can be elicited by stimuli to which perceptual significance is attached^2,5–8. We have examined the evoked potential correlates of sensory overload in forced-paced auditory tasks and find that the cerebral “decision” potential can reveal intermittency in the perceptual channel.     

Current advances in biological production of propionic acid

Propionic acid and its derivatives are considered “Generally Recognized As Safe” food additives and are generally used as an anti-microbial and anti-inflammatory agent, herbicide, and artificial flavor in diverse industrial applications. It is produced via biological pathways using Propionibacterium and some anaerobic bacteria. However, its commercial chemical synthesis from the petroleum-based feedstock is the conventional production process bit results in some environmental issues. Novel biological approaches using microorganisms and renewable biomass have attracted considerable recent attention due to economic advantages as well as great adaptation with the green technology. This review provides a comprehensive overview of important biotechnological aspects of propionic acid production using recent technologies such as employment of co-culture, genetic and metabolic engineering, immobilization technique and efficient bioreactor systems.     

Role of Contractile Microfilaments in Macrophage Movement and Endocytosis

PHAGOCYTOSIS of bacteria and other large particles and pinocytosis of colloids—two processes collectively termed endocytosis—are among the characteristic properties of macrophages. When mouse peritoneal macrophages in culture are observed by phase contrast microscopy, most small endocytotic vesicles (pinosomes) are seen to be formed in the region of ruffled membrane activity, usually in a pseudopod¹. The phase-lucent pinosomes move rapidly towards the Golgi region where they unite with phase-dense granules to form secondary lysosomes. Although there is evidence that both phagocytosis and pinocytosis in macrophages have a high temperature coefficient and require metabolic energy¹, the mechanism of endocytosis is unknown. Clearly, movement of the plasma membrane and directional movement of pinosomes is involved. During the past few years attention has been drawn to the apparent association in many cells between movement and the presence of contractile microfilaments of about 50 Â diameter^2,3. Some of these are actin-like and can bind heavy meromyosin to give distinctive “arrowhead” structures in electron micrographs⁴. One of us (S. de P., in preparation) has found that the peripheral or cortical cytoplasm of macrophages contains a network of microfilaments, some of which may be inserted into the plasma membrane. These filaments bind heavy meromyosin (Figs. 1 and 2) and details of their structure and disposition will be published later.     

Arguments against the significance of the Fenton reaction contributing to signal pathways under in vivo conditions

One of the common explanations for oxidative stress in the physiological milieu is based on the Fenton reaction, i.e. the assumption that radical chain reactions are initiated by metal-catalyzed electron transfer to hydrogen peroxide yielding hydroxyl radicals. On the other hand — especially in the context of so-called “iron switches” — it is postulated that cellular signaling pathways originate from the interaction of reduced iron with hydrogen peroxide.

Using fluorescence detection and EPR for identification of radical intermediates, we determined the rate of iron complexation by physiological buffer together with the reaction rate of concomitant hydroxylations of aromatic compounds under aerobic and anaerobic conditions. With the obtained overall reaction rate of 1,700 M^-1s^-1 for the buffer-dependent reactions and the known rates for Fenton reactions, we derive estimates for the relative reaction probabilities of both processes.

As a consequence we suggest that under in vivo conditions initiation of chain reactions by hydroxyl radicals generated by the Fenton reaction is of minor importance and hence metal-dependent oxidative stress must be rather independent of the so-called “peroxide tone”. Furthermore, it is proposed that — in the low (subtoxic) concentration range — hydroxylated compounds derived from reactions of “non-free” (crypto) OH radicals are better candidates for iron-dependent sensing of redox-states and for explaining the origin of cellular signals than the generation of “free” hydroxyl radicals.     

Systems & Synthetic Industrial Biotechnology

Cover illustration This Special Issue on “Systems and Synthetic Approaches to Industrial Biotechnology” compiles the outcomes of the minisymposiumat the 31^st General Assembly of the International Union of Biological Sciences (IUBS). Implementation of systems biology and synthetic biology approaches in engineering industrial microbes and processes provides a promising and straight-forward approach to linking basic and application-inspired research. The cover represents the various concepts involved in systems and synthetic biotechnology. Image: © kytalpa – Fotolia.com.     

Morphogenetic networks which determine the spatial expression of zygotic genes in early <Emphasis Type="Italic">Drosophila</Emphasis> embryo

This review deals with the recent studies expanding the idea of positional information in the early embryogenesis of Drosophila melanogaster. Previous studies showed that, in the course of segment determination in Drosophila, information created by gradients of products of maternal coordinate genes is not “read” statically, being interpreted by their zygotic target genes via regulatory interactions. This leads to spatial shifts in the expression of target genes relative to the original positions as well as to dynamic reduction in the zygotic expression variability. However, according to recent data, interpretation of positional information includes the interaction between not only zygotic target genes but also the maternal coordinate genes themselves. Different systems of maternal coordinate genes (maternal systems)—the posterior-anterior, terminal, and dorsoventral—can interact with each other. This is usually expressed in the regulation of zygotic target genes of one maternal system by other maternal systems. The concept of a “morphogenetic network” was introduced to define the interaction of maternal systems during determination of spatial gene expression in the early Drosophila embryo.     

SONG DIVERGENCE BY SENSORY DRIVE IN AMAZONIAN BIRDS

Visual signals are shaped by variation in the signaling environment through a process termed sensory drive, sometimes leading to speciation. However, the evidence for sensory drive in acoustic signals is restricted to comparisons between highly dissimilar habitats, or single‐species studies in which it is difficult to rule out the influence of undetected ecological variables, pleiotropic effects, or chance. Here we assess whether this form of sensory drive—often termed “acoustic adaptation”—can generate signal divergence across ecological gradients. By studying avian communities in two Amazonian forest types, we show that songs of 17 “bamboo‐specialist” bird species differ in predictable ways from their nearest relatives in adjacent terra firme forest. We also demonstrate that the direction of song divergence is correlated with the sound transmission properties of habitats, rather than with genetic divergence, ambient noise, or pleiotropic effects of mass and bill size. Our findings indicate that acoustic adaptation adds significantly to stochastic processes underlying song divergence, even when comparing between habitats with relatively similar structure. Furthermore, given that song differences potentially contribute to reproductive isolation, these findings are consistent with a wider role for sensory drive in the diversification of lineages with acoustic mating signals.     

Characterization of the Paracoccidioides Hypoxia Response Reveals New Insights into Pathogenesis Mechanisms of This Important Human Pathogenic Fungus

Background

Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America.

Methodology/Principal Findings

In this work, a detailed hypoxia characterization was performed in Paracoccidioides. Using NanoUPLC-MS^E proteomic approach, we obtained a total of 288 proteins differentially regulated in 12 and 24 h of hypoxia, providing a global view of metabolic changes during this stress. In addition, a functional characterization of the homologue to the most important molecule involved in hypoxia responses in other fungi, the SREBP (sterol regulatory element binding protein) was performed. We observed that Paracoccidioides species have a functional homologue of SREBP, named here as SrbA, detected by using a heterologous genetic approach in the srbA null mutant in Aspergillus fumigatus. Paracoccidioides srbA (PbsrbA), in addition to involvement in hypoxia, is probable involved in iron adaptation and azole drug resistance responses.

Conclusions/Significance

In this study, the hypoxia was characterized in Paracoccidioides. The first results can be important for a better understanding of the fungal adaptation to the host and improve the arsenal of molecules for the development of alternative treatment options in future, since molecules related to fungal adaptation to low oxygen levels are important to virulence and pathogenesis in human pathogenic fungi.