Table of Contents

Volume 5, Issue 3

  May/June 2012

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VIEW POINT

Open Access Article

Do we eat gene regulators?

Guenther Witzany
http://dx.doi.org/10.4161/cib.19621
Abstract | Full Text

In a recent study, plant microRNAs (miRNAs) have been found in the sera and tissues of various animals including humans. These miRNAs are acquired orally by food intake and can pass through the mammalian gastrointestinal tract into sera and organs. In vitro and in vivo studies have demonstrated that these plant microRNAs in food can regulate the expression of target genes in mammals. Correct regulation or dysregulation of miRNAs is linked to important gene expression patterns and diseases, such as cancer and arteriosclerosis. Interestingly, plant miRNA function in mammalian cells is similar to the function of mammalian miRNAs; this gives rise to some notable questions.




OPINION ARTICLE

Open Access Article

Some new speculative ideas about the “behavioral homeostasis theory” as to how the simple learned behaviors of habituation and sensitization improve organism survival throughout phylogeny

E. M. Eisenstein, D. L. Eisenstein, J. S. M. Sarma, H. Knapp and J.C. Smith
Abstract | Full Text

This paper explores further the ‘behavioral homeostasis theory’ (BHT) regarding the evolutionary significance for organism survival of the two simple non-associative rapidly learned behaviors of habituation and sensitization. The BHT postulates that the evolutionary function of habituation and sensitization throughout phylogeny is to rapidly maximize an organism’s overall readiness to cope with new stimuli and to minimize unnecessary energy expenditure. These behaviors have survived with remarkable similarity throughout phylogeny from aneural protozoa to humans. The concept of ‘behavioral homeostasis’ emphasizes that the homeostatic process is more than just maintaining internal equilibrium in the face of changing internal and external conditions. It emphasizes the rapid internal and external effector system changes that occur to optimize organism readiness to cope with any new external stimulus situation. Truly life-threatening stimuli elicit instinctive behavior such as fight, flee, or hide. If the stimulus is not life-threatening, the organism rapidly learns to adjust to an appropriate level of overall responsiveness over stimulus repetitions. The rapid asymptotic level approached by those who decrease their overall responsiveness to the second stimulus (habituaters) and those who increase their overall responsiveness to an identical second stimulus (sensitizers) not only optimizes readiness to cope with any new stimulus situation but also reduces unnecessary energy expenditure. This paper is based on a retrospective analysis of data from 4 effector system responses to 8 repetitive tone stimuli in adult human males. The effector systems include the galvanic skin response, finger pulse volume, muscle frontalis and heart rate. The new information provides the basis for further exploration of the BHT including new predictions and proposed relatively simple experiments to test them.




SHORT COMMUNICATIONS

Open Access Article

Caged intracellular NMDA receptor blockers for the study of subcellular ion channel function

James E. Reeve, Michael M. Kohl, Antonio Rodríguez-Moreno, Ole Paulsen and Harry L. Anderson
Abstract | Full Text

We have previously synthesized a caged form of the use dependent N-methyl-d-aspartate (NMDA) receptor ion channel blocker MK801 and used intracellular photolysis of this compound to demonstrate the subcellular location of NMDA receptor ion channels involved in synaptic plasticity. Here, we discuss considerations regarding the choice of caging molecule, synthesis and the potential uses for caged ion channel blockers in neurophysiology.

Open Access Article

An integrated model for the nucleo-cytoplasmic transport of cytoplasmic poly(A)-binding proteins

Hannah Burgess and Nicola Gray
Abstract | Full Text

Cytoplasmic poly(A)-binding proteins (PABPs) regulate mRNA stability and translation. Although predominantly localized in the cytoplasm, PABP proteins also cycle through the nucleus. Recent work has established that their steady-state localization can be altered by cellular stresses such as UV (UV) radiation, and infection by several viruses, resulting in nuclear accumulation of PABPs. Here, we present further evidence that their interaction with and release from mRNA and translation complexes are important in determining their sub-cellular distribution and propose an integrated model for regulated nucleo-cytoplasmic transport of PABPs.

Open Access Article

Astroglial gap junctions shape neuronal network activity

Ulrike Pannasch, Mickael Derangeon, Oana Chever and Nathalie Rouach
Abstract | Full Text

Astrocytes, the third element of the tripartite synapse, are active players in neurotransmission. Up to now, their involvement in neuronal functions has primarily been investigated at the single cell level. However, a key property of astrocytes is that they communicate via extensive networks formed by gap junction channels. Recently, we have shown that this networking modulates the moment to moment basal synaptic transmission and plasticity via the regulation of extracellular potassium and glutamate levels. Here we show that astroglial gap junctional communication also regulates neuronal network activity. We discuss these findings and their implications for brain information processing.

Open Access Article

Cytoplasmic superoxide radical: a possible contributing factor to intracellular Aβ oligomerization in Alzheimer disease

Kazuma Murakami and Takahiko Shimizu
Abstract | Full Text

Soluble amyloid β (Aβ) oligomers cause memory loss and synaptic dysfunction in Alzheimer disease (AD). Despite intensive studies on Aβ assembly in vitro and in vivo, the localization and cellular mechanism of Aβ oligomerization are not fully understood. Previously, we demonstrated that cytoplasmic superoxide radicals contribute to drusen deposition, a hallmark of age-related macular degeneration as well as other geriatric diseases (fatty liver, skin thinning, and osteoporosis). Using a transgenic mouse model of AD, we recently clarified the role of cytoplasmic oxidative stress in cognitive impairment and oligomer formation. Moreover, we also found that these phenomena were associated with neuroinflammation, tau phosphorylation, and synaptic loss. Notably, studies using human brains support the involvement of cytoplasmic superoxide radicals in AD pathology. In this addendum to Murakami et al. (JBC 2011), we discuss and comment on intracellular Aβ oligomer formation and the possible therapeutic effects of intracellular redox state modulators.

Open Access Article

Neural Correlates of Unpredictability in Behavioral Patterns of Wild-type and R6/2 Mice

S. Lee Hong, Scott Barton and George Rebec
Abstract | Full Text

This paper expands on recent findings that link dynamic patterns of striatal activity with patterns of movement and exploration in wild-type and transgenic mice (R6/2) that model Huntington’s disease (HD), a fatally inherited neurological condition. Here, with HD as a backdrop, we further develop the concept of entropy conservation in brain and behavior. In particular, we propose that entropy conservation could serve as a rule that guides the process of redistributing brain activity dynamics in order to alter behavior, allowing the adaptation to an ever-changing external environment. This concept is further linked to recent neuroimaging studies in human aging, building a new bridge between our recent findings of entropy conservation and the extant literature.

Open Access Article

Pupal vibratory signals of a group-living beetle that deter larvae: are they mimics of predator cues?

Wataru Kojima, Yukio Ishikawa and Takuma Takanashi
Abstract | Full Text

Pupae of some insects produce sounds or vibrations, but the function of the sounds/vibrations has not been clarified in most cases. Recently, we found vibratory communication between pupae and larvae of a group-living beetle Trypoxylus dichotoma, which live in humus soil. The vibratory signals produced by pupae were shown to deter approaching larvae, thereby protecting themselves. In the present study, we tested our hypothesis that pupal signals are mimics of vibratory noises associated with foraging of moles, the most common predators of T. dichotoma. Mole vibrations played back in laboratory experiments deterred larval approaches in the same way as pupal signals. These findings suggest that to deter conspecific larvae, pupae of T. dichotoma may have exploited a preexisting response of larvae to predator vibrations by emitting deceptive signals.




MINI-REVIEW

Open Access Article

Ensuring the faithful execution of cytokinesis in Schizosaccharomyces pombe

Jim Karagiannis
Abstract | Full Text

Eukaryotic cells ensure error-free progress through the cell cycle by monitoring 1) the completion of cell cycle events, 2) damage to critical cellular components, or 3) structural changes such as the attachment of kinetochores to the mitotic spindle. In the presence of damage, or in the face of a reduced capacity to complete essential events, cells are capable of delaying the cell cycle so that damage can be repaired, or previous cell cycle phases can proceed to completion. Although such “checkpoints” have been extensively studied in many organisms – and much is understood with respect to the monitoring of DNA replication and DNA damage – little is known with regards to mechanisms that might monitor the completion of cytokinesis. In this review I summarize recent work from the fission yeast, Schizosaccharomyces pombe, describing the existence of regulatory modules that aid in ensuring the faithful and reliable execution of cytokinesis. Together, these modules promote the maintenance of a “cytokinesis- competent” state characterized by delayed progression into mitosis and the continuous repair and/or re-establishment of the acto-myosin ring. In this way, fission yeast cells are able to increase the likelihood of successful cell division prior to committing to a subsequent cell cycle. The recent demonstration of conservation between S. pombe components of these modules, and human proteins with defined roles in preventing cell division failure, suggest that the lessons learned in S. pombe may be applicable to other eukaryotes.




ARTICLE ADDENDA

Open Access Article

Evolutionary developmental biology in cycad phenology

Root Gorelick and Thomas E. Marler
Abstract | Full Text

We recently described lack of phenotypic plasticity in reproductive organ development and substantial plasticity in vegetative organ development for the cycad Cycas micronesica. Is there an evo-devo explanation for the disparity in phenotypic plasticity of vegetative vs. reproductive organs? Despite modularity, might evolution of cycad phenology be controlled more by drift than selection?

Open Access Article

Phenol-soluble modulins in staphylococci: what are they originally for?

Saravanan Periasamy, Som S. Chatterjee, Gordon Y. C. Cheung and Michael Otto
Abstract | Full Text

Phenol-soluble modulins (PSMs) are amphipathic peptides produced by staphylococci that have multiple functions in pathogenesis. For example, they may function as cytotoxins and pro-inflammatory agents. Additionally, in a recent study we demonstrated that Staphylococcus aureus PSMs structure biofilms and cause dissemination during biofilm infection. Based on those results suggesting a surfactant-like mechanism by which PSMs work, we here propose that all PSM functions in pathogenesis arose from an original role in non-pathogenic surface colonization. This original role may have included overcoming surface tension in environments of strongly varying hydrophobicity and emulsification of hydrophobic molecules for use as food sources.

Open Access Article

CK2 as anti-stress factor

Masahiko Watabe and Toshio Nakaki
Abstract | Full Text

Misfolded proteins are prone to form aggregates, which interfere with normal cellular functions. In general, the ubiquitin-proteasome system degrades such misfolded proteins to avoid aggregation. If this system becomes impaired or overloaded, an inclusion-body-like organelle, aggresome will operate. Misfolded protein aggregates are transported to aggresome with a deacetylase HDAC6 and dynein motors along the microtubule network, and are then removed by autophagic degradation. Although it is well known that the aggresome has evolved to cope with an excess of protein aggregates, the mechanisms underlying its formation remain unclear. It is now established that the protein kinase CK2 is a crucial factor in aggresome assembly and clearance. In particular, this kinase phosphorylates HDAC6 on serine 458 in response to cellular stress which is caused by misfolded proteins. The resultant increase in HDAC6 deacetylase activity is crucial for both the recruitment of misfolded proteins to the aggresome and its clearance. Interestingly, serine 458 is conserved only in higher primates such as the humans and chimpanzee, but not in the mouse, rat, dog, bovine or rhesus macaque. This regulatory mechanism by phosphorylation of the serine residue may have evolutional significance.

Open Access Article

Bowerbirds, art and aesthetics: Are bowerbirds artists and do they have an aesthetic sense?

John A. Endler
Abstract | Full Text

Male bowerbirds create and decorate a structure called a bower which serves only to attract females for mating, and females visit and choose one among many bower owners before deciding which male to mate with. Is what they do art, and do they have an aesthetic sense? I propose operational definitions of art, judgement, and an aesthetic sense which depend upon communication theory which allow one to get explicit answers to this question. By these definitions Great Bowerbirds are artists, judge art, and therefore have an aesthetic sense.

Open Access Article

Antennal carboxylesterases in a moth, structural and functional diversity

Nicolas Durand, Thomas Chertemps and Martine Maïbèche-Coisne
Abstract | Full Text

Pheromone-Degrading Enzymes (PDEs) are supposed to be involved in the signal inactivation step within the olfactory sensilla of insects by quickly degrading pheromone molecules. Because esters are widespread insect pheromone components, PDEs belonging to the carboxylesterase (CCE) family have been the most studied. However, only two CCEs were both identified at the molecular level and functionally characterized as PDEs until recently. In the pest moth Spodoptera littoralis, we have identified an unsuspected diversity of antennal CCEs, with a total number of 30 genes. Two CCEs, enriched in antennae and belonging to distinct clades, were shown to present different substrate specificities toward pheromone and plant compounds. A same CCE was also shown to efficiently degrade both pheromone and plant components. Our results suggest that the structural evolution of antennal CCEs reflects their functional diversity and that a complex set of CCE-mediated reactions take place is the olfactory organs of moths.

Open Access Article

Evolution of the Discs large gene family provides new insights into the establishment of apical epithelial polarity and the etiology of mental retardation

Heiko Lickert and Claude A. Van Campenhout
Abstract | Full Text

Cell polarity is essential to the function of many cell types, such as epithelial cells and neurons. The Discs large (Dlg) scaffolding protein was identified in Drosophila as a major regulator of basolateral epithelial identity. Four Dlg orthologs (Dlg1 through 4) are found in vertebrates, and mutations in the human Dlg3 gene are associated with X-linked mental retardation. We recently found that Dlg3 controls apical epithelial polarity and tight junction formation and contributes to neural induction in mouse development.¹ During evolution, Dlg3 acquired specific PPxY motifs, which bind to the WW domains of the E3 ubiquitin ligases, Nedd4 and Nedd4–2. This interaction results in monoubiquitination of Dlg3, leading to directed microtubule-dependent protein trafficking, via the exocyst complex, in different polarized cell types. Directed trafficking of Dlg3 plays an important role, during both mammalian development and in adulthood, in the establishment and maintenance of specialized apical cell junctions, such as tight junctions in epithelial cells and synapses in neurons.

Open Access Article

The unexpected role of Drosophila OCRL during cytokinesis

Khaled Ben El Kadhi, Grégory Emery and Sebastien Carreno
Abstract | Full Text

inositides are intrinsic components of cell membranes that regulate a wide variety of cellular functions. PtdIns(4,5)P_2, one of the most abundant phosphoinositides, is restricted at the plasma membrane where it regulates numerous functions including cell division. We have recently established that the Drosophila inositol 5-phosphatase, dOCRL, is essential for cytokinesis, the last step of cell division (Ben El Kadhi et al. 2011). We demonstrated that dOCRL is required for the dephosphorylation of PtdIns(4,5)P₂ at the surface of endosomes, resulting in the restriction of this phosphoinositide to the cell cortex during cytokinesis. dOCRL is the Drosophila ortholog of human OCRL1, a PtdIns(4,5)P₂ phosphatase mutated in the X-linked disorder oculocerebrorenal Lowe syndrome. Here, we discuss the relevance of our findings with reference to the role of human OCRL1 in non-pathological and pathological conditions.

Open Access Article

Myosin I: A new pip₃ effector in chemotaxis and phagocytosis

Chun-Lin Chen and Miho Iijima
Abstract | Full Text

Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P₃) is a key signaling molecule in chemotaxis, a directed cell migration toward chemoattractants. PtdIns(3,4,5)P₃ is transiently generated by chemotactic stimulation and activates reorganization of the actin cytoskeleton at the leading edge of migrating cells. In a recent study, we demonstrated that PtdIns(3,4,5)P₃ directly binds to three members of the actin-based motor protein myosin I (myosin ID, IE and IF) in Dictyostelium discoideum and recruits these proteins to the plasma membrane of the leading edge. The PtdIns(3,4,5)P₃-regulated membrane recruitment of myosin I induced chemoattractant-stimulated actin polymerization and was therefore required for chemotaxis. Similarly, human myosin IF was translocated to the plasma membrane through interactions with PtdIns(3,4,5)P₃ upon chemotactic stimulation in a neutrophil cell line. Interestingly, we also found that the three PtdIns(3,4,5)P₃-binding myosin I proteins function in phagocytosis, which involves both PtdIns(3,4,5)P₃ signaling and actin cytoskeleton remodeling. Our findings provide an evolutionarily conserved mechanism by which class I myosin transmits PtdIns(3,4,5)P₃ signals to the actin cytoskeleton.

Open Access Article

Physarum attraction: why slime mold behaves as cats do?

Andrew Adamatzky and Ben De Lacy Costello
Abstract | Full Text

We discuss potential chemical substances responsible for attracting acellular slime mold Physarun polycephalum to valerian root. The contributes toward fundamental research into pheromones and chemo-attracts of primitive organisms such as slime molds. The results show that significant information could be gained about the action of compounds on higher organisms.