The Origin of Patterning Systems in Bilateria——Insights from the Hox and ParaHox Genes in Acoelomorpha

Hox and ParaHox genes constitute two families of developmental regulators that pattern the Anterior-Posterior body axis in all bilaterians.The members of these two groups of genes are usually arranged in genomic clusters and work in a coordinated fashion,both in space and in time. While the mechanistic aspects of their action are relatively well known,it is still unclear how these systems evolved. For instance,we still need a proper model of how the Hox and ParaHox clusters were assembled over time.This problem is due to the shortage of information on gene complements for many taxa (mainly basal metazoans) and the lack of a consensus phylogenetic model of animal relationships to which we can relate our new findings.Recently, several studies have shown that the Acoelomorpha most probably represent the first offshoot of the Bilateria. This finding has prompted us,and others, to study the Hox and ParaHox complements in these animals,as well as their activity during development.In this review,we analyze how the current knowledge of Hox and ParaHox genes in the Acoelomorpha is shaping our view of bilaterian evolution.     

What Are Imprinted Genes Doing in the Brain?

As evidence for the existence of brain?expressed imprinted genes accumulates, we need to address exactly what they are doing in this tissue, especially in terms of organizational themes and the major challenges posed by reconciling imprinted gene action in brain with current evolutionary theories attempting to explain the origin and maintenance of genomic imprinting. We are at the beginning of this endeavor and much work remains to be done but already it is clear that imprinted genes have the potential to influence diverse behavioral processes via multiple brain mechanisms. There are also grounds to believe that imprinting may contribute to risk of mental and neurological disease. As well as being a source of basic information about imprinted genes in the brain (e.g., via the newly established website, www.bgg.cardiff.ac.uk/imprinted_tables/index.html), we have used this chapter to identify and focus on a number of key questions. How are brain?expressed imprinted genes organized at the molecular and cellular levels? To what extent does imprinted action depend on neurodevelopmental mechanisms? Do imprinted gene effects interact with other epigenetic influences, especially early on in life? Are imprinted effects on adult behaviors adaptive or just epiphenomena? If they are adaptive, what areas of brain function and behavior might be sensitive to imprinted effects? These are big questions and, as shall become apparent, we need much more data, arising from interactions between behavioral neuroscientists, molecular biologists and evolutionary theorists, if we are to begin to answer them.     

Are Podoplanin and Ezrin Involved in the Invasion Process of the Ameloblastomas?

The association between podoplanin and ezrin in the process of odontogenic tumors invasion has been suggested, but was not studied yet. Our purpose was to investigate the relationship between podoplanin and ezrin expressions in the odontogenic epithelium of ameloblastomas. Forty-seven ameloblastomas were analyzed by immunohistochemistry using anti-podoplanin and anti-ezrin antibodies. The expressions of both proteins were evaluated using a score method and the comparison and association between these proteins were verified, respectively, by Wilcoxon Signed-Rank test and by Spearman’s rank correlation coefficient, using a statistical significance level of 0.05. The majority of tumors (87.2%) exhibited strong membranous expression of podoplanin in the peripheral cells. Cytoplasmic expression of ezrin in the peripheral cells of ameloblastomas was stronger than its membranous expression. No statistically significant correlation was observed between podoplanin and ezrin. However, there was statistically significant difference between membranous podoplanin and membranous ezrin expressions, between cytoplasmic podoplanin and membranous ezrin expressions, and between cytoplasmic podoplanin and cytoplasmic ezrin expressions. There was no statistical difference between membranous podoplanin and cytoplasmic ezrin expressions. These results suggest a synergistic role of both proteins in the process of invasion of ameloblastomas.Key words: Odontogenic tumor, ameloblastoma, podoplanin, ezrin, adhesion molecule     

Are Free Radicals Involved in the Pathobiology of Human Essential Hypertension?

Possible involvement of reactive oxygen species and nitric oxide in the pathogenesis of human essential hypertension was investigated. It was observed that both superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes and the plasma levels of lipid peroxides are higher in uncontrolled essential hypertension compared with normal controls. Nitric oxide levels measured as its stable metabolite nitrite, as an index of nitric oxide synthesis, revealed its levels to be low in hypertensive patients. Superoxide anion, hydrogen peroxide, lipid peroxides and nitric oxide levels reverted to normal values after the control of hypertension by drugs. The concentrations of anti-oxidants such as vitamin E and superoxide dismutase were found to be decreased in patients with uncontrolled hypertension. Several anti-hypertensive drugs inhibited lipid peroxidation in vitro. Angiotensin-II, a potent vasoconstrictor, stimulated free radical generation in normal leukocytes which could be blocked by calmodulin antagonists. These results suggest that an increase in free radical generation and a simultaneous decrease in the production of nitric oxide and anti-oxidants such as SOD and vitamin E occurs in essential hypertension. This increase in free radical generation can inactivate prostacyclin and nitric oxide and decrease their half life which can lead to an increase in peripheral vascular resistance and hypertension.     

Who Are the True Fans? Evidence from an Event-Related Potential Study

Fans of celebrities commonly exist in modern society. Researchers from social science have been concerned with this problem for years. Furthermore, such researchers have attempted to measure people’s involvement with celebrities in various ways. However, no study measured the degree of addiction to a specific celebrity at the neurological level. Therefore, the current study employed visually evoked event related potentials (ERPs) to examine people’s attitude toward celebrities by comparing different brain activities of fans and non-fans when they were shown a set of photos. These photos include a specific celebrity, a familiar person, a stranger and a butterfly. Furthermore, to examine the validity of the detected neural index, we also investigated the correlation between brain activity and the score of the Celebrity Attitude Scale (CAS), which was a questionnaire used to explore people’s attitude toward celebrities at behavioral level. Two groups of subjects were asked to complete an implicit task, i.e., to press a button when a picture of a butterfly appeared. Results revealed that fans showed significant positive N2 and P300 deflection when viewing the photos of their favorite celebrity, whereas in the non-fan group, the subjects only showed larger P300 amplitude as a response to the celebrity’s photos. Furthermore, a positive correlation between P300 amplitude elicited by the stimuli of a celebrity face and CAS scores was also observed. These findings indicated fan attitude to a specific celebrity can also be observed at the neurological level and suggested the potential utility of using ERP component as an index of fandom involvement.     

Are Toxic Oxygen Radicals Involved in the Pathogenesis of Reflex Sympathetic Dystrophy?

A crossover study was performed for patients with RSD to evaluate the therapeutic efficacy of the hydroxyl radical scavenger DMSO. All patients were given DMSO locally 5 times a day during one week, and a placebo during one week. Before and after each treatment, subjective evaluation was performed by both the patient and the examinor as to clinical activity of RSD, and measurement was performed of the range of motion (ROM) of all joints in the affected extremity.

DMSO was the most effective treatment as to improvement of ROM (p = 0.035) and as to overall improvement (p = 0.001). The efficacy of the hydroxyl radical scavenger DMSO indicates that RSD primarily involves an inflammatory process rather than a sympathetic reflex. As during the last 20 years no single report was published studying RSD in terms of inflammation, it is suggested that such studies are urgently needed to elucidate the real nature of RSD.     

Are Toxic Oxygen Radicals Involved in the Pathogenesis of Reflex Sympathetic Dystrophy?

A crossover study was performed for patients with RSD to evaluate the therapeutic efficacy of the hydroxyl radical scavenger DMSO. All patients were given DMSO locally 5 times a day during one week, and a placebo during one week. Before and after each treatment, subjective evaluation was performed by both the patient and the examinor as to clinical activity of RSD, and measurement was performed of the range of motion (ROM) of all joints in the affected extremity.

DMSO was the most effective treatment as to improvement of ROM (p = 0.035) and as to overall improvement (p = 0.001). The efficacy of the hydroxyl radical scavenger DMSO indicates that RSD primarily involves an inflammatory process rather than a sympathetic reflex. As during the last 20 years no single report was published studying RSD in terms of inflammation, it is suggested that such studies are urgently needed to elucidate the real nature of RSD.     

What Are the Main Drivers of the Bitcoin Price? Evidence from Wavelet Coherence Analysis

The Bitcoin has emerged as a fascinating phenomenon in the Financial markets. Without any central authority issuing the currency, the Bitcoin has been associated with controversy ever since its popularity, accompanied by increased public interest, reached high levels. Here, we contribute to the discussion by examining the potential drivers of Bitcoin prices, ranging from fundamental sources to speculative and technical ones, and we further study the potential influence of the Chinese market. The evolution of relationships is examined in both time and frequency domains utilizing the continuous wavelets framework, so that we not only comment on the development of the interconnections in time but also distinguish between short-term and long-term connections. We find that the Bitcoin forms a unique asset possessing properties of both a standard financial asset and a speculative one.     

Life After Death: Are Autophagy Genes Involved in Cell Death and Survival During Plant Innate Immune Responses?

It has not escaped the attention of the plant disease resistance community that the vacuole is rapidly emerging as a central player in the execution of cell death. On the one hand the targeted destruction of the vacuole—from the inside out—by vacuolar processing enzymes (VPE) is required to induce PCD in pathogen-infected cells. On the other hand, an intact vacuole is vital for a functional autophagic response to ensure survival of uninfected cells. At face value, the two responses seem to represent distinct resistance mechanisms that operate at divergent branch points and their use of the vacuole merely coincidental. However, closer examination has led us to propose an interesting hypothesis that accounts for these two opposing roles of the vacuole in both VPE-mediated PCD and autophagy-dependent cell survival. During initial infection, we propose a mechanism similar to the CPY transport pathway in yeast wherein select ATG genes are needed for VPE transport, vacuolar processing and initiation of PCD. Later during infection, autophagy-specific genes are needed for autophagosome formation, sequestration of VPE preproteins and VPE degradation.     

Shrinking genomes? Evidence from genome size variation in Crepis (Compositae)

Large-scale surveys of genome size evolution in angiosperms show that the ancestral genome was most likely small, with a tendency towards an increase in DNA content during evolution. Due to polyploidisation and self-replicating DNA elements, angiosperm genomes were considered to have a 'one-way ticket to obesity' (Bennetzen & Kellogg 1997). New findings on how organisms can lose DNA challenged the hypotheses of unidirectional evolution of genome size. The present study is based on the classical work of Babcock (1947a) on karyotype evolution within Crepis and analyses karyotypic diversification within the genus in a phylogenetic context. Genome size of 21 Crepis species was estimated using flow cytometry. Additional data of 17 further species were taken from the literature. Within 30 diploid Crepis species there is a striking trend towards genome contraction. The direction of genome size evolution was analysed by reconstructing ancestral character states on a molecular phylogeny based on ITS sequence data. DNA content is correlated to distributional aspects as well as life form. Genome size is significantly higher in perennials than in annuals. Within sampled species, very small genomes are only present in Mediterranean or European species, whereas their Central and East Asian relatives have larger 1C values.     

Are Movements Necessary for the Sense of Body Ownership? Evidence from the Rubber Hand Illusion in Pure Hemiplegic Patients

A question still debated within cognitive neuroscience is whether signals present during actions significantly contribute to the emergence of human’s body ownership. In the present study, we aimed at answer this question by means of a neuropsychological approach. We administered the classical rubber hand illusion paradigm to a group of healthy participants and to a group of neurological patients affected by a complete left upper limb hemiplegia, but without any propriceptive/tactile deficits. The illusion strength was measured both subjectively (i.e., by a self-report questionnaire) and behaviorally (i.e., the location of one’s own hand is shifted towards the rubber hand). We aimed at examining whether, and to which extent, an enduring absence of movements related signals affects body ownership. Our results showed that patients displayed, respect to healthy participants, stronger illusory effects when the left (affected) hand was stimulated and no effects when the right (unaffected) hand was stimulated. In other words, hemiplegics had a weaker/more flexible sense of body ownership for the affected hand, but an enhanced/more rigid one for the healthy hand. Possible interpretations of such asymmetrical distribution of body ownership, as well as limits of our results, are discussed. Broadly speaking, our findings suggest that the alteration of the normal flow of signals present during movements impacts on human’s body ownership. This in turn, means that movements have a role per se in developing and maintaining a coherent body ownership.     

Are Normal Decision-Makers Sensitive to Changes in Value Contrast under Uncertainty? Evidence from the Iowa Gambling Task

The Iowa Gambling Task (IGT) developed by Bechara et al. in 1994 is used to diagnose patients with Ventromedial Medial Prefrontal Cortex (VMPFC) lesions, and it has become a landmark in research on decision making. According to Bechara et al., the manipulation of progressive increments of monetary value can normalize the performance of patients with VMPFC lesions; thus, they developed a computerized version of the IGT. However, the empirical results showed that patients'' performances did not improve as a result of this manipulation, which suggested that patients with VMPFC lesions performed myopically for future consequences. Using the original version of the IGT, some IGT studies have demonstrated that increments of monetary value significantly influence the performance of normal subjects in the IGT. However, other research has resulted in inconsistent findings. In this study, we used the computerized IGT (1X-IGT) and manipulated the value contrast of progressive increments (i.e., by designing the 10X-IGT, which contained 10 times of progressive increment) to investigate the influence of value contrast on the performance of normal subjects. The resulting empirical observations indicated that the value contrast (1X- vs. 10X-IGT) of the progressive increment had no effect on the performance of normal subjects. This study also provides a discussion of the issue of value in IGT-related studies. Moreover, we found the “prominent deck B phenomenon” in both versions of the IGT, which indicated that the normal subjects were guided mostly by the gain-loss frequency, rather than by the monetary value contrast. In sum, the behavioral performance of normal subjects demonstrated a low correlation with changes in monetary value, even in the 10X-IGT.     

Diurnal Changes in the Regulatory Properties of Phosphoenolpyruvate Carboxylase in CAM Plants: Are Alterations in the Quaternary Structure Involved?

Day — and night-forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) (PEP-C) were extracted from leaves of the CAM plant Kalanchoë daigremontiana. During storage after extraction, the day-form spontaneously lost its sensitivity towards the allosteric inhibitor l -malate. This effect was accelerated by inorganic phosphate, PEP, 3-PGA and G-6-P. l -Malate however stabilized the malate sensitivity of the day-form of PEP-C. Crude desalted extracts of the day-form and of the night-form of PEP-C were subjected to ultracentrifugation on a continuous sucrose gradient in the presence of malate and of marker enzymes. Both forms of PEP-C were found to have relative molecular masses of about 200,000. This suggests that both forms represent the dimers of the enzyme protein. The result also suggests that reversible dissociation and association of enzyme subunits is not the mechanism which brings about the interconversion of the two PEP-C forms during the diurnal CAM cycle in vivo.     

How Universal Are Preferences for Female Waist-to-Hip Ratios? Evidence from the Hadza of Tanzania

Female waist-to-hip ratio (WHR) has been proposed by evolutionary psychologists to be an important component of human male mate choice, because this trait is thought to provide a reliable cue to a woman's reproductive value. Based largely on work conducted in industrialized societies, the claim has been made that preferences for low WHR are culturally invariant. Presumably, the preferences evolved before the advent of agriculture, making foraging populations the best place to test the hypothesis. This was done with the Hadza of Tanzania, who were shown figures of females that varied by weight and waist-to-hip ratio. Low WHR was not preferred. Hadza men did not consider waist-to-hip ratio when expressing preferences for mates. Instead, they were most interested in the weight of potential partners. Research by others with subjects who practice swidden agriculture also revealed that low WHR was not preferred. The data from the Hadza coupled with the information derived from this horticultural group bring into question whether preferences for low WHR are culturally invariant.     

Playing Charades in the fMRI: Are Mirror and/or Mentalizing Areas Involved in Gestural Communication?

Communication is an important aspect of human life, allowing us to powerfully coordinate our behaviour with that of others. Boiled down to its mere essentials, communication entails transferring a mental content from one brain to another. Spoken language obviously plays an important role in communication between human individuals. Manual gestures however often aid the semantic interpretation of the spoken message, and gestures may have played a central role in the earlier evolution of communication. Here we used the social game of charades to investigate the neural basis of gestural communication by having participants produce and interpret meaningful gestures while their brain activity was measured using functional magnetic resonance imaging. While participants decoded observed gestures, the putative mirror neuron system (pMNS: premotor, parietal and posterior mid-temporal cortex), associated with motor simulation, and the temporo-parietal junction (TPJ), associated with mentalizing and agency attribution, were significantly recruited. Of these areas only the pMNS was recruited during the production of gestures. This suggests that gestural communication relies on a combination of simulation and, during decoding, mentalizing/agency attribution brain areas. Comparing the decoding of gestures with a condition in which participants viewed the same gestures with an instruction not to interpret the gestures showed that although parts of the pMNS responded more strongly during active decoding, most of the pMNS and the TPJ did not show such significant task effects. This suggests that the mere observation of gestures recruits most of the system involved in voluntary interpretation.     

Mechanotransduction from the ECM to the genome: Are the pieces now in place?

A multitude of biochemical signaling processes have been characterized that affect gene expression and cellular activity. However, living cells often need to integrate biochemical signals with mechanical information from their microenvironment as they respond. In fact, the signals received by shape alone can dictate cell fate. This mechanotrasduction of information is powerful, eliciting proliferation, differentiation, or apoptosis in a manner dependent upon the extent of physical deformation. The cells internal "prestressed" structure and its "hardwired" interaction with the extra-cellular matrix (ECM) appear to confer this ability to filter biochemical signals and decide between divergent cell functions influenced by the nature of signals from the mechanical environment. In some instances mechanical signaling through the tissue microenvironment has been shown to be dominant over genomic defects, imparting a normal phenotype on cells that otherwise have transforming genetic lesions. This mechanical control of phenotype is postulated to have a central role in embryogenesis, tissue physiology as well as the pathology of a wide variety of diseases, including cancer. We will briefly review studies showing physical continuity between the external cellular microenvironment and the interior of the cell nucleus. Newly characterized structures, termed nuclear envelope lamina spanning complexes (NELSC), and their interactions will be described as part of a model for mechanical transduction of extracellular cues from the ECM to the genome.