Apoptosis and proliferation in the trigeminal placode

The neurogenic trigeminal placode develops from the crescent-shaped panplacodal primordium which delineates the neural plate anteriorly. We show that, in Tupaia belangeri, the trigeminal placode is represented by a field of focal ectodermal thickenings which over time changes positions from as far rostral as the level of the forebrain to as far caudal as opposite rhombomere 3. Delamination proceeds rostrocaudally from the ectoderm adjacent to the rostral midbrain, and contributes neurons to the trigeminal ganglion as well as to the ciliary ganglion/oculomotor complex. Proliferative events are centered on the field prior to the peak of delamination. They are preceded, paralleled and, finally, outnumbered by apoptotic events which proceed rostrocaudally from non-delaminating to delaminating parts of the field. Apoptosis persists upon regression of the placode, thereby exhibiting a massive “wedge” of apoptotic cells which includes the postulated position of the “ventrolateral postoptic placode” (Lee et al. in Dev Biol 263:176–190, 2003), merges with groups of lens-associated apoptotic cells, and disappears upon lens detachment. In conjunction with earlier work (Washausen et al. in Dev Biol 278:86–102, 2005) our findings suggest that apoptosis contributes repeatedly to the disintegration of the panplacodal primordium, to the elimination of subsets of premigratory placodal neuroblasts, and to the regression of placodes

From uncertainty to reward: BOLD characteristics differentiate signaling pathways

<p>Abstract</p> <p>Background</p> <p>Reward value and uncertainty are represented by dopamine neurons in monkeys by distinct phasic and tonic firing rates. Knowledge about the underlying differential dopaminergic pathways is crucial for a better understanding of dopamine-related processes. Using functional magnetic resonance blood-oxygen level dependent (BOLD) imaging we analyzed brain activation in 15 healthy, male subjects performing a gambling task, upon expectation of potential monetary rewards at different reward values and levels of uncertainty.</p> <p>Results</p> <p>Consistent with previous studies, ventral striatal activation was related to both reward magnitudes and values. Activation in medial and lateral orbitofrontal brain areas was best predicted by reward uncertainty. Moreover, late BOLD responses relative to trial onset were due to expectation of different reward values and likely to represent phasic dopaminergic signaling. Early BOLD responses were due to different levels of reward uncertainty and likely to represent tonic dopaminergic signals.</p> <p>Conclusions</p> <p>We conclude that differential dopaminergic signaling as revealed in animal studies is not only represented locally by involvement of distinct brain regions but also by distinct BOLD signal characteristics.</p

Facilitated Variation: How Evolution Learns from Past Environments To Generalize to New Environments

One of the striking features of evolution is the appearance of novel structures in organisms. Recently, Kirschner and Gerhart have integrated discoveries in evolution, genetics, and developmental biology to form a theory of facilitated variation (FV). The key observation is that organisms are designed such that random genetic changes are channeled in phenotypic directions that are potentially useful. An open question is how FV spontaneously emerges during evolution. Here, we address this by means of computer simulations of two well-studied model systems, logic circuits and RNA secondary structure. We find that evolution of FV is enhanced in environments that change from time to time in a systematic way: the varying environments are made of the same set of subgoals but in different combinations. We find that organisms that evolve under such varying goals not only remember their history but also generalize to future environments, exhibiting high adaptability to novel goals. Rapid adaptation is seen to goals composed of the same subgoals in novel combinations, and to goals where one of the subgoals was never seen in the history of the organism. The mechanisms for such enhanced generation of novelty (generalization) are analyzed, as is the way that organisms store information in their genomes about their past environments. Elements of facilitated variation theory, such as weak regulatory linkage, modularity, and reduced pleiotropy of mutations, evolve spontaneously under these conditions. Thus, environments that change in a systematic, modular fashion seem to promote facilitated variation and allow evolution to generalize to novel conditions

The combined effect of two mutations that alter serially homologous color pattern elements on the fore and hindwings of a butterfly

<p>Abstract</p> <p>Background</p> <p>The ability for serially homologous structures to acquire a separate identity has been primarily investigated for structures dependent on Hox gene input but is still incompletely understood in other systems. The fore and hindwings of butterflies are serially homologous structures as are the serially homologous eyespots that can decorate each of these wings. Eyespots can vary in number between fore and hindwings of the same individual and mutations of large effect can control the total number of eyespots that each of the wings displays. Here we investigate the genetics of a new spontaneous color pattern mutation, <it>Missing</it>, that alters eyespot number in the nymphalid butterfly, <it>Bicyclus anynana</it>. We further test the interaction of <it>Missing </it>with a previously described mutation, <it>Spotty</it>, describe the developmental stage affected by <it>Missing</it>, and test whether <it>Missing </it>is a mutant variant of the gene <it>Distal-less </it>via a linkage association study.</p> <p>Results</p> <p><it>Missing </it>removes or greatly reduces the size of two of the hindwing eyespots from the row of seven eyespots, with no detectable effect on the rest of the wing pattern. Offspring carrying a single <it>Missing </it>allele display intermediate sized eyespots at these positions. <it>Spotty </it>has the opposite effect of <it>Missing</it>, i.e., it introduces two extra eyespots in homologous wing positions to those affected by <it>Missing</it>, but on the forewing. When <it>Missing </it>is combined with <it>Spotty </it>the size of the two forewing eyespots decreases but the size of the hindwing spots stays the same, suggesting that these two mutations have a combined effect on the forewing such that <it>Missing </it>reduces eyespot size when in the presence of a <it>Spotty </it>mutant allele, but that <it>Spotty </it>has no effect on the hindwing. <it>Missing </it>prevents the complete differentiation of two of the eyespot foci on the hindwing. We found no evidence for any linkage between the <it>Distal-less </it>and <it>Missing </it>genes.</p> <p>Conclusion</p> <p>The spontaneous mutation <it>Missing </it>controls the differentiation of the signaling centers of a subset of the serial homologous eyespots present on both the fore and the hindwing in a dose-dependent fashion. The effect of <it>Missing </it>on the forewing, however, is only observed when the mutation <it>Spotty </it>introduces additional eyespots on this wing. <it>Spotty</it>, on the other hand, controls the differentiation of eyespot centers only on the forewing. <it>Spotty</it>, unlike <it>Missing</it>, may be under Ubx gene regulation, since it affects a subset of eyespots on only one of the serially homologous wings.</p

Persistent export of 231Pa from the deep central Arctic Ocean over the past 35,000 years

The Arctic Ocean has an important role in Earth’s climate, both through surface processes such as sea-ice formation and transport, and through the production and export of waters at depth that contribute to the global thermohaline circulation. Deciphering the deep Arctic Ocean’s palaeo-oceanographic history is a crucial part of understanding its role in climatic change. Here we show that sedimentary ratios of the radionuclides thorium-230 (230Th) and protactinium-231 (231Pa), which are produced in sea water and removed by particle scavenging on timescales of decades to centuries, respectively, record consistent evidence for the export of 231Pa from the deep Arctic and may indicate continuous deep-water exchange between the Arctic and Atlantic oceans throughout the past 35,000 years. Seven well-dated box-core records provide a comprehensive overview of 231Pa and 230Th burial in Arctic sediments during glacial, deglacial and interglacial conditions. Sedimentary 231Pa/230Th ratios decrease nearly linearly with increasing water depth above the core sites, indicating efficient particle scavenging in the upper water column and greater influence of removal by lateral transport at depth. Although the measured 230Th burial is in balance with its production in Arctic sea water, integrated depth profiles for all time intervals reveal a deficit in 231Pa burial that can be balanced only by lateral export in the water column. Because no enhanced sink for 231Pa has yet been found in the Arctic, our records suggest that deep-water exchange through the Fram strait may export 231Pa. Such export may have continued for the past 35,000 years, suggesting a century-scale replacement time for deep waters in the Arctic Ocean since the most recent glaciation and a persistent contribution of Arctic waters to the global ocean circulation

Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion

Vertebrate cranial sensory ganglia, responsible for sensation of touch, taste and pain in the face and viscera, are composed of both ectodermal placode and neural crest cells. The cellular and molecular interactions allowing generation of complex ganglia remain unknown. Here, we show that proper formation of the trigeminal ganglion, the largest of the cranial ganglia, relies on reciprocal interactions between placode and neural crest cells in chick, as removal of either population resulted in severe defects. We demonstrate that ingressing placode cells express the Robo2 receptor and early migrating cranial neural crest cells express its cognate ligand Slit1. Perturbation of this receptor-ligand interaction by blocking Robo2 function or depleting either Robo2 or Slit1 using RNA interference disrupted proper ganglion formation. The resultant disorganization mimics the effects of neural crest ablation. Thus, our data reveal a novel and essential role for Robo2-Slit1 signaling in mediating neural crest–placode interactions during trigeminal gangliogenesis

Fourier descriptors and handwritten digit recognition

This paper presents the results of a comparative study of various Fourier descriptor representations and their use in recognition of unconstrained handwritten digits. Certain characteristics of five distinct Fourier descriptor representations of handwritten digits are discussed, and illustrations of ambiguous digit classes introduced by use of these Fourier descriptor representations are presented. It is concluded that Fourier descriptors are practically effective only within the framework of an intelligent system, capable of reasoning about digit hypotheses. We describe a hypothesisgenerating algorithm based on Fourier descriptors which allows a classifier to associate more than one digit class with each input. Such hypothesis-generating schemes can be very effective in systems employing multiple classifiers. We compare the performance of the five Fourier descriptor representations based on experiment results produced by a particular hypothesis-generating classifier for a test set of 14000 handwritten digits. It is found that some Fourier descriptor formulations are more successful than others for handwritten digit recognition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46057/1/138_2005_Article_BF01212429.pd

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding

Fluctuations in active membranes

Active contributions to fluctuations are a direct consequence of metabolic energy consumption in living cells. Such metabolic processes continuously create active forces, which deform the membrane to control motility, proliferation as well as homeostasis. Membrane fluctuations contain therefore valuable information on the nature of active forces, but classical analysis of membrane fluctuations has been primarily centered on purely thermal driving. This chapter provides an overview of relevant experimental and theoretical approaches to measure, analyze and model active membrane fluctuations. In the focus of the discussion remains the intrinsic problem that the sole fluctuation analysis may not be sufficient to separate active from thermal contributions, since the presence of activity may modify membrane mechanical properties themselves. By combining independent measurements of spontaneous fluctuations and mechanical response, it is possible to directly quantify time and energy-scales of the active contributions, allowing for a refinement of current theoretical descriptions of active membranes.Comment: 38 pages, 9 figures, book chapte

Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics

BACKGROUND: Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. METHODOLOGY/PRINCIPAL FINDINGS: Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. CONCLUSIONS/SIGNIFICANCE: These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses