Thalidomide-induced Teratogenesis : History and Mechanisms

Peer reviewedPublisher PD

Climate Driven Egg and Hatchling Mortality Threatens Survival of Eastern Pacific Leatherback Turtles

Egg-burying reptiles need relatively stable temperature and humidity in the substrate surrounding their eggs for successful development and hatchling emergence. Here we show that egg and hatchling mortality of leatherback turtles (Dermochelys coriacea) in northwest Costa Rica were affected by climatic variability (precipitation and air temperature) driven by the El Niño Southern Oscillation (ENSO). Drier and warmer conditions associated with El Niño increased egg and hatchling mortality. The fourth assessment report of the Intergovernmental Panel on Climate Change (IPCC) projects a warming and drying in Central America and other regions of the World, under the SRES A2 development scenario. Using projections from an ensemble of global climate models contributed to the IPCC report, we project that egg and hatchling survival will rapidly decline in the region over the next 100 years by ∼50–60%, due to warming and drying in northwestern Costa Rica, threatening the survival of leatherback turtles. Warming and drying trends may also threaten the survival of sea turtles in other areas affected by similar climate changes

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Dynamic 3D Cell Rearrangements Guided by a Fibronectin Matrix Underlie Somitogenesis

Somites are transient segments formed in a rostro-caudal progression during vertebrate development. In chick embryos, segmentation of a new pair of somites occurs every 90 minutes and involves a mesenchyme-to-epithelium transition of cells from the presomitic mesoderm. Little is known about the cellular rearrangements involved, and, although it is known that the fibronectin extracellular matrix is required, its actual role remains elusive. Using 3D and 4D imaging of somite formation we discovered that somitogenesis consists of a complex choreography of individual cell movements. Epithelialization starts medially with the formation of a transient epithelium of cuboidal cells, followed by cell elongation and reorganization into a pseudostratified epithelium of spindle-shaped epitheloid cells. Mesenchymal cells are then recruited to this medial epithelium through accretion, a phenomenon that spreads to all sides, except the lateral side of the forming somite, which epithelializes by cell elongation and intercalation. Surprisingly, an important contribution to the somite epithelium also comes from the continuous egression of mesenchymal cells from the core into the epithelium via its apical side. Inhibition of fibronectin matrix assembly first slows down the rate, and then halts somite formation, without affecting pseudopodial activity or cell body movements. Rather, cell elongation, centripetal alignment, N-cadherin polarization and egression are impaired, showing that the fibronectin matrix plays a role in polarizing and guiding the exploratory behavior of somitic cells. To our knowledge, this is the first 4D in vivo recording of a full mesenchyme-to-epithelium transition. This approach brought new insights into this event and highlighted the importance of the extracellular matrix as a guiding cue during morphogenesis

Ontogenetic phase shifts in metabolism in a flounder Paralichthys olivaceus

Size-scaling metabolism is widely considered to be of significant importance in biology and ecology. Thus, allometric relationships between metabolic rate (VO2) and body mass (M), V O25aiMb, have long been a topic of interest and speculation. It has been proposed that intraspecifically metabolic rate scales isometrically or near isometrically with body mass during the early life history in fishes, invertebrates, birds and mammals. We developed a new perspective on intraspecific size-scaling metabolism through determination of metabolic rate in the Japanese flounder, Paralichthys olivaceus, during their early life stages spanning approximately four orders of magnitude in body mass. With the increase of body mass, the Japanese flounder had four distinct negative allometric phases in which three stepwise increases in scaling constants (ai, i51?4), i.e. ontogenetic phase shifts in metabolism, occurred with growth during its early life stages at around 0.002, 0.01 and 0.2 g, maintaining each scaling exponent constant in each phase (b50.831).These shifts in metabolism during the early life stages are similar to the tiger puffer, Takifugu rubripes. Our results indicate that ontogenetic phase shifts in metabolism are key to understanding intraspecific size-scaling metabolism in fishes

The Overlapping Community Structure of Structural Brain Network in Young Healthy Individuals

Community structure is a universal and significant feature of many complex networks in biology, society, and economics. Community structure has also been revealed in human brain structural and functional networks in previous studies. However, communities overlap and share many edges and nodes. Uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks. Here, using regional gray matter volume, we investigated the structural brain network among 90 brain regions (according to a predefined anatomical atlas) in 462 young, healthy individuals. Overlapped nodes between communities were defined by assuming that nodes (brain regions) can belong to more than one community. We demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well-known brain systems, such as the auditory/language, visuospatial, emotion, decision-making, social, control of action, memory/learning, and visual systems. The overlapped nodes were mostly involved in an inferior-posterior pattern and were primarily related to auditory and visual perception. The overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of informa- tion through the structural brain network. Our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain. This study provides the first report of the overlapping community structure of the structural network of the human brain

A gene expression fingerprint of C. elegans embryonic motor neurons

BACKGROUND: Differential gene expression specifies the highly diverse cell types that constitute the nervous system. With its sequenced genome and simple, well-defined neuroanatomy, the nematode C. elegans is a useful model system in which to correlate gene expression with neuron identity. The UNC-4 transcription factor is expressed in thirteen embryonic motor neurons where it specifies axonal morphology and synaptic function. These cells can be marked with an unc-4::GFP reporter transgene. Here we describe a powerful strategy, Micro-Array Profiling of C. elegans cells (MAPCeL), and confirm that this approach provides a comprehensive gene expression profile of unc-4::GFP motor neurons in vivo. RESULTS: Fluorescence Activated Cell Sorting (FACS) was used to isolate unc-4::GFP neurons from primary cultures of C. elegans embryonic cells. Microarray experiments detected 6,217 unique transcripts of which ~1,000 are enriched in unc-4::GFP neurons relative to the average nematode embryonic cell. The reliability of these data was validated by the detection of known cell-specific transcripts and by expression in UNC-4 motor neurons of GFP reporters derived from the enriched data set. In addition to genes involved in neurotransmitter packaging and release, the microarray data include transcripts for receptors to a remarkably wide variety of signaling molecules. The added presence of a robust array of G-protein pathway components is indicative of complex and highly integrated mechanisms for modulating motor neuron activity. Over half of the enriched genes (537) have human homologs, a finding that could reflect substantial overlap with the gene expression repertoire of mammalian motor neurons. CONCLUSION: We have described a microarray-based method, MAPCeL, for profiling gene expression in specific C. elegans motor neurons and provide evidence that this approach can reveal candidate genes for key roles in the differentiation and function of these cells. These methods can now be applied to generate a gene expression map of the C. elegans nervous system

Bipolar disorders

Bipolar disorder is characterized by (hypo)manic episodes and depressive episodes which alternate with euthymic periods. It causes serious disability with poor outcome, increased suicidality risk, and significant societal costs. This chapter describes the findings of the PET/SPECT research efforts and the current ideas on the pathophysiology of bipolar disorder. First, the cerebral blood flow and cerebral metabolism findings in the prefrontal cortex, limbic system, subcortical structures, and other brain regions are discussed, followed by an overview of the corticolimbic theory of mood disorders that explains these observations. Second, the neurotransmitter studies are discussed. The serotonin transporter alterations are described, and the variation in study results is explained, followed by an overview of the results of the various dopamine receptor and transporter molecules studies, taking into account also the relation to psychosis. Third, a concise overview is given of dominant bipolar disorder pathophysiological models, proposing starting points for future molecular imaging studies. Finally, the most important conclusions are summarized, followed by remarks about the observed molecular imaging study designs specific for bipolar disorder.</p