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Chemerin, which is encoded by retinoic acid receptor responder 2 (RARRES2), has been found to be related to malignant tumours, but its role in the development of oral squamous cell carcinoma (OSCC) is largely unexplored. In the present study, a higher serum level of chemerin was evident in patients with OSCC than in healthy individuals, and this high level of chemerin significantly decreased after tumour resection. In addition, high chemerin levels were positively associated with advanced tumour stage and lymph node metastasis. The expression levels of chemerin and Chemerin Receptor 23 (ChemR23) were positively correlated with the migration and invasion of OSCC cell lines. Recombinant chemerin (R-chemerin) enhanced the in vitro migration, invasion and proliferation of OSCC cells in a concentration-dependent manner, and short hairpin RNAs (shRNAs) targeting RARRES2 decreased chemerin expression and inhibited OSCC cell metastasis and proliferation both in vitro and in vivo. Additionally, R-chemerin activated manganese superoxide dismutase (SOD2) and increased the amount of intracellular hydrogen peroxide (H2O2), leading to a significant decrease in E-cadherin expression and dramatic increase in the expression of phosphorylated ERK1/2 (p-ERK1/2), Slug, Vimentin and N-cadherin, but shRNAs targeting RARRES2 reversed these effects. Moreover, knockdown of ChemR23 with small interfering RNAs (siRNA) significantly inhibited chemerin-induced OSCC cell migration/invasion and SOD2 activity. Our results revealed that chemerin is a novel biomarker for OSCC. Chemerin/ChemR23 promotes tumorigenesis and metastasis in OSCC and may be a new therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

A 51-year-old man with an incomplete C6 spinal cord injury sustained 26 yrs ago attended twenty 2-hr visits over 10 wks for robot-assisted hand training driven by myoelectric pattern recognition. In each visit, his right hand was assisted to perform motions by an exoskeleton robot, while the robot was triggered by his own motion intentions. The hand robot was designed for this study, which can perform six kinds of motions, including hand closing/opening; thumb, index finger, and middle finger closing/opening; and middle, ring, and little fingers closing/opening. After the training, his grip force increased from 13.5 to 19.6 kg, his pinch force remained the same (5.0 kg), his score of Box and Block test increased from 32 to 39, and his score from the Graded Redefined Assessment of Strength, Sensibility, and Prehension test Part 4.B increased from 22 to 24. He accomplished the tasks in the Graded Redefined Assessment of Strength, Sensibility, and Prehension test Part 4.B 28.8% faster on average. The results demonstrate the feasibility and effectiveness of robot-assisted training driven by myoelectric pattern recognition after spinal cord injury. [ABSTRACT FROM AUTHOR]

Left-right asymmetries in brains are usually minor or cryptic. We report brain asymmetries in the tiny, dorsal tubular nervous system of the ascidian tadpole larva, Ciona intestinalis. Chordate in body plan and development, the larva provides an outstanding example of brain asymmetry. Although early neural development is well studied, detailed cellular organization of the swimming larva's CNS remains unreported. Using serial-section EM we document the synaptic connectome of the larva's 177 CNS neurons. These formed 6618 synapses including 1772 neuromuscular junctions, augmented by 1206 gap junctions. Neurons are unipolar with at most a single dendrite, and few synapses. Some synapses are unpolarised, others form reciprocal or serial motifs; 922 were polyadic. Axo-axonal synapses predominate. Most neurons have ciliary organelles, and many features lack structural specialization. Despite equal cell numbers on both sides, neuron identities and pathways differ left/right. Brain vesicle asymmetries include a right ocellus and left coronet cells. [ABSTRACT FROM AUTHOR]

Ectopic expression of the retinal determination gene eyeless (ey) induces the formation of supernumerary eyes on antennae, legs, wings, and halteres. These ectopic eyes form ommatidia that contain photoreceptors and accessory cells and respond to light. Here, we demonstrate that ectopic eyes on antennae and legs extend axonal projections to the central nervous system. Furthermore, electroretinograms and morphological evidence indicate that the photoreceptor axons of at least the antennal ectopic eyes can form completely constituted ectopic synapses with foreign postsynaptic elements and suggest that transmission at these sites may be functional. However, the ectopic axons do not connect to their correct optic lobe targets and do not project deeply into the neuropile, but rather form synapses at superficial positions in the neuropils. By means of confocal and electron microscopy we show that these ectopic synapses resemble normal synapses, albeit with some distinct morphological differences. Our data strongly suggest that the developmental programs controlling photoreceptor synaptogenesis and visual map formation depend to a considerable extent on presynaptic and thus photoreceptor-autonomous steps. Our data also suggest that photoreceptor axon projections and the establishment of the highly stereotypical neural circuitry in the optic lobe, the normal target neuropil, may depend on target-specific cues that appear to be absent from the antennal lobe and thoracic ganglion. [ABSTRACT FROM AUTHOR]

Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically generate 3D images with superior z-axis resolution, yielding data that needs minimal image registration and related post-processing. Obstacles blocking wider adoption of FIB-SEM include slow imaging speed and lack of long-term system stability, which caps the maximum possible acquisition volume. Here we present techniques that accelerate image acquisition while greatly improving FIB-SEM reliability, allowing the system to operate for months and generating continuously imaged volumes > 106 μm³. These volumes are large enough for connectomics, where the excellent z resolution can help in tracing of small neuronal processes and accelerate the tedious and time-consuming human proofreading effort. Even higher resolution can be achieved on smaller volumes. We present example data sets from mammalian neural tissue, Drosophila brain, and Chlamydomonas reinhardtii to illustrate the power of this novel high-resolution technique to address questions in both connectomics and cell biology. [ABSTRACT FROM AUTHOR]

We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly's compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla's neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E-). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics. [ABSTRACT FROM AUTHOR]

Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of their bioenergetic machinery to ensure these power demands are met, but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified. Here, we estimated the power demands of six motor nerve terminals in female Drosophila larvae through direct measurements of neurotransmitter release and Ca21 entry, and via theoretical estimates of Na1 entry and power demands at rest. Electron microscopy revealed that terminals with the highest power demands contained the greatest volume of mitochondria, indicating that mitochondria are allocated according to presynaptic power demands. In addition, terminals with the greatest power demand-to-volume ratio (;66 nmol·min21·ml21) harbor the largest mitochondria packed at the greatest density. If we assume sequential and complete oxidation of glucose by glycolysis and oxidative phosphorylation, then these mitochondria are required to produce ATP at a rate of 52 nmol·min21·ml21 at rest, rising to 963 during activity. Glycolysis would contribute ATP at 0.24 nmol·min21·ml21 of cytosol at rest, rising to 4.36 during activity. These data provide a quantitative framework for presynaptic bioenergetics in situ, and reveal that, beyond an immediate capacity to accelerate ATP output from glycolysis and oxidative phosphorylation, over longer time periods presynaptic terminals optimize mitochondrial volume and density to meet power demand. [ABSTRACT FROM AUTHOR]

Ningqiao 1 was selected as the material to study the effects of planting density on physiological indices, agronomic traits and yield of buckwheat. The results showed that high density resulted in decreases of chlorophyll content, soluble protein content and activity of SOD, POD and CAT, and acceleration of MDA accumulation under drought conditions. Low density could effectively improve the grain number per plant, grain weight per plant, 1 000-grain weight and yield in drought conditions. [ABSTRACT FROM AUTHOR]

Ningqiao 1 was selected as the material to study the effects of planting density on physiological indices, agronomic traits and yield of buckwheat. The results showed that high density resulted in decreases of chlorophyll content, soluble protein content and activity of SOD, POD and CAT, and acceleration of MDA accumulation under drought conditions. Low density could effectively improve the grain number per plant, grain weight per plant, 1 000-grain weight and yield in drought conditions. [ABSTRACT FROM AUTHOR]

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed Animal brains of all sizes, from the smallest to the largest, work in broadly similar ways. Studying the brain of any one animal in depth can thus reveal the general principles behind the workings of all brains. The fruit fly Drosophila is a popular choice for such research. With about 100,000 neurons - compared to some 86 billion in humans - the fly brain is small enough to study at the level of individual cells. But it nevertheless supports a range of complex behaviors, including navigation, courtship and learning. Thanks to decades of research, scientists now have a good understanding of which parts of the fruit fly brain support particular behaviors. But exactly how they do this is often unclear. This is because previous studies showing the connections between cells only covered small areas of the brain. This is like trying to understand a novel when all you can see is a few isolated paragraphs. To solve this problem, Scheffer, Xu, Januszewski, Lu, Takemura, Hayworth, Huang, Shinomiya et al. prepared the first complete map of the entire central region of the fruit fly brain. The central brain consists of approximately 25,000 neurons and around 20 million connections. To prepare the map - or connectome - the brain was cut into very thin 8nm slices and photographed with an electron microscope. A three-dimensional map of the neurons and connections in the brain was then reconstructed from these images using machine learning algorithms. Finally, Scheffer et al. used the new connectome to obtain further insights into the circuits that support specific fruit fly behaviors. The central brain connectome is freely available online for anyone to access. When used in combination with existing methods, the map will make it easier to understand how the fly brain works, and how and why it can fail to work correctly. Many of these findings will likely apply to larger brains, including our own. In the long run, studying the fly connectome may therefore lead to a better understanding of the human brain and its disorders. Performing a similar analysis on the brain of a small mammal, by scaling up the methods here, will be a likely next step along this path. [ABSTRACT FROM AUTHOR]

The dogma that the synaptic cleft acidifies during neurotransmission is based on the corelease of neurotransmitters and protons from synaptic vesicles, and is supported by direct data from sensory ribbon-type synapses. However, it is unclear whether acidification occurs at non-ribbon-type synapses. Here we used genetically encoded fluorescent pH indicators to examine cleft pH at conventional neuronal synapses. At the neuromuscular junction of female Drosophila larvae, we observed alkaline spikes of over 1 log unit during fictive locomotion in vivo. Ex vivo, single action potentials evoked alkalinizing pH transients of only ~--0.01 log unit, but these transients summated rapidly during burst firing. A chemical pH indicator targeted to the cleft corroborated these findings. Cleft pH transients were dependent on Ca2+ movement across the postsynaptic membrane, rather than neurotransmitter release per se, a result consistent with cleft alkalinization being driven by the Ca2+/H + antiporting activity of the plasma membrane Ca2+-ATPase at the postsynaptic membrane. Targeting the pH indicators to the microenvironment of the presynaptic voltage gated Ca2+ channels revealed that alkalinization also occurred within the cleft proper at the active zone and not just within extrasynaptic regions. Application of the pH indicators at the mouse calyx of Held, a mammalian central synapse, similarly revealed cleft alkalinization during burst firing in both males and females. These findings, made at two quite different non-ribbon type synapses, suggest that cleft alkalinization during neurotransmission, rather than acidification, is a generalizable phenomenon across conventional neuronal synapses. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of short regulatory RNAs encoded in the genome of DNA viruses, some single cell organisms, plants and animals. With the rapid development of technology, more and more miRNAs are being discovered. However, the origin and evolution of most miRNAs remain obscure. Here we report the origin and evolution dynamics of a human miRNA family. Results: We have shown that all members of the miR-1302 family are derived from MER53 elements. Although the conservation scores of the MER53-derived pre-miRNA sequences are low, we have identified 36 potential paralogs of MER53-derived miR-1302 genes in the human genome and 58 potential orthologs of the human miR-1302 family in placental mammals. We suggest that in placental species, this miRNA family has evolved following the birth-and-death model of evolution. Three possible mechanisms that can mediate miRNA duplication in evolutionary history have been proposed: the transposition of the MER53 element, segmental duplications and Alu-mediated recombination. Finally, we have found that the target genes of miR-1302 are over-represented in transportation, localization, and system development processes and in the positive regulation of cellular processes. Many of them are predicted to function in binding and transcription regulation. Conclusions: The members of miR-1302 family that are derived from MER53 elements are placental-specific miRNAs. They emerged at the early stage of the recent 180 million years since eutherian mammals diverged from marsupials. Under the birth-and-death model, the miR-1302 genes have experienced a complex expansion with some members evolving by segmental duplications and some by Alu-mediated recombination events. [ABSTRACT FROM AUTHOR]