Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states

Glutamate is a neurotransmitter critical for spinal excitatory synaptic transmission and for generation and maintenance of spinal states of pain hypersensitivity via activation of glutamate receptors. Understanding the regulation of synaptically and non-synaptically released glutamate associated with pathological pain is important in exploring novel molecular mechanisms and developing therapeutic strategies of pathological pain. The glutamate transporter system is the primary mechanism for the inactivation of synaptically released glutamate and the maintenance of glutamate homeostasis. Recent studies demonstrated that spinal glutamate transporter inhibition relieved pathological pain, suggesting that the spinal glutamate transporter might serve as a therapeutic target for treatment of pathological pain. However, the exact function of glutamate transporter in pathological pain is not completely understood. This report will review the evidence for the role of the spinal glutamate transporter during normal sensory transmission and pathological pain conditions and discuss potential mechanisms by which spinal glutamate transporter is involved in pathological pain

The H₃⁺ ionosphere of Uranus: decades-long cooling and local-time morphology

The upper atmosphere of Uranus has been observed to be slowly cooling between 1993 and 2011. New analysis of near-infrared observations of emission from H₃⁺ obtained between 2012 and 2018 reveals that this cooling trend has continued, showing that the upper atmosphere has cooled for 27 years, longer than the length of a nominal season of 21 years. The new observations have offered greater spatial resolution and higher sensitivity than previous ones, enabling the characterization of the H₃⁺ intensity as a function of local time. These profiles peak between 13 and 15 h local time, later than models suggest. The NASA Infrared Telescope Facility iSHELL instrument also provides the detection of a bright H₃⁺ signal on 16 October 2016, rotating into view from the dawn sector. This feature is consistent with an auroral signal, but is the only of its kind present in this comprehensive dataset

Insulin trafficking in a glucose responsive engineered human liver cell line is regulated by the interaction of ATP-sensitive potassium channels and voltage- gated calcium channels

Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions

My Hand or Yours? Markedly Different Sensitivity to Egocentric and Allocentric Views in the Hand Laterality Task

In the hand laterality task participants judge the handedness of visually presented stimuli – images of hands shown in a variety of postures and views - and indicate whether they perceive a right or left hand. The task engages kinaesthetic and sensorimotor processes and is considered a standard example of motor imagery. However, in this study we find that while motor imagery holds across egocentric views of the stimuli (where the hands are likely to be one's own), it does not appear to hold across allocentric views (where the hands are likely to be another person's). First, we find that psychophysical sensitivity, d', is clearly demarcated between egocentric and allocentric views, being high for the former and low for the latter. Secondly, using mixed effects methods to analyse the chronometric data, we find high positive correlation between response times across egocentric views, suggesting a common use of motor imagery across these views. Correlations are, however, considerably lower between egocentric and allocentric views, suggesting a switch from motor imagery across these perspectives. We relate these findings to research showing that the extrastriate body area discriminates egocentric (‘self’) and allocentric (‘other’) views of the human body and of body parts, including hands

Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer

Background: Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC). Methods and Findings: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. Conclusions: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression

Laser-induced etching of few-layer graphene synthesized by Rapid-Chemical Vapour Deposition on Cu thin films

The outstanding electrical and mechanical properties of graphene make it very attractive for several applications, Nanoelectronics above all. However a reproducible and non destructive way to produce high quality, large-scale area, single layer graphene sheets is still lacking. Chemical Vapour Deposition of graphene on Cu catalytic thin films represents a promising method to reach this goal, because of the low temperatures (T < 900 Celsius degrees) involved during the process and of the theoretically expected monolayer self-limiting growth. On the contrary such self-limiting growth is not commonly observed in experiments, thus making the development of techniques allowing for a better control of graphene growth highly desirable. Here we report about the local ablation effect, arising in Raman analysis, due to the heat transfer induced by the laser incident beam onto the graphene sample.Comment: v1:9 pages, 8 figures, submitted to SpringerPlus; v2: 11 pages, PDFLaTeX, 9 figures, revised peer-reviewed version resubmitted to SpringerPlus; 1 figure added, figure 1 and 4 replaced,typos corrected, "Results and discussion" section significantly extended to better explain etching mechanism and features of Raman spectra, references adde

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

High-Throughput Sequencing to Reveal Genes Involved in Reproduction and Development in Bactrocera dorsalis (Diptera: Tephritidae)

BACKGROUND: Tephritid fruit flies in the genus Bactrocera are of major economic significance in agriculture causing considerable loss to the fruit and vegetable industry. Currently, there is no ideal control program. Molecular means is an effective method for pest control at present, but genomic or transcriptomic data for members of this genus remains limited. To facilitate molecular research into reproduction and development mechanisms, and finally effective control on these pests, an extensive transcriptome for the oriental fruit fly Bactrocera dorsalis was produced using the Roche 454-FLX platform. RESULTS: We obtained over 350 million bases of cDNA derived from the whole body of B. dorsalis at different developmental stages. In a single run, 747,206 sequencing reads with a mean read length of 382 bp were obtained. These reads were assembled into 28,782 contigs and 169,966 singletons. The mean contig size was 750 bp and many nearly full-length transcripts were assembled. Additionally, we identified a great number of genes that are involved in reproduction and development as well as genes that represent nearly all major conserved metazoan signal transduction pathways, such as insulin signal transduction. Furthermore, transcriptome changes during development were analyzed. A total of 2,977 differentially expressed genes (DEGs) were detected between larvae and pupae libraries, while there were 1,621 DEGs between adults and larvae, and 2,002 between adults and pupae. These DEGs were functionally annotated with KEGG pathway annotation and 9 genes were validated by qRT-PCR. CONCLUSION: Our data represent the extensive sequence resources available for B. dorsalis and provide for the first time access to the genetic architecture of reproduction and development as well as major signal transduction pathways in the Tephritid fruit fly pests, allowing us to elucidate the molecular mechanisms underlying courtship, ovipositing, development and detailed analyses of the signal transduction pathways