Neuroblastomas are characterized by hemizygous 1p deletions, suggesting that a tumor suppressor gene resides in this region. We previously mapped the smallest region of consistent deletion to 2-Mb 1p36.31 encodes 23 genes. Based on mutation analysis, expression pattern, and putative function, we identified CHD5 as best candidate.We determined methylation status promoter NLF IMR5 (with deletion) SK-N-SH SK-N-FI neuroblastoma cell lines using methylation-specific sequencing measured mRNA...

Changes in DNA methylation the mammalian genome during development are frequent events and play major roles regulating gene expression other developmental processes. It is necessary to identify these so that we may understand how changes affect normal aberrant impact disease.In this study Methylated ImmunoPrecipitation (MeDIP) was used conjunction with a NimbleGen promoter plus CpG island (CpGi) array Tissue Developmental Stage specific Differentially Regions (T-DMRs DS-DMRs) on genome-wide...

State-of-the-art software tools for neuronal network simulations scale to the largest computing systems available today and enable investigations of large-scale networks up 10 % human cortex at a resolution individual neurons synapses. Due an upper limit on number incoming connections single neuron, connectivity becomes extremely sparse this scale. To manage computational costs, simulation ultimately targeting brain needs fully exploit sparsity. Here we present two-tier connection...

Brain-scale networks exhibit a breathtaking heterogeneity in the dynamical properties and parameters of their constituents. At cellular resolution, entities theory are neurons synapses over past decade researchers have learned to manage with efficient data structures. Already early parallel simulation codes stored distributed fashion such that synapse solely consumes memory on compute node harboring target neuron. As petaflop computers some 100,000 nodes become increasingly available for...

Quorum sensing (QS) controls certain behaviors of bacteria in response to population density. In gram-negative bacteria, QS is often mediated by N-acyl-L-homoserine lactones (acyl-HSLs). Because influences the virulence many pathogenic synthetic inhibitors acyl-HSL synthases might be useful therapeutically for controlling pathogens. However, rational design a potent antagonist has been thwarted lack information concerning binding interactions between and their ligands. bacterium Burkholderia...

Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-β and examined its synthesis. The 166 residue polypeptide chain was prepared by covalent condensation two synthetic peptide segments glycosylated bearing complex-type glycan biological origin. peptides were covalently condensed native chemical ligation. Selective desulfurization followed deprotection the...

The cerebellum plays an essential role in adaptive motor control. Once we are able to build a cerebellar model that runs realtime, which means computer simulation of 1 s the simulated world completes within real world, could be used as realtime neural controller for physical hardware such humanoid robots. In this paper, introduce "Realtime Cerebellum (RC)", new implementation our large-scale spiking network cerebellum, was originally built study mechanisms simultaneous gain and timing...

Sequential motor behavior requires a progression of discrete preparation and execution states. However, the organization state-dependent activity in neuronal ensembles cortex is poorly understood. Here, we recorded spiking local field potential from rat during reward-motivated movement observed robust behavioral coordination between spiking, γ oscillations, θ oscillations. Slow fast oscillations appeared distinct states entrained firing. turn, were coupled to neurons encoding different fired...

ABSTRACT The Burkholderia pseudomallei KHW quorum-sensing systems produced N -octanoyl-homoserine lactone, -decanoyl-homoserine -(3-hydroxy)-octanoyl-homoserine -(3-hydroxy)-decanoyl-homoserine -(3-oxo)-decanoyl-homoserine and -(3-oxo)-tetradecanoyl-homoserine lactone. extracellular secretion of these acyl-homoserine lactones is dependent absolutely on the function B. BpeAB-OprB efflux pump.

NEST is a widely used tool to simulate biological spiking neural networks. Here we explain the improvements, guided by mathematical model of memory consumption, that enable us exploit for first time computational power K supercomputer neuroscience. Multi-threaded components wiring and simulation combine 8 cores per MPI process achieve excellent scaling. capable simulating networks corresponding brain area with 10^8 neurons 10^12 synapses in worst case scenario random connectivity; larger its...

OBJECTIVE: α-Fetoprotein (AFP)-producing gastric cancer has been associated with a poor prognosis. In the present study, cell proliferation, apoptosis, and angiogenesis of this were studied histochemically to determine its malignant potential. METHODS: Tissue samples taken from four patients AFP-producing 26 AFP-negative cancer. Cell proliferation was evaluated by Ki-67 immunostaining, labeling index (LI) determined. Apoptosis terminal deoxynucleotidyl transferase-mediated deoxyuridine...

( Cancer Sci 2010; 101: 759–766) Matrix metalloproteinase (MMP)‐9, the 92‐kDa type IV collagenase, contributes to tumor invasion and metastases, strategies down‐regulate its expression could ultimately be of clinical utility. A pyrrole‐imidazole (PI) polyamide that targets activator protein‐1 (AP‐1)‐binding site MMP‐9 promoter was designed synthesized as a gene‐silencing agent for metastases. The product showed selective DNA binding ability. PI significantly inhibited MMP‐9’s mRNA...

Computer simulation of the human brain at an individual neuron resolution is ultimate goal computational neuroscience. The Japanese flagship supercomputer, K, provides unprecedented capability toward this goal. cerebellum contains 80% neurons in whole brain. Therefore, computer human-scale will be a challenge for modern supercomputers. In study, we built spiking network model cerebellum, composed 68 billion neurons, on K computer. As benchmark, performed cerebellum-dependent eye movement...

We report a preclinical study of pyrrole-imidazole (PI) polyamide that targets the human transforming growth factor (hTGF)-β1 gene as novel transcriptional silencer in common marmoset primate model. designed and then synthesized PI polyamides to target hTGF-β1 promoter. examined effects seven (GB1101-1107) on expression mRNA stimulated with phorbol 12-myristate 13-acetate (PMA) vascular smooth muscle cells. GB1101, GB1105 GB1106 significantly inhibited expression. GB1101 for hypertrophic...

One of the grand challenges for computational neuroscience and high-performance computing is computer simulation a human-scale whole brain model with spiking neurons synaptic plasticity using supercomputers. To achieve such simulation, target network must be partitioned onto number nodes, sub-network models are executed in parallel while communicating spike information across different nodes. However, it remains unclear how should efficient on next generation Specifically, reducing...

n-3 Polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for ulcerative colitis (UC). However, the efficacy of PUFAs against UC has not examined in children. Therefore, authors investigated effects eicosapentaenoic acid (EPA) on composition and leukotriene (LT) production children with UC.For 2 months administered highly purified EPA ethyl ester (EPA-E) (1.8 g/d) to remission. Colonic mucosal histology, erythrocyte membrane phospholipids, LTB4 by leukocytes colonic mucosa...

Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) susceptible PWK/Rbrc strain. is a member trefoil factor family peptides, which are small secreted proteins regulating mucosal regeneration and repair, overexpressed during inflammatory processes cancer progression. We, therefore, analyzed extensively human HCCs. gene was significantly increased 6 out 7 HCCs PWK spontaneous tumor model all an SV40T...

Corneal alkali burns are a serious clinical problem that often leads to permanent visual impairment. In this process, transforming growth factor (Tgf)-β1 is upregulated and involved in the response corneal injury process of stromal scarring. To develop an efficient compound inhibit Tgf-β1 cornea, we designed GB1201, pyrrole–imidazole (PI) polyamide targeting rat gene promoter activator protein-1 (AP-1) binding site. GB1201 showed high affinity target DNA sequence gel mobility shift Biacore...

The gram-negative anaerobic rod Porphyromonas gingivalis in oral biofilms is a primary etiological agent of periodontal disease. Biofilm formation various bacteria regulated by quorum-sensing circuit that relies on N-acyl homoserine lactones (HSLs). Some synthetic HSL analogues act as inhibitors and suppress biofilm Pseudomonas aeruginosa. Development chemical control agents against necessary, because until now, have been removed only mechanical debridement. present study investigated the...

In Gram‐negative bacteria, N‐acylhomoserine lactone ( HSL ) is used as a signal in cell–cell communication and quorum sensing QS ). The model prokaryote E scherichia coli lacks the system of synthesis, but capable monitoring signals environment. Transcription factor SdiA for cell division control believed to play role sensor. Using collection 477 species chemically synthesized analogues, we identified three synthetic molecules SSM s) that bind vitro purified SdiA. After SELEX ‐chip screening...