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Nature é uma das mais prestigiosas e antigas revistas científicas do mundo: sua primeira edição é de 4 de novembro de 1869. Entre as inúmeras descobertas científicas publicadas na Nature estão a dos raios X, da estrutura em dupla hélice do ADN e o buraco na camada de ozônio.

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‣ Control of konzo in the Democratic Republic of Congo

J. Howard Bradbury; Chretienne Mandombi; D Nahimana; J. P. Banea; Ian C. Denton; N Kuwa
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Konzo is an upper motor neuron disease that causes irreversible paralysis of the legs mainly in children and young women^1,2^, due to consumption of large amounts of cyanogens from poorly processed cassava, the staple food of tropical Africa^3^. Konzo occurs in the Democratic Republic of Congo (DRC),Mozambique, Tanzania, Cameroon, Central African Republic and Angola. In March 2010 the wetting method, which removes cyanogens from cassava flour^4,5,6^, was taught to and used by the mothers of Kay Kalenge village. This reduced the total cyanide content of cassava flour to the FAO/WHO limit of 10ppm^7^. Cyanogen intake of school children, monitored by urinary thiocyanate analyses, decreased from mean values of 332 to 130 μmole/L. The percentage of urine samples that exceeded the danger level of about 350 μmole/L decreased from 26 in March 2010 to zero by May 2011. In 2009 there were many new cases of konzo, but none in 2010-2011. Konzo was first identified in1938 in Popokabaka area^8^ and it has now been prevented for the first time in the same area. This methodology is being used in three villages in Boko area and we believe it is the way to control konzo in tropical Africa.

‣ Accelerated Macromolecular Solution Structure Recovery

Petrus Zwart; Haiguang Liu
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Small Angle X-ray Scattering (SAXS) is a standard technique for the determination of low-resolution shapes of macromolecules and their complexes, adding important insights in understanding biological function. We present a novel and computationally efficient method for shape reconstruction from SAXS data. High-quality molecular shapes are calculated in less than two minutes, providing real-time feedback during SAXS experiments.

‣ Antidepressant suppression of REM and spindle sleep impairs hippocampus-dependent learning and memory but fosters striatal-dependent strategies

Alain Watts; Howard Gritton; Jamie Sweigart; Gina Poe
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
REM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dependent procedural learning. Antidepressant medications like desipramine (DMI) inhibit rapid-eye-movement (REM) sleep but it is little understood how antidepressant treatments affect learning. We found that DMI strongly suppressed REM sleep in rats for several hours and impaired reconsolidation of a familiar maze and consolidation of moved baited positions (reversal learning) in a sleep-dependent fashion. Unexpectedly, DMI also reduced the spindle-rich transition-to-REM sleep state (TR) and spatial memory changes were more related to TR than to REM sleep. Working memory was unaffected, but overnight reference memory was significantly impaired and subjects increased reliance on non-hippocampal strategies. Procedural memory performance was positively correlated with increases in non-REM sleep after DMI serving to offset memory declines, partially preserving performance. Our results suggest that familiar memories are re-consolidated during REM sleep, reversal memories consolidated during TR, and procedural memories consolidated during non-REM sleep.

‣ Docking-based virtual screening for the exploration of potential antagonists for human IGFBP6

Bhuvanagiri Sravani; Dibyabhaba Pradhan; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
Design of potential drug-like candidates for cardiovascular therapy is of interest in recent years. Elevated level of IGFBP-6 leads to perilous diseases like atherosclerosis, high output cardiac failure and myocardial infarction. The current IGFBP-6 inhibitors available in clinical practice are not having satisfactory anti-cardiovascular effects, leaving room for further improvement. Therefore, with an aim to propose a potent inhibitor to arrest the cardiovascular disease caused by IGFBP-6, tools of computer-aided drug designing were used for virtual screening from small molecule databases. Accordingly, IGFBP-6 tertiary structure was solved through nuclear magnetic resonance techniques retrieved from the protein data bank. Fifteen IGFBP-6 inhibitors were acquired from literature databases and subsequent 2D searching protocol of Ligand.Info yielded 5759 structural analogs. The 3D structural conversion and multiple conformations for each compound were generated using LigPrep with constraints of ADME evaluation and toxicity assessments. The docking and scoring calculations were performed using Glide v5.7. The Glide extra precision (XP) docking had reported 138 leads and ranked based on XP Gscore. Six leads having better XP Gscore compared to current IGFBP-6 inhibitors were proposed as potential inhibitors. Chelidamic acid showed the highest XP Gscore (-7.094 Kcal/mol) with good pharmacological properties and molecular interaction with IGFBP-6. Therefore...

‣ Prediction of novel inhibitors for human RNase1 involved in cardiovascular disease through in silico screening

Kanipakam Hema; Sadnala Giribabu; Sandeep Swargam; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Human pancreatic ribonuclease (RNase1) is a small digestive and pyramidine specific enzyme secreted by the pancreas. RNase1 contributes in the regulation of extracellular RNA by hydrolyzing RNA phosphodiester bonds. High levels of RNase1 in cardiovascular disease patients project the enzyme as an attractive drug target. The known RNase1 inhibitors, citric acid and U1S were searched for structural analogs from Ligand.info database to compile 783 ligands. The ligands' 3D structures and their tautomeric states were generated using LigPrep. The 3424 prepared conformations were subjected to QikProp analysis and filtered based on Lipinski rule of five and zero reactive functional group. The 3376 conformations with good ADME (absorption, desorption, metabolism, excretion) profile were passed through multistage docking in virtual screening workflow of Schrodinger software 2011. Seventy five ligands with good binding affinity towards RNase1 were ranked based on XPGscore, through Glide extra precision (XP) docking. Twenty three ligands with better XPGscore compared to published inhibitors (citric acid and U1S) were proposed as potential RNase1 inhibitors. Analysis of docking complexes, their binding orientations, XPGscores and through stringent correlation with published data lead ‘1’ that showed least XPGscore (-12.284 Kcal/mol) was proposed as the best molecule to consider for rational drug designing for treatment of cardiovascular disease.

‣ Identification of small molecule inhibitor of cyclophilin-A using high throughput virtual screening and molecular docking Studies

Pallapotu Navya; I Vani Priyadarshini; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
The inhibitors of cyclophilin A (CyPA) have drawn a great deal of attention due to their promising potential as small-molecule therapeutics for the treatment of cardiovascular diseases. This ultimately prompts to explore structural geometries of these inhibitors to obtain insights on next generation CyPA inhibitors through rational drug designing. Herein, 2D similarity search for the seven CyPA inhibitors was performed using Ligand.Info database. Small subsets of 2800 molecules from one million compounds were predicted to have activity against cardiovascular drug target CyPA. The binding strength of 2800 ligands with CyPA was assessed through molecular docking analysis using Schrödinger software 2011. The CyPA co-crystal structure and ligand dataset were preprocessed using protein preparation wizard and LigPrep, respectively. Lipinski filter and reactive filter evaluations were applied to 10,351 tautomeric states of 2800 ligands to achieve conformations with good pharmacological properties. Further, systematic Glide HTVS, SP and XP docking had resulted 151 ligands with good binding affinities towards CyPA. Ten best ranked compounds having good correlation with seven published CyPA inhibitors were proposed as potential leads. These ten leads had the advantage of good drug like properties compared to experimentally validated inhibitors. Lead1 (SQ29548) showed XP GScore of -12.11 Kcal/mol and two hydrogen bonds with Asp102 of CyPA which is in well agreement with crystallographic data of ‘CyPA - Sanglifehrin A’ complex. SQ29548 is already used as an antagonist for human recombinant thromboxane receptor which supports ten proposed potential inhibitors identified through virtual screening approach as a starting point for new generation drug designing to combat cardiovascular associated diseases.

‣ In-silico analysis and identification of novel lead molecule for human IGFBP-4 involved in cardiovascular diseases

Kavali Roopesh; Manne Munikumar; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
Cardiovascular disease is the major cause of disability and premature death throughout the world and contributes substantially to the escalating costs of health care. Insulin like growth factor binding protein 4 (IGFBP-4) mainly belongs to the family of IGFB protein. Over expression of IGFBP-4 leads to cardiovascular diseases namely stroke, acute myocardial infarction and heart failure. IGFBP-4 serves as an effective drug target against cardiovascular disease. Hence, ligand based virtual screening was persuaded in the present study to propose potential inhibitors of IGFBP-4. Two inhibitors (mainly from literature search) were selected to initiate high throughput virtual screening from small molecule databases namely, NCI, ChemBank, ChemPDB, AKos GmbH, Asinex Ltd and KEGG ligand. The structures listed through database search were docked with IGFBP-4 using virtual screening workflow of Maestro v9.2. Three leads that showed better binding affinity and good correlation with two published inhibitors were proposed as potential IGFBP-4 inhibitors. The three proposed leads showed good pharmacological properties in comparison to the two existing inhibitors. The analyses supported efficiency of three leads for next generation drug designing for cardiovascular diseases.

‣ Exploring NAG active site of human CD59 towards discovery of novel activators for treatment of atherosclerosis

Challa Lakshmi Narayana Rao; Dibyabhaba Pradhan; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
CD59 is a potent inhibitor of the complement membrane attack complex (MAC) action that acts by binding to the C8 and C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. Human CD59 low expression leads to atherosclerosis. Therefore, computational approach methods were implemented herein to design novel activators for CD59. Crystal structure (PDB ID: 1CDR) of CD59 was investigated to locate N-acetyl glucosamine (NAG) active site residues (Leu1, Gln2, Val17, Asn18, Ser20, Ser21, Asp22 and Asp67). CD59 is known for its binding affinity towards NAG and Alpha-L-Fucose, hence, were explored against more than one million entries of Ligand.Info metadatabase to create an in-house library of 708 compounds. Ligand dataset was prepared using LigPrep and filtered based on Lipinski’s rule of five and reactive group constraints. The crystal structure was optimized and energy was minimized applying OPLS force field in Maestro v9.2. Sixty four ligands were found to have binding affinity towards CD59 through virtual screening workflow of Maestro. Two ligands namely mizoribine (-8.56 kcal/mol) and gluconolactone (-8.39 kcal/mol) with better XPG score compared to NAG (-8.02 kcal/mol) were proposed potential CD59 activators. Analysis of docking complexes for both proposed leads revealed a stable hydrogen bond network...

‣ Mizoribin as a inhibitor for leukocyte immunoglobulin receptor sub family A member3

Varala Sravani; I Vani Priyadarshini; Amineni Umamaheswari
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
The Leukocyte Immunoglobulin-like Receptors (LILRs) are a family of receptors that was broadly expressed on all leukocytes and have the ability to regulate their function. The increased levels of human LILRA3 in rheumatoid arthritis patients leads to stroke. In quest of designing novel inhibitors against LILRA3 an accurate homology model for the protein was based on crystal structures of 1GOX and 3P2T using Modeller 9V9. The use of multiple templates for structure prediction led us to propose a structure comprising all 439 amino acids of human LILRA3 for the first time. The best model was selected based on GA341 and DOPE score and further assessed through ProSA and PROCHECK. The validated structure was subjected to CASTp analysis ligand binding site determination. N-acetyl-glucosamine (NAG) that has binding affinity towards human LILRA3 was searched for structural analogs from Ligan.Info database. The structural analogs were docked with LILRA3 using Glide v5.7 to propose 17 potential inhibitors with better binding affinity compared to NAG (-7.13 Kcal/mol). Analysis of LILRA3-Lead1 (mizoribin) docking showed best XPGscore of -10.70 Kcal/mol with four hydrogen bonds with Thr425, Glu360, Ser433,Val419. The binding orientations of mizoribin correlated well with NAG binding orientations. Therefore...

‣ Sonic Layer Depth estimated from XBT temperatures and climatological salinities

TVS Udaya Bhaskar; Debadatta Swain
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Sonic layer depth (SLD) plays an important role in antisubmarine warfare in terms of identifying the shadow zones for submarine safe parking. SLD is estimated from sound velocity profiles (SVP) which is in turn obtained from temperature and salinity (T/S) profiles. Given the limited availability of salinity data in comparison to temperature, SVPs need to be obtained from alternate methods. In the present work, to make use of voluminous temperature data sets from XBT, CTD and other source for estimating SLD, we propose a method of utilizing XBT measurements and World Ocean Atlas climatological salinities to compute SVP and then extract SLD. This approach is demonstrated by utilizing T/S data from Argo floats in the Arabian Sea (40° – 80° E and 0 – 30° N). SLD is estimated from SVP obtained from Argo T/S profiles first and again by replacing the Argo salinity with climatological salinity. It is found that in more than 90% of cases, SLD matched exactly, with the root mean square deviation ranging from 3 – 12 m with an average of 7 m.

‣ The Starving Cell: Metabolic Syndrome as an Adaptive Process

Beatrice A. Golomb
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Metabolic syndrome (MetS) is commonly presumed to stem from obesity, with both propelled by energy surfeit: positive balance of calories consumed to energy expended. A complementary thesis is proposed: that episodes of cell energy deficit (not expressly calorie deficit) drive MetS – the “Starving Cell.” Risk factors for MetS include hypoxemia from sleep apnea, severe calorie debt, mitochondrial dysfunction, oxidative stress; and sleep restriction, illness, surgery, trauma, cold. Each fosters inadequate cell energy, hampering production or boosting demand. MetS factors support energy: glucose, triglycerides, abdominal/visceral fat – and blood pressure, sustaining perfusion. Additional energy-supportive adaptations co-occur in MetS: e.g. increased free fatty acids and deposition of metabolically active ectopic fat. Indeed, increased appetite/calories and reduced activity – features of the energy surfeit model – also arise as adaptations to cell energy deprivation. Among persons who are overweight, the risk for MetS remains determined by energy deprivation contributors. The Thrifty Gene hypothesis, and MetS promotion by fetal energy deprivation, prefigure the Starving Cell thesis. However...

‣ Invasive monitoring of the clinical effects of high intra-abdominal pressure for insertion of the first trocar.

Octavio H. M. Hypolito; Joao-Luiz Azevedo; Fernanda A. B. Gama; Otavio C. Azevedo; Otavio M. Becker Junior; Afonso C. C. G. Machado; Susana A. Miyahira; Glicia C. Azevedo; Bianca Marigliani; José F. Borborema; Linda Bernardes; Gustavo P. S. Mi
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Background: To analyze the effects of transitory, high intra-abdominal pressure on clinical, hemodynamic, blood gas and metabolic parameters. Methods: Sixty-seven laparoscopic patients were divided into groups P12 (n = 30, maximum intra-abdominal pressure of 12 mmHg) and P20 (n = 37, maximum intra-abdominal pressure of 20 mmHg). Through radial artery cannulation, mean arterial pressure (MAP) was assessed and blood gas analysis – pH, arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), bicarbonate (HCO3) and base excess (BE) – was performed. These parameters were evaluated in both groups at time point zero, before CO2 insufflation; at time point one (TP1), when intra-abdominal pressure of 12 mmHg was reached in both groups; at time point two (TP2), 5 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and of 20 mmHg in group P20; and at time point three (TP3), 10 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and 10 minutes after TP1 in group P20, when intra-abdominal pressure decreased from 20 mmHg to 12 mmHg. Values out of the normal range or the occurrence of atypical phenomena suggestive of organic disease indicated clinical changes. Results: Significant variations in MAP...

‣ Missouri River Watershed: the Object for Hydrological Study and Uncertainty of Models

Boris Shmagin
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
The longest river (2540 mi) and the second drainage area (529 346 mi2) in the North America the Missouri River is one from the most interesting hydrological objects to study. The issue of uncertainty is the basis for any application of knowledge (“Uncertainty is an attribute of information.” From Zadeh, 2005) and has to be one of the main tasks in Earth’s systems study. Knowledge about natural systems (watershed in our case) may be only obtained by the analysis of the empirical (instrumental) data (observations). Principle of Uncertainty is the basic low in Physic. In Hydrology, the Uncertainty starts from the unveiling of the research task by the researcher. The main source of the uncertainty comes from the natural system “extraction” (unit’s boundaries) for modeling and from the limitations of data representing both time and space variability. The watershed has the formal determined boundary and this property places hydrology in the center of regional climate research. The uncertainty is considered in context of time and space with use of cybernetic model of the watershed and described on base of specification of the system in the coordinates on the Earth. The math model does not have criteria to verify itself (Gödel's incompleteness theorems) – multitasks & multiscales studies have to be completed. The data analysis for Upper Missouri River provide a base for regionalization...

‣ Relationship of arterial and exhaled CO2 during elevated artificial pneumoperitoneum pressure for introduction of the first trocar.

Octavio H. M. Hypolito; Joao-Luiz Azevedo; Susana A. Miyahira; Fabiana Scarpelli; Otavio M. Becker Junior; Afonso C. C. G. Machado; Otavio C. Azevedo; Glicia C. Azevedo; Bianca Marigliani; Jose F. Borborema; Linda Bernardes; Gustavo P. S. Miguel
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The present study evaluated the correlation between arterial CO2 and exhaled CO2 during brief high-pressure pneumoperitoneum. Patients were randomly distributed into two groups: P12 group (n=30) received a maximum intraperitoneal pressure of 12mmHg, and P20 group (n=37) received a maximum intraperitoneal pressure of 20mmHg. Arterial CO2 was evaluated by radial arterial catheter and exhaled CO2 was measured by capnometry at the following time points: before insufflation, once intraperitoneal pressure reached 12mmHg , 5 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or 20mmHg for the P20 group, and 10 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or when intraperitoneal pressure had decreased from 20mmHg to 12mmHg, for the P20 group. During brief durations of very high intraperitoneal pressure (20mmHg), there was a strong correlation between arterial CO2 and exhaled CO2. Capnometry can be effectively used to monitor patients during transient increases in artificial pneumoperitoneum pressure.

‣ Density alteration in non-physiological cells

Yu Liu; Yuan-Chang Zhu; Bin-Bin Wu; Xiao-Hua Wu; Fei-Fei Lan; Jian-Ge Wei; Ming Wang; Hai-Cheng Li; Lin-Na Li; Ju-Xiang Li; Jia Fei
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
In the present study an important phenomenon of cells was discovered: the change of intracellular density in cell's response to drug and environmental factors. For convenience, this phenomenon is named as "density alteration in non-physiological cells" ( DANCE). DANCE was determined by discontinuous sucrose gradient centrifugation (DSGC), in which cells were separated into several bands. The number and position of the bands in DSGC varied with the change of cell culture conditions, drugs, and physical process, indicating that cell's response to these factors was associated with alteration of intracellular density. Our results showed that the bands of cells were molecularly different from each other, such as the expression of some mRNAs. For most cells tested, intracellular density usually decreased when the cells were in bad conditions, in presence of drugs, or undergoing pathological changes. However, unlike other tissue cells, brain cells showed increased intracellular density in 24 hrs after the animal death. In addition, DANCE was found to be related to drug resistance, with higher drug-resistance in cells of lower intracellular density. Further study found that DANCE also occurred in microorganisms including bacteria and fungus...

‣ The Five Stars of Online Journal Articles – an article evaluation framework

David Shotton
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
I propose five factors – peer review, open access, enriched content, available datasets and machine-readable metadata – as the Five Stars of Online Journal Articles, a constellation of five independent criteria within a multi-dimensional publishing universe against which online journal articles can be evaluated, to see how well they match up to current visions for research communications. Achievement along each of these publishing axes can vary, analogous to the different stars within the constellation shining with varying luminosities. I suggest a five-point scale for each by which a journal article can be evaluated, and a diagrammatic representation for such evaluations. While the criteria adopted for these scales are somewhat arbitrary, and while the rating of a particular article on each axis may involve elements of subjective judgment, these Five Stars of Online Journal Articles provide a conceptual framework by which to judge the degree to which any article achieves or falls short of the ideal, which should be useful to authors, editors and publishers. I exemplify such evaluations using my own recent publications of relevance to semantic publishing.

‣ Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice

Ul’yana A. Boyarskikh; Natalya P. Bondar; Maxim L. Filipenko; Natalia N. Kudryavtseva
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Background: There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. Methodology/Principal Findings: The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels...

‣ Slug-based epithelial-mesenchymal transition gene signature is associated with prolonged time to recurrence in glioblastoma

Wei-Yi Cheng; Jessica J. Kandel; Darrell J. Yamashiro; Peter Canoll; Dimitris Anastassiou
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Background We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types. The expression levels of the co-expressed genes vary in a continuous and coordinate manner across the samples, ranging from absence of expression to strong co-expression of all genes. These data suggest that tumor cells may pass through an EMT like process of mesenchymal transition to varying degrees. Findings Here we show that this signature in glioblastoma multiforme (GBM) is associated with time to recurrence following initial treatment. By analyzing data from The Cancer Genome Atlas (TCGA), we found that GBM patients who responded to therapy and had long time to recurrence had low levels of the signature in their tumor samples (P = 3x10^-7^). We also found that the signature is strongly correlated in gliomas with the putative stem cell marker CD44, and is highly enriched among the differentially expressed genes in glioblastomas vs. lower grade gliomas. Conclusions Our results suggest that long delay before tumor recurrence is associated with absence of the mesenchymal transition signature...

‣ Combining Transfer of TTF-1 and Pax-8 Gene: a Potential Strategy to Promote Radioiodine Therapy of Thyroid Carcinoma

Da Mu; Rui Huang; Xiaojuan Ma; Suping Li; Anren Kuang
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Cotransfer of TTF-1 and Pax-8 gene to tumor cells, resulting in the reexpression of iodide metabolism-associated proteins, such as sodium iodide symporter (NIS), thyroglobulin (Tg), thyroperoxidase (TPO), offers the possibility of radioiodine therapy to non-iodide-concentrating tumor because the expression of iodide metabolism-associated proteins in thyroid are mediated by the thyroid transcription factors TTF-1 and Pax-8. The human TTF-1 and Pax-8 gene were transducted into the human thyroid carcinoma (K1 and F133) cells by the recombinant adenovirus, AdTTF-1 and AdPax-8. Reexpression of NIS mRNA and protein, but not TPO and Tg mRNA and protein, was detected in AdTTF-1-infected F133 cells, following with increasing radioiodine uptake (6.1~7.4 times), scarcely iodide organification and rapid iodide efflux (t1/2≈8 min in vitro, t1/2≈4.7 h in vivo). In contrast, all of the reexpression of NIS, TPO and Tg mRNA and proteins in F133 cells were induced by the synergetic effect of TTF-1 and Pax-8. AdTTF-1 and AdPax-8 coinfected K1 and F133 cells could effectively accumulate radioiodine (6.6-7.5 times) and obviously retarded radioiodine retention (t1/2≈25-30 min in vitro, t1/2≈12 h in vivo) (p<0.05). Accordingly...

‣ Ten thousand times faster: Classifying multidimensional data on a spiking neuromorphic hardware system.

Michael Schmuker; Daniel Brüderle; Sven Schrader; Martin Nawrot
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Discrimination of sensory inputs is a computational task that biological neuronal systems perform very efficiently. Assessing the principles in those systems is a promising approach to develop technical solutions for many problems, such as data classification. A particular problem here is to train a classifier in a supervised fashion to discriminate classes in multidimensional data. We implemented a network of spiking neurons that solves this task using a neuromorphic hardware system, that is, analog neuronal circuits on a silicon substrate. This system enables us to do high-performance computation in a biologically inspired way, with spiking neurons as computational units. In this contribution, we illustrate solutions to technical challenges that occur when implementing a classifier on neuromorphic hardware. The network topology of the insect olfactory system provides a well suited template for a neuronal architecture processing multidimensional data. In our classifier network, the value of each dimension of a data vector determines the rate of a stochastically generated spike train. The spike trains are fed into non-overlapping populations of neurons. Those populations project onto an association layer with winner-take-all properties representing the output of the classifier. During classifier training...