Últimos itens adicionados do Acervo: Proceedings Nature

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.

Página 22 dos resultados de 3453 itens digitais encontrados em 0.002 segundos

‣ Low dose IR-induced IGF-1-sCLU expression: a p53-repressed expression cascade that interferes with TGFß1 signaling to confer survival

Dmitry Klokov; Konstantin Leskov; Shinako Araki; Yonglong Zou; Eva Goetz; Xiuquan Luo; David Willson; David Boothman
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
To better understand tissue responses after low IR doses, we generated a reporter system using human clusterin promoter fused to firefly luciferase (hCLUp-Luc). Secretory clusterin (sCLU), an extra-cellular molecular chaperone, induced by low doses of cytotoxic agents, clears cell debris promoting survival. Low dose IR (>2 cGy) exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with endogenous sCLU levels. As doses increased (>1 Gy), sCLU induction amplitudes increased and time to peak response decreased. sCLU expression was stimulated by IGF-1, but suppressed by p53. Responses in transgenic hCLUp-Luc reporter mice after low IR doses showed that specific tissues (i.e., colon, spleen, mammary, thymus, bone marrow) of female mice induced hCLUp-Luc activity more than male mice after whole body >10 cGy. Tissue-specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow responded with delayed, but prolonged and elevated expression. Intraperitoneal administration of the α-TGFß1 (1D11) antibody, but not a control antibody (13C4), immediately following IR exposure abrogated CLU induction responses. Induction in vivo also correlated with Smad signaling via activated TGFß1 after IR. Mechanistically...

‣ Arrhenius' theory of partial dissociation and hydration of electrolytes in solutions replaces existing activity concepts

Raji Heyrovska
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The author shows that Arrhenius's theory of partial electrolytic dissociation was immaturely displaced about eight decades ago by the empirical concept of ionic activities and the assumption of complete dissociation of electrolytes at all concentrations. The latter brought the theory of electrolytes over the next decades into a complicated state without any physical significance. Therefore, the author started a systematic investigation of the available data and could completely restore the original theory of partial dissociation. Now solution properties can be easily understood and quantitatively explained in terms of absolute concentrations and volumes of ions and ion pairs and hydration.

‣ Probing the connectivity of neural circuits at single-neuron resolution using high-throughput DNA sequencing

Hassana Oyibo; Gang Cao; Huiqing Zhan; Alex Koulakov; Lynn Enquist; Joshua Dubnau; Anthony Zador
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
There is growing excitement in determining the complete connectivity diagram of the brain—the "connectome". So far, the complete connectome has been established for only one organism, C. elegans, with 302 neurons connected by about 7000 synapses—and even this was a heroic task, requiring over 50 person-years of labor. Like all current approaches, this reconstruction was based on microscopy. Unfortunately, microscopy is poorly suited to the study of neural connectivity because brains are macroscopic structures, whereas synapses are microscopic. Nevertheless, there are several large-scale projects underway to scale up high-throughput microscopic approaches to the connectome. Here we present a completely novel method for determining the brain's wiring diagram based on high-throughput DNA sequencing technology, which has not previously been applied in the context of neural connectivity. The appeal of using sequencing is that it is getting faster and cheaper exponentially: it will soon be routine to sequence an entire human genome (~3B nucleotides) within one day for $1000. Our approach has three main components. First, we express a unique sequence of nucleotides—a DNA "barcode"—in individual neurons. A barcode consisting of a random string of even 30 nucleotides can uniquely label 10^{18} neurons...

‣ Is your phylogeny informative? Measuring the power of comparative methods

Peter Ralph; Graham Coop; Carl Boettiger
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
Phylogenetic comparative methods have become all but ubiquitous in only a few decades, forcing us to reconsider if information from a phylogenetic tree can justify the results. Existing approaches to this question have been inadequate and do not scale with tree size or the ability to resolve branches. For instance, selection between phylogenetic models typically based on information criteria fails to adequately reflect this uncertainty, and can lead to preference for arbitrarily complicated models. Common measures of phylogenetic signal tend to characterize the goodness-of-fit of a Brownian motion model to the data, rather than indicate whether the data is sufficient to confidently distinguish between different hypotheses. We present a Monte Carlo based approach that allows us to reliably select models of the appropriate complexity and identify when a given phylogenetic tree contains insufficient information to test the hypothesis. We conclude that researchers should not assume a model such as Brownian motion a priori but test alternate hypotheses; not test for correlations between traits and branch lengths before applying a phylogenetic model but rather analyze the power of the tree to identify the chosen model from the alternative hypotheses.

‣ Firing statistics and correlations in spiking neurons: a level-crossing approach

Laurent Badel
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
We present a time-dependent level-crossing theory for linear dynamical systems perturbed by colored Gaussian noise. We apply these results to approximate the firing statistics of conductance-based integrate-and-fire neurons receiving excitatory and inhibitory Poissonian inputs. Analytical expressions are obtained for three key quantities characterizing the neuronal response to time-varying inputs: the mean firing rate, the linear response to sinusoidally-modulated inputs, and the pairwise spike-correlation for neurons receiving correlated inputs. The theory yields tractable results that are shown to accurately match numerical simulations, and provides useful tools for the analysis of interconnected neuronal populations.

‣ Novel network pharmacology methods for drug mechanism of action identification, pre-clinical drug screening and drug repositioning

Jianghui Xiong
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
The high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Here we present two methodology innovations on network pharmacology modeling. (1) We hypothesize that the gene network associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. We proposed a novel in vivo genetic interaction between genes as ‘synergistic outcome determination’, in a similar way to ‘synthetic lethality’. We scanned above genetic interactions based on microarray profiling for cancer prognosis, and identified a cluster of important yet epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to this network, we could define a perturbation index for each drug based upon its characteristic perturbation pattern. Finally, by using this index, we significantly discriminated successful drugs from the candidate pool, and revealed the mechanisms of drug combinations. Thus, the prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies. Part of this work was published...

‣ The Strauss-Kahn Syndrome

Robert Skopec
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Accumulating evidence shows that the central nervous system (CNS) regulates the activity of the immune system. Concerning the role of immune system in cancer, psychosocial influences on immune function provide a mechanism of association between psychosocial factors (like interpersonal aggression) and cancer prognosis. Social conflicts between males, involving high aggression stress and threat (psychosocial conflicts) produce both an allostatic state and allostatic load. The costs for aggressors (Hawks) and victims (losers) tested under semi laboratory conditions are quite different. Testosterone does not cause aggression, only exaggerates the pre-existing pattern and response to environmental triggers of aggression. The individual's personality type (authoritarian Hawk or Dove) has major impact on psychoneuroimmune mechanisms linking aggression stress through inflammation to cancer. Due to the latest connotations we propose this personality phenomenon label as "the Strauss-Kahn syndrome".

‣ A G4/W1BD theoretical study into the gas phase enthalpies of formation for potential high energy materials

Sierra Rayne; Kaya Forest
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Enthalpies of formation (Δ~f~H~(g)~) at 298.15 K and 0 K were calculated for various potential high energy materials (HEMs) using the high-level Gaussian-4 (G4) and W1BD methods with the atomization approach. Where prior high level estimates are available in the literature, the G4 and W1BD Δ~f~H~(g)~ are in good agreement. The results presented herein represent the highest level calculations performed to date on this suite of HEMs. These G4/W1BD enthalpies of formation should provide utility among the research community as a benchmark set of values against which to assess future experimental and/or theoretical data.

‣ Singlet-triplet excitation energies of R~1~R~2~Si=Si silylene derivatives: A G4/W1BD theoretical study

Sierra Rayne; Kaya Forest
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Well-to-well (WWE~S-T~) and adiabatic (AE~S-T~) singlet-triplet excitation energies were calculated at the Gaussian-4 (G4) and W1BD levels of theory for a suite of mono- and disubstituted R~1~R~2~Si=Si silylene derivatives (where R~1~/R~2~=H, CH~3~, NH~2~, OH, and F), as well as H~2~C=Si and HN=Si. Reasonable agreement was obtained with prior E~S-T~ estimates at the CCSD(T)/6-311++G(d,p)//QCISD/6-31G(d) and B3LYP/AUG-cc-pVTZ//B3LYP/6-31+G(d) levels of theory. The G4/W1BD E~S-T~ are systematically higher than these prior estimates by between 1 to 5 kcal/mol, averaging positive deviations of about 1-2 and 3-4 kcal/mol from the CCSD(T) and B3LYP estimates, respectively. Qualitative ground state multiplicity agreement between the four levels of theory was found for H~2~C=Si, H~2~Si=Si, HN=Si, (H~3~C)HSi=Si, (H~3~C)~2~Si=Si, (H~2~N)HSi=Si, (H~2~N)~2~Si=Si, (HO)~2~Si=Si, and F~2~Si=Si. However, there is disagreement as to the ground state multiplicity for (HO)HSi=Si and FHSi=Si using the different theoretical methods. For (HO)HSi=Si, G4 and W1BD methods predict either a slightly energetically favored ground state singlet (G4) or an energetic degeneracy between the two multiplicities (W1BD). For FHSi=Si, both the G4 and W1BD methods predict a clear ground state singlet...

‣ Large scale expansion of mobile elements in specific hotspot regions of the German outbreak _Escherichia coli_ O104:H4

Lisa C. Crossman
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The outbreak strain of _E. coli_ O104:H4 has been sequenced by several groups and made available publicly for CrowdSourcing purposes. Genome comparisons of the complete finished sequence of TY2482 (BGI), have been made with the draft assemblies of c22711 (PacBio) and an historical outbreak strain from 2001 (U. Münster & Life Technologies). A plasmid, pTY2, carrying the _agg_ operon specifying the genes for aggregative adherence fimbriae reveals a frameshift in a gene, _aggB_, that may result in altered binding _in vivo_ compared to the unframeshifted state. Comparisons additionally reveal the presence of genomic islands specific to the outbreak strain relative to other sequenced _E. coli_ strains. These regions, and islands shared with the closest previously sequenced relative _E. coli_ 55989 have been analyzed for insertion sequences and transposable elements. Several islands found in the above strains that are not present in other sequenced _E. coli_ are found to harbor a large-scale expansion of mobile elements that are by and large confined to these hotspot or permissive areas of the chromosome. The implication is that these regions are in genomic flux and may represent specific areas of future concern due to the possibility of mobilisation of the associated genomic features likely responsible for the pathogenic features and antibiotic resistance seen in these strains.

‣ Estimated carboxylic acid ester hydrolysis rate constants for food and beverage aroma compounds

Sierra Rayne; Kaya Forest
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Aroma compounds in the Flavornet database were screened for potentially hydrolyzable carboxylic acid ester functionalities. Of the 738 aroma compounds listed in this database, 140 molecules contain carboxylic acid ester groups that may be amenable to hydrolysis in various food and beverage products. Acid- (k~A~) and base- (k~B~) catalyzed and neutral (k~N~) hydrolysis rate constants in pure water at 25°C were estimated for these aroma compounds. Where available, good agreement between theoretical and experimental hydrolytic half-lives was obtained at various pH values. Wide ranges and broad frequency distributions for k~A~, k~B~, and k~N~ are expected among the various hydrolyzable aroma compounds, with estimated k~A~ ranging from 3.7×10^-8^ to 4.7×10^-4^ M^-1^ s^-1^, estimated k~B~ ranging from 4.3×10^-4^ to 43 M^-1^ s^-1^, and estimated k~N~ ranging from 4.2×10^-17^ to 7.6×10^-9^ M^-1^ s^-1^. The resulting hydrolytic half-lives also range widely, from 10 days to 370 years at pH 2.8, 18 days to 4,900 years at pH 4.0, 1.8 days to 470 years at pH 7.0, and 26 minutes to 5.1 years at pH 9.0. The findings presented herein attest to the importance of considering abiotic hydrolysis and matrix pH when modeling the evolution of sensory characteristics for foods and beverages with carboxylic acid ester based aroma compounds.

‣ Effect of a single Dialysis session on plasma Lp(a) levels in patients on Maintenance haemodialysis

Varikasuvu Seshadri Reddy; MM Suchitra; Prabhakar E. Reddy; Aparna R. Bitla; Siva V. Kumar; PVLN Srinivasa Rao
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Background: Cardiovascular disease (CVD) is a major cause of mortality in End stage renal disease (ESRD) patients on Maintenance haemodialysis (MHD). Lp (a), is a specialized form of glycoprotein-LDL-cholesterol complex and is an independent risk factor for myocardial infarction. The risk is related to its atherogenic and thrombogenic properties. The present study was taken up to evaluate changes in Lp(a) and Lipid profile in patients undergoing hemodialysis session. Methodology: Twenty seven patients with end stage renal disease who were on maintenance hemodialysis were included. Plasma samples were collected hourly during a dialysis session with polysulfone membrane using bicarbonate dialysate. Plasma cholesterol, triglycerides, and Lp(a) were estimated on Beckmann CX9 Fully Automated Analyzer using commercial kits. Statistical analysis was performed using SPSS for windows version 11.5. Results: Results of analysis of variance for repeated measures after correction for hemoconcentration where necessary revealed a decrease in Lp(a) (p=0.022) and triglycerides (p=0.001) levels and no change in cholesterol (p=0.48) levels. Conclusion: Maintenance dialysis program is known to produce Dyslipidemia. Study of Lp(a) in dialysis patients is important as this is an independent risk marker. However there are very few reports on changes in Lp(a) due to the dialysis session. Our findings will be discussed in comparison with other reports.

‣ Effect Of A Dialysis Session On Plasma Branched Chain Aminio Acids In Hemodialysis Patients

Varikasuvu Seshadri Reddy; PVLN Srinivasa Rao; Aparna R. Bitla; Siva V. Kumar; MM Suchitra; Prabhakar E. Reddy
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
Protein and amino acid (AA) metabolism is abnormal in End stage renal disease (ESRD). Hemodialysis (HD) procedure is a strong catabolic stimulus. Branched chain amino acids (BCAAs) can affect other AA levels by reducing AA efflux from muscle due to inhibition of muscle protein degradation. Essential amino acids and keto acid supplements including BCAA and branched-chain keto acid (BCKA) are proposed to decrease protein intake while maintaining protein status. This study was taken up to evaluate the effect of a dialysis session on plasma BCAA’s for which fifteen patients of ESRD on Maintenance HD, thrice a week were recruited into the study. Analysis was done on samples drawn at the beginning (pre-HD) and after the end of each dialysis session (post-HD). Plasma BCAA’s were estimated by Reverse phase High performance liquid chromatography using pre column derivatization with O-pthalaldehyde-Mercaptoethanol. A significant decrease in plasma concentration of Valine and Isoleucine were observed post-HD compared to the pre-HD levels (p<0.05). After correcting the data by creatinine, the decrease in plasma concentrations of Valine and Isoleucine were still found to be statistically significant. The percentage losses after the completion of HD were –24.45...

‣ Genetic and Immune Predictors for Hypersensitivity Syndrome to Antiepileptic Drugs

Manuela G. Neuman; Radu M. Nanau; Lawrence Cohen; Paul A. Hwang
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR).Our aims are: to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically, to correlate LTA results with the clinical syndrome, to correlate LTA results with the human leukocyte antigen (HLA) allele B*1502 (HLA-B*1502) positivity in a Han Chinese-Canadian population, and to determine the cytokine network in this population. HSR patients developed fever and cutaneous eruptions in the presence or absence of organ involvement within 8 weeks of exposure to carbamazepine (CBZ), phenytoin (PHY) or lamotrigine (LTG). Control patients received AEDs without presenting HSR. We investigated 10 CBZ-HSR (4 presented with Stevens-Johnson syndrome (SJS)), 24 CBZ-controls, 10 PHY-HSR (4 presented with drug-induced liver injury (DILI)), 24 PHY-controls, 6 LTG-HSR (1 SJS and 1 DILI) and 24 LTG-controls. There were 30 Han Chinese individuals (14 HSR patients and 16 controls) in our cohort. LTA toxicity greater than 12.5%±2.5% was considered positive. Differences among groups were determined by analysis of variance. In addition, we measured cytokine secretion in the patient sera between 1 month and 3 years after the event. All Han Chinese individuals and 30% of Caucasians were genotyped for HLA-B*1502.A perfect correlation (r=0.92) was observed between positive LTA and clinical diagnosis of DILI and SJS/toxic epidermal necrolysis (TEN). HLA-B*1502 positivity in Han Chinese is a predictor of CBZ-HSR and PHY-HSR. HLA-B*1502-negative Han Chinese receiving only CBZ or a combination of CBZ-PHY tolerated the drug(s) clinically...

‣ Involvement of proteasome b1i subunit, LMP2, on uterine leiomyosarcma tumorigenesis

Takuma Hayashi; Akiko Horiuchi; Ikuo Konishi
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine LMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with human uterine LMS, in order to establish a clinical treatment method. Homozygous deficient mice for a proteasome subunit b1i/LMP2 spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine LMS was demonstrated, but present in human LMA. Therefore, loss in LMP2 expression may be one of the risk factors for human uterine LMS. LMP2 may be a potential diagnostic-biomarker and targeted- molecule for a new therapeutic approach.

‣ Identifiers.org and MIRIAM Registry: perennial identifiers for crossreferencing purposes

Camille Laibe
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
The MIRIAM Registry provides unique, perennial and location independent identifiers for data used in the biomedical domain. At its core is a shared catalogue of data collections, for each of which a unique namespace is created, and extensive metadata recorded. This namespace allows the generation of Uniform Resource Identifiers (URIs) to uniquely identify any record in a collection. We present here the new Identifiers.org service which is built upon the information stored in the Registry and which provides directly resolvable identifiers, in the form of Uniform Resource Locators (URLs). The flexibility of the identification scheme and resolving system allows its use in many different fields, where unambiguous and perennial identification of data entities is necessary.

‣ Preservation of C Hexagons in C Allotrope Transformations

Michael J. Bucknum; Eduardo A. Castro
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
In this Letter is described the analogous hexagon preserving C allotrope transformations of graphite to diamond, as a packing of C spheres on the one hand, and alternatively C nanotubes to the C allotrope hexagonite, as a packing of C cylinders on the other hand.

‣ Niche Overlap and Diet Breadth: Can bumble bee (Bombus spp.) foraging behavior reveal species vulnerabilities?

Rosemary Malfi; T'ai Roulston
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Within the last two decades, notable shifts have taken place within the bumble bee (_Bombus_ spp.) communities of North America: some species have experienced substantial, rapid declines, while others appear to be stable or even experiencing range expansion. Studies from the UK and Europe implicate the loss of natural habitat and associated floral resources in overall bumble bee declines and species losses. Research also indicates that loss of host plants disproportionately impacts species with narrower diet breadths, and that these species are more likely to be long-tongued (presumably due to the reduction of long-tubed floral hosts). In contrast, species with more generalized diets have been shown to be more abundant. In this study we examined resource utilization by the bumble bee community at Blandy Experimental Farm in Boyce, VA in order to evaluate (1) whether the diet of a potentially declining long-tongued species (_B. fervidus_) overlaps strongly with a more competitive, expanding species (_B. impatiens_), (2) whether the potentially declining species specializes on host plants relative to the other bumble bee species in the community, and (3) if bumble bee species abundance is associated with diet breadth or the relative abundance of preferred host plants. We surveyed and quantified all mass flowering species in two large meadows on a weekly basis from June 1 to August 15...

‣ On the Hydrides of B, C, N, O and F

Michael J. Bucknum; Eduardo A. Castro
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
This paper reports a productive discussion of bonding principles in the non-metallic 2nd row hydrides. It suggests the inversion of a bonding character, potentially from hydrides of B & C, which may display unsaturation and electronic deficiency accompanied by electronic delocalization in 1D or 2D or 3D. Contrasted with the opposite possibility, within the finite number of hydrides of N, O and F, that display apparently extensive H-bonding and subsequently proton delocalization in 1D and 2D (in HF & ice polymorphs, respectively), and now potentially in 3D in a corresponding hydride of N called Rice's blue material, or perhaps polyimidogen. Where polyimidogen is a crystalline NH lattice that is a polymorph of the ammonium azide structure-type thus.

‣ Chemical Topology of Crystalline Matter and the Transcendental Numbers ϕ , e and π

Michael J. Bucknum; Eduardo A. Castro
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
This work is intended as a review and extension of the seminal work in chemical topology developed by the crystallographer A.F. Wells in the 20th century.