The Hydroxamate Reaction of Aminoacyl-tRNA Synthetases

Amino acids are activated as aminoacyladenylates which remain bound to the aminoacyl-tRNA synthetases that catalyze their formation. The activated amino acids are then esterified to specific transfer RNA molecules. By this reaction sequence, the specificity and energetics necessary for polypeptide synthesis are conferred upon the amino acids. The first method of determining acyl group activation was the hydroxamate assay. The activated amino acids can be trapped as the stable amino acid hydroxamates by carrying out the activation reactions in high concentrations of hydroxylamine

Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney disease.

Abstract The renin-angiotensin system (RAS), bone morphogenetic protein (BMP), and WNT pathways are involved in pathogenesis of diabetic kidney disease (DKD). This study characterized assays for urinary angiotensinogen (AGT), gremlin-1, and matrix metalloproteinase 7 (MMP-7), components of the RAS, BMP, and WNT pathways and examined their excretion in DKD. We measured urine AGT, gremlin-1, and MMP-7 in individuals with type 1 diabetes and prevalent DKD (n = 20) or longstanding (n = 61) or new-onset (n = 10) type 1 diabetes without DKD. These urine proteins were also quantified in type 2 DKD (n = 11) before and after treatment with candesartan. The utilized immunoassays had comparable inter- and intra-assay and intraindividual variation to assays used for urine albumin. Median (IQR) urine AGT concentrations were 226.0 (82.1, 550.3) and 13.0 (7.8, 20.0) μg/g creatinine in type 1 diabetes with and without DKD, respectively (P < 0.001). Median (IQR) urine gremlin-1 concentrations were 48.6 (14.2, 254.1) and 3.6 (1.7, 5.5) μg/g, respectively (P < 0.001). Median (IQR) urine MMP-7 concentrations were 6.0 (3.8, 10.5) and 1.0 (0.4, 2.9) μg/g creatinine, respectively (P < 0.001). Treatment with candesartan was associated with a reduction in median (IQR) urine AGT/creatinine from 23.5 (1.6, 105.1) to 2.0 (1.4, 13.7) μg/g, which did not reach statistical significance. Urine gremlin-1 and MMP-7 excretion did not decrease with candesartan. In conclusion, DKD is characterized by markedly elevated urine AGT, MMP-7, and gremlin-1. AGT decreased in response to RAS inhibition, suggesting that this marker reflects therapeutic response. Urinary components of the RAS, BMP, and WNT pathways may identify risk of DKD and aid development of novel therapeutics

Relation algebras from cylindric algebras, II

Accepted versio

Understanding fuel expenditure: fuel poverty and spending on fuel

A report to Consumer Focus funded by the Joseph Rowntree Foundation that seeks a better understanding of consumers’ actual expenditure on fuel and how this affects our understanding of fuel poverty

SUMMARY – living on different incomes in London: can public consensus identify a 'riches line'?

There is widespread public and political concern about economic inequality in the UK today but relatively little research exploring people’s opinions about high incomes, wealth and what it means to be rich. This innovative study aimed to explore what members of the public with lower and higher incomes living in London think defines higher living standards and whether there is a point at which financial resources (income and wealth) are excessive or undesirable for society. London was chosen as the location for the study because economic inequality is particularly pronounced and plainly visible in the capital

Novelty Improves the Formation and Persistence of Memory in a Naturalistic School Scenario

One of the top challenges in education and neuroscience consists in translating laboratory results into strategies to improve learning and memory in teaching environments. In that sense, during the last two decades, researchers have discovered specific temporal windows around learning, during which the intervention with some experiences induces modulatory effects on the formation and/or persistence of memory. Based on these results, the aim of the present study was to design a specific strategy to improve the memory of students in a high-school scenario, by assessing the effect of a novel situation experienced close to learning. We found that the long-term memory about a geometrical figure was more precise in the group of students that faced a novel situation 1 h before or after learning the figure than the control group of students who did not face the novelty. This enhancement was probably triggered by processes acting on memory formation mechanisms that remained evident 45 days after learning, indicating that the improvement was sustained over time. In addition, our results showed that novelty no longer improved the memory if it was experienced 4 h before or after learning. However, far beyond this window of efficacy, when it was faced around 10 h after learning, the novel experience improved the memory persistence tested 7 days later. In summary, our findings characterized different temporal windows of the effectiveness of novelty acting on memory processing, providing a simple and inexpensive strategy that could be used to improve memory formation and persistence in high-school students.Fil: Ramírez Butavand, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Hirsch, Ian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tomaiuolo, Micol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Moncada, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Viola, Haydée. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Ballarini, Fabricio Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals

Background: Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCVinfected and HIV/HCV-coinfected individuals. Results: Intracellular flow cytometry was used to assess IL-2, IL-10, IL-12, and IFN-γ production by freshly isolated PBMC incubated for 16 hours with recombinant HCV core, non-structural protein 3 (NS3), and NS4 proteins. Anti-HCV cellular responses were assessed in HIV/HCVcoinfected individuals by 3H-thymidine proliferation assay. Exposure to HCV antigens increased IL- 10 production by PBMC, especially in uninfected and HIV-monoinfected individuals. This IL-10 response was attenuated in chronic HCV infection even with HCV/HIV-coinfection. The cells producing IL-10 in response to HCV proteins in vitro matched a PBMC subset recently shown to constitutively produce IL-10 in vivo. This subset was found at similar frequencies in uninfected, HIVinfected, HCV-infected and HIV/HCV-coinfected individuals before exposure to HCV proteins. HCV-specific T cell proliferation was detectable in only one HIV/HCV-coinfected individual who demonstrated no HCV-induced IL-10 response. Conclusion: This pattern suggests that selective induction of IL-10 in uninfected individuals and especially in HIV-monoinfected individuals plays a role in establishing chronic HCV infection and conversely, that attenuation of this response, once chronic infection is established, favours development of hepatic immunopathology

The California-Kepler Survey. III. A Gap in the Radius Distribution of Small Planets

The size of a planet is an observable property directly connected to the physics of its formation and evolution. We used precise radius measurements from the California-Kepler Survey (CKS) to study the size distribution of 2025 $\textit{Kepler}$ planets in fine detail. We detect a factor of $\geq$2 deficit in the occurrence rate distribution at 1.5-2.0 R$_{\oplus}$. This gap splits the population of close-in ($P$ < 100 d) small planets into two size regimes: R$_P$ < 1.5 R$_{\oplus}$ and R$_P$ = 2.0-3.0 R$_{\oplus}$, with few planets in between. Planets in these two regimes have nearly the same intrinsic frequency based on occurrence measurements that account for planet detection efficiencies. The paucity of planets between 1.5 and 2.0 R$_{\oplus}$ supports the emerging picture that close-in planets smaller than Neptune are composed of rocky cores measuring 1.5 R$_{\oplus}$ or smaller with varying amounts of low-density gas that determine their total sizes.Comment: Paper III in the California-Kepler Survey series, accepted to the Astronomical Journa

Plant-microbe networks in soil are weakened by century-long use of inorganic fertilizers.

Understanding the changes in plant-microbe interactions is critically important for predicting ecosystem functioning in response to human-induced environmental changes such as nitrogen (N) addition. In this study, the effects of a century-long fertilization treatment (&gt; 150 years) on the networks between plants and soil microbial functional communities, detected by GeoChip, in grassland were determined in the Park Grass Experiment at Rothamsted Research, UK. Our results showed that plants and soil microbes have a consistent response to long-term fertilization-both richness and diversity of plants and soil microbes are significantly decreased, as well as microbial functional genes involved in soil carbon (C), nitrogen (N) and phosphorus (P) cycling. The network-based analyses showed that long-term fertilization decreased the complexity of networks between plant and microbial functional communities in terms of node numbers, connectivity, network density and the clustering coefficient. Similarly, within the soil microbial community, the strength of microbial associations was also weakened in response to long-term fertilization. Mantel path analysis showed that soil C and N contents were the main factors affecting the network between plants and microbes. Our results indicate that century-long fertilization weakens the plant-microbe networks, which is important in improving our understanding of grassland ecosystem functions and stability under long-term agriculture management

The California-Kepler Survey. I. High Resolution Spectroscopy of 1305 Stars Hosting Kepler Transiting Planets

The California-Kepler Survey (CKS) is an observational program to improve our knowledge of the properties of stars found to host transiting planets by NASA's Kepler Mission. The improvement stems from new high-resolution optical spectra obtained using HIRES at the W. M. Keck Observatory. The CKS stellar sample comprises 1305 stars classified as Kepler Objects of Interest, hosting a total of 2075 transiting planets. The primary sample is magnitude-limited (Kp < 14.2) and contains 960 stars with 1385 planets. The sample was extended to include some fainter stars that host multiple planets, ultra short period planets, or habitable zone planets. The spectroscopic parameters were determined with two different codes, one based on template matching and the other on direct spectral synthesis using radiative transfer. We demonstrate a precision of 60 K in effective temperature, 0.10 dex in surface gravity, 0.04 dex in [Fe/H], and 1.0 km/s in projected rotational velocity. In this paper we describe the CKS project and present a uniform catalog of spectroscopic parameters. Subsequent papers in this series present catalogs of derived stellar properties such as mass, radius and age; revised planet properties; and statistical explorations of the ensemble. CKS is the largest survey to determine the properties of Kepler stars using a uniform set of high-resolution, high signal-to-noise ratio spectra. The HIRES spectra are available to the community for independent analyses.Comment: 20 pages, 19 figures, accepted for publication in AJ; a full version of Table 5 is included as tab_cks.csv and tab_cks.te