A study of the correlations between jet quenching observables at RHIC

Focusing on four types of correlation plots, $R_{\rm AA}$ vs. $v_2$, $R_{\rm AA}$ vs. $I_{\rm AA}$, $I_{\rm AA}$ vs. $v_2^{I_{\rm AA}}$ and $v_2$ vs.\ $v_2^{I_{\rm AA}}$, we demonstrate how the centrality dependence of \emph{correlations} between multiple jet quenching observables provide valuable insight into the energy loss mechanism in a quark-gluon plasma. In particular we find that a qualitative energy loss model gives a good description of $R_{\rm AA}$ vs.\ $v_2$ only when we take $\Delta E\sim l^3$ and a medium geometry generated by a model of the Color Glass Condensate. This same $\Delta E\sim l^3$ model also qualitatively describes the trigger $p_T$ dependence of $R_{\rm AA}$ vs.\ $I_{\rm AA}$ data and makes novel predictions for the centrality dependence for this $R_{\rm AA}$ vs.\ $I_{\rm AA}$ correlation. Current data suggests, albeit with extremely large uncertainty, that $v_2^{I_{\rm AA}}\gg v_2$, a correlation that is difficult to reproduce in current energy loss models.Comment: 6 pages, 6 figure

Caenorhabditis elegans RIG-I Homolog Mediates Antiviral RNA Interference Downstream of Dicer-Dependent Biogenesis of Viral Small Interfering RNAs.

Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection. However, it remains unclear if DRH-1 acts analogously to initiate antiviral RNAi in C. elegans Here, we performed a forward genetic screen to characterize antiviral RNAi in C. elegans Using a mapping-by-sequencing strategy, we uncovered four loss-of-function alleles of drh-1, three of which caused mutations in the helicase and C-terminal domains conserved in RLRs. Deep sequencing of small RNAs revealed an abundant population of Dicer-dependent virus-derived small interfering RNAs (vsiRNAs) in drh-1 single and double mutant animals after infection with Orsay virus, a positive-strand RNA virus. These findings provide further genetic evidence for the antiviral function of DRH-1 and illustrate that DRH-1 is not essential for the sensing and Dicer-mediated processing of the viral dsRNA replicative intermediates. Interestingly, vsiRNAs produced by drh-1 mutants were mapped overwhelmingly to the terminal regions of the viral genomic RNAs, in contrast to random distribution of vsiRNA hot spots when DRH-1 is functional. As RIG-I translocates on long dsRNA and DRH-1 exists in a complex with Dicer, we propose that DRH-1 facilitates the biogenesis of vsiRNAs in nematodes by catalyzing translocation of the Dicer complex on the viral long dsRNA precursors.IMPORTANCE The helicase and C-terminal domains of mammalian RLRs sense intracellular viral RNAs to initiate the interferon-regulated innate immunity against RNA virus infection. Both of the domains from human RIG-I can substitute for the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans, suggesting an analogous role for DRH-1 as an intracellular dsRNA sensor to initiate antiviral RNAi. Here, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in C. elegans Characterization of four distinct drh-1 mutants obtained from the screen revealed that DRH-1 did not function to initiate antiviral RNAi. We show that DRH-1 acted in a downstream step to enhance Dicer-dependent biogenesis of viral siRNAs in C. elegans As mammals produce Dicer-dependent viral siRNAs to target RNA viruses, our findings suggest a possible role for mammalian RLRs and interferon signaling in the biogenesis of viral siRNAs

The Role of Tryptophan in π Interactions in Proteins:An Experimental Approach

In proteins, the amino acids Phe, Tyr, and especially Trp are frequently involved in π interactions such as π-π, cation-π, and CH-π bonds. These interactions are often crucial for protein structure and protein-ligand binding. A powerful means to study these interactions is progressive fluorination of these aromatic residues to modulate the electrostatic component of the interaction. However, to date no protein expression platform is available to produce milligram amounts of proteins labeled with such fluorinated amino acids. Here, we present a Lactococcus lactis Trp auxotroph-based expression system for efficient incorporation (≥95%) of mono-, di-, tri-, and tetrafluorinated, as well as a methylated Trp analog. As a model protein we have chosen LmrR, a dimeric multidrug transcriptional repressor protein from L. lactis. LmrR binds aromatic drugs, like daunomycin and riboflavin, between Trp96 and Trp96' in the dimer interface. Progressive fluorination of Trp96 decreased the affinity for the drugs 6- to 70-fold, clearly establishing the importance of electrostatic π-π interactions for drug binding. Presteady state kinetic data of the LmrR-drug interaction support the enthalpic nature of the interaction, while high resolution crystal structures of the labeled protein-drug complexes provide for the first time a structural view of the progressive fluorination approach. The L. lactis expression system was also used to study the role of Trp68 in the binding of riboflavin by the membrane-bound riboflavin transport protein RibU from L. lactis. Progressive fluorination of Trp68 revealed a strong electrostatic component that contributed 15-20% to the total riboflavin-RibU binding energy

Impacts of Drought on Maize and Soybean Production in Northeast China During the Past Five Decades.

Climate change has a distinct impact on agriculture in China, particularly in the northeast, a key agriculture area sensitive to extreme hydroclimate events. Using monthly climate and agriculture data, the influence of drought on maize and soybean yields-two of the main crops in the region-in northeast China since 1961 to 2017 were investigated. The results showed that the temperature in the growing season increased by 1.0 °C from the period 1998-2017 to the period 1961-1980, while the annual precipitation decreased slightly. However, precipitation trends varied throughout the growing season (May-September), increasing slightly in May and June, but decreasing in July, August and September, associated with the weakening of the East Asian summer monsoon. Consequently, the annual and growing season drought frequency increased by 15%, and 25%, respectively, in the period 1998-2017 relative to the period 1961-1980. The highest drought frequency (55%) was observed in September. At the same time, the drought intensity during the growing season increased by 7.8%. The increasing frequency and intensity of drought had negative influences on the two crops. During moderate drought years in the period 1961-2017, 3.2% and 10.4% of the provincial maize and soybean yields were lost, respectively. However, during more severe drought years, losses doubled for soybean (21.8%), but increased more than four-fold for maize (14.0%). Moreover, in comparison to the period 1961-1980, a higher proportion of the yields were lost in the period 1998-2017, particularly for maize, which increased by 15% (increase for soybean was 2.4%). This change largely depends on increasing droughts in August and September, when both crops are in their filling stages. The impact of drought on maize and soybean production was different during different growth stages, where a strong relationship was noted between drought and yield loss of soybean in its filling stage. Given the sensitivity of maize and soybean yields in northeast China to drought, and the observed production trends, climate change will likely have significant negative impacts on productivity in the future

Bovine testicular [beta]-galactosidase: Purification of enzyme fractions that exhibit high affinity for phosphomannosyl receptors

An improved method is described for the preparation of bovine testicular [beta]-galactosidase that allows the isolation of enzyme fractions that bind avidly to phosphomannosyl receptors. The procedure permits removal of a contaminating [beta]-hexosaminidase and yields nearly homogeneous [beta]-galactosidase. Enzyme eluted from DEAE-Sephacel was arbitrarily divided into pools that exhibited differing ability to bind phosphomannosyl receptors. A high binding fraction was rapidly assimilated by cultured cells and bound to both low and high molecular weight phosphomannosyl receptors. Carbohydrate analysis of the high binding fraction indicates an average content of one complex and one high mannose oligosaccharide chain per molecule and an average mannose 6-phosphate content of two residues per molecule. However, electrofocusing studies indicated that all the fractions were heterogeneous with respect to sialic acid and phosphate content. The purification procedure also provides highly purified [beta]-galactosidase suitable for removing [beta]-galactosidase residues from a variety of complex carbohydrates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27707/1/0000093.pd

Augmented Cardiac Hypertrophy in Response to Pressure Overload in Mice Lacking ELTD1

BACKGROUND: Epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) is developmentally upregulated in the heart. Little is known about the relationship between ELTD1 and cardiac diseases. Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT) mice and ELTD1-knockout (KO) mice were subjected to left ventricular pressure overload by descending aortic banding (AB). KO mice exhibited more unfavorable cardiac remodeling than WT mice 28 days post AB; this remodeling was characterized by aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls, dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac function. Analysis of signaling pathways revealed enhanced extracellular signal-regulated kinase (ERK) and the c-Jun amino-terminal kinase (JNK) phosphorylation in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac hypertrophy and cardiac function induced by AB-induced pressure overload by promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are suggested to originate from the activation of the ERK and JNK pathways, suggesting that ELTD1 is a potential target for therapies that prevent the development of cardiac disease

Geographical Detector-Based Risk Assessment of the Under-Five Mortality in the 2008 Wenchuan Earthquake, China

On 12 May, 2008, a devastating earthquake registering 8.0 on the Richter scale occurred in Sichuan Province, China, taking tens of thousands of lives and destroying the homes of millions of people. Many of the deceased were children, particular children less than five years old who were more vulnerable to such a huge disaster than the adult. In order to obtain information specifically relevant to further researches and future preventive measures, potential risk factors associated with earthquake-related child mortality need to be identified. We used four geographical detectors (risk detector, factor detector, ecological detector, and interaction detector) based on spatial variation analysis of some potential factors to assess their effects on the under-five mortality. It was found that three factors are responsible for child mortality: earthquake intensity, collapsed house, and slope. The study, despite some limitations, has important implications for both researchers and policy makers

Post-Zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development

Post-zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development