Creation of a ternary complex between a crown ether, 4-aminobenzoic acid and 3,5-dinitrobenzoic acid

YesThe creation of ternary multi-component crystals through the introduction of 18-crown-6 to direct the hydrogen-bonding motifs of the other molecular components was investigated for 3,5-dinitrobenzoic acid (3,5-dnba) with 4-aminobenzoic acid (4-aba). The creation of a binary complex between 18-crown-6 and 4-aba (C12H24O6·2C7H7NO2)2 and a ternary salt between 3,5-dnba, 18-crown-6 and 4-aba (C12H24O6·C7H8NO2+·C7H3N2O6−·C7H4N2O6) were confirmed by single-crystal structure determination. In both structures, the amino molecules bind to the crown ether through N—H...O hydrogen bonds, leaving available only a single O atom site on the crown with restricted geometry to potentially accept a hydrogen bond from 3,5-dnba. While 3,5-dnba and 4-aba form a binary co-crystal containing neutral molecules, the shape-selective nature of 18-crown-6 preferentially binds protonated amino molecules, thereby leading to the formation of the ternary salt, despite the predicted low concentration of the protonated species in the crystallizing solution. Thus, through the choice of crown ether it may be possible to control both location and nature of the available bonding sites for the designed creation of ternary crystals

Sersiclets - A Matched Filter Extension of Shapelets for Weak Lensing Studies

The precision study of dark matter using weak lensing by large scale structure is strongly constrained by the accuracy with which one can measure galaxy shapes. Several methods have been devised but none have demonstrated the ability to reach the level of precision required by future weak lensing surveys. In this Letter we explore new avenues to the existing Shapelets approach, combining a priori knowledge of the galaxy profile with the power of orthogonal basis function decomposition. This Letter discusses the new issues raised by this matched filter approach and proposes promising alternatives to shape measurement techniques. In particular it appears that the use of a matched filter (e.g. Sersic profile) restricted to elliptical radial fitting functions resolves several well known Shapelet issues.Comment: 6 pages, 6 figures. MNRAS Accepte

Inheritance of parthenocarpy in gynoecious cucumber (Cucumis sativus L.) cultivar PPC-2

The gynoecious and parthenocarpic inbred line, Pant Parthenocarpic Cucumber-2 (PPC- 2) was crossed with Indian monoecious and non-parthenocarpic cultivar Pusa Uday to develop F1, F2, B1 and B2 to determine the inheritance of parthenocarpy.The crop was grown under insect proof net house of 40 mesh. The pistillate buds were covered using butter paper bags before anthesis to prevent out-crossing.The observations were recorded separately for the development of early parthenocarpic fruits (i.e.1-7th nodes), late parthenocarpy (8th and above nodes) and non-parthenocarpic fruits. In F1 generation, out of 40 plants screened, 2 plants produced parthenocarpic fruits at lower nodes (1-7th nodes), 37 plants produced parthenocarpic fruits at upper nodes (8th and above), whereas,only 1 plant that did not produced any fruit was considered as non-parthenocarpic. The segregation of F2 population and test crosses for parthenocarpic fruit development suggested that parthenocarpy in gynoecious and parthenocarpic cucumber line PPC-2 is under the control of incomplete dominant gene

Essential residues for the enzyme activity of ATP-dependent MurE ligase from Mycobacterium tuberculosis

The emergence of total drug-resistant tuberculosis (TDRTB) has made the discovery of new therapies for tuberculosis urgent. The cytoplasmic enzymes of peptidoglycan biosynthesis have generated renewed interest as attractive targets for the development of new anti-mycobacterials. One of the cytoplasmic enzymes, uridine diphosphate (UDP)-MurNAc-tripeptide ligase (MurE), catalyses the addition of meso-diaminopimelic acid (m-DAP) into peptidoglycan in Mycobacterium tuberculosis coupled to the hydrolysis of ATP. Mutants of M. tuberculosis MurE were generated by replacing K157, E220, D392, R451 with alanine and N449 with aspartate, and truncating the first 24 amino acid residues at the N-terminus of the enzyme. Analysis of the specific activity of these proteins suggested that apart from the 24 Nterminal residues, the other mutated residues are essential for catalysis. Variations in K m values for one or more substrates were observed for all mutants, except the N-terminal truncation mutant, indicating that these residues are involved in binding substrates and form part of the active site structure. These mutant proteins were also tested for their specificity for a wide range of substrates. Interestingly, the mutations K157A, E220A and D392A showed hydrolysis of ATP uncoupled from catalysis. The ATP hydrolysis rate was enhanced by at least partial occupation of the uridine nucleotide dipeptide binding site. This study provides an insight into the residues essential for the catalytic activity and substrate binding of the ATP-dependent MurE ligase. Since ATP-dependent MurE ligase is a novel drug target, the understanding of its function may lead to development of novel inhibitors against resistant forms of M. tuberculosis

Cosmological model differentiation through weak gravitational lensing

We investigate the potential of weak gravitational lensing maps to differentiate between distinct cosmological models, considering cosmic variance due to a limited map extension and the presence of noise. We introduce a measure of the differentiation between two models under a chosen lensing statistics. That enables one to determine in which circumstances (map size and noise level), and for which lensing measures two models can be differentiated at a desired confidence level. As an application, we simulate convergence maps for three cosmological models (SCDM, OCDM, and $\Lambda$CDM), calculate several lensing analyses for them, and compute the differentiation between the models under these analyses. We use first, second, and higher order statistics, including Minkowski functionals, which provide a complete morphological characterization of the lensing maps. We examine for each lensing measure used how noise affects its description of the convergence, and how this affects its ability to differentiate between cosmological models. Our results corroborate to the valuable use of weak gravitational lensing as a cosmological tool.Comment: 12 pages, 8 figures. Submitted to MNRA

QGP Susceptibilities from PNJL Model

An improved version of the PNJL model is used to calculate various thermodynamical quantities, {\it viz.}, quark number susceptibility, isospin susceptibility, specific heat, speed of sound and conformal measure. Comparison with Lattice data is found to be encouraging.Comment: 4 pages, 2 figures, poster presented at Quark Matter'0

Ethnicity and survival after a dementia diagnosis: a retrospective cohort study using electronic health record data

BackgroundIndividuals from minority ethnic groups in the UK are thought to be at higher risk of developing dementia while facing additional barriers to receiving timely care. However, few studies in the UK have examined if there are ethnic disparities in survival once individuals receive a dementia diagnosis.MethodsWe conducted a retrospective cohort study using electronic health record data of individuals diagnosed with dementia from a large secondary mental healthcare provider in London. Patients from Black African, Black Caribbean, South Asian, White British, and White Irish ethnic backgrounds were followed up for a 10-year period between 01 January 2008 and 31 December 2017. Data were linked to death certificate data from the Office of National Statistics to determine survival from dementia diagnosis. Standardised mortality ratios were calculated to estimate excess deaths in each ethnicity group as compared to the gender- and age-standardised population of England and Wales. We used Cox regression models to compare survival after dementia diagnosis across each ethnicity group.ResultsMortality was elevated at least twofold across all ethnicity groups with dementia compared to the general population in England and Wales. Risk of death was lower in Black Caribbean, Black African, White Irish, and South Asian groups as compared to the White British population, even after adjusting for age, gender, neighbourhood-level deprivation, indicators of mental and physical comorbidities. Risk of death remained lower after additionally accounting for those who emigrated out of the cohort.ConclusionsWhile mortality in dementia is elevated across all ethnic groups as compared to the general population, reasons for longer survival in minority ethnic groups in the UK as compared to the White British group are unclear and merit further exploration. Implications of longer survival, including carer burden and costs, should be considered in policy and planning to ensure adequate support for families and carers of individuals with dementia.Introductio

CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis

Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APCMIN/+ mice) to generate APCMIN/+ mice with CCR6 knocked out (CCR6KO-APCMIN/+ mice). CCR6KO-APCMIN/+ mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APCMIN/+ also had normal sized spleens as compared to the enlarged spleens found in APCMIN/+ mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APCMIN/+ as compared to APCMIN/+ mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy

A novel rapid-onset high-penetrance plasmacytoma mouse model driven by deregulation of cMYC cooperating with KRAS12V in BALB/c mice

Our goal is to develop a rapid and scalable system for functionally evaluating deregulated genes in multiple myeloma (MM). Here, we forcibly expressed human cMYC and KRAS12V in mouse T2 B cells (IgM+B220+CD38+IgD+) using retroviral transduction and transplanted these cells into lethally irradiated recipient mice. Recipients developed plasmacytomas with short onset (70 days) and high penetrance, whereas neither cMYC nor KRAS12V alone induced disease in recipient mice. Tumor cell morphology and cell surface biomarkers (CD138+B220−IgM−GFP+) indicate a plasma cell neoplasm. Gene set enrichment analysis further confirms that the tumor cells have a plasma cell gene expression signature. Plasmacytoma cells infiltrated multiple loci in the bone marrow, spleen and liver; secreted immunoglobulins; and caused glomerular damage. Our findings therefore demonstrate that deregulated expression of cMYC with KRAS12V in T2 B cells rapidly generates a plasma cell disease in mice, suggesting utility of this model both to elucidate molecular pathogenesis and to validate novel targeted therapies

Born into adversity: psychological distress in two birth cohorts of second-generation Irish children growing up in Britain

This work was supported by the Medical Research Council (MRC), in the form of a fellowship awarded to J.D.-M. (grant no. G0701595/1).