Designing zeolite catalysts for shape-selective reactions: Chemical modification of surfaces for improved selectivity to dimethylamine in synthesis from methanol and ammonia

The relative contributions of external and intracrystalline acidic sites of small pore H-RHO zeolite for the selective synthesis of methylamines from methanol and ammonia have been studied. Nonselective surface reactions which produce predominantly trimethylamine can be eliminated by “capping” the external acidic sites with trimethylphosphite (TMP) and other reagents, thus improving the selectivity toward the formation of dimethylamine. For small pore zeolites, neither the zeolite pore size nor the internal acidic sites is significantly affected by this treatment. In situ infrared and MAS-NMR studies show that TMP reacts irreversibly with the zeolite acidic sites via a modified Arbusov rearrangement to form surface-bound dimethylmethylphosphonate

Antigen stimulation of peripheral blood mononuclear cells from Mycobacterium bovis infected cattle yields evidence for a novel gene expression program

<p>Abstract</p> <p>Background</p> <p>Bovine tuberculosis (BTB) caused by <it>Mycobacterium bovis </it>continues to cause substantial losses to global agriculture and has significant repercussions for human health. The advent of high throughput genomics has facilitated large scale gene expression analyses that present a novel opportunity for revealing the molecular mechanisms underlying mycobacterial infection. Using this approach, we have previously shown that innate immune genes in peripheral blood mononuclear cells (PBMC) from BTB-infected animals are repressed <it>in vivo </it>in the absence of exogenous antigen stimulation. In the present study, we hypothesized that the PBMC from BTB-infected cattle would display a distinct gene expression program resulting from exposure to <it>M. bovis</it>. A functional genomics approach was used to examine the immune response of BTB-infected (<it>n </it>= 6) and healthy control (<it>n </it>= 6) cattle to stimulation with bovine tuberculin (purified protein derivative – PPD-b) <it>in vitro</it>. PBMC were harvested before, and at 3 h and 12 h post <it>in vitro </it>stimulation with bovine tuberculin. Gene expression changes were catalogued within each group using a reference hybridization design and a targeted immunospecific cDNA microarray platform (BOTL-5) with 4,800 spot features representing 1,391 genes.</p> <p>Results</p> <p>250 gene spot features were significantly differentially expressed in BTB-infected animals at 3 h post-stimulation contrasting with only 88 gene spot features in the non-infected control animals (<it>P </it>≤ 0.05). At 12 h post-stimulation, 56 and 80 gene spot features were differentially expressed in both groups respectively. The results provided evidence of a proinflammatory gene expression profile in PBMC from BTB-infected animals in response to antigen stimulation. Furthermore, a common panel of eighteen genes, including transcription factors were significantly expressed in opposite directions in both groups. Real-time quantitative reverse transcription PCR (qRT-PCR) demonstrated that many innate immune genes, including components of the TLR pathway and cytokines were differentially expressed in BTB-infected (<it>n </it>= 8) versus control animals (<it>n </it>= 8) after stimulation with bovine tuberculin.</p> <p>Conclusion</p> <p>The PBMC from BTB-infected animals exhibit different transcriptional profiles compared with PBMC from healthy control animals in response to <it>M. bovis </it>antigen stimulation, providing evidence of a novel gene expression program due to <it>M. bovis </it>exposure.</p

The interaction of human and Epstein–Barr virus miRNAs with Multiple Sclerosis risk loci

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly

Parent Involvement and Student Academic Performance: A Multiple Mediational Analysis

Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student–teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student–teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed

Generic Continuous Spectrum for Ergodic Schr"odinger Operators

We consider discrete Schr"odinger operators on the line with potentials generated by a minimal homeomorphism on a compact metric space and a continuous sampling function. We introduce the concepts of topological and metric repetition property. Assuming that the underlying dynamical system satisfies one of these repetition properties, we show using Gordon's Lemma that for a generic continuous sampling function, the associated Schr"odinger operators have no eigenvalues in a topological or metric sense, respectively. We present a number of applications, particularly to shifts and skew-shifts on the torus.Comment: 14 page

Detection of a glitch in the pulsar J1709-4429

We report the detection of a glitch event in the pulsar J1709$-$4429 (also known as B1706$-$44) during regular monitoring observations with the Molonglo Observatory Synthesis Telescope (UTMOST). The glitch was found during timing operations, in which we regularly observe over 400 pulsars with up to daily cadence, while commensally searching for Rotating Radio Transients, pulsars, and FRBs. With a fractional size of $\Delta\nu/\nu \approx 52.4 \times10^{-9}$, the glitch reported here is by far the smallest known for this pulsar, attesting to the efficacy of glitch searches with high cadence using UTMOST.Comment: 3 pages, 1 figur

Effects of empagliflozin on fluid overload, weight and blood pressure in chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is associated with fluid excess which can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived “Fluid Overload” and adiposity in a CKD population. METHODS: EMPA-KIDNEY was a 6609-participant double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a 660-participant substudy, bioimpedance measurements were added to the main trial procedures at randomization, 2- and 18-month follow-up visits. The substudy’s primary outcome was the study-average difference in absolute “Fluid Overload” (an estimate of excess extracellular water) analyzed using a mixed-model repeated measures approach. RESULTS: The 660 substudy participants were broadly representative of the 6609- participant trial population. Substudy mean baseline absolute “Fluid Overload” was 0.4±1.7 L. Compared to placebo, the overall mean absolute “Fluid Overload” difference among those allocated empagliflozin was -0.24 L (95%CI -0.38, -0.11), with similar-sized differences at 2- and 18-months, and in pre-specified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95%CI -0.69, -0.30, including the -0.24 L “Fluid Overload” difference); and a -0.30 L (95%CI -0.57, -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (- 0.28 [95%CI -1.41, 0.85] kg). The between-group difference in weight was -0.7 kg (95%CI -1.3, -0.1). CONCLUSIONS: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass

Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.

A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis.This work was supported by the National Institutes of Health (R37AI054503, LR, R01NS082567, CBM, 5F30HL110455, RB, 1DP2-OD008614, DMT), the Wellcome Trust (LR), the National Institute of Health Research Cambridge Biomedical Research Centre (LR), the Health Research Board of Ireland (HRA_POR/2013/387, MO’S and CSA/2012/16, JK), and The Royal City of Dublin Hospital Trust (Grant 146, JK).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.02.034