The cobalt(II) salt of the azo dye Orange G

Crystallizing the cobalt(II) salt of the azo dye Orange G from water was found to give the solvent-separated ion-pair species hexa­aqua­cobalt(II) 7-oxo-8-(2-phenyl­hydrazin-1-ylidene)-7,8-dihydro­naphthalene-1,3-disulfonate tetra­hydrate, [Co(H2O)6](C16H10N2O7S2)·4H2O. The asymmetric unit of the cobalt(II) salt contains three independent octa­hedral [Co(OH2)6]2+ cations, three azo anions, all with similar configurations, and 12 uncoordinated water mol­ecules. The structure is closely related to that of one of the known magnesium analogues. Both structures have Z′ = 3, feature nearly planar azo anions [maximum displacement of azo-N atoms from the plane of the phenyl ring = 0.058 (7) Å] in their hydrazone tautomeric form, form layer structures with hydro­philic and hydro­phobic layers alternating along the b-axis direction, and are stabilized by an extensive network of hydrogen bonds.

Crystal structure of N,N-dimethyl-2-[(4-methylbenzyl)sulfonyl]ethanamine

In the crystal, the title compound, C12H19NO2S, has a disordered structure with two equally populated conformations of the amine fragment. A pair of weak C—HO intermolecular interactions between the CH2 and SO2 groups gives a one-dimensional supramolecular structure that propagates through translation along the a-axis direction

Forks, pincers, and triggers: the tools for nucleotide incorporation and translocation in multi-subunit RNA polymerases

The central role of RNA polymerase (RNAP) is to catalyze the processive synthesis of a growing RNA transcript. Recent structural and biophysical data have lead to a deeper understanding of the nucleotide addition cycle and insight into the structure-function relationships that govern transcription elongation. In this review, we discuss kinetic data on nucleotide incorporation in the context of crystal structures, which show RNAP in multiple conformations. We present a facilitated Brownian ratchet model of nucleotide incorporation, in which templated NTP binding to a non-catalytic site in the main channel promotes the conformational changes that lead to opening of the catalytic site and translocation

The Characteristics of Occupational Students in Postsecondary Education

This Brief presents a profile of the enrollment, demographic, and educational characteristics, and the educational goals, of community college students in occupational programs. It compares their features with those of community college students in academic programs and with baccalaureate students. This analysis further considers the distinct features of occupational students enrolled in certificate degree programs. The Brief stands alone as a comparative description of these students, but also provides important background material for CCRC’s companion Briefs on postsecondary occupational students, Educational Outcomes of Postsecondary Occupational Students and Who Benefits from Postsecondary Occupational Education? Findings from the 1980s and 1990s

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells

After exposure to DNA-damaging agents that block the progress of the replication fork, monoubiquitination of proliferating cell nuclear antigen (PCNA) mediates the switch from replicative to translesion synthesis DNA polymerases. We show that in human cells, PCNA is monoubiquitinated in response to methyl methanesulfonate and mitomycin C, as well as UV light, albeit with different kinetics, but not in response to bleomycin or camptothecin. Cyclobutane pyrimidine dimers are responsible for most of the PCNA ubiquitination events after UV-irradiation. Failure to ubiquitinate PCNA results in substantial sensitivity to UV and methyl methanesulfonate, but not to camptothecin or bleomycin. PCNA ubiquitination depends on Replication Protein A (RPA), but is independent of ATR-mediated checkpoint activation. After UV-irradiation, there is a temporal correlation between the disappearance of the deubiquitinating enzyme USP1 and the presence of PCNA ubiquitination, but this correlation was not found after chemical mutagen treatment. By using cells expressing photolyases, we are able to remove the UV lesions, and we show that PCNA ubiquitination persists for many hours after the damage has been removed. We present a model of translesion synthesis behind the replication fork to explain the persistence of ubiquitinated PCNA

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage – results from the Virtual International Stroke Trials Archive

Introduction: Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods: Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results: A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale ≤ 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3–3.6).  Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3–5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion: It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion: Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days

The ambivalent shadow of the pre-Wilsonian rise of international law

The generation of American international lawyers who founded the American Society of International Law in 1906 and nurtured the soil for what has been retrospectively called a “moralistic legalistic approach to international relations” remains little studied. A survey of the rise of international legal literature in the U.S. from the mid-19th century to the eve of the Great War serves as a backdrop to the examination of the boosting effect on international law of the Spanish American War in 1898. An examination of the Insular Cases before the US Supreme Court is then accompanied by the analysis of a number of influential factors behind the pre-war rise of international law in the U.S. The work concludes with an examination of the rise of natural law doctrines in international law during the interwar period and the critiques addressed.by the realist founders of the field of “international relations” to the “moralistic legalistic approach to international relation

Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of <i>Burkholderia pseudomallei</i>

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain, and conferred resistance to the antimicrobial sphingolipid D-erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection.We thank HL Ho & K Haynes (University of Exeter) for provision of strains and relevant vectors for yeast complementation studies. This work was supported by the Defence Science 26 and Technology Laboratory under contract DSTLX-1000060221 (WP1). CJM was funded by the EASTBIO Doctoral Training Partnership. The funders had no role in study design, data collection and analysis, or preparation of the manuscript