Structural Correspondence of Solution, Liquid Crystal, and Crystalline Phases of the Chromonic Mesogen Sunset Yellow

The azo dye, sunset yellow, is a prototypical, chromonic liquid crystal in which assembly in aqueous solution at high volume fraction leads to lyotropic mesophases with a “package of properties distinct in almost every aspect” (Lydon, J. Curr. Opin. Colloid Interface Sci. 2004, 8, 480). In particular, the isotropic to nematic transition in such phases, the consequence of stacking of dye molecules in chains, is difficult to bring into correspondence with athermal theories for rigid rods as well as modifications that consider chain interactions with one another. Chromonic mesogens, small molecules that stack to form lyotropic liquid crystals, prompt structural questions that have yet to be answered; a full understanding of structure should inform colligative properties. Herein, the single crystal structure of a guanidinium salt of the sunset yellow dianion, a known chromonic mesogen, is reported. The compound crystallizes as a dihydrate, tetrahydrofuran solvate in the orthorhombic space group Pnna, with a = 6.8426(5) Å, b = 20.048(1) Å, c = 21.466(2) Å. The sunset yellow molecules, point group approximately Cs, are disordered about a crystallographic diad axis.The structure is informative because pairwise interactions in the disordered crystal structure show a remarkable correspondence with the stereochemistry of sunset yellow molecules in solution and in the liquid crystal phase. The solution structure is here simulated by the combination of molecular dynamics,metadynamics, and quantum chemical computations. The comparable disorder in the fluid and solid states suggests the possibility that stacked aggregates adhere to growing crystals intact. Computations were used to evaluate proposals that stacking faults and branching points lower the X-ray correlation lengths while preserving extended structures. Evidence is found forstacking faults but not branches. The solution stereochemistry and stereodynamics has implications for the geometry of long rods, for which understanding is a prerequisite for reckoning properties of vexing chromonic mesophases

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases

OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. APPROACH AND RESULTS: Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13dJinx mice). CONCLUSIONS: Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide-sensitive fusion protein attachment receptor/Munc13-4-dependent vesicular-plasma membrane fusion

A route to high surface area, porosity and inclusion of large molecules in crystals

One of the outstanding challenges in the field of porous materials is the design and synthesis of chemical structures with exceptionally high surface areas(1). Such materials are of critical importance to many applications involving catalysis, separation and gas storage. The claim for the highest surface area of a disordered structure is for carbon, at 2,030 m(2) g(-1) (ref. 2). Until recently, the largest surface area of an ordered structure was that of zeolite Y, recorded at 904 m(2) g(-1) (ref. 3). But with the introduction of metal-organic framework materials, this has been exceeded, with values up to 3,000 m(2) g(-1) (refs 4-7). Despite this, no method of determining the upper limit in surface area for a material has yet been found. Here we present a general strategy that has allowed us to realize a structure having by far the highest surface area reported to date. We report the design, synthesis and properties of crystalline Zn4O(1,3,5-benzenetribenzoate)(2), a new metal-organic framework with a surface area estimated at 4,500 m(2) g(-1). This framework, which we name MOF-177, combines this exceptional level of surface area with an ordered structure that has extra-large pores capable of binding polycyclic organic guest molecules-attributes not previously combined in one material.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62609/1/nature02311.pd

Impact of tunable oligophosphonates on barium sulfate crystallization

Calixarenes can be used as well-defined scaffolds for investigating structure–activity relationships of additives and their impact on crystallization. In this work, we present the crystal growth modification of barium sulfate by p-phosphonic acid calix[n]arenes that vary in size (n = 4, 5, 6, and 8) and thus vary in the size of the internal cavity for the same functionality in the upper rim. The tetrameric, hexameric, and octameric macrocycles induce nanoparticle formation with clear superstructure. In the case of the hexameric calix[6]arene, the initial mesocrystalline superstructure fuses over time to form almost hollow spheres, while the mesocrystals formed in the presence of the tetramer and octamer are stable over an extended period. The pentameric calix[5]arene forms more disordered aggregates of single crystals. Thermogravimetric data shows that a significant proportion of the mass of the barium sulfate-containing solid is the macrocycle, regardless of the choice of macrocycle

Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation

Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria

Views on and experiences of electronic cigarettes: a qualitative study of women who are pregnant or have recently given birth.

Background Electronic cigarettes (ECs) are increasingly used for reducing or stopping smoking, with some studies showing positive outcomes. However, little is known about views on ECs during pregnancy or postpartum and previous studies have nearly all been conducted in the US and have methodological limitations, such as not distinguishing between smokers and ex/non-smokers. A greater understanding of this topic will help to inform both clinicians and EC interventions. We elicited views and experiences of ECs among UK pregnant or recently pregnant women. Methods We conducted semi-structured telephone interviews, using topic guides, with pregnant or recently pregnant women, who were current or recent ex-smokers. To ensure broad views of ECs were obtained, recruitment was from several geographical locations and via various avenues of recruitment. This included stop smoking services, antenatal and health visitor clinics, a pregnancy website and an informal network. Participants were 15 pregnant and 15 postpartum women, including nine current EC users, 11 ex-users, and 10 never-users. Five women who were interviewed in pregnancy were later interviewed in postpartum to explore if their views had changed. Audio data was transcribed verbatim and framework analysis was applied. Results Five main themes emerged: motivations for use (e.g., for stopping or reducing smoking), social stigma (e.g., avoiding use in public, preferring ‘discrete’ NRT), using the EC (e.g., mostly used at home); consumer aspects (e.g., limited advice available), and harm perceptions (e.g., viewed as less harmful than smoking; concerns about safety and addiction). Conclusions ECs were viewed positively by some pregnant and postpartum women and seen as less harmful than smoking and useful as aids for reducing and stopping smoking. However, due to perceived social stigma, some women feel uncomfortable using ECs in public, especially during pregnancy, and had concerns about safety and nicotine dependence. Health professionals and designers of EC interventions need to provide women with up-to-date and consistent information and advice about safety and dependence, as well as considering the influence of social stigma

In vitro mycorrhization of micropropagated plants: studies on Castanea sativa Mill.

In vitro mycorrhization can be made by several axenic and nonaxenic techniques but criticism exists about their artificiality and inability to reproduce under natural conditions. However, artificial mycorrhization under controlled conditions can provide important information about the physiology of symbiosis. Micropropagated Castanea sativa plants were inoculated with the mycorrhizal fungus Pisolithus tinctorius after in vitro rooting. The mycorrhizal process was monitored at regular intervals in order to evaluate the mantle and hartig net formation, and the growth rates of mycorrhizal and nonmycorrhizal plants. Plant roots show fungal hyphae adhesion at the surface after 24 hours of mycorrhizal induction. After 20 days a mantle can be observed and a hartig net is forming although the morphology of the epidermal cells remains unaltered. At 30 days of root–fungus contact the hartig net is well developed and the epidermal cells are already enlarged. After 50 days of mycorrhizal induction, growth was higher for mycorrhizal plants than for nonmycorrhizal ones. The length of the major roots was lower in mycorrhizal plants after 40 days. Fresh and dry weights were higher in mycorrhizal plants after 30 days. The growth rates of chestnut mycorrhizal plants are in agreement with the morphological development of the mycorrhizal structures observed at each mycorrhizal time. The assessment of symbiotic establishment takes into account the formation of a mantle and a hartig net that were already developed at 30 days, when differences between fresh and dry weights of mycorrhizal and nonmycorrhizal plants can be quantified. In vitro conditions, mycorrhization influences plant physiology after 20 days of root–fungus contact, namely in terms of growth rates. Fresh and dry weights, heights, stem diameter and growth rates increased while major root growth rate decreased in mycorrhizal plants.Springe