Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.The authors thank the Niagara University Academic Center for Integrated Science and the Rochester Academy of Science for their financial support. MLI would like to thank the Barbara S. Zimmer Memorial Research Award for financial aid. MLC gratefully acknowledges generous allocations of supercomputing time from the Australian National Computational Infrastructure, support from the Australian Research Council under its Centers of Excellence program, and an ARC Future Fellowship. RP would also like to thank Western New England University, College of Pharmacy for generous financial support

Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform

Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants

Scrapie-Specific Pathology of Sheep Lymphoid Tissues

Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrPd within endosomes and lysosomes. In addition, TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrPd is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrPd/cell membrane interactions occur in different cell types

A public health response to the methamphetamine epidemic: the implementation of contingency management to treat methamphetamine dependence

BACKGROUND: In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM) field program called the Positive Reinforcement Opportunity Project (PROP). METHODS: Methamphetamine-using men who have sex with men (MSM) in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time), impact (clinical response to treatment and cost-effectiveness as cost per patient treated). RESULTS: Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42%) methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD =$165) in vouchers or 35.1% of the maximum possible ($453) was provided for these participants. The average cost per participant of the 143 treated was$800. CONCLUSION: Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs like PROP could address the increasing need for acceptable, feasible and cost-effective methamphetamine treatment in this group with exceptionally high rates of HIV-infection

Spin chirality on a two-dimensional frustrated lattice

The collective behavior of interacting magnetic moments can be strongly influenced by the topology of the underlying lattice. In geometrically frustrated spin systems, interesting chiral correlations may develop that are related to the spin arrangement on triangular plaquettes. We report a study of the spin chirality on a two-dimensional geometrically frustrated lattice. Our new chemical synthesis methods allow us to produce large single crystal samples of KFe3(OH)6(SO4)2, an ideal Kagome lattice antiferromagnet. Combined thermodynamic and neutron scattering measurements reveal that the phase transition to the ordered ground-state is unusual. At low temperatures, application of a magnetic field induces a transition between states with different non-trivial spin-textures.Comment: 7 pages, 4 figure

Pembrolizumab Enhances the Anti-Leukemia Activity of Antigen Specific Cytotoxic T Lymphocytes

https://openworks.mdanderson.org/sumexp23/1074/thumbnail.jp

Cacao seeds are a "Super Fruit": A comparative analysis of various fruit powders and products

<p>Abstract</p> <p>Background</p> <p>Numerous popular media sources have developed lists of "Super Foods" and, more recently, "Super Fruits". Such distinctions often are based on the antioxidant capacity and content of naturally occurring compounds such as polyphenols within those whole fruits or juices of the fruit which may be linked to potential health benefits. Cocoa powder and chocolate are made from an extract of the seeds of the fruit of <it>the Theobroma cacao </it>tree. In this study, we compared cocoa powder and cocoa products to powders and juices derived from fruits commonly considered "Super Fruits".</p> <p>Results</p> <p>Various fruit powders and retail fruit products were obtained and analyzed for antioxidant capacity (ORAC (μM TE/g)), total polyphenol content (TP (mg/g)), and total flavanol content (TF (mg/g)). Among the various powders that were tested, cocoa powder was the most concentrated source of ORAC and TF. Similarly, dark chocolate was a significantly more concentrated source of ORAC and TF than the fruit juices.</p> <p>Conclusions</p> <p>Cocoa powder and dark chocolate had equivalent or significantly greater ORAC, TP, and TF values compared to the other fruit powders and juices tested, respectively. Cacao seeds thus provide nutritive value beyond that derived from their macronutrient composition and appear to meet the popular media's definition of a "Super Fruit".</p

Circulating Angiopoietin-2 as a Biomarker in ANCA-Associated Vasculitis

The endothelial-specific Angiopoietin-Tie2 ligand-receptor system is an important regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to Tie2 receptor renders the endothelial barrier responsive to pro-inflammatory cytokines. We previously showed that circulating Ang-2 correlated with disease severity in a small cohort of critically ill patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The current study reassessed Ang-2 as a biomarker of disease activity and relapse in AAV. Circulating Ang-2 was measured in 162 patients with severe AAV (BVAS/WG≥3, with or without glomerulonephritis) in a clinical trial. Ang-2 levels during active AAV were compared to levels in the same patients during remission (BVAS/WG = 0). Levels in clinical subsets of AAV were compared, and association with future disease course was assessed. Ang-2 levels were elevated in severe disease (median 3.0 ng/ml, interquartile range 1.9–4.4) compared to healthy controls (1.2, 0.9–1.5). However, they did not reliably decline with successful treatment (median 2.6 ng/ml, interquartile range 1.9–3.8, median change −0.1). Ang-2 correlated weakly with BVAS/WG score (r = 0.17), moderately with markers of systemic inflammation (r = 0.25–0.41), and inversely with renal function (r = −0.36). Levels were higher in patients with glomerulonephritis, but levels adjusted for renal dysfunction were no different in patients with or without glomerulonephritis. Levels were higher in patients with newly diagnosed AAV and lower in patients in whom treatment had recently been started. Ang-2 levels during active disease did not predict response to treatment, and Ang-2 levels in remission did not predict time to flare. Thus, Ang-2 appears to have limited practical value in AAV as a biomarker of disease activity at time of measurement or for predicting future activity

Coexistence of Several Novel Hantaviruses in Rodents Indigenous to North America

AbstractThree genetically distinct members of the Hantavirus genus have been detected in Nevada rodents by RT-PCR and nucleotide sequence analysis. These include Sin Nombre (SN), El Moro Canyon (ELMC), and Prospect Hill (PH)-like viruses which are primarily associated with Peromyscus maniculatus (deer mouse), Reithrodontomys megalotis (western harvest mouse), and Microtus spp. (voles), respectively. Although this region of the United States is ecologically diverse, rodents infected with different hantaviruses appear to coexist in several different geographical and ecological zones. In two widely separated states, Nevada and North Dakota, PH-like viruses are present in three different species of vole. In addition, ELMC-like virus has been detected in both R. megalotis and M. montanus (mountain vole). SN virus is a cause of hantavirus pulmonary syndrome throughout much of the United States. SN virus RNA is found in 12.5% of P. maniculatus in Nevada and eastern California. Two lineages of SN virus coexist in this region and differ from SN viruses originally found in infected rodents in New Mexico, Arizona, and Colorado. These data show the complexity of hantavirus maintenance in rodents. Distinct hantaviruses or virus lineages can coexist either in different or the same rodent species and in either different or tile same geographic or ecological zones