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The 2021-22 Professional Affairs Committee was charged to (1) Develop a resource guide for member institutions and faculty regarding payment for the practice-related activities of pharmacy faculty; (2) Nominate at least one person for an elected AACP or Council Office; and (3) Consider ways that AACP can improve its financial health. This report describes the methodology and content utilized for the development of an online resource guide for member institutions, faculty, and practice sites regarding the integration of clinical faculties' patient care services into patient care settings, including models for payment and value-based payment structures that can be utilized to support the practice-related activities of faculty. The committee offers a revision to a current association policy statement, a proposed policy statement as well as recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

Cell-cell adhesion is one the most fundamental mechanisms regulating collective cell migration during tissue development, homeostasis, and repair, allowing cell populations to self-organize and eventually form and maintain complex tissue shapes. Cells interact with each other via the formation of protrusions or filopodia and they adhere to other cells through binding of cell surface proteins. The resulting adhesive forces are then related to cell size and shape and, often, continuum models represent them by nonlocal attractive interactions. In this paper, we present a new continuum model of cell-cell adhesion which can be derived from a general nonlocal model in the limit of short-range interactions. This new model is local, resembling a system of thin-film type equations, with the various model parameters playing the role of surface tensions between different cell populations. Numerical simulations in one and two dimensions reveal that the local model maintains the diversity of cell sorting patterns observed both in experiments and in previously used nonlocal models. In addition, it also has the advantage of having explicit stationary solutions, which provides a direct link between the model parameters and the differential adhesion hypothesis.

Phloem transport of photoassimilates from leaves to non-photosynthetic organs, such as the root and shoot apices and reproductive organs, is crucial to plant growth and yield. For nearly 90 years, evidence has been generally consistent with the theory of a pressure-flow mechanism of phloem transport. Central to this hypothesis is the loading of osmolytes, principally sugars, into the phloem to generate the osmotic pressure that propels bulk flow. Here we used genetic and light manipulations to test whether sugar import into the phloem is required as the driving force for phloem sap flow. Using carbon-11 radiotracer, we show that a maize sucrose transporter1 (sut1) loss-of-function mutant has severely reduced export of carbon from photosynthetic leaves (only ~4% of the wild type level). Yet, the mutant remarkably maintains phloem pressure at ~100% and sap flow speeds at ~50–75% of those of wild type. Potassium (K+) abundance in the phloem was elevated in sut1 mutant leaves. Fluid dynamic modelling supports the conclusion that increased K+ loading compensated for decreased sucrose loading to maintain phloem pressure, and thereby maintained phloem transport via the pressure-flow mechanism. Furthermore, these results suggest that sap flow and transport of other phloem-mobile nutrients and signalling molecules could be regulated independently of sugar loading into the phloem, potentially influencing carbon–nutrient homoeostasis and the distribution of signalling molecules in plants encountering different environmental conditions.

Background: Effective interactions for elastic nucleon-nucleus scattering from first principles require the use of the same nucleon-nucleon interaction in the structure and reaction calculations, as well as a consistent treatment of the relevant operators at each order. Purpose: Previous work using these interactions has shown good agreement with available data. Here, we study the physical relevance of one of these operators, which involves the spin of the struck nucleon, and examine the interpretation of this quantity in a nuclear structure context. Methods: Using the framework of the spectator expansion and the underlying framework of the no-core shell model, we calculate and examine spin-projected, one-body momentum distributions required for effective nucleon-nucleus interactions in $J=0$ nuclear states. Results: The calculated spin-projected, one-body momentum distributions for $^4$He, $^6$He, and $^8$He display characteristic behavior based on the occupation of protons and neutrons in single particle levels, with more nucleons of one type yielding momentum distributions with larger values. Additionally, we find this quantity is strongly correlated to the magnetic moment of the $2^+$ excited state in the ground state rotational band for each nucleus considered. Conclusions: We find that spin-projected, one-body momentum distributions can probe the spin content of a $J=0$ wave function. This feature may allow future \textit{ab initio} nucleon-nucleus scattering studies to inform spin properties of the underlying nucleon-nucleon interactions. The observed correlation to the magnetic moment of excited states illustrates a previously unknown connection between reaction observables such as the analyzing power and structure observables like the magnetic moment., 13 pages, 7 figures, 1 table

No abstract available

The maize Carbohydrate partitioning defective1 mutant causes ectopic callose formation in sieve elements, which partially inhibits carbohydrate partitioning and is associated with hyperactive defense responses under insect pest exposure., Plants synthesize carbohydrates in photosynthetic tissues, with the majority of plants transporting sucrose to non-photosynthetic tissues to sustain growth and development. While the anatomical, biochemical, and physiological processes regulating sucrose long-distance transport are well characterized, little is known concerning the genes controlling whole-plant carbohydrate partitioning. To identify loci influencing carbon export from leaves, we screened mutagenized maize plants for phenotypes associated with reduced carbohydrate transport, including chlorosis and excessive starch and soluble sugars in leaves. Carbohydrate partitioning defective1 (Cpd1) was identified as a semi-dominant mutant exhibiting these phenotypes. Phloem transport experiments suggested that the hyperaccumulation of starch and soluble sugars in the Cpd1/+ mutant leaves was due to inhibited sucrose export. Interestingly, ectopic callose deposits were observed in the phloem of mutant leaves, and probably underlie the decreased transport. In addition to the carbohydrate hyperaccumulation phenotype, Cpd1/+ mutants overaccumulate benzoxazinoid defense compounds and exhibit increased tolerance when attacked by aphids. However, double mutant studies between Cpd1/+ and benzoxazinoid-less plants indicate that the ectopic callose and carbon hyperaccumulation are independent of benzoxazinoid production. Based on the formation of callose occlusions in the developing phloem, we hypothesize that the cpd1 gene functions early in phloem development, thereby impacting whole-plant carbohydrate partitioning.

The 2018-2019 Professional Affairs Committee examined the potential roles and needs of clinical educators (faculty and preceptors) in leading transformation in pharmacy practice. The committee was charged to (1) discuss the potential roles and responsibilities of faculty and preceptors leading transformation and enhanced patient care services in pharmacy practice; (2) describe factors, including clinician well-being and resilience, which may influence faculty and preceptor involvement in practice transformation and the enhancement of patient care services; and (3) recommend how the efforts and successes of faculty and preceptors involved in pharmacy practice transformation can be replicated and recognized as well as identify the types of continuing professional development (CPD) that should be available to enable the influence and implementation of patient care services. This report provides a framework for addressing the committee charges by examining the roles of advocacy, collaboration, continuing professional development, and clinician resilience and well-being. The committee provides a revision to a current AACP policy regarding continuing professional development as well as several recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

The synthesis, characterization and reactivity of several bi- and tridentate, N-ligated manganese carbonyl trifluoromethyl complexes are presented. These complexes exhibit elongated Mn&ndash, CCF3 bonds (versus Mn(CF3)(CO)5), suggesting a lability that could be utilized for the transfer or insertion of the CF3 functional group into organic substrates. Unlike their Mn&ndash, X congeners (X = Cl, Br), these Mn&ndash, CF3 complexes exhibit a preference for hard donor ancillary ligands, thus enabling the synthesis of 4 N-ligated Mn&ndash, CF3 complexes including a mixed-donor tridentate complex using an NNS Schiff base ([2-(methylthio)-N-(1-(pyridin-2-yl)ethylidene)aniline]). Although we have not yet identified efficient CF3 transfer reactions, fluoride abstraction from the Mn&ndash, CF3 complexes using trimethylsilyl triflate affords the first stable Mn fluorocarbenes as evidenced by 19F NMR spectroscopy.

We discuss the role of clustering on monopole, dipole, and quadrupole excitations in nuclei in the framework of the ab initio symmetry-adapted no-core shell model (SA-NCSM). The SA-NCSM starts from nucleon-nucleon potentials and, by exploring symmetries known to dominate the nuclear dynamics, can reach nuclei up through the calcium region by accommodating ultra-large model spaces critical to descriptions of clustering and collectivity. The results are based on calculations of electromagnetic sum rules and discretized responses using the Lanczos algorithm, that can be used to determine response functions, and for 4He are benchmarked against exact solutions of the hyperspherical harmonics method. In particular, we focus on He, Be, and O isotopes, including giant resonances and monopole sum rules., 6 pages, 4 figures, Proceedings of the Fourth International Workshop on State of the Art in Nuclear Cluster Physics, Galveston, TX, USA, May 13-18, 2018

International audience; Catalyzed hydrolysis of sodium borohydride (SBH) has demonstrated promise for generation of a pure hydrogen stream for use with fuel cells. In designing an improved continuous hydrogen generator that uses the substantial heat released in the hydrolysis reaction to more effectively separate the sodium borate by-product, we sought a robust base-metal catalyst that could tolerate the exothermic reaction under flow conditions. Working under base-free conditions in ethanol solvent we identified reduced nickel and iron-containing particles supported on layered double hydroxides (LDHs) as robust catalysts. Catalytic activity was enhanced further using high surface area hierarchical supports prepared using the ‘inverse opal’ method. In particular, macroporous NiMgAl and FeMgAl LDHs produced 0.4 and 1.0 mol of hydrogen per minute per mole of active metal of the supported catalyst in aqueous ethanol solvent.

We present a detailed discussion of the structure of the low-lying positive-parity energy spectrum of $^{12}$C from a no-core shell-model perspective. The approach utilizes a fraction of the usual shell-model space and extends its multi-shell reach via the symmetry-based no-core symplectic shell model (NCSpM) with a simple, physically-informed effective interaction. We focus on the ground-state rotational band, the Hoyle state and its $2^+$ and $4^+$ excitations, as well as the giant monopole $0^+$ resonance, which is a vibrational breathing mode of the ground state. This, in turn, allows us to address the open question about the structure of the Hoyle state and its rotational band. In particular, we find that the Hoyle state is best described through deformed prolate collective modes rather than vibrational modes, while we show that the higher-lying giant monopole $0^+$ resonance resembles the oblate deformation of the $^{12}$C ground state. In addition, we identify the giant monopole $0^+$ and quadrupole $2^+$ resonances of selected light and intermediate-mass nuclei, along with other observables of $^{12}$C, including matter rms radii, electric quadrupole moments, as well as $E2$ and $E0$ transition rates., 12 pages, 5 figures; to be submitted to Phys. Rev. C

Background and Charges According to the Bylaws of the American Association of Colleges of Pharmacy (AACP), the Professional Affairs Committee is to study issues associated with the professional practice of pharmacy as they relate to pharmaceutical education, and to establish and improve working relationships with other organizations in the field of health affairs. The Committee is encouraged to address related agenda items relevant to its Bylaws charge and to identify issues for consideration by subsequent committees, task forces, commissions, or other groups. President Patricia Chase established the themes of Access, Affordability and Accountability for the 20142015 standing committees. (1) The 2014-2015 Professional Affairs Committee (PAC) was charged with examining the contributions of experiential education to the development of "practice-ready" pharmacy school graduates who are educated and trained for current and future practice. Experiential education, comprised of Introductory Pharmacy Practice Experiences (IPPEs) and Advanced Pharmacy Practice Experiences (APPEs) and represents up to 30% of the pharmacy school curricula, are the entry points for student pharmacists into pharmacy and patient care practice. Specifically, the 2014-2015 Professional Affairs Committee is charged to: (1) Describe the elements that should be present for access to exemplary experiential sites; (2) Identify how student pharmacist readiness for and contributions to experiential education should be considered to illustrate the value to experiential practice sites; and (3) Recommend strategies to the academy to demonstrate its accountability that graduates are "practiceready." Members of the 2015 PAC include individuals representing multiple disciplines across various colleges and schools of pharmacy, as well as professional staff representation from the American Pharmacists Association (APhA), the American Society of Health-Systems Pharmacy (ASHP) and the National Association of Chain Drug Stores (NACDS). The committee began its work by reviewing pertinent background information and resource materials and participating in a conference call to develop an initial strategy for addressing committee charges. The committee members met for a day and a half in Crystal City, Virginia on October 27-28, 2014 to discuss the various facets related to the committee charges, as well as to develop a process and strategies for addressing the charges. Following the process development and delegation of assignments related to the committee charges, the PAC communicated via electronic communications as well as through personal exchanges via telephone and email. In developing the strategy to address their charges, the PAC considered numerous factors that contribute to the current needs, future needs and contributions of "practice-ready" pharmacists. Examination of pertinent issues relevant to both experiential education and pharmacy practice were explored from the perspectives of access, value (the PAC examined the value of experiential education as an applicable aspect of affordability) and accountability. The continued evolution of the healthcare environment, including implications for pharmacists and team-based care from the Patient Protection and Affordable Care Act (PPACA), (2) the expanding role of pharmacists in a dynamically-changing health care system, (3, 4 5 6) and emerging interprofessional, collaborative practice models, such as Patient Centered Medical Homes (4, 7 8) and Affordable Care Organizations, (9) were discussed. The Accreditation Council for Pharmacy Education (ACPE) release of Draft Standards 2016 (10) and the Guidance Document to Draft Standards 2016, (11) which was finalized February 2015, (12,13) are other important aspects that should forecast the content and impact of experiential education. The recently revised Joint Commission of Pharmacy Practitioners (JCPP) Vision for Pharmacists' Practice (14) and the recently approved Pharmacist Patient Care Model, (15) which describes a consistent process of care in the delivery of patient care services by pharmacists, are additional avenues that must be included in all aspects of pharmacy education. …

This is a protocol for a Cochrane Review (overview). The objectives are as follows: This overview intends to: a) summarise the existing evidence on interventions that aim to increase PA; b) explore whether any effects of the intervention are different within and between populations, and whether these differences form an equity gradient such as an effect that differs according the advantage/disadvantage (e.g. low income and ethnic minorities); c) highlight gaps in the present evidence base that may warrant a Cochrane systematic review to be completed; and c) identify 'up to date' Cochrane reviews. .

BACKGROUND AND CHARGES According to the Bylaws of the American Association of Colleges of Pharmacy (AACP), the Professional Affairs Committee is to study issues associated with the professional practice as they relate to pharmaceutical education, and to establish and improve working relationships with all other organizations in the field of health affairs. The Committee is also encouraged to address related agenda items relevant to its Bylaws charge and to identify issues for consideration by subsequent committees, task forces, commissions, or other groups. President Peggy Piascik established the theme for 2013-2014 as "the relentless pursuit of excellence." (1) President Piascik acknowledges that academic pharmacy is at the crossroads of many areas of change, including the continuing evolution of pharmacy as a profession, how health care is delivered in America and rapid changes in higher education. As the roles of pharmacists continue to change, pharmacy technician roles must also evolve, necessitating changes in pharmacy technician training and education. Specifically, the 2013-2014 Professional Affairs Committee is charged to: (1) Describe the elements that should be present in a quality technician education/ training program; (2) Identify potential role(s) of pharmacy academic institutions and pharmacy faculty in the education, training, and certification of pharmacy technicians; and (3) Recommend strategies to develop collaborations/relationships between schools/colleges of pharmacy and pharmacy technician education/training programs to advance pharmacy practice in the evolving health care system. Members of the Professional Affairs Committee (PAC) include faculty representing multiple disciplines from various schools/colleges of pharmacy, a coordinator from an American Society of Health-Systems Pharmacists (ASHP) accredited pharmacy technician education/ training program as well as professional staff from ASHP, the Pharmacy Technician Certification Board (PTCB) and the Pharmacy Technician Educators Council (PTEC). Prior to an in-person meeting of the committee, pertinent background information and resource materials were distributed, and a conference call was held to develop a strategy for addressing committee charges. The committee members met for a day and a half in Crystal City, Virginia on October 28-29, 2013, to discuss the various facets related to this issue as well as to develop a process and strategies for addressing the charges. Following the process development and delegation of assignments related to the committee charges, the PAC communicated via electronic communications, as well as through personal exchanges via telephone and email. The result is the following report, which discusses the elements and importance of a well educated and trained pharmacy technician workforce and also provides information on current collaborations between schools/ colleges of pharmacy and pharmacy technician education/ training programs. Disseminating the purpose and framework behind these collaborations may assist members of the academy to identify potential strategies and roles for schools/colleges of pharmacy in the education, training and certification of pharmacy technicians. In addition, these examples may help to guide the development of these collaborations at other member institutions. Pharmacy technicians are viable members of the health care sector and are necessary to the pharmacy profession for pharmacists to satisfy the Joint Commissioners of Pharmacy Practice (JCPP)Vision for Pharmacy Practice: (2) Patients achieve optimal health and medication outcomes with pharmacists as essential and accountable providers within patient-centered, team-based health care. Charge 1: Describe the elements that should be present in a quality technician education/training program A pharmacy technician is an individual who, under the supervision of a licensed pharmacist, assists in pharmacy activities that do not require the professional judgment of a pharmacist. …

Peroxisome proliferator activated receptor-gamma (PPAR gamma) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR gamma ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR gamma. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR gamma discrimination of various naturally occurring fatty acid derivatives.

Objective: To determine any differences in career paths and career attributes of pharmacists who have completed a PGY1 community pharmacy residency program (CPRP) as compared to those that have not completed a PGY1 CPRP. Methods: A web-based survey evaluating various aspects of community pharmacists' careers was distributed to 274 CPRP graduates in addition to a random sample of 7,376 community pharmacists. The survey contained 32 questions evaluating various career attributes. Questions that assessed level of agreement were on a 6-point Likert-type Scale (1=strongly disagree; 6=strongly agree). Results: A total of 353 participants completed the survey, with 224 indicating that they had not completed a CPRP. Pharmacists who completed a CPRP responded that they spend significantly more time on patient care services, teaching, and research, and spend less time dispensing medications compared to those that have not completed a CPRP. Compared to those that did not complete a CPRP, CPRP graduates were less likely to agree that current level of workload negatively impacts job performance, motivation to work, job satisfaction, mental/emotional health, and physical health. Conclusion: Pharmacists completing a CPRP noted significant differences in their current employment and job responsibilities. Additional expansion and education regarding the importance of CPRPs should be considered. Type: Original Research

The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the primary endogenous substrate for fatty acid nitration in vitro and in vivo, yielding up to 105 greater extent of nitration products as compared with bis-allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification. Nitroalkene derivatives of CLA and their metabolites are detected in the plasma of healthy humans and are increased in tissues undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite supplementation in rodents elevates NO2-CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic epithelium. These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms. Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Baker, Paul R. S.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Salvatore, Sonia Rosana. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Shores, Darla. University of Pittsburgh; Estados Unidos Fil: Khoo, Nicholas K. H.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Koenitzer, Jeffrey R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Vitturi, Dario A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Woodcock, Steven R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Golin-Bisello, Franca. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Cole, Marsha P.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Watkins, Simon. University of Pittsburgh; Estados Unidos Fil: St. Croix, Claudette. University of Pittsburgh; Estados Unidos Fil: Batthyany, Carlos I.. Instituto Pasteur; Uruguay. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Freeman, Bruce A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos Fil: Schopfer, Francisco J.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unidos

12/15-Lipoxygenase (LOX) mediates immune-regulatory activities not accounted for by its known free acid eicosanoids, suggesting that additional lipids may be generated by activated cells. To characterize novel LOX-derived lipids, a lipidomic approach was utilized. Ionophore-activated interleukin-4-treated human peripheral monocytes generated up to 10-fold more esterified 15-hydroxyeicosatetraenoic acid (15-HETE) than free in a phosphatidylinositol 3-kinase- and protein kinase C-sensitive manner. Precursor scanning electrospray ionization/tandem spectroscopy for m/z 319 (HETE, [M-H](-)) showed 4 ions at m/z 738, 764, 766, and 782 that were identified using tandem spectroscopy and MS3 as specific diacyl and plasmalogen 15-HETE phosphatidylethanolamines. Using H (18)(2)O water, the compounds were shown to form by direct oxidation of endogenous phosphatidylethanolamine (PE) by 15-LOX, with PE being the preferred phospholipid pool containing 15-HETE. Similarly, human platelets generated 4 analogous PE lipids that contained 12-HETE and increased significantly in response to ionophore, collagen, or convulxin. These products were retained in the cells, in contrast to free acids, which are primarily secreted. Precursor scanning of platelet extracts for the major platelet-derived prostanoid, thromboxane B2 (m/z 369.2), did not reveal PE esters, indicating that this modification is restricted to the LOX pathway. In summary, we show formation of PE-esterified HETEs in immune cells that may contribute to LOX signaling in inflammation.

Nitrated fatty acids (NO(2)-FA) have been identified as endogenous anti-inflammatory signalling mediators generated by oxidative inflammatory reactions. Herein the in vivo generation of nitro-oleic acid (OA-NO(2)) and nitro-linoleic acid (LNO(2)) was measured in a murine model of myocardial ischaemia and reperfusion (I/R) and the effect of exogenous administration of OA-NO(2) on I/R injury was evaluated.In C57/BL6 mice subjected to 30 min of coronary artery ligation, endogenous OA-NO(2) and LNO(2) formation was observed after 30 min of reperfusion, whereas no NO(2)-FA were detected in sham-operated mice and mice with myocardial infarction without reperfusion. Exogenous administration of 20 nmol/g body weight OA-NO(2) during the ischaemic episode induced profound protection against I/R injury with a 46% reduction in infarct size (normalized to area at risk) and a marked preservation of left ventricular function as assessed by transthoracic echocardiography, compared with vehicle-treated mice. Administration of OA-NO(2) inhibited activation of the p65 subunit of nuclear factor kappaB (NFkappaB) in I/R tissue. Experiments using the NFkappaB inhibitor pyrrolidinedithiocarbamate also support that protection lent by OA-NO(2) was in part mediated by inhibition of NFkappaB. OA-NO(2) inhibition of NFkappaB activation was accompanied by suppression of downstream intercellular adhesion molecule 1 and monocyte chemotactic protein 1 expression, neutrophil infiltration, and myocyte apoptosis.This study reveals the de novo generation of fatty acid nitration products in vivo and reveals the anti-inflammatory and potential therapeutic actions of OA-NO(2) in myocardial I/R injury.

Atmospheric deposition of anthropogenic Hg has led to increased Hg concentrations in many ecosystems. Modeling is an effective method for predicting the complex dynamics of Hg transport in watersheds. Such models require accurate concentrations of water column methylmercury, CH3Hg+, for input parameters, yet these concentrations are very difficult to measure precisely because they are so low. We developed a method for aqueous CH3Hg+ quantification in Lake Champlain, VT, where ambient CH3Hg+ concentrations are < 0.04 ng L(-1). The analysis utilized species-specific isotope dilution, purge and trap gas chromatography inductively coupled plasma mass spectrometry and provided instrument detection limits of about 0.3 fM (0.06 pg L(-1)) and method detection limits of 15 fM (0.003 ng L(-1)) for CH3Hg+, which are among the lowest reported. Artifactual methylation of inorganic Hg(2+) was shown to be minor, and the precision of the isotope dilution method was generally

Nitrated derivatives of fatty acids (NO2-FA) are pluripotent cell-signaling mediators that display anti-inflammatory properties. Current understanding of NO2-FA signal transduction lacks insight into how or if NO2-FA are modified or metabolized upon formation or administration in vivo. Here the disposition and metabolism of nitro-9-cis-octadecenoic (18:1-NO2) acid was investigated in plasma and liver after intravenous injection in mice. High performance liquid chromatography-tandem mass spectrometry analysis showed that no 18:1-NO2 or metabolites were detected under basal conditions, whereas administered 18:1-NO2 is rapidly adducted to plasma thiol-containing proteins and glutathione. NO2-FA are also metabolized via β-oxidation, with high performance liquid chromatography-tandem mass spectrometry analysis of liver lipid extracts of treated mice revealing nitro-7-cis-hexadecenoic acid, nitro-5-cis-tetradecenoic acid, and nitro-3-cis-dodecenoic acid and corresponding coenzyme A derivatives of 18:1-NO2 as metabolites. Additionally, a significant proportion of 18:1-NO2 and its metabolites are converted to nitroalkane derivatives by saturation of the double bond, and to a lesser extent are desaturated to diene derivatives. There was no evidence of the formation of nitrohydroxyl or conjugated ketone derivatives in organs of interest, metabolites expected upon 18:1-NO2 hydration or nitric oxide (•NO) release. Plasma samples from treated mice had significant extents of protein-adducted 18:1-NO2 detected by exchange to added β-mercaptoethanol. This, coupled with the observation of 18:1-NO2 release from glutathione-18:1-NO2 adducts, supports that reversible and exchangeable NO2-FA-thiol adducts occur under biological conditions. After administration of [3H]18:1-NO2, 64% of net radiolabel was recovered 90 min later in plasma (0.2%), liver (18%), kidney (2%), adipose tissue (2%), muscle (31%), urine (6%), and other tissue compartments, and may include metabolites not yet identified. In aggregate, these findings show that electrophilic FA nitroalkene derivatives (a) acquire an extended half-life by undergoing reversible and exchangeable electrophilic reactions with nucleophilic targets and (b) are metabolized predominantly via saturation of the double bond and β-oxidation reactions that terminate at the site of acyl-chain nitration.

In vivo and in vitro studies revealed that nitroalkenes serve as protective mediators in the lung by inducing the cytoprotective enzyme heme oxygenase-1 (HO-1). Nitrolinoleic acid (LNO2) increased HO-1 mRNA, protein, and activity in cultured pulmonary epithelial cells treated with 5 to 50 microM LNO2 and in lungs of rats injected intraperitoneally with 2.6 mg/kg LNO2 twice daily for 20 days. Western blotting revealed that HO-1 protein increased significantly within 4 h of in vitro LNO2 addition and was preceded by an increase in HO-1 mRNA, consistent with transcriptional regulation of HO-1 expression by LNO2. LNO2 also dephosphorylated and activated eukaryotic initiation factor 2alpha, a key translational regulatory protein, indicating that increased translation may also contribute to LNO2-induced increases in HO-1. Exposure of cells to LNO2 activated ERK and JNK, as evidenced by increased phosphorylation. Downstream targets of ERK and JNK, Elk-1 and c-Jun, respectively, were also phosphorylated in response to LNO2 exposure. However, inhibitor studies revealed that only the ERK pathway is necessary for the LNO2-mediated increase in HO-1 mRNA and protein. These data reveal that LNO2 induces pulmonary epithelial HO-1 expression and downstream adaptive responses to inflammation via both transcriptional and translational regulatory mechanisms.

Nitration products of unsaturated fatty acids are formed via NO-dependent oxidative reactions and appear to be a new class of endogenous antiinflammatory mediators. Nitroalkene derivatives of nitrated linoleic acid (LNO(2)) and nitrated oleic acid (OA-NO(2)) alleviate inflammatory responses in macrophages, but the underlying mechanisms remain to be fully defined. Herein we report that LNO(2) and OA-NO(2) suppress proinflammatory signal transducer and activator of transcription (STAT) signaling in macrophages. In RAW264.7 cells, a murine macrophage cell line, LNO(2) and OA-NO(2) inhibited the lipopolysaccharide (LPS)-induced STAT1 phosphorylation and the STAT1-dependent transcriptional activity, thereby suppressing expression of its target gene such as iNOS and MCP-1. The nitroalkene-mediated inhibition of STAT1 activity was not affected by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (a NO scavenger), GW9662 (a peroxisome proliferator-activated receptor-gamma-specific antagonist) or glutathione (an antioxidant), suggesting an underlying mechanism independent of NO, peroxisome proliferator-activated receptor-gamma, or thio-nitralkylation. In contrast, LNO(2) or OA-NO(2) alone up-regulated both mRNA and protein levels of MAPK phosphatase 1 (MKP-1) and strongly augmented the LPS-induced MKP-1 protein expression. Knockdown of MKP-1 by MKP-1 small interfering RNA enhanced the LPS-induced STAT1 phosphorylation, suggesting that MKP-1 acts as a negative regulator for LPS-induced STAT signaling. In addition, the nitroalkene-mediated inhibitory effects on STAT1 phosphorylation, iNOS expression, and MCP-1 secretion were also largely attenuated by the MKP-1 small interfering RNA approach. Taken together, our data demonstrate that nitroalkenes inhibit proinflammatory STAT signaling through inducting MKP-1 in macrophages.

The Archaeological Journal, 35, 339-352

Enzymatic and non-enzymatic oxygenations of unsaturated fatty acids yield a broad family of autocrine and paracrine cell signaling mediators. Soon after nitric oxide (•NO) was described as a mediator of vascular relaxation, it was appreciated that this lipophilic free radical species strongly influences fatty acid oxygenation at multiple levels. For example, •NO terminates peroxyl radical-induced chain propagation reactions of lipid peroxidation at rate constants >103 faster than tocopherols (1, 2). Also, the gene expression and catalytic activity of enzymes responsible for prostaglandin, thromboxane, and leukotriene biosynthesis are regulated by •NO (3–5). Another convergence of lipid and •NO signaling is manifested in the form of nitrated unsaturated fatty acids. Fatty acid nitration is induced by •NO-derived species reacting via multiple mechanisms that share a proclivity for the homolytic addition of nitrogen dioxide (•NO2) to the double bond, yielding an array of regio- and stereoisomers (6). NO2-FAs3 display both cGMP-independent and receptor-dependent signaling actions as well as robust electrophilic reactivity, facilitating reversible adduction by nucleophilic targets (e.g. protein Cys and His residues) (7, 8). This reactivity in turn supports the post-translational modification of protein distribution and function. Both NO2-FAs and their protein or GSH adduction products are detected clinically in healthy individuals, become elevated postprandially, and are formed by oxidative inflammatory reactions (8–12). Current data indicate that NO2-FAs signal via predominantly •NO-independent mechanisms, acting via electrophilic and receptor-mediated reactions to exert adaptive and anti-inflammatory cell responses.

Nearfield models for [math] and the Hughes plane of order [math] , based on the well-known field-theoretic model of [math] , are described. By way of the correspondences between these models, certain unitals, ovals, and a Baer subplane are easily described in the Hughes plane. Moreover, a partition of the Hughes plane into maximal [math] -arcs is presented.