Glucose hydrochar consists of linked phenol, furan, arene, alkyl, and ketone structures revealed by advanced solid-state nuclear magnetic resonance.

The molecular structure of hydrochars produced from 13C-enriched glucose under various conditions has been elucidated based on advanced one- and two-dimensional (2D) 1H-13C and 13C-13C solid-state nuclear magnetic resonance (NMR) with spectral editing. Regardless of synthesis conditions, hydrochars consist mostly of oxygen-substituted arene rings (including diphenols) and furans connected by alkyl linkers rich in ketones. Cross-linking nonprotonated and methyne (C-H) alkyl carbons have been identified through spectrally edited 2D NMR. Alkenes and 'quaternary' C-O are observed only at low synthesis temperature, while some clusters of fused arene rings are generated at high temperature. Hydrochar composition is nearly independent of reaction time in the range from 1 to 5 h. Equilibration of 13C magnetization within 1 s shows that the materials are homogeneous on the 5-nm scale, refuting core-shell models of hydrochar microspheres. While furan C-O carbons bonded to alkyl groups or ketones show distinctive cross peaks in 2D NMR, phenolic C-OH is observed unambiguously by hydroxyl-proton selection. While methylene-linked furan rings are fairly common, the signal previously assigned to furan Cα-Cα linkages is shown to arise from abundant, stable catecholic ortho-diphenols, whose HO-C=C-OH structure is proved by 2D13C-13C NMR after hydroxyl-proton selection. Quantitative 13C NMR spectra of low- and high-temperature hydrochars have been matched by chemical-shift simulations for representative structural models. Mixed phenol and furan rings connected by ketones and alkyl linkers provide good fits of the experimental spectra, while literature models dominated by large clusters of fused rings and with few phenols or alkyl-linked ketones do not.

A systems approach reveals species differences in hepatic stress response capacity.

To minimize the occurrence of unexpected toxicities in early phase preclinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical species and humans. Species differences in sensitivity to acetaminophen (APAP) liver injury have been related to differences in the fraction of the drug that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). We have used physiologically based pharmacokinetic modeling to identify oral doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult. Despite pharmacokinetic and biochemical verification of the equivalent NAPQI insult, serum biomarker and tissue histopathology analyses revealed that mice still exhibited a greater degree of liver injury than rats. Transcriptomic and proteomic analyses highlighted the stronger activation of stress response pathways (including the Nrf2 oxidative stress response and autophagy) in the livers of rats, indicative of a more robust transcriptional adaptation to the equivalent insult. Components of these pathways were also found to be expressed at a higher basal level in the livers of rats compared with both mice and humans. Our findings exemplify a systems approach to understanding differential species sensitivity to hepatotoxicity. Multiomics analysis indicated that rats possess a greater basal and adaptive capacity for hepatic stress responses than mice and humans, with important implications for species selection and human translation in the safety testing of new drug candidates associated with reactive metabolite formation.

Optical and physical properties of annealed amorphous niobium oxide thin films.

The physical and optical properties of coatings deposited using physical vapor deposition techniques exhibit changes during post deposition annealing. Optical properties including the index of refraction and spectral transmission vary when coatings are annealed. Physical and mechanical properties such as thickness, density, and stress are also impacted by annealing. In this paper, we study the source of these changes by examining the impact of 150-500°C annealing on N b 2 O 5 films deposited using thermal evaporation and reactive magnetron sputtering. Models based on the Lorentz-Lorenz equation and potential energy considerations explain the data, and rationalize conflicts between previously reported results.

Tenant-Based Housing Voucher Programs: A Community Guide Systematic Review.

CONTEXT: Unaffordable or insecure housing is associated with poor health in children and adults. Tenant-based housing voucher programs (voucher programs) limit rent to 30% or less of household income to help households with low income obtain safe and affordable housing. OBJECTIVE: To determine the effectiveness of voucher programs in improving housing, health, and other health-related outcomes for households with low income. DESIGN: Community Guide systematic review methods were used to assess intervention effectiveness and threats to validity. An updated systematic search based on a previous Community Guide review was conducted for literature published from 1999 to July 2019 using electronic databases. Reference lists of included studies were also searched. ELIGIBILITY CRITERIA: Studies were included if they assessed voucher programs in the United States, had concurrent comparison populations, assessed outcomes of interest, were written in English, and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing quality and stability, neighborhood opportunity (safety and poverty), education, income, employment, physical and mental health, health care use, and risky health behavior. RESULTS: Seven studies met inclusion criteria. Compared with low-income households not offered vouchers, voucher-using households reported increased housing quality (7.9 percentage points [pct pts]), decreased housing insecurity or homelessness (-22.4 pct pts), and decreased neighborhood poverty (-5.2 pct pts).Adults in voucher-using households had improved health care access and physical and mental health. Female youth experienced better physical and mental health but not male youth. Children who entered the voucher programs under 13 years of age had improved educational attainment, employment, and income in their adulthood; children's gains in these outcomes were inversely related to their age at program entry. CONCLUSION: Voucher programs improved health and several health-related outcomes for voucher-using households, particularly young children. Research is still needed to better understand household's experiences and contextual factors that influence achievement of desired outcomes.

Intercostal Cryo Nerve Block in Minimally Invasive Cardiac Surgery: The Prospective Randomized FROST Trial.

INTRODUCTION: Intercostal cryo nerve block has been shown to enhance pulmonary function recovery and pain management in post-thoracotomy procedures. However, its benefit have never been demonstrated in minimal invasive thoracotomy heart valve surgery (Mini-HVS). The purpose of the study was to determine whether intraoperative intercostal cryo nerve block in conjunction with standard of care (collectively referred to hereafter as CryoNB) provided superior analgesic efficacy in patients undergoing Mini-HVS compared to standard-of-care (SOC). METHODS: FROST was a prospective, 3:1 randomized (CryoNB vs. SOC), multicenter trial in patients undergoing Mini-HVS. The primary endpoint was the 48-h postoperative forced expiratory volume in 1 s (FEV1) result. Secondary endpoints were visual analog scale (VAS) scores for pain at the surgical site and general pain, intensive care unit and hospital length-of-stay, total opioid consumption, and allodynia at 6 months postoperatively. RESULTS: A total of 84 patients were randomized to the two arms of the trial CryoNB (n = 65) and SOC (n = 19). Baseline Society of Thoracic Surgeons Predictive Risk of Mortality (STS PROM) score, ejection fraction, and FEV1 were similar between cohorts. A higher 48-h postoperative FEV1 result was demonstrated in the CryoNB cohort versus the SOC cohort (1.20 ± 0.46 vs. 0.93 ± 0.43 L; P = 0.02, one-sided two-sample t test). Surgical site VAS scores were similar between the CryoNB and SOC cohorts at all postoperative timepoints evaluated, but VAS scores not related to the surgical site were lower in the SOC group at 72, 94, and 120 h postoperatively. The SOC cohort had a 13% higher opioid consumption than the CryoNB cohort. One of 64 CryoNB patients reported allodynia that did not require pain medication at 10 months. CONCLUSIONS: The results of FROST demonstrated that intercostal CryoNB provided enhanced FEV1 score at 48 h postoperatively with optimized analgesic effectiveness versus SOC. Future larger prospective randomized trials are warranted to determine whether intercostal CryoNB has an opioid-sparing effect in patients undergoing Mini-HVS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02922153.

Use of Herbarium Voucher Specimens To Investigate Phytochemical Composition in Poisonous Plant Research.

Poisonous plants cause large losses to the livestock industry through death, reduced production efficiency, reproductive dysfunction, and compromised harvesting of rangeland and pasture forages. Research investigating poisonous plants is complex because there are hundreds of genera of toxic plants representing thousands of species. To investigate the effects of poisonous plants on livestock, a clear understanding of the taxonomic identity of the plant and the ability to collect the plant in sufficient quantities for scientific studies is required. Subsequently, the active principles must be defined and investigated in the taxa of interest to better predict risk and make recommendations to reduce losses. Herbaria are collections of preserved plant specimens and are an important resource in poisonous plant research. Voucher specimens have often been used in the identification of the plant for the experimental reproduction of suspected livestock poisoning associated with a spontaneous case. More recently, herbarium specimens have been used to investigate the chemical composition of toxic plants as well as the distribution of different chemotypes over the landscape. The primary purpose of this review is to highlight the chemical analysis of herbarium specimens in poisonous plant research.

Permanent Supportive Housing With Housing First to Reduce Homelessness and Promote Health Among Homeless Populations With Disability: A Community Guide Systematic Review.

CONTEXT: Poor physical and mental health and substance use disorder can be causes and consequences of homelessness. Approximately 2.1 million persons per year in the United States experience homelessness. People experiencing homelessness have high rates of emergency department use, hospitalization, substance use treatment, social services use, arrest, and incarceration. OBJECTIVES: A standard approach to treating homeless persons with a disability is called Treatment First, requiring clients be "housing ready"-that is, in psychiatric treatment and substance-free-before and while receiving permanent housing. A more recent approach, Housing First, provides permanent housing and health, mental health, and other supportive services without requiring clients to be housing ready. To determine the relative effectiveness of these approaches, this systematic review compared the effects of both approaches on housing stability, health outcomes, and health care utilization among persons with disabilities experiencing homelessness. DESIGN: A systematic search (database inception to February 2018) was conducted using 8 databases with terms such as "housing first," "treatment first," and "supportive housing." Reference lists of included studies were also searched. Study design and threats to validity were assessed using Community Guide methods. Medians were calculated when appropriate. ELIGIBILITY CRITERIA: Studies were included if they assessed Housing First programs in high-income nations, had concurrent comparison populations, assessed outcomes of interest, and were written in English and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing stability, physical and mental health outcomes, and health care utilization. RESULTS: Twenty-six studies in the United States and Canada met inclusion criteria. Compared with Treatment First, Housing First programs decreased homelessness by 88% and improved housing stability by 41%. For clients living with HIV infection, Housing First programs reduced homelessness by 37%, viral load by 22%, depression by 13%, emergency departments use by 41%, hospitalization by 36%, and mortality by 37%. CONCLUSIONS: Housing First programs improved housing stability and reduced homelessness more effectively than Treatment First programs. In addition, Housing First programs showed health benefits and reduced health services use. Health care systems that serve homeless patients may promote their health and well-being by linking them with effective housing services.

Effects of chloride ions in acid-catalyzed biomass dehydration reactions in polar aprotic solvents.

The use of polar aprotic solvents in acid-catalyzed biomass conversion reactions can lead to improved reaction rates and selectivities. We show that further increases in catalyst performance in polar aprotic solvents can be achieved through the addition of inorganic salts, specifically chlorides. Reaction kinetics studies of the Brønsted acid-catalyzed dehydration of fructose to hydroxymethylfurfural (HMF) show that the use of catalytic concentrations of chloride salts leads to a 10-fold increase in reactivity. Furthermore, increased HMF yields can be achieved using polar aprotic solvents mixed with chlorides. Ab initio molecular dynamics simulations (AIMD) show that highly localized negative charge on Cl- allows the chloride anion to more readily approach and stabilize the oxocarbenium ion that forms and the deprotonation transition state. High concentrations of polar aprotic solvents form local hydrophilic environments near the reactive hydroxyl group which stabilize both the proton and chloride anions and promote the dehydration of fructose.

Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy.

Diabetic nephropathy (DN) is a primary cause of end-stage renal disease and is becoming more prevalent because of the global rise in type 2 diabetes. A model of DN, the db/db uninephrectomized ( db/db-uni) mouse, is characterized by obesity, as well as compromised renal function. This model also manifests defects in mineral metabolism common in DN, including hyperphosphatemia, which leads to severe endocrine disease. The FGF23 coreceptor, α-Klotho, circulates as a soluble, cleaved form (cKL) and may directly influence phosphate handling. Our study sought to test the effects of cKL on mineral metabolism in db/db-uni mice. Mice were placed into either mild or moderate disease groups on the basis of the albumin-to-creatinine ratio (ACR). Body weights of db/db-uni mice were significantly greater across the study compared with lean controls regardless of disease severity. Adeno-associated cKL administration was associated with increased serum Klotho, intact, bioactive FGF23 (iFGF23), and COOH-terminal fragments of FGF23 ( P < 0.05). Blood urea nitrogen was improved after cKL administration, and cKL corrected hyperphosphatemia in the high- and low-ACR db/db-uni groups. Interestingly, 2 wk after cKL delivery, blood glucose levels were significantly reduced in db/db-uni mice with high ACR ( P < 0.05). Interestingly, several genes associated with stabilizing active iFGF23 were also increased in the osteoblastic UMR-106 cell line with cKL treatment. In summary, delivery of cKL to a model of DN normalized blood phosphate levels regardless of disease severity, supporting the concept that targeting cKL-affected pathways could provide future therapeutic avenues in DN. NEW & NOTEWORTHY In this work, systemic and continuous delivery of the "soluble" or "cleaved" form of the FGF23 coreceptor α-Klotho (cKL) via adeno-associated virus to a rodent model of diabetic nephropathy (DN), the db/db uninephrectomized mouse, normalized blood phosphate levels regardless of disease severity. This work supports the concept that targeting cKL-affected pathways could provide future therapeutic avenues for the severe mineral metabolism defects associated with DN.

Examining the Effectiveness of Year-Round School Calendars on Improving Educational Attainment Outcomes Within the Context of Advancement of Health Equity: A Community Guide Systematic Review.

Students may lose knowledge and skills achieved in the school year during the summer break, with losses greatest for students from low-income families. Community Guide systematic review methods were used to summarize evaluations (published 1965-2015) of the effectiveness of year-round school calendars (YRSCs) on academic achievement, a determinant of long-term health. In single-track YRSCs, all students participate in the same school calendar; summer breaks are replaced by short "intersessions" distributed evenly throughout the year. In multi-track YRSCs, cohorts of students follow separate calendar tracks, with breaks at different times throughout the year. An earlier systematic review reported modest gains with single-track calendars and no gains with multi-track calendars. Three studies reported positive and negative effects for single-track programs and potential harm with multi-track programs when low-income students were assigned poorly resourced tracks. Lack of clarity about the role of intersessions as simple school breaks or as additional schooling opportunities in YRSCs leaves the evidence on single-track programs insufficient. Evidence on multi-track YRSCs is also insufficient.

Expanded In-School Instructional Time and the Advancement of Health Equity: A Community Guide Systematic Review.

Expanded in-school instructional time (EISIT) may reduce racial/ethnic educational achievement gaps, leading to improved employment, and decreased social and health risks. When targeted to low-income and racial/ethnic minority populations, EISIT may thus promote health equity. Community Guide systematic review methods were used to search for qualified studies (through February 2015, 11 included studies) and summarize evidence of the effectiveness of EISIT on educational outcomes. Compared with schools with no time change, schools with expanded days improved students' test scores by a median of 0.05 standard deviation units (range, 0.0-0.25). Two studies found that schools with expanded day and year improved students' standardized test scores (0.04 and 0.15 standard deviation units). Remaining studies were inconclusive. Given the small effect sizes and a lack of information about the use of added time, there is insufficient evidence to determine the effectiveness of EISIT on academic achievement and thus health equity.

Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration.

NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anticancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective and has a potent and broad spectrum of anticancer activity. Its inhibitory activity can be rescued with nicotinic acid (NA) against the cell lines proficient, but not those deficient in NAPRT1, essential for converting NA to NAD+ LSN3154567 also exhibits robust efficacy in multiple tumor models deficient in NAPRT1. Importantly, this molecule when coadministered with NA does not cause observable retinal and hematological toxicities in the rodents, yet still retains robust efficacy. Thus, LSN3154567 has the potential to be further developed clinically into a novel cancer therapeutic. Mol Cancer Ther; 16(12); 2677-88. ©2017 AACR.

Vitamin D Receptor-Dependent Signaling Protects Mice From Dextran Sulfate Sodium-Induced Colitis.

Low vitamin D status potentiates experimental colitis, but the vitamin D-responsive cell in colitis has not been defined. We hypothesized that vitamin D has distinct roles in colonic epithelial cells and in nonepithelial cells during colitis. We tested this hypothesis by using mice with vitamin D receptor (VDR) deletion from colon epithelial cells (CEC-VDRKO) or nonintestinal epithelial cells (NEC-VDRKO). Eight-week-old mice were treated with 1.35% dextran sulfate sodium (DSS) for 5 days and then euthanized 2 or 10 days after removal of DSS. DSS induced body weight loss and increased disease activity index and spleen size. This response was increased in NEC-VDRKO mice but not CEC-VDRKO mice. DSS-induced colon epithelial damage and immune cell infiltration scores were increased in both mouse models. Although the epithelium healed between 2 and 10 days after DSS administration in control and CEC-VDRKO mice, epithelial damage remained high in NEC-VDRKO mice 10 days after removal of DSS, indicating delayed epithelial healing. Gene expression levels for the proinflammatory, M1 macrophage (Mɸ) cytokines tumor necrosis factor-α, nitric oxide synthase 2, and interleukin-1ß were significantly elevated in the colon of NEC-VDRKO mice at day 10. In vitro experiments in murine peritoneal Mɸs demonstrated that 1,25 dihydroxyvitamin D directly inhibited M1 polarization, facilitated M2 polarization, and regulated Mɸ phenotype switching toward the M2 and away from the M1 phenotype. Our data revealed unique protective roles for vitamin D signaling during colitis in the colon epithelium as well as nonepithelial cells in the colon microenvironment (i.e., modulation of Mɸ biology).

Characterizing Substrate-Surface Interactions on Alumina-Supported Metal Catalysts by Dynamic Nuclear Polarization-Enhanced Double-Resonance NMR Spectroscopy.

The characterization of nanometer-scale interactions between carbon-containing substrates and alumina surfaces is of paramount importance to industrial and academic catalysis applications, but it is also very challenging. Here, we demonstrate that dynamic nuclear polarization surface-enhanced NMR spectroscopy (DNP SENS) allows the unambiguous description of the coordination geometries and conformations of the substrates at the alumina surface through high-resolution measurements of 13C-27Al distances. We apply this new technique to elucidate the molecular-level geometry of 13C-enriched methionine and natural abundance poly(vinyl alcohol) adsorbed on γ-Al2O3-supported Pd catalysts, and we support these results with element-specific X-ray absorption near-edge measurements. This work clearly demonstrates a surprising bimodal coordination of methionine at the Pd-Al2O3 interface.

Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble Klotho.

αKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase-deficient mice or αKL-null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in αKL-null mice supporting direct actions of cKL in the absence of mKL. αKL-null mice with sustained AAV-cKL expression had a 74%-78% reduction in aorta mineral content and a 72%-77% reduction in mineral volume compared with control-treated counterparts (P<0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal-regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen-activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous αKL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC.

Molecular and morphological evidence for Penstemon luculentus (Plantaginaceae): a replacement name for Penstemon fremontii var. glabrescens.

Penstemon luculentus R.L.Johnson & M.R.Stevens, nom. nov. replaces Penstemon fremontii var. glabrescens Dorn & Lichvar. The varietal name glabrescens was not elevated because it was already occupied by Penstemon glabrescens Pennell, a different species. This new arrangement is supported by molecular and morphological evidence. An analysis of genetic diversity in populations of both varieties of Penstemon fremontii Torr. & A. Gray (glabrescens and fremontii) from the Piceance Basin, Colorado, using SSR (simple sequences repeats) or microsatellites markers, revealed significant genetic differentiation between the two. Penstemon fremontii var. glabrescens was also genetically different from Penstemon gibbensii Dorn and Penstemon scariosus var. garrettii (Pennell) N.H. Holmgren. The combination of hirtellous stems, glabrous leaves, non-glandular inflorescence, and long anther hairs distinguish Penstemon luculentus from other morphologically similar species.

School-Based Health Centers to Advance Health Equity: A Community Guide Systematic Review.

CONTEXT: Children from low-income and racial or ethnic minority populations in the U.S. are less likely to have a conventional source of medical care and more likely to develop chronic health problems than are more-affluent and non-Hispanic white children. They are more often chronically stressed, tired, and hungry, and more likely to have impaired vision and hearing-obstacles to lifetime educational achievement and predictors of adult morbidity and premature mortality. If school-based health centers (SBHCs) can overcome educational obstacles and increase receipt of needed medical services in disadvantaged populations, they can advance health equity. EVIDENCE ACQUISITION: A systematic literature search was conducted for papers published through July 2014. Using Community Guide systematic review methods, reviewers identified, abstracted, and summarized available evidence of the effectiveness of SBHCs on educational and health-related outcomes. Analyses were conducted in 2014-2015. EVIDENCE SYNTHESIS: Most of the 46 studies included in the review evaluated onsite clinics serving urban, low-income, and racial or ethnic minority high school students. The presence and use of SBHCs were associated with improved educational (i.e., grade point average, grade promotion, suspension, and non-completion rates) and health-related outcomes (i.e., vaccination and other preventive services, asthma morbidity, emergency department use and hospital admissions, contraceptive use among females, prenatal care, birth weight, illegal substance use, and alcohol consumption). More services and more hours of availability were associated with greater reductions in emergency department overuse. CONCLUSIONS: Because SBHCs improve educational and health-related outcomes in disadvantaged students, they can be effective in advancing health equity.

Early Childhood Education to Promote Health Equity: A Community Guide Systematic Review.

CONTEXT: Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center-based early childhood education. DESIGN: A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review. RESULTS: There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting. CONCLUSIONS: Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity.

Identifying low-coverage surface species on supported noble metal nanoparticle catalysts by DNP-NMR.

DNP-NMR spectroscopy has been applied to enhance the signal for organic molecules adsorbed on γ-Al2O3-supported Pd nanoparticle catalysts. By offering >2500-fold time savings, the technique enabled the observation of (13)C-(13)C cross-peaks for low coverage species, which were assigned to products from oxidative degradation of methionine adsorbed on the nanoparticle surface.

An Inducible, Large-Intestine-Specific Transgenic Mouse Model for Colitis and Colitis-Induced Colon Cancer Research.

BACKGROUND: Animal models are an important tool to understand intestinal biology. Our laboratory previously generated C57BL/6-Tg(Car1-cre)5Flt transgenic mice (CAC) with large-intestine-specific Cre recombinase (Cre) expression as a model to study colon health. AIM: To expand the utility of the CAC mouse model by determining the impact of chemically induced colitis on CAC transgene expression. METHODS: CAC mice were crossed to Rosa reporter mice (Rosa26R (flox/flox) ) with a lox-STOP-lox signal controlling ß-galactosidase (ßgal) expression and then further crossed with Apc(CKO/CKO) mice in some experiments to delete Apc alleles (Apc (Δ580) ). Initially, 8-week-old CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice were treated with dextran sulfate sodium (DSS) in drinking water (5 days, 0, 0.65, 1.35, or 2.0 %). Colon tissue damage and ßgal labeling were analyzed 10 day after stopping DSS. Next, 8-week-old CAC(Tg/WT);Rosa26R(flox/flox) mice were treated with 0 or 1.35 % DSS, and colonic ßgal labeling was assessed at 30 day post-DSS treatment. Finally, 10-week-old CAC(Tg/WT);Apc (Δ580/WT) mice were treated with DSS (0 or 2 %) for 5 days and colonic tumors were analyzed at 20 weeks. RESULTS: CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice had a DSS dose-dependent increase in colon epithelial damage that correlated with increased epithelial ßgal labeling at 10 days (r (2) = 0.9, ß = 0.75). The ßgal labeling in CAC(Tg/WT);Rosa26R(flox/flox) mice colon remained high at 30 days, especially in the crypts of the healed ulcer. DSS also increased colon tumor incidence and multiplicity in CAC(Tg/WT);Apc (Δ580/WT) mice. CONCLUSIONS: DSS-mediated epithelial damage induces a persistent, Cre-mediated recombination of floxed alleles in CAC mice. This enables the examination of gene function in colon epithelium during experimental colitis and colitis-induced colon cancer.