Biochemical characterization of rice xylan O-acetyltransferases.

MAIN CONCLUSION: Rice xylan is predominantly monoacetylated at O-2 and O-3, and 14 rice DUF231 proteins were demonstrated to be xylan acetyltransferases. Acetylated xylans are the principal hemicellulose in the cell walls of grass species. Because xylan acetylation impedes the conversion of cellulosic biomass into biofuels, knowledge on acetyltransferases catalyzing xylan acetylation in grass species will be instrumental for a better utilization of grass biomass for biofuel production. Xylan in rice (Oryza sativa) is predominantly monoacetylated at O-2 and O-3 with a total degree of acetylation of 0.19. In this report, we have characterized 14 rice DUF231 proteins (OsXOAT1 to OsXOAT14) that are phylogenetically grouped together with Arabidopsis xylan acetyltransferases ESK1 and its close homologs. Complementation analysis demonstrated that the expression of OsXOAT1 to OsXOAT7 in the Arabidopsis esk1 mutant was able to rescue its defects in 2-O- and 3-O-monoacetylation and 2,3-di-O-acetylation. Activity assay of recombinant proteins revealed that all 14 OsXOATs exhibited acetyltransferase activities capable of transferring acetyl groups from acetyl-CoA to the xylohexaose acceptor with 10 of them having high activities. Structural analysis of the OsXOAT-catalyzed products showed that the acetylated structural units consisted mainly of 2-O- and 3-O-monoacetylated xylosyl residues with a minor amount of 2,3-di-O-acetylated xylosyl units, which is consistent with the acetyl substitution pattern of rice xylan. Further kinetic studies revealed that OsXOAT1, OsXOAT2, OsXOAT5, OsXOAT6 and OsXOAT7 had high affinity toward the xylohexaose acceptor. Our results provide biochemical evidence indicating that OsXOATs are acetyltransferases involved in xylan acetylation in rice.

Comparative Effectiveness of a Technology-Facilitated Depression Care Management Model in Safety-Net Primary Care Patients With Type 2 Diabetes: 6-Month Outcomes of a Large Clinical Trial.

BACKGROUND: Comorbid depression is a significant challenge for safety-net primary care systems. Team-based collaborative depression care is effective, but complex system factors in safety-net organizations impede adoption and result in persistent disparities in outcomes. Diabetes-Depression Care-management Adoption Trial (DCAT) evaluated whether depression care could be significantly improved by harnessing information and communication technologies to automate routine screening and monitoring of patient symptoms and treatment adherence and allow timely communication with providers. OBJECTIVE: The aim of this study was to compare 6-month outcomes of a technology-facilitated care model with a usual care model and a supported care model that involved team-based collaborative depression care for safety-net primary care adult patients with type 2 diabetes. METHODS: DCAT is a translational study in collaboration with Los Angeles County Department of Health Services, the second largest safety-net care system in the United States. A comparative effectiveness study with quasi-experimental design was conducted in three groups of adult patients with type 2 diabetes to compare three delivery models: usual care, supported care, and technology-facilitated care. Six-month outcomes included depression and diabetes care measures and patient-reported outcomes. Comparative treatment effects were estimated by linear or logistic regression models that used generalized propensity scores to adjust for sampling bias inherent in the nonrandomized design. RESULTS: DCAT enrolled 1406 patients (484 in usual care, 480 in supported care, and 442 in technology-facilitated care), most of whom were Hispanic or Latino and female. Compared with usual care, both the supported care and technology-facilitated care groups were associated with significant reduction in depressive symptoms measured by scores on the 9-item Patient Health Questionnaire (least squares estimate, LSE: usual care=6.35, supported care=5.05, technology-facilitated care=5.16; P value: supported care vs usual care=.02, technology-facilitated care vs usual care=.02); decreased prevalence of major depression (odds ratio, OR: supported care vs usual care=0.45, technology-facilitated care vs usual care=0.33; P value: supported care vs usual care=.02, technology-facilitated care vs usual care=.007); and reduced functional disability as measured by Sheehan Disability Scale scores (LSE: usual care=3.21, supported care=2.61, technology-facilitated care=2.59; P value: supported care vs usual care=.04, technology-facilitated care vs usual care=.03). Technology-facilitated care was significantly associated with depression remission (technology-facilitated care vs usual care: OR=2.98, P=.04); increased satisfaction with care for emotional problems among depressed patients (LSE: usual care=3.20, technology-facilitated care=3.70; P=.05); reduced total cholesterol level (LSE: usual care=176.40, technology-facilitated care=160.46; P=.01); improved satisfaction with diabetes care (LSE: usual care=4.01, technology-facilitated care=4.20; P=.05); and increased odds of taking an glycated hemoglobin test (technology-facilitated care vs usual care: OR=3.40, P<.001). CONCLUSIONS: Both the technology-facilitated care and supported care delivery models showed potential to improve 6-month depression and functional disability outcomes. The technology-facilitated care model has a greater likelihood to improve depression remission, patient satisfaction, and diabetes care quality.

Cytosol-Localized UDP-Xylose Synthases Provide the Major Source of UDP-Xylose for the Biosynthesis of Xylan and Xyloglucan.

Xylan and xyloglucan are the two major cell wall hemicelluloses in plants, and their biosynthesis requires a steady supply of the sugar donor, UDP-xylose. UDP-xylose is synthesized through conversion of UDP-glucuronic acid (UDP-GlcA) by the activities of UDP-xylose synthase (UXS). There exist six UXS genes in the Arabidopsis thaliana genome; three of them (UXS1, UXS2 and UXS4) encode Golgi-localized enzymes and the other three (UXS3, UXS5 and UXS6) encode cytosol-localized enzymes. In this report, we investigated the contributions of these UXS genes in supplying UDP-xylose for the biosynthesis of xylan and xyloglucan. Expression analyses revealed that the six UXS genes exhibited distinct and overlapping expression patterns in different cell types of stems, root-hypocotyls and young seedlings, and that the relative enzymatic activity of UXS in the cytosol was 17 times higher than that in the Golgi. Among the six UXS genes, UXS3, UXS5 and UXS6 showed the highest expression in stems and were expressed predominantly in xylem cells and interfascicular fibers. Their predominant expression in secondary wall-forming cells was consistent with the finding that the expression of UXS3, UXS5 and UXS6 was directly activated by the secondary wall NAC master switches. Although simultaneous mutations of UXS1, UXS2 and UXS4 did not cause any apparent effects on plant growth and xylan biosynthesis, simultaneous down-regulation/mutations of UXS3, UXS5 and UXS6 led to a drastic reduction in secondary wall thickening, a severe deformation of xylem vessels, a significant decrease in xylan content without an apparent reduction in its chain length and an absence of GlcA side chains in xylan, which are reminiscent of the phenotypes of some known xylan-deficient mutants. Moreover, Immunolocalization with two xyloglucan monoclonal antibodies, LM15 and LM25, revealed a significant reduction in the amount of xylogulcan in the primary walls. These results demonstrate that the cytosol-localized UXS3, UXS5 and UXS6 play a predominant role in the supply of UDP-xylose for the biosynthesis of xylan and xyloglucan.

Minimizing weight gain for patients taking antipsychotic medications: The potential role for early use of metformin.

BACKGROUND: Patients taking antipsychotic medications are at high risk for weight gain, which in turn leads to poor health outcomes, nonadherence with treatment, and low self-esteem. METHODS: We reviewed published studies of pharmacologic interventions aimed at minimizing antipsychotic-induced weight gain. Treatments initiated prior to onset of weight gain were compared with those that started once weight gain already had occurred. RESULTS: Although data are limited, adjunctive medications for weight management appear to be more effective when initiated at or near the time when patients are first exposed to antipsychotic medications. Interventions initiated later in the course of treatment-typically after weight gain already has occurred-rarely help patients return to their pretreatment weight. The most commonly used adjunctive intervention has been metformin. CONCLUSIONS: Certain patients benefit from initiating metformin early in their exposure to second-generation antipsychotic agents. In particular, young, healthy patients beginning olanzapine or clozapine probably will experience less weight gain if they concomitantly initiate metformin.

Using Virtual Reality to Improve Antiretroviral Therapy Adherence in the Treatment of HIV: Open-Label Repeated Measure Study.

BACKGROUND: Nonadherence to HIV medications is a serious unsolved problem and is a major cause of morbidity and mortality in the HIV-positive population. Although treatment efficacy is high if compliance is greater than 90%, about 40% of people with HIV do not meet this threshold. OBJECTIVE: This study aimed to test a novel approach to improve medication adherence by using a low-cost virtual reality (VR) experience to educate people with HIV about their illness. We hypothesized that people with HIV would be more likely to be compliant with the treatment following the 7-minute experience and, therefore, should have decreasing viral load (VL), increasing cluster of differentiation 4+ (CD4+) cell counts, and improved self-reported adherence. METHODS: We showed the VR experience to 107 participants with HIV at a county hospital in Los Angeles, California. Participants were asked to self-report how often they take their medications on a Likert-scale. The self-reported question (SRQ) was given before and at least 2 weeks after the VR experience. We also compared VL and CD4+ cell counts before and on average 101 days after the experience. VL and CD4+ were obtained per the clinic's standard care protocol. Two-tailed paired t tests were performed on the initial and follow-up SRQ scores, VL, and CD4+. We restricted the CD4+ analysis to participants who had a pre-CD4+ below normal (defined as 500 cells/mm3). To reduce the possibility that VL were trending down and CD4+ were trending up regardless of the VR experience, 2 serial VL and CD4+ obtained before the experience were also compared and analyzed. Immediately following the VR experience, participants were given a 4-question Likert-type postexperience questionnaire (PEQ) that assessed their opinions about the experience. RESULTS: SRQ scores improved from pre to post experience with high significance (P<.001). VL decreased from pre to post experience by 0.38 log10 copies/mL (95% CI 0.06-0.70; P=.02). In contrast, the 2 serial VL obtained before the experience showed no statistically significant changes. There was also a statistically significant increase in CD4+ (95% CI -3.4 to -54.3 cells/mm3; P=.03). Analysis of the PEQ revealed that VR was comfortable for almost all of the participants and that most participants believed the experience to be educational and that it would improve their medication adherence. CONCLUSIONS: The findings suggest that the low-cost VR experience caused an increased rate of antiretroviral therapy adherence that resulted in a decrease of VL and an increase of CD4+. Further studies are required to explore the duration of this effect and whether these results are generalizable to other treatment settings and populations.