399 research outputs found
Applications for activity-based probes in biomedical research on glycosidases
Lysosomal glycosidases are acid hydrolases that fragment
glycoconjugates in lysosomes. Their inherited deficiency in human is the
cause of a number of lysosomal storage disorders (LSDs), showing
characteristic lysosomal accumulation of undegraded glycoconjugates. In the
past, activity-based probes (ABPs) based on cyclophellitol or cyclophellitol
aziridine scaffold have emerged as powerful tools enabling sensitive
quantification of a number of lysosomal glycosidases in extracts of cells and
tissue, as well as in intact cells. This thesis describes the
characterization of several novel ABP classes targeting α-glucosidase,
β-glucuronidase, α-L-iduronidase, α-mannosidase, β-mannosidase, and
β-galactosidase, as well as a broad scale of applications for ABPs in LSD
research. Novel glucocerebrosidase inhibitors based on the cyclophellitol
scaffold are also described, which are brain-permeable, selective, and
potently inactivate the enzyme in adult zebrafish. Additionally, a protocol
for gel-based and microscopy-based detection of glucocerebrosidase is
described.
Medical Biochemistr
Associations between fruit and vegetable consumption and psychological distress: results from a population-based study.
BACKGROUND: Several studies observed associations of various aspects of diet with mental health, but little is known about the relationship between following the 5-a-day recommendation for fruit and vegetables consumption and mental health. Thus, we examined the associations of the Swiss daily recommended fruit and vegetable intake with psychological distress.
METHODS: Data from 20,220 individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The recommended portions of fruit and vegetables per day were defined as 5-a-day (at least 2 portions of fruit and 3 of vegetables). The outcome was perceived psychological distress over the previous 4 weeks (measured by the 5-item mental health index [MHI-5]). High distress (MHI-5 score ≤ 52), moderate distress (MHI-5 > 52 and ≤ 72) and low distress (MHI-5 > 72 and ≤ 100) were differentiated and multinomial logistic regression analyses adjusted for known confounding factors were performed.
RESULTS: The 5-a-day recommendation was met by 11.6 % of the participants with low distress, 9.3 % of those with moderate distress, and 6.2 % of those with high distress. Consumers fulfilling the 5-a-day recommendation had lower odds of being highly or moderately distressed than individuals consuming less fruit and vegetables (moderate vs. low distress: OR = 0.82, 95 % confidence interval [CI] 0.69-0.97; high vs. low distress: OR = 0.55, 95 % CI 0.41-0.75).
CONCLUSIONS: Daily intake of 5 servings of fruit and vegetable was associated with lower psychological distress. Longitudinal studies are needed to further determine the causal nature of this relationship
Asymbiotic germination of immature seeds, plantlet development and ex vitro establishment of plants of Dendrobium tosaense Makino - A medicinally important orchid
Shi-hu (Dendrobium spp. or Dendrobii Herba) is one of the important traditional Chinese medicines. The commercially available crude drug in the traditional medicine market is composed mainly of three species: Dendrobium tosaense, D. nobile, and D. moniliforme. An efficient method of propagation has been developed via asymbiotic germination of seeds in vitro for the medicinally important D. tosaense. Seeds from capsules of D. tosaense collected 8-14 wk after artificial pollination germinated after being cultured on full-strength or half-strength Murashige and Skoog (MS) medium devoid of plant growth regulators and with 3% sucrose. Germination of seeds varied with the medium type and seed maturity. Germinated seedlings after transfer to MS medium with 1.5% sucrose and 8% banana homogenate or potato juice or coconut water and 20 wk of incubation developed into healthy plantlets. Well-developed plantlets were transplanted to moss or moss and tree fern or tree fern as substrates in plastic trays and transferred to a greenhouse for hardening. All plants survived, attained maturity, and developed normal flower and capsule after one and a half years. This protocol of successful plant regeneration by asymbiotic seed germination should permit rapid propagation and conservation of this medicinally important Dendrobium species
Study of the Anti-Proliferative Activity of 5-Substituted 4,7-Dimethoxy-1,3-Benzodioxole Derivatives of SY-1 from Antrodia camphorata on Human COLO 205 Colon Cancer Cells
A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated from Antrodia camphorata, were evaluated for their in vitro inhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named “apiole” exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue “apiole” decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by apiole (75–225 μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150 μM) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation
Characterization study of GaN-based epitaxial layer and light-emitting diode on nature-patterned sapphire substrate
[[abstract]]Chemical wet etching on c-plane sapphire wafers by three etching solutions (H3PO4, H2SO4, and H3PO4/H2SO4 mixing solution) was studied. Among these etching agents, the mixing H3PO4/H2SO4 solution has the fastest etching rate (1.5 μm/min). Interestingly, we found that H2SO4 does not etch the c-plane sapphire wafer in thickness; instead, a facet pyramidal pattern is formed on the c-plane sapphire wafer. GaN light-emitting diode (LED) epitaxial structure was grown on the sapphire wafer with the pyramidal pattern and the standard flat sapphire wafer. X-ray diffraction and photoluminescence measurement show that the pyramidal pattern on the sapphire wafer improved crystalline quality but augmented the compressive stress level in the GaN LED epilayer. The horizontal LED chips fabricated on the pyramidal-patterned sapphire wafer have a larger light output than the horizontal LED chips fabricated on the standard flat sapphire wafer by 20%.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子
Precision Primordial He Measurement with CMB Experiments
Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) are
two major pillars of cosmology. Standard BBN accurately predicts the primordial
light element abundances (He, D, He and Li), depending on one
parameter, the baryon density. Light element observations are used as a
baryometers. The CMB anisotropies also contain information about the content of
the universe which allows an important consistency check on the Big Bang model.
In addition CMB observations now have sufficient accuracy to not only determine
the total baryon density, but also resolve its principal constituents, H and
He. We present a global analysis of all recent CMB data, with special
emphasis on the concordance with BBN theory and light element observations. We
find and
(fraction of baryon mass as He) using CMB data alone, in agreement with
He abundance observations. With this concordance established we show that
the inclusion of BBN theory priors significantly reduces the volume of
parameter space. In this case, we find
and . We also find that the inclusion of deuterium
abundance observations reduces the and ranges by a factor
of 2. Further light element observations and CMB anisotropy experiments
will refine this concordance and sharpen BBN and the CMB as tools for precision
cosmology.Comment: 7 pages, 3 color figures made minor changes to bring inline with
journal versio
Effects of dark sectors' mutual interaction on the growth of structures
We present a general formalism to study the growth of dark matter
perturbations when dark energy perturbations and interactions between dark
sectors are present. We show that dynamical stability of the growth of
structure depends on the type of coupling between dark sectors. By taking the
appropriate coupling to ensure the stable growth of structure, we observe that
the effect of the dark sectors' interaction overwhelms that of dark energy
perturbation on the growth function of dark matter perturbation. Due to the
influence of the interaction, the growth index can differ from the value
without interaction by an amount within the observational sensibility, which
provides a possibility to disclose the interaction between dark sectors through
future observations on the growth of large structure.Comment: 15 pages, 4 figures, revised version, to appear in JCA
Validation of a 5-Year Mortality Prediction Model among U.S. Medicare Beneficiaries
BACKGROUND/OBJECTIVES: A claims-based model predicting 5-year mortality (Lund-Lewis) was developed in a 2008 cohort of North Carolina (NC) Medicare beneficiaries and included indicators of comorbid conditions, frailty, disability, and functional impairment. The objective of this study was to validate the Lund-Lewis model externally within a nationwide sample of Medicare beneficiaries. DESIGN: Retrospective validation study. SETTING: U.S. Medicare population. PARTICIPANTS: From a random sample of Medicare beneficiaries, we created four annual cohorts from 2008 to 2011 of individuals aged 66 and older with an office visit in that year. The annual cohorts ranged from 1.13 to 1.18 million beneficiaries. MEASUREMENTS: The outcome was 5-year all-cause mortality. We assessed clinical indicators in the 12 months before the qualifying office visit and estimated predicted 5-year mortality for each beneficiary in the nationwide sample by applying estimates derived in the original NC cohort. Model performance was assessed by quantifying discrimination, calibration, and reclassification metrics compared with a model fit on a comorbidity score. RESULTS: Across the annual cohorts, 5-year mortality ranged from 24.4% to 25.5%. The model had strong discrimination (C-statistics ranged across cohorts from.823 to.826). Reclassification measures showed improvement over a comorbidity score model for beneficiaries who died but reduced performance among beneficiaries who survived. The calibration slope ranged from.83 to.86; the model generally predicted a higher risk than observed. CONCLUSION: The Lund-Lewis model showed strong and consistent discrimination in a national U.S. Medicare sample, although calibration indicated slight overfitting. Future work should investigate methods for improving model calibration and evaluating performance within specific disease settings
WMAP constraints on inflationary models with global defects
We use the cosmic microwave background angular power spectra to place upper
limits on the degree to which global defects may have aided cosmic structure
formation. We explore this under the inflationary paradigm, but with the
addition of textures resulting from the breaking of a global O(4) symmetry
during the early stages of the Universe. As a measure of their contribution, we
use the fraction of the temperature power spectrum that is attributed to the
defects at a multipole of 10. However, we find a parameter degeneracy enabling
a fit to the first-year WMAP data to be made even with a significant defect
fraction. This degeneracy involves the baryon fraction and the Hubble constant,
plus the normalization and tilt of the primordial power spectrum. Hence,
constraints on these cosmological parameters are weakened. Combining the WMAP
data with a constraint on the physical baryon fraction from big bang
nucleosynthesis calculations and high-redshift deuterium abundance, limits the
extent of the degeneracy and gives an upper bound on the defect fraction of
0.13 (95% confidence).Comment: 10pp LaTeX/RevTeX, 6 eps figs; matches accepted versio
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