437,577 research outputs found
DataSheet1_Mg-HA-C/C Composites Promote Osteogenic Differentiation and Repair Bone Defects Through Inhibiting miR-16.zip
No full textThe hydroxyapatite (HA) coating on carbon/carbon (C/C) is reasonable and feasible to obtain bone graft materials with appropriate mechanical and biological properties. However, improvement of the physical and chemical properties of HA-C/C composites to promote bone regeneration and healing remains a challenge. In our present study, the HA coatings on C/C with magnesium (Mg) (Mg-HA-C/C) composites were synthesized that Ca (NO3)2, Mg (NO3)2, and NH4H2PO4 were mixed and coatings were made by electromagnetic induction deposition’s heating. As determined with in vitro experiments, Mg-HA-C/C composites containing 10 and 20% Mg decreased miR-16 levels, increased cell viability, elevated the levels of osteogenesis-related genes, and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) seeded on their surfaces. In a rat model of skull defects, compared to the control group, at 4 and 12 weeks after the operation, the bone volume fraction (BV/TV) of Mg-HA-C/C composite group was increased by 8.439 ± 2.681% and 23.837 ± 7.845%, as well as the trabecular thickness (Tb.Th) was 56.247 ± 24.238 μm and 114.911 ± 34.015 μm more. These composites also increased the levels of ALP and RUNX2 in skull. The Mg-HA-C/C composite-enhanced bone regeneration and healing were blocked by in situ injection of an miR-16 mimic lentivirus vector. Thus, Mg-HA-C/C composites promote osteogenic differentiation and repair bone defects through inhibiting miR-16.</p
HA-tagged COMTD1 localizes to mitochondria in immortalized mouse melanocytes.
No full text(A-D) Immortalized melan-Ink4a cells from Ink4a-deficient C57BL/6J mice were transiently transfected to express COMTD1 fused with the HA11 epitope at either the N-terminus (HA-COMTD1; A, C) or C-terminus (COMTD1-HA; B, D). Two days later, cells were fixed and analyzed by bright field (BF) and immunofluorescence microscopy for HA and either the mitochondrial resident protein MAVS (A, B) or the ER resident protein calnexin (CNX; C, D). Individual images of labelled cells or the bright field image are shown in addition to an overlay of HA (green) with MAVS (red; HA/ MAVS), CNX (red; HA/ CNX), or the pseudocolored bright field image (magenta; HA/BF). Insets show a 5-fold magnified image of the boxed region to emphasize overlap or lack thereof. Main scale bar, 10 μm; inset scale bar, 2 μm. (E) Quantification of the degree of overlap of COMTD1-HA or HA-COMTD1, as indicated, with markers of the ER (CNX; N = 29 for COMTD1-HA, N = 17 for HA-COMTD1), mitochondria (MAVS; N = 25 for COMTD1-HA, N = 16 for HA-COMTD1), mature melanosomes (TYRP1; N = 16), immature melanosomes (PMEL; N = 17), late endosomes/ lysosomes (LAMP2; N = 15), or early endosomes (STX13; N = 21). Data from 4–5 individual experiments are presented as a box and whiskers plot in which the area of overlap is shown relative to the total area occupied by HA (e.g., CNX vs. HA) or by the indicated marker (e.g., HA vs. CNX). See S2 Fig for examples of the data for TYRP1, PMEL, LAMP2 and STX13. Statistical significance was determined by ordinary one-way ANOVA with Tukey’s tests for multiple comparisons; ****, P < 0.0001.</p
The impact of meningococcal serogroup C conjugate vaccine in Scotland
No full textThe increasing number of cases of serogroup C meningococcal disease in Scotland in the late 1990s coincided with the availability of a new meningococcal conjugate serogroup C (MCC) vaccine that, from 1999 onwards, was offered to all individuals aged <20 years. Annual incidence rates between 1994 and 2003 were calculated in 3 age groups (<5 years old; 5-19 years old; and 20 years old), and Poisson regression models were used to verify disease trends over time. Dramatic reductions ( ) in the incidence of serogroup C meningococcal disease were seen in target age groups: from 15.8 incidents per 100,000 subjects in 1999 (95% confidence interval [CI], 11.3-20.3) to 0.7 incidents per 100,000 subjects in 2001 (95% CI, −0.3 to 1.6), for subjects <5 years old, and from 6.7 incidents per 100,000 subjects in 1999 (95% CI, 5.1-8.3) to 1.5 incidents per 100,000 subjects in 2001 (95% CI, 0.7-2.3), for subjects 5-19 years old. An increasing incidence of serogroup B meningococcal disease in individuals 5-19 years old was clearly established before the campaign began. A 30% decrease in the case‐fatality rate for individuals <20 years old was not significant ( ). The MCC vaccine program has been highly effective in Scotland, leading to substantial reductions in serogroup C meningococcal disease and meningococcal mortality, with no adverse effects on other groups
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Template-directed self-assembly and growth of insulin amyloid fibrils
No full textThe formation of amyloid aggregates in tissue is a pathological feature of many neurodegenerative diseases and type II diabetes. Amyloid deposition, the process of amyloid growth by the association of individual soluble amyloid molecules with a pre-existing amyloid template (i.e., plaque), is known to be critical for amyloid formation in vivo. The requirement for a natural amyloid template, however, has made amyloid deposition study difficult and cumbersome. In the present work, we developed a novel, synthetic amyloid template by attaching amyloid seeds covalently onto an N-hydroxy-succinimide-activated surface, where insulin was chosen as a model amyloidogenic protein. According to ex situ atomic force microscopy observations,insulin monomers in solution were deposited onto the synthetic amyloid template to form fibrils, like hair growth. The fibril formation on the template occurred without lag time, and its rate was highly accelerated than in the solution. The fibrils were long, over 2 mu m, and much thinner than those in the solution, which was caused by limited nucleation sites on the template surface and lack of lateral twisting between fibrils. According to our investigations using thioflavin T-induced fluorescence, birefringent Congo red binding, and circular dichroism, fibrils grown on the template were identified to be amyloids that formed through a conformational rearrangement of insulin monomers upon interaction with the template. The amyloid deposition rate followed saturation kinetics with respect to insulin concentration in the solution. The characteristics of amyloid deposition on the synthetic template were in agreement with previous studies performed with human amyloid plaques. It is demonstrated that the synthetic amyloid template can be used for the screening of inhibitors on amyloid deposition in vitro. (c) 2005 Wiley Periodicals, Inc
Insulin amyloid fibrillation at above 100 degrees C: New insights into protein folding under extreme temperatures
No full textTo investigate the folding behavior of amyloidogenic proteins under extreme temperatures, the kinetics of fibrillation and accompanying secondary structure transitions of bovine insulin were studied for temperatures ranging tip to 140degreesC. The presence of extreme heat stress had. traditionally been associated with irreversible denaturation of protein while the initial steps of such a denaturation process may be common with a fibril formation pathway of amyloidogenic proteins. The present work demonstrates the ability of insulin to form amyloid fibrils at above 100degreesC. Amyloid formation was gradually replaced by random coil generation after similar to80degreesC until no amyloid was detected at 140degreesC. The morphology of insulin amyloid fibrils underwent sharp changes with increasing the temperature. The dependence of amyloid formation rate on incubation temperature followed non-Arrhenius kinetics, which is explained by temperature-dependent enthalpy change for amyloid formation. The intermediate stage of amyloid formation and random coil generation consisted of a partially folded intermediate common to both pathways. The fully unfolded monomers in random coil conformation showed partial reversibility through this intermediate by reverting back to the amyloid pathway when formed at 140degreesC and incubated at 100degreesC. This Study highlights the non-Arrhenius kinetics of amyloid fibrillation under extreme temperatures, and elucidates its intermediate stage common with random coil formation
HA-COMTD1 does not localize to melanosomes or endolysosomes.
No full textImmortalized melan-Ink4a cells were transiently transfected to express COMTD1 fused with the HA11 epitope at the N-terminus (HA-COMTD1) (A-D) or the HA11 epitope at the C-terminus (COMTD1-HA) (E-H). Two days later, cells were fixed and analyzed by bright field (BF) and dIFM for HA and markers of either mature melanosomes (TYRP1; A, E), early stage melanosomes (PMEL; B, F), late endosomes/ lysosomes (LAMP2 C, G), or early endosomes (STX13; D, H). Individual images of labeled cells or the bright field image are shown in addition to an overlay of HA (green) with the indicated marker (red). Insets show a 7-fold magnified image of the boxed region to emphasize the lack of overlap. Main scale bar, 10 μm; inset scale bar, 2 μm. (PDF)</p
Part2_Petromurin C induces protective autophagy and apoptosis in FLT3-ITD-positive AML: synergy with gilteritinib
No full textTreatment of acute myeloid leukemia (AML) remains inefficient due to drug resistance and relapse, particularly in patients with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD). Marine-derived natural products have recently been used for drug development against AML. We show here that petromurin C, isolated from the culture extract of the marine-derived fungus Aspergillus candidus KUFA0062, which was isolated from the marine sponge Epipolasis sp., induces early autophagy followed by apoptotic cell death via activation of the intrinsic cell death pathway concomitant with mitochondrial stress and downregulation of Mcl-1 in FLT3-ITD mutated MV4-11 cells. Moreover, petromurin C synergized with the clinically-used FLT3 inhibitor gilteritinib at sub-toxic concentrations. Altogether our results suggest that petromurin C could act as an anti-leukemic agent alone or in combination with gilteritinib
Using C-Tool to simulate soil carbon and radiocarbon development
No full textTho model framework C-TOOL was used to simulate soil carbon and radiocarbon development. A simple three-compartment model was sufficient for describing the data
Part3_Petromurin C induces protective autophagy and apoptosis in FLT3-ITD-positive AML: synergy with gilteritinib
No full textTreatment of acute myeloid leukemia (AML) remains inefficient due to drug resistance and relapse, particularly in patients with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD). Marine-derived natural products have recently been used for drug development against AML. We show here that petromurin C, isolated from the culture extract of the marine-derived fungus Aspergillus candidus KUFA0062, which was isolated from the marine sponge Epipolasis sp., induces early autophagy followed by apoptotic cell death via activation of the intrinsic cell death pathway concomitant with mitochondrial stress and downregulation of Mcl-1 in FLT3-ITD mutated MV4-11 cells. Moreover, petromurin C synergized with the clinically-used FLT3 inhibitor gilteritinib at sub-toxic concentrations. Altogether our results suggest that petromurin C could act as an anti-leukemic agent alone or in combination with gilteritinib
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