Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid ...mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr961 null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr961 mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor1 mutation results in females that lack the germ-line and produce no eggs. Maternal tudor1 mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w1118 mutant mated females, but did not increase life span in w1118 mutant virgin females. Mifepristone decreased egg production in w1118 mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white+ and mini-white+ strains. Backcrossing of mini-white+ transgenes into the w1118 background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms.
Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human ...embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.
This paper presents a data set derived from the analysis of bottled and canned ciders that may be used for comparison with suspected counterfeit or substitute products. Isotopic analysis of the solid ...residues from ciders (predominantly sugar) provided a means to determine the addition of C4 plant sugars. The added sugars were found to comprise cane sugar, high-fructose corn syrup, glucose, or combinations. The majority of ciders from Australia and New Zealand were found to contain significant amounts of added sugar, which provided a limited means to distinguish these ciders from European ciders. The hydrogen and oxygen isotopic compositions of the whole ciders (predominantly water) were shown to be controlled by two factors, the water available to the parent plant and evaporation. Analysis of data derived from both isotopic and chemical analysis of ciders provided a means to discriminate between regions and countries of manufacture.
Abstract Objectives To study the color stability of dental composite resins using a thermocycling stain challenge model accounting for the complex effects of oral environment and tooth brushing. ...Methods Composite resin discs were made from Filtek Supreme Ultra (FiltekSU), TPH3 and Renamel, and subjected to thermocycling challenges in warm coffee (55 °C/pH 5.2) and a cold tea and fruit juice mixtures (5 °C/pH 3.6) for a total of 1000 cycles with 30 seconds dwell time in each solution per cycle. Color was assessed in the CIELAB color space using a Crystaleye dental spectrophotometer before and after thermocycling, and after brushing vigorously for 3 min. The thermocycling stain challenge was repeated for a second 1000 cycles and the discs were brushed again. Color changes were compared among the 3 groups using Kruskal–Wallis test. Results All 3 groups showed statistically significant color changes after stain challenge, with Δ E * as 5.74 for FiltekSU, 3.21 for TPH3 and 2.52 for Renamel. Color change was more significant in FiltekSU than in TPH3 and Renamel ( p < 0.05). After brushing, color recovered mostly to its original CIELAB values in TPH3 and Renamel but less so in FiltekSU. The second round of thermocycling stain challenge resulted in color changes in FiltekSU that largely could not be removed by vigorous brushing. Conclusions Color stability of FiltekSU is inferior to that of TPH3 and Renamel. The thermocycling stain challenge model can potentially differentiate surface staining that can be removed by brushing from true discoloration of the material that is refractory to oral hygiene procedures.
Beliefs about the malleability of global attributes like personality and intelligence – known as mindsets – are well-established predictors of resilience to challenges in educational contexts. Recent ...research further suggests that mindsets about anxiety may act in a similar fashion with mental health resilience. In this study we examined whether anxiety mindset would moderate relations between history of stressful life events and psychological distress and coping. Consistent with predictions, relations between number of stressful life events and posttraumatic stress symptoms, depression, substance use, and motivations for non-suicidal self-injury were weaker among those with more of a growth mindset relative to those with more of a fixed mindset. These initial results suggest that anxiety mindsets function in a similar way for mental health resilience as how mindsets of intelligence function for academic outcomes.
•Stressful life events relate to adverse psychological outcomes.•This study tested moderating role of growth mindset in this relationship.•Growth mindset of anxiety buffered impact of stressful life events.•This relationship was weaker among individuals with a growth mindset.•Growth mindset of anxiety may be promising treatment target.
A promising personal immunotherapy is autologous dendritic cells (DC) loaded ex vivo with autologous tumor antigens (ATA) derived from self-renewing autologous cancer cells. DC-ATA are suspended in ...granulocyte-macrophage colony stimulating factor at the time of each subcutaneous injection. Previously, irradiated autologous tumor cell vaccines have produced encouraging results in 150 cancer patients, but the DC-ATA vaccine demonstrated superiority in single-arm and randomized trials in metastatic melanoma. DC-ATA have been injected into more than 200 patients with melanoma, glioblastoma, and ovarian, hepatocellular, and renal cell cancers. Key observations include: 1 greater than 95% success rates for tumor cell cultures and monocyte collection for dendritic cell production; 2 injections are well-tolerated; 3 the immune response is rapid and includes primarily TH1/TH17 cellular responses; 4 efficacy has been suggested by delayed but durable complete tumor regressions in patients with measurable disease, by progression-free survival in glioblastoma, and by overall survival in melanoma.
To study if human embryonic stem cell-derived photoreceptors could survive and function without the support of retinal pigment epithelium (RPE) after transplantation into Royal College of Surgeons ...rats, a rat model of retinal degeneration caused by RPE dysfunction.
CSC14 human embryonic stem cells were differentiated into primordial eye structures called retinal organoids. Retinal organoids were analyzed by quantitative PCR and immunofluorescence and compared with human fetal retina. Retinal organoid sheets (30-70 day of differentiation) were transplanted into immunodeficient RCS rats, aged 44 to 56 days. The development of transplant organoids in vivo in relation to the host was examined by optical coherence tomography. Visual function was assessed by optokinetic testing, electroretinogram, and superior colliculus electrophysiologic recording. Cryostat sections were analyzed for various retinal, synaptic, and donor markers.
Retinal organoids showed similar gene expression to human fetal retina transplanted rats demonstrated significant improvement in visual function compared with RCS nonsurgery and sham surgery controls by ERGs at 2 months after surgery (but not later), optokinetic testing (up to 6 months after surgery) and electrophysiologic superior colliculus recordings (6-8 months after surgery). The transplanted organoids survived more than 7 months; developed photoreceptors with inner and outer segments, and other retinal cells; and were well-integrated within the host.
This study, to our knowledge, is the first to show that transplanted photoreceptors survive and function even with host's dysfunctional RPE. Our findings suggest that transplantation of organoid sheets from stem cells may be a promising approach/therapeutic for blinding diseases.
![Dhr96[1] mutation and mater...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1932-6203/small "Dhr96[1] mutation and maternal tudor[1] mutation increase life span and reduce the beneficial effects of mifepristone in mated female Drosophila")
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