115 research outputs found
The Color of Lactotroph Secretory Granules Stained with FM1-43 Depends on Dye Concentration
AbstractWhen pituitary lactotroph granules undergo exocytosis in the presence of FM1-43, their cores absorb dye and fluoresce brightly. We report that different granules fluoresce with different colors, despite being stained with a single fluorescent dye; emission spectra from individual granules show up to a 25nm difference between the greenest and reddest granules. We found a correlation between granule color and average fluorescence intensity, suggesting that granule color depends upon dye concentration. We confirmed this in two ways: by increasing FM dye concentration in granules, which red shifted granule color, and by partially photobleaching the FM dye in granules, which green shifted granule color. Increasing stimulation intensity (by increasing KCl concentration) increased the proportion of red granules, indicating that granules exocytosing during intense stimulation bound more dye. This, perhaps, reflects differences in granule core maturation and condensation in which mature granules with condensed cores bind more FM dye but require more intense stimulation to be released. Concentration-dependent color shifts of FM dyes may be useful for monitoring aggregation processes occurring on a size scale smaller than the optical limit
Multi-layer atom chips for versatile atom micro manipulation
We employ a combination of optical UV- and electron-beam-lithography to
create an atom chip combining sub-micron wire structures with larger
conventional wires on a single substrate. The new multi-layer fabrication
enables crossed wire configurations, greatly enhancing the flexibility in
designing potentials for ultra cold quantum gases and Bose-Einstein
condensates. Large current densities of >6 x 10^7 A/cm^2 and high voltages of
up to 65 V across 0.3 micron gaps are supported by even the smallest wire
structures. We experimentally demonstrate the flexibility of the next
generation atom chip by producing Bose-Einstein condensates in magnetic traps
created by a combination of wires involving all different fabrication methods
and structure sizes.Comment: 4 pages, 5 figure
Application of immunocytochemistry and BRAF mutational analysis to direct smears of metastatic melanoma
BACKGROUND: The cytodiagnosis of melanoma in fineâneedle aspiration (FNA) specimens can be challenging, often requiring the use of immunocytochemistry. As constitutively activating mutations in the BRAF oncogene are present in at least 40% of melanomas, the use of FNA material to interrogate the BRAF mutational status is likely to increase. Because cell blocks, traditionally used for these studies, can occasionally exhibit insufficient tumor cellularity, the authors investigated the utility of direct smears for immunocytochemistry and BRAF mutational analysis. METHODS: Immunocytochemistry for Sâ100, HMBâ45, and Martâ1 was prospectively performed on direct smears in 17 FNAs of metastatic melanoma. Next, BRAF sequencing was performed using DNA isolated from archived DiffâQuikâstained direct smears for 15 cases. In parallel, sequencing was performed using DNA obtained from corresponding cell blocks. RESULTS: Sâ100 positivity in the tumor cells was observed in all 17 cases. HMBâ45 and Martâ1 positivity was noted in 81% and 88% of cases, respectively. All 3 markers were positive in 76% of cases. Next, of the 15 archived melanoma FNAs tested, BRAF mutations were observed in 8 (53%); 5 and 3 melanomas harbored the V600E and V600K mutation, respectively. Corresponding cell blocks were also tested for all 15 cases, yielding concordant BRAF results in 14 (93%); 1 cell block yielded a falseânegative result. CONCLUSIONS: Cytologic direct smears represent a robust and valuable source of cellular material for immunocytochemistry and molecular studies, especially in instances in which inadequate cell block cellularity is anticipated or encountered. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. This study demonstrates that direct smears represent a robust and valuable source of cellular material for ancillary studies used in the cytologic diagnosis of melanoma. Direct smears can be effectively used for confirmatory immunocytochemical studies and molecular assays designed to interrogate the BRAF mutational status of melanoma, especially in scenarios in which inadequate cell block cellularity is anticipated or encountered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90193/1/20180_ftp.pd
Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial
Background
Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS.
Methods
In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358.
Results
Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6â8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64â1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58â1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen.
Conclusions
No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences
Effect of garlic on cardiovascular disorders: a review
Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Recommended from our members
Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation
Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score â„65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was â„70, who were assessed for ASD, and who had proteins measured in blood collected on â„2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2â5.3) and IL-6 (OR; 95% CI: 2.6; 1.03â6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2â6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3â5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1â3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1â4.2)
Session 2: The NIH Office Of Dietary Supplements: A Twenty-Five Year Retrospective
The Dietary Supplement Health and Education Act (DSHEA) of 1994 amended the U.S. Federal Food, Drug, and Cosmetic Act. The DSHEA also amended the U.S. Public Health Service Act in order to establish the Office of Dietary Supplements (ODS) and place it within the National Institutes of Health (NIH). Passage of the DSHEA assured consumer access to supplements, defined dietary supplements as a special category of foods, laid out a regulatory framework enforced by the Food and Drug Administration (FDA), and provided a basis for creating and disseminating research to strengthen knowledge and understanding of dietary supplements.
As directed by Congress, ODSâs mission to foster an enhanced quality of life and health for the U.S. population is achieved by providing resources for evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public. The ODS budget has grown over the years from a bit less that 25 million in 2018. This amount is relatively modest by NIH standards, but ODS effectively leverages its resources with other parts of the NIH and with other collaborators to create a disproportionately large impact on our understanding of dietary supplements.
Over the past 25 years, ODS and its partners have created the NIH Centers for Advancing Research on Botanical and other Natural products (CARBON) program[1], the ODS Analytical Methods and Reference Materials Program[2], the ODS Evidence-based Review Program[3], the ODS Population Studies Program[4], and a brand new Biochemical Mediators of Resilience Program.
The Office has also created free public databases of dietary supplement labels[5] and ingredients[6], and a series of dietary supplement fact sheets[7]. Other research initiatives include creation and oversight of an international program for standardization of vitamin D metabolite measurements, support of measurement of total nutrient intake through the National Health and Nutrition Examination Survey and similar activities, a program for evaluation of the sufficiency of iodine intake, a program for studying nutrient biomarkers that includes collection and evaluation of information on intake, status, and associated health effects. Finally, the Office of Dietary Supplements co-funds dietary supplement grants with many other NIH Institutes and Centers. Last yearâs co-fund commitment was approximately $14 million, about half of the total ODS budget.
Going forward, ODS will continue to pursue its Congressionally mandated mission by continuing successful programs and by creating new programs as emerging needs are identified
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