139 research outputs found
Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly(N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy
Copyright © 2018 American Chemical Society. A novel poly(N-isopropylacrylamide) (PNIPAM) hydrogel containing different photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a significant improvement in water solubility and potential for PDT applications compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and PpIX-DME to the poly(N-isopropylacrylamide) chain was achieved using the dispersion polymerization method. This study describes how the use of nanohydrogel structures to deliver a photosensitizer with low water solubility and high aggregation tendencies in polar solvents overcomes these limitations. FT-IR spectroscopy, UV-vis spectroscopy, 1 H NMR, fluorescence spectroscopy, SEM, and DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels. Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers are covalently conjugated to the polymer chains, which prevents aggregation and thus allows significant singlet oxygen production upon illumination. Likewise, the lower critical solution temperature was raised to âŒ44 °C in the new PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with > 90% cell viability even at high concentrations of the photosensitizer in vitro. Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based nanohydrogel in the nanomolar range and a more modest, but significant, photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest that the new hydrogels have potential for applications in photodynamic therapy
Comparing Galaxy Morphology at Ultraviolet and Optical Wavelengths
We have undertaken an imaging survey of 34 nearby galaxies in far-ultraviolet
(FUV, ~1500A) and optical (UBVRI) passbands to characterize galaxy morphology
as a function of wavelength. This sample, which includes a range of classical
Hubble types from elliptical to irregular with emphasis on spirals at low
inclination angle, provides a valuable database for comparison with images of
high-z galaxies whose FUV light is redshifted into the optical and near-
infrared bands. Ultraviolet data are from the UIT Astro-2 mission. We present
images and surface brightness profiles for each galaxy, and we discuss the
wavelength-dependence of morphology for different Hubble types in the context
of understanding high-z objects. In general, the dominance of young stars in
the FUV produces the patchy appearance of a morphological type later than that
inferred from optical images. Prominent rings and circumnuclear star formation
regions are clearly evident in FUV images of spirals, while bulges, bars, and
old, red stellar disks are faint to invisible at these short wavelengths.
However, the magnitude of the change in apparent morphology ranges from
dramatic in early--type spirals with prominent optical bulges to slight in
late-type spirals and irregulars, in which young stars dominate both the UV and
optical emission. Starburst galaxies with centrally concentrated, symmetric
bursts display an apparent ``E/S0'' structure in the FUV, while starbursts
associated with rings or mergers produce a peculiar morphology. We briefly
discuss the inadequacy of the optically-defined Hubble sequence to describe FUV
galaxy images and estimate morphological k-corrections, and we suggest some
directions for future research with this dataset.Comment: Accepted for publication in the ApJS. 15 pages, 17 JPEG figures, 10
GIF figures. Paper and full resolution figures available at
http://nedwww.ipac.caltech.edu/level5/Kuchinski/frames.htm
The glycolytic enzyme phosphofructokinase-1 assembles into filaments.
Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that nonglycolytic metabolic enzymes regulating diverse pathways can assemble into polymers. We now show tetramer- and substrate-dependent filament assembly by phosphofructokinase-1 (PFK1), which is considered the "gatekeeper" of glycolysis because it catalyzes the step committing glucose to breakdown. Recombinant liver PFK1 (PFKL) isoform, but not platelet PFK1 (PFKP) or muscle PFK1 (PFKM) isoforms, assembles into filaments. Negative-stain electron micrographs reveal that filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer. Electron micrographs and biochemical data with a PFKL/PFKP chimera indicate that the PFKL regulatory domain mediates filament assembly. Quantified live-cell imaging shows dynamic properties of localized PFKL puncta that are enriched at the plasma membrane. These findings reveal a new behavior of a key glycolytic enzyme with insights on spatial organization and isoform-specific glucose metabolism in cells
Ultraviolet Signposts of Resonant Dynamics in the Starburst-Ringed Sab Galaxy, M94 (NGC 4736)
M94 (NGC 4736) is investigated using images from the Ultraviolet Imaging
Telescope (FUV-band), Hubble Space Telescope (NUV-band), Kitt Peak 0.9-m
telescope (H-alpha, R, and I bands), and Palomar 5-m telescope (B-band), along
with spectra from the International Ultraviolet Explorer and Lick 1-m
telescopes. The wide-field UIT image shows FUV emission from (a) an elongated
nucleus, (b) a diffuse inner disk, where H-alpha is observed in absorption, (c)
a bright inner ring of H II regions at the perimeter of the inner disk (R = 48
arcsec. = 1.1 kpc), and (d) two 500-pc size knots of hot stars exterior to the
ring on diametrically opposite sides of the nucleus (R= 130 arcsec. = 2.9 kpc).
The HST/FOC image resolves the NUV emission from the nuclear region into a
bright core and a faint 20 arcsec. long ``mini-bar'' at a position angle of 30
deg. Optical and IUE spectroscopy of the nucleus and diffuse inner disk
indicates an approximately 10^7 or 10^8 yr-old stellar population from
low-level starbirth activity blended with some LINER activity. Analysis of the
H-alpha, FUV, NUV, B, R, and I-band emission along with other observed tracers
of stars and gas in M94 indicates that most of the star formation is being
orchestrated via ring-bar dynamics involving the nuclear mini-bar, inner ring,
oval disk, and outer ring. The inner starburst ring and bi-symmetric knots at
intermediate radius, in particular, argue for bar-mediated resonances as the
primary drivers of evolution in M94 at the present epoch. Similar processes may
be governing the evolution of the ``core-dominated'' galaxies that have been
observed at high redshift. The gravitationally-lensed ``Pretzel Galaxy''
(0024+1654) at a redshift of approximately 1.5 provides an important precedent
in this regard.Comment: revised figure 1 (corrected coordinate labels on declination axis);
19 pages of text + 19 figures (jpg files); accepted for publication in A
Genealogies of Slavery
This chapter addresses the concept of slavery, exploring its character and significance as a dark page in history, but also as a specifically criminological and zemiological problem, in the context of international law and human rights. By tracing the ambiguities of slavery in international law and international development, the harms associated with slavery are considered. Harms include both those statutorily proscribed, and those that are not, but that can still be regarded as socially destructive. Traditionally, antislavery has been considered within the parameters of abolition and criminalization. In this context recently, anti-trafficking has emerged as a key issue in contemporary anti-slavery work. While valuable, anti-trafficking is shown to have significant limitations. It advances criminalization and stigmatization of the most vulnerable and further perpetuates harm. At the same time, it identifies structural conditions like poverty, vulnerability, and âunfreedomâ of movement only to put them aside. Linked to exploitation, violence and zemia, the chapter brings to the fore some crucial questions concerning the prospects of systemic theory in the investigation of slavery, that highlight the root causes of slavery, primarily poverty and inequality. Therefore, the chapter counterposes an alternative approach in which the orienting target is not abolition of slavery but advancing structural changes against social harm
The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT)
To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively). Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes
Joining S100 proteins and migration:for better or for worse, in sickness and in health
The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel
Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes
Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: âSome Collegeâ (yes/no, for any education beyond high school) and âGraduated Collegeâ (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 Ă 10â8) and suggestive (p < 1 Ă 10â6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.</p
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