106 research outputs found
Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes
Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa
Hypernovae and Other Black-Hole-Forming Supernovae
During the last few years, a number of exceptional core-collapse supernovae
(SNe) have been discovered. Their kinetic energy of the explosions are larger
by more than an order of magnitude than the typical values for this type of
SNe, so that these SNe have been called `Hypernovae'. We first describe how the
basic properties of hypernovae can be derived from observations and modeling.
These hypernovae seem to come from rather massive stars, thus forming black
holes. On the other hand, there are some examples of massive SNe with only a
small kinetic energy. We suggest that stars with non-rotating black holes are
likely to collapse "quietly" ejecting a small amount of heavy elements (Faint
supernovae). In contrast, stars with rotating black holes are likely to give
rise to very energetic supernovae (Hypernovae). We present distinct
nucleosynthesis features of these two types of "black-hole-forming" supernovae.
Hypernova nucleosynthesis is characterized by larger abundance ratios
(Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is
characterized by a large amount of fall-back. We show that the abundance
pattern of the most Fe deficient star, HE0107-5240, and other extremely
metal-poor carbon-rich stars are in good accord with those of
black-hole-forming supernovae, but not pair-instability supernovae. This
suggests that black-hole-forming supernovae made important contributions to the
early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and
Space Science; Kluwer) ed. C. L. Fryer (2003
Long gamma-ray bursts and core-collapse supernovae have different environments
When massive stars exhaust their fuel they collapse and often produce the
extraordinarily bright explosions known as core-collapse supernovae. On
occasion, this stellar collapse also powers an even more brilliant relativistic
explosion known as a long-duration gamma-ray burst. One would then expect that
long gamma-ray bursts and core-collapse supernovae should be found in similar
galactic environments. Here we show that this expectation is wrong. We find
that the long gamma-ray bursts are far more concentrated on the very brightest
regions of their host galaxies than are the core-collapse supernovae.
Furthermore, the host galaxies of the long gamma-ray bursts are significantly
fainter and more irregular than the hosts of the core-collapse supernovae.
Together these results suggest that long-duration gamma-ray bursts are
associated with the most massive stars and may be restricted to galaxies of
limited chemical evolution. Our results directly imply that long gamma-ray
bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9
February 2006, online publication 10 May 2006. Supplementary material
referred to in the text can be found at
http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new
version contains minor changes to match the final published versio
Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence
Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence
EVEREST: automatic identification and classification of protein domains in all protein sequences
BACKGROUND: Proteins are comprised of one or several building blocks, known as domains. Such domains can be classified into families according to their evolutionary origin. Whereas sequencing technologies have advanced immensely in recent years, there are no matching computational methodologies for large-scale determination of protein domains and their boundaries. We provide and rigorously evaluate a novel set of domain families that is automatically generated from sequence data. Our domain family identification process, called EVEREST (EVolutionary Ensembles of REcurrent SegmenTs), begins by constructing a library of protein segments that emerge in an all vs. all pairwise sequence comparison. It then proceeds to cluster these segments into putative domain families. The selection of the best putative families is done using machine learning techniques. A statistical model is then created for each of the chosen families. This procedure is then iterated: the aforementioned statistical models are used to scan all protein sequences, to recreate a library of segments and to cluster them again. RESULTS: Processing the Swiss-Prot section of the UniProt Knoledgebase, release 7.2, EVEREST defines 20,230 domains, covering 85% of the amino acids of the Swiss-Prot database. EVEREST annotates 11,852 proteins (6% of the database) that are not annotated by Pfam A. In addition, in 43,086 proteins (20% of the database), EVEREST annotates a part of the protein that is not annotated by Pfam A. Performance tests show that EVEREST recovers 56% of Pfam A families and 63% of SCOP families with high accuracy, and suggests previously unknown domain families with at least 51% fidelity. EVEREST domains are often a combination of domains as defined by Pfam or SCOP and are frequently sub-domains of such domains. CONCLUSION: The EVEREST process and its output domain families provide an exhaustive and validated view of the protein domain world that is automatically generated from sequence data. The EVEREST library of domain families, accessible for browsing and download at [1], provides a complementary view to that provided by other existing libraries. Furthermore, since it is automatic, the EVEREST process is scalable and we will run it in the future on larger databases as well. The EVEREST source files are available for download from the EVEREST web site
An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains
During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)
A survey of integral α-helical membrane proteins
Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior studies have explored the functional breadth and evolution of proteins and families of particular interest, such as the diversity of transport-associated membrane protein families in prokaryotes and eukaryotes, the composition of integral membrane proteins, and family classification of all human G-protein coupled receptors. However, a comprehensive analysis of the content and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was developed to define the integral membrane genome and associations between 21,379 proteins from 34 genomes; most, but not all of these proteins belong to 598 defined families. The pipeline was used to provide target input for a structural genomics project that successfully cloned, expressed, and purified 61 of our first 96 selected targets in yeast. Furthermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmembrane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated membrane proteins in whole genomes, and (3) to identify putative new membrane protein families
A non-spherical core in the explosion of supernova SN 2004dj
An important and perhaps critical clue to the mechanism driving the explosion
of massive stars as supernovae is provided by the accumulating evidence for
asymmetry in the explosion. Indirect evidence comes from high pulsar
velocities, associations of supernovae with long-soft gamma-ray bursts, and
asymmetries in late-time emission-line profiles. Spectropolarimetry provides a
direct probe of young supernova geometry, with higher polarization generally
indicating a greater departure from spherical symmetry. Large polarizations
have been measured for 'stripped-envelope' (that is, type Ic) supernovae, which
confirms their non-spherical morphology; but the explosions of massive stars
with intact hydrogen envelopes (type II-P supernovae) have shown only weak
polarizations at the early times observed. Here we report multi-epoch
spectropolarimetry of a classic type II-P supernova that reveals the abrupt
appearance of significant polarization when the inner core is first exposed in
the thinning ejecta (~90 days after explosion). We infer a departure from
spherical symmetry of at least 30 per cent for the inner ejecta. Combined with
earlier results, this suggests that a strongly non-spherical explosion may be a
generic feature of core-collapse supernovae of all types, where the asphericity
in type II-P supernovae is cloaked at early times by the massive, opaque,
hydrogen envelope.Comment: Accepted for publication by Nature (results embargoed until 23 March
2006); 14 pages, 2 figure
Possible involvement of distinct phylogenetic clusters of HIV-1 variants in the discrepancies between coreceptor tropism predictions based on viral RNA and proviral DNA
The Evolution of Compact Binary Star Systems
We review the formation and evolution of compact binary stars consisting of
white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and
BHs are thought to be the primary astrophysical sources of gravitational waves
(GWs) within the frequency band of ground-based detectors, while compact
binaries of WDs are important sources of GWs at lower frequencies to be covered
by space interferometers (LISA). Major uncertainties in the current
understanding of properties of NSs and BHs most relevant to the GW studies are
discussed, including the treatment of the natal kicks which compact stellar
remnants acquire during the core collapse of massive stars and the common
envelope phase of binary evolution. We discuss the coalescence rates of binary
NSs and BHs and prospects for their detections, the formation and evolution of
binary WDs and their observational manifestations. Special attention is given
to AM CVn-stars -- compact binaries in which the Roche lobe is filled by
another WD or a low-mass partially degenerate helium-star, as these stars are
thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure
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