357 research outputs found
Exploring neurotransmitters and their receptors for breast cancer prevention and treatment
While psychological factors have long been linked to breast cancer pathogenesis and outcomes, accumulating evidence is revealing how the nervous system contributes to breast cancer development, progression, and treatment resistance. Central to the psychological-neurological nexus are interactions between neurotransmitters and their receptors expressed on breast cancer cells and other types of cells in the tumor microenvironment, which activate various intracellular signaling pathways. Importantly, the manipulation of these interactions is emerging as a potential avenue for breast cancer prevention and treatment. However, an important caveat is that the same neurotransmitter can exert multiple and sometimes opposing effects. In addition, certain neurotransmitters can be produced and secreted by non-neuronal cells including breast cancer cells that similarly activate intracellular signaling upon binding to their receptors. In this review we dissect the evidence for the emerging paradigm linking neurotransmitters and their receptors with breast cancer. Foremost, we explore the intricacies of such neurotransmitter-receptor interactions, including those that impinge on other cellular components of the tumor microenvironment, such as endothelial cells and immune cells. Moreover, we discuss findings where clinical agents used to treat neurological and/or psychological disorders have exhibited preventive/therapeutic effects against breast cancer in either associative or pre-clinical studies. Further, we elaborate on the current progress to identify druggable components of the psychological-neurological nexus that can be exploited for the prevention and treatment of breast cancer as well as other tumor types. We also provide our perspectives regarding future challenges in this field where multidisciplinary cooperation is a paramount requirement
Evolutionary distances in the twilight zone -- a rational kernel approach
Phylogenetic tree reconstruction is traditionally based on multiple sequence
alignments (MSAs) and heavily depends on the validity of this information
bottleneck. With increasing sequence divergence, the quality of MSAs decays
quickly. Alignment-free methods, on the other hand, are based on abstract
string comparisons and avoid potential alignment problems. However, in general
they are not biologically motivated and ignore our knowledge about the
evolution of sequences. Thus, it is still a major open question how to define
an evolutionary distance metric between divergent sequences that makes use of
indel information and known substitution models without the need for a multiple
alignment. Here we propose a new evolutionary distance metric to close this
gap. It uses finite-state transducers to create a biologically motivated
similarity score which models substitutions and indels, and does not depend on
a multiple sequence alignment. The sequence similarity score is defined in
analogy to pairwise alignments and additionally has the positive semi-definite
property. We describe its derivation and show in simulation studies and
real-world examples that it is more accurate in reconstructing phylogenies than
competing methods. The result is a new and accurate way of determining
evolutionary distances in and beyond the twilight zone of sequence alignments
that is suitable for large datasets.Comment: to appear in PLoS ON
Quasi-Normal Modes of Stars and Black Holes
Perturbations of stars and black holes have been one of the main topics of
relativistic astrophysics for the last few decades. They are of particular
importance today, because of their relevance to gravitational wave astronomy.
In this review we present the theory of quasi-normal modes of compact objects
from both the mathematical and astrophysical points of view. The discussion
includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om,
Kerr and Kerr-Newman) and relativistic stars (non-rotating and
slowly-rotating). The properties of the various families of quasi-normal modes
are described, and numerical techniques for calculating quasi-normal modes
reviewed. The successes, as well as the limits, of perturbation theory are
presented, and its role in the emerging era of numerical relativity and
supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in
Relativity
Gravitational Waves from Gravitational Collapse
Gravitational wave emission from the gravitational collapse of massive stars
has been studied for more than three decades. Current state of the art
numerical investigations of collapse include those that use progenitors with
realistic angular momentum profiles, properly treat microphysics issues,
account for general relativity, and examine non--axisymmetric effects in three
dimensions. Such simulations predict that gravitational waves from various
phenomena associated with gravitational collapse could be detectable with
advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for
publication in Living Reviews in Relativity (http://www.livingreviews.org
Accreting Black Holes
This chapter provides a general overview of the theory and observations of
black holes in the Universe and on their interpretation. We briefly review the
black hole classes, accretion disk models, spectral state classification, the
AGN classification, and the leading techniques for measuring black hole spins.
We also introduce quasi-periodic oscillations, the shadow of black holes, and
the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and
Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer
Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin
note: substantial text overlap with arXiv:1711.1025
Reaction rates and transport in neutron stars
Understanding signals from neutron stars requires knowledge about the
transport inside the star. We review the transport properties and the
underlying reaction rates of dense hadronic and quark matter in the crust and
the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of
Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes,
references updated, overview graphic added in the introduction, improvements
in Sec IV.A.
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
Gravitational waves from single neutron stars: an advanced detector era survey
With the doors beginning to swing open on the new gravitational wave
astronomy, this review provides an up-to-date survey of the most important
physical mechanisms that could lead to emission of potentially detectable
gravitational radiation from isolated and accreting neutron stars. In
particular we discuss the gravitational wave-driven instability and
asteroseismology formalism of the f- and r-modes, the different ways that a
neutron star could form and sustain a non-axisymmetric quadrupolar "mountain"
deformation, the excitation of oscillations during magnetar flares and the
possible gravitational wave signature of pulsar glitches. We focus on progress
made in the recent years in each topic, make a fresh assessment of the
gravitational wave detectability of each mechanism and, finally, highlight key
problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and
Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor
corrections to match published versio
The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7
<p>Abstract</p> <p>Background</p> <p>CD44, a hyaluronan (HA) receptor, is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. The CD44 gene contains 20 exons that are alternatively spliced, giving rise to many CD44 isoforms, perhaps including tumor-specific sequences.</p> <p>Methods</p> <p>Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to detect CD44st mRNA and CD44 protein in sensitive MCF-7, Lovo, K562 and HL-60 cell lines as well as their parental counterparts, respectively. The full length cDNA encoding CD44st was obtained from the total RNA isolated from MCF-7/Adr cells by RT-PCR, and subcloned into the pMD19-T vector. The CD44st gene sequence and open reading frame were confirmed by restriction enzyme analysis and nucleotide sequencing, and then inserted into the eukaryotic expression vector pcDNA3.1. The pcDNA3.1-CD44st was transfected into MCF-7 cells using Lipofectamine. After transfection, the positive clones were obtained by G418 screening. The changes of the MMP-2 and MMP-9 genes and protein levels were detected by RT-PCR and gelatin zymography, respectively. The number of the cells penetrating through the artificial matrix membrane in each group (MCF-7, MCF-7+HA, MCF-7/neo, MCF-7/neo+HA, MCF-7/CD44st, MCF-7/CD44st+HA and MCF-7/CD44st+Anti-CD44+HA) was counted to compare the change of the invasion capability regulated by the CD44st. Erk and P-Erk were investigated by Western blotting to approach the molecular mechanisms of MMP-2 and MMP-9 expression regulated by the CD44st.</p> <p>Results</p> <p>Sensitive MCF-7, Lovo, K562 and HL-60 cells did not contain CD44st mRNA and CD44 protein. In contrast, the multidrug resistance MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cells expressed CD44st mRNA and CD44 protein. The CD44st mRNA gene sequence was successfully cloned into the recombinant vector pcDNA3.1 and identified by the two restriction enzymes. It was confirmed that the reconstructed plasmid contained the gene sequence of CD44st that was composed of exons 1 to 4, 16 to 17, and 1 to 205 bases of exons 18. The new gene sequence was sent to NCBI for publication, and obtained the registration number FJ216964. The up-regulated level of the mRNA of the CD44 gene and the CD44 protein were detected, respectively, by RT-PCR and flow cytometry in MCF-7 cells transfected with pcDNA3.1-CD44st. The invasiveness of the cells and the activity of MMP-2 and MMP-9 were clearly activated by HA treatment, and blocked by CD44 neutralizing antibody. MCF-7/CD44st cells pretreated with the neutralizing antibody against CD44, and the inhibitor of MAPKs signaling pathway, could strongly block the expression of P-Erk.</p> <p>Conclusions</p> <p>A new CD44st was expressed in multidrug resistant MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cells. The expression vector pcDNA3.1-CD44st was cloned and constructed successfully, and stably transfected into MCF-7 cells. HA could interact with the new CD44st and regulate the expression of MMP-2 and MMP-9, which could increase the invasion capability of MCF-7 cells through the Ras/MAPK signaling pathway.</p
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