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

On the complexity of color-avoiding site and bond percolation

The mathematical analysis of robustness and error-tolerance of complex networks has been in the center of research interest. On the other hand, little work has been done when the attack-tolerance of the vertices or edges are not independent but certain classes of vertices or edges share a mutual vulnerability. In this study, we consider a graph and we assign colors to the vertices or edges, where the color-classes correspond to the shared vulnerabilities. An important problem is to find robustly connected vertex sets: nodes that remain connected to each other by paths providing any type of error (i.e. erasing any vertices or edges of the given color). This is also known as color-avoiding percolation. In this paper, we study various possible modeling approaches of shared vulnerabilities, we analyze the computational complexity of finding the robustly (color-avoiding) connected components. We find that the presented approaches differ significantly regarding their complexity.Comment: 14 page

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Universal features of correlated bursty behaviour

Inhomogeneous temporal processes, like those appearing in human communications, neuron spike trains, and seismic signals, consist of high-activity bursty intervals alternating with long low-activity periods. In recent studies such bursty behavior has been characterized by a fat-tailed inter-event time distribution, while temporal correlations were measured by the autocorrelation function. However, these characteristic functions are not capable to fully characterize temporally correlated heterogenous behavior. Here we show that the distribution of the number of events in a bursty period serves as a good indicator of the dependencies, leading to the universal observation of power-law distribution in a broad class of phenomena. We find that the correlations in these quite different systems can be commonly interpreted by memory effects and described by a simple phenomenological model, which displays temporal behavior qualitatively similar to that in real systems

Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis. Materials and Methods: We included 780 PWH with suppressed viral replication (<50 copies/mL) and absence of hepatitis B and hepatitis C co-infection and 65 uninfected controls from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study. Flow cytometry was used to determine T-cell activation (CD38+HLA-DR+), senescence (CD28-CD57+), and apoptosis (CD28-CD95+). T-cell subsets are reported as proportions of CD4+ and CD8+ T-cells. We defined an elevated proportion of a given T-cell subset as above the 75th percentile. Regression models were used to determine the association between HIV status and T-cell subset and in PWH to determine the association between age or HIV-specific risk factors and T-cell subsets. Furthermore, an interaction between HIV status and age on T-cell subsets was investigated with an interaction term in models including both PWH and controls. Models were adjusted for age, sex, BMI, and smoking status. Results: In adjusted models a positive HIV status was associated with elevated proportions of CD8+ activated (p = 0.009), CD4+ senescent (p = 0.004), CD4+ apoptotic (p = 0.002), and CD8+ apoptotic (p = 0.003) T-cells. In PWH a 10-year increase in age was associated with higher proportions of CD4+ and CD8+ senescent (p = 0.001 and p < 0.001) and CD4+ and CD8+ apoptotic T-cells (p < 0.001 and p < 0.001). However, no interaction between HIV status and age was found. Furthermore, in PWH a CD4+/CD8+ ratio < 1 was associated with elevated proportions of T-cell activation, senescence, and apoptosis. Discussion: We found evidence of residual T-cell immune dysfunction in well-treated PWH without HBV or HCV co-infection, and age was associated with T-cell senescence and apoptosis. Our data supports that HIV infection has similar effects as aging on T-cell subsets. However, since no interaction between HIV status and age was found on these parameters, we found no evidence to support accelerated immunological aging in PWH

Observation of anomalous decoherence effect in a quantum bath at room temperature

Decoherence of quantum objects is critical to modern quantum sciences and technologies. It is generally believed that stronger noises cause faster decoherence. Strikingly, recent theoretical research discovers the opposite case for spins in quantum baths. Here we report experimental observation of the anomalous decoherence effect for the electron spin-1 of a nitrogen-vacancy centre in high-purity diamond at room temperature. We demonstrate that under dynamical decoupling, the double-transition can have longer coherence time than the single-transition, even though the former couples to the nuclear spin bath as twice strongly as the latter does. The excellent agreement between the experimental and the theoretical results confirms the controllability of the weakly coupled nuclear spins in the bath, which is useful in quantum information processing and quantum metrology.Comment: 22 pages, related paper at http://arxiv.org/abs/1102.557

The tumor suppressor Fat1 is dispensable for normal murine hematopoiesis

Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis

Application of a portable coordinate measuring machine onto automotive door panel for quality inspection activity

An experimental investigation was conducted to explore the feasibility of replacing the current inspection method by a portable coordinate measuring machine (CMM) for daily quality inspection in automotive industry. The experiment focusses on inspecting stamped body parts due to the significant number of inspection points that could be time consuming for inspection activities. Two inspection methods were performed, i.e. the application of checking fixture (CF) which is the current method and the second method was using a portable CMM. Both inspections were performed onto the same loose freeform surface of an outer door panel. Factors related to inspection duration, economical and data reliability were all compared to understand the practicality of replacing the current inspection method with a portable CMM. It was found that a portable CMM provide a significant shorter inspection duration, more economical and better data reliability but at the same time is unable to match the performance of conventional inspection onto freeform surface. The conclusion was made that a portable CMM alone is not sufficient to replace the current inspection method thus require further study

Room temperature plasmonic lasing in a continuous wave operation mode from an InGaN/GaN single nanorod with a low threshold

It is crucial to fabricate nano photonic devices such as nanolasers in order to meet the requirements for the integration of photonic and electronic circuits on the nanometre scale. The great difficulty is to break down a bottleneck as a result of the diffraction limit of light. Nanolasers on a subwavelength scale could potentially be fabricated based on the principle of surface plasmon amplification by stimulated emission of radiation (SPASER). However, a number of technological challenges will have to be overcome in order to achieve a SPASER with a low threshold, allowing for a continuous wave (cw) operation at room temperature. We report a nano-SPASER with a record low threshold at room temperature, optically pumped by using a cw diode laser. Our nano-SPASER consists of a single InGaN/GaN nanorod on a thin SiO2 spacer layer on a silver film. The nanorod containing InGaN/GaN multi-quantum-wells is fabricated by means of a cost-effective post-growth fabrication approach. The geometry of the nanorod/dielectric spacer/plasmonic metal composite allows us to have accurate control of the surface plasmon coupling, offering an opportunity to determine the optimal thickness of the dielectric spacer. This approach will open up a route for further fabrication of electrically injected plasmonic lasers

Statistical and visual differentiation of subcellular imaging

<p>Abstract</p> <p>Background</p> <p>Automated microscopy technologies have led to a rapid growth in imaging data on a scale comparable to that of the genomic revolution. High throughput screens are now being performed to determine the localisation of all of proteins in a proteome. Closer to the bench, large image sets of proteins in treated and untreated cells are being captured on a daily basis to determine function and interactions. Hence there is a need for new methodologies and protocols to test for difference in subcellular imaging both to remove bias and enable throughput. Here we introduce a novel method of statistical testing, and supporting software, to give a rigorous test for difference in imaging. We also outline the key questions and steps in establishing an analysis pipeline.</p> <p>Results</p> <p>The methodology is tested on a high throughput set of images of 10 subcellular localisations, and it is shown that the localisations may be distinguished to a statistically significant degree with as few as 12 images of each. Further, subtle changes in a protein's distribution between nocodazole treated and control experiments are shown to be detectable. The effect of outlier images is also examined and it is shown that while the significance of the test may be reduced by outliers this may be compensated for by utilising more images. Finally, the test is compared to previous work and shown to be more sensitive in detecting difference. The methodology has been implemented within the iCluster system for visualising and clustering bio-image sets.</p> <p>Conclusion</p> <p>The aim here is to establish a methodology and protocol for testing for difference in subcellular imaging, and to provide tools to do so. While iCluster is applicable to moderate (<1000) size image sets, the statistical test is simple to implement and will readily be adapted to high throughput pipelines to provide more sensitive discrimination of difference.</p