Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

Challenges in lifestyle and community interventions research; a call for innovation

Earlier this year the BMC portfolio was enriched by a new journal BMC Obesity. Here, we present the aims and objectives of the section on Lifestyle and Community Interventions. Innovative research is needed. Preventing or managing obesity requires addressing different determinants across multiple levels where diverse levers and stakeholders can play a critical role. Interactions of these determinants within and between systems need to be studied. How to leverage, manage and measure this complexity underlies the innovation that is needed in the next generation of obesity interventions. The ambition of the Lifestyle and Community Interventions section is to provide a space for innovative research, including research that falls outside the traditional comfort zone. We welcome studies of heterogeneous designs, including those of qualitative, quantitative, mixed and systems methodologies. Studies of interest include not only outcomes research of interventions but also process evaluation, cost-effectiveness or cost-benefit analysis, and implementation and dissemination research. Innovations that integrate diverse intervention levers or combine primary and secondary levels of prevention are particularly encouraged. The general aim of BMC Obesity’s Lifestyle and Community Interventions section is to advance our ability to decide on what combinations of approaches will be required to effectively and equitably prevent obesity

Quantum spin liquid states in the two dimensional kagome antiferromagnets, ZnxCu4-x(OD)6Cl2

A three-dimensional system of interacting spins typically develops static long-range order when it is cooled. If the spins are quantum (S = 1/2), however, novel quantum paramagnetic states may appear. The most highly sought state among them is the resonating valence bond (RVB) state in which every pair of neighboring quantum spins form entangled spin singlets (valence bonds) and the singlets are quantum mechanically resonating amongst all the possible highly degenerate pairing states. Here we provide experimental evidence for such quantum paramagnetic states existing in frustrated antiferromagnets, ZnxCu4-x(OD)6Cl2, where the S = 1/2 magnetic Cu2+ moments form layers of a two-dimensional kagome lattice. We find that in Cu4(OD)6Cl2, where distorted kagome planes are weakly coupled to each other, a dispersionless excitation mode appears in the magnetic excitation spectrum below ~ 20 K, whose characteristics resemble those of quantum spin singlets in a solid state, known as a valence bond solid (VBS), that breaks translational symmetry. Doping nonmagnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens the interplane coupling but also dilutes the magnetic occupancy of the kagome lattice. The VBS state is suppressed and for ZnCu3(OD)6Cl2 where the kagome planes are undistorted and 90% occupied by the Cu2+ ions, the low energy spin fluctuations in the spin liquid phase become featureless

Serial optical coherence microscopy for label-free volumetric histopathology

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents

SUCI02 inhibits the erbB-2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G 1 phase in breast cancer cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73321/1/j.1349-7006.2006.00143.x.pd

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

Electrically Tunable Excitonic Light Emitting Diodes based on Monolayer WSe2 p-n Junctions

Light-emitting diodes are of importance for lighting, displays, optical interconnects, logic and sensors. Hence the development of new systems that allow improvements in their efficiency, spectral properties, compactness and integrability could have significant ramifications. Monolayer transition metal dichalcogenides have recently emerged as interesting candidates for optoelectronic applications due to their unique optical properties. Electroluminescence has already been observed from monolayer MoS2 devices. However, the electroluminescence efficiency was low and the linewidth broad due both to the poor optical quality of MoS2 and to ineffective contacts. Here, we report electroluminescence from lateral p-n junctions in monolayer WSe2 induced electrostatically using a thin boron nitride support as a dielectric layer with multiple metal gates beneath. This structure allows effective injection of electrons and holes, and combined with the high optical quality of WSe2 it yields bright electroluminescence with 1000 times smaller injection current and 10 times smaller linewidth than in MoS2. Furthermore, by increasing the injection bias we can tune the electroluminescence between regimes of impurity-bound, charged, and neutral excitons. This system has the required ingredients for new kinds of optoelectronic devices such as spin- and valley-polarized light-emitting diodes, on-chip lasers, and two-dimensional electro-optic modulators.Comment: 13 pages main text with 4 figures + 4 pages upplemental material

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD