Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.

Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures

Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters

Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed

A Computation in a Cellular Automaton Collider Rule 110

A cellular automaton collider is a finite state machine build of rings of one-dimensional cellular automata. We show how a computation can be performed on the collider by exploiting interactions between gliders (particles, localisations). The constructions proposed are based on universality of elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and computing on rings.Comment: 39 pages, 32 figures, 3 table

The J-triplet Cooper pairing with magnetic dipolar interactions

Recently, cold atomic Fermi gases with the large magnetic dipolar interaction have been laser cooled down to quantum degeneracy. Different from electric-dipoles which are classic vectors, atomic magnetic dipoles are quantum-mechanical matrix operators proportional to the hyperfine-spin of atoms, thus provide rich opportunities to investigate exotic many-body physics. Furthermore, unlike anisotropic electric dipolar gases, unpolarized magnetic dipolar systems are isotropic under simultaneous spin-orbit rotation. These features give rise to a robust mechanism for a novel pairing symmetry: orbital p-wave (L=1) spin triplet (S=1) pairing with total angular momentum of the Cooper pair J=1. This pairing is markedly different from both the $^3$He-B phase in which J=0 and the $^3$He-$A$ phase in which $J$ is not conserved. It is also different from the p-wave pairing in the single-component electric dipolar systems in which the spin degree of freedom is frozen

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Driven coherent oscillations of a single electron spin in a quantum dot

The ability to control the quantum state of a single electron spin in a quantum dot is at the heart of recent developments towards a scalable spin-based quantum computer. In combination with the recently demonstrated exchange gate between two neighbouring spins, driven coherent single spin rotations would permit universal quantum operations. Here, we report the experimental realization of single electron spin rotations in a double quantum dot. First, we apply a continuous-wave oscillating magnetic field, generated on-chip, and observe electron spin resonance in spin-dependent transport measurements through the two dots. Next, we coherently control the quantum state of the electron spin by applying short bursts of the oscillating magnetic field and observe about eight oscillations of the spin state (so-called Rabi oscillations) during a microsecond burst. These results demonstrate the feasibility of operating single-electron spins in a quantum dot as quantum bits.Comment: Total 25 pages. 11 pages main text, 5 figures, 9 pages supplementary materia

T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1