Differential expression of microRNA-206 and its target genes in pre-eclampsia

Objectives: Pre-eclampsia is a multi-system disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with pre-eclampsia. Methods: Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed pre-eclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with pre-eclampsia matched with 19 women with normotensive pregnancies. Results: From the microarray, we identified 1 miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and 6 miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation only one, miR-206, was found to be significantly increased in 28 week samples in women who later developed pre-eclampsia (1.4 fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with pre-eclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be down-regulated (0.41 ± 0.04) in placental tissue from women with pre-eclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. Conclusions: Our pilot study has identified miRNA-206 as a novel factor up-regulated in pre-eclampsia within the maternal circulation and in placental tissue

Multimodal Imaging of Alzheimer Pathophysiology in the Brain's Default Mode Network

The spatial correlations between the brain's default mode network (DMN) and the brain regions known to develop pathophysiology in Alzheimer's disease (AD) have recently attracted much attention. In this paper, we compare results of different functional and structural imaging modalities, including MRI and PET, and highlight different patterns of anomalies observed within the DMN. Multitracer PET imaging in subjects with and without dementia has demonstrated that [C-11]PIB- and [F-18]FDDNP-binding patterns in patients with AD overlap within nodes of the brain's default network including the prefrontal, lateral parietal, lateral temporal, and posterior cingulate cortices, with the exception of the medial temporal cortex (especially, the hippocampus) where significant discrepancy between increased [F-18]FDDNP binding and negligible [C-11]PIB-binding was observed. [F-18]FDDNP binding in the medial temporal cortex—a key constituent of the DMN—coincides with both the presence of amyloid and tau pathology, and also with cortical areas with maximal atrophy as demonstrated by T1-weighted MR imaging of AD patients

Protein kinase C and rho activated coiled coil protein kinase 2 (ROCK2) modulate Alzheimer's APP metabolism and phosphorylation of the Vps10-domain protein, SorL1

<p>Abstract</p> <p>Background</p> <p>Generation of the amyloid β (Aβ) peptide of Alzheimer's disease (AD) is differentially regulated through the intracellular trafficking of the amyloid β precursor protein (APP) within the secretory and endocytic pathways. Protein kinase C (PKC) and rho-activated coiled-coil kinases (ROCKs) are two "third messenger" signaling molecules that control the relative utilization of these two pathways. Several members of the Vps family of receptors (Vps35, SorL1, SorCS1) play important roles in post-<it>trans</it>-Golgi network (<it>TGN</it>) sorting and generation of APP derivatives, including Aβ at the TGN, endosome and the plasma membrane. We now report that Vps10-domain proteins are candidate substrates for PKC and/or ROCK2 and act as phospho-state-sensitive physiological effectors for post-<it>TGN </it>sorting of APP and its derivatives.</p> <p>Results</p> <p>Analysis of the SorL1 cytoplasmic tail revealed multiple consensus sites for phosphorylation by protein kinases. SorL1 was subsequently identified as a phosphoprotein, based on sensitivity of its electrophoretic migration pattern to calf intestine alkaline phosphatase and on its reaction with anti-phospho-serine antibodies. Activation of PKC resulted in increased shedding of the ectodomains of both APP and SorL1, and this was paralleled by an apparent increase in the level of the phosphorylated form of SorL1. ROCK2, the neuronal isoform of another protein kinase, was found to form complexes with SorL1, and both ROCK2 inhibition and ROCK2 knockdown enhanced generation of both soluble APP and Aβ.</p> <p>Conclusion</p> <p>These results highlight the potential importance of SorL1 in elucidating phospho-state sensitive mechanisms in the regulation of metabolism of APP and Aβ by PKC and ROCK2.</p

Measuring Temperature Gradients over Nanometer Length Scales

When a quantum dot is subjected to a thermal gradient, the temperature of electrons entering the dot can be determined from the dot's thermocurrent if the conductance spectrum and background temperature are known. We demonstrate this technique by measuring the temperature difference across a 15 nm quantum dot embedded in a nanowire. This technique can be used when the dot's energy states are separated by many kT and will enable future quantitative investigations of electron-phonon interaction, nonlinear thermoelectric effects, and the effciency of thermoelectric energy conversion in quantum dots.Comment: 6 pages, 5 figure

Cultivating equality: delivering just and sustainable food systems in a changing climate

T oday, the world faces a greater challenge perhaps than ever before: tackling hunger and malnutrition in the face of climate change and increasing natural resource scarcity. Civil society, governments, researchers, donors, and the private sector are simultaneously debating and collaborating to find solutions. But the dialogue is over-emphasizing food production. Improving yields is important, particularly in places where there is not enough food or where food producers live in poverty. But simply producing more is not enough to tackle hunger. Furthermore, acknowledging that lack of food is not the sole cause of hunger is important. Inequality shapes who has access to food and the resources to grow it and buy it. It governs who eats first and who eats worst. Inequality determines who can adapt more readily to a changing climate. Hunger and poverty are not an accident – they are the result of social and economic injustice and inequality at all levels, from household to global. The reality of inequality is no truer for anyone than it is for women – half the world’s population, with far less than their fair share of the world’s resources. If we are to achieve the new Sustainable Development Goal of ending hunger by 2030, we must address the underlying inequalities in food systems. In a changing climate, agriculture and food systems must be sustainable and productive – but our efforts cannot end there. They must be profitable for those for whom it is a livelihood; they must be equitable, to facilitate a level playing field in the market, to secure rights to resources for food producers, and to ensure access to nutritious food for all; they must be resilient to build the capacity of populations vulnerable to economic shocks, political instability, and increasing, climate-induced natural hazards to recover and still lift themselves out of poverty

On the Cosmological Evolution of the Luminosity Function and the Accretion Rate of Quasars

We consider a class of models for the redshift evolution (between 0\lsim z \lsim 4) of the observed optical and X-ray quasar luminosity functions (LFs), with the following assumptions: (i) the mass-function of dark matter halos follows the Press-Schechter theory, (ii) the black hole (BH) mass scales linearly with the halo mass, (iii) quasars have a constant universal lifetime, and (iv) a thin accretion disk provides the optical luminosity of quasars, while the X-ray/optical flux ratio is calibrated from a sample of observed quasars. The mass accretion rate $\dot{M}$ onto quasar BHs is a free parameter of the models, that we constrain using the observed LFs. The accretion rate $\dot M$ inferred from either the optical or X-ray data under these assumptions generally decreases as a function of cosmic time from $z \simeq 4$ to $z \simeq 0$. We find that a comparable accretion rate is inferred from the X-ray and optical LF only if the X-ray/optical flux ratio decreases with BH mass. Near $z\simeq 0$, $\dot M$ drops to substantially sub-Eddington values at which advection-dominated accretion flows (ADAFs) exist. Such a decline of $\dot M$, possibly followed by a transition to radiatively inefficient ADAFs, could explain both the absence of bright quasars in the local universe and the faintness of accreting BHs at the centers of nearby galaxies. We argue that a decline of the accretion rate of the quasar population is indeed expected in cosmological structure formation models.Comment: Latex, 23 pages, 9 figures, accepted for publication in Ap

Optimal control strategies for tuberculosis treatment: a case study in Angola

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201

On a conjecture of Goodearl: Jacobson radical non-nil algebras of Gelfand-Kirillov dimension 2

For an arbitrary countable field, we construct an associative algebra that is graded, generated by finitely many degree-1 elements, is Jacobson radical, is not nil, is prime, is not PI, and has Gelfand-Kirillov dimension two. This refutes a conjecture attributed to Goodearl