PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL. We find spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) to be the key mediators of inflammation after PCSK9-CAP1 binding. In human peripheral blood mononuclear cells, serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. The CAP1-fragment crystallizable region (CAP1-Fc) mitigates PCSK9-mediated inflammatory signal transduction more than the PCSK9 blocking antibody evolocumab does.

Deposition of Fukushima nuclear power plant accident-derived radiocesium in the soils of Jeju Island, Korea, and evidence for long- and short-lived radionuclides in rainwater.

In this study, we investigated the concentrations of Fukushima nuclear power plant accident (FNPPA)-derived radiocesium (134Cs, 137Cs) deposited in the topsoil of Jeju Island, Korea. We also evaluated the soil inventories of radionuclides and compared the concentrations deposited by rainwater and fallout. We present the first evidence of FNPPA-derived radionuclides directly entering the environment of Jeju Island. In the case of FNPPA-derived 134Cs in soil, only a trace amount was identified in the surface layer (1 cm depth), whereas 137Cs derived from past atmospheric deposition of nuclear testing were detected along with those derived from the nuclear power plant accident. The total measured radiocesium (134Cs + 137Cs) indicates that although the value obtained from soils was slightly lower, both values were within the same order of magnitude. Of the FNPPA-derived radiocesium deposited in the soil, the impact from April 2011 was the largest at most sampling sites indicating that the radioactive plume directly covered Jeju Island. Furthermore, a variety of long- and short-lived gamma-emitting radionuclides were detected in the rainwater samples collected on April 7, 2011. Among them, short-lived radionuclides such as 140La, 110mAg, 95Nb, 125Sb, 113Sn, 129Te, 129mTe, 132Te, 132I, and 136Cs, were observed. The findings of this study provide evidence for the direct effects of FNPPA-derived radionuclides in Jeju Island. This is the first location in Korea and the first in the entire East Asian region, excluding Japan that is confirmed to have been directly affected FNPP accident.

Modulation of Phenol Oxidation in Cofacial Dyads.

The presentation of two phenols on a xanthene backbone is akin to the tyrosine dyad (Y730 and Y731) of ribonucleotide reductase. X-ray crystallography reveals that the two phenol moieties are cofacially disposed at 4.35 Å. Cyclic voltammetry reveals that phenol oxidation is modulated within the dyad, which exhibits a splitting of one-electron waves with the second oxidation of the phenol dyad occurring at larger positive potential than that of a typical phenol. In contrast, a single phenol appended to a xanthene exhibits a two-electron process, consistent with reported oxidation pathways of phenols in acetonitrile. The perturbation of the phenol potential by stacking is reminiscent of a similar effect for guanines stacked within DNA base pairs.

Formation and analysis of topographical domains between lipid membranes tethered by DNA hybrids of different lengths.

We recently described a strategy to prepare DNA-tethered lipid membranes either to fixed DNA on a surface or to DNA displayed on a supported bilayer [Boxer et al., J. Struct. Biol., 2009, 168, 190; Boxer et al., Langmuir, 2011, 27, 5492]. With the latter system, the DNA hybrids are laterally mobile; when orthogonal sense-antisense pairs of different lengths are used, the DNA hybrids segregate by height and the tethered membrane deforms to accommodate the height difference. This architecture is particularly useful for modelling interactions between membranes mediated by molecular recognition and resembles cell-to-cell junctions. The length, affinity and population of the DNA hybrids between the membranes are completely controllable. Interesting patterns of height segregation are observed by fluorescence interference contrast microscopy. Diverse behavior is observed in the segregation and pattern forming process and possible mechanisms are discussed. This model system captures some of the essential physics of synapse formation and is a step towards understanding lipid membrane behaviour in cell-to-cell junctions.

A root exudates based approach to assess the long-term phytoavailability of metals in biosolids-amended soils.

Organic acids present in the rhizosphere of growing plants are widely recognized to be responsible for dissolving the solid phase metals in the soil and making them available for plant absorption. We proposed a root exudates-based model to assess the long-term phytoavailability of metals in biosolids-amended soils. The phytoavailability of biosolids-borne metals was defined in terms of a capacity factor and an intensity factor. The plant available metal pool, C(0) (capacity factor, mgkg(-1)), can be estimated by fitting the successive organic acids extraction data to an exponential decay kinetic equation. The field metal removal rate, k (intensity factor, yr(-1)), can be estimated from the successive extraction-based metal release rate through an effective annual organic acid production in the rhizosphere which was found to be characteristic of plant species. The protocol was successfully used to assess the long-term phytoavailability of metals in biosolids-amended soil from two biosolids land application sites.