Long-term memory and synapse-like dynamics in two-dimensional nanofluidic channels.

Fine-tuned ion transport across nanoscale pores is key to many biological processes, including neurotransmission. Recent advances have enabled the confinement of water and ions to two dimensions, unveiling transport properties inaccessible at larger scales and triggering hopes of reproducing the ionic machinery of biological systems. Here we report experiments demonstrating the emergence of memory in the transport of aqueous electrolytes across (sub)nanoscale channels. We unveil two types of nanofluidic memristors depending on channel material and confinement, with memory ranging from minutes to hours. We explain how large time scales could emerge from interfacial processes such as ionic self-assembly or surface adsorption. Such behavior allowed us to implement Hebbian learning with nanofluidic systems. This result lays the foundation for biomimetic computations on aqueous electrolytic chips.

Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells.

The biochemical mechanisms underlying the inhibitory effects of lycopene, the main tomato carotenoid, on the growth of cancer cells are largely unknown. It has been hypothesized that lycopene derivatives may act as ligands for a nuclear receptor in analogy to retinoic acid, the hormone derived from beta-carotene. The inhibition of human mammary cancer (MCF-7) cell growth and the transactivation of the retinoic acid receptor (RAR) reporter gene by synthetic acyclo-retinoic acid, the open chain analog of retinoic acid, was compared to the effects of lycopene and retinoic acid in the same systems. Acyclo-retinoic acid activated the DR-5 retinoic acid response element with a approximately 100-fold lower potency than retinoic acid. This effect was independent of cotransfection with the RARalpha receptor. Lycopene exhibited only very modest activity in this system. In contrast to the results from the transactivation studies, acyclo-retinoic acid, retinoic acid, and lycopene inhibited cell growth with a similar potency. Preincubation with each of the three compounds slowed down cell cycle progression from G1 to S phase. In summary, acyclo-retinoic acid inhibited cancer cell growth and interacted with RAR. However, it exhibited low affinity for RAR and a correspondingly low efficacy in activating this receptor, indicating that RAR does not mediate the growth inhibitory effect of the compound. In addition, the concentrations of acyclo-retinoic acid and of lycopene required for inducing inhibition of cell growth were similar, suggesting that acyclo-retinoic acid is unlikely to be the active metabolite of lycopene.

Stimulation of gap junctional communication: comparison of acyclo-retinoic acid and lycopene.

Carotenoids and retinoids stimulate gap junctional communication (GJC), thought to be related to cancer-preventive properties. Lycopene, a nonprovitamin A carotenoid and its possible oxidation product, acyclo-retinoic acid, were tested for their effect on GJC, on stabilization of connexin43 mRNA, and on the transactivation of the RAR-beta2-promoter in vitro. In human fetal skin fibroblasts, GJC was stimulated by lycopene and acyclo-retinoic acid. Lycopene was effective at a concentration of 0.1 microM, whereas higher amounts of acyclo-retinoic acid (1 microM) were needed for comparable stimulation. Stabilizing effects of acyclo-retinoic acid on the mRNA of connexin43 via elements located in the 3'-UTR were weak. In comparison to retinoic acid (0.1 microM), considerably higher concentrations of the acyclo analog (50 microM) were required for similar effects; lycopene (0.1 microM) was not active in this system. Likewise, unphysiologically high levels of acyclo-retinoic acid (50 microM) were necessary to transactivate the RAR-beta2 promoter. The data demonstrate that acyclo-retinoic acid is much less active than retinoic acid with respect to GJC and retinoid-related signaling. Therefore, we conclude that lycopene affects GJC independent of the formation of acyclo-retinoic acid.

Report on intrauterine drug exposure during second trimester of pregnancy in a heroin-associated death.

A 17-year-old girl was found dead in a public toilet with fresh needle puncture marks. She was 18-20 weeks pregnant with a male fetus. Drug screening of her blood and urine indicated recent heroin use. Chronic drug use was confirmed by hair analysis. Amniotic fluid as well as fetal and maternal tissues and body fluids were analyzed by GC/MS and HPLC. All the fetal specimens were investigated, and the following levels of drugs were found: 6-monoacetyl-morphine (blood: 152 ng/g; amniotic fluid: 128 ng/g; brain: 140 ng/g; lung: 110 ng/g; liver: 2 ng/g; kidney: 40 ng/g), morphine (blood: 1360 ng/g; amniotic fluid: 604 ng/g; brain: 710 ng/g; lung: 1030 ng/g; liver: 2060 ng/g; kidney: 1100 ng/g), codeine (blood: 70 ng/g; brain: 60 ng/g; lung: 60 ng/g; liver: 90 ng/g; kidney: 70 ng/g), and morphine-3-glucuronide (amniotic fluid: 209 ng/g; brain: 170 ng/g; lung: 325 ng/g; kidney: 231 ng/g). Morphine-6-glucuronide was present in the maternal circulation but could not be detected in the fetal circulation.

Monocyte-reactive antibodies in patients with systemic lupus erythematosus.

Cold-reactive antibodies cytotoxic for peripheral monocytes from more than half of normal donors were found in the sera of 2 of 25 patients with systemic lupus erythematosus (SLE) and 1 of 26 with rheumatoid arthritis (RA), and they were absent in 25 normal sera. In contrast, lymphocytotoxic activity for T or B lymphocytes was found in over half of the lupus sera. The antibodies to monocytes were primarily IgM and exhibited varying specificities. Some of the antibodies were directed against antigenic determinants common to monocytes, T and B cells, or against determinants shared between monocytes and one lymphocyte type. One serum possessed a high titer of antibodies that were specific for monocytes. The clinical significance of antimonocyte antibodies remains to be established.