Background: IL-6 signaling is a key component of inflammatory diseases.Results: Modified DNA aptamers that inhibit IL-6 signaling were discovered and optimized.Conclusion: Modified aptamers are stable in serum and block the interaction of IL-6 with its receptor IL-6Rα.Significance: Modified aptamers are a new class of antagonist with properties potentially suitable for clinical treatment of inflammation.

Background: Traditional aptamers favor polar interactions with protein binding partners.Results: The IL-6·SOMAmer structure reveals an interface rich in hydrophobic interactions that overlap the binding sites of IL-6 receptors.Conclusion: Hydrophobic modifications on DNA scaffolds generate diverse and novel structural motifs.Significance: Synthetic SOMAmers are potent, specific, and chemically versatile ligands with distinct binding properties compared with conventional aptamers.

The ocean is an important sink for anthropogenic CO2 emissions, but there are only a few measurements which confirm the oceanic CO2 uptake. Since 1981, partial pressure of CO2 (pCO2) in the western North Pacific (35°N−3°N, 128°E−155°E) and the overlying air have been measured periodically to clarify the seasonal and long‐term trends of the oceanic carbonate system. The partial pressure of CO2 in surface seawater (pCO2sea) observed every boreal winter during the period from 1984 to 1993 give a growth rate of 1.8 ± 0.6 µatm yr−1 (n = 27) north of 15°N and 0.5 ± 0.7 µatm yr−1 (n = 23) south of 14°N with an average of 1.2 ± 0.9 µatm yr−1 (n = 50). The rate of pCO2sea a increase north of 15°N is equal to that of atmospheric CO2 (1.8 µatm yr−1) during the same period but that south of 14°N is lower. The difference in rate of pCO2sea a increase is suggestive of temporal variations in ΔpCO2 distribution. After removing the long‐term trend from the pCO2sea data, the seasonal variation of pCO2sea in the western North Pacific (132°E−142°E) was evaluated with a linear regression between the pCO2sea and sea surface temperature (SST). Generally, a thermodynamic process (temperature effect) plays a predominant role in determining the seasonal variations of pCO2sea. South of 14°N, however, a clear interannual variability is significant relative to the seasonal changes if an El Niño event is accompanied by enhanced vertical mixing. The annual air‐sea CO2 flux showed a large influx of CO2 into the ocean north of 27°N (Kuroshio Counter Current) because of a large negative ΔpCO2 (− 60 µatm) and strong wind during the winter season. Toward the south, the annual average air‐sea CO2 flux increased by 9 mmol m−2 day−1 from – 8 mmol m−2 day−1 at 31°N to 1 mmol M−2 day−1 at 5°N. South of 10°N, the ocean acts as a source for atmospheric CO2 (0.2‐0.7 mmol m−2 day−1), but this is a considerably weaker source as compared with those of the central and eastern equatorial Pacific. The observed increase of pCO2sea and the estimated air/sea CO2 flux suggest the importance of carbon transport from the mixed layer to the intermediate/deep water in the area of Subtropical Mode Water formation, south of the Kuroshio and east of Japan.

BackgroundChoroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer’s disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown.MethodsAdult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery. Choroid plexus tissues were collected and analyzed for Vcam1, Madcam1, Cx3cl1, Ccl2, Nt5e, and Ifnγ expression at different timepoints after stroke using qPCR. Changes of MDMs in CP and cerebrospinal fluid (CSF) at 1 day and 3 days after stroke were analyzed using flow cytometry. Infiltration of MDMs into CP and CSF were validated using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. CD115+ monocytes were isolated using a magnetic cell separation system from bone marrow of Cx3cr1-GFP or wild-type C57BL/6 donor mice. The freshly isolated monocytes or M2-like MDMs primed in vitro with IL4 and IL13 were stereotaxically injected into the lateral ventricle of stroke-affected mice to trace for their migration into ischemic hemisphere or to assess their effect on post-stroke recovery using open field, corridor, and active avoidance behavioral tests.ResultsWe found that CP responded to cortical stroke by upregulation of gene expression for several possible mediators of MDM trafficking and, concomitantly, MDMs increased in CP and cerebrospinal fluid (CSF). We then confirmed that MDMs infiltrated from blood into CP and CSF after the insult using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. When MDMs were directly administered into CSF following stroke, they homed to the ischemic hemisphere. If they had been primed in vitro prior to their administration to become M2-like macrophages, they promoted post-stroke recovery of motor and cognitive function without influencing infarct volume.ConclusionsOur findings suggest the possibility that autologous transplantation of M2-like MDMs into CSF might be developed into a new strategy for promoting recovery also in patients with stroke.

A B S T R A C TAircraft observation under the Pacific Atmospheric Chemistry Experiment (PACE) program was performed from February 13 to 21, 2000 to examine in detail the distributions of CO 2 in the free troposphere between 5 and 11 km. Continuous measurements of CO 2 mixing ratios were made using an on-board measuring system over the northern North Pacific between Nagoya, Japan and Anchorage, Alaska, and the western North Pacific between Nagoya and Saipan. Other trace gases, such as CO and O 3 , were also observed using continuous measuring systems at the same time. CO 2 over the northern Pacific (35 • N and higher) showed highly variable mixing ratios, ranging from 374 ppm in the upper troposphere to 366 ppm in the lowermost stratosphere. This highly variable distribution of CO 2 was quite similar to that of CO, but the relationship between CO 2 and O 3 showed a strong negative correlation. These results indicated that the exchange process between the stratosphere and the troposphere significantly influences the large CO 2 variation. On the other hand, the CO 2 over the western North Pacific to the south of Japan showed no significant variation in the upper troposphere at 11 km but a relatively larger variability at 5 km. The CO 2 enhancement at lower altitudes coincided with the CO elevation due to the intrusion of a polluted air mass. Trajectory analysis indicated that the Asian continental outflow perturbed the CO 2 distributions over the western Pacific. Very low mixing ratios of O 3 of less than 20 ppb were distributed in the latitude band of 15-30 • N at 11 km, reflecting the effects of transport from the equatorial region.