Toxin-induced pore formation is hindered by intermolecular hydrogen bonding in sphingomyelin bilayers

Sticholysin I and II (StnI and StnII) are pore-forming toxins that use sphingomyelin (SM) for membrane binding. We examined how hydrogen bonding among membrane SMs affected the StnI- and StnII-induced pore formation process, resulting in bilayer permeabilization. We compared toxin-induced permeabilization in bilayers containing either SM or dihydro-SM (lacking the trans 4 double bond of the long-chain base), since their hydrogen-bonding properties are known to differ greatly. We observed that whereas both StnI and StnII formed pores in unilamellar vesicles containing palmitoyl-SM or oleoyl-SM, the toxins failed to similarly form pores in vesicles prepared from dihydro-PSM or dihydro-OSM. In supported bilayers containing OSM, StnII bound efficiently, as determined by surface plasmon resonance. However, StnII binding to supported bilayers prepared from dihydro-OSM was very low under similar experimental conditions. The association of the positively charged StnII (at pH 7.0) with unilamellar vesicles prepared from OSM led to a concentration-dependent increase in vesicle charge, as determined from zeta-potential measurements. With dihydro-OSM vesicles, a similar response was not observed. Benzyl alcohol, which is a small hydrogen-bonding compound with affinity to lipid bilayer interfaces, strongly facilitated StnII-induced pore formation in dihydro-OSM bilayers, suggesting that hydrogen bonding in the interfacial region originally prevented StnII from membrane binding and pore formation. We conclude that interfacial hydrogen bonding was able to affect the membrane association of StnI- and StnII, and hence their pore forming capacity. Our results suggest that other types of protein interactions in bilayers may also be affected by hydrogen-bonding origination from SMs.

Draft of law related to the settling of chambers after Commencement, 1742

One-page handwritten draft of a law created by the president and tutors requiring juniors to inform the Faculty of their intent to stay in dormitory rooms following Commencement. The document is undated and unsigned, but appears to be in the hand of President Edward Holyoke, and has a note in shorthand in the left margin. The text is included in College Book IV and was presented at a meeting of the Harvard Corporation on September 6, 1742.

The petitioners for settling His Majesties lands and islands lying between Nova Scotia and the province of Main in New England in America : manuscript, [ca. 1720]

Written in an unidentified hand, signed by Barkstead.

Copy of Gov[erno]r Philips's additional instructions about settling some Palatine families in Nova Scotia: Copy Col. Dunbar's additional instruction about settling some Irish families in Nova Scotia : manuscript, [1730]

Copies of two documents, approved 20 Apr. 1730; instructions to Richard Philips state that a number of Protestant Irish and Palatine families have been granted land in Nova Scotia, to be surveyed by David Dunbar; and instructions to Dunbar to survey and lay out land for the families.

Ukraine and Russia: a hindered rapprochement. OSW Commentary No. 44, 2010-12-15

The policy of rapprochement with Russia that President Victor Yanukovych and his entourage had been actively promoting in the first months of his presidency has slowed down notably. One of the reasons for this lowered pace is that current talks between Russia and Ukraine concern the spheres in which Kyiv is not ready to make concessions to Russia. Despite numerous top-level meetings, recent months have failed to bring a breakthrough in energy issues of key importance. First of all, no compromise was reached in gas issues where the divergence of interests is particularly large and where Ukraine has adopted a tough stance to negotiate the best conditions possible. Even though some agreements were signed during the October session of the inter-governmental committee presided over by the prime ministers (the agreement on linking the two states’ aircraft production and on the joint construction of a nuclear fuel production plant), these resulted from prior agreements. Economic negotiations will continue in the coming months but the observed deadlock is not likely to be broken any time soon. The results of these talks are likely to reflect the interests of both Russia and Ukraine, as well as the competition among Ukrainian business groups, some of which opt for closer cooperation with their Eastern neighbour. Ukraine’s consent to send oil to Belarus along the Odessa-Brody pipeline shows that the government in Kyiv is ready to engage in projects they consider profitable, even those that run counter to Russian interests. Ukraine’s adoption of this stance may trigger irritation in Moscow and lead to a cooling in bilateral relations.

An Agricultural continuum : a descriptive study of the farmworker population and the settling-out process : based on information collected under Contract no. HEW-OS-72-217.

"Jointly funded by the Department of Health, Education & Welfare and the Office of Economic Opportunity."

Settling plant grievances; a review of grievance procedure under collective bargaining.

Mode of access: Internet.

Applicability of two mathematical models to the batch settling of activated sludge.

"Supported by Federal Water Pollution Control Administration, U.S. Department of the Interior. Research project WP-01011."

The effect of induced flocculation on the settling and thickening behavior of activated sludge /

"Supported by U.S. Public Health Service Traineeship EH66-616 and U.S. Dept. of Interior Research Project WP 01011-01."

Principles of claim adjusting; a manual explaining the procedure , with background material, for settling claims under life, health and accident insurance policies.

Mode of access: Internet.