Engineering novel complement activity into a pulmonary surfactant protein

Complement neutralizes invading pathogens, stimulates inflammatory and adaptive immune responses, and targets non- or altered-self structures for clearance. In the classical and lectin activation pathways, it is initiated when complexes composed of separate recognition and activation subcomponents bind to a pathogen surface. Despite its apparent complexity, recognition-mediated activation has evolved independently in three separate protein families, C1q, mannose-binding lectins (MBLs), and serum ficolins. Although unrelated, all have bouquet-like architectures and associate with complement-specific serine proteases: MBLs and ficolins with MBL-associated serine protease-2 (MASP-2) and C1q with C1r and C1s. To examine the structural requirements for complement activation, we have created a number of novel recombinant rat MBLs in which the position and orientation of the MASP-binding sites have been changed. We have also engineered MASP binding into a pulmonary surfactant protein (SP-A), which has the same domain structure and architecture as MBL but lacks any intrinsic complement activity. The data reveal that complement activity is remarkably tolerant to changes in the size and orientation of the collagenous stalks of MBL, implying considerable rotational and conformational flexibility in unbound MBL. Furthermore, novel complement activity is introduced concurrently with MASP binding in SP-A but is uncontrolled and occurs even in the absence of a carbohydrate target. Thus, the active rather than the zymogen state is default in lectin·MASP complexes and must be inhibited through additional regions in circulating MBLs until triggered by pathogen recognition

Paths reunited: initiation of the classical and lectin pathways of complement activation

Understanding the structural organisation and mode of action of the initiating complex of the classical pathway of complement activation (C1) has been a central goal in complement biology since its isolation almost 50 years ago. Nevertheless, knowledge is still incomplete, especially with regard to the interactions between its subcomponents C1q, C1r and C1s that trigger activation upon binding to a microbial target. Recent studies have provided new insights into these interactions, and have revealed unexpected parallels with initiating complexes of the lectin pathway of complement: MBL–MASP and ficolin–MASP. Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways

Probing the reactivity of a 2,2′-bipyridyl-3,3′-bis-imine ligand by X-ray crystallography

The reactivity of a Schiff-base bis-imine ligand 3 is probed by X-ray diffraction studies. Its susceptibility to hydrolysis, oxidation and nucleophilic addition reactions is demonstrated by the isolation of the methanol adduct 4 and two diazapene heterocycles 5 and 6. This reactivity is also reflected in the molecular structures of two coordination complexes isolated by the reaction of 3 with MIJhfac)2 salts, to afford [Cu(5)-(hfac)(tfa)] (8) and [Zn(6)(hfac)2] (9)

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

Chiral molecular crystals built up by chiral molecules without inversion centers have attracted much interest owing to their versatile functionalities related to optical, magnetic, and electrical properties. However, there is a difficulty in chiral crystal growth due to the lack of symmetry. Therefore, we made the molecular design to introduce intermolecular hydrogen bonds in chiral crystals. Racemic and enantiopure bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) derivatives possessing hydroxymethyl groups as the source of hydrogen bonds were designed. The novel racemic trans-vic-(hydroxymethyl)(methyl)-BEDT-TTF 1, and racemic and enantiopure trans-vic-bis(hydroxymethyl)-BEDT-TTF 2 were synthesized. Moreover, the preparations, crystal structure analyses, and electrical resistivity measurements of the novel achiral charge transfer salt θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2 and the chiral salt α’-[(R,R)-2]ClO4(H2O) were carried out. In the former θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2, there are two sets of three crystallographically independent donor molecules [(S,S)-2]2[(R,R)-2] in a unit cell, where the two sets are related by an inversion center. The latter α’-[(R,R)-2]ClO4(H2O) is the chiral salt with included solvent H2O, which is not isostructural with the reported chiral salt α’-[(S,S)-2]ClO4 without H2O, but has a similar donor arrangement. According to the molecular design by introduction of hydroxy groups and a ClO4− anion, many intermediate-strength intermolecular hydrogen bonds (2.6–3.0 Å) were observed in these crystals between electron donor molecules, anions, and included H2O solvent, which improve the crystallinity and facilitate the extraction of physical properties. Both salts are semiconductors with relatively low resistivities at room temperature and activation energies of 1.2 ohm cm with Ea = 86 meV for θ21-[(S,S)-2]3[(R,R)-2]3(ClO4)2 and 0.6 ohm cm with Ea = 140 meV for α'-[(R,R)-2]2ClO4(H2O), respectively. The variety of donor arrangements, θ21 and two kinds of α’-types, and their electrical conductivities of charge transfer complexes based upon the racemic and enantiopure (S,S)-2, and (R,R)-2 donors originates not only from the chirality, but also the introduced intermolecular hydrogen bonds involving the hydroxymethyl groups, perchlorate anion, and the included solvent H2O

Narrow-line magneto-optical cooling and trapping of strongly magnetic atoms

Laser cooling on weak transitions is a useful technique for reaching ultracold temperatures in atoms with multiple valence electrons. However, for strongly magnetic atoms a conventional narrow-line magneto-optical trap (MOT) is destabilized by competition between optical and magnetic forces. We overcome this difficulty in Er by developing an unusual narrow-line MOT that balances optical and magnetic forces using laser light tuned to the blue side of a narrow (8 kHz) transition. The trap population is spin-polarized with temperatures reaching below 2 microkelvin. Our results constitute an alternative method for laser cooling on weak transitions, applicable to rare-earth-metal and metastable alkaline earth elements.Comment: To appear in Phys. Rev. Lett. 4 pages, 5 figure

Self-help and rural development in Kenya

One of the main emphases of the Special Rural Development Programme in Kenya was supposed to be the involvement of local communities in economic development efforts. Self-help activity in the past has been strongly preoccupied with projects which absorb, rather than produce resources. In this paper the six S.R.D.P. areas are examined in terms of the intensity of socalled 'economic' or 'economy developing' self-help activity versus the 'social/domestic' or 'welfare' variety, and a comparison is made with selected non-S.R.D.P. areas. It is found that the preponderance of 'welfare' projects is as strong or stronger in the S.R.D.P. areas as elsewhere. Various means for promoting self-help along more economically productive lines are then discussed, along with the existing approaches and structures, and some alternatives are suggested

Panel. Breeding, Feuding, and Forging Families

Breeding Dogs, Breeding Men: Faulkner’s Search for a Hybrid Masculinity in Times of War / Isadora J. Wagner, U. S. Military Academy at West PointThis paper contributes to genealogical studies of Faulkner’s families by tracing a lineage between Virginius MacCallum’s disastrous, hybrid “litter” of hound-fox puppies and “passel” of five sons in Faulkner’s first novel about Yoknapatawpha County, Flags in the Dust, to the McCaslin family’s more successful canine and human crossbreeds in the later novel Go Down, Moses (1942). Working with the intermediary texts “The Tall Men” (1941) and the 1946 printing of the Yoknapatawpha County map, in which Faulkner replaced the MacCallums with the McCaslins, the paper demonstrates how Flags in the Dust, written in 1926-27 in the wake of World War I, but published in 1973, inaugurates a line of hereditary questioning that Faulkner continues through breeding experiments with dogs and men into World War II to identify a hybrid masculinity that can survive the ravages of modern warfare.The Lynching of Homer Barron: Feuding \u27Families\u27 in Faulkner’s “A Rose for Emily” / Wallis Tinnie, Miami-Dade CollegeIn response to a critic’s comment that the likelihood of mutual love between a black man and white woman during the 1880s would be “unthinkable,“ John T. Matthews points out that the situation was less unthinkable than unthought and posits that“governing illusions” of Faulkner\u27s Jefferson in “A Rose for Emily” have origins related to institutional slavery, illusions, Matthews submits, that have been left “unthought.” This paper examines the unthought in this Faulkner classic as it relates to the governing illusions of race and violence to secure a white democracy. The central thesis is that the “innocent” Jefferson “family” unites to murder both Emily’s father, whose name Grierson is anathema in post-Civil War Mississippi, and Homer Barron during the volatile 1870’s and 1880’s. The story\u27s choric narrator offers partial truths, deceptive rhetoric, alternative facts and nostalgic appeals with splashes of notarial rhetoric to achieve legitimacy.Family and/as Forgery: Writing Race and Gender in The Unvanquished / Jeff Allred, Hunter College/City University of New YorkWe all know that Faulkner’s families are bound by talk. This paper explores the less-examined relationship between family and writing in Yoknapatawpha one finds in The Unvanquished. Woven into that text\u27s discourse is a series of depictions of writing undertaken chiefly by subjects on the periphery of antebellum Southern society using stolen and/or repurposed materials. My paper focuses on the darkly funny gambit devised by the unlikely writing team of Rosa Millard and Ringo, an elderly white woman and an enslaved youth. Their use of stolen letterhead to forge Union Army “orders” aligns them with the emergence of modern “business communications” in the mid-nineteenth century, and I will explore the implications of this alignment, comparing their corporate mode of writing with other writerly modes present in the text. I argue that the circuitry they inhabit, so to speak, troubles the note of reactionary “redemption” that ostensibly resolves the text. Moreover, this circuitry mounts an implicit critique of populist and fascist modes of politics that links The Unvanquished with other, better-studied Faulkner texts from the 1930s

Mesoscopic Fermi gas in a harmonic trap

We study the thermodynamical properties of a mesoscopic Fermi gas in view of recent possibilities to trap ultracold atoms in a harmonic potential. We focus on the effects of shell closure for finite small atom numbers. The dependence of the chemical potential, the specific heat and the density distribution on particle number and temperature is obtained. Isotropic and anisotropic traps are compared. Possibilities of experimental observations are discussed.Comment: 8 pages, 9 eps-figures included, Revtex, submitted to Phys. Rev. A, minor changes to figures and captions, corrected typo

Electrical Control of Dynamic Spin Splitting Induced by Exchange Interaction as Revealed by Time Resolved Kerr Rotation in a Degenerate Spin-Polarized Electron Gas

The manipulation of spin degree of freedom have been demonstrated in spin polarized electron plasma in a heterostructure by using exchange-interaction induced dynamic spin splitting rather than the Rashba and Dresselhaus types, as revealed by time resolved Kerr rotation. The measured spin splitting increases from 0.256meV to 0.559meV as the bias varies from -0.3V to -0.6V. Both the sign switch of Kerr signal and the phase reversal of Larmor precessions have been observed with biases, which all fit into the framework of exchange-interaction-induced spin splitting. The electrical control of it may provide a new effective scheme for manipulating spin-selected transport in spin FET-like devices.Comment: 8 pages, 3 figures ; added some discussion