Effects of the N2144S mutation on backbone dynamics of a TB-cbEGF domain pair from human fibrillin-1

The calcium-binding epidermal growth factor-like (cbEGF) module and the transforming growth factor beta-binding protein-like (TB) module are the two major structural motifs found in fibrillin-1, the extracellular matrix (ECM) protein defective in the Marfan syndrome (MFS). An MFS-causing mutation, N2144S, which removes a calcium ligand in cbEGF32, does not detectably affect fibrillin-1 biosynthesis, rate of secretion, processing, or deposition of reducible fibrillin-1 into the ECM. Since the residue at position 2144 is normally engaged in calcium ligation, it is unable to mediate intermolecular interactions. We have shown previously that this mutation does not affect the folding properties of the TB or cbEGF domains in vitro, but does decrease calcium-binding in cbEGF and TB-cbEGF domain constructs. Here, we use NMR spectroscopy to probe the effects of the N2144S mutation on backbone dynamic properties of TB6-cbEGF32. Analysis of the backbone (15)N relaxation data of wild-type TB6-cbEGF32 has revealed a flexible inter-domain linkage. Parallel dynamics analysis of the N2144S mutant has shown increased flexibility in the region joining the two domains as well as in the calcium-binding site at the N terminus of cbEGF32. This research demonstrates that a small change in peptide backbone flexibility, which does not enhance proteolytic susceptibility of the domain pair, is associated with an MFS phenotype. Flexibility of the TB-cbEGF linkage is likely to contribute to the biomechanical properties of fibrillin-rich connective tissue microfibrils, and may play a role in the microfibril assembly process.     

Anaerobic Biooxidation of Fe(II) by Dechlorosoma suillum

Anaerobic microbial oxidation of Fe(II) was only recently discovered and very little is known about this metabolism. We recently demonstrated that several dissimilatory perchlorate-reducing bacteria could utilize Fe(II) as an electron donor under anaerobic conditions. Here we report on a more in-depth analysis of Fe(II) oxidation by one of these organisms, Dechlorosoma suillum. Similarly to most known nitrate-dependent Fe(II) oxidizers, D. suillum did not grow heterotrophically or lithoautotrophically by anaerobic Fe(II) oxidation. In the absence of a suitable organic carbon source, cells rapidly lysed even though nitrate-dependent Fe(II) oxidation was still occurring. The coupling of Fe(II) oxidation to a particular electron acceptor was dependent on the growth conditions of cells of D. suillum. As such, anaerobically grown cultures of D. suillum did not mediate Fe(II) oxidation with oxygen as the electron acceptor, while conversely, aerobically grown cultures did not mediate Fe(II) oxidation with nitrate as the electron acceptor. Anaerobic washed cell suspensions of D. suillum rapidly produced an orange/brown precipitate which X-ray diffraction analysis identified as amorphous ferric oxyhydroxide or ferrihydrite. This is similar to all other identified nitrate-dependent Fe(II) oxidizers but is in contrast to what is observed for growth cultures of D. suillum, which produced a mixed-valence Fe(II)-Fe(III) precipitate known as green rust. D. suillum rapidly oxidized the Fe(II) content of natural sediments. Although the form of ferrous iron in these sediments is unknown, it is probably a component of an insoluble mineral, as previous studies indicated that soluble Fe(II) is a relatively minor form of the total Fe(II) content of anoxic environments. The results of this study further enhance our knowledge of a poorly understood form of microbial metabolism and indicate that anaerobic Fe(II) oxidation by D. suillum is significantly different from previously described forms of nitrate-dependent microbial Fe(II) oxidation.     

Alkaline iron(III) reduction by a novel alkaliphilic,halotolerant, <Emphasis Type="Italic">Bacillus</Emphasis> sp. isolated from salt flat sediments of Soap Lake

A halotolerant, alkaliphilic dissimilatory Fe(III)-reducing bacterium, strain SFB, was isolated from salt flat sediments collected from Soap Lake, WA. 16S ribosomal ribonucleic acid gene sequence analysis identified strain SFB as a novel Bacillus sp. most similar to Bacillus agaradhaerens (96.7% similarity). Strain SFB, a fermentative, facultative anaerobe, fermented various hexoses including glucose and fructose. The fructose fermentation products were lactate, acetate, and formate. Under fructose-fermenting conditions in a medium amended with Fe(III), Fe(II) accumulated concomitant with a stoichiometric decrease in lactate and an increase in acetate and CO₂. Strain SFB was also capable of respiratory Fe(III) reduction with some unidentified component(s) of Luria broth as an electron donor. In addition to Fe(III), strain SFB could also utilize nitrate, fumarate, or O₂ as alternative electron acceptors. Optimum growth was observed at 30°C and pH 9. Although the optimal salinity for growth was 0%, strain SFB could grow in a medium with up to 15% NaCl by mass. These studies describe a novel alkaliphilic, halotolerant organism capable of dissimilatory Fe(III) reduction under extreme conditions and demonstrate that Bacillus species can contribute to the microbial reduction of Fe(III) in environments at elevated pH and salinity, such as soda lakes.     

在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 …

根据２２个等位酶位点遗传变异,探讨了韩国境内委陵菜（Ｐｏｔｅｎｔｉｌｌａ ｆｒａｇａｒｉｏｉｄｅｓ Ｌ．ｖａｒ．ｓｐｒｅｎｇｅｌｉａｎａ）的遗传多样性和种群结构。酶位点的多态位点百分比为５９．１％。种和种群水平上的遗传多样性比较高,分别为Ｈｅｓ＝０．２１０,Ｈｅｐ＝０．１９９;而种群的分化水平则相对较低（ＧＳＴ＝０．０７４）。１９个种群中随机交配的偏差为ＦＩＳ＝０．３３１。每代迁移数的间接估计     

Proton magnetic resonance studies of the aggregation of taurine-conjugated bile salts.

The concentration dependence of the 500 MHz 1H-NMR spectra of taurocholate, taurochenodeoxycholate, taurodeoxycholate, and the monosulfate esters of taurochenodeoxycholate has been examined at 0.154 M NaCl in D2O. The resonances of the C18, C19, and C21 methyl groups and the C23 methylene group are differentially broadened with respect to the C25 and C26 methylene and C7 (or C12) methine groups with increasing bile salt concentration for each of the bile salts studied. These data confirm hydrophobic association and indicate that the side chain contributes to the hydrophobic surface of the bile salt. The chemical shift difference of the anisochronous C23 methylene protons is different in monomer and aggregate form. The C25 methylene protons are isochronous in monomeric form but anisochronous in aggregate form. The concentration dependence of the observed chemical shifts has been analyzed to estimate the critical concentration associated with the onset of these changes. The conformer population about the C22-C23 bond changes before the anisochronicity of the C25 methylene protons develops. This indicates that the C23 methylene group is affected by the initial stages of self-association, whereas specific motional constraints about the N-C25 bond in the taurine moiety are only induced in large primary micelles. The difference in the chemical shift of the C25 methylene protons depends on the structure of the bile salt. The relative magnitude of the shift differences is not altered by the presence of phosphatidylcholine. The data suggest that in primary micelles or mixed micelles the taurine moiety conforms to segregate the hydrophilic groups of the bile salt and effects greater van der Waals' contact between the hydrophobic surfaces.     

MIGRATION ACROSS THE SOUTHERN NORTH SEA STUDIED BY RADAR PART 5. MOVEMENTS IN AUGUST, WINTER AND SPRING, AND CONCLUSION

Arrivals of gulls S.W. seem almost confined to late July.
In August, the main movements are W. by day and night of Lapwings and S.S.E. by night of warblers. Sand Martins migrated at dawn directly from a large roost at 34 m.p.h.
In midwinter, migration occurred in at least one direction almost every morning and night. "Hard-weather movements" west or south are initiated primarily by easterly or northerly winds respectively, and not by cold. The corresponding return movements, which sometimes follow immediately, arc initiated primarily by westerly or southerly winds respectively, but warmth has an influence in February. In midwinter, various species are evidently ready to travel in either the autumn or the spring direction, and wind-direction is the paramount factor determining which occurs.
The big eastward departures in March and April occur mainly with westerly winds and in warm weather, both factors being important, but proportionately more departures occur against strong head or cross-winds than in autumn. The general weather situation has no direct influence.
Starlings migrated directly from their roosts on a few mornings each spring, normally at sunrise but on one occasion some did so much earlier.
In late April and May the chief movements are N.N.W. arrivals and onward passages of British summer visitors, N.E. departures of shore-birds, and N.N.E. departures of small passerines, presumably en route between Iberia and Norway. These movements occur mainly with southerly winds, but sometimes against the wind.
"Reversed movements" W. or S.S.E. are much more frequent in spring than has previously been supposed. They occur exclusively with easterly or northerly winds respectively (like the midwinter movements).
The frequency of each migratory movement throughout the year is summarized in Table 6.
The main findings of the 5-year study are reviewed under four heads in the Conclusion.     

Regulation of complement and modulation of its activity in monoclonal antibody therapy of cancer

The complement system is a powerful tool of the innate immune system to eradicate pathogens. Both in vitro and in vivo evidence indicates that therapeutic anti-tumor monoclonal antibodies (mAbs) can activate the complement system by the classical pathway. However, the contribution of complement to the efficacy of mAbs is still debated, mainly due to the lack of convincing data in patients. A beneficial role for complement during mAb therapy is supported by the fact that cancer cells often upregulate complement-regulatory proteins (CRPs). Polymorphisms in various CRPs were previously associated with complement-mediated disorders.In this review the role of complement in anti-tumor mAb therapy will be discussed with special emphasis on strategies aiming at modifying complement activity. In the future, clinical efficacy of mAbs with enhanced effector functions together with comprehensive analysis of polymorphisms in CRPs in mAb-treated patients will further clarify the role of complement in mAb therapy.