Amino-acid Sequence of Extracellular Ribonuclease (Barnase) of <Emphasis Type="Italic">Bacillus amyloliquefaciens</Emphasis>

THE ribonuclease, barnase, produced by Bacillus amyloliquefaciens has a molecular weight of 12,382, consisting of 110 amino-acid residues. It is one of the smallest proteins containing neither disulphide bonds nor non-peptide cross-Bnks which nevertheless maintain a well defined tertiary structure^1,2. The next smallest reported enzyme of similar nature is the lysozyme of phage T4, with 160 residues. The barnase structure is reversibly destroyed by denaturing solvents or heat², in what approximates a one step, highly cooperative, transition. Studies of this reaction should be very useful in illustration approaching the general problem of sequence-determined folding in proteins. In particular, thermodynamically meaningful quantitative differences in the stability of various genetic variants and chemically modified, or synthetic, barnases could be measured. Some work has been reported on the effect of various environmental parameters on the transition³ as well as the effects of modification by carboxypeptidases⁴. Full utilization of such data requires knowledge of both amino-acid sequence and three dimensional structurs. The complete amino-acid sequence is reported here (Fig. 1). The sequence was obtained by conventional procedures involving analysis of peptides isolated after hydrolysis of the native or modified protein by various proteases.

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Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy

Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy.     

Ecosystem feedbacks and cascade processes: understanding their role in the responses of Arctic and alpine ecosystems to environmental change

Global environmental change, related to climate change and the deposition of airborne N‐containing contaminants, has already resulted in shifts in plant community composition among plant functional types in Arctic and temperate alpine regions. In this paper, we review how key ecosystem processes will be altered by these transformations, the complex biological cascades and feedbacks that might result, and some of the potential broader consequences for the earth system. Firstly, we consider how patterns of growth and allocation, and nutrient uptake, will be altered by the shifts in plant dominance. The ways in which these changes may disproportionately affect the consumer communities, and rates of decomposition, are then discussed. We show that the occurrence of a broad spectrum of plant growth forms in these regions (from cryptogams to deciduous and evergreen dwarf shrubs, graminoids and forbs), together with hypothesized low functional redundancy, will mean that shifts in plant dominance result in a complex series of biotic cascades, couplings and feedbacks which are supplemental to the direct responses of ecosystem components to the primary global change drivers. The nature of these complex interactions is highlighted using the example of the climate‐driven increase in shrub cover in low‐Arctic tundra, and the contrasting transformations in plant functional composition in mid‐latitude alpine systems. Finally, the potential effects of the transformations on ecosystem properties and processes that link with the earth system are reviewed. We conclude that the effects of global change on these ecosystems, and potential climate‐change feedbacks, cannot be predicted from simple empirical relationships between processes and driving variables. Rather, the effects of changes in species distributions and dominances on key ecosystem processes and properties must also be considered, based upon best estimates of the trajectories of key transformations, their magnitude and rates of change.     

Identification of novel DNA repair proteins via primary sequence, secondary structure, and homology

Background  

DNA repair is the general term for the collection of critical mechanisms which repair many forms of DNA damage such as methylation or ionizing radiation. DNA repair has mainly been studied in experimental and clinical situations, and relatively few information-based approaches to new extracting DNA repair knowledge exist. As a first step, automatic detection of DNA repair proteins in genomes via informatics techniques is desirable; however, there are many forms of DNA repair and it is not a straightforward process to identify and classify repair proteins with a single optimal method. We perform a study of the ability of homology and machine learning-based methods to identify and classify DNA repair proteins, as well as scan vertebrate genomes for the presence of novel repair proteins. Combinations of primary sequence polypeptide frequency, secondary structure, and homology information are used as feature information for input to a Support Vector Machine (SVM).     

Quantification of angiogenesis in estrogen receptor-positive and negative breast carcinoma

Background

The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.

Methods

This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).

Results

The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).

Conclusion

ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.

     

Hatching asynchrony and growth trade‐offs within domesticated and wild zebra finch,Taeniopygia guttata,broods

The Australian zebra finch, Taeniopygia guttata, is a widely used model organism, yet few studies have compared domesticated and wild birds with the aim of examining its relevance as an evolutionary model species. Domestic and wild broods hatch over approximately 4 and 2 days, respectively, which is important given that nestlings can fledge after as little as 12 days, although 16–18 days is common. We aimed to evaluate the extent to which the greater hatching asynchrony in domestic stock may effect reproductive success through greater variance in size hierarchies, variance in within‐brood growth rates, and partial brood mortality. Therefore, by simultaneously controlling brood sizes and experimentally manipulating hatching intervals in both domesticated and wild birds, we investigated the consequences of hatching intervals for fledging success and nestling growth patterns, as well as trade‐offs. Fledging success was similarly high in domestic and wild broods of either hatching pattern. Nonetheless, between‐brood analyses revealed that domestic nestlings had significantly higher masses, larger skeletal characters, and longer wings than their wild counterparts, although wild nestlings had comparable wing lengths at the pre‐fledging stage. Moreover, within‐brood analyses revealed only negligible differences between domestic and wild nestlings, and larger effects of hatching order and hatching pattern. Therefore, despite significant differences in the hatching intervals, and the ultimate size achieved by nestlings, the domestication process does not appear to have significantly altered nestling growth trade‐offs. The present study provides reassuring evidence that studies involving domesticated zebra finches, or other domesticated model organisms, may provide reasonable adaptive explanations in behavioural and evolutionary ecology. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 763–773.