Investigating species incidence over habitat fragments of different areas—a look at error estimation

The use of incidence functions and their error structure is explored as a means of interpreting patterns present in fragmented systems. Incidence functions describe the probability of a species' presence on a fragment. The only information required for an incidence function is presence/absence data for a number of fragments of known size. Methods are developed for establishing prediction bounds on the incidence function. The example developed uses data from mammals on isolated mountaintops. Distributions of number of species expected on a fragment predicted the actual number of species well, but prediction of identities of species on small fragments was poor. Although the number of species expected on an assembly of small fragments compared to a single large fragment of the same total area was nearly always equal, the identity of species differed. Species with large area requirements were never found on any number of small fragments; species which occurred with a medium probability over most fragments had a higher probability of being present in an assembly of small fragments than on a single large fragment.     

The importance of Quaternary records in reducing risk from tropical cyclones

Numerous late Holocene records of tropical cyclones have been collected from north-east Queensland, Australia. They are in the form of multiple sedimentary ridges paralleling the shore. The ridges are composed of coral fragments, or shell and sand or pure sand. A method to determine the intensity of the tropical cyclone responsible for deposition of the ridges at each site has been applied and the results suggest that in the majority of cases these features were deposited by very high magnitude events. The results suggest that extrapolations of long-term cyclone magnitude and frequencies from the 30- to 40-year-long instrumental record, which is the method commonly used to assess risk from this hazard, substantially underestimate the risk from this hazard. This is confirmed for the Cairns region by an 800-year-long high-resolution isotope record of tropical cyclones preserved in a limestone stalagmite. Together the sedimentary and isotope records suggest that tropical cyclone activity in north-east Queensland has been in a phase of quiescence since before European settlement of the region in approximately AD 1870. It is suggested that the incorporation of the palaeo record into risk assessments will provide a more realistic guide to the magnitude frequency relationship of tropical cyclones and help reduce risk from this hazard as a consequence.     

Under-smoothed kernel confidence intervals for the hazard ratio based on censored data

In cancer clinical trials, it is often of interest in estimating the ratios of hazard rates at some specific time points during the study from two independent populations. In this paper, we consider nonparametric confidence interval procedures for the hazard ratio based on kernel estimates for the hazard rates with under-smoothing bandwidths. Two methods are used to derive the confidence intervals: one based on the asymptotic normality of the ratio of the kernel estimates for the hazard rates in two populations and another through Fieller's Theorem. The performances of the proposed confidence intervals are evaluated through Monte-Carlo simulations and applied to the analysis of data from a clinical trial on early breast cancer.     

Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types

The structure of asparagine-linked oligosaccharides attached to the antibody constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, it is still unclear how differences in the N-linked oligosaccharide structures impact the biological activities of antibodies, especially those lacking core fucose. Here, we succeeded in generating core fucose-lacking human IgG1 antibodies with three different N-linked Fc oligosaccharides, namely, a high-mannose, hybrid, and complex type, using the same producing clone, and compared their activities. Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout Chinese hamster ovary cell line in the presence or absence of a glycosidase inhibitor (either swainsonine or kifunensine) yielded antibody production of each of the three types without contamination by the others. Two of three types of nonnaturally occurring atypical oligosaccharide IgG1, except the complex type, reduced the affinity for both human lymphocyte receptor IIIa (FcgammaRIIIa) and the C1q component of the complement, resulting in reduction of ADCC and CDC. The bulky structure of the nonreducing end of N-linked Fc oligosaccharides is considered to contribute the CDC change, whereas the structural change in the reducing end, i.e. the removal of core fucose, causes ADCC enhancement through improved FcgammaRIIIa binding. In the pharmacokinetic profile, although no significant difference of human neonatal Fc receptor (FcRn)-binding affinity was observed among the three types, the complex type showed longer serum half-lives than the other types irrespective of core fucosylation in mice, which also suggests the contribution of the nonreducing end structure. The present study provides basic information on the effects of core fucose-lacking N-linked Fc oligosaccharides on antibody biological activities.     

Computing van der Waals energies in the context of the rotamer approximation

The rotamer approximation states that protein side-chain conformations can be described well using a finite set of rotational isomers. This approximation is often applied in the context of computational protein design and structure prediction to reduce the complexity of structural sampling. It is an effective way of reducing the structure space to the most relevant conformations. However, the appropriateness of rotamers for sampling structure space does not imply that a rotamer-based energy landscape preserves any of the properties of the true continuous energy landscape. Specifically, because the energy of a van der Waals interaction can be very sensitive to small changes in atomic separation, meaningful van der Waals energies are particularly difficult to calculate from rotamer-based structures. This presents a problem for computational protein design, where the total energy of a given structure is often represented as a sum of precalculated rigid rotamer self and pair contributions. A common way of addressing this issue is to modify the van der Waals function to reduce its sensitivity to atomic position, but excessive modification may result in a strongly nonphysical potential. Although many different van der Waals modifications have been used in protein design, little is known about which performs best, and why. In this paper, we study 10 ways of computing van der Waals energies under the rotamer approximation, representing four general classes, and compare their performance using a variety of metrics relevant to protein design and native-sequence repacking calculations. Scaling van der Waals radii by anywhere from 85 to 95% gives the best performance. Linearizing and capping the repulsive portion of the potential can give additional improvement, which comes primarily from getting rid of unrealistically large clash energies. On the other hand, continuously minimizing individual rotamer pairs prior to evaluating their interaction works acceptably in native-sequence repacking, but fails in protein design. Additionally, we show that the problem of predicting relevant van der Waals energies from rotamer-based structures is strongly nonpairwise decomposable and hence further modifications of the potential are unlikely to give significant improvement.     

Systematic comparison of catalytic mechanisms of hydrolysis and transfer reactions classified in the EzCatDB database

Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and transferases, were analyzed based on their enzyme structures. A method of systematic comparison and classification of the catalytic reactions was developed. Hydrolysis and transfer reactions closely resemble one another, displaying common mechanisms, single displacement, and double displacement. These displacement mechanisms might be further subclassified according to the type of catalytic factors and nucleophilic substitution involved. Several types of catalytic factors exist: nucleophile, acid, base, stabilizer, modulator, cofactors. Nucleophilic substitution might be categorized as S(N)1/S(N)2 (or dissociative/associative) reactions. The classification indicates that some mechanisms favor particular types of catalytic factors. In hydrolyses of amide bonds and phosphoric ester bonds, mechanisms with single displacement tend to use inorganic cofactors such as zinc and magnesium ions as important catalysts, whereas those with double displacement frequently do not use such cofactors. In contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one exception. The trypsin-like hydrolytic reaction, which is catalyzed by the classic catalytic triad comprising serine/histidine/aspartate, can be considered as a "super-reaction" because it is observed in at least three nonhomologous enzymes, whereas most reactions are singlets without any nonhomologous enzymes. By dividing complex reactions into several reactions, correlations between active site structures and catalytic functions can be suggested. This classification method is applicable to other reactions such as elimination and isomerization. Furthermore, it will facilitate annotation of enzyme functions from 3D patterns of enzyme active sites. The classification is available at http://mbs.cbrc.jp/EzCatDB/RLCP/index.html.     

Ecology of testate amoebae from mires in the Central Rhodope Mountains, Greece and development of a transfer function for palaeohydrological reconstruction

Testate amoebae are useful environmental indicators in ecological and palaeoecological studies from peatlands. Previous quantitative studies have focused on the peatlands of Northern and Central Europe, North America, and New Zealand and have considered a relatively restricted variety of peatland types, mostly ombrotrophic or Sphagnum-dominated while more minerotrophic fens have been less studied. Here we present the first quantitative ecological study of testate amoebae from four small mesotrophic fens (pH 5.5-8.1) in the Elatia Forest, northern Macedonia province, Greece. Relationships with the environmental data were investigated using redundancy analysis and mantel tests. Transfer function models were derived using a variety of techniques. Results demonstrate that as for Sphagnum-dominated mires hydrology is the most important control on amoebae community composition. Transfer function models should enable water tables to be predicted within 2.5 cm, when data selection is used this is reduced to less than 2 cm. pH is also an important environmental control on testate amoebae communities, a transfer function model enables pH prediction within 0.4 pH units. The hydrological transfer function is the best performing such model yet produced in terms of prediction error. This study provides new data on the ecology of testate amoebae in fens, and the transfer function models should allow quantitative palaeohydrological reconstruction.     

Schistosoma japonicum translationally controlled tumour protein,which is associated with the development of female worms,as a target for control of schistosomiasis

Schistosomiasis is a globally important helminthic disease of both humans and animals, and is the second most common parasitic disease after malaria. Although praziquantel is extensively used for treatment of parasitic diseases, drug resistance has been reported. Therefore, new drugs and effective vaccines are needed for continuous control of schistosomiasis. Eggs produced by schistosomes are responsible for the occurrence and spread of schistosomiasis. Revealing the reproductive mechanism of schistosomes will help to control this disease. In this study, the proteomic profiles of single-sex infected female worms and bisexual infected mature female worms of Schistosoma japonicum at 18, 21, 23 and 25 days p.i. were identified with isobaric tags for relative quantitation-coupled liquid chromatography–tandem mass spectrometry. Differentially expressed proteins were subsequently used for bioinformatic analysis. Six highly expressed differentially expressed proteins in mature female worms were selected and long-term interference with small interfering RNA (siRNA) was conducted to determine biological functions. SiRNA against S. japonicum translationally controlled tumour protein (SjTCTP) resulted in the most significant effect on the growth and development of MF worms. Sjtctp mRNA expression gradually increased over time with a high level of expression maintained at 25–42 days p.i., while levels were significantly higher in mature female worms than male and SF worms. The subsequent animal immune protection experiments showed that recombinant SjTCTP (rSjTCTP) reduced the number of adults by 44.7% (P < 0.01), average egg burden per gram of liver by 57.94% (P < 0.01), egg hatching rate by 47.57% (P < 0.01), and oviposition of individual females by 43.16%. rSjTCTP induced higher levels of serum IgG, IL-2, and IL-10 in mice. Collectively, these results show that SjTCTP is vital to reproduction of female worms and, thus, is a candidate antigen for immune protection.     

When cooperation begets cooperation: the role of key individuals in galvanizing support

Life abounds with examples of conspecifics actively cooperating to a common end, despite conflicts of interest being expected concerning how much each individual should contribute. Mathematical models typically find that such conflict can be resolved by partial-response strategies, leading investors to contribute relatively equitably. Using a case study approach, we show that such model expectations can be contradicted in at least four disparate contexts: (i) bi-parental care; (ii) cooperative breeding; (iii) cooperative hunting; and (iv) human cooperation. We highlight that: (a) marked variation in contributions is commonplace; and (b) individuals can often respond positively rather than negatively to the contributions of others. Existing models have surprisingly limited power in explaining these phenomena. Here, we propose that, although among-individual variation in cooperative contributions will be influenced by differential costs and benefits, there is likely to be a strong genetic or epigenetic component. We then suggest that selection can maintain high investors (key individuals) when their contributions promote support by increasing the benefits and/or reducing the costs for others. Our intentions are to raise awareness in—and provide testable hypotheses of—two of the most poorly understood, yet integral, questions regarding cooperative ventures: why do individuals vary in their contributions and when does cooperation beget cooperation?     

Engineering of 2-Cys peroxiredoxin for enhanced stress-tolerance

A typical 2-cysteine peroxiredoxin (2-Cys Prx)-like protein (PpPrx) that alternatively acts as a peroxidase or a molecular chaperone in Pseudomonas putida KT2440 was previously characterized. The dual functions of PpPrx are regulated by the existence of an additional Cys(112) between the active Cys(51) and Cys(171) residues. In the present study, additional Cys residues (Cys(31), Cys(112), and Cys(192)) were added to PpPrx variants to improve their enzymatic function. The optimal position of the additional Cys residues for the dual functionality was assessed. The peroxidase activities of the S31C and Y192C mutants were increased 3- to 4-fold compared to the wild-type, while the chaperone activity was maintained at > 66% of PpPrx. To investigate whether optimization of the dual functions could enhance stress-tolerance in vivo, a complementation study was performed. The S31C and Y192C mutants showed a much greater tolerance than other variants under a complex condition of heat and oxidative stresses. The optimized dual functions of PpPrx could be adapted for use in bioengineering systems and industries, such as to develop organisms that are more resistant to extreme environments.