How accurately can we discriminate G-protein-coupled receptors as 7-tms TM protein sequences from other sequences?

The group of 2502 transmembrane (TM) protein sequences with seven TM segments (7-tms) registered in SWISS-PROT 46.0 contains 2200 G-protein-coupled receptors (GPCRs), indicating that GPCR candidates can be detected with a reliability of 87.9% in the eukaryotic genomes merely by correctly predicting the number of TM segments as 7-tms. The predictive accuracies of TM topology-prediction methods proposed so far are not as high as expected; even the best method, HMMTOP 2.0, can only achieve a capture rate of 7-tms sequences of 77.6%. It is necessary to improve this performance as much as possible, even if by only a few percentage points, in order to identify as many novel GPCR candidate genes as possible among the increasing number of newly sequenced genomes. In this study, we propose a simple but useful prediction method for detecting as many 7-tms TM protein sequences as GPCR candidates in eukaryotic genomes as possible. This is achieved by employing a two-step prediction procedure. The first step involves collecting 7-tms sequences by the best prediction method (HMMTOP 2.0), and the second involves picking up the remaining 7-tms sequences by the second-best method (TMHMM 2.0). By this procedure, the capture rate of 7-tms TM protein sequences in SWISS-PROT can be improved considerably from 77.6% to 84.5%, and the number of GPCR candidate sequences predicted as 7-tms in the human genome (Build 35) is increased from 790 (by HMMTOP 2.0) to 903. These 790 and 903 candidate sequences include, respectively, 587 and 636 of the known human GPCRs of the 717 registered in SWISS-PROT 46.0, demonstrating that the proposed combinatorial method is effective in detecting GPCR candidate genes in eukaryotic genomes.     

Rather rule than exception? How to evaluate the relevance of dual protein targeting to mitochondria and chloroplasts

Dual targeting of a nuclearly encoded protein into two different cell organelles is an exceptional event in eukaryotic cells. Yet, the frequency of such dual targeting is remarkably high in case of mitochondria and chloroplasts, the two endosymbiotic organelles of plant cells. In most instances, it is mediated by “ambiguous” transit peptides, which recognize both organelles as the target. A number of different approaches including in silico, in organello as well as both transient and stable in vivo assays are established to determine the targeting specificity of such transit peptides. In this review, we will describe and compare these approaches and discuss the potential role of this unusual targeting process. Furthermore, we will present a hypothetical scenario how dual targeting might have arisen during evolution.     

How does photorespiration modulate leaf amino acid contents? A dual approach through modelling and metabolite analysis

The aim of this work was to establish the quantitative impact of photorespiration on leaf amino acid contents. Attached leaves of wheat and potato were incubated for 30–40 min under defined conditions in which net CO₂ uptake (A) was manipulated by irradiance, ambient CO₂ or ambient O₂. The incubated portion of the leaf was sampled by a rapid‐quench method and photorespiratory flux (v_o) was modelled from the measured rate of net CO₂ uptake. In both wheat and potato, the ratio between glycine and serine showed a strong positive correlation with v_o. Aspartate and alanine correlated negatively with v_o but glutamate and glutamine showed less clear relationships. In potato, glutamate and glutamine did not correlate clearly with either A or v_o. In wheat, glutamine showed a general increase with A but no relationship with v_o, whereas 2‐oxoglutarate contents correlated positively with v_o and negatively with A. As a result, glutamine : glutamate and glutamine : 2‐oxoglutarate increased with net CO₂ uptake in wheat, observations that are attributed primarily to imperfect and variable coupling between the supply of NH₃ in primary nitrogen assimilation and the associated delivery of 2‐oxoglutarate to the chloroplast. A simple theoretical analysis is used to illustrate the potentially marked impact of primary nitrogen assimilation on leaf glutamine, even against a background of high rates of photorespiratory ammonia recycling.     

How well can the accuracy of comparative protein structure models be predicted?

Comparative structure models are available for two orders of magnitude more protein sequences than are experimentally determined structures. These models, however, suffer from two limitations that experimentally determined structures do not: They frequently contain significant errors, and their accuracy cannot be readily assessed. We have addressed the latter limitation by developing a protocol optimized specifically for predicting the Calpha root-mean-squared deviation (RMSD) and native overlap (NO3.5A) errors of a model in the absence of its native structure. In contrast to most traditional assessment scores that merely predict one model is more accurate than others, this approach quantifies the error in an absolute sense, thus helping to determine whether or not the model is suitable for intended applications. The assessment relies on a model-specific scoring function constructed by a support vector machine. This regression optimizes the weights of up to nine features, including various sequence similarity measures and statistical potentials, extracted from a tailored training set of models unique to the model being assessed: If possible, we use similarly sized models with the same fold; otherwise, we use similarly sized models with the same secondary structure composition. This protocol predicts the RMSD and NO3.5A errors for a diverse set of 580,317 comparative models of 6174 sequences with correlation coefficients (r) of 0.84 and 0.86, respectively, to the actual errors. This scoring function achieves the best correlation compared to 13 other tested assessment criteria that achieved correlations ranging from 0.35 to 0.71.     

How accurately can direct and indirect inguinal hernias be distinguished?

An inguinal hernia was clinically diagnosed as direct or indirect by paired surgeons of 134 occasions. When compared with the findings at operation the hernia was correctly diagnosed in 60 of 78 observations when it was indirect and in 33 of 56 when it was direct. The level of accuracy does not warrant continuing the practice of attempting to distinguish one type of inguinal hernia from another.     

How do floating aquatic weeds affect wetland conservation and development? How can these effects be minimised?

The most important floating aquatic weeds (FAWs) are Eichhornia crassipes, Salvinia molesta and Pistia stratiotes. E. crassipes and P. stratiotes reproduce sexually. All three species reproduce asexually. E. crassipes and S. molesta have particularly high growth rates. All can form dense mats and growth rates are increased by high nutrient levels and temperatures. Spread between continents and watersheds is largely the result of human activities. Spread within watersheds is mostly via floating propagules. FAWs are known to affect water resource management, the continued existence of human riverine and wetland communities, and conservation of biodiversity. Waterways can be blocked, and the efficiency of irrigation and hydro generation impaired. People are affected by reduction of the fish catch, inability to travel by boat and consequent isolation from gardens, markets and health services, and also changes in populations of vectors of human and animal diseases. Biodiversity can be reduced and conservation value affected. It is proposed that rational application of physical, chemical and biological control of FAWs, and reduction of nutrient input should be part of every strategy for the sustainable management of wetlands.     

Quorum sensing: How bacteria can coordinate activity and synchronize their response to external signals?

Quorum sensing is used by a large variety of bacteria to regulate gene expression in a cell-density-dependent manner. Bacteria can synchronize population behavior using small molecules called autoinducers that are produced by cognate synthases and recognized by specific receptors. Quorum sensing plays critical roles in regulating diverse cellular functions in bacteria, including bioluminescence, virulence gene expression, biofilm formation, and antibiotic resistance. The best-studied autoinducers are acyl homoserine lactone (AHL) molecules, which are the primary quorum sensing signals used by Gram-negative bacteria. In this review we focus on the AHL-dependent quorum sensing system and highlight recent progress on structural and mechanistic studies of AHL synthases and the corresponding receptors. Crystal structures of LuxI-type AHL synthases provide insights into acyl-substrate specificity, but the current knowledge is still greatly limited. Structural studies of AHL receptors have facilitated a more thorough understanding of signal perception and established the molecular framework for the development of quorum sensing inhibitors.     

When less can be better: How can we make genomic selection more cost-effective and accurate in barley?

Key message

We were able to obtain good prediction accuracy in genomic selection with ~?2000 GBS-derived SNPs. SNPs in genic regions did not improve prediction accuracy compared to SNPs in intergenic regions.

Abstract

Since genotyping can represent an important cost in genomic selection, it is important to minimize it without compromising the accuracy of predictions. The objectives of the present study were to explore how a decrease in the unit cost of genotyping impacted: (1) the number of single nucleotide polymorphism (SNP) markers; (2) the accuracy of the resulting genotypic data; (3) the extent of coverage on both physical and genetic maps; and (4) the prediction accuracy (PA) for six important traits in barley. Variations on the genotyping by sequencing protocol were used to generate 16 SNP sets ranging from ~?500 to ~?35,000 SNPs. The accuracy of SNP genotypes fluctuated between 95 and 99%. Marker distribution on the physical map was highly skewed toward the terminal regions, whereas a fairly uniform coverage of the genetic map was achieved with all but the smallest set of SNPs. We estimated the PA using three statistical models capturing (or not) the epistatic effect; the one modeling both additivity and epistasis was selected as the best model. The PA obtained with the different SNP sets was measured and found to remain stable, except with the smallest set, where a significant decrease was observed. Finally, we examined if the localization of SNP loci (genic vs. intergenic) affected the PA. No gain in PA was observed using SNPs located in genic regions. In summary, we found that there is considerable scope for decreasing the cost of genotyping in barley (to capture ~?2000 SNPs) without loss of PA.

     

Splits or waves? Trees or webs? How divergence measures and network analysis can unravel language histories

Linguists have traditionally represented patterns of divergence within a language family in terms of either a 'splits' model, corresponding to a branching family tree structure, or the wave model, resulting in a (dialect) continuum. Recent phylogenetic analyses, however, have tended to assume the former as a viable idealization also for the latter. But the contrast matters, for it typically reflects different processes in the real world: speaker populations either separated by migrations, or expanding over continuous territory. Since history often leaves a complex of both patterns within the same language family, ideally we need a single model to capture both, and tease apart the respective contributions of each. The 'network' type of phylogenetic method offers this, so we review recent applications to language data. Most have used lexical data, encoded as binary or multi-state characters. We look instead at continuous distance measures of divergence in phonetics. Our output networks combine branch- and continuum-like signals in ways that correspond well to known histories (illustrated for Germanic, and particularly English). We thus challenge the traditional insistence on shared innovations, setting out a new, principled explanation for why complex language histories can emerge correctly from distance measures, despite shared retentions and parallel innovations.     

How can quantum mechanics of material evolution be possible?: Symmetry and symmetry-breaking in protobiological evolution

Material self-assembly as a self-organizing process is always accompanied by symmetry-breaking in the material configuration. Self-sequencing of amino acids during their thermal polymerization has lost a certain property of permutation symmetry that was observed in the mixture of free amino acids. The evolutionary precursor state is more symmetrical about its internal material configuration and more degenerate due to the multitude of the indistinguishable individuals. The evolution proceeds in the direction along which the degeneracy in the internal states dissolves owing to the symmetry-breaking originating in material flow equilibrium of open material aggregates. Protobiological information is latent in the material system which is highly symmetrical and highly degenerate in its internal states. Evolution of matter is an endogenous process in which the earlier symmetric property is lost and less degenerate states are approached. Quantum-mechanically, the generation of protobiological information is due to the symmetry-breaking of the Hamiltonian originating in the interaction with the exterior through material flow, in contrast to the Schrödinger equation which preserves a symmetry and the associated invariants.     

Somatic cell nuclear transfer efficiency: How can it be improved through nuclear remodeling and reprogramming?

Fertile offspring from somatic cell nuclear transfer (SCNT) is the goal of most cloning laboratories. For this process to be successful, a number of events must occur correctly. First the donor nucleus must be in a state that is amenable to remodeling and subsequent genomic reprogramming. The nucleus must be introduced into an oocyte cytoplasm that is capable of facilitating the nuclear remodeling. The oocyte must then be adequately stimulated to initiate development. Finally the resulting embryo must be cultured in an environment that is compatible with the development of that particular embryo. Much has been learned about the incredible changes that occur to a nucleus after it is placed in the cytoplasm of an oocyte. While we think that we are gaining an understanding of the reorganization that occurs to proteins in the donor nucleus, the process of cloning is still very inefficient. Below we will introduce the procedures for SCNT, discuss nuclear remodeling and reprogramming, and review techniques that may improve reprogramming. Finally we will briefly touch on other aspects of SCNT that may improve the development of cloned embryos.     

Human population dynamics revisited with the logistic model: How much can be modeled and predicted?

Decrease or growth of population comes from the interplay of death and birth (and locally, migration). We revive the logistic model, which was tested and found wanting in early-20th-century studies of aggregate human populations, and apply it instead to life expectancy (death) and fertility (birth), the key factors totaling population. For death, once an individual has legally entered society, the logistic portrays the situation crisply. Human life expectancy is reaching the culmination of a two-hundred year-process that forestalls death until about 80 for men and the mid-80's for women. No breakthroughs in longevity are in sight unless genetic engineering comes to help. For birth, the logistic covers quantitatively its actual morphology. However, because we have not been able to model this essential parameter in a predictive way over long periods, we cannot say whether the future of human population is runaway growth or slow implosion. Thus, we revisit the logistic analysis of aggregate human numbers. From a niche point of view, resources are the limits to numbers, and access to resources depends on technologies. The logistic makes clear that for homo faber, the limits to numbers keep shifting. These moving edges may most confound forecasting the long-run size of humanity.     

How accurately can oligonucleotide structures be determined from the hybrid relaxation rate matrix/NOESY distance restrained molecular dynamics approach?

The accuracy and precision of structures derived from a combined hybrid relaxation rate matrix/NOESY distance restrained molecular dynamics methodology were examined with simulations that included typical experimental errors. NOESY data were simulated for a DNA dodecamer duplex, d-(CGCGAATTCGCG)2, with added volume error of approximately 20% and low-level thermal noise. Distances derived from a hybrid relaxation matrix analysis of the NOE data were used as constraints in molecular dynamics driven structural refinements of several initial model geometries. The final structures were compared against results obtained from the traditional isolated two-spin approximation treatment of these NOESY volumes and also against refined structures that employed error-free data. Results show that the structures derived from the relaxation rate matrix analysis of the NOESY data are more accurate than those derived from a simple two-spin approximation analysis and it is possible to achieve refinement to the level of simulated experimental error. Results may be significantly improved with the use of either more accurately measured NOESY volumes or additional matrix-derived constraints. Many of the helical parameters and backbone torsional angles may be accurately reproduced by the hybrid matrix methodology.     

How much land‐based greenhouse gas mitigation can be achieved without compromising food security and environmental goals?

Feeding 9–10 billion people by 2050 and preventing dangerous climate change are two of the greatest challenges facing humanity. Both challenges must be met while reducing the impact of land management on ecosystem services that deliver vital goods and services, and support human health and well‐being. Few studies to date have considered the interactions between these challenges. In this study we briefly outline the challenges, review the supply‐ and demand‐side climate mitigation potential available in the Agriculture, Forestry and Other Land Use AFOLU sector and options for delivering food security. We briefly outline some of the synergies and trade‐offs afforded by mitigation practices, before presenting an assessment of the mitigation potential possible in the AFOLU sector under possible future scenarios in which demand‐side measures codeliver to aid food security. We conclude that while supply‐side mitigation measures, such as changes in land management, might either enhance or negatively impact food security, demand‐side mitigation measures, such as reduced waste or demand for livestock products, should benefit both food security and greenhouse gas (GHG) mitigation. Demand‐side measures offer a greater potential (1.5–15.6 Gt CO₂‐eq. yr^?1) in meeting both challenges than do supply‐side measures (1.5–4.3 Gt CO₂‐eq. yr^?1 at carbon prices between 20 and 100 US$ tCO₂‐eq. yr^?1), but given the enormity of challenges, all options need to be considered. Supply‐side measures should be implemented immediately, focussing on those that allow the production of more agricultural product per unit of input. For demand‐side measures, given the difficulties in their implementation and lag in their effectiveness, policy should be introduced quickly, and should aim to codeliver to other policy agenda, such as improving environmental quality or improving dietary health. These problems facing humanity in the 21st Century are extremely challenging, and policy that addresses multiple objectives is required now more than ever.