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 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.     

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.     

How can a beta-sheet peptide be both a potent antimicrobial and harmfully toxic? Molecular dynamics simulations of protegrin-1 in micelles

In this work, the naturally occurring beta-hairpin antimicrobial peptide protegrin-1 (PG-1) is studied by molecular dynamics simulation in all-atom sodium dodecylsulfate and dodecylphosphocholine micelles. These simulations provide a high-resolution picture of the interactions between the peptide and simple models of bacterial and mammalian membranes. Both micelles show significant disruption, as is expected for a peptide that is both active against bacteria and toxic to host cells. There is, however, clear differentiation between the behavior in SDS versus DPC, which suggests different mechanisms of interaction for PG-1 with mammalian and bacterial membranes. Specifically, the equilibrium orientation of the peptide relative to SDS is a mirror image of its position relative to DPC. In both systems, the arginine residues of PG-1 strongly interact with the head groups of the micelles. In DPC, the peptide prefers a location closer to the core of the micelle with Phe12, Val14, and Val16 imbedded in the core and the other side of the hairpin, which includes Leu5 and Tyr7, located closer to the surface of the micelle. In SDS, the peptide prefers a location at the micelle-water interface. The peptide position is reversed, with Leu5 and Cys6 imbedded furthest in the micelle core and Phe12, Val14, and Val16 on the surface of the micelle. We discuss the implications of these results with respect to activity and toxicity.     

How can soil monitoring networks be used to improve predictions of organic carbon pool dynamics and CO2 fluxes in agricultural soils?

As regional and continental carbon balances of terrestrial ecosystems become available, it becomes clear that the soils are the largest source of uncertainty. Repeated inventories of soil organic carbon (SOC) organized in soil monitoring networks (SMN) are being implemented in a number of countries. This paper reviews the concepts and design of SMNs in ten countries, and discusses the contribution of such networks to reducing the uncertainty of soil carbon balances. Some SMNs are designed to estimate country-specific land use or management effects on SOC stocks, while others collect soil carbon and ancillary data to provide a nationally consistent assessment of soil carbon condition across the major land-use/soil type combinations. The former use a single sampling campaign of paired sites, while for the latter both systematic (usually grid based) and stratified repeated sampling campaigns (5?C10 years interval) are used with densities of one site per 10?C1,040 km². For paired sites, multiple samples at each site are taken in order to allow statistical analysis, while for the single sites, composite samples are taken. In both cases, fixed depth increments together with samples for bulk density and stone content are recommended. Samples should be archived to allow for re-measurement purposes using updated techniques. Information on land management, and where possible, land use history should be systematically recorded for each site. A case study of the agricultural frontier in Brazil is presented in which land use effect factors are calculated in order to quantify the CO₂ fluxes from national land use/management conversion matrices. Process-based SOC models can be run for the individual points of the SMN, provided detailed land management records are available. These studies are still rare, as most SMNs have been implemented recently or are in progress. Examples from the USA and Belgium show that uncertainties in SOC change range from 1.6?C6.5 Mg C ha^?1 for the prediction of SOC stock changes on individual sites to 11.72 Mg C ha^?1 or 34% of the median SOC change for soil/land use/climate units. For national SOC monitoring, stratified sampling sites appears to be the most straightforward attribution of SOC values to units with similar soil/land use/climate conditions (i.e. a spatially implicit upscaling approach).     

Simultaneous dual targeting of Par-4 and G6PD: a promising new approach in cancer therapy? Quintessence of a literature review on survival requirements of tumor cells

The aim of this hypothesis is to propose a new approach in targeted therapy of cancer: The simultaneous, dual targeting of two single molecules, Par-4 and G6PD, rather than inhibition of full-length signaling pathways. Rationale: Targeted inhibition of especially two survival signaling pathways (PI3K/AKT/mTOR and MAPK/ERK) is frequently tried, however, a major breakthrough has not yet been reported. Inhibition of complete pathways naturally goes along with a variety of dose-limiting side effects thus contributing to poor efficacy of the administered drugs. This essay offers a synopsis of relevant studies to support the above mentioned idea—targeting of two single molecules which either are crucial for tumor growth and cancer-cell-survival: on one side, Par-4-activation selectively triggers apoptosis of tumor cells thus reversing their characteristic feature—immortality. On the other side inhibition of G6PD breaks the energy supply of tumor cells, weakens their defence against oxidative stress and thereby enhances the sensitivity of tumor cells to oxidative agents (e.g. chemotherapy). Advantage of the proposed dual Par-4/G6PD-therapy is good tolerability and—especially when administered along with conventional therapy—less frequent emergence of resistance.     

How can an agri-environmental scheme be designed for farmland bird protection,and what does it mean for the CAP 2023–2027?

Biodiversity loss is recognized as a major global threat. The European Commission has addressed this issue with vigour in its current strategy papers. Farmland birds, such as the lapwing (Vanellus vanellus), whose population has been rapidly declining in Germany, have been particularly affected. To date, the European Union has tried to tackle the problem of biodiversity loss mainly with voluntary agri-environmental schemes (AESs), which are financed by the European Agricultural Fund for Rural Development (EAFRD). However, only a small fraction of agricultural land is enrolled in such programs. We identify the possible drivers and inhibitors of farmers’ acceptance of a potential AES that, if introduced, could contribute to lapwing conservation. Our analysis is based on a discrete choice experiment conducted with 252 arable farmers in Germany. The results suggest that scheme attributes tied with EAFRD compliance, i.e., a minimum participation period of five years and the nature of the relevant sanctions regime, reduce farmers’ potential acceptance of the proposed AES. Furthermore, farmers and farm characteristics have an influence on preferences for specific AES attributes. Finally, this article outlines how the identified weaknesses of AES may be addressed in the new “Green Architecture” of the Common Agricultural Policy 2023–2027.     

Stimulation of phospholipase Cβ by membrane interactions,interdomain movement,and G protein binding — How many ways can you activate an enzyme?

Signaling proteins are usually composed of one or more conserved structural domains. These domains are usually regulatory in nature by binding to specific activators or effectors, or species that regulate cellular location, etc. Inositol-specific mammalian phospholipase C (PLC) enzymes are multidomain proteins whose activities are controlled by regulators, such as G proteins, as well as membrane interactions. One of these domains has been found to bind membranes, regulators, and activate the catalytic region. The recently solved structure of a major region of PLC-beta2 together with the structure of PLC-delta1 and a wealth of biochemical studies poises the system towards an understanding of the mechanism through which their regulations occurs.     

How can two soft bodied animals be precisely connected? a miniature quick‐connect system in the slugs,Arion lusitanicus and Arion rufus

Among stylommatophoran gastropods, many species have simplified or reduced their copulatory organs, for example, within the Arionidae, many species lack penes. In this study, I ask two questions 1) How are soft bodied slugs which do not possess a penis connected during copulation? and 2) Is there a mechanical isolating barrier between related sympatric slug species? Observations on the mating behavior and the functional morphology of the distal genital apparatus were made in a mixed population of Arion lusitanicus and Arion rufus. The investigated Arion species exhibit an elaborate copulation process with a quick genital coupling. Prior to full eversion of the distal genitalia, the genital coupling proceeds inside the atrium cavity of one of the partners. This is in contrast to the symmetrical mutual eversion in penis‐bearing species. The donor–recipient channels are tightly connected to one after another and fit precisely. During copulation, the jelly‐coated spermatophore of the donor is pressed out into the connected channel of the partner, where it is implanted only with its frontal part. In the field, successful interspecific matings in terms of spermatophore transfer were rarely observed. The observations presented indicate a mechanical barrier which may profoundly influence the intraspecific and interspecific mating success. J. Morphol. 276:631–648, 2015. © 2014 Wiley Periodicals, Inc.