ProRule: a new database containing functional and structural information on PROSITE profiles

MOTIVATION: Increase the discriminatory power of PROSITE profiles to facilitate function determination and provide biologically relevant information about domains detected by profiles for the annotation of proteins. SUMMARY: We have created a new database, ProRule, which contains additional information about PROSITE profiles. ProRule contains notably the position of structurally and/or functionally critical amino acids, as well as the condition they must fulfill to play their biological role. These supplementary data should help function determination and annotation of the UniProt Swiss-Prot knowledgebase. ProRule also contains information about the domain detected by the profile in the Swiss-Prot line format. Hence, ProRule can be used to make Swiss-Prot annotation more homogeneous and consistent. The format of ProRule can be extended to provide information about combination of domains. AVAILABILITY: ProRule can be accessed through ScanProsite at http://www.expasy.org/tools/scanprosite. A file containing the rules will be made available under the PROSITE copyright conditions on our ftp site (ftp://www.expasy.org/databases/prosite/) by the next PROSITE release.     

FindPept,a tool to identify unmatched masses in peptide mass fingerprinting protein identification

FindPept (http://www.expasy.org/tools/findpept.html) is a software tool designed to identify the origin of peptide masses obtained by peptide mass fingerprinting which are not matched by existing protein identification tools. It identifies masses resulting from unspecific proteolytic cleavage, missed cleavage, protease autolysis or keratin contaminants. It also takes into account post-translational modifications derived from the annotation of the SWISS-PROT database or supplied by the user, and chemical modifications of peptides. Based on a number of experimental examples, we show that the commonly held rules for the specificity of tryptic cleavage are an oversimplification, mainly because of effects of neighboring residues, experimental conditions, and contaminants present in the enzyme sample.     

Amperometric determination of total phenolic content in wine by laccase immobilized onto silver nanoparticles/zinc oxide nanoparticles modified gold electrode

Tyrosine sulfation is a ubiquitous posttranslational modification that regulates extracellular protein-protein interactions, intracellular protein transportation modulation, and protein proteolytic process. However, identifying tyrosine sulfation sites remains a challenge due to the lability of sulfation sequences. In this study, we developed a method called PredSulSite that incorporates protein secondary structure, physicochemical properties of amino acids, and residue sequence order information based on support vector machine to predict sulfotyrosine sites. Three types of encoding algorithms-secondary structure, grouped weight, and autocorrelation function-were applied to mine features from tyrosine sulfation proteins. The prediction model with multiple features achieved an accuracy of 92.89% in 10-fold cross-validation. Feature analysis showed that the coil structure, acidic amino acids, and residue interactions around the tyrosine sulfation sites all contributed to the sulfation site determination. The detailed feature analysis in this work can help us to understand the sulfation mechanism and provide guidance for the related experimental validation. PredSulSite is available as a community resource at http://www.bioinfo.ncu.edu.cn/inquiries_PredSulSite.aspx.     

The PROSITE database, its status in 1999.

The PROSITE database (http://www.expasy.ch/sprot/prosite.htm l) consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contains.     

Tyrosine-phosphorylation of the scaffold protein ADAP and its role in T cell signaling

Introduction: The Adhesion and Degranulation promoting Adaptor Protein (ADAP) is phosphorylated upon T cell activation and acts as a scaffold for the formation of a signaling complex that integrates molecular interactions between T cell or chemokine receptors, the actin cytoskeleton, and integrin-mediated cellular adhesion and migration.

Areas covered: This article reviews current knowledge of the functions of the adapter protein ADAP in T cell signaling with a focus on the role of individual phosphotyrosine (pY) motifs for SH2 domain mediated interactions. The data presented was obtained from literature searches (PubMed) as well as the authors own research on the topic.

Expert commentary: ADAP can be regarded as a paradigmatic example of how tyrosine phosphorylation sites serve as dynamic interaction hubs. Molecular crowding at unstructured and redundant sites (pY595, pY651) is contrasted by more specific interactions enabled by the three-dimensional environment of a particular phosphotyrosine motif (pY571).     

Probabilistic alignment of motifs with sequences

MOTIVATION: Motif detection is an important component of the classification and annotation of protein sequences. A method for aligning motifs with an amino acid sequence is introduced. The motifs can be described by the secondary (i.e. functional, biophysical, etc.) characteristics of a signal or pattern to be detected. The results produced are based on the statistical relevance of the alignment. The method was targeted to avoid the problems (i.e. over-fitting, biological interpretation and mathematical soundness) encountered in other methods currently available. RESULTS: The method was tested on lipoprotein signals in B. subtilis yielding stable results. The results of signal prediction were consistent with other methods where literature was available. AVAILABILITY: An implementation of the motif alignment, refining and bootstrapping is available for public use online at http://www.expasy.org/tools/patoseq/     

Advances,challenges and tools in characterizing bacterial serine,threonine and tyrosine kinases and phosphorylation target sites.

Introduction: The cellular response to infection by bacterial pathogens involves a complex and highly regulated series of pathways that carry messages to various parts of the cell. These messages are transferred using post-translational modifications including phosphorylation by kinases. Understanding the host’s signaling pathways is valuable in identifying potential treatment targets, but the bacterial signaling pathways and host-pathogen crosstalk are equally important to the development of therapeutics.

Areas covered: This review summarizes some of the recent findings related to the bacterial phosphoproteome and especially serine/threonine/tyrosine sites, including methods and considerations for identifying novel phosphosites. We also consider the bioinformatics tools that have been developed to sift through the large volume of data in these studies and connect them to biologically relevant knowledge about pathways and function. Literature databases used include PubMed and Google Scholar from April 2018 to December 2018.

Expert opinion: While the field has developed significantly in the past decade of research, high-quality experimental sequence data remains the limiting factor to future research into bacterial phosphoproteomics. As more proteomes are explored, it will be easier to tailor tools and techniques to prokaryotes. It will be necessary to consider the phosphoproteome in the broader biological context, through interdisciplinary collaborations.     

Kleptoparasitism in gulls Laridae at an urban and a coastal foraging environment: an assessment of ecological predictors

Capsule: Kleptoparasitism in gulls occurred at a greater rate at an urban compared with a coastal site. Population density and prey size predicted the rate of kleptoparasitism at the urban site.

Aims: To investigate and assess the ecological variables associated with kleptoparasitism among gulls at urban and rural sites.

Methods: Field observations were conducted at Brancaster (coastal rural) and Billingsgate Market (urban) to examine differences in the rate of kleptoparasitism in mixed-species flocks of gulls. Four key variables (prey size, population density, season and species) were assessed as predictors of kleptoparasitism.

Results: Generalized linear models revealed significant effects on kleptoparasitism rate of site, population density and prey size, and two-way interactions between these main terms. Population density and prey size differed significantly between sites, but population density appeared to predict the rate of kleptoparasitism.

Conclusion: Kleptoparasitism may well aid invasion and increase the range of environments a gull can tolerate by helping them meet their energy needs in novel environments where normal foraging behaviours are difficult to implement.     

Emerging single-cell technologies for functional proteomics in oncology

Introduction: Cellular heterogeneity has challenged current cancer therapeutics and hindered the discovery and development of cancer drugs. The heterogeneity in functional proteome is of particular interest because many cancer drugs are developed to target signaling proteins. The complex nature of tumor systems calls for more advanced multiplexed single-cell tools to address the heterogeneity issue.

Area covered: Over the past five years, there are a few single-cell functional proteomics tools introduced with unprecedented multiplexity and performance that are transforming the oncology field. Those tools are generally categorized as cytometry-based tools and microfluidics-based tools, and we discuss the representatives in both categories.

Expert commentary: The single-cell tools have provided an avenue to understand the multifaceted differences of cancer cells, the complex signaling networks, and the relationship of intercellular interaction and tumor architecture. We also provide an outlook of single-cell tools in five years and the challenges to address before a greater impact on oncology can be made.     

Transplanting the leafy liverwort Herbertus hutchinsiae: a suitable conservation tool to maintain oceanic-montane liverwort-rich heath?

Background: Translocating plants for conservation purposes can be a useful tool to enhance existing populations, restore lost populations or create new ones, but has rarely been done for bryophytes, especially liverworts.

Aims: Here, the leafy liverwort Herbertus hutchinsiae, a representative species of oceanic-montane liverwort-rich heath, was translocated to unoccupied habitat within its current range, to establish whether its restricted distribution is due to habitat or dispersal limitation.

Methods: Feasibility of establishing new populations outside the current distribution range was assessed, to test the suitability of the species for assisted colonisation. Furthermore, transplants were grown at degraded sites where the species had declined to assess potential for restoration.

Results: Although maximal growth rates occurred within-range, transplants grew at all sites, indicating that the species could be dispersal limited; a conclusion supported by distribution modelling.

Conclusions: Assisted colonisation is thus an option for this species to overcome dispersal limitation and to track future climate space. Reinforcement of populations at degraded sites is only recommended if the pressure causing the degradation has been removed. These findings provide an evidence base for practical conservation management.     

P2BAT: a massive parallel implementation of PBAT for genome-wide association studies in R

The software tool P2BAT provides a massive parallel and user friendly implementation of the PBAT-analysis tools for family-based association tests (FBATs) in large-scale studies, including genome-wide association studies with several thousand subjects. Built on the original PBAT-implementation of the Lange-Van Steen algorithm to bypass the multiple testing problem in family-based association studies, P2BAT integrates all PBAT-analysis tools for binary and complex traits into R and makes them accessible through a user-friendly GUI. The genome-wide analysis tools are fully automated and can be ran massively parallel directly through the GUI. P2BAT is fully documented and contains graphical output tools for time-to-onset analysis. P2BAT also features the ability to test for gene and environment/drug interaction. AVAILABILITY: The P2BAT package is available as the R package 'pbatR' which can be downloaded from http://cran.r-project.org/. The PBAT-software is available at http://www.biostat.harvard.edu/~clange/.     

The diversity and community dynamics of hazelwood lichens and bryophytes along a major gradient of human impact

Background: Oceanic hazelwoods in western Scotland are hypothesised to be unmanaged post-glacial relicts, representing an unusual type of old-growth forest habitat in Europe. They are characterised by an exceptionally high epiphytic diversity, including their status as ‘hotspots’ for indicators of woodland ecological continuity.

Aims: The aim of this study was to evaluate the effects of climate, pollution and management on the occurrence of epiphytic lichens and bryophytes on Corylus avellana.

Methods: Thirteen hazelwood study sites were systematically sampled along a climate, pollution and management gradient in Britain. Epiphyte composition and richness were examined in a strict hierarchical framework, and compared against site-, stool- and stem-scale environmental predictors.

Results: The study showed that along the gradient from ‘clean-air’ relict sites to ‘polluted’ coppiced sites: (i) epiphytic local stem-scale diversity declined, (ii) there was a loss of late-successional species including foliose cyano- and tripartite lichens and bryophytes and (iii) stem sizes were reduced, providing a further limit to the accumulation of species richness within a site.

Conclusions: Relict hazelwoods in western Scotland are confirmed as an example of the most intact epiphyte communities. In particular, we show that the transition to coppicing can be clearly linked to ecological processes causing species loss.     

Nocturnal bird migration in the Bay of Biscay as observed by a thermal-imaging camera

Capsule: Bird migration was recorded by an infrared device at three sites in the southeastern Bay of Biscay, indicating seasonal east–west differences in migration flow.

Aims: The main aims of this study were to quantify and describe nocturnal migration dynamics in proximity of a sea barrier, and to assess seasonal and geographical drivers of migration patterns.

Methods: A thermal-imaging camera was used at two coastal study sites (Punta Galea, Cape Higuer) in spring and three study sites (coast: Punta Galea, Cape Higuer; inland: Iregua Valley) in autumn for four hours from sunset over 90 nights in 2014 and 2015.

Results: Migration was strong at both coastal sites in early spring. Autumn migration was weak at the western coast, but strong at the eastern coast and inland. Tailwind had no significant effect on migration intensity, but migration ceased during strong cross- or headwinds despite clear skies. The majority of the targets were passerines.

Conclusions: The patterns observed suggest spring migration occurs on a broader front, potentially involving sea crossing further to the west, while autumn migration concentrates more eastwards over land. In both seasons, there was no significant response to wind conditions.     

ExPASy: The proteomics server for in-depth protein knowledge and analysis

The ExPASy (the Expert Protein Analysis System) World Wide Web server (http://www.expasy.org), is provided as a service to the life science community by a multidisciplinary team at the Swiss Institute of Bioinformatics (SIB). It provides access to a variety of databases and analytical tools dedicated to proteins and proteomics. ExPASy databases include SWISS-PROT and TrEMBL, SWISS-2DPAGE, PROSITE, ENZYME and the SWISS-MODEL repository. Analysis tools are available for specific tasks relevant to proteomics, similarity searches, pattern and profile searches, post-translational modification prediction, topology prediction, primary, secondary and tertiary structure analysis and sequence alignment. These databases and tools are tightly interlinked: a special emphasis is placed on integration of database entries with related resources developed at the SIB and elsewhere, and the proteomics tools have been designed to read the annotations in SWISS-PROT in order to enhance their predictions. ExPASy started to operate in 1993, as the first WWW server in the field of life sciences. In addition to the main site in Switzerland, seven mirror sites in different continents currently serve the user community.     

Habitat use and tree selection of a declining Afro-Palaearctic migrant at sub-Saharan staging and wintering sites

Capsule: Wood Warblers Phylloscopus sibilatrix showed significant selection for tree species and woodland characteristics at staging and wintering sites in sub-Saharan Africa.

Aims: To investigate home range size, habitat and tree species selection of Wood Warblers at a staging site in Burkina Faso (Koubri) and a wintering site in Ghana (Pepease).

Methods: Comparing habitat recorded at locations of radio-tagged birds and at control points, we investigated whether there was habitat and tree species selection. We also compared home range size of individual birds between the two sites.

Results: Home range size did not differ between the two sites. There was significant selection for tree species at both Koubri and Pepease: Anogeissus leiocarpus and Albizia zygia, respectively. At Koubri, there was significant avoidance of the most common tree species (Azadirachta indica, Mangifera indica (both non-native), Vitellaria paradoxa and Acacia spp.). In addition, there was a preference for taller trees and greater tree density at both sites. However, the probability of a point being used declined with increasing number of taller (>14?m) trees.

Conclusion: Fine-scale selection of woodland habitats suggests that Wood Warblers are likely to suffer the consequences of ongoing land-use change in their West African wintering grounds.     

Habitat preference of female Corncrakes Crex crex: implications for the conservation of breeding sites in a secretive species

Capsule: Forb-rich and diverse, annually mown vegetation is the preferred Corncrake Crex crex breeding habitat in floodplains.

Aims: To identify habitat preferences of female Corncrakes and characteristics of breeding sites in floodplain habitats and derive recommendations for management.

Methods: We tracked six female Corncrakes and compared vegetation characteristics at 78 male calling sites with regard to breeding records and diurnal call activity of males, because we expect the latter to indicate female occurrence. Additionally, we analysed how practice and timing of land use in the preceding year affected vegetation structure.

Results: Females preferred areas with high cover of forbs and a distinct relief heterogeneity, which was associated with overall vegetation diversity. All calling sites with breeding records and diurnal call incidence of males showed high forb and low sedge cover, low litter heights and a close location to ditches. Favourable conditions were best provided by mowing in the preceding year.

Conclusion: In eutrophic habitats, female Corncrakes preferred a vegetation structure created by annual mowing. Because nests and unfledged chicks are threatened by mowing operations, we recommend an alternating management regime based on the identification of breeding sites using male diurnal calling activity.     

A proposed explanation for thunderstorm asthma and leukemia risk near high-voltage power lines: a supported hypothesis

Thunderstorm asthma and increased childhood leukemia risk near high-voltage power lines (HVPL) are occurrences whose mechanism of effect is not fully understood.

This paper proposes and discusses a key similarity: both thunderstorms and HVPL generate a high enough electrical field in the environment to ionize nearby air and air-borne particles.

I argue that the repeatedly demonstrated acute asthma response to pollen-laden air during thunderstorms is largely due to ionization of air-borne allergens, which adhere more readily and in greater quantity in the lungs than non-ionized particles. If these bind to mucous or phagocytic cells, it would enhance immune response. A rapid temperature drop and high ozone also seem to be drivers of thunderstorm asthma.

This causal nexus provides strong support for the parallel situation of prolonged exposure to ionized particles near HVPL and an increased rate of childhood leukemia. Here, it is proposed that upwind carcinogens are ionized when passing HVPL and then residential and business areas. Published evidence for most steps are presented, but have not previously been published as a coherent whole, nor has it been suggested that the inhaled ionized micro-particle explanation for acute asthma may also explain development of childhood leukemia over time.

The demonstrated series of events leading to increased deposition and retention of ionized particles in airways provides support for explaining both adverse health outcomes: acute thunderstorm asthma and increased risk of childhood leukemia near HVPL. Further support for this explanation of both outcomes is provided by effects of on-going proximity to highways.     

Future breeding and foraging sites of a southern edge population of the locally endangered Black Guillemot Cepphus grylle

Capsule: One of the southernmost populations of the Black Guillemot Cepphus grylle is currently endangered, and the risk may be exacerbated by climate change.

Aims: We evaluated the future vulnerability of the Black Guillemot by predicting the impact of climate change on the geographic distribution of its breeding and foraging range in the Baltic Sea.

Methods: We used MaxEnt, a species distribution modelling technique, to predict the current and future breeding grounds and foraging sites.

Results: We found that although the foraging range is expected to increase in the southern Baltic Sea in future, these areas will no longer be suitable as breeding grounds due to a changing climate, creating a spatial mismatch.

Conclusion: Our predictions indicate where threats to the species may be most severe and can be used to guide conservation planning. We advocate conservation measures which integrate potential future threats and focus on breeding sites across the current and future potential geographic range of the Black Guillemot.     

Exploring the biochemistry of the prenylome and its role in disease through proteomics: progress and potential

Introduction: Protein prenylation is a ubiquitous covalent post-translational modification characterized by the addition of farnesyl or geranylgeranyl isoprenoid groups to a cysteine residue located near the carboxyl terminal of a protein. It is essential for the proper localization and cellular activity of numerous proteins, including Ras family GTPases and G-proteins. In addition to its roles in cellular physiology, the prenylation process has important implications in human diseases and in the recent years, it has become attractive target of inhibitors with therapeutic potential.

Areas covered: This review attempts to summarize the basic aspects of prenylation integrating them with biological functions in diseases and giving an account of the current status of prenylation inhibitors as potential therapeutics. We also summarize the methodologies for the characterization of this modification.

Expert commentary: The growing body of evidence suggesting an important role of prenylation in diseases and the subsequent development of inhibitors of the enzymes responsible for this modification lead to the urgent need to identify the full spectrum of prenylated proteins that are altered in the disease or affected by drugs. Proteomic tools to analyze prenylated proteins are recently emerging, thanks to the advancement in the field of mass spectrometry coupled to enrichment strategies.