A framework for protein structure classification and identification of novel protein structures

BACKGROUND: Protein structure classification plays a central role in understanding the function of a protein molecule with respect to all known proteins in a structure database. With the rapid increase in the number of new protein structures, the need for automated and accurate methods for protein classification is increasingly important. RESULTS: In this paper we present a unified framework for protein structure classification and identification of novel protein structures. The framework consists of a set of components for comparing, classifying, and clustering protein structures. These components allow us to accurately classify proteins into known folds, to detect new protein folds, and to provide a way of clustering the new folds. In our evaluation with SCOP 1.69, our method correctly classifies 86.0%, 87.7%, and 90.5% of new domains at family, superfamily, and fold levels. Furthermore, for protein domains that belong to new domain families, our method is able to produce clusters that closely correspond to the new families in SCOP 1.69. As a result, our method can also be used to suggest new classification groups that contain novel folds. CONCLUSION: We have developed a method called proCC for automatically classifying and clustering domains. The method is effective in classifying new domains and suggesting new domain families, and it is also very efficient. A web site offering access to proCC is freely available a

Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.Portuguese Fundacao para Ciencia e Tecnologia (FCT) [PTDC/EXPL/MARBIO/0430/2013]; CCMAR FCT Plurianual financing [UID/Multi/04326/2013]; FCT [SFRH/BD/111226/2015, SFRH/BD/108842/2015, SFRH/BPD/89889/2012]; FCT-IF Starting Grant [IF/01274/2014]info:eu-repo/semantics/publishedVersio

A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Surveillance of testicular microlithiasis?: Results of an UK based national questionnaire survey

BACKGROUND: The association of testicular microlithiasis with testicular tumour and the need for follow-up remain largely unclear. METHODS: We conducted a national questionnaire survey involving consultant BAUS members (BAUS is the official national organisation (like the AUA in USA) of the practising urologists in the UK and Ireland), to provide a snapshot of current attitudes towards investigation and surveillance of patients with testicular microlithiasis. RESULTS: Of the 464 questionnaires sent to the BAUS membership, 263(57%) were returned. 251 returns (12 were incomplete) were analysed, of whom 173(69%) do and 78(31%) do not follow-up testicular microlithiasis. Of the 173 who do follow-up, 119(69%) follow-up all patients while 54(31%) follow-up only a selected group of patients. 172 of 173 use ultra sound scan while 27(16%) check tumour makers. 10(6%) arrange ultrasound scan every six months, 151(88%) annually while 10(6%) at longer intervals. 66(38%) intend to follow-up these patients for life while, 80(47%) until 55 years of age and 26(15%) for up to 5 years. 173(68.9%) believe testicular microlithiasis is associated with CIS in < 1%, 53(21%) think it is between 1&10% while 7(3%) believe it is > 10%. 109(43%) believe those patients who develop a tumour, will have survival benefit with follow-up while 142(57%) do not. Interestingly, 66(38%) who follow-up these patients do not think there is a survival benefit. CONCLUSION: There is significant variability in how patients with testicular microlithiasis are followed-up. However a majority of consultant urologists nationally, believe surveillance of this patient group confers no survival benefit. There is a clear need to clarify this issue in order to recommend a coherent surveillance policy

Clinical implications of gait analysis in the rehabilitation of adult patients with "Prader-Willi" Syndrome: a cross-sectional comparative study ("Prader-Willi" Syndrome vs matched obese patients and healthy subjects)

<p>Abstract</p> <p>Background</p> <p>Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). PWS is a complex multisystem disorder, representing the most common form of genetic obesity. The aim of this study was the analysis of the gait pattern of adult subjects with PWS by using three-Dimensional Gait Analysis. The results were compared with those obtained in a group of obese patients and in a group of healthy subjects.</p> <p>Methods</p> <p>Cross-sectional, comparative study: 19 patients with PWS (11 males and 8 females, age: 18–40 years, BMI: 29.3–50.3 kg/m²); 14 obese matched patients (5 males and 9 females, age: 18–40 years, BMI: 34.3–45.2 kg/m²); 20 healthy subjects (10 males and 10 females, age: 21–41 years, BMI: 19.3–25.4 kg/m²). Kinematic and kinetic parameters during walking were assessed by an optoelectronic system and two force platforms.</p> <p>Results</p> <p>PWS adult patients walked slower, had a shorter stride length, a lower cadence and a longer stance phase compared with both matched obese, and healthy subjects. Obese matched patients showed spatio-temporal parameters significantly different from healthy subjects.</p> <p>Furthermore, Range Of Motion (ROM) at knee and ankle, and plantaflexor activity of PWS patients were significantly different between obese and healthy subjects. Obese subjects revealed kinematic and kinetic data similar to healthy subjects.</p> <p>Conclusion</p> <p>PWS subjects had a gait pattern significantly different from obese patients. Despite that, both groups had a similar BMI. We suggest that PWS gait abnormalities may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in early childhood of PWS patients could prevent gait pattern changes.</p

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

Discriminative structural approaches for enzyme active-site prediction

<p>Abstract</p> <p>Background</p> <p>Predicting enzyme active-sites in proteins is an important issue not only for protein sciences but also for a variety of practical applications such as drug design. Because enzyme reaction mechanisms are based on the local structures of enzyme active-sites, various template-based methods that compare local structures in proteins have been developed to date. In comparing such local sites, a simple measurement, RMSD, has been used so far.</p> <p>Results</p> <p>This paper introduces new machine learning algorithms that refine the similarity/deviation for comparison of local structures. The similarity/deviation is applied to two types of applications, single template analysis and multiple template analysis. In the single template analysis, a single template is used as a query to search proteins for active sites, whereas a protein structure is examined as a query to discover the possible active-sites using a set of templates in the multiple template analysis.</p> <p>Conclusions</p> <p>This paper experimentally illustrates that the machine learning algorithms effectively improve the similarity/deviation measurements for both the analyses.</p