The structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases

UNLABELLED: Cyclic-di-GMP is a near-ubiquitous bacterial second messenger that is important in localized signal transmission during the control of various processes, including virulence and switching between planktonic and biofilm-based lifestyles. Cyclic-di-GMP is synthesized by GGDEF diguanylate cyclases and hydrolyzed by EAL or HD-GYP phosphodiesterases, with each functional domain often appended to distinct sensory modules. HD-GYP domain proteins have resisted structural analysis, but here we present the first structural representative of this family (1.28 Å), obtained using the unusual Bd1817 HD-GYP protein from the predatory bacterium Bdellovibrio bacteriovorus. Bd1817 lacks the active-site tyrosine present in most HD-GYP family members yet remains an excellent model of their features, sharing 48% sequence similarity with the archetype RpfG. The protein structure is highly modular and thus provides a basis for delineating domain boundaries in other stimulus-dependent homologues. Conserved residues in the HD-GYP family cluster around a binuclear metal center, which is observed complexed to a molecule of phosphate, providing information on the mode of hydroxide ion attack on substrate. The fold and active site of the HD-GYP domain are different from those of EAL proteins, and restricted access to the active-site cleft is indicative of a different mode of activity regulation. The region encompassing the GYP motif has a novel conformation and is surface exposed and available for complexation with binding partners, including GGDEF proteins.

IMPORTANCE: It is becoming apparent that many bacteria use the signaling molecule cyclic-di-GMP to regulate a variety of processes, most notably, transitions between motility and sessility. Importantly, this regulation is central to several traits implicated in chronic disease (adhesion, biofilm formation, and virulence gene expression). The mechanisms of cyclic-di-GMP synthesis via GGDEF enzymes and hydrolysis via EAL enzymes have been suggested by the analysis of several crystal structures, but no information has been available to date for the unrelated HD-GYP class of hydrolases. Here we present the multidomain structure of an unusual member of the HD-GYP family from the predatory bacterium Bdellovibrio bacteriovorus and detail the features that distinguish it from the wider structural family of general HD fold hydrolases. The structure reveals how a binuclear iron center is formed from several conserved residues and provides a basis for understanding HD-GYP family sequence requirements for c-di-GMP hydrolysis.

Children's use of interventions to learn causal structure

Children aged between 5 and 8 years freely intervened on a three-variable causal system, with their task being to discover whether it was a common-cause structure or one of two causal chains. From 6-7 years, children were able to use information from their interventions to correctly disambiguate the structure of a causal chain. We used a Bayesian model to examine children’s interventions on the system; this showed that with development children became more efficient in producing the interventions needed to disambiguate the causal structure and that the quality of interventions, as measured by their informativeness, improved developmentally. The latter measure was a significant predictor of children’s correct inferences about the causal structure. A second experiment showed that levels of performance were not reduced in a task in which children did not select and carry out interventions themselves, indicating no advantage for self-directed learning. However, children’s performance was not related to intervention quality in these circumstances, suggesting that children learn in a different way when they carry out interventions themselves.

Developing an information booklet to meet the needs of intensive care patients and relatives

Changes in the economic climate and the delivery of health care require that pre-operative information programmes are effective and efficiently implemented. In order to be effective the pre-operative programme must meet the information needs of intensive care unit (ICU) patients and their relatives. Efficiency can be achieved through a structured pre-operative programme which provides a framework for teaching. The need to develop an ICU information booklet in a large teaching hospital in Northern Ireland has become essential to provide relevant information and improve the quality of service for patients and relatives, as set out in the White Paper, ‘Working for Patients’, (DoH, 1989). The first step in establishing a patient education programme was to ascertain patients' and relatives' informational needs. A ‘needs assessment’ identified the pre-operative information needs of ICU patients and their relatives (McGaughey, 1994) and the findings were used to plan and publish an information booklet. The ICU booklet provides a structure for pre-operative visits to ensure that patients and relatives information needs are met.

Building Information Modelling (BIM) Software Interoperability: A Review of the Construction Sector

Building Information Modelling (BIM) is continuing to evolve and develop as the construction industry progresses towards level 2 maturity. However, one of the core barriers in this progression is the aspect of interoperability between software packages. This research and paper stems from a Knowledge Transfer Partnership (KTP) where both industry and academia come together to address this shortcoming within the sector. One of the core objectives of this partnership and the aim of this study is investigating potential solutions to this barrier, while also developing best working practices to be applied in industry. Using one of the case studies from this partnership (a temporary steel structure), this paper demonstrates a potential solution to addressing interoperability within structural analysis and detailing packages, MasterSeries and Revit respectively. The findings of the research indicate that a process based approach rather than that of additional software coding as being the preferred solution. The results of this preliminary research will aid in the development of the topic of interoperability within the sector, while also developing the knowledge and competencies of the parties within the KTP. The findings are explored further, by providing an overview of the resolution process adopted in this case study, in overcoming the interoperability that arose as the project progressed. It is envisaged that this study will assist the construction sector and its adoption of BIM technologies, while also addressing the critical aspect of operability between software.

Genetic structure of the lumpfish Cyclopterus lumpus across the North Atlantic

Lumpfish, or lumpsucker, Cyclopterus lumpus (Linnaeus, 1758) is widely distributed in the North Atlantic Ocean. It has a considerable economic value and substantial fisheries occur in several North Atlantic regions owing to the use of its fully ripe internal egg masses in the ovaries as an alternative to sturgeon caviar. Despite being intensively fished in several locations, biological knowledge is limited and no genetic structure information is available. In this study, the stock structure of C. lumpus was investigated across the North Atlantic using ten microsatellite loci. Out of ten loci, two exhibited higher level of differentiation but their inclusion/ exclusion from the analyses did not drastically change the observed genetic pattern. A total of three distinct genetic groups were detected: Maine-Canada-Greenland, Iceland-Norway and Baltic Sea. These results, discussed in terms of origin of differentiation, gene flow, and selection, showed that gene flow was rather limited among the detected groups, and also between Greenland and Maine-Canada.

Retrieving Similar Discussion Forum Threads: A Structure based Approach

Online forums are becoming a popular way of finding useful
information on the web. Search over forums for existing discussion
threads so far is limited to keyword-based search due
to the minimal effort required on part of the users. However,
it is often not possible to capture all the relevant context in a
complex query using a small number of keywords. Examplebased
search that retrieves similar discussion threads given
one exemplary thread is an alternate approach that can help
the user provide richer context and vastly improve forum
search results. In this paper, we address the problem of
finding similar threads to a given thread. Towards this, we
propose a novel methodology to estimate similarity between
discussion threads. Our method exploits the thread structure
to decompose threads in to set of weighted overlapping
components. It then estimates pairwise thread similarities
by quantifying how well the information in the threads are
mutually contained within each other using lexical similarities
between their underlying components. We compare our
proposed methods on real datasets against state-of-the-art
thread retrieval mechanisms wherein we illustrate that our
techniques outperform others by large margins on popular
retrieval evaluation measures such as NDCG, MAP, Precision@k
and MRR. In particular, consistent improvements of
up to 10% are observed on all evaluation measures

A Hybrid Imperialist Approach in Solving University Timetabling Problems. Information Sciences. Vol. 283, 1-21

Generating timetables for an institution is a challenging and time consuming task due to different demands on the overall structure of the timetable. In this paper, a new hybrid method which is a combination of a great deluge and artificial bee colony algorithm (INMGD-ABC) is proposed to address the university timetabling problem. Artificial bee colony algorithm (ABC) is a population based method that has been introduced in recent years and has proven successful in solving various optimization problems effectively. However, as with many search based approaches, there exist weaknesses in the exploration and exploitation abilities which tend to induce slow convergence of the overall search process. Therefore, hybridization is proposed to compensate for the identified weaknesses of the ABC. Also, inspired from imperialist competitive algorithms, an assimilation policy is implemented in order to improve the global exploration ability of the ABC algorithm. In addition, Nelder–Mead simplex search method is incorporated within the great deluge algorithm (NMGD) with the aim of enhancing the exploitation ability of the hybrid method in fine-tuning the problem search region. The proposed method is tested on two differing benchmark datasets i.e. examination and course timetabling datasets. A statistical analysis t-test has been conducted and shows the performance of the proposed approach as significantly better than basic ABC algorithm. Finally, the experimental results are compared against state-of-the art methods in the literature, with results obtained that are competitive and in certain cases achieving some of the current best results to those in the literature.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

Implication of modified molecular structure of lipid through heat-related process to fatty acids supply in Brassica carinata seed.

This study was conducted to explore the effect of different autoclave heating times (30, 60 and 90 min) on fatty acids supply and molecular stability in Brassica carinata seed. Multivariate spectral analyses and correlation analyses were also carried out in our study. The results showed that autoclaving treatments significantly decreased the total fatty acids content in a linear fashion in B. carinata seed as heating time increased. Reduced concentrations were also observed in C18:3n3, C20:1, C22:1n9, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), omega 3 (ω-3) and 9 (ω-9) fatty acids. Correspondingly, the heated seeds showed dramatic reductions in all the peak intensities within lipid-related spectral regions. Results from agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA) indicated that the raw oilseed had completely different structural make-up from the autoclaved seeds in both CH3 and CH2 asymmetric and symmetric stretching region (ca. 2999–2800 cm−1) and lipid ester Cdouble bond; length as m-dashO carbonyl region (ca. 1787–1706 cm−1). However, the oilseeds heated for 30, 60 and 90 min were not grouped into separate classes or ellipses in all the lipid-related regions, indicating that there still exhibited similarities in lipid biopolymer conformations among autoclaved B. carinata seeds. Moreover, strong correlations between spectral information and fatty acid compositions observed in our study could imply that lipid-related spectral parameters might have a potential to predict some fatty acids content in oilseed samples, i.e. B. carinata. However, more data from large sample size and diverse range would be necessary and helpful to draw up a final conclusion.