Workflow management systems for gene sequence analysis and evolutionary studies – A Review

Post ‘omic’ era has resulted in the development of many primary, secondary and derived databases. Many analytical and visualization bioinformatics tools have been developed to manage and analyze the data available through large sequencing projects. Availability of heterogeneous databases and tools make it difficult for researchers to access information from varied sources and run different bioinformatics tools to get desired analysis done. Building integrated bioinformatics platforms is one of the most challenging tasks that bioinformatics community is facing. Integration of various databases, tools and algorithm is a challenging problem to deal with. This article describes the bioinformatics analysis workflow management systems that are developed in the area of gene sequence analysis and phylogeny. This article will be useful for biotechnologists, molecular biologists, computer scientists and statisticians engaged in computational biology and bioinformatics research.     

Alternative hormone replacement regimens: is there a need for further clinical trials?

PURPOSE OF REVIEW: To review the randomized trials of hormone replacement therapy. RECENT FINDINGS: Studies have shown that conjugated equine estrogen 0.625 mg a day plus medroxyprogesterone acetate 2.5 mg a day increased the risk of cardiovascular events during the first year of treatment in women both with and without coronary heart disease. Conjugated equine estrogen plus medroxyprogesterone acetate also increased the overall risk of myocardial infarction and stroke in women without coronary heart disease, and myocardial infarction or death in women with coronary heart disease, and also increased the risk of breast cancer, cognitive decline and dementia. Unopposed, oral 17B-estradiol increased the risk of stroke during the first 6 months of treatment in women with a previous stroke. Oral 17B-estradiol with or without cyclic progestin had no effect on the progression of atherosclerosis or reinfarction. Transdermal 17B-estradiol plus cyclic progestin was associated with a non-significant increase in coronary heart disease events in women with coronary heart disease. Compared with placebo, cardiovascular events increased in the ongoing estrogen-only arm of the Women's Health Initiative, indicating that unopposed conjugated equine estrogen is unlikely to be cardioprotective. However, oral 17B-estradiol retarded the progression of subclinical atherosclerosis in younger women without coronary heart disease. SUMMARY: Hormone replacement therapy should not be initiated for the primary or secondary prevention of coronary heart disease in women. A trial of 17B-estradiol started at menopause in women without coronary heart disease should be considered.     

Lead editorial: Trials – using the opportunities of electronic publishing to improve the reporting of randomised trials

Background

The purpose of this study is to compare the efficacy of prophylactic antibiotic for prevention of meningitis in acute traumatic pneumocephalus patients.

Methods

In this prospective, randomized controlled clinical trial, 200 selected head injury patients with traumatic pneumocephalus are randomly assigned to receive intravenous antibiotics (2 grams Ceftriaxone twice a day), oral antibiotics (Azithromycin) or placebo for at least 7 days after trauma. The patients will be followed for one month posttrauma.

Conclusion

The authors hope that this study helps clarifying the effectiveness and indications of antibiotics in prevention of meningitis in traumatic pneumocephalus after head injury and in specific subgroup of these patients.     

Laboratory information management system for membrane protein structure initiative – from gene to crystal

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.     

Rating species sensitivity throughout gradient systems – a consistent approach for the Baltic Sea

Evaluating the state of benthic communities has played an important role in water quality assessments. Indices incorporating species sensitivities, richness and densities are commonly applied. In Europe, the importance of benthic indices has increased in the last years with the implementation of the European Marine Strategy Framework Directive (MSFD) which at the same time demands the applicability of an index across regional scales. To date, environmental variability is rarely considered in benthic indices and most sensitivity rankings have the disadvantages of static values (i.e. the same value in all areas), expert judgement and a limited geographical range.This study presents species sensitivity values calculated along environmental gradients for the Baltic Sea. Sensitivities were calculated according to the procedure of the Benthic Quality Index (BQI). We created a matrix of subregions, classes of salinity, depth and gear to identify comparable subsets for data analysis. Altogether, 19 subsets were defined within the Baltic Sea basins. Sensitivity values were calculated for 329 species out of a total of 678 species that were recorded in this study. Sensitivity values of taxa vary between subsets as it was expected for different environmental conditions. Most sensitivity values can be assigned to species occurring in euhaline and polyhaline waters. Distribution of species with high and low sensitivity values differed along the salinity gradient. In euhaline waters more species with high sensitivity values occurred than species with low sensitivity values, while in mesohaline waters the ratio of high and low sensitivity values among species was almost equal. In oligohaline waters more species with lower sensitivity values were present.For the first time, sensitivity values were calculated for a large number of species using the same method for the entire Baltic Sea. This results in a Baltic-wide comprehensive set of sensitivity values based on a dataset across subregional borders, and divided along environmental gradients and gear type. The same principles can be applied to transient waters from rivers to coastal lagoons as well as to other environments with gradients of, e.g. hydrodynamic characteristics. Publicly available sensitivity values will increase transparency and support the improvement of state assessments under the MSFD.     

Vasculature deprivation – induced osteonecrosis of the rat femoral head as a model for therapeutic trials

Experimental Osteonecrosis  

The authors' experience with experimentally produced femoral capital osteonecrosis in rats is reviewed: incising the periosteum at the base of the neck of the femur and cutting the ligamentum teres leads to coagulation necrosis of the epiphysis. The necrotic debris is substituted by fibrous tissue concomitantly with resorption of the dead soft and hard tissues by macrophages and osteoclasts, respectively. Progressively, the formerly necrotic epiphysis is repopulated by hematopoietic-fatty tissue, and replaced by architecturally abnormal and biomechanically weak bone. The femoral heads lose their smooth-surfaced hemispherical shape in the wake of the load transfer through the hip joint such that, together with regressive changes of the joint cartilage and inflammatory-hyperplastic changes of the articular membrane, an osteoarthritis-like disorder ensues.     

Presence of qacEΔ1 gene and susceptibility to a hospital biocide in clinical isolates of Pseudomonas aeruginosa resistant to antibiotics

Biocides play an important role in healthcare-associated infection control by either minimizing or preventing microorganism dissemination. This study evaluated the susceptibility of Pseudomonas aeruginosa clinical isolates to a quaternary ammonium (QAC) disinfectant and antibiotics, and verified the presence of qacEΔ1, a determinant of resistance to QAC. The disinfectant test was the Association of Official Analytical Chemists Use-Dilution Test, and polymerase chain reaction was used to examine for qacEΔ1. The qacEΔ1 gene was detected in 48% of the isolates. Eighty-eight percent of the multiresistant isolates carried qacEΔ1 gene, while 35% of the non-multiresistant isolates was positive to this gene, and multiresistance well correlated with its presence. Among isolates tested for the disinfectant, 46% showed a reduced susceptibility to the disinfectant. qacEΔ1 gene was present in 70% of the susceptible isolates to the biocide, whereas 90% of the less susceptible strains harbored this gene. Reduced susceptibility to the disinfectant was independent of presence of qacEΔ1 suggesting that it does not play an important role in biocide resistance in P. aeruginosa. As far as we know, it is the first report confirming this fact and testing with disinfectant at its in-use concentration. The evidence of less susceptible strains than the reference bacterium used in disinfectant testing, and the high percentage of qacEΔ1 gene detected are of special concern and suggests continued investigation in laboratory and in situ, not only in healthcare settings, but also in all areas of biocide usage, including different micro-organisms and biocides.     

BIOFRAG – a new database for analyzing BIOdiversity responses to forest FRAGmentation

Habitat fragmentation studies have produced complex results that are challenging to synthesize. Inconsistencies among studies may result from variation in the choice of landscape metrics and response variables, which is often compounded by a lack of key statistical or methodological information. Collating primary datasets on biodiversity responses to fragmentation in a consistent and flexible database permits simple data retrieval for subsequent analyses. We present a relational database that links such field data to taxonomic nomenclature, spatial and temporal plot attributes, and environmental characteristics. Field assessments include measurements of the response(s) (e.g., presence, abundance, ground cover) of one or more species linked to plots in fragments within a partially forested landscape. The database currently holds 9830 unique species recorded in plots of 58 unique landscapes in six of eight realms: mammals 315, birds 1286, herptiles 460, insects 4521, spiders 204, other arthropods 85, gastropods 70, annelids 8, platyhelminthes 4, Onychophora 2, vascular plants 2112, nonvascular plants and lichens 320, and fungi 449. Three landscapes were sampled as long-term time series (>10 years). Seven hundred and eleven species are found in two or more landscapes. Consolidating the substantial amount of primary data available on biodiversity responses to fragmentation in the context of land-use change and natural disturbances is an essential part of understanding the effects of increasing anthropogenic pressures on land. The consistent format of this database facilitates testing of generalizations concerning biologic responses to fragmentation across diverse systems and taxa. It also allows the re-examination of existing datasets with alternative landscape metrics and robust statistical methods, for example, helping to address pseudo-replication problems. The database can thus help researchers in producing broad syntheses of the effects of land use. The database is dynamic and inclusive, and contributions from individual and large-scale data-collection efforts are welcome.     

Plant improvement for tolerance to aluminum in acid soils – a review

Development of acid soils that limit crop production is an increasing problem worldwide. Many factors contribute to phytotoxicity of these soils, however, in acid soils with a high mineral content, aluminum (Al) is the major cause of toxicity. The target of Al toxicity is the root tip, in which Al exposure causes inhibition of cell elongation and cell division, leading to root stunting accompanied by reduced water and nutrient uptake. Natural variation for Al tolerance has been identified in many crop species and in some crops tolerance to Al has been introduced into productive, well-adapted varieties. Aluminum tolerance appears to be a complex multigenic trait. Selection methodology remains a limiting factor in variety development as all methods have particular drawbacks. Molecular markers have been associated with Al tolerance genes or quantitative trait loci in Arabidopsis and in several crops, which should facilitate development of additional tolerant varieties. A variety of genes have been identified that are induced or repressed upon Al exposure. Most induced genes characterized so far are not specific to Al exposure but are also induced by other stress conditions. Ectopic over-expression of some of these genes has resulted in enhanced Al tolerance. Additionally, expression of genes involved in organic acid synthesis has resulted in enhanced production of organic acids and an associated increase in Al tolerance. This review summarizes the three main approaches that have been taken to develop crops with Al tolerance: recurrent selection and breeding, development of Al tolerant somaclonal variants and ectopic expression of transgenes to reduce Al uptake or limit damage to cells by Al.     

Is there evidence for a shift in fish growth and recruitment success linked to climate change?

This study investigated whether a putative shift in climate regime in the North Atlantic in the 1990s coincided with changes in the growth and recruitment of roach Rutilus rutilus in the north-east of England. The relationships between R. rutilus growth and recruitment and the environment were significantly different before and after the putative shift in climate regime. Water temperature, river discharge, growth, recruitment success and the Gulf Stream Index co-varied until the late 1990s, indicating a gradual progression between periods of warm-and-dry and cold-and-wet summers. Since the late 1990s, there has been an increased prevalence of warm-and-wet summers, and recruitment success has oscillated between extremes on an almost annual basis. The north wall (northern boundary) of the Gulf Stream has been undergoing a displacement south since the late 1990s, and the speed and amplitude of the change appears to support the hypothesis that there was a regime shift in the climate of the North Atlantic Ocean. It is possible that a continued displacement south of the north wall of the Gulf Stream will lead to further increases in river discharge, reductions in water temperature and reduced fish growth and recruitment success in the long term.     

A geographical information system model for creating bioclimatic maps – examples from a high,mid-latitude city

This paper presents a method for creating large-scale bioclimatic maps with the aid of a geographical information system, GIS. Meteorological data are linked with geographical information about land use, elevation and distance to the coast, in order to generate spatial distributions of physiological equivalent temperature, PET. The model combines an air temperature map and a wind map in order to create different zones for which the thermal component is to be calculated. The advantage of the model presented is that it uses generally available information about land use, altitude and distance to the coast. Further, the model uses a GIS application, which makes it non-static. Compared to most other models, a wide range of observations are used as input. Few biometeorological studies have been performed in high-latitude areas. This paper presents bioclimatic maps for the G?teborg urban area, in Sweden, for the month of July. The results show large variations in PET during a clear, calm day at 1200 hours (Delta T 13.4 degrees C) and during average conditions in July (Delta T 6.8 degrees C), which gives an indication of the magnitude and the spatial variations within high, midlatitude, urban area in summer. The highest PET values were found in the central built-up areas and the lowest PET values in the coastal and green areas. The model generates valuable information for urban planners and decision makers when planning and constructing new areas for outdoor activities etc. This information is also useful in the fields of health and energy.     

Engineering a hydroxysteroid dehydrogenase to improve its soluble expression for the asymmetric reduction of cortisone to 11β-hydrocortisone

11β-Hydrocortisone (11β-HC) is an important anti-inflammatory drug and intermediate for the synthesis of other steroids. One of the methods for the synthesis of 11β-HC is the asymmetric reduction of cortisone catalyzed by a highly regioselective and stereoselective 11β-hydroxysteroid dehydrogenase (11β-HSDH). However, this process has been prohibited by the poor soluble expression of the membrane-anchoring protein 11β-HSDH in prokaryotes. To overcome this obstacle, a mutant III-1G1 (Phe80Leu/Thr105Ser/Ala260Thr/Tyr274Stop) truncated at position 274 with improved yield of soluble protein was stepwise obtained from the 11β-HSDH from guinea pig by random mutagenesis combining with structural complementation assay and C-terminal truncating library screening. The improved 11β-HSDH mutant and glucose dehydrogenase (GDH) from Bacillus subtilis were coexpressed in Escherichia coli. The resulting whole-cell biocatalyst catalyzed the reduction of cortisone to 11β-HC with 98 % conversion in 20 h, laying foundation for the development of an asymmetric reduction process for the production of 11β-HC.     

Is exploration a metric for information gathering? Attraction to novelty and plasticity in black-capped chickadees

Animals can learn about the value of resources and predation risk by exploring novel environments or exploring novel stimuli in their regular environments. Still, there is a disconnect in the way that exploration has been defined and measured; exploration is defined in terms of information acquisition, while measured in terms of movement speed and diversity of contacted items in a novel environment. If exploration is indeed a measurement of information gathering, fast explorers should seek to reduce uncertainty about their environment more than slow explorers. Exploration speed has also been linked to behavioral plasticity, where fast explorers move fast but collect less detailed information, thereby forming routines and expressing less plasticity than slow explorers. We test these two hypotheses by comparing exploration in a novel environment to individuals' attraction to novelty and behavioral plasticity. Our results support the view that exploration is a measurement of information-gathering tendencies as fast explorers were more likely to collect novel information, which should reduce uncertainty further than sampling familiar information sources, compared with slower explorers. Furthermore, faster explorers switched to sampling novel information more quickly than slow explorers when the value of the familiar option decreased, opposing the widely held view that faster explorers present more routine-like behavior. By providing familiar and novel foraging options in close spatial contiguity, we demonstrate an attraction to novelty in faster explorers that cannot be confounded by activity rate, thereby suggesting that these individuals seek to reduce uncertainty. In conclusion, our results support the biological validity of the term “exploration” through its association with information gathering.     

Proteomic evidence of a paedomorphic evolutionary process within a marine snail species: a strategy for adapting to extreme ecological conditions?

The exposed and sheltered ecotypes of the marine snail Littorina saxatilis from European rocky shores are considered a key model system to study adaptation and ecological speciation. Previous studies showed that two ecotypes (RB and SU) of this species in NW Spain have adapted differently to different shore levels and microhabitats. In order to understand how this divergent adaptive process has been accomplished, we followed a quantitative proteomic approach to investigate the proteome variation in a number of different biological factors, that is, ecotype, ontogeny and their interactions. This approach allowed testing the hypothesis that one of the ecotypes has evolved by paedomorphosis, and also whether or not the molecular mechanisms related to ecotype differentiation are set up in early developmental stages. Additionally, the identification of some candidate proteins using mass spectrometry provides some functional insights into these evolutionary processes. Results from this study provided evidence of higher ontogenetic differentiation at proteome level in the RB (metamorphic) than in SU (paedomorphic) ecotype that point to the possibility of juvenile stage retention in this latter ecotype. The level of protein expression (proteome) differences between ecotypes maintained nearly constant from late embryonic stages to adulthood, although some proteins involved in these changes considerably differed in embryonic compared to other ontogenetic stages. Paedomorphosis may be the evolutionary response of the SU ecotype of solving the trade‐off during sexually immaturity that is caused by the evolution of small size arising from adaptation to the wave‐exposed habitat. Some potential candidate genes of adaptation related to energetic metabolism have been identified, providing a promising baseline for future functional analyses.