Scaffolding and validation of bacterial genome assemblies using optical restriction maps

Motivation: New, high-throughput sequencing technologies have made it feasible to cheaply generate vast amounts of sequence information from a genome of interest. The computational reconstruction of the complete sequence of a genome is complicated by specific features of these new sequencing technologies, such as the short length of the sequencing reads and absence of mate-pair information. In this article we propose methods to overcome such limitations by incorporating information from optical restriction maps

Voltage-gated sodium channels as targets for pyrethroid insecticides

The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods. Modelling of the channel/pyrethroid interactions, coupled with the ability to express mutant channels in oocytes and study function, has led to knowledge of both how the channels function and potentially how to design novel insecticides with greater species selectivity

Mechanisms of toxic action and structure-activity relationships for organochlorine and synthetic pyrethroid insecticides.

The mechanisms and sites of action of organochlorine (DDT-types and chlorinated alicyclics) and synthetic pyrethroid insecticides are presented with discussion of symptoms, physiological effects, and selectivity. The structural requirements for toxicity are assessed, and structure-activity relationships are considered for each subclass. Lipophilicity is important for all the groups because it facilitates delivery of these neurotoxicants to the site of action in the nerve. Steric factors including molecular volume, shape, and isomeric configuration greatly influence toxicity. Electronic parameters also have been demonstrated to affect biological activity in some of the groups of insecticides, e.g., Hammett's sigma and Taft's sigma * as indicators of electronegativity. New synthetic pyrethroids continue to be developed, with varied structures and different physicochemical and biological properties

Dipolar versus multipolar dynamos: the influence of the background density stratification

Context: dynamo action in giant planets and rapidly rotating stars leads to a broad variety of magnetic field geometries including small scale multipolar and large scale dipole-dominated topologies. Previous dynamo models suggest that solutions become multipolar once inertia becomes influential. Being tailored for terrestrial planets, most of these models neglected the background density stratification. Aims: we investigate the influence of the density stratification on convection-driven dynamo models. Methods: three-dimensional nonlinear simulations of rapidly rotating spherical shells are employed using the anelastic approximation to incorporate density stratification. A systematic parametric study for various density stratifications and Rayleigh numbers allows to explore the dependence of the magnetic field topology on these parameters. Results: anelastic dynamo models tend to produce a broad range of magnetic field geometries that fall on two distinct branches with either strong dipole-dominated or weak multipolar fields. As long as inertia is weak, both branches can coexist but the dipolar branch vanishes once inertia becomes influential. The dipolar branch also vanishes for stronger density stratifications. The reason is the concentration of the convective columns in a narrow region close to the outer boundary equator, a configuration that favors non-axisymmetric solutions. In multipolar solutions, zonal flows can become significant and participate in the toroidal field generation. Parker dynamo waves may then play an important role close to onset of dynamo action leading to a cyclic magnetic field behavior. Conclusion: Our simulations also suggest that the fact that late M dwarfs have dipolar or multipolar magnetic fields can be explained in two ways. They may differ either by the relative influence of inertia or fall into the regime where both types of solutions coexist.Comment: 13 pages, 13 figures, 2 tables, accepted for publication in A&

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Efficient Plant Gene Identification Based on Interspecies Mapping of Full-Length cDNAs

We present an annotation pipeline that accurately predicts exon–intron structures and protein-coding sequences (CDSs) on the basis of full-length cDNAs (FLcDNAs). This annotation pipeline was used to identify genes in 10 plant genomes. In particular, we show that interspecies mapping of FLcDNAs to genomes is of great value in fully utilizing FLcDNA resources whose availability is limited to several species. Because low sequence conservation at 5′- and 3′-ends of FLcDNAs between different species tends to result in truncated CDSs, we developed an improved algorithm to identify complete CDSs by the extension of both ends of truncated CDSs. Interspecies mapping of 71 801 monocot FLcDNAs to the Oryza sativa genome led to the detection of 22 142 protein-coding regions. Moreover, in comparing two mapping programs and three ab initio prediction programs, we found that our pipeline was more capable of identifying complete CDSs. As demonstrated by monocot interspecies mapping, in which nucleotide identity between FLcDNAs and the genome was ∼80%, the resultant inferred CDSs were sufficiently accurate. Finally, we applied both inter- and intraspecies mapping to 10 monocot and dicot genomes and identified genes in 210 551 loci. Interspecies mapping of FLcDNAs is expected to effectively predict genes and CDSs in newly sequenced genomes

The pharmaceutical use of permethrin: Sources and behavior during municipal sewage treatment

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media, LLC.Permethrin entered use in the 1970s as an insecticide in a wide range of applications, including agriculture, horticultural, and forestry, and has since been restricted. In the 21st century, the presence of permethrin in the aquatic environment has been attributed to its use as a human and veterinary pharmaceutical, in particular as a pedeculicide, in addition to other uses, such as a moth-proofing agent. However, as a consequence of its toxicity to fish, sources of permethrin and its fate and behavior during wastewater treatment are topics of concern. This study has established that high overall removal of permethrin (approximately 90%) was achieved during wastewater treatment and that this was strongly dependent on the extent of biological degradation in secondary treatment, with more limited subsequent removal in tertiary treatment processes. Sources of permethrin in the catchment matched well with measured values in crude sewage and indicated that domestic use accounted for more than half of the load to the treatment works. However, removal may not be consistent enough to achieve the environmental quality standards now being derived in many countries even where tertiary treatment processes are applied.United Utilities PL

The long-term prognostic value of serum 25(OH)D, albumin, and LL-37 levels in acute respiratory diseases among older adults

Background: Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers.Aim: To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection.Methods: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes.Results: In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (Conclusions: Serum albumin level on admission seems to give valuable information about the patients' general health and recovery potential in treating older adults with respiratory symptoms. Serum 25(OH)D and LL-37 had no associations with disease severity or long- and short-term prognosis among older adults hospitalized with respiratory symptoms.</p

Respiratory tract virus infections in the elderly with pneumonia

Background: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia.Methods: Consecutive episodes of hospital care of patients 65years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints.Results: Median age of the patients was 83years (range 76-90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 x 10(9)/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes.Conclusion: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons