How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression

Aims: This study aimed at evaluating the potential anti-proliferative effects of the microRNA let-7 family in nasopharyngeal carcinoma (NPC) cells. In addition, the association between let-7 suppression and DNA hypermethylation is examined. Materials and methods: Levels of mature let-7 family members (-a,-b,-d,-e,-g, and-i) in normal nasopharyngeal cells (NP69 and NP460) and nasopharyngeal carcinoma cells (HK1 and HONE1) were measured by real-time quantitative PCR. Cell-proliferation assay and c-Myc immunohistochemical staining were performed on NPC cells transfected with let-7 precursor molecules. In addition, expression changes in let-7 family members in response to demethylating agents (5-azacytidine and zebularine) were also examined. Results: In comparison with the normal nasopharyngeal cells, let-7 (-a,-b,-d,-e,-g, and-i) levels were reduced in nasopharyngeal carcinoma cells. Ectopic expression of the let-7 family in nasopharyngeal carcinoma cells resulted in inhibition of cell proliferation through downregulation of c-Myc expression. Demethylation treatment of nasopharyngeal carcinoma cells caused activation of let-7 expression in poorly differentiated nasopharyngeal carcinoma cells only. Conclusion: Our results suggested that miRNA let-7 might play a role in the proliferation of NPC. DNA methylation is a potential regulatory pathway, which is affected when let-7 is suppressed in NPC cells. However, the extent of DNA hypermethylation/hypomethylation in regulating let-7 expression requires further elucidation. © The Author(s) 2010. This article is published with open access at Springerlink.com.published_or_final_versionSpringer Open Choice, 21 Feb 201

Relationship between nano-architectured Ti1−xCux thin film and electrical resistivity for resistance temperature detectors

Ti1−xCux thin films were produced by the glancing angle deposition technique (GLAD) for resistance temperature measurements. The deposition angle was fixed at α = 0° to growth columnar structures and α = 45° to growth zigzag structures. The Ti-to-Cu atomic concentration was tuned from 0 to 100 at.% of Cu in order to optimize the temperature coefficient of resistance (TCR) value. Increasing the amount of Cu in the Ti1−xCux thin films, the electrical conductivity was gradually changed from 4.35 to 7.87 × 105 Ω−1 m−1. After thermal “stabilization,” the zigzag structures of Ti1−xCux films induce strong variation of the thermosensitive response of the materials and exhibited a reversible resistivity versus temperature between 35 and 200 °C. The results reveal that the microstructure has an evident influence on the overall response of the films, leading to values of TCR of 8.73 × 10−3 °C−1 for pure copper films and of 4.38 × 10−3 °C−1 for a films of composition Ti0.49Cu0.51. These values are very close to the ones reported for the bulk platinum (3.93 × 10−3 °C−1), which is known to be one of the best material available for these kind of temperature-related applications. The non-existence of hysteresis in the electrical response of consecutive heating and cooling steps indicates the viability of these nanostructured zigzag materials to be used as thermosensitive sensors.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013 and Project PTDC/EEI-SII/5582/2014. A. Ferreira and C. Lopes thanks the FCT for Grant SFRH/BPD/102402/2014 and SFRH/BD/103373/2014. The authors thank financial support from the Basque Government Industry Department under the ELKARTEK Programinfo:eu-repo/semantics/publishedVersio

State-dependent distributed-delay model of orthogonal cutting

In this paper we present a model of turning operations with state-dependent distributed time delay. We apply the theory of regenerative machine tool chat- ter and describe the dynamics of the tool-workpiece sys- tem during cutting by delay-diferential equations. We model the cutting-force as the resultant of a force sys- tem distributed along the rake face of the tool, which results in a short distributed delay in the governing equation superimposed on the large regenerative de- lay. According to the literature on stress distribution along the rake face, the length of the chip-tool inter- face, where the distributed cutting-force system is act- ing, is function of the chip thickness, which depends on the vibrations of the tool-workpiece system due to the regenerative efect. Therefore, the additional short de- lay is state-dependent. It is shown that involving state- dependent delay in the model does not afect linear sta- bility properties, but does afect the nonlinear dynamics of the cutting process. Namely, the sense of the Hopf bi- furcation along the stability boundaries may turn from sub- to supercritical at certain spindle speed regions

Health-related quality of life of patients following selected types of lumbar spinal surgery: A pilot study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A sweetpotato gene index established by de novo assembly of pyrosequencing and Sanger sequences and mining for gene-based microsatellite markers

<p>Abstract</p> <p>Background</p> <p>Sweetpotato (<it>Ipomoea batatas </it>(L.) Lam.), a hexaploid outcrossing crop, is an important staple and food security crop in developing countries in Africa and Asia. The availability of genomic resources for sweetpotato is in striking contrast to its importance for human nutrition. Previously existing sequence data were restricted to around 22,000 expressed sequence tag (EST) sequences and ~ 1,500 GenBank sequences. We have used 454 pyrosequencing to augment the available gene sequence information to enhance functional genomics and marker design for this plant species.</p> <p>Results</p> <p>Two quarter 454 pyrosequencing runs used two normalized cDNA collections from stems and leaves from drought-stressed sweetpotato clone <it>Tanzania </it>and yielded 524,209 reads, which were assembled together with 22,094 publically available expressed sequence tags into 31,685 sets of overlapping DNA segments and 34,733 unassembled sequences. Blastx comparisons with the UniRef100 database allowed annotation of 23,957 contigs and 15,342 singletons resulting in 24,657 putatively unique genes. Further, 27,119 sequences had no match to protein sequences of UniRef100database. On the basis of this gene index, we have identified 1,661 gene-based microsatellite sequences, of which 223 were selected for testing and 195 were successfully amplified in a test panel of 6 hexaploid (<it>I. batatas</it>) and 2 diploid (<it>I. trifida</it>) accessions.</p> <p>Conclusions</p> <p>The sweetpotato gene index is a useful source for functionally annotated sweetpotato gene sequences that contains three times more gene sequence information for sweetpotato than previous EST assemblies. A searchable version of the gene index, including a blastn function, is available at <url>http://www.cipotato.org/sweetpotato_gene_index</url>.</p

Global Analysis of Proline-Rich Tandem Repeat Proteins Reveals Broad Phylogenetic Diversity in Plant Secretomes

Cell walls, constructed by precisely choreographed changes in the plant secretome, play critical roles in plant cell physiology and development. Along with structural polysaccharides, secreted proline-rich Tandem Repeat Proteins (TRPs) are important for cell wall function, yet the evolutionary diversity of these structural TRPs remains virtually unexplored. Using a systems-level computational approach to analyze taxonomically diverse plant sequence data, we identified 31 distinct Pro-rich TRP classes targeted for secretion. This analysis expands upon the known phylogenetic diversity of extensins, the most widely studied class of wall structural proteins, and demonstrates that extensins evolved before plant vascularization. Our results also show that most Pro-rich TRP classes have unexpectedly restricted evolutionary distributions, revealing considerable differences in plant secretome signatures that define unexplored diversity

A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus

In this study, genome-wide expression profiling based on Affymetrix ATH1 arrays was used to identify discriminating responses of Arabidopsis thaliana to five herbicides, which contain active ingredients targeting two different branches of amino acid biosynthesis. One herbicide contained glyphosate, which targets 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), while the other four herbicides contain different acetolactate synthase (ALS) inhibiting compounds. In contrast to the herbicide containing glyphosate, which affected only a few transcripts, many effects of the ALS inhibiting herbicides were revealed based on transcriptional changes related to ribosome biogenesis and translation, secondary metabolism, cell wall modification and growth. The expression pattern of a set of 101 genes provided a specific, composite signature that was distinct from other major stress responses and differentiated among herbicides targeting the same enzyme (ALS) or containing the same chemical class of active ingredient (sulfonylurea). A set of homologous genes could be identified in Brassica napus that exhibited a similar expression pattern and correctly distinguished exposure to the five herbicides. Our results show the ability of a limited number of genes to classify and differentiate responses to closely related herbicides in A. thaliana and B. napus and the transferability of a complex transcriptional signature across species

Motor control or graded activity exercises for chronic low back pain? A randomised controlled trial

Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient