H+/K+ ATPase activity is required for biomineralization in sea urchin embryos

AbstractThe bioelectrical signatures associated with regeneration, wound healing, development, and cancer are changes in the polarization state of the cell that persist over long durations, and are mediated by ion channel activity. To identify physiologically relevant bioelectrical changes that occur during normal development of the sea urchin Lytechinus variegatus, we tested a range of ion channel inhibitors, and thereby identified SCH28080, a chemical inhibitor of the H+/K+ ATPase (HKA), as an inhibitor of skeletogenesis. In sea urchin embryos, the primary mesodermal lineage, the PMCs, produce biomineral in response to signals from the ectoderm. However, in SCH28080-treated embryos, aside from randomization of the left-right axis, the ectoderm is normally specified and differentiated, indicating that the block to skeletogenesis observed in SCH28080-treated embryos is PMC-specific. HKA inhibition did not interfere with PMC specification, and was sufficient to block continuing biomineralization when embryos were treated with SCH28080 after the initiation of skeletogenesis, indicating that HKA activity is continuously required during biomineralization. Ion concentrations and voltage potential were abnormal in the PMCs in SCH28080-treated embryos, suggesting that these bioelectrical abnormalities prevent biomineralization. Our results indicate that this effect is due to the inhibition of amorphous calcium carbonate precipitation within PMC vesicles

RNA-SeQC: RNA-seq metrics for quality control and process optimization

Summary: RNA-seq, the application of next-generation sequencing to RNA, provides transcriptome-wide characterization of cellular activity. Assessment of sequencing performance and library quality is critical to the interpretation of RNA-seq data, yet few tools exist to address this issue. We introduce RNA-SeQC, a program which provides key measures of data quality. These metrics include yield, alignment and duplication rates; GC bias, rRNA content, regions of alignment (exon, intron and intragenic), continuity of coverage, 3′/5′ bias and count of detectable transcripts, among others. The software provides multi-sample evaluation of library construction protocols, input materials and other experimental parameters. The modularity of the software enables pipeline integration and the routine monitoring of key measures of data quality such as the number of alignable reads, duplication rates and rRNA contamination. RNA-SeQC allows investigators to make informed decisions about sample inclusion in downstream analysis. In summary, RNA-SeQC provides quality control measures critical to experiment design, process optimization and downstream computational analysis

Neural correlates of suspiciousness and interactions with anxiety during emotional and neutral word processing

Suspiciousness is usually classified as a symptom of psychosis, but it also occurs in depression and anxiety disorders. Though how suspiciousness overlaps with depression is not obvious, suspiciousness does seem to overlap with anxious apprehension and anxious arousal (e.g., verbal iterative processes and vigilance about environmental threat). However, suspiciousness also has unique characteristics (e.g., concern about harm from others and vigilance about social threat). Given that both anxiety and suspiciousness have been associated with abnormalities in emotion processing, it is unclear whether it is the unique characteristics of suspiciousness or the overlap with anxiety that drive abnormalities in emotion processing. Event-related brain potentials were obtained during an emotion-word Stroop task. Results indicated that suspiciousness interacts with anxious apprehension to modulate initial stimulus perception processes. Suspiciousness is associated with attention to all stimuli regardless of emotion content. In contrast, anxious arousal is associated with a later response to emotion stimuli only. These results suggest that suspiciousness and anxious apprehension share overlapping processes, but suspiciousness alone is associated with a hyperactive early vigilance response. Depression did not interact with suspiciousness to predict response to emotion stimuli. These findings suggest that it may be informative to assess suspiciousness in conjunction with anxiety in order to better understand how these symptoms interact and contribute to dysfunctional emotion processing

Interventions to improve or maintain lower-limb function among ambulatory adolescents with cerebral palsy: a cross-sectional survey of current practice in the UK.

2 Objectives: To describe physiotherapy management to improve or maintain lower-limb 1 function among adolescents with cerebral palsy, classified in Gross Motor Function 2 Classification System levels I-III, in the United Kingdom. 3 Methods: A list of interventions was identified using a nominal group technique and 4 developed into a survey, which was distributed to approximately 2,100 paediatric 5 physiotherapists in the UK through the Association of Paediatric Chartered Physiotherapists 6 and a private physiotherapy clinic in London between April and June 2015. One-hundred and 7 thirty-five physiotherapists completed the survey. Survey respondents indicated how 8 frequently they used each intervention (i.e. “frequently”, “sometimes”, “rarely”, “never”) in 9 the past year. 10 Results: Provision of explanations to the child, liaison with families, liaison with health 11 professionals, provision of advice to schools, and stretching were the most frequently used 12 interventions with 90%, 90%, 86%, 79%, and 76% of respondents, respectively, reporting 13 that they frequently used each. The interventions most commonly reported as “never” used 14 were conductive education (88%), MOVE programme (85%), functional electrical 15 stimulation (82%), body-weight supported treadmill training (80%), and rebound therapy 16 (71%). 17 Conclusions: This study suggests that a large number of interventions are used by 18 physiotherapists in the UK to improve or maintain lower-limb function among adolescents 19 with CP, not all of which are evidence-based

Patterns of gene recombination shape var gene repertoires in Plasmodium falciparum: comparisons of geographically diverse isolates

BACKGROUND: Var genes encode a family of virulence factors known as PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) which are responsible for both antigenic variation and cytoadherence of infected erythrocytes. Although these molecules play a central role in malaria pathogenesis, the mechanisms generating variant antigen diversification are poorly understood. To investigate var gene evolution, we compared the variant antigen repertoires from three geographically diverse parasite isolates: the 3D7 genome reference isolate; the recently sequenced HB3 isolate; and the IT4/25/5 (IT4) parasite isolate which retains the capacity to cytoadhere in vitro and in vivo. RESULTS: These comparisons revealed that only two var genes (var1csa and var2csa) are conserved in all three isolates and one var gene (Type 3 var) has homologs in IT4 and 3D7. While the remaining 50 plus genes in each isolate are highly divergent most can be classified into the three previously defined major groups (A, B, and C) on the basis of 5' flanking sequence and chromosome location. Repertoire-wide sequence comparisons suggest that the conserved homologs are evolving separately from other var genes and that genes in group A have diverged from other groups. CONCLUSION: These findings support the existence of a var gene recombination hierarchy that restricts recombination possibilities and has a central role in the functional and immunological adaptation of var genes