Flip‐flop organization in the chloroplast genome of Capsosiphon fulvescens (Ulvophyceae,Chlorophyta)

To better understand organelle genome evolution of the ulvophycean green alga Capsosiphon fulvescens, we sequenced and characterized its complete chloroplast genome. The circular chloroplast genome was 111,561 bp in length with 31.3% GC content that contained 108 genes including 77 protein‐coding genes, two copies of rRNA operons, and 27 tRNAs. In this analysis, we found the two types of isoform, called heteroplasmy, were likely caused by a flip‐flop organization. The flip‐flop mechanism may have caused structural variation and gene conversion in the chloroplast genome of C. fulvescens. In a phylogenetic analysis based on all available ulvophycean chloroplast genome data, including a new C. fulvescens genome, we found three major conflicting signals for C. fulvescens and its sister taxon Pseudoneochloris marina within 70 individual genes: (i) monophyly with Ulotrichales, (ii) monophyly with Ulvales, and (iii) monophyly with the clade of Ulotrichales and Ulvales. Although the 70‐gene concatenated phylogeny supported monophyly with Ulvales for both species, these complex phylogenetic signals of individual genes need further investigations using a data‐rich approach (i.e., organelle genome data) from broader taxon sampling.     

Insights in to the pathogenesis of axial spondyloarthropathy based on gene expression profiles

Introduction  

Axial spondyloarthropathy (SpA) is a group of inflammatory diseases, with ankylosing spondylitis as the prototype. SpA affects the axial skeleton, entheses, joints and, at times, the eyes. This study tested the hypothesis that SpA is characterized by a distinct pattern of gene expression in peripheral blood of affected individuals compared with healthy controls.     

FET-based nanobiosensors for the detection of smell and taste

Various nanobiosensors composed of biomaterials and nanomaterials have been developed, due to their demonstrated advantage of showing high performance. Among various biomaterials for biological recognition elements of the nanobiosensor, sensory receptors, such as olfactory and taste receptors, are promising biomaterials for developing nanobiosensors, because of their high selectivity to target molecules. Field-effect transistors(FET) with nanomaterials such as carbon nanotube(CNT), graphene, and conducting polymer nanotube(CPNT), can be combined with the biomaterials to enhance the sensitivity of nanobiosensors.Recently, many efforts have been made to develop nanobiosensors using biomaterials, such as olfactory receptors and taste receptors for detecting various smells and tastes. This review focuses on the biomaterials and nanomaterials used in nanobiosensor systems and studies of various types of nanobiosensor platforms that utilize olfactory receptors and taste receptors which could be applied to a wide range of industrial fields, including the food and beverage industry, environmental monitoring, the biomedical field, and anti-terrorism.     

The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment

Background

Although thyroid eye disease is a common complication of Graves’ disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray.

Methods

An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets.

Results

Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED.

Conclusion

This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.     

Condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome

Deciphering genetic regulatory codes remains a challenge. Here, we present an effective approach to identifying in vivo condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome. A resampling-based algorithm was adopted to cluster our microarray data of a stress response, which generated 35 tight clusters with unique expression patterns containing 811 genes of 5652 genes significantly altered. Database searches identified many known motifs within the 3-kb regulatory regions of 40 genes from 3 clusters and modules with six to nine motifs that were commonly shared by 60-100% of these genes. The upstream regulatory region contained the highest frequency of these common motifs. CisModule program predictions were comparable with the results from database searches and found four potentially novel motifs. This result indicates that these motifs and modules could be responsible for gene coregulation of the stress response in the lacrimal gland.     

ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points

The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell’s cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24^KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed–TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24^KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience.     

Otitis Media Impacts Hundreds of Mouse Middle and Inner Ear Genes

Objective

Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.

Methods

To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.

Results

Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.

Conclusion

Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.     

Standardizing global gene expression analysis between laboratories and across platforms

To facilitate collaborative research efforts between multi-investigator teams using DNA microarrays, we identified sources of error and data variability between laboratories and across microarray platforms, and methods to accommodate this variability. RNA expression data were generated in seven laboratories, which compared two standard RNA samples using 12 microarray platforms. At least two standard microarray types (one spotted, one commercial) were used by all laboratories. Reproducibility for most platforms within any laboratory was typically good, but reproducibility between platforms and across laboratories was generally poor. Reproducibility between laboratories increased markedly when standardized protocols were implemented for RNA labeling, hybridization, microarray processing, data acquisition and data normalization. Reproducibility was highest when analysis was based on biological themes defined by enriched Gene Ontology (GO) categories. These findings indicate that microarray results can be comparable across multiple laboratories, especially when a common platform and set of procedures are used.