Spatiomechanical Modulation of EphB4-Ephrin-B2 Signaling in Neural Stem Cell Differentiation.

Interactions between EphB4 receptor tyrosine kinases and their membrane-bound ephrin-B2 ligands on apposed cells play a regulatory role in neural stem cell differentiation. With both receptor and ligand constrained to move within the membranes of their respective cells, this signaling system inevitably experiences spatial confinement and mechanical forces in conjunction with receptor-ligand binding. In this study, we reconstitute the EphB4-ephrin-B2 juxtacrine signaling geometry using a supported-lipid-bilayer system presenting laterally mobile and monomeric ephrin-B2 ligands to live neural stem cells. This experimental platform successfully reconstitutes EphB4-ephrin-B2 binding, lateral clustering, downstream signaling activation, and neuronal differentiation, all in a configuration that preserves the spatiomechanical aspects of the natural juxtacrine signaling geometry. Additionally, the supported bilayer system allows control of lateral movement and clustering of the receptor-ligand complexes through patterns of physical barriers to lateral diffusion fabricated onto the underlying substrate. The results from this study reveal a distinct spatiomechanical effect on the ability of EphB4-ephrin-B2 signaling to induce neuronal differentiation. These observations parallel similar studies of the EphA2-ephrin-A1 system in a very different biological context, suggesting that such spatiomechanical regulation may be a common feature of Eph-ephrin signaling

Mitophagy coordination with retrograde transport ensures the integrity of synaptic mitochondria

Mitochondria sustain various essential functions at synaptic terminals. Synaptic mitochondria deficits have been implicated in early Alzheimer disease (AD) pathophysiology. Mitophagy, a selective autophagy for removal of damaged mitochondria, plays a key role in mitochondrial quality control in neurons. However, fundamental questions remain unanswered as to whether mitophagy regulates synaptic mitochondrial integrity and whether AD-associated early deficits in synaptic mitochondria are attributed to mitophagy failure. We have recently revealed that the integrity of synaptic mitochondria is maintained by a coordination of RHEB-mediated mitophagy with dynein- and SNAPIN-driven retrograde transport. We demonstrate that increased mitophagy initiation, coupled with defective retrograde transport, triggers mitophagy stress at AD synapses. Excitingly, SNAPIN-enhanced retrograde transport reduces synaptic mitophagy stress and ameliorates mitochondrial deficits, thereby counteracting synaptic damage in AD mouse brains. Therefore, our study provides new mechanistic insights into how mitophagy facilitates synaptic mitochondrial maintenance and how mitophagy failure exacerbates AD-linked mitochondrial defects and synaptic degeneration. Abbreviation: AD: Alzheimer disease; Aβ: amyloid-β; APP: amyloid beta precursor protein; CCCP: carbonyl cyanide m-chlorophenylhydrazone; LE: late endosome; Δψm, mitochondrial membrane potential; RHEB: Ras homolog enriched in brain; RNAi: RNA interference; shRNA: small hairpin RNA; Tg: transgenic

Interactive hypothesis testing with communication constraints

Abstract—This paper studies the problem of interactive hypothesis testing with communication constraints, in which two communication nodes separately observe one of two correlated sources and interact with each other to decide between two hypotheses on the joint distribution of the sources. When testing against independence, that is, the joint distribution of the sources under the alternative hypothesis is the product of the marginal distributions under the null hypothesis, a computable characterization is provided for the optimal tradeoff between the communication rates in two-round interaction and the testing performance measured by the type II error exponent such that the type I error probability asymptotically vanishes. An example is provided to show that interaction is strictly helpful. I

Fractures of implant fixtures: a retrospective clinical study

Background The aim of this study was to evaluate the factors that may affect implant fixture fractures. Methods Patients who experienced implant fixture removal at Seoul National University Bundang Hospital from 2007 to 2015 due to implant fixture fracture were included. Implant/crown ratio, time of implant fracture, clinical symptoms before implant fracture, treatment of fractured implants, and the success and survival rate of the replaced implants were evaluated retrospectively. Results Thirteen implants were fractured in 12 patients. Patient mean age at the time of fracture was 59.3 years. Of the 13 implants, 7 implants were placed at our hospital, and 6 were placed at a local clinic. The mean crown/implant ratio was 0.83:1. The clinical symptoms before fracture were screw loosening in five implants, marginal bone loss in five implants, and the presence of peri-implant diseases in five implants. All the fractured implants were removed, and 12 out of the 13 sites were re-implanted. Parafunctions were observed in two patients: one with bruxism and one with attrition due to a strong chewing habit. Conclusions Several clinical symptoms before the fracture of an implant can predict implant fixture failure. Therefore, if these clinical symptoms are observed, appropriate treatments can be taken before more serious complications result

GOChase-II: correcting semantic inconsistencies from Gene Ontology-based annotations for gene products

<p>Abstract</p> <p>Background</p> <p>The Gene Ontology (GO) provides a controlled vocabulary for describing genes and gene products. In spite of the undoubted importance of GO, several drawbacks associated with GO and GO-based annotations have been introduced. We identified three types of semantic inconsistencies in GO-based annotations; semantically redundant, biological-domain inconsistent and taxonomy inconsistent annotations.</p> <p>Methods</p> <p>To determine the semantic inconsistencies in GO annotation, we used the hierarchical structure of GO graph and tree structure of NCBI taxonomy. Twenty seven biological databases were collected for finding semantic inconsistent annotation.</p> <p>Results</p> <p>The distributions and possible causes of the semantic inconsistencies were investigated using twenty seven biological databases with GO-based annotations. We found that some evidence codes of annotation were associated with the inconsistencies. The numbers of gene products and species in a database that are related to the complexity of database management are also in correlation with the inconsistencies. Consequently, numerous annotation errors arise and are propagated throughout biological databases and GO-based high-level analyses. GOChase-II is developed to detect and correct both syntactic and semantic errors in GO-based annotations.</p> <p>Conclusions</p> <p>We identified some inconsistencies in GO-based annotation and provided software, GOChase-II, for correcting these semantic inconsistencies in addition to the previous corrections for the syntactic errors by GOChase-I.</p

Electrical current suppression in Pd-doped vanadium pentoxide nanowires caused by reduction in PdO due to hydrogen exposure

Pd nanoparticle-doped vanadium pentoxide nanowires (Pd-VONs) were synthesized. Electrical current suppression was observed when the Pd-VON was exposed to hydrogen gas, which cannot be explained by the work function changes mentioned in previous report such as Pd-doped carbon nanotubes and SnO 2 nanowires. Using the x-ray photoelectron spectroscopy, we found that the reduction in PdO due to hydrogen exposure plays an important role in the current suppression of the Pd-VON.open4

Interpretable pap smear cell representation for cervical cancer screening

Screening is critical for prevention and early detection of cervical cancer but it is time-consuming and laborious. Supervised deep convolutional neural networks have been developed to automate pap smear screening and the results are promising. However, the interest in using only normal samples to train deep neural networks has increased owing to class imbalance problems and high-labeling costs that are both prevalent in healthcare. In this study, we introduce a method to learn explainable deep cervical cell representations for pap smear cytology images based on one class classification using variational autoencoders. Findings demonstrate that a score can be calculated for cell abnormality without training models with abnormal samples and localize abnormality to interpret our results with a novel metric based on absolute difference in cross entropy in agglomerative clustering. The best model that discriminates squamous cell carcinoma (SCC) from normals gives 0.908 +- 0.003 area under operating characteristic curve (AUC) and one that discriminates high-grade epithelial lesion (HSIL) 0.920 +- 0.002 AUC. Compared to other clustering methods, our method enhances the V-measure and yields higher homogeneity scores, which more effectively isolate different abnormality regions, aiding in the interpretation of our results. Evaluation using in-house and additional open dataset show that our model can discriminate abnormality without the need of additional training of deep models.Comment: 20 pages, 6 figure

Fiber-bundle illumination: realizing high-degree time-multiplexed multifocal multiphoton microscopy with simplicity

High-degree time-multiplexed multifocal multiphoton microscopy was expected to provide a facile path to scanningless optical-sectioning and the fast imaging of dynamic three-dimensional biological systems. However, physical constraints on typical time multiplexing devices, arising from diffraction in the free-space propagation of light waves, lead to significant manufacturing difficulties and have prevented the experimental realization of high-degree time multiplexing. To resolve this issue, we have developed a novel method using optical fiber bundles of various lengths to confine the diffraction of propagating light waves and to create a time multiplexing effect. Through this method, we experimentally demonstrate the highest degree of time multiplexing ever achieved in multifocal multiphoton microscopy (~50 times larger than conventional approaches), and hence the potential of using simply-manufactured devices for scanningless optical sectioning of biological systems