Interactions between species and their environment play a key role in the evolution of diverse communities, and numerous studies have emphasized that interactions among microbes and among trophic levels play an important role in maintaining microbial diversity and ecosystem functioning. In this study, we investigate how two of these types of interactions, public goods cooperation through the production of iron scavenging siderophores and predation by the social amoeba Dictyostelium discoideum, mediate competition between two strains of Pseudomonas fluorescens that were co-isolated from D. discoideum. We find that although we are able to generally predict the competitive outcomes between strains based on the presence and absence of either D. discoideum or iron, predator-by-environment interactions result in unexpected competitive outcomes. This suggests that while both cooperation and predation can mediate the competitive abilities and potentially the coexistence of these strains, predicting how combinations of different environments affect even the relatively simple microbiome of D. discoideum remains challenging.

Titanium dioxide (TiO2) is commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, a risk of intestinal barrier disruption, including dysbiosis of the gut microbiota, is increasingly suspected because of the presence of a nano-sized fraction in this additive. We hypothesized that food-grade E171 and Aeroxyde P25 (identical to the NM-105 OECD reference nanomaterial in the European Union Joint Research Centre) interact with both commensal intestinal bacteria and transient food-borne bacteria under non-UV-irradiated conditions. Based on differences in their physicochemical properties, we expect a difference in their respective effects. To test these hypotheses, we chose a panel of eight Gram-positive/Gram-negative bacterial strains, isolated from different biotopes and belonging to the species Escherichia coli, Lactobacillus rhamnosus, Lactococcus lactis (subsp. lactis and cremoris), Streptococcus thermophilus, and Lactobacillus sakei. Bacterial cells were exposed to food-grade E171 vs. P25 in vitro and the interactions were explored with innovative (nano)imaging methods. The ability of bacteria to trap TiO2 was demonstrated using synchrotron UV fluorescence imaging with single cell resolution. Subsequent alterations in the growth profiles were shown, notably for the transient food-borne L. lactis and the commensal intestinal E. coli in contact with food-grade TiO2. However, for both species, the reduction in cell cultivability remained moderate, and the morphological and ultrastructural damages, observed with electron microscopy, were restricted to a small number of cells. E. coli exposed to food-grade TiO2 showed some internalization of TiO2 (7% of cells), observed with high-resolution nano-secondary ion mass spectrometry (Nano-SIMS) chemical imaging. Taken together, these data show that E171 may be trapped by commensal and transient food-borne bacteria within the gut. In return, it may induce some physiological alterations in the most sensitive species, with a putative impact on gut microbiota composition and functioning, especially after chronic exposure.

T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I) are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL) and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR-/-) or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections.

The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant-antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression. The objective of the current study was to establish the role of Nrf2 in shaping innate immune responses, clinical disease, airway inflammation, and viral replication in established experimental models of intranasal RSV and human metapneumovirus (hMPV) infections, by employing mice genetically deficient for the Nrf2 gene. Compared to control wild type (WT), mice genetically deficient in Nrf2 (Nrf2 KO) developed enhanced clinical disease, airway inflammation and pathology, and significantly greater lung viral titers following experimental infection with either RSV or hMPV. In particular, compared to control mice, RSV-infected Nrf2 KO mice lost more body weight and had increased airway obstruction at time points characterized by a remarkable increase in inflammatory cytokines and airway neutrophilia. Airway levels of AOEs and enzymes that regulate synthesis of the endogenous hydrogen sulfide (H2S) pathway, which we showed to play an important antiviral function, were also decreased in RSV-infected Nrf2 KO compared to WT. In conclusion, these results suggest that Nrf2 is a critical regulator of innate, inflammatory, and disease-associated responses in the airways of mice infected with viruses that are members of the Pneumoviridae family. Importantly, the results of this study suggest that Nrf2-dependent genes, including those controlling the cellular antioxidant and H2S-generating enzymes and cytokines can affect several aspects of the antiviral response, such as airway neutrophilia, clinical disease, airway obstruction, and viral replication.

Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1-H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model.

Barley stripe rust is caused by Puccinia striiformis f.sp. hordei, (Psh), occurs worldwide, and is a major disease in South Asia. The aim of this work was to identify and estimate effects of loci underlying quantitative resistance to rust at seedling and adult plant stages. HI-AM panel of 261 barley genotypes consisting of released cultivars from North and South America, Europe, Australia, advanced breeding lines, and local landraces from ICARDA barley program were screened at seedling and adult plant stages for resistance to Psh. Seedling resistance was evaluated with the five prevalent Psh races in India. Screening for the adult plant stage resistance was also performed in two different locations by inoculating with a mixture of the five races used for seedling screeing. The panel was genotyped using DaRT-Seq high-throughput genotyping platform. The genome-wide association mapping (GWAM) showed a total of 45 QTL located across the seven barley chromosomes for seedling resistance to the five races and 18 QTL for adult plant stage resistance. Common QTL for different races at seedling stage were found on all chromosomes except on chromosome 1H. Four common QTL associated with seedling and adult plant stage resistance were found on chromosomes 2, 5, and 6H. Moreover, one of the QTL located on the long arm of chromosome 5H showed stable effects across environments for adult plant stage resistance. Several QTL identified in this study were also reported before in bi-parental and association mapping populations studies validating current GWAM. However 15 new QTL were found at adult plant stage on all chromosomes except the 4H, explaining up to 36.79% of the variance. The promising QTL detected at both stages, once validated, can be used for MAS in Psh resistance breeding program globally.

A well-developed root system in rice and other crops can ensure plants to efficiently absorb nutrients and water. Auxin is a key regulator for various aspect of root development, but the detailed molecular mechanisms by which auxin controls crown root development in rice are not understood. We show that overexpression of a YUC gene, which encodes the rate-limiting enzyme in auxin biosynthesis, causes massive proliferation of crown roots. On the other hand, we find that disruption of TAA1, which functions upstream of YUC genes, greatly reduces crown root development. We find that YUC overexpression-induced crown root proliferation requires the presence of the transcription factor WOX11. Moreover, the crown rootless phenotype of taa1 mutants was partially rescued by overexpression of WOX11. Furthermore, we show that WOX11 expression is induced in OsYUC1 overexpression lines, but is repressed in the taa1 mutants. Our results indicate that auxin synthesized by the TAA/YUC pathway is necessary and sufficient for crown root development in rice. Auxin activates WOX11 transcription, which subsequently drives crown root initiation and development, establishing the YUC-Auxin-WOX11 module for crown root development in rice.

Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized, and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through "Real-Time" reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93, p < 0.0001) with data obtained in silico. The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues.

The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated (R2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year (R2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality.

MicroRNA-137 (miR-137) functions as a tumor suppressor and is silenced by aberrant promoter methylation. Previous studies have demonstrated that miR-137 is downregulated in lung cancer. The purpose of the present study was to investigate miR-137 promoter methylation and to assess its prognostic value in non-small cell lung cancer (NSCLC). The expression of miR-137 was analyzed inhuman lung cancer A549 and H1299 cells and normal bronchial epithelial BEAS-2B cells, 10 paired formalin-fixed paraffin-embedded lung cancer and normal tissue samples, and 56 archived paraffin-embedded lung cancer tissues. Quantitative methylation-specific polymerase chain reaction analysis was used to assess the miR-137 methylation status. The associations between miR-137 promoter methylation and the clinicopathological features and prognosis of patients with NSCLC (n=56) were analyzed using analysis of variance. miR-137 was markedly downregulated in lung cancer cells and lung cancer tissue specimens compared with expression in BEAS-2B cells and matched adjacent normal lung tissues. A significant negative correlation between miR-137 expression and miR-137 promoter methylation was observed in human lung cancer tissues (r=-0.343; P=0.01). Smoking, lymph node metastasis and advanced clinical stage were associated with significantly lower expression of miR-137 in variance analysis. High levels of miR-137 promoter methylation were associated with a significantly poorer disease-free survival rate (P=0.034), but were not associated with overall survival, in Kaplan-Meier analysis and univariate analysis. In conclusion, the results of the present study indicated that miR-137 is downregulated and that its promoter is aberrantly methylated in lung cancer, and that high levels of miR-137 promoter methylation may have prognostic value for poor disease-free survival.

Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in various types of tumors. The presnet study examined the clinical significance of EBI3 expression for predicting tumor recurrence and survival after resection in hepatocellular carcinoma (HCC). EBI3 expression in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples were detected using western blot analysis. Immunohistochemical staining using tissue microarray with 312 samples from randomly selected patients with HCC who underwent surgery. Survival analysis was performed using univariate and multivariate analyses. EBI3 protein level was higher in L-02 cells and in peri-tumor tissues compared with tumor tissues. Immunohistochemical staining of EBI3 was reduced in HCC tissues in comparison with adjacent normal tissues and significantly associated with tumor invasive characteristics, including tumor thrombus, poor differentiation and large size. Notably, the results suggested that EBI3 was a predictor for tumor recurrence and patient survival, and multivariate analysis indicated EBI3 to be an independent prognostic factor. Even in early-stage disease, low EBI3 expression was also independently associated with increased tumor recurrence and shortened survival. Downregulation of EBI3 in HCC indicated aggressive tumor behaviors and predicted a more severe clinical outcome, which suggests that EBI2 may be a useful biomarker to identify patients at high risk of post-operative recurrence.

Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases. HCC-associated lncRNAs, including HOX antisense intergenic RNA (HOTAIR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were selected based on established databases of lncRNAs. The interaction between the HCC-associated lncRNAs and miRNAs (hsa-miR-1, hsa-miR-20a-5p) was predicted using starBase2.0. Signal transducer and activator of transcription 1, hepatocyte nuclear factor 4α (HNF4A), octamer-binding transcription factor 4, Nanog homeobox (NANOG), caudal type homeobox 2 (CDX2), DEAD-box helicase 5, brahma-related gene 1, MYC-associated factor X and MYC proto-oncogene, bHLH transcription factor have been identified as the transcription factors for HOTAIR and MALAT1 using ChIPBase. Additionally, CDX2, HNF4A, NANOG, ETS transcription factor, Jun proto-oncogene and forkhead box protein A1 were identified as the transcription factors for hsa-miR-1 and hsa-miR-20a-5p. CDX2, HNF4A and NANOG were the transcriptional factors in common between the lncRNAs and miRNAs. Cyclin D1, E2F transcription factor 1, epithelial growth factor receptor, MYC, MET proto-oncogene, receptor tyrosine kinase and vascular endothelial growth factor A were identified as target genes for the HCC progression, two of which were also the target genes of hsa-miR-1 and hsa-miR-20a-5p using the miRwalk and OncoDN. HCC databases. Additionally, these target genes may be involved in biological functions, including the regulation of cell growth, cell cycle progression and mitosis, and in disease progression, as demonstrated using DAVID clustering analysis. The present study aimed to predict a regulatory network of lncRNAs in HCC progression using bioinformatics analysis.

Carotid artery stenosis, both symptomatic and asymptomatic, has been well studied with several multicenter randomized trials. The superiority of carotid endarterectomy (CEA) to medical therapy alone in both symptomatic and asymptomatic carotid artery stenosis has been well established in previous trials in the 1990s. The consequent era of endovascular carotid artery stenting (CAS) has offered another option for treating carotid artery stenosis. A series of randomized trials have now been conducted to compare CEA and CAS in the treatment of carotid artery disease. The large number of similar trials has created some confusion due to inconsistent results. Here, the authors review the trials that compare CEA and CAS in the management of carotid artery stenosis.

Thyroid cancer is one of the most common endocrine malignancies. Multiple evidences revealed that a large number of microRNAs and mRNAs were abnormally expressed in thyroid cancer tissues. These microRNAs and mRNAs play important roles in tumorigenesis. In the present study, we identified 72 microRNAs and 1,766 mRNAs differentially expressed between thyroid cancer tissues and normal thyroid tissues and evaluated their prognostic values using Kaplan-Meier survival curves by log-rank test. Seven microRNAs (miR-146b, miR-184, miR-767, miR-6730, miR-6860, miR-196a-2 and miR-509-3) were associated with the overall survival. Among them, three microRNAs were linked with six differentially expressed mRNAs (miR-767 was predicted to target COL10A1, PLAG1 and PPP1R1C; miR-146b was predicted to target MMP16; miR-196a-2 was predicted to target SYT9). To identify the key genes in the protein-protein interaction network , we screened out the top 10 hub genes (NPY, NMU, KNG1, LPAR5, CCR3, SST, PPY, GABBR2, ADCY8 and SAA1) with higher degrees. Only LPAR5 was associated with the overall survival. Multivariate analysis demonstrated that miR-184, miR-146b, miR-509-3 and LPAR5 were an independent risk factors for prognosis. Our results of the present study identified a series of prognostic microRNAs and mRNAs that have the potential to be the targets for treatment of thyroid cancer.

Mycobacterium avium subsp. hominissuis (M. avium) is a member of the non-tuberculous mycobacteria (NTM), and is a common cause of lung infection in patients with chronic NTM lung conditions. M. avium is an environmental bacterium believed to be transmitted from environmental sources. In this work we used a recently developed model in Caenorhabditis elegans to ask whether M. avium can be transmitted from host-to-host, and the bacterial genes associated with host colonization. Infection of C. elegans was carried out by placing the nematode in cultured with M. avium. Bacteria eliminated from the intestines of infected C. elegans were used to infect naïve nematodes. In parallel experiments, to identify colonization associated genes, a transposon library of M. avium was screened for the ability to bind to HEp-2 mucosal cells. Thirty clones were identified and five selected clones with impaired adherence to HEp-2 epithelial cells were used to infect C. elegans to determine the degree of colonization. It was determined that M. avium eliminated from infected C. elegans were able to colonize a naïve C. elegans with high efficiency. Thirty of the most adherence-deficient M. avium clones obtained from the HEp-2 cell screening were sequenced to identify the location of the transposon. Many of the genes associated with the bacterial cell wall synthesis were shown to be inactivated in the selected mutants. Five out of the 30 bacterial clones were then used to infect C. elegans. All five mutants had impaired ability to colonize C. elegans compared with the wild type bacteria (decrease of 1.5-2.0 logs, p < 0.05). The limitation of this work is that the model can be used for initial screening, but other more complex systems should be used to confirm the findings. C. elegans can be used as a model to test for M. avium adherence/colonization-associated virulence determinants. All the tested adherence-deficient clones that were examined had impaired ability to colonize the host C. elegans, and some can be potentially used to prevent colonization.

Heart valves are organized connective tissues of high mechanical demand. They open and close over 100,000 times a day to preserve unidirectional blood flow by maintaining structure-function relationships throughout life. In affected individuals, structural failure compromises function and often leads to regurgitant blood flow and progressive heart failure. This is most common in degenerative valve disease due to age-related wear and tear, or congenital malformations. At present, the only effective treatment of valve disease is surgical repair or replacement and this is often impermanent and requires anti-coagulation therapy throughout life. Therefore, there is a critical need to discover new alternatives. A promising therapeutic area is tissue regeneration and in non-valvular tissues this requires a tightly regulated genetic "growth program" involving cell proliferation. To explore this in heart valves, we performed RNA-seq analysis to compare transcriptional profiles of aortic valve tissue isolated from mice during stages of growth (postnatal day (PND) 2) and adult maintenance (4 months). Data analysis reveals distinct mRNA profiles at each time point and pathway ontology identifies associated changes in biological functions. The PND2 aortic valve is characterized by extensive cell proliferation and expression of mRNAs related to the extracellular matrix (ECM). At 4 months, proliferation is not significant and a differential set of ECM-related genes are expressed. Interestingly there is enrichment of the defense response biological process at this later time point. Together, these data highlight the unique transcriptome of the postnatal valve during stages of growth and maturation, as well as biological functions associated with adult homeostatic valves. These studies create a platform for future work exploring the molecular programs altered in the onset of heart valve disease after birth and provide insights for the development of mechanistic-based therapies.

Some rats are especially prone to attribute incentive salience to a cue (conditioned stimulus, CS) paired with food reward (sign-trackers, STs), but the extent they do so varies as a function of the form of the CS. Other rats respond primarily to the predictive value of a cue (goal-trackers, GTs), regardless of its form. Sign-tracking is associated with greater cue-induced activation of mesolimbic structures than goal-tracking; however, it is unclear how the form of the CS itself influences activity in neural systems involved in incentive salience attribution. Thus, our goal was to determine how different cue modalities affect neural activity in the ventral pallidum (VP), which is known to encode incentive salience attribution, as rats performed a two-CS Pavlovian conditioned approach task in which both a lever-CS and a tone-CS predicted identical food reward. The lever-CS elicited sign-tracking in some rats (STs) and goal-tracking in others (GTs), whereas the tone-CS elicited only goal-tracking in all rats. The lever-CS elicited robust changes in neural activity (sustained tonic increases or decreases in firing) throughout the VP in STs, relative to GTs. These changes were not seen when STs were exposed to the tone-CS, and in GTs there were no differences in firing between the lever-CS and tone-CS. We conclude that neural activity throughout the VP encodes incentive signals and is especially responsive when a cue is of a form that promotes the attribution of incentive salience to it, especially in predisposed individuals.

Ultrasonic imaging has been implemented as a powerful tool for noninvasive subsurface inspections of both structural and biological media. Current ultrasound probes are rigid and bulky and cannot readily image through nonplanar three-dimensional (3D) surfaces. However, imaging through these complicated surfaces is vital because stress concentrations at geometrical discontinuities render these surfaces highly prone to defects. This study reports a stretchable ultrasound probe that can conform to and detect nonplanar complex surfaces. The probe consists of a 10 × 10 array of piezoelectric transducers that exploit an "island-bridge" layout with multilayer electrodes, encapsulated by thin and compliant silicone elastomers. The stretchable probe shows excellent electromechanical coupling, minimal cross-talk, and more than 50% stretchability. Its performance is demonstrated by reconstructing defects in 3D space with high spatial resolution through flat, concave, and convex surfaces. The results hold great implications for applications of ultrasound that require imaging through complex surfaces.

The formation of emulsions from multiple immiscible fluids is governed by classical concepts such as surface tension, differential chemical affinity and viscosity, and the action of surface-active agents. Much less is known about emulsification when one of the components is active and thus inherently not constrained by the laws of thermodynamic equilibrium. We demonstrate one such realization consisting in the encapsulation of an active liquid crystal (LC)-like gel, based on microtubules and kinesin molecular motors, into a thermotropic LC. These active nematic emulsions exhibit a variety of dynamic behaviors that arise from the cross-talk between topological defects separately residing in the active and passive components. Using numerical simulations, we show a feedback mechanism by which active flows continuously drive the passive defects that, in response, resolve the otherwise degenerated trajectories of the active defects. Our experiments show that the choice of surfactant, which stabilizes the active/passive interface, allows tuning the regularity of the self-sustained dynamic events. The hybrid active-passive system demonstrated here provides new perspectives for dynamic self-assembly driven by an active material but regulated by the equilibrium properties of the passive component.

During development of the peripheral nervous system in mammals, Schwann cells wrap their plasma membranes around neuronal axons, forming multiple myelin sheaths. A mature myelin sheath insulates axons and increases nerve conduction velocity while protecting nerve fibers from various stresses such as physical ones. Despite this functional importance, the molecular units that underlie dynamic morphological changes in formation of myelin sheaths are not sufficiently understood. Arf1 is a small guanosine triphosphate-binding protein that plays multiple roles in intracellular trafficking and related signaling, both of which are processes involved in cell morphogenesis. We demonstrate that the Arf1 guanine nucleotide exchange factor, brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1)/Arfgef1, and the effector Arf1 regulate the initiation of myelination of axons by Schwann cells. Schwann cell-specific BIG1 conditional knockout mice, which have been generated here, exhibit reduced myelin thickness and decreased localization of myelin protein zero in the myelin membrane, compared with their littermate controls. BIG1 knockout mouse nerves specifically decrease the amounts of Arf1 in the AP1 clathrin adaptor protein subunits but not the Arf1 binding to GGA1 (Golgi-localized, gamma-adaptin ear-containing, Arf-binding protein 1) transporting proteins. The amounts of Arf1 in the COPI coatomer protein subunits were comparable in the knockout mice and controls. Similar results in myelin thickness are observed in Arf1 conditional knockout mice, which have also been generated here. Thus, the BIG1 and Arf1 unit plays a key role in Schwann cell myelination, newly adding it to the list of molecular units controlling myelination.