bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes
Authors: Burguera Demian , Marquez Yamile , Racioppi Claudia , Permanyer Jon , Torres-Méndez Antonio , Esposito Rosaria , Albuixech-Crespo Beatriz , Fanlo Lucía , D’Agostino Ylenia , Gohr Andre , Navas-Perez Enrique , Riesgo Ana , Cuomo Claudia , Benvenuto Giovanna , Christiaen Lionel A. , Martí Elisa , D’Aniello Salvatore , Spagnuolo Antonietta , Ristoratore Filomena , Arnone Maria Ina , Garcia-Fernàndez Jordi , Irimia Manuel
Published: November 2017

Epithelial-mesenchymal interactions are crucial for the development of numerous animal structures. Thus, unraveling how molecular tools are recruited in different lineages to control interplays between these tissues is key to understanding morphogenetic evolution. Here, we study Esrp genes, which regulate extensive splicing programs and are essential for mammalian organogenesis. We find that Esrp homologs have been independently recruited for the development of multiple structures across deuterostomes. Although Esrp is involved in a wide variety of ontogenetic processes, our results suggest ancient roles in non-neural ectoderm and regulating specific mesenchymal-to-epithelial transitions in deuterostome ancestors. However, consistent with the extensive rewiring of Esrp-dependent splicing programs between phyla, most developmental defects observed in vertebrate mutants are related to other types of morphogenetic processes. This is likely connected to the origin of an event in Fgfr, which was recruited as an Esrp target in stem chordates and subsequently co-opted into the development of many novel traits in vertebrates.
Ingestion of artificial sweeteners leads to caloric frustration memory in Drosophila
Authors: Musso Pierre-Yves , Lampin-Saint-Amaux Aurélie , Tchenio Paul , Preat Thomas
Published: November 2017

Non-caloric artificial sweeteners (NAS) are widely used in modern human food, raising the question about their health impact. Here we have asked whether NAS consumption is a neutral experience at neural and behavioral level, or if NAS can be interpreted and remembered as negative experience. We used behavioral and imaging approaches to demonstrate that Drosophila melanogaster learn the non-caloric property of NAS through post-ingestion process. These results show that sweet taste is predictive of an energy value, and its absence leads to the formation of what we call Caloric Frustration Memory (CFM) that devalues the NAS or its caloric enantiomer. CFM formation involves activity of the associative memory brain structure, the mushroom bodies (MBs). In vivo calcium imaging of MB-input dopaminergic neurons that respond to sugar showed a reduced response to NAS after CFM formation. Altogether, these findings demonstrate that NAS are a negative experience for the brain.
The influence of the solid to plasma phase transition on the generation of plasma instabilities
Authors: Kaselouris E. , Dimitriou V. , Fitilis I. , Skoulakis A. , Koundourakis G. , Clark E. L. , Bakarezos Μ. , Nikolos I. K. , Papadogiannis N. A. , Tatarakis M.
Published: November 2017

The study of plasma instabilities is a research topic with fundamental importance since for the majority of plasma applications they are unwanted and there is always the need for their suppression. The initiating physical processes that seed the generation of plasma instabilities are not well understood in all plasma geometries and initial states of matter. For most plasma instability studies, using linear or even nonlinear magnetohydrodynamics (MHD) theory, the most crucial step is to correctly choose the initial perturbations imposed either by a predefined perturbation, usually sinusoidal, or by randomly seed perturbations as initial conditions. Here, we demonstrate that the efficient study of the seeding mechanisms of plasma instabilities requires the incorporation of the intrinsic real physical characteristics of the solid target in an electro-thermo-mechanical multiphysics study. The present proof-of-principle study offers a perspective to the understanding of the seeding physical mechanisms in the generation of plasma instabilities.
Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor
Authors: Solt Andras S. , Bostock Mark J. , Shrestha Binesh , Kumar Prashant , Warne Tony , Tate Christopher G. , Nietlispach Daniel
Published: November 2017

A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., Gs and β-arrestin. Using 13C methyl methionine NMR for the β1-adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with Gs-mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody–receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamics are observed ranging from rigid nanobody-coupled states to extensive μs-to-ms timescale dynamics when bound to a full agonist. We suggest that the mobility of the full agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary complex, ligand efficacy determines the quality of the interaction between the rigidified receptor and an IBP and consequently the signalling level.
Structural basis for TNA synthesis by an engineered TNA polymerase
Authors: Chim Nicholas , Shi Changhua , Sau Sujay P. , Nikoomanzar Ali , Chaput John C.
Published: November 2017

Darwinian evolution experiments carried out on xeno-nucleic acid (XNA) polymers require engineered polymerases that can faithfully and efficiently copy genetic information back and forth between DNA and XNA. However, current XNA polymerases function with inferior activity relative to their natural counterparts. Here, we report five X-ray crystal structures that illustrate the pathway by which α-(l)-threofuranosyl nucleic acid (TNA) triphosphates are selected and extended in a template-dependent manner using a laboratory-evolved polymerase known as Kod-RI. Structural comparison of the apo, binary, open and closed ternary, and translocated product detail an ensemble of interactions and conformational changes required to promote TNA synthesis. Close inspection of the active site in the closed ternary structure reveals a sub-optimal binding geometry that explains the slow rate of catalysis. This key piece of information, which is missing for all naturally occurring archaeal DNA polymerases, provides a framework for engineering new TNA polymerase variants.
Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome
Authors: Brooks Brandon , Olm Matthew R. , Firek Brian A. , Baker Robyn , Thomas Brian C. , Morowitz Michael J. , Banfield Jillian F.
Published: November 2017

Preterm infants exhibit different microbiome colonization patterns relative to full-term infants, and it is speculated that the hospital room environment may contribute to infant microbiome development. Here, we present a genome-resolved metagenomic study of microbial genotypes from the gastrointestinal tracts of infants and from the neonatal intensive care unit (NICU) room environment. Some strains detected in hospitalized infants also occur in sinks and on surfaces, and belong to species such as Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae, which are frequently implicated in nosocomial infection and preterm infant gut colonization. Of the 15 K. pneumoniae strains detected in the study, four were detected in both infant gut and room samples. Time series experiments showed that nearly all strains associated with infant gut colonization can be detected in the room after, and often before, detection in the gut. Thus, we conclude that a component of premature infant gut colonization is the cycle of microbial exchange between the room and the occupant.
Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport
Authors: Toba Shiori , Jin Mingyue , Yamada Masami , Kumamoto Kanako , Matsumoto Sakiko , Yasunaga Takuo , Fukunaga Yuko , Miyazawa Atsuo , Fujita Sakiko , Itoh Kyoko , Fushiki Shinji , Kojima Hiroaki , Wanibuchi Hideki , Arai Yoshiyuki , Nagai Takeharu , Hirotsune Shinji
Published: November 2017

Although α-synuclein (αSyn) has been linked to Parkinson’s disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that αSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs). Live-cell imaging showed that αSyn co-transported with dynein and mobile βIII-tubulin fragments in the anterograde transport. Furthermore, bi-directional axonal transports are severely affected in αSyn and γSyn depleted dorsal root ganglion neurons. SR-PALM analyses further revealed the fibrous co-localization of αSyn, dynein and βIII-tubulin in axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue, and they increased approximately 19 fold the control in quantify upon nerve ligation, indicating the unconventional MTs are mobile. Our findings indicate that αSyn facilitates to form short, mobile tMTs that play an important role in the axonal transport. This unexpected and intriguing discovery related to axonal transport provides new insight on the pathogenesis of PD.
Integrated Proteomic and Metabolomic prediction of Term Preeclampsia
Authors: Bahado-Singh Ray , Poon Liona C. , Yilmaz Ali , Syngelaki Argyro , Turkoglu Onur , Kumar Praveen , Kirma Joseph , Allos Matthew , Accurti Veronica , Li Jiansheng , Zhao Peng , Graham Stewart F. , Cool David R. , Nicolaides Kypros
Published: November 2017

Term preeclampsia (tPE), ≥37 weeks, is the most common form of PE and the most difficult to predict. Little is known about its pathogenesis. This study aims to elucidate the pathogenesis and assess early prediction of tPE using serial integrated metabolomic and proteomic systems biology approaches. Serial first- (11–14 weeks) and third-trimester (30–34 weeks) serum samples were analyzed using targeted metabolomic (1H NMR and DI-LC-MS/MS) and proteomic (MALDI-TOF/TOF-MS) platforms. We analyzed 35 tPE cases and 63 controls. Serial first- (sphingomyelin C18:1 and urea) and third-trimester (hexose and citrate) metabolite screening predicted tPE with an area under the receiver operating characteristic curve (AUC) (95% CI) = 0.817 (0.732–0.902) and a sensitivity of 81.6% and specificity of 71.0%. Serial first [TATA box binding protein-associated factor (TBP)] and third-trimester [Testis-expressed sequence 15 protein (TEX15)] protein biomarkers highly accurately predicted tPE with an AUC (95% CI) of 0.987 (0.961–1.000), sensitivity 100% and specificity 98.4%. Integrated pathway over-representation analysis combining metabolomic and proteomic data revealed significant alterations in signal transduction, G protein coupled receptors, serotonin and glycosaminoglycan metabolisms among others. This is the first report of serial integrated and combined metabolomic and proteomic analysis of tPE. High predictive accuracy and potentially important pathogenic information were achieved.
Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus
Authors: Voets Natalie L. , Hodgetts Carl J. , Sen Arjune , Adcock Jane E. , Emir Uzay
Published: November 2017

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.
Inhibition of the inflammatory response to stress by targeting interaction between PKR and its cellular activator PACT
Authors: Dabo Stephanie , Maillard Patrick , Collados Rodriguez Milagros , Hansen Marianne Doré , Mazouz Sabrina , Bigot Donna-Joe , Tible Marion , Janvier Geneviève , Helynck Olivier , Cassonnet Patricia , Jacob Yves , Bellalou Jacques , Gatignol Anne , Patel Rekha C. , Hugon Jacques , Munier-Lehmann Hélène , Meurs Eliane F.
Published: November 2017

PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy. We identified the flavonoid luteolin as an inhibitor of the PKR/PACT interaction at the level of their DRBDs using high-throughput screening of chemical libraries by homogeneous time-resolved fluorescence. This was further validated using NanoLuc-Based Protein Complementation Assay. Luteolin inhibits PKR phosphorylation, the ISR and the induction of pro-inflammatory cytokines in human THP1 macrophages submitted to oxidative stress and toll-like receptor (TLR) agonist. Similarly, luteolin inhibits induction of pro-inflammatory cytokines in murine microglial macrophages. In contrast, luteolin increased activation of the inflammasome, in a PKR-independent manner. Collectively, these data delineate the importance of PKR in the inflammation process to the ISR and induction of pro-inflammatory cytokines. Pharmacological inhibitors of PKR should be used in combination with drugs targeting directly the inflammasome.
Asymmetrical bipolar nanosecond electric pulse widths modify bipolar cancellation
Authors: Valdez Chris M. , Barnes Ronald A. , Roth Caleb C. , Moen Erick K. , Throckmorton Graham A. , Ibey Bennett L.
Published: November 2017

A bipolar (BP) nanosecond electric pulse (nsEP) exposure generates reduced calcium influx compared to a unipolar (UP) nsEP. This attenuated physiological response from a BP nsEP exposure is termed “bipolar cancellation” (BPC). The predominant BP nsEP parameters that induce BPC consist of a positive polarity (↑) front pulse followed by the delivery of a negative polarity (↓) back pulse of equal voltage and width; thereby the duration is twice a UP nsEP exposure. We tested these BPC parameters, and discovered that a BP nsEP with symmetrical pulse widths is not required to generate BPC. For example, our data revealed the physiological response initiated by a ↑900 nsEP exposure can be cancelled by a second pulse that is a third of its duration.  However, we observed a complete loss of BPC from a ↑300 nsEP followed by a ↓900 nsEP exposure. Spatiotemporal analysis revealed these asymmetrical BP nsEP exposures generate distinct local YO-PRO®-1 uptake patterns across the plasma membrane. From these findings, we generated a conceptual model that suggests BPC is a phenomenon balanced by localized charging and discharging events across the membrane.
Differential prognostic value of MYC immunohistochemistry in subtypes of papillary renal cell carcinoma
Authors: Bellut Julia , Bertz Simone , Nolte Elke , Stöhr Christine , Polifka Iris , Lieb Verena , Herrmann Edwin , Jung Rudolf , Hartmann Arndt , Wullich Bernd , Taubert Helge , Wach Sven
Published: November 2017

The histomorphological subtyping of papillary renal cell carcinomas (pRCCs) has improved the predictions of patients’ long-term survival. Based on our previous results, we hypothesized that the MYC proto-oncogene would show differential expression in pRCC subtypes. Using a multi-institutional cohort of 204 pRCC patients we assessed the additional value of the immunohistochemical markers MYC, MINA53, and Ki67 in predicting patient’s long-term survival. The clinical endpoints were overall survival (OS) and cancer-specific survival (CSS). Nomograms were constructed to predict each patient’s risk of death (OS). The incorporation of the MYC staining patterns allowed the stratification of pRCC type 1 patients into better and worse prognostic groups. None of the patients with pRCC type 1 tumors and favorable MYC staining patterns died from tumor-related causes. This prognostic value was independent of the patient’s age at surgery, the pathological tumor stage and presence of lymph node invasion. we could show that the immunohistochemical assessment of MYC and the histomorphological subtyping of pRCC stratifies pRCC type 1 tumors with regard to OS and CSS. The determination of the histomorphologic pRCC subtype in combination with the MYC immunohistochemical staining patterns allows a more accurate prediction of patients’ individual risk of death.
Topology-commanded optical properties of bistable electric-field-induced torons in cholesteric bubble domains
Authors: Varanytsia Andrii , Posnjak Gregor , Mur Urban , Joshi Vinay , Darrah Kelsey , Muševič Igor , Čopar Simon , Chien Liang-Chy
Published: November 2017

Nowadays, complicated topological defects enable many experimental manipulations and configurational simulations of active soft matter for optical and photonic applications. Investigation of topological defects in soft anisotropic materials enables one to better understand three-dimensional orientation fields in cholesteric liquid crystals. Here, we describe optical properties of bistable bubble domain (BD) texture torons in a thin layer of cholesteric liquid crystal (CLC), frustrated by homeotropic anchoring conditions, and reliably switchable by a random process. The control of macroscopic optical density and diffraction efficiency of the BD texture is demonstrated by a selection of a confinement ratio of the CLC. Experimentally reconstructed CLC director profile reveals the topology of BD torons allowing consideration of naturally occurring BD texture for applications in optical and photonic devices, which are bistably switchable between active and transparent optical states.
Remotely Triggered Locomotion of Hydrogel Mag-bots in Confined Spaces
Authors: Shen Tong , Font Marti Garriga , Jung Sukwon , Gabriel Millicent L. , Stoykovich Mark P. , Vernerey Franck J.
Published: November 2017

In this study, soft hydrogel crawlers with remote magnetic-responsive motility in confined spaces have been developed. Inspired by the motion of maggots, the hydrogel crawlers can reversibly contract and elongate their body controlled by repeatedly switching on/off an alternating magnetic field. Based on the cyclic deformation, the hydrogel crawlers can move peristaltically in a confined space that is coated with asymmetric micro-patterns. The dependence of the hydrogel motility on the pattern structures and lubrication is characterized using experimental measurements. Such a hydrogel system pioneers the study of active motile systems in porous media and has the potential to impact the fields of targeted drug delivery and active actuators.
Determination of Asphaltene Critical Nanoaggregate Concentration Region Using Ultrasound Velocity Measurements
Authors: Svalova Aleksandra , Parker Nicholas G. , Povey Malcolm J. W. , Abbott Geoffrey D.
Published: November 2017

Asphaltenes constitute the heaviest, most polar and aromatic fraction of petroleum crucial to the formation of highly-stable water-in-crude oil emulsions. The latter occur during crude oil production as well as spills and cause difficulties to efficient remediation practice. It is thought that in nanoaggregate form, asphaltenes create elastic layers around water droplets enhancing stability of the emulsion matrix. Ultrasonic characterisation is a high-resolution non-invasive tool in colloidal analysis shown to successfully identify asphaltene nanoaggregation in toluene. The high sensitivity of acoustic velocity to molecular rearrangements and ease in implementation renders it an attractive method to study asphaltene phase properties. Currently, aggregation is thought to correspond to an intersection of two concentration-ultrasonic velocity regressions. Our measurements indicate a variation in the proximity of nanoaggregation which is not accounted for by present models. We attribute this uncertainty to physico-chemical heterogeneity of the asphaltene fraction driven by variation in molecular size and propose a critical nanoaggregation region. We treated asphaltenes from North and South American crude oils with ruthenium ion catalysed oxidation to characterize their n-alkyl appendages attached to aromatic cores. Principal component analysis was performed to investigate the coupling between asphaltene structures and velocity measurements and their impact on aggregation.
Beliefs about Others’ Abilities Alter Learning from Observation
Authors: Selbing Ida , Olsson Andreas
Published: November 2017

Learning what is dangerous by observing others can be safer and more efficient than individual learning. The efficiency of observational learning depends on how observational information is used, something we propose depends on our beliefs’ about others. Here, we investigated how described and actual abilities of another individual (a demonstrator) influenced performance and psychophysiology during learning of an observational avoidance task. Participants were divided into two groups. In each group there were two demonstrators who were described as either high (Described-High group) or low (Described-Low group) in their ability to learn the task. In both groups, one demonstrator had a high ability (Actual-High) and the other had a low ability (Actual-Low) to learn. Participants performed worse in the Described-Low compared to the Described-High group. Pupil dilation, and behavioral data in combination with reinforcement learning modeling, suggested that the described ability influenced performance by affecting the level of attention towards the observational information. Skin conductance responses and pupil dilation provided us with a separate measure of learning in addition to choice behavior.
The electron-phonon interaction at deep Bi
2
Te3-semiconductor interfaces from Brillouin light scattering
Authors: Wiesner M. , Trzaskowska A. , Mroz B. , Charpentier S. , Wang S. , Song Y. , Lombardi F. , Lucignano P. , Benedek G. , Campi D. , Bernasconi M. , Guinea F. , Tagliacozzo A.
Published: November 2017

It is shown that the electron-phonon interaction at a conducting interface between a topological insulator thin film and a semiconductor substrate can be directly probed by means of high-resolution Brillouin light scattering (BLS). The observation of Kohn anomalies in the surface phonon dispersion curves of a 50 nm thick Bi2Te3 film on GaAs, besides demonstrating important electron-phonon coupling effects in the GHz frequency domain, shows that information on deep interface electrons can be obtained by tuning the penetration depth of optically-generated surface phonons so as to selectively probe the interface region, as in a sort of quantum sonar.
Polarization of the Majorana quasiparticles in the Rashba chain
Authors: Maśka Maciej M. , Domański Tadeusz
Published: November 2017

We demonstrate that the selective equal–spin Andreev reflection (SESAR) spectroscopy can be used in STM experiments to distinguish the zero–energy Majorana quasiparticles from the ordinary fermionic states of the Rashba chain. Such technique, designed for probing the p–wave superconductivity, could be applied to the intersite pairing of equal–spin electrons in the chain of magnetic Fe atoms deposited on the superconducting Pb substrate. Our calculations of the effective pairing amplitude for individual spin components imply the magnetically polarized Andreev conductance, which can be used to ‘filter’ the Majorana quasiparticles from the ordinary in–gap states, although the pure spin current (i.e., perfect polarization) is impossible.
Genome-wide analysis of circular RNAs in prenatal and postnatal pituitary glands of sheep
Authors: Li Cunyuan , Li Xiaoyue , Ma Qiman , Zhang Xiangyu , Cao Yang , Yao Yang , You Shuang , Wang Dawei , Quan Renzhe , Hou Xiaoxu , Liu Zhijin , Zhan Qianqian , Liu Li , Zhang Mengdan , Yu Shuting , Ni Wei , Hu Shengwei
Published: November 2017

Circular RNAs (circRNAs) are a class of animal non-coding RNAs and play an impor-tant role in animal growth and development. However, the expression and function of circRNAs in the pituitary gland of sheep are unclear. Transcriptome profiling of circRNAs in the pituitary gland of sheep may enable us to understand their biological functions. In the present study, we identified 10,226 circRNAs from RNA-seq data in the pituitary gland of prenatal and postnatal sheep. Reverse transcription PCR and DNA sequencing analysis confirmed the presence of several circRNAs. Real-time RT-PCR analysis showed that sheep circRNAs are resistant to RNase R digestion and are expressed in prenatal and postnatal pituitary glands. GO and KEGG enrichment analysis showed that host genes of differentially expressed circRNAs are involved in the regulation of hormone secretion as well as in several pathways related to these processes. We determined that numerous circRNAs interact with pituitary-specific miRNAs that are involved in the biologic functions of the pituitary gland. Moreover, several circRNAs contain at least one IRES element and open reading frame, indicating their potential to encode proteins. Our study provides comprehensive expression profiles of circRNAs in the pituitary gland, thereby offering a valuable resource for circRNA biology in sheep.
Free-running Sn precipitates: an efficient phase separation mechanism for metastable Ge1−xSnx epilayers
Authors: Groiss Heiko , Glaser Martin , Schatzl Magdalena , Brehm Moritz , Gerthsen Dagmar , Roth Dietmar , Bauer Peter , Schäffler Friedrich
Published: November 2017

The revival of interest in Ge1−xSnx alloys with x ≥ 10% is mainly owed to the recent demonstration of optical gain in this group-IV heterosystem. Yet, Ge and Sn are immiscible over about 98% of the composition range, which renders epilayers based on this material system inherently metastable. Here, we address the temperature stability of pseudomorphic Ge1−xSnx films grown by molecular beam epitaxy. Both the growth temperature dependence and the influence of post-growth annealing steps were investigated. In either case we observe that the decomposition of epilayers with Sn concentrations of around 10% sets in above ≈230 °C, the eutectic temperature of the Ge/Sn system. Time-resolved in-situ annealing experiments in a scanning electron microscope reveal the crucial role of liquid Sn precipitates in this phase separation process. Driven by a gradient of the chemical potential, the Sn droplets move on the surface along preferential crystallographic directions, thereby taking up Sn and Ge from the strained Ge1−xSnx layer. While Sn-uptake increases the volume of the melt, single-crystalline Ge becomes re-deposited by a liquid-phase epitaxial process at the trailing edge of the droplet. This process makes phase separation of metastable GeSn layers particularly efficient at rather low temperatures.
Resident Microbiome Disruption with Antibiotics Enhances Virulence of a Colonizing Pathogen
Authors: Thomason Courtney A. , Mullen Nathan , Belden Lisa K. , May Meghan , Hawley Dana M.
Published: November 2017

There is growing evidence that symbiotic microbes play key roles in host defense, but less is known about how symbiotic microbes mediate pathogen-induced damage to hosts. Here, we use a natural wildlife disease system, house finches and the conjunctival bacterial pathogen Mycoplasma gallisepticum (MG), to experimentally examine the impact of the ocular microbiome on host damage and pathogen virulence factors during infection. We disrupted the ocular bacterial community of healthy finches using an antibiotic that MG is intrinsically resistant to, then inoculated antibiotic- and sham-treated birds with MG. House finches with antibiotic-disrupted ocular microbiomes had more severe MG-induced conjunctival inflammation than birds with unaltered microbiomes, even after accounting for differences in conjunctival MG load. Furthermore, MG cultures from finches with disrupted microbiomes had increased sialidase enzyme and cytadherence activity, traits associated with enhanced virulence in Mycoplasmas, relative to isolates from sham-treated birds. Variation in sialidase activity and cytadherence among isolates was tightly linked with degree of tissue inflammation in hosts, supporting the consideration of these traits as virulence factors in this system. Overall, our results suggest that microbial dysbiosis can result in enhanced virulence of colonizing pathogens, with critical implications for the health of wildlife, domestic animals, and humans.
Bamboo sheath—A modified branch based on the anatomical observations
Authors: Wang Shuguang
Published: November 2017

Culm sheath has always been considered a modified leaf. In this study, the anatomical structure of the culm sheath from Fargesia yunnanensis was analyzed to determine whether it originated from the foliage leaf blade or from the branch. The vascular bundles of the culm sheath showed greater similarity to the branches in shape and anatomical structure. In contrast to foliage blades, there are no midribs in culm sheaths. Stomatal density in the culm sheath is greater in the adaxial than it is in the abaxial epidermis, which is the opposite of that found in foliage leaf blades, and that density shows greater similarity to branches than it does to foliage blades. Fusoid cells are distributed on both sites of the vascular bundles in foliage blades, whereas culm sheaths have, instead, a few parenchyma cells that disintegrate and form air cavities when the sheath matures. Additionally, the culm sheath has no bulliform cells or trichome in its epidermis, and the shape of its long cells shows greater similarity to those of branches. Therefore, culm sheath is a modified branch, rather than a modified leaf.
Toughness amplification in copper/epoxy joints through pulsed laser micro-machined interface heterogeneities
Authors: Hernandez Edwin , Alfano Marco , Pulungan Ditho , Lubineau Gilles
Published: November 2017

This work addresses the mechanics of debonding along copper/epoxy joints featuring patterned interfaces. Engineered surface heterogeneities with enhanced adhesion properties are generated through pulsed laser irradiation. Peel tests are carried out to ascertain the effect of patterns shape and area fraction on the mechanical response. Experimental results are evaluated with the support of three-dimensional finite element simulations based on the use of cohesive surfaces. Results discussion is largely framed in terms of effective peel force and energy absorbed to sever the samples. It is shown that surface heterogeneities act as sites of potential crack pinning able to trigger crack initiation, propagation and arrest. Surface patterns ultimately enable a remarkable increase in the effective peel force and dissipated energy with respect to baseline homogeneous sanded interface.
Autophagy protects pancreatic beta cell mass and function in the setting of a high-fat and high-glucose diet
Authors: Sheng Qingfeng , Xiao Xiangwei , Prasadan Krishna , Chen Congde , Ming Yungching , Fusco Joseph , Gangopadhyay Nupur N. , Ricks David , Gittes George K.
Published: November 2017

Autophagy is a major regulator of pancreatic beta cell homeostasis. Altered autophagic activity has been implicated in the beta cells of patients with type 2 diabetes, and in the beta cells of obese diabetic rodents. Here, we show that autophagy was induced in beta cells by either a high-fat diet or a combined high-fat and high-glucose diet, but not by high-glucose alone. However, a high-glucose intake alone did increase beta cell mass and insulin secretion moderately. Depletion of Atg7, a necessary component of the autophagy pathway, in beta cells by pancreatic intra-ductal AAV8-shAtg7 infusion in C57BL/6 mice, resulted in decreased beta cell mass, impaired glucose tolerance, defective insulin secretion, and increased apoptosis when a combined high-fat and high-glucose diet was given, seemingly due to suppression of autophagy. Taken together, our findings suggest that the autophagy pathway may act as a protective mechanism in pancreatic beta cells during a high-calorie diet.
Enhanced strength and ductility in a friction stir processing engineered dual phase high entropy alloy
Authors: Nene S. S. , Liu K. , Frank M. , Mishra R. S. , Brennan R. E. , Cho K. C. , Li Z. , Raabe D.
Published: November 2017

The potential of high-entropy alloys (HEAs) to exhibit an extraordinary combination of properties by shifting the compositional regime from the corners towards the centers of phase diagrams has led to worldwide attention by material scientists. Here we present a strong and ductile non-equiatomic HEA obtained after friction stir processing (FSP). A transformation-induced plasticity (TRIP) assisted HEA with composition Fe50Mn30Co10Cr10 (at.%) was severely deformed by FSP and evaluated for its microstructure-mechanical property relationship. The FSP-engineered microstructure of the TRIP HEA exhibited a substantially smaller grain size, and optimized fractions of face-centered cubic (f.c.c., γ) and hexagonal close-packed (h.c.p., ε) phases, as compared to the as-homogenized reference material. This results in synergistic strengthening via TRIP, grain boundary strengthening, and effective strain partitioning between the γ and ε phases during deformation, thus leading to enhanced strength and ductility of the TRIP-assisted dual-phase HEA engineered via FSP.
CB2 receptor activation causes an ERK1/2-dependent inflammatory response in human RPE cells
Authors: Hytti M. , Andjelic S. , Josifovska N. , Piippo N. , Korhonen E. , Hawlina M. , Kaarniranta K. , Nevalainen T. J. , Petrovski G. , Parkkari T. , Kauppinen A.
Published: November 2017

A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 µM JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2 activation increased, rather than reduced inflammation in RPE cells.
Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in mice
Authors: Milet Cécile , Bléher Marianne , Allbright Kassandra , Orgeur Mickael , Coulpier Fanny , Duprez Delphine , Havis Emmanuelle
Published: November 2017

Beige adipocyte differentiation within white adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and leads to an increase of Ucp1 expression, which encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal white adipose tissue. Transcriptomic analysis of subcutaneous inguinal white adipose tissue in the absence of Egr1 identifies the molecular signature of white adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and a decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige adipocyte differentiation, while increasing extracellular matrix production. These results reveal a role for Egr1 in blocking energy expenditure via direct Ucp1 transcription repression and highlight Egr1 as a therapeutic target for counteracting obesity.
Transcriptome profile analysis reveals the regulation mechanism of floral sex differentiation in Jatropha curcas L
Authors: Hui Wenkai , Yang Yuantong , Wu Guojiang , Peng Changcao , Chen Xiaoyang , Zayed Mohamed Zaky
Published: November 2017

The seeds of Jatropha curcas contain a high percentage of biodiesel. However, low seed yield which was limited by its poor female flowers was a bottleneck for its utilization. Here, we compared the transcriptomic profiles of five different samples during floral sex differentiation stages using Illumina Hiseq 4000. Our results showed that hundreds of differentially expressed genes (DEGs) were detected in floral sex initiation period, but thousands of DEGs were involved in the stamens and ovules development process. Moreover, the DEGs were mainly shown up-regulation in male floral initiation, but mainly down-regulation in female floral initiation. Male floral initiation was associated with the flavonoid biosynthesis pathway while female floral initiation was related to the phytohormone signal transduction pathway. Cytokinin (CTK) signaling triggered the initiation of female floral primordium, thereafter other phytohormones co-promoted the female floral development. In addition, the floral organ identity genes played important roles in floral sex differentiation process and displayed a general conservation of the ABCDE model in J. curcas. To the best of our knowledge, this data is the first comprehensive analysis of the underlying regulatory mechanism and the related genes during floral sex differentiation in J. curcas, which help in engineering high-yielding varieties of J. curcas.
Rare non-coding variants are associated with plasma lipid traits in a founder population
Authors: Igartua Catherine , Mozaffari Sahar V. , Nicolae Dan L. , Ober Carole
Published: November 2017

Founder populations are ideally suited for studies on the clinical effects of alleles that are rare in general populations but occur at higher frequencies in these isolated populations. Whole genome sequencing in 98 Hutterites, a founder population of European descent, and subsequent imputation revealed 660,238 single nucleotide polymorphisms that are rare (<1%) or absent in European populations, but occur at frequencies >1% in the Hutterites. We examined the effects of these rare in European variants on plasma lipid levels in 828 Hutterites and applied a Bayesian hierarchical framework to prioritize potentially causal variants based on functional annotations. We identified two novel non-coding rare variants associated with LDL cholesterol (rs17242388 in LDLR) and HDL cholesterol (rs189679427 between GOT2 and APOOP5), and replicated previous associations of a splice variant in APOC3 (rs138326449) with triglycerides and HDL-C. All three variants are at well-replicated loci in GWAS but are independent from and have larger effect sizes than the known common variation in these regions. Candidate eQTL analyses in in LCLs in the Hutterites suggest that these rare non-coding variants are likely to mediate their effects on lipid traits by regulating gene expression.
Transient locking of the hook procures enhanced motility to flagellated bacteria
Authors: Duchesne Ismaël , Galstian Tigran , Rainville Simon
Published: November 2017

Flagellated bacteria often proliferate in inhomogeneous environments, such as biofilms, swarms and soil. In such media, bacteria are observed to move efficiently only if they can get out of “dead ends” by changing drastically their swimming direction, and even to completely reverse it. Even though these reorientations are ubiquitous, we have only recently begun to describe and understand how they happen. In the present work, we visualized the flagella of bacteria swimming in a soft agar solution. The surprising observation that the filaments do not rotate while being flipped from one side of the cell to the other suggests that reversals are driven directly by the motor rather than by the thrust created by the rotating filament. This was confirmed by observing bacteria in a liquid crystal, where the linear movement of bacteria greatly simplifies the analysis. These observations suggest that the reversal and reorientation processes involve a temporary locking of the flagellum’s hook, which is the normally flexible joint between the rotary motor and the long helical filament that propels the cell. This newly described locked-hook mode occurs only when the motor switches to a clockwise rotation. That correlates with other phenomena that are triggered by a switch in one direction and not the other.
ATF4 overexpression induces early onset of hyperlipidaemia and hepatic steatosis and enhances adipogenesis in zebrafish
Authors: Yeh Kun-Yun , Lai Chi-Yu , Lin Chiu-Ya , Hsu Chia-Chun , Lo Chung-Ping , Her Guor Mour
Published: November 2017

Activating transcription factor 4 (ATF4) is constitutively expressed in a variety of tissues, and regulates several pathological features associated with metabolic diseases such as non-alcoholic fatty liver diseases (NAFLD) and obesity. However, the role of ATF4 in animal model systems is poorly understood. To investigate ATF4 functions in zebrafish, we conditionally expressed ATF4 proteins, using a Tet-off transgenic system. We observed early-onset hyperlipidaemia and liver steatosis in ATF4 transgenic zebrafish (ATs) without doxycycline treatment (ATs − Dox). Oil Red O (ORO)-stained signals were predominant in the intravascular blood vessels and liver buds of larval ATs − Dox, indicating that ATF4 functionally promotes lipogenesis. Further, ATF4 overexpression accompanied the stimulation of the unfolded protein response. Therefore, adult ATs − Dox showed increased lipid accumulation, which led, in turn, to liver steatosis. Liver histology and ORO staining of ATs − Dox hepatocytes also indicated oxidative stress and induced NASH-like phenotypes. Moreover, ATF4 overexpression accelerated adipocyte differentiation via CCAAT enhancer binding protein-beta and peroxisome proliferator activated receptor-gamma inducible expression. ATs-Dox zebrafish showed increased weight gain with larger fat pads due to adipocyte hyperplasia. In this study, we report that ATF4 is a potential stimulator of lipid biosynthesis and adipogenesis in zebrafish.
Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO
Authors: Kang Ping , Chang Kai , Liu Ying , Bouska Mark , Birnbaum Allison , Karashchuk Galina , Thakore Rachel , Zheng Wenjing , Post Stephanie , Brent Colin S. , Li Sheng , Tatar Marc , Bai Hua
Published: November 2017

Transcriptional coordination is a vital process contributing to metabolic homeostasis. As one of the key nodes in the metabolic network, the forkhead transcription factor FOXO has been shown to interact with diverse transcription co-factors and integrate signals from multiple pathways to control metabolism, oxidative stress response, and cell cycle. Recently, insulin/FOXO signaling has been implicated in the regulation of insect development via the interaction with insect hormones, such as ecdysone and juvenile hormone. In this study, we identified an interaction between Drosophila FOXO (dFOXO) and the zinc finger transcription factor Kruppel homolog 1 (Kr-h1), one of the key players in juvenile hormone signaling. We found that Kr-h1 mutants show delayed larval development and altered lipid metabolism, in particular induced lipolysis upon starvation. Notably, Kr-h1 physically and genetically interacts with dFOXO in vitro and in vivo to regulate the transcriptional activation of insulin receptor (InR) and adipose lipase brummer (bmm). The transcriptional co-regulation by Kr-h1 and dFOXO may represent a broad mechanism by which Kruppel-like factors integrate with insulin signaling to maintain metabolic homeostasis and coordinate organism growth.
Longitudinal study of visual field changes determined by Humphrey Field Analyzer 10-2 in patients with Retinitis Pigmentosa
Authors: Sayo Akira , Ueno Shinji , Kominami Taro , Nishida Kazuki , Inooka Daiki , Nakanishi Ayami , Yasuda Shunsuke , Okado Satoshi , Takahashi Kunihiko , Matsui Shigeyuki , Terasaki Hiroko
Published: November 2017

The aim of this study is to determine the progress of the visual field defects obtained by the Humphrey Field Analyzer 10-2 program (HFA 10-2) in patients with retinitis pigmentosa (RP). The medical records of 45 eyes of 45 RP patients who had at least 3 visual field tests were reviewed. Linear mixed models were used to follow the changes of the mean deviation and the average sensitivity of 4, 12, and 20 points in three concentric squares, designated as S4, S12, and S20. The median follow-up time was 3.86 years [range: 1.93 to 9.86, IQR (Interquartile range): 3.01 to 4.93]. The median number of the visual field tests was 3 (range: 3 to 15, IQR: 3 to 4). The mean change of the MD was −0.46 dB/year (−5.80%/year). When the patients were grouped by the average initial MD, the less advanced group had slower progressions than the more advanced group in S4, S12, and S20. These results should be useful in understanding the pathological changes of RP in the central visual field.