bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection for increased quorum-sensing cooperation in Pseudomonas aeruginosa through the shut-down of a drug resistance pump
Authors: Oshri Ron D , Zrihen Keren S , Shner Itzhak , Omer Bendori Shira , Eldar Avigdor
Published: June 2018

The opportunistic pathogen Pseudomonas aeruginosa employs a hierarchical quorum-sensing network to regulate virulence factor production that cooperatively benefit the population at a cost to the individual. It has been argued that the evolution of a cooperative mutant in a quorum sensing-suppressed population would be hampered through its exploitation by neighboring non-mutant cells. It remains unclear whether mechanisms which overcome this exploitation exist. Here we investigate the regain of quorum-sensing cooperation by evolving a mutant of the lasR master quorum-sensing regulator. The mutant regained partial cooperative growth through null mutations in mexT, which codes for an activator of the MexEF-OprN multidrug-resistant pump. We find that these mutations enhance cooperative growth in both the lasR mutant and wild-type backgrounds through the activation of the RhlIR system. We show that the regain of cooperation in mexT mutants is mediated by the reduction in MexEF-OprN activity, whereas an additional source of private benefit is mostly mexEF-oprN-independent. Finally, we show that addition of antibiotics for which resistance is mediated by MexEF-OprN prevents the selection of increased cooperation at sub-MIC concentrations. MexT, therefore, not only links private and public goods, but also exposes conflicts between selection for antibiotic resistance and enhanced cooperation.
SERPINB2 is a novel indicator of stem cell toxicity
Authors: Lee Na-Hee , Cho Ara , Park Se-Ra , Lee Jin Woo , Sung Taek Park , Park Chan Hum , Choi Yoon-Hyeong , Lim Soyi , Baek Min-Kwan , Kim Dong Young , Jin Mirim , Lee Hwa-Yong , Hong In-Sun
Published: June 2018

The toxicological evaluation of potential drug candidates is very important in the preclinical phase of drug development. Toxic materials may cause serious decline in stem cell function and loss of stemness. Indeed, we found that toxic exposure more profoundly suppressed the growth of stem cells than terminally differentiated fibroblasts. Importantly, toxic exposure suppressed stem cell migration and multi-lineage differentiation potential in vitro and in vivo. Moreover, early-response genes involved in stem cell properties such as self-renewal and differentiation capabilities can be used as specific markers to predict toxicity. In the present study, we also identified a labile toxic response gene, SERPINB2, which is significantly increased in response to various toxic agents in human stem cells in vitro and in vivo. Consistently, self-renewal, migration, and multi-lineage differentiation potential were markedly decreased following SERPINB2 overexpression. To the best of our knowledge, this is the first study to focus on the functions of SERPINB2 on the regenerative potential of stem cells in response to various existing chemicals, and the findings will facilitate the development of promising toxicity test platforms for newly developed chemicals.
Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting
Authors: Routledge Isobel , Chevéz José Eduardo Romero , Cucunubá Zulma M. , Rodriguez Manuel Gomez , Guinovart Caterina , Gustafson Kyle B. , Schneider Kammerle , Walker Patrick G.T. , Ghani Azra C. , Bhatt Samir
Published: June 2018

In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, Rc, describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in Rc between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.
miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models
Authors: Cerro-Herreros Estefania , Sabater-Arcis Maria , Fernandez-Costa Juan M. , Moreno Nerea , Perez-Alonso Manuel , Llamusi Beatriz , Artero Ruben
Published: June 2018

Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs enhance MBNL protein levels and rescue pathogenic missplicing events in DM1 myoblasts. Systemic delivery of these “antagomiRs” similarly boost MBNL expression and improve DM1-like phenotypes, including splicing alterations, histopathology, and myotonia in the HSALR DM1 model mice. These mammalian data provide evidence for therapeutic blocking of the miRNAs that control Muscleblind-like protein expression in myotonic dystrophy.
In utero nanoparticle delivery for site-specific genome editing
Authors: Ricciardi Adele S. , Bahal Raman , Farrelly James S. , Quijano Elias , Bianchi Anthony H. , Luks Valerie L. , Putman Rachael , López-Giráldez Francesc , Coşkun Süleyman , Song Eric , Liu Yanfeng , Hsieh Wei-Che , Ly Danith H. , Stitelman David H. , Glazer Peter M. , Saltzman W. Mark
Published: June 2018

Genetic diseases can be diagnosed early during pregnancy, but many monogenic disorders continue to cause considerable neonatal and pediatric morbidity and mortality. Early intervention through intrauterine gene editing, however, could correct the genetic defect, potentially allowing for normal organ development, functional disease improvement, or cure. Here we demonstrate safe intravenous and intra-amniotic administration of polymeric nanoparticles to fetal mouse tissues at selected gestational ages with no effect on survival or postnatal growth. In utero introduction of nanoparticles containing peptide nucleic acids (PNAs) and donor DNAs corrects a disease-causing mutation in the β-globin gene in a mouse model of human β-thalassemia, yielding sustained postnatal elevation of blood hemoglobin levels into the normal range, reduced reticulocyte counts, reversal of splenomegaly, and improved survival, with no detected off-target mutations in partially homologous loci. This work may provide the basis for a safe and versatile method of fetal gene editing for human monogenic disorders.
An antifungal polyketide associated with horizontally acquired genes supports symbiont-mediated defense in Lagria villosa beetles
Authors: Flórez Laura V. , Scherlach Kirstin , Miller Ian J. , Rodrigues Andre , Kwan Jason C. , Hertweck Christian , Kaltenpoth Martin
Published: June 2018

Microbial symbionts are often a source of chemical novelty and can contribute to host defense against antagonists. However, the ecological relevance of chemical mediators remains unclear for most systems.Lagriabeetles live in symbiosis with multiple strains ofBurkholderiabacteria that protect their offspring against pathogens. Here, we describe the antifungal polyketide lagriamide, and provide evidence supporting that it is produced by an uncultured symbiont,Burkholderia gladioliLv-StB, which is dominant in field-collectedLagria villosa. Interestingly, lagriamide is structurally similar to bistramides, defensive compounds found in marine tunicates. We identify a gene cluster that is probably involved in lagriamide biosynthesis, provide evidence for horizontal acquisition of these genes, and show that the naturally occurring symbiont strains on the egg are protective in the soil environment. Our findings highlight the potential of microbial symbionts and horizontal gene transfer as influential sources of ecological innovation.
TP53 protein levels, RNA-based pathway assessment, and race among invasive breast cancer cases
Authors: Williams Lindsay A. , Butler Ebonee N. , Sun Xuezheng , Allott Emma H. , Cohen Stephanie M. , Fuller Ashley M. , Hoadley Katherine A. , Perou Charles M. , Geradts Joseph , Olshan Andrew F. , Troester Melissa A.
Published: June 2018

Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008–2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA)). Frequency of TP53 status (IHC, RNA-based) was estimated in association with tumor characteristics, PAM50 intrinsic subtype, age, and race using relative frequency differences (RFDs) and 95% confidence intervals (95% CI) as the measure of association. Approximately 60% of basal-like tumors were TP53 protein positive (IHC), while nearly 100% were TP53 mutant-like (RNA). Luminal A tumors had low frequency of TP53 positivity (IHC: 7.9%) and mutant-like status (RNA: 1.7%). Mutant-like TP53 (RNA) was strongly associated with age ≤50 years, high tumor grade, advanced stage of disease, large tumor size, and basal-like and HER2 intrinsic subtypes. Black race was strongly associated with TP53 mutant-like status (RNA) (RFD: 24.8%, 95% CI: 20.5, 29.0) even after adjusting for age, grade, stage (RFD: 11.3%; 95% CI: 7.6, 15.0). Associations were attenuated and non-significant when measured by IHC. IHC-based TP53 status is an insensitive measurement of TP53 functional status. RNA-based methods suggest a role for TP53 in tumor prognostic features and racial disparities.
Author Correction: Methods for estimating disease transmission rates: Evaluating the precision of Poisson regression and two novel methods
Authors: Kirkeby Carsten , Halasa Tariq , Gussmann Maya , Toft Nils , Græsbøll Kaare
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation
Authors: Fainberg Hernan P. , Birtwistle Mark , Alagal Reham , Alhaddad Ahmad , Pope Mark , Davies Graeme , Woods Rachel , Castellanos Marcos , May Sean T. , Ortori Catharine A. , Barrett David A. , Perry Viv , Wiens Frank , Stahl Bernd , van der Beek Eline , Sacks Harold , Budge Helen , Symonds Michael E.
Published: June 2018

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the first month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confirmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life.
Host-plant induced changes in microbial community structure and midgut gene expression in an invasive polyphage (Anoplophora glabripennis)
Authors: Scully Erin D. , Geib Scott M. , Mason Charles J. , Carlson John E. , Tien Ming , Chen Han-Yi , Harding Scott , Tsai Chung-Jui , Hoover Kelli
Published: June 2018

Polyphagous insect herbivores possess diverse mechanisms to overcome challenges of feeding in multiple plant species including, but not limited to, transcriptional plasticity and associations with obligate or facultative symbionts. The Asian longhorned beetle (Anoplophora glabripennis) is a polyphagous wood-feeder capable of developing on over 100 tree species and, like other polyphages, its genome contains amplifications of digestive and detoxification genes. This insect also possesses a diverse gut microbial community, which has the metabolic potential to augment digestive physiology. While the genomic repertoires of A. glabripennis and its microbial community have been studied previously, comparatively less is known about how the gut transcriptome and community change in response to feeding in different hosts. In this study, we show that feeding in two suitable hosts (Acer spp. and Populus nigra) altered the expression levels of multicopy genes linked to digestion and detoxification. However, feeding in a host with documented resistance (Populus tomentosa) induced changes in the transcriptome and community beyond what was observed in insects reared in P. nigra, including the downregulation of numerous β-glucosidases, odorant binding proteins, and juvenile hormone binding proteins, the upregulation of several cuticular genes, and the loss of one major bacterial family from the gut community.
Ultrathin amorphous carbon films synthesized by filtered cathodic vacuum arc used as protective overcoats of heat-assisted magnetic recording heads
Authors: Matlak J. , Komvopoulos K.
Published: June 2018

Despite numerous investigations of amorphous carbon (a-C) films, a comprehensive study of the feasibility and optimization of sub-5-nm-thick a-C films deposited onto the write pole of heat-assisted magnetic recording (HAMR) heads is lacking. The main objective of this study was to identify the role of pulse substrate bias voltage and C+ ion incidence angle on the structure and thickness of 1–4-nm-thick a-C films deposited by a rather new thin-film deposition method, known as filtered cathodic vacuum arc (FCVA). The cross-sectional structure of a-C films synthesized under various FCVA conditions was examined by high-resolution transmission electron microscopy (HRTEM), scanning transmission electron microscopy (STEM), and electron energy loss spectroscopy (EELS). It was found that film growth under process conditions of low-to-intermediate substrate bias voltage (in the range of −25 to −100  V), low ion incidence angle (10°), very short deposition time (6 s), and fixed other deposition parameters (65% duty cycle of substrate pulse biasing and 1.48 × 1019 ions/m2·s ion flux) yields a-C films of thickness ≤4 nm characterized by a significant content (~50–60 at%) of tetrahedral (sp3) carbon atom hybridization. A threshold where sp3 hybridization is greatly reduced due to limited film growth was determined from the HRTEM/STEM and EELS measurements. The results of this study demonstrate the viability of FCVA to produce extremely thin and uniform protective a-C films with relatively high sp3 contents for HAMR heads.
Omics approaches revealed how arbuscular mycorrhizal symbiosis enhances yield and resistance to leaf pathogen in wheat
Authors: Fiorilli Valentina , Vannini Candida , Ortolani Francesca , Garcia-Seco Daniel , Chiapello Marco , Novero Mara , Domingo Guido , Terzi Valeria , Morcia Caterina , Bagnaresi Paolo , Moulin Lionel , Bracale Marcella , Bonfante Paola
Published: June 2018

Besides improved mineral nutrition, plants colonised by arbuscular mycorrhizal (AM) fungi often display increased biomass and higher tolerance to biotic and abiotic stresses. Notwithstanding the global importance of wheat as an agricultural crop, its response to AM symbiosis has been poorly investigated. We focused on the role of an AM fungus on mineral nutrition of wheat, and on its potential protective effect against Xanthomonas translucens. To address these issues, phenotypical, molecular and metabolomic approaches were combined. Morphological observations highlighted that AM wheat plants displayed an increased biomass and grain yield, as well as a reduction in lesion area following pathogen infection. To elucidate the molecular mechanisms underlying the mycorrhizal phenotype, we investigated changes of transcripts and proteins in roots and leaves during the double (wheat-AM fungus) and tripartite (wheat-AM fungus-pathogen) interaction. Transcriptomic and proteomic profiling identified the main pathways involved in enhancing plant biomass, mineral nutrition and in promoting the bio-protective effect against the leaf pathogen. Mineral and amino acid contents in roots, leaves and seeds, and protein oxidation profiles in leaves, supported the omics data, providing new insight into the mechanisms exerted by AM symbiosis to confer stronger productivity and enhanced resistance to X. translucens in wheat.
Elucidating the hypoxic stress response in barley (Hordeum vulgare L.) during waterlogging: A proteomics approach
Authors: Luan Haiye , Shen Huiquan , Pan Yuhan , Guo Baojian , Lv Chao , Xu Rugen
Published: June 2018

Waterlogging is one of the major abiotic stresses that affects barley production and yield quality. Proteomics techniques have been widely utilized to explore the mechanisms involved in the responses to abiotic stress. In this study, two barley genotypes with contrasting responses to waterlogging stress were analyzed with proteomic technology. The waterlogging treatment caused a greater reduction in biomass and photosynthetic performance in the waterlogging-sensitive genotype TF57 than that in the waterlogging-tolerant genotype TF58. Under waterlogging stress, 30, 30, 20 and 20 differentially expressed proteins were identified through tandem mass spectrometry analysis in the leaves, adventitious roots, nodal roots and seminal roots, respectively. Among these proteins, photosynthesis-, metabolism- and energy-related proteins were differentially expressed in the leaves, with oxygen-evolving enhancer protein 1, ATP synthase subunit and heat shock protein 70 being up-regulated in TF58. Pyruvate decarboxylase (PDC), 1-amino cyclopropane 1-carboxylic acid oxidase (ACO), glutamine synthetase (GS), glutathione S-transferases (GST) and beta-1, 3-glucanase in adventitious, nodal and seminal roots were more abundant in TF58 than those in TF57 under waterlogging stress. Ten representative genes were selected for validation by qRT-PCR in different genotypes with known waterlogging tolerance, and the expression levels of three candidate genes (PDC, ACO and GST) increased in the roots of all genotypes in response to the waterlogging stress. These three genes might play a significant role in the adaptation process of barley under waterlogging stress. The current results partially determined the mechanisms of waterlogging tolerance and provided valuable information for the breeding of barley with enhanced tolerance to waterlogging.
Coherent control theory and experiment of optical phonons in diamond
Authors: Sasaki Hiroya , Tanaka Riho , Okano Yasuaki , Minami Fujio , Kayanuma Yosuke , Shikano Yutaka , Nakamura Kazutaka G.
Published: June 2018

The coherent control of optical phonons has been experimentally demonstrated in various physical systems. While the transient dynamics for optical phonons can be explained by phenomenological models, the coherent control experiment cannot be explained due to the quantum interference. Here, we theoretically propose the generation and detection processes of the optical phonons and experimentally confirm our theoretical model using the diamond optical phonon by the doublepump-probe type experiment.
Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA
Authors: Narcís J. Oriol , Tapia Olga , Tarabal Olga , Piedrafita Lídia , Calderó Jordi , Berciano Maria T. , Lafarga Miguel
Published: June 2018

Spinal muscular atrophy (SMA) is a severe motor neuron (MN) disease caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene, which results in reduced levels of the SMN protein and the selective degeneration of lower MNs. The best-known function of SMN is the biogenesis of spliceosomal snRNPs, the major components of the pre-mRNA splicing machinery. Therefore, SMN deficiency in SMA leads to widespread splicing abnormalities. We used the SMN∆7 mouse model of SMA to investigate the cellular reorganization of polyadenylated mRNAs associated with the splicing dysfunction in MNs. We demonstrate that SMN deficiency induced the abnormal nuclear accumulation in euchromatin domains of poly(A) RNA granules (PARGs) enriched in the splicing regulator Sam68. However, these granules lacked other RNA-binding proteins, such as TDP43, PABPN1, hnRNPA12B, REF and Y14, which are essential for mRNA processing and nuclear export. These effects were accompanied by changes in the alternative splicing of the Sam68-dependent Bcl-x and Nrnx1 genes, as well as changes in the relative accumulation of the intron-containing Chat, Chodl, Myh9 and Myh14 mRNAs, which are all important for MN functions. PARG-containing MNs were observed at presymptomatic SMA stage, increasing their number during the symptomatic stage. Moreover, the massive accumulations of poly(A) RNA granules in MNs was accompanied by the cytoplasmic depletion of polyadenylated mRNAs for their translation. We suggest that the SMN-dependent abnormal accumulation of polyadenylated mRNAs and Sam68 in PARGs reflects a severe dysfunction of both mRNA processing and translation, which could contribute to SMA pathogenesis.
Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy
Authors: Vorobyeva Anzhelika , Westerlund Kristina , Mitran Bogdan , Altai Mohamed , Rinne Sara , Sörensen Jens , Orlova Anna , Tolmachev Vladimir , Karlström Amelie Eriksson
Published: June 2018

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation.
Silk protein nanofibers for highly efficient, eco-friendly, optically translucent, and multifunctional air filters
Authors: Min Kyungtaek , Kim Sookyoung , Kim Sunghwan
Published: June 2018

New types of air filter technologies are being called because air pollution by particulate matters (PMs) and volatile organic compounds has raised serious concerns for public health. Conventional air filters have limited application and poor degradability and they become non-disposable wastes after use. Here, we report a highly efficient, eco-friendly, translucent, and multifunctional air purification filter that is highly effective for reducing air pollution, protecting the environment, and detecting hazardous chemical vapors encountered in everyday life. Uniform silk protein nanofibers were directly generated on a window screen by an electrospinning process. Optical properties (translucence and scattering) of the silk nanofibrous air filters (SNAFs) are advantageous for achieving viewability and controlling the room temperature. Air filtration efficiencies of the fabricated SNAFs could reach up to 90% and 97% for PMs with sizes under 2.5 and 10 μm, respectively, exceeding the performances of commercial semi-high-efficiency particulate air (semi-HEPA) filters. After use, the SNAFs could be naturally degraded. Furthermore, we demonstrate the ability of SNAFs impregnated with organic dyes to sense hazardous and volatile vapors encountered in everyday life.
Descending neurons from the lateral accessory lobe and posterior slope in the brain of the silkmoth Bombyx mori
Authors: Namiki Shigehiro , Wada Satoshi , Kanzaki Ryohei
Published: June 2018

A population of descending neurons connect the brain and thoracic motor center, playing a critical role in controlling behavior. We examined the anatomical organization of descending neurons (DNs) in the brain of the silkmoth Bombyx mori. Moth pheromone orientation is a good model to investigate neuronal mechanisms of behavior. Based on mass staining and single-cell staining, we evaluated the anatomical organization of neurite distribution by DNs in the brain. Dense innervation was observed in the posterior–ventral part of the brain called the posterior slope (PS). We analyzed the morphology of DNs innervating the lateral accessory lobe (LAL), which is considered important for moth olfactory behavior. We observed that all LAL DNs also innervate the PS, suggesting the integration of signals from the LAL and PS. We also identified a set of DNs innervating the PS but not the LAL. These DNs were sensitive to the sex pheromone, suggesting a role of the PS in motor control for pheromone processing. Here we discuss the organization of descending pathways for pheromone orientation.
Bryozoans are Major Modern Builders of South Atlantic Oddly Shaped Reefs
Authors: Bastos Alex C. , Moura Rodrigo L. , Moraes Fernando C. , Vieira Laura S. , Braga Juan Carlos , Ramalho Laís V. , Amado-Filho Gilberto M. , Magdalena Ulises R. , Webster Jody M.
Published: June 2018

In major modern reef regions, either in the Indo-Pacific or the Caribbean, scleractinian corals are described as the main reef framework builders, often associated with crustose coralline algae. We used underwater cores to investigate Late Holocene reef growth and characterise the main framework builders in the Abrolhos Shelf, the largest and richest modern tropical reef complex in the South Western Atlantic, a scientifically underexplored reef province. Rather than a typical coralgal reef, our results show a complex framework building system dominated by bryozoans. Bryozoans were major components in all cores and age intervals (2,000 yrs BP), accounting for up to 44% of the reef framework, while crustose coralline algae and coral accounted for less than 28 and 23%, respectively. Reef accretion rates varied from 2.7 to 0.9 mm yr−1, which are similar to typical coralgal reefs. Bryozoan functional groups encompassed 20 taxa and Celleporaria atlantica (Busk, 1884) dominated the framework at all cores. While the prevalent mesotrophic conditions may have driven suspension-feeders’ dominance over photoautotrophs and mixotrophs, we propose that a combination of historical factors with the low storm-disturbance regime of the tropical South Atlantic also contributed to the region’s low diversity, and underlies the unique mushroom shape of the Abrolhos pinnacles.
Gut microbiota components are associated with fixed airway obstruction in asthmatic patients living in the tropics
Authors: Buendía Emiro , Zakzuk Josefina , San-Juan-Vergara Homero , Zurek Eduardo , Ajami Nadim J. , Caraballo Luis
Published: June 2018

Microbiome composition has been associated to several inflammatory diseases, including asthma. There are few studies exploring the relationships of gut microbiota with airway obstruction pheonotypes in adult asthma, especially those living in the tropics. We sought to evaluate the relationships of gut microbiota with the airway obstruction and other variables of interest in asthmatic patients living in the tropics according to three phenotypes: No Airway Obstruction (NAO), Reversible Airway Obstruction (RAO) or Fixed Airway Obstruction (FAO). We found that Streptococcaceae:Streptococcus and Enterobacteriaceae:Escherichia-Shigella consistently discriminated asthmatic individuals suffering FAO from NAO or RAO, plus Veillonellaceae:Megasphaera when comparing FAO and RAO (p < 0.05; FDR < 0.05). In the FAO, the network showing the genus relations was less complex and interconnected. Several Rumminococcaceae, Lachnospiraceae and Clostridiales were enriched in patients with low specific IgE levels to mites and Ascaris. All patients shared a common exposure framework; control medication usage and smoking habit were uncommon and equally distributed between them. In conclusion, in this tropical asthmatic population, components of human gut microbiota are associated with the presence of a FAO phenotype and lower specific IgE response to mites and Ascaris.
Optical Properties and Local Structure Evolution during Crystallization of Ga16Sb84 Alloy
Authors: Dong F. , Guo Y. R. , Qiao C. , Wang J. J. , Shen H. , Su W. S. , Zheng Y. X. , Zhang R. J. , Chen L. Y. , Wang S. Y. , Miao X. S. , Xu M.
Published: June 2018

Phase-change memory is one of the most promising candidates for future memory technologies. However, most of the phase-change memories are based on chalcogenides, while other families of materials for this purpose remain insufficiently studied. In this work, we investigate the optical properties and microstructure of Ga16Sb84 by an in-situ ellipsometer and X-ray diffraction. Our experimental results reveal that the Ga16Sb84 films exhibit a relatively high crystallization temperature of ~250 °C, excelling in long data retention. In addition, a large optical contrast exists between the amorphous and crystalline states, which may make it suitable for use in optical discs. Molecular dynamics simulations indicate that a unique local structure order in the amorphous and crystalline phases is responsible for the optical properties observed in the experiment. The similarity found in the short-range orders of the amorphous and crystalline phases is beneficial to better understanding the fast phase transition of phase-change memory.
Towards a gene regulatory network shaping the fins of the Princess cichlid
Authors: Ahi Ehsan Pashay , Sefc Kristina M.
Published: June 2018

Variation in fin shape and size contributes to the outstanding morphological diversity of teleost fishes, but the regulation of fin growth has not yet been studied extensively outside the zebrafish model. A previous gene expression study addressing the ornamental elongations of unpaired fins in the African cichlid fish Neolamprologus brichardi identified three genes (cx43, mmp9 and sema3d) with strong and consistent expression differences between short and elongated fin regions. Remarkably, the expression patterns of these genes were not consistent with inferences on their regulatory interactions in zebrafish. Here, we identify a gene expression network (GRN) comprising cx43, mmp9, and possibly also sema3d by a stepwise approach of identifying co-expression modules and predicting their upstream regulators. Among the transcription factors (TFs) predicted as potential upstream regulators of 11 co-expressed genes, six TFs (foxc1, foxp1, foxd3, myc, egr2, irf8) showed expression patterns consistent with their cooperative transcriptional regulation of the gene network. Some of these TFs have already been implicated in teleost fish fin regeneration and formation. We particularly discuss the potential function of foxd3 as driver of the network and its role in the unexpected gene expression correlations observed in N. brichardi.
Learning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy are Associated with Structural and Functional Connectivity Alterations in Hippocampus
Authors: García-García Raquel , Cruz-Gómez Álvaro Javier , Urios Amparo , Mangas-Losada Alba , Forn Cristina , Escudero-García Desamparados , Kosenko Elena , Torregrosa Isidro , Tosca Joan , Giner-Durán Remedios , Serra Miguel Angel , Avila César , Belloch Vicente , Felipo Vicente , Montoliu Carmina
Published: June 2018

Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment associated with alterations in attentional and executive networks. There are no studies evaluating the relationship between memory in MHE and structural and functional connectivity (FC) changes in the hippocampal system. This study aimed to evaluate verbal learning and long-term memory in cirrhotic patients with (C-MHE) and without MHE (C-NMHE) and healthy controls. We assessed the relationship between alterations in memory and the structural integrity and FC of the hippocampal system. C-MHE patients showed impairments in learning, long-term memory, and recognition, compared to C-NMHE patients and controls. Cirrhotic patients showed reduced fimbria volume compared to controls. Larger volumes in hippocampus subfields were related to better memory performance in C-NMHE patients and controls. C-MHE patients presented lower FC between the L-presubiculum and L-precuneus than C-NMHE patients. Compared to controls, C-MHE patients had reduced FC between L-presubiculum and subiculum seeds and bilateral precuneus, which correlated with cognitive impairment and memory performance. Alterations in the FC of the hippocampal system could contribute to learning and long-term memory impairments in C-MHE patients. This study demonstrates the association between alterations in learning and long-term memory and structural and FC disturbances in hippocampal structures in cirrhotic patients.
Body-size increase in crinoids following the end-Devonian mass extinction
Authors: Brom Krzysztof R. , Salamon Mariusz A. , Gorzelak Przemysław
Published: June 2018

The Devonian period ended with one of the largest mass extinctions in the Earth history. It comprised a series of separate events, which eliminated many marine species and led to long-term post-extinction reduction in body size in some groups. Surprisingly, crinoids were largely unaffected by these extinction events in terms of diversity. To date, however, no study examined the long-term body-size trends of crinoids over this crucial time interval. Here we compiled the first comprehensive data sets of sizes of calyces for 262 crinoid genera from the Frasnian-Visean. We found that crinoids have not experienced long-term reduction in body size after the so-called Hangenberg event. Instead, size distributions of calyces show temporal heterogeneity in the variance, with an increase in both the mean and maximum biovolumes between the Famennian and Tournaisian. The minimum biovolume, in turn, has remained constant over the study interval. Thus, the observed pattern seems to fit a Brownian motion-like diffusion model. Intriguingly, the same model has been recently invoked to explain morphologic diversification within the eucladid subclade during the Devonian-early Carboniferous. We suggest that the complex interplay between abiotic and biotic factors (i.e., expansion of carbonate ramps and increased primary productivity, in conjunction with predatory release after extinction of Devonian-style durophagous fishes) might have been involved not only in the early Mississippian diversity peak of crinoids, but possibly also in their overall passive expansion into larger body-size niches.
Association of microRNA-7 and its binding partner CDR1-AS with the prognosis and prediction of 1st-line tamoxifen therapy in breast cancer
Authors: Uhr K. , Sieuwerts A. M. , de Weerd V. , Smid M. , Hammerl D. , Foekens J. A. , Martens J. W. M.
Published: June 2018

The large number of non-coding RNAs (ncRNAs) and their breadth of functionalities has fuelled many studies on their roles in cancer. We previously linked four microRNAs to breast cancer prognosis. One of these microRNAs, hsa-miR-7, was found to be regulated by another type of ncRNA, the circular non-coding RNA (circRNA) CDR1-AS, which contains multiple hsa-miR-7 binding sites. Based on this finding, we studied the potential clinical value of this circRNA on breast cancer prognosis in a cohort based on a cohort that was previously analysed for hsa-miR-7 and in an adjuvant hormone-naïve cohort for 1st-line tamoxifen treatment outcomes, in which we also analysed hsa-miR-7. A negative correlation was observed between hsa-miR-7 and CDR1-AS in both cohorts. Despite associations with various clinical metrics (e.g., tumour grade, tumour size, and relapse location), CDR1-AS was neither prognostic nor predictive of relevant outcomes in our cohorts. However, we did observe stromal CDR1-AS expression, suggesting a possible cell-type specific interaction. Next to the known association of hsa-miR-7 expression with poor prognosis in primary breast cancer, we found that high hsa-miR-7 expression was predictive of an adverse response to tamoxifen therapy and poor progression-free and post-relapse overall survival in patients with recurrent disease.
Dalbavancin for treatment of implant-related methicillin-resistant Staphylococcus aureus osteomyelitis in an experimental rat model
Authors: Kussmann Manuel , Obermueller Markus , Berndl Florian , Reischer Veronika , Veletzky Luzia , Burgmann Heinz , Poeppl Wolfgang
Published: June 2018

Dalbavancin is a new semisynthetic lipoglycopeptide with improved antimicrobial activity against various gram-positive pathogens. It demonstrates an extensive plasma half-life which permits outpatient parenteral antimicrobial therapy with weekly intervals and might therefore be an excellent treatment alternative for patients requiring prolonged antimicrobial therapy. The present study investigated dalbavancin monotherapy in an experimental implant-related methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. A clinical MRSA isolate and a Kirschner-wire were inserted into the proximal tibia of anaesthetized Sprague-Dawley rats. Four weeks after infection 34 animals were treated over 4 weeks with either dalbavancin (20 mg/kg loading-dose; 10 mg/kg daily), vancomycin (50 mg/kg twice daily) or left untreated. Twenty-four hours after the last treatment dose tibial bones and Kirschner-wires were harvested for microbiological examination. Based on quantitative bacterial cultures of osseous tissue, dalbavancin was as effective as vancomycin and both were superior to no treatment. No emergence of an induced glycopeptide-/lipoglycopeptide- resistance was observed after a treatment period of four weeks with either dalbavancin or vancomycin. In conclusion, monotherapy with dalbavancin was shown to be as effective as vancomycin for treatment of experimental implant-related MRSA osteomyelitis in rats, but both antimicrobials demonstrated only limited efficacy. Further studies are warranted to evaluate the clinical efficacy of dalbavancin for the treatment of periprosthetic S. aureus infections.
Relationship between Optical Intensity on Optical Coherence Tomography and Retinal Ischemia in Branch Retinal Vein Occlusion
Authors: Chen Jian , Chen Weiqi , Xia Honghe , Jin Chuang , Lu Xuehui , Chen Haoyu
Published: June 2018

Branch retinal vein occlusion (BRVO) may be complicated with retinal ischemia in some cases. The purpose of the current study is to investigate the relationship between optical intensity on optical coherence tomography (OCT) and retinal ischemia in BRVO. Twenty-seven eyes diagnosed with BRVO without macular edema were classified into two groups based on the presence or absence of retinal ischemia. The optical intensity of inner retinal layers and photoreceptor inner segment ellipsoid zone/retinal pigment epithelium layer (ISe/RPE) in the affected and unaffected regions were measured on OCT. Their ratio (Optical intensity ratio, OIR) was calculated and compared between affected and unaffected region. In the retinal ischemia group, the optical intensity of inner retinal layers was higher in the affected region compared to the unaffected region while the optical intensity of ISe/RPE was low. The OIR was significantly higher in the affected region compared to control (0.83 ± 0.17 vs 0.68 ± 0.09, p < 0.001). However, in the non-ischemic group, there was no significant difference between the affected and unaffected region. The BCVA was moderately correlated with OIR of affected region (r = 0.489, p = 0.010). Our study suggests that optical intensity ratio on OCT is correlated with retinal ischemia in BRVO.
Influence of the 2-methylimidazole/zinc nitrate hexahydrate molar ratio on the synthesis of zeolitic imidazolate framework-8 crystals at room temperature
Authors: Zhang Yongyong , Jia Ying , Li Ming , Hou Li’an
Published: June 2018

The effect of the 2-methylimidazole (Hmim)/zinc nitrate hexahydrate (Zn) molar ratio on the physicochemical characteristics of the zeolitic imidazolate framework-8 (ZIF-8) was investigated. ZIF-8 crystals were synthesized by mixing Hmim with Zn at room temperature without any additives in methanol solution. It was found that Hmim/Zn molar ratio had significant influence on the crystallinity, yield, particle size and porosity of ZIF-8. The samples synthesized at low Hmim/Zn molar ratio showed a cubic shape, whereas at higher Hmim/Zn ratios truncated rhombic dodecahedron or rhombic dodecahedron morphologies were obtained. The particle size is decreased upon increasing the Hmim/Zn molar ratio. Besides, higher Hmim/Zn molar ratio in a certain range resulted in improving crystallinity, yield, surface area and micropore volume of ZIF-8. The ZIF-8 crystals produced at Hmim/Zn molar ratio of 8 exhibited the best characteristics. The present work provides new insights in relation to the role of Hmim/Zn molar ratio on the synthesis process of ZIF-8.
Adaptable, illumination patterning light sheet microscopy
Authors: Power Rory M. , Huisken Jan
Published: June 2018

Minimally-invasive optical imaging requires that light is delivered efficiently to limit the detrimental impact of photodamage on delicate biological systems. Light sheet microscopy represents the exemplar in tissue specific optical imaging of small and mesoscopic samples alike. However, further gains towards gentler imaging require a more selective imaging strategy to limit exposure to multiple yet discrete tissues without overexposing the sample, particularly where the information content is sparse or particularly optically sensitive tissues are present. The development of sample-adaptive imaging techniques is crucial in pursuit of the next generation of smart, autonomous microscopes. Herein, we report a microscope capable of performing 4D (x, y, z, t) light patterning to selectively illuminate multiple, rapidly reconfigurable regions of interest while maintaining the rapid imaging speed and high contrast associated with light sheet microscopy. We illustrate this utility in living zebrafish larvae and phantom samples.
High-performance solid state supercapacitors assembling graphene interconnected networks in porous silicon electrode by electrochemical methods using 2,6-dihydroxynaphthalen
Authors: Romanitan Cosmin , Varasteanu Pericle , Mihalache Iuliana , Culita Daniela , Somacescu Simona , Pascu Razvan , Tanasa Eugenia , Eremia Sandra A. V. , Boldeiu Adina , Simion Monica , Radoi Antonio , Kusko Mihaela
Published: June 2018

The challenge for conformal modification of the ultra-high internal surface of nanoporous silicon was tackled by electrochemical polymerisation of 2,6-dihydroxynaphthalene using cyclic voltammetry or potentiometry and, notably, after the thermal treatment (800 °C, N2, 4 h) an assembly of interconnected networks of graphene strongly adhering to nanoporous silicon matrix resulted. Herein we demonstrate the achievement of an easy scalable technology for solid state supercapacitors on silicon, with excellent electrochemical properties. Accordingly, our symmetric supercapacitors (SSC) showed remarkable performance characteristics, comparable to many of the best high-power and/or high-energy carbon-based supercapacitors, their figures of merit matching under battery-like supercapacitor behaviour. Furthermore, the devices displayed high specific capacity values along with enhanced capacity retention even at ultra-high rates for voltage sweep, 5 V/s, or discharge current density, 100 A/g, respectively. The cycling stability tests performed at relatively high discharge current density of 10 A/g indicated good capacity retention, with a superior performance demonstrated for the electrodes obtained under cyclic voltammetry approach, which may be ascribed on the one hand to a better coverage of the porous silicon substrate and, on the other hand, to an improved resilience of the hybrid electrode to pore clogging.
A novel EM concentrator with open-concentrator region based on multi-folded transformation optics
Authors: Madni Hamza Ahmad , Hussain Khurram , Jiang Wei Xiang , Liu Shuo , Aziz Asad , Iqbal Shahid , Mahboob Athar , Cui Tie Jun
Published: June 2018

Conventional concentrators with inhomogeneous coating materials that fully enclose the destined region pose great challenges for fabrication. In this paper, we propose to design an EM concentrator with homogeneous materials. Distinguished from conventional ones, the elaborately designed EM concentrator features a concentrator region that is open to the outer-world, which is achieved with multi-folded transformation optics method by compressing and folding the coating materials to create window(s). Based on this concept, we also investigate open-rotator and open rotational-concentrator devices, which could simultaneously rotate and store the EM waves in the central destined region. Due to the open nature of our proposed designs, we believe they will find potential applications in remote controlling with impressive new functionalities.
A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration
Authors: Yang Shanzheng , Toledo Enrique M. , Rosmaninho Pedro , Peng Changgeng , Uhlén Per , Castro Diogo S. , Arenas Ernest
Published: June 2018

Zeb2 is a homeodomain transcription factor that plays pleiotropic functions during embryogenesis, but its role for midbrain dopaminergic (mDA) neuron development is unknown. Here we report that Zeb2 is highly expressed in progenitor cells in the ventricular zone of the midbrain floor plate and downregulated in postmitotic neuroblasts. Functional experiments show that Zeb2 expression in the embryonic ventral midbrain is dynamically regulated by a negative feedback loop that involves miR-200c. We also find that Zeb2 overexpression reduces the levels of CXCR4, NR4A2, and PITX3 in the developing ventral midbrain in vivo, resulting in migration and mDA differentiation defects. This phenotype was recapitulated by miR-200c knockdown, suggesting that the Zeb2-miR-200c loop prevents the premature differentiation of mDA progenitors into postmitotic cells and their migration. Together, our study establishes Zeb2 and miR-200c as critical regulators that maintain the balance between mDA progenitor proliferation and neurogenesis.