bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Awareness of a Bacterial Swarm
Authors: Kotian Harshitha S. , Harkar Shalini , Joge Shubham , Mishra Ayushi , Zafal Amith , Singh Varsha , Varma Manoj M.
Published: June 2018

Bacteria are perhaps the simplest living systems capable of complex behaviour involving sensing and coherent, collective behaviour an example of which is the phenomena of swarming on agar surfaces. Two fundamental questions in bacterial swarming is how the information gathered by individual members of the swarm is shared across the swarm leading to coordinated swarm behaviour and what specific advantages does membership of the swarm provide its members in learning about their environment. In this article, we show a remarkable example of the collective advantage of a bacterial swarm which enables it to sense inert obstacles along its path. Agent based computational model of swarming revealed that independent individual behaviour in response to a two-component signalling mechanism could produce such behaviour. This is striking because independent individual behaviour without any explicit communication between agents was found to be sufficient for the swarm to effectively compute the gradient of signalling molecule concentration across the swarm and respond to it.
Worldwide survey reveals lower susceptibility of African Aedes aegypti mosquitoes to diverse strains of Zika virus
Authors: Aubry Fabien , Martynow Daria , Baidaliuk Artem , Merkling Sarah H. , Dickson Laura B. , Romero-Vivas Claudia M. , Vega-Rúa Anubis , Dusfour Isabelle , Jiolle Davy , Paupy Christophe , Mayanja Martin N. , Lutwama Julius J. , Kohl Alain , Duong Veasna , Ponlawat Alongkot , Cao-Lormeau Van-Mai , Jarman Richard G. , Diagne Cheikh T. , Faye Oumar , Faye Ousmane , Sall Amadou A. , Lambrechts Louis
Published: June 2018

Zika virus (ZIKV) is a flavivirus mainly transmitted to humans through the bite of infected Aedes aegypti mosquitoes. First isolated in Uganda in 1947, ZIKV was shown to circulate in enzootic sylvatic cycles in Africa and Asia for at least half a century before the first reported human epidemic occurred in 2007 on the Pacific island of Yap, Micronesia. Subsequently, larger ZIKV outbreaks were recorded in French Polynesia and other South Pacific islands during 2013-2014. In 2015, ZIKV reached Brazil from where it rapidly spread across the Americas and the Caribbean, causing hundreds of thousands of human cases. The factors that have fueled the explosiveness and magnitude of ZIKV emergence in the Pacific and the Americas are poorly understood. Reciprocally, the lack of major human epidemics of ZIKV in regions with seemingly favorable conditions, such as Africa or Asia, remains largely unexplained. To evaluate the potential contribution of vector population diversity to ZIKV epidemiological patterns, we established dose-response curves for eight field-derived Ae. aegypti populations representing the global range of the species, following experimental exposure to six low-passage ZIKV strains spanning the current viral genetic diversity. Our results reveal that African Ae. aegypti are significantly less susceptible than non-African Ae. aegypti across all ZIKV strains tested. We suggest that low susceptibility of vector populations may have contributed to prevent large-scale human transmission of ZIKV in Africa.
Choanoflagellate transfection illuminates their cell biology and the ancestry of animal septins
Authors: Booth David S. , Szmidt-Middleton Heather , King Nicole
Published: June 2018

As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign genes. Here we report the establishment of a robust method for expressing transgenes in the choanoflagellateSalpingoeca rosetta, overcoming barriers that have previously hampered DNA delivery and expression. To demonstrate how this method accelerates the study ofS. rosettacell biology, we engineered a panel of fluorescent protein markers that illuminate key features of choanoflagellate cells. We then investigated the localization of choanoflagellate septins, a family of GTP-binding cytoskeletal proteins that are hypothesized to regulate the multicellular rosette development inS. rosetta.Fluorescently tagged septins localized to the basal pole ofS. rosettasingle cells and rosettes in a pattern resembling septin localization in animal epithelia. The establishment of transfection inS. rosettaand its application to the study of septins represent critical advances in the growth ofS. rosettaas an experimental model for investigating choanoflagellate cell biology, core mechanisms underlying animal cell biology, and the origin of animals.
Bigger and Better? Representativeness of the Influenza A surveillance using one consolidated clinical microbiology laboratory data set as compared to the Belgian Sentinel Network of Laboratories
Authors: Wijngaert Sigi Van den , Bossuyt Nathalie , Ferns Bridget , Busson Laurent , Serrano Gabriela , Wautier Magali , Thomas Isabelle , Byott Matthew , Dupont Yves , Nastouli Eleni , Hallin Marie , Kozlakidis Zisis , Vandenberg Olivier
Published: June 2018

Infectious diseases remain a serious public health concern globally, while the need for reliable and representative surveillance systems remains as acute as ever. The public health surveillance of infectious diseases uses reported positive results from sentinel clinical laboratories or laboratory networks, to survey the presence of specific microbial agents known to constitute a threat to public health in a given population. This monitoring activity is commonly based on a representative fraction of the microbiology laboratories nationally reporting to a single central reference point. However in recent years a number of clinical microbiology laboratories (CML) have undergone a process of consolidation involving a shift towards laboratory amalgamation and closer real-time informational linkage. This report aims to investigate whether such merging activities might have a potential impact on infectious diseases surveillance. Influenza data was used from Belgian public health surveillance 2014-2017, to evaluate whether national infection trends could be estimated equally as effectively from only just one centralised CML serving the wider Brussels area (LHUB-ULB). The overall comparison reveals that there is a close correlation and representativeness of the LHUB-ULB data to the national and international data for the same time periods, both on epidemiological and molecular grounds. Notably, the effectiveness of the LHUB-ULB surveillance remains partially subject to local regional variations. These results illustrate that centralised CML-derived data are not only credible but also advantageous to use for future surveillance and prediction purposes, especially for automatic detection systems that might include multiple layers of information and timely implementation of control strategies.
Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage
Authors: Rylance Jamie , de Steenhuijsen Piters Wouter A. A. , Pojar Sherin , Nikolaou Elissavet , German Esther , Mitsi Elena , Jochems Simon P. , Carniel Beatriz , Solórzano Carla , Reiné Jesús , Gritzfeld Jenna F. , Chu Mei Ling J.N. , Arp Kayleigh , Hyder-Wright Angela D , Hill Helen , Hales Caz , Robinson Rachel , Lowe Cath , Adler Hugh , Zaidi Seher R. , Connor Victoria , Lazarova Lepa , Piddock Katherine , Wheeler India , Smith Emma , Morton Ben , Blakey John , Burhan Hassan , Koukounari Artemis , Wang Duolao , Mina Michael J. , Gordon Stephen B. , Bogaert Debby , French Neil , Ferreira Daniela M.
Published: June 2018

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage ofStreptococcus pneumoniaein animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density ofS. pneumoniaein those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density ofS. pneumoniaewas determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density ofS. pneumoniae.Transmission effects should therefore be considered in the timing design of vaccine schedules.

Trial registration

The study was registered on EudraCT (2014-004634-26)

Funding

The study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.
Intracellular delivery of mRNA to human primary T cells with microfluidic vortex shedding
Authors: Jarrell Justin A. , Twite Amy A. , Lau Katherine H. W. J. , Kashani Moein N. , Lievano Adrian A. , Acevedo Julyana , Priest Craig , Nieva Jorge , Gottlieb David , Pawell Ryan S.
Published: June 2018

Intracellular delivery of functional macromolecules, such as DNA and RNA, across the cell membrane and into the cytosol, is a critical process in both biology and medicine. Herein, we develop and use microfluidic chips containing post arrays to induce microfluidic vortex shedding, or μVS, for cell membrane poration that permits delivery of mRNA into primary human T lymphocytes. We demonstrate transfection with μVS by delivery of a 996-nucleotide mRNA construct encoding enhanced green fluorescent protein (EGFP) and assessed transfection efficiencies by quantifying levels of EGFP protein expression. We achieved high transfection efficiency (63.6 ± 3.44% EGFP+ viable cells) with high cell viability (77.3 ± 0.58%) and recovery (88.7 ± 3.21%) in CD3+ T cells 19 hrs after μVS processing. Importantly, we show that processing cells via μVS does not negatively affect cell growth rates or alter cell states. We also demonstrate processing speeds of greater than 2.0 × 106 cells s−1 at volumes ranging from 0.1 to 1.5 milliliters. Altogether, these results highlight the use of μVS as a rapid and gentle delivery method with promising potential to engineer primary human cells for research and clinical applications.
Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in liveDrosophila
Authors: Bischof J. , Duffraisse M. , Furger E. , Ajuria L. , Giraud G. , Vanderperre S. , Paul R. , Björklund M. , Ahr D. , Ahmed A.W. , Spinelli L. , Brun C. , Basler K. , Merabet S.
Published: June 2018

Transcription factors achieve specificity by establishing intricate interaction networks that will change depending on the cell context. Capturing these interactions in live condition is however a challenging issue that requires sensitive and non-invasive methods. We present a set of fly lines, called “multicolor BiFC library”, which covers most of theDrosophilatranscription factors for performing Bimolecular Fluorescence Complementation (BiFC). The multicolor BiFC library can be used to probe binary or tripartite interactions and is compatible for large-scale interaction screens. The library can also be coupled with establishedDrosophilagenetic resources to analyze interactions in the developmentally relevant expression domain of each protein partner. We provide proof of principle experiments of these various applications, using Hox proteins in the liveDrosophilaembryo as a case study. Overall this novel collection of ready-to-use fly lines constitutes an unprecedented genetic toolbox for the identification and analysis of protein-protein interactionsin vivo.
Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1
Authors: Gao Ce , Huang Weidong , Gao Yuqi , Lo Ji Jan , Luo Lingfei , Huang Honghui , Chen Jun , Peng Jinrong
Published: June 2018

The hepatopancreatic duct (HPD) system links the liver and pancreas to the intestinal tube and is composed of the extrahepatic biliary duct, gallbladder and pancreatic duct. Haematopoietically-expressed-homeobox (Hhex) protein plays an essential role in the establishment of HPD, however, the molecular mechanism remains elusive. Here we show that zebrafish hhex-null mutants fail to develop the HPD system characterized by lacking the biliary marker Annexin A4 and the HPD marker sox9b. The mutant HPD system is replaced by an intrahepatic intestinal tube characterized by expressing the intestinal marker fatty-acid-binding–protein 2a (fabp2a). Cell lineage analysis showed that this intrahepatic intestinal tube is not originated from hepatocytes or cholangiocytes. Further analysis revealed that cdx1b and pdx1 were expressed ectopically in the intrahepatic intestinal tube and knockdown of cdx1b and pdx1 restored the expression of sox9b in the mutant. Chromatin-immunoprecipitation analysis shows that Hhex binds to the promoters of pdx1 and cdx1b genes to repress their expression. We therefore propose that Hhex, Cdx1b and Pdx1 form a genetic network governing the patterning and morphogenesis of the HPD and digestive tract systems in zebrafish.
Decreased green autofluorescence intensity of lung parenchyma is a potential non-invasive diagnostic biomarker for lung cancer
Authors: Zhang Mingchao , Li Yujia , Zhang Jie , Teng Haohua , Zhang Qing , Xiang Zhenzhen , Chang Qing , Tao Yue , Chu Tianqing , Ying Weihai
Published: June 2018

Early and non-invasive diagnosis is critical for enhancing the survival rates of lung cancer. In current study we determined the green autoflorescence (AF) of the pulmonary parenchyma of lung cancer patients, using 488 nm and 500 - 550 nm as excitation wavelength and emission wavelength, respectively. Our study has suggested that decreased green AF intensity of pulmonary parenchyma may be a potential diagnostic biomarker for lung cancer: First, the green AF intensity of the cancerous tissues is less than 40% of those of distant non-neoplastic tissues and peri-neoplastic tissues; second, the green AF intensity of both the distant non-neoplastic tissues and cancerous tissues of squamous carcinoma is significantly lower than that of adenocarcinoma; third, the AF intensity of the peri-neoplastic tissues of the lung cancer patients is negatively correlated with the stages of lung cancer; and fourth, our study on the AF spectrum of pulmonary parenchyma has suggested that the AF may result from the AF of the keratins or FAD of the pulmonary parenchyma. Collectively, our study has suggested that decreased green AF intensity of pulmonary parenchyma may become a novel biomarker for non-invasive diagnosis of lung cancer. The green AF intensity may also be used to non-invasively differentiate squamous carcinoma and adenocarcinoma, as well as the stages of lung cancer. Moreover, our diagnostic approach for lung cancer may be used for image-guided surgery of lung cancer for lesions that have not been identified by CT.
Distinctive diffusive properties of swimming planktonic copepods in different environmental conditions
Authors: Pastore Raffaele , Uttieri Marco , Bianco Giuseppe , d’Alcalá Maurizio Ribera , Mazzocchi Maria Grazia
Published: June 2018

Suspensions of small planktonic copepods represent a special category in the realm of active matter, as their size falls within the range of colloids, while their motion is so complex that it cannot be rationalized according to basic self-propelled particle models. Indeed, the wide range of individual variability and swimming patterns resemble the behaviour of much larger animals. By analysing hundreds of three dimensional trajectories of the planktonic copepod Clausocalanus furcatus we investigate the possibility of detecting how the motion of this species is affected by different external conditions, such as the presence of food and the effect of gravity. While this goal is hardly achievable by direct inspection of single organism trajectories, we show that this is possible by focussing on simple average metrics commonly used to characterize colloidal suspensions, such as the mean square displacement and the dynamic correlation functions. We find that the presence of food leads to the onset of a clear localization that separates a short-time ballistic from a long-time diffusive regime. Such a benchmark reflects the tendency of C. furcatus to remain temporally feeding in a limited space and disappears when food is absent. Localization is clearly evident in the horizontal plane, but is negligible in the vertical direction, due to the effect of gravity. Our results suggest that simple average descriptors may provide concise and useful information on the swimming properties of planktonic copepods, even though single organism behaviours are strongly heterogeneous.
The Effects of Statistical Multiplicity of Infection on Virus Quantification and Infectivity Assays
Authors: Mistry Bhaven , D’Orsogna Maria R. , Chou Tom
Published: June 2018

Many biological assays are employed in virology to quantify parameters of interest. Two such classes of assays, virus quantification assays (VQA) and infectivity assays (IA), aim to estimate the number of viruses present in a solution, and the ability of a viral strain to successfully infect a host cell, respectively. VQAs operate at extremely dilute concentrations and results can be subject to stochastic variability in virus-cell interactions. At the other extreme, high viral particle concentrations are used in IAs, resulting in large numbers of viruses infecting each cell, enough for measurable change in total transcription activity. Furthermore, host cells can be infected at any concentration regime by multiple particles, resulting in a statistical multiplicity of infection (SMOI) and yielding potentially significant variability in the assay signal and parameter estimates. We develop probabilistic models for SMOI at low and high viral particle concentration limits and apply them to the plaque (VQA), endpoint dilution (VQA), and luciferase reporter (IA) assays. A web-based tool implementing our models and analysis is also developed and presented. We test our proposed new methods for inferring experimental parameters from data using numerical simulations and show improvement on existing procedures in all limits.
Transiently depleting RNPS1 leads to perdurable changes in alternative splicing
Authors: Barbier Jérôme , Cloutier Alexandre , Toutant Johanne , Durand Mathieu , Lapointe Elvy , Thibault Philippe , Chabot Benoit
Published: June 2018

While robust regulatory mechanisms are expected to control the production of splice variants that confer distinct functions, a low level of stochasticity may be tolerated. To investigate stringency of regulation, we followed changes in the splicing of 192 alternative cassette exons after growth of cancer-derived HCT116 cells and embryonic colonocytes. In both cell lines approximately 15% of alternative splicing events changed by more than 10 percentage points over a 42-day period. We then carried out a cycle of transient depletions targeting RNPS1, a splicing regulator implicated in genomic stability. For alternative splicing units not regulated by RNPS1, the level of splicing changes was similar to the stochastic value obtained after normal growth. However, the frequency of perdurable changes was at least twice that value for splicing events regulated by RNPS1. A swap allele assay performed on four RNPS1-responsive units that underwent splicing changes indicated the presence of mutations mediating this effect. Specifically, a T to C mutation in a RNPS1-responsive exon of ADARB1 confered exon skipping. Our results suggest that fluctuations in the level of a splicing regulator preferentially impact the integrity of genes encoding transcripts that are regulated by this splicing factor to produce perdurable changes in alternative splicing. We discuss the potential implication of this process in human evolution.
Type III interferon signaling restricts Enterovirus 71 infection of goblet cells
Authors: Good Charles , Wells Alexandra I. , Coyne Carolyn B.
Published: June 2018

Recent worldwide outbreaks of enterovirus (EV71) have caused major epidemics of hand, foot, and mouth disease (HFMD) with severe neurological complications, including acute flaccid paralysis. EV71 is transmitted by the enteral route, but very little is known about the mechanisms it utilizes to cross the human gastrointestinal (GI) tract. Using primary human intestinal epithelial monolayers, we show that EV71 infects the GI epithelium from the apical surface, where it preferentially infects goblet cells. Unlike echovirus 11 (E11), an enterovirus that infects enterocytes, EV71 infection did not alter epithelial barrier function, but did reduce the expression of a goblet cell-derived mucin, suggesting it alters goblet cell function. We also show that the intestinal epithelium responds to EV71 infection through the selective induction of type III IFNs, which potently restrict EV71 replication. Collectively, these findings define the early events associated with EV71 infections of the human intestinal epithelium and show that host IFN signaling controls replication in an IFN-specific manner.
Cardioprotection by the mitochondrial unfolded protein response (UPRmt) is mediated by activating transcription factor 5 (ATF5)
Authors: Wang Yves T. , Lim Yunki , McCall Matthew N. , Haynes Cole M. , Nehrke Keith , Brookes Paul S.
Published: June 2018

The mitochondrial unfolded protein response (UPRmt)1is a cytoprotective signaling pathway triggered by mitochondrial dysfunction. Activation of the UPRmtupregulates nuclear-encoded mitochondrial genes, including those for chaperones, proteases, and antioxidants, as well as glycolysis, to restore proteostasis and cell energetics. Activating transcription factor 5 (ATF5), a protein with both mitochondrial and nuclear targeting sequences, is proposed to mediate mammalian UPRmtsignaling. Since proteostasis and bioenergetics are important in the response of organs such as the heart to injury, we hypothesized that pharmacologic UPRmtactivation may be cardioprotective against ischemia-reperfusion (IR) injury and that such protection would require ATF5. Using a perfused heart IR injury model in wild-type and globalAtf5−/−mice, we found thatin-vivoadministration of the UPRmtinducers oligomycin or doxycycline 6 h prior toex-vivoIR injury was cardioprotective. Such protection was absent in hearts fromAtf5−/−mice, and no protection was observed with acuteex-vivocardiac administration of doxycycline. Loss of ATF5 also did not alter baseline IR injury (without UPRmtinduction). Cardiac gene expression analysis by RNA-Seq revealed mild induction of numerous genes in an ATF5-dependent manner, which may be important for cardioprotection. Analysis of hearts by qPCR showed that oligomycin at 6 h significantly induced genes encoding ATF5 and several known UPRmt-linked proteins. We conclude that ATF5 is required for cardioprotection induced by drugs that activate the UPRmt.
Conditions for optimal mechanical power generation by a bundle of growing actin filaments
Authors: Martiel Jean-Louis , Michelot Alphée , Boujema-Paterski Rajaa , Blanchoin Laurent , Berro Julien
Published: June 2018

Bundles of actin filaments are central to a large variety of cellular structures, such as filopodia, stress fibers, cytokinetic rings or focal adhesions. The mechanical properties of these bundles are critical for proper force transmission and force bearing. Previous mathematical modeling efforts have focused on bundles’ rigidity and shape. However, it remains unknown how bundle length and thickness are controlled by external physical factors, and how the attachment of the bundle to a load affects its ability to transmit forces. In this paper, we present a biophysical model for dynamic bundles of actin filaments that takes into account individual filaments, their interaction with each other and with an external load. In combination with in vitro motility assays of beads coated with formins, our model allowed us to characterize conditions for bead movement and bundle buckling. From the deformation profiles, we determined key biophysical properties of tethered actin bundles, such as their rigidity and filament density. Our model also demonstrated that filaments undulate under lateral constraints applied by external forces or by neighboring filaments of the bundle. Last, our model allowed us to identify optimum conditions in filament density and barbed end tethering to the load for a maximal yield of mechanical power by a dynamic actin bundle.
Competitive Tolerance And Yield Response Of Maize, Cowpea And Tomato In Mixed Culture And Pure Stand
Authors: Olowolaju Ezekiel Dare , Okunlola Gideon Olarewaju , Adelusi Adekunle AJayi
Published: June 2018

This study investigated the competitive effect and yield response of maize, cowpea and tomato in mixed and pure stand.

The experiment was carried out under a screenhouse to minimize extraneous factors such as pests and rodents using a randomized complete block design (RCBD). The treatments where T1 = sole maize (SM); T2 = Maize intercrop with cowpea (MC); T3 = Maize intercrop with tomato (MT); T4 = Sole tomato (ST); T5 = Tomato intercrop with Cowpea (TC); T6 = Sole cowpea (SC); T7 = Maize intercrop with cowpea and tomato (MCT). At harvest the yields parameters of maize, tomato and cowpea were taken. Some of the indices for intensity of competition were computed using standard formulas and statistical analysis was performed using statistical analytical software SAS version 9.12.

The result showed that the yield of maize, cowpea and tomato were enhanced in the intercropped than the sole crops. Most of the intensity of competition indices of maize, tomato and cowpea in the mixed cultured were greater than 1, while that of the sole culture equals 1.

The study concluded that competition for shared resources in the mixed culture of tomato, maize and cowpea enhanced their yield.
Private information leakage from functional genomics data: Quantification with calibration experiments and reduction via data sanitization protocols
Authors: Gürsoy Gamze , Emani Prashant , Brannon Charlotte M. , Jolanki Otto A. , Harmanci Arif , Strattan J. Seth , Miranker Andrew D. , Gerstein Mark
Published: June 2018

The generation of functional genomics datasets is surging, as they provide insight into gene regulation and organismal phenotypes (e.g., genes upregulated in cancer). The intention of functional genomics experiments is not necessarily to study genetic variants, yet they pose privacy concerns due to their use of next-generation sequencing. Moreover, there is a great incentive to share raw reads for better analyses and general research reproducibility. Thus, we need new modes of sharing beyond traditional controlled-access models. Here, we develop a data-sanitization procedure allowing raw functional genomics reads to be shared while minimizing privacy leakage, thus enabling principled privacy-utility trade-offs. It works with traditional Illumina-based assays and newer technologies such as 10x single-cell RNA-sequencing. The procedure depends on quantifying the privacy leakage in reads by statistically linking study participants to known individuals. We carried out these linkages using data from highly accurate reference genomes and more realistic environmental samples.
Live Mouse Tracker: real-time behavioral analysis of groups of mice
Authors: Chaumont Fabrice de , Ey Elodie , Torquet Nicolas , Lagache Thibault , Dallongeville Stéphane , Imbert Albane , Legou Thierry , Sourd Anne-Marie Le , Faure Philippe , Bourgeron Thomas , Olivo-Marin Jean-Christophe
Published: June 2018

Preclinical studies of psychiatric disorders require the use of animal models to investigate the impact of environmental factors or genetic mutations on complex traits such as decision-making and social interactions. Here, we present a real-time method for behavior analysis of mice housed in groups that couples computer vision, machine learning and Triggered-RFID identification to track and monitor animals over several days in enriched environments. The system extracts a thorough list of individual and collective behavioral traits and provides a unique phenotypic profile for each animal. On mouse models, we study the impact of mutations of genes Shank2 and Shank3 involved in autism. Characterization and integration of data from behavioral profiles of mutated female mice reveals distinctive activity levels and involvement in complex social configuration.
Model-based assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-cell Immune Responses
Authors: Girel Simon , Arpin Christophe , Marvel Jacqueline , Gandrillon Olivier , Crauste Fabien
Published: June 2018

Activation of naive CD8 T-cells can lead to the generation of multiple effector and memory subsets. Multiple parameters associated with activation conditions are involved in generating this diversity that is associated with heterogeneous molecular contents of activated cells. Naive cell polarisation upon antigenic stimulation and the asymmetric division that results are known to be a major source of heterogeneity and cell fate regulation. The consequences of stochastic uneven partitioning of molecular content upon subsequent divisions remain unclear. Here we aim at studying the impact of uneven partitioning on molecular-content heterogeneity and then on the immune response dynamics at the cellular level. To do so, we introduce a multiscale mathematical model of the CD8 T-cell immune response in the lymph node. In the model, cells are described as agents evolving and interacting in a 2D environment while a set of differential equations, embedded in each cell, models the regulation of intra and extracellular proteins involved in cell differentiation. Based on the analysis of in silico data at the single cell level, we show that immune response dynamics can be explained by the molecular-content heterogeneity generated by uneven partitioning at cell division. In particular, uneven partitioning acts as a regulator of cell differentiation and induces the emergence of two coexisting subpopulations of cells exhibiting antagonistic fates. We show that the degree of unevenness of molecular partitioning, along all cell divisions, affects the outcome of the immune response and can promote the generation of memory cells.
Barnaba: Software for Analysis of Nucleic Acids Structures and Trajectories
Authors: Bottaro Sandro , Bussi Giovanni , Pinamonti Giovanni , Reißer Sabine , Boomsma Wouter , Lindorff-Larsen Kresten
Published: June 2018

RNA molecules are highly dynamic systems characterized by a complex interplay between sequence, structure, dynamics, and function. Molecular simulations can potentially provide powerful insights into the nature of these relationships. The analysis of structures and molecular trajectories of nucleic acids can be non-trivial because it requires processing very high-dimensional data that are not easy to visualize and interpret.

Here we introduce Barnaba, a Python library aimed at facilitating the analysis of nucleic acids structures and molecular simulations. The software consists of a variety of analysis tools that allow the user to i) calculate distances between three-dimensional structures using different metrics, ii) back-calculate experimental data from three-dimensional structures, iii) perform cluster analysis and dimensionality reductions, iv) search three-dimensional motifs in PDB structures and trajectories and v) construct elastic network models (ENM) for nucleic acids and nucleic acids-protein complexes.

In addition, Barnaba makes it possible to calculate torsion angles, pucker conformations and to detect base-pairing/base-stacking interactions. Barnaba produces graphics that conveniently visualize both extended secondary structure and dynamics for a set of molecular conformations. The software is available as a command-line tool as well as a library, and supports a variety of 1le formats such as PDB, dcd and xtc 1les. Source code, documentation and examples are freely available athttps://github.com/srnas/barnabaunder GNU GPLv3 license.
Direct evidence for prediction signals in frontal cortex independent of prediction error
Authors: Dürschmid Stefan , Reichert Christoph , Hinrichs Hermann , Heinze Hans-Jochen , Kirsch Heidi E. , Knight Robert T. , Deouell Leon Y.
Published: June 2018

Predictive coding (PC) has been suggested as one of the main mechanisms used by brains to interact with complex environments. PC theories posit top-down prediction signals, which are compared with actual outcomes, yielding in turn prediction-error signals, which are used, bottom-up, to modify the ensuing predictions. However, disentangling prediction from prediction-error signals has been challenging. Critically, while many studies found indirect evidence for predictive coding in the form of prediction-error signals, direct evidence for the prediction signal is mostly lacking. Here we provide clear evidence, obtained from intracranial cortical recordings in human surgical patients, that the human lateral prefrontal cortex generates prediction signals while anticipating an event. Patients listened to task-irrelevant sequences of repetitive tones including infrequent predictable or unpredictable pitch deviants. The amplitude of high frequency broadband (HFB) neural activity was decreased prior to the onset of expected relative to unexpected deviants in the frontal cortex only, and its amplitude was sensitive to the increasing likelihood of deviants following longer trains of standards in the unpredictable condition. Single trial HFB amplitudes predicted deviations and correlated with post-stimulus response to deviations. These results provide direct evidence for frontal cortex prediction signals independent of prediction-error signals.
Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1 infected individuals
Authors: Uzzan Mathieu , Tokuyama Minami , Rosenstein Adam K. , Tomescu Costin , SahBandar Ivo N. , Ko Huaibin M. , Leyre Louise , Chokola Anupa , Kaplan-Lewis Emma , Rodriguez Gabriela , Seki Akihiro , Corley Michael J. , Aberg Judith , La Porte Annalena , Park Eun-young , Ueno Hideki , Oikonomou Ioannis , Doron Itai , Iliev Iliyan D. , Chen Benjamin K. , Lui Jennifer , Schacker Timothy W. , Furtado Glaucia C. , Lira Sergio A. , Colombel Jean-Frederic , Horowitz Amir , Lim Jean K. , Chomont Nicolas , Montaner Luis J. , Ndhlovu Lishomwa C. , Mehandru Saurabh
Published: June 2018

Herein, we present the first human study of anti-α4β7 therapy in a cohort of HIV-1 infected subjects with mild inflammatory bowel disease. α4β7+gut homing CD4+T cells are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although, simianized anti-α4β7 monoclonal antibodies (Mab) have shown promise in preventing or attenuating the disease course of SIV in Non-Human Primate studies, the mechanisms of drug action remain elusive and the impact on HIV-1 persistence remains unanswered. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for establishing and maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts, and defines a rational basis for the continued evaluation of anti-α4β7 therapy in HIV-1 infection.

One Sentence Summary

Anti-α4β7 integrin therapy results in attrition of lymphoid aggregates within the gastrointestinal tract of HIV-1 infected individuals
Myosin driven Actin Filament Sliding is Responsible for Endoplasmic Reticulum and Golgi Movement
Authors: McKenna Joseph F , Webb Stephen E D , Kriechbaumer Verena , Hawes Chris
Published: June 2018

The plant secretory pathway is responsible for the production of the majority of proteins and carbohydrates consumed on the planet. The early secretory pathway is composed of Golgi bodies and the endoplasmic reticulum (ER) and is highly mobile in plants with rapid remodelling of the ER network. The dynamics of the ER and Golgi bodies is driven by the actin cytoskeleton and myosin motor proteins play a key role in this. However, exactly how myosin motor proteins drive remodelling in plants is currently a contentious issue. Here, using a combination of live cell microscopy and over-expression of non-functional myosins we demonstrate that myosin motor proteins drive actin filament sliding and subsequently the dynamics of the secretory pathway.

In plants, the actin cytoskeleton and myosins are fundamental for normal dynamics of the endomembrane system and cytoplasmic streaming. We demonstrate that this is in part due to myosin driven sliding of actin filaments within a bundle. This generates, at least in part, the motive force required for cell dynamicsin planta.
Neuronal Cells Confinement by Micropatterned Cluster-Assembled Dots with Mechanotransductive Nanotopography
Authors: Schulte Carsten , Lamanna Jacopo , Moro Andrea Stefano , Piazzoni Claudio , Borghi Francesca , Chighizola Matteo , Ortoleva Serena , Racchetti Gabriella , Lenardi Cristina , Podestà Alessandro , Malgaroli Antonio , Milani Paolo
Published: June 2018

The in vitro fabrication of neural networks able to simulate brain circuits and to maintain their native connectivity is of strategic importance to gain a deep understanding of neural circuit physiology and brain natural computational algorithm(s). This would also enable a wide-range of applications including the development of efficient brain-on-chip devices or brain-computer interfaces. Chemical and mechanotransductive cues cooperate to promote proper development and functioning of neural networks. Since the 80’s, controlled growth of mammalian neuronal cells on micrometric patterned chemical cues with the development of synaptic connections and electrical activity has been reported, however the role of mechanotransductive signaling on the growth/organization of neural networks has not been investigated so far. Here we report the fabrication and characterization of patterned substrates for neuronal culture with a controlled structure both at the nano- and microscale suitable for the selective adhesion of neuronal cells. Nanostructured micrometric dots were patterned on passivated cell-repellent glass substrates by supersonic cluster beam deposition of zirconia nanoparticles through stencil masks. Cluster-assembled nanostructured zirconia surfaces are characterized by nanotopographical features that can direct the maturation of neural networks by mechanotransductive signaling. Our approach produces a controlled microscale pattern of adhesive areas with predetermined nanoscale morphology. We have validated these micropatterned substrates using a neuronal cell line (PC12 cells) and cultured hippocampal neurons. While cells have been uniformly plated on the substrates, they adhered only on the nanostructured zirconia regions, remaining effectively confined inside the nanostructured dots on which they were found to grow, move and differentiate.
Active fluctuations modulate gene expression in mouse oocytes
Authors: Almonacid Maria , El-Hayek Stephany , Othmani Alice , Queguiner Isabelle , Coulpier Fanny , Lemoine Sophie , Bastianelli Leila , Klein Christophe , Piolot Tristan , Mailly Philippe , Voituriez Raphaël , Genovesio Auguste , Verlhac Marie-Hélène
Published: June 2018

In mammals, the nucleus is central in oocytes, not defining the future embryo axis. Nucleus centring depends on an F-actin mediated pressure gradient. InFmn2−/−oocytes, lacking the F-actin nucleator Formin 2, the nucleus is off-centre and can be centred by re-expressing Formin 2. Here, we addressed the biological significance of nucleus positioning in mammalian oocytes. Using a dedicated computational 3D imaging approach, we observed nuclear architecture alterations in mouseFmn2−/−oocytes. RNA sequencing of control versusFmn2−/−oocytes detected 2285 mis-regulated genes. Rescue experiments showed that the process of nuclear positioning impacts nuclear architecture and gene expression. Using signal processing methods coupled to biophysical modelling allowing the extraction ofin vivomechanical properties of the nuclear envelope, we showed that F-actin-mediated activity promotes nuclear envelope shape fluctuations and chromatin motion. We thus propose a mechano-transduction model whereby nucleus positioning via microfilaments modulates oocyte transcriptome, essential for further embryo development.
Obesity and overweight issues could undermine Malaysia’s competitiveness
Authors: Hassan Hasliza , Sade Abu Bakar , Rahman Muhammad Sabbir
Published: June 2018

Purpose

The Malaysian lifestyle has been undergoing changes over time. With better socio-economic conditions, Malaysians tend to consume more food today than they did previously. Excessive intakes of high calorie foods combined with little daily physical activity have led to increased numbers of overweight and obese people in the population. The purpose of this paper is to compare the incidence of overweight and obesity in the population in Malaysia with other Southeast Asian countries.

Design/methodology/approach

Data for this research were based on secondary data of average weight, overweight and obese people for populations in the Southeast Asian countries. The analysis for this research focused on the population in Malaysia and compared it with populations from neighboring countries.

Findings

The population in Malaysia was ranked the second highest in the number of overweight and obese people in the Southeast Asian region. In addition, the rate of increase overweight and obese people in the population of Malaysia was found to be the highest in the region. Since the percentage of overweight and obese people had increased consistently from 2010 to 2014, there was a high possibility that the momentum would continue into the following few years.

Originality/value

Being overweight and obese was not desirable by the majority of people as it could lead to various health diseases and psychological problems. Unfortunately, the percentage of overweight and obese people in Malaysia seems to be increasing. Improved socio-economic conditions have increased the amount of food normally consumed by people. Although many people were found to be aware of the negative impact of being overweight and obese, the majority of them did not seem to take the initiative to reduce their body weight. This research is expected to create awareness of the alarming rate of increase in the number of overweight and obese people in Malaysia in order to encourage a healthier lifestyle.
Emotions and satisfaction at the hospital
Authors: Pinna Mariella , Del Chiappa Giacomo , Atzeni Marcello
Published: June 2018

Purpose

This study aims to compare public and private hospitals based on both cognitive and affective components of patients’ satisfaction.

Design/methodology/approach

A survey of 770 Italian patients from public and private hospitals was conducted. Then, hierarchical and non-hierarchical cluster analyses and a series of chi-squared tests were run with the aim of segmenting patients’ emotional response.

Findings

Respondents show different levels of satisfaction and a different emotional status based on the private or public nature of the service provider. The cluster analysis helped to identify two segments. Specifically, the cluster with the highest positive emotions is reported to have a higher level of satisfaction and a higher intention to return; this evidence is much stronger when a private service provider rather than a public one is considered. A series of chi-squared tests reveal that no significant differences exist among clusters based on socio-demographic characteristics.

Research limitations/implications

This study uses a convenience sample and is highly context specific, and thus the authors are unable to make generalizations.

Practical implications

Hospital managers should develop a customer-oriented approach, for example, by paying greater attention to patients’ emotions and experience, via conducting systematic surveys on patients’ emotions and improving the servicescape.

Originality/value

The main contribution of this study resides in simultaneously considering the role of cognitive and affective components on patients’ satisfaction and behavioural intention, and segmenting patients based on their emotional responses. Moreover, only few studies provide a comparison of public and private hospitals in Italy.
The good coach: implementation and sustainment factors that affect coaching as evidence-based intervention fidelity support
Authors: Gunderson Lara M. , Willging Cathleen E. , Trott Jaramillo Elise M. , Green Amy E. , Fettes Danielle L. , Hecht Debra B. , Aarons Gregory A.
Published: June 2018

Purpose

Evidence-based interventions (EBIs) for human services unfold within complicated social and organizational circumstances and are influenced by the attitudes and behaviors of diverse stakeholders situated within these environments. Coaching is commonly regarded as an effective strategy to support service providers in delivering EBIs and attaining high levels of fidelity over time. The purpose of this paper is to address a lacuna in research examining the factors influencing coaching, an important EBI support component.

Design/methodology/approach

The authors use the Exploration, Preparation, Implementation, and Sustainment framework to consider inner- and outer-context factors that affect coaching over time. This case study of coaching draws from a larger qualitative data set from three iterative investigations of implementation and sustainment of a home visitation program, SafeCare®. SafeCare is an EBI designed to reduce child neglect.

Findings

The authors elaborate on six major categories of findings derived from an iterative data coding and analysis process: perceptions of “good” and “bad” coaches by system sustainment status; coach as peer; in-house coaching capacity; intervention developer requirements vs other outer-context needs; outer-context support; and inner-context support.

Practical implications

Coaching is considered a key component for effective implementation of EBIs in public-sector systems, yet is under-studied. Understanding inner- and outer-context factors illuminates the ways they affect the capacity of coaches to support service delivery.

Originality/value

This paper demonstrates that coaching can accomplish more than provision of EBI fidelity support. Stakeholders characterized coaches as operating as boundary spanners who link inner and outer contexts to enable EBI implementation and sustainment.