bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding multivariate brain activity: evaluating the effect of voxelwise noise correlations on population codes in functional magnetic resonance imaging
Authors: Zhang Ru-Yuan , Wei Xue-Xin , Kay Kendrick
Published: April 2019

Previous studies have shown that neurons exhibit trial-by-trial correlated activity and that such noise correlations (NCs) greatly impact the accuracy of population codes. Meanwhile, multivariate pattern analysis (MVPA) has become a mainstream approach in functional magnetic resonance imaging (fMRI), but it remains unclear how NCs between voxels influence MVPA performance. Here, we tackle this issue by combining voxel-encoding modeling and MVPA. We focus on a well-established form of NC, tuning-compatible noise correlation (TCNC), whose sign and magnitude are systematically related to the tuning similarity between two units. We first replicate the classical finding that TCNCs impair population codes in a standard neuronal population. We then extend our analysis to fMRI data, and show that voxelwise TCNCs do not impair and can even improve MVPA performance when TCNCs are strong or the number of voxels is large. We also confirm these results using standard information-theoretic analyses in computational neuroscience. Further computational analyses demonstrate that the discrepancy between the effect of TCNCs in neuronal and voxel populations can be explained by tuning heterogeneity and pool sizes. Our results provide a theoretical foundation to understand the effect of correlated activity on population codes in macroscopic fMRI data. Our results also suggest that future fMRI research could benefit from a closer examination of the correlational structure of multivariate responses, which is not directly revealed by conventional MVPA approaches.
Stability of Nitroxide Biradical TOTAPOL in Biological Samples
Authors: McCoy Kelsey , Rogawski Rivkah , Stovicek Olivia , McDermott Ann
Published: April 2019

We characterize chemical reduction of a nitroxide biradical, TOTAPOL, used in dynamic nuclear polarization (DNP) experiments, specifically probing the stability in whole-cell pellets and lysates, and present a few strategies to stabilize the biradicals for DNP studies. DNP solid-state NMR experiments use paramagnetic species such as nitroxide biradicals to dramatically increase NMR signals. Although there is considerable excitement about using nitroxide-based DNP for detecting the NMR spectra of proteins in whole cells, nitroxide radicals are reduced in minutes in bacterial cell pellets, which we confirm and quantify here. We show that addition of the covalent cysteine blocker N-ethylmaleimide to whole cells significantly slows the rate of reduction, suggesting that cysteine thiol radicals are important toin vivoradical reduction. The use of cell lysates rather than whole cells also slows TOTAPOL reduction, which suggests a possible role for the periplasm and oxidative phosphorylation metabolites in radical degradation. Reduced TOTAPOL in lysates can also be efficiently reoxidized with potassium ferricyanide. These results point to a practical and robust set of strategies for DNP of cellular preparations.
PLANT NATRIURETIC PEPTIDE A antagonizes salicylic acid-primed cell death
Authors: Lee Keun Pyo , Liu Kaiwei , Kim Eun Yu , Medina-Puche Laura , Duan Jianli , Li Yingrui , Dong Haihong , Lv Ruiqing , Li Zihao , Lozano-Duran Rosa , Kim Chanhong
Published: April 2019

Peptide hormones perceived in the cell surface via receptor proteins enable cell-to-cell communication and act in multiple biological processes through the activation of intracellular signaling. Even though Arabidopsis is predicted to have more than 1,000 secreted peptides, the biological relevance of the majority of these is yet to be established. Here, we demonstrate that PLANT NATRIURETIC PEPTIDE A (PNP-A), a functional analog to vertebrate atrial natriuretic peptides, antagonizes the salicylic acid (SA)-mediated cell death in the Arabidopsis lesion-stimulating disease 1 (lsd1) mutant. While loss of PNP-A potentiates SA signaling, exogenous application of the PNP-A synthetic peptide or overexpression of PNP-A significantly compromises the SA-mediated cell death. Moreover, we identified a plasma membrane-localized receptor-like protein, which we name PNPAR (for PNP-A receptor), that binds PNP-A and is required to counteract SA responses. Our work identifies a novel peptide-receptor pair which modulates SA responses in Arabidopsis.
Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection with Transcriptome Analysis
Authors: Shen Hanyuan , Qu Zhipeng , Harata-Lee Yuka , Aung Thazin Nwe , Cui Jian , Wang Wei , Kortschak R. Daniel , Adelson David L.
Published: April 2019

Herbal compatibility is the knowledge of which herbs to combine in traditional Chinese medicine (TCM) formulations. The lack of understanding of herbal compatibility is one of the key problems for the application and popularization of TCM in western society. Because of the chemical complexity of herbal medicines, it is simpler to begin to conduct compatibility research based on herbs rather than component plant secondary metabolites. We have used transcriptome analysis to explore the effects and interactions of two plant extracts (Kushen and Baituling) combined in Compound Kushen Injection (CKI). Based on shared chemical compounds andin vitrocytotoxicity comparisons, we found that both the major compounds in CKI, and the cytotoxicity effects of CKI were mainly derived from the extract of Kushen (Sophorae flavescentis). We generated and analyzed transcriptome data from MDA-MB-231 cells treated with single-herb extracts or CKI and results showed that Kushen contributed to the perturbation of the majority of cytotoxicity/cancer related pathways in CKI such as cell cycle and DNA replication. We also found that Baituling (Heterosmilax yunnanensis Gagnep) could not only enhance the cytotoxic effects of Kushen in CKI, but also activate immune-related pathways. Our analyses predicted that IL-1βgene expression was upregulated by Baituling in CKI and we confirmed that IL-1βprotein expression was increased using an ELISA assay. Altogether, these findings help to explain the rationale for combining Kushen and Baituling in CKI, and transcriptome analysis using single herb extracts is an effective method for understanding herbal compatibility in TCM.
Modeling longitudinal imaging biomarkers with parametric Bayesian multi-task learning
Authors: Aksman Leon M. , Scelsi Marzia A. , Marquand Andre F. , Alexander Daniel C. , Ourselin Sebastien , Altmann Andre ,   for ADNI
Published: April 2019

Longitudinal imaging biomarkers are invaluable for understanding the course of neurodegeneration, promising the ability to track disease progression and to detect disease earlier than cross-sectional biomarkers. To properly realize their potential, biomarker trajectory models must be robust to both under-sampling and measurement errors and should be able to integrate multi-modal information to improve trajectory inference and prediction. Here we present a parametric Bayesian multi-task learning based approach to modeling univariate trajectories across subjects that addresses these criteria.

Our approach learns multiple subjects’ trajectories within a single model that allows for different types of information sharing, i.e.coupling, across subjects. It optimizes a combination of uncoupled, fully coupled and kernel coupled models. Kernel-based coupling allows linking subjects’ trajectories based on one or more biomarker measures. We demonstrate this using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, where we model longitudinal trajectories of MRI-derived cortical volumes in neurodegeneration, with coupling based on APOE genotype, cerebrospinal fluid (CSF) and amyloid PET-based biomarkers. In addition to detecting established disease effects, we detect disease related changes within the insula that have not received much attention within the literature.

Due to its sensitivity in detecting disease effects, its competitive predictive performance and its ability to learn the optimal parameter covariance from data rather than choosing a specific set of random and fixed effects a priori, we propose that our model can be used in place of or in addition to linear mixed effects models when modeling biomarker trajectories. A software implementation of the method is publicly available.
Catching the big picture of the Mediterranean Sea biodiversity with an end-to-end model of climate and fishing impacts
Authors: Moullec Fabien , Velez Laure , Verley Philippe , Barrier Nicolas , Ulses Caroline , Carbonara Pierluigi , Esteban Antonio , Follesa Cristina , Gristina Michele , Jadaud Angélique , Ligas Alessandro , López Díaz Eduardo , Maiorano Porzia , Peristeraki Panagiota , Spedicato Maria Teresa , Thasitis Ioannis , Valls Maria , Guilhaumon François , Shin Yunne-Jai
Published: April 2019

The Mediterranean Sea is among the main hotspots of marine biodiversity in the world. Under combined pressures of fishing activities and climate change it has also become a hotspot of global change, with increased concern about the worsening status of marine exploited species. More integrated modelling approaches are needed to anticipate global change impacts in the Mediterranean Sea, in order to help decision makers prioritizing management actions and strategies, mitigating impacts and adapting to changes. Our challenge was to develop a holistic model of the marine biodiversity in the Mediterranean Sea with an explicit representation of the spatial multispecies dynamics of exploited resources under the combined influence of climate variability and fishing pressure. An individual-based ecosystem model OSMOSE (Object-oriented Simulator of Marine ecOSystEms), including 100 marine species (fish, cephalopods and crustaceans) and representing about 95 % of the total declared catches, has been implemented for the first time at a high spatial resolution (400 km2) and at a large spatial scale (whole Mediterranean basin). The coupling of OSMOSE to the NEMOMED 12 physical model, and to the Eco3M-S biogeochemical and low trophic level model has been achieved to build the OSMOSE-MED end-to-end model. We fitted OSMOSE-MED to observed and estimated data of biomass and commercial catches using a likelihood approach and an evolutionary optimization algorithm. The outputs of OSMOSE-MED were then verified against observed biomass and catches, and confronted to independent datasets (MEDITS data, diet compositions and trophic levels). Although some improvements are suggested for future developments, the model results at different hierarchical levels, from individuals up to the ecosystem scale, were consistent with current knowledge and observations on the structure, the functioning and the dynamics of the ecosystems in the Mediterranean Sea. All the modelling steps, from the comprehensive representation of key ecological processes and feedbacks, the careful parameterization of the model, the confrontation to observed data, and the positive outcome from the validation process, allowed to strengthen the degree of realism of OSMOSE-MED and its relevance as an impact model to explore the futures of marine biodiversity under scenarios of global change, and as a tool to support the implementation of ecosystem-based fisheries management in the Mediterranean Sea.
Breaking barriers: The effect of protected characteristics and their intersectionality on career transition in academics
Authors: Wanelik Klara M. , Griffin Joanne S. , Head Megan , Ingleby Fiona C. , Lewis Zenobia
Published: April 2019

Lay summary

In the past decade the scientific community has been trying to tackle the historical underrepresentation of women in science and the fact that gender can constitute a barrier to career success. However, other characteristics, such as being of an ethnic minority or coming from an under-privileged background, have received less attention. In this study we find that ethnicity and socioeconomic status impact detrimentally on career progression in early career scientists, despite the fact that gender is more likely to be reported as a barrier. Our data suggest we need to widen the discussion regarding diversity and equality in science to incorporate potential barriers to career success in addition to gender.

The academic disciplines of Science Technology Engineering and Mathematics (STEM) have long suffered from a lack of diversity. While in recent years there has been some progress in addressing the underrepresentation of women in STEM subjects, other protected characteristics have received less attention. In this study, we survey early career scientists in the fields of ecology, evolutionary biology, behaviour, and related disciplines. We (i) quantitatively examine the effect of protected characteristics and their intersectionality on career transition, and (ii) provide practical suggestions, based on the qualitative responses of those surveyed, for overcoming some of the barriers we identified. We found that socioeconomic background and ethnicity impacted negatively on the quantitative measures of career progression we examined. Respondents that were female, LGBT, and from a lower socioeconomic background were more likely to report having faced a barrier, and the most frequent barrier named was related to gender. Our results suggest that respondents may have felt more confident discussing the experiences they have had related to their gender, potentially because there is now widespread discourse on this subject. However, respondents were less likely to discuss barriers they have faced in relation to ethnicity and socioeconomic status, despite the fact that the data indicates these are more detrimental to career progression. This may reflect the fact that these characteristics have received less attention, and are therefore deemed more sensitive. We hope that this study will stimulate wider discussion, and help to inform strategies to address the underrepresentation of minority groups in STEM subjects.
First-principles prediction of the information processing capacity of a simple genetic circuit
Authors: Razo-Mejia Manuel , Marzen Sarah , Chure Griffin , Taubman Rachel , Morrison Muir , Phillips Rob
Published: April 2019

Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hypothesized to have consequences for how cells are able to survive in changing environments. Recent work has explored the use of information theory as a framework to understand the accuracy with which cells can ascertain the state of their surroundings. Yet the predictive power of these approaches is limited and has not been rigorously tested using precision measurements. To that end, we generate a minimal model for a simple genetic circuit in which all parameter values for the model come from independently published data sets. We then predict the information processing capacity of the genetic circuit for a suite of biophysical parameters such as protein copy number and protein-DNA affinity. We compare these parameter-free predictions with an experimental determination of protein expression distributions and the resulting information processing capacity of E. coli cells. We find that our minimal model captures the scaling of the cell-to-cell variability in the data and the inferred information processing capacity of our simple genetic circuit up to a systematic deviation.
Activation of a zinc metallochaperone by the alarmone ZTP
Authors: Chandrangsu Pete , Huang Xiaojuan , Helmann John D.
Published: April 2019

Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the client proteins and the metabolic processes served by these chaperones are unclear. Here, we demonstrate that theBacillus subtilisYciC zinc metallochaperone (here renamed ZagA forZTPactivatedGTPaseA) supportsde novofolate biosynthesis under conditions of zinc limitation through direct interaction with the zinc dependent GTP cyclohydrolase, FolE. Furthermore, we identify a role for the alarmone ZTP, a modified purine biosynthesis intermediate, in the response to zinc limitation. ZTP, a signal of 10-formyl-tetrahydrofolate deficiency (10f-THF) in bacteria, transiently accumulates as the Zn dependent GTP cyclohydrolase FolE begins to fail and stimulates the interaction between ZagA and FolE to sustain folate synthesis despite declining zinc availability.

Importance

Metallochaperones provide a mechanism for cells to regulate the delivery of metals to newly synthesized apoproteins. By selectively targeting specific proteins for metallation, cells can ensure that key pathways remain functional even as metals become limiting for growth. The COG0523 family of proteins contain a subgroup of candidate metallochaperones (the YciC subfamily) induced under conditions of zinc limitation. Although YciC family proteins have been suggested to be GTP-dependent metallochaperones, specific interactions with client proteins have not been demonstrated. Here, we show that theBacillus subtilisYciC (renamed ZagA) protein responds to ZTP as an activating ligand rather than GTP, and interacts specifically with a Zn-dependent enzyme critical for folate synthesis (FolE). Thus, under conditions of Zn limitation ZagA is synthesized, and as folate synthesis fails, it selectively delivers Zn to FolE to sustain folate synthesis.
SNPs associated withHHIPexpression have differential effects on lung function in males and females
Authors: Fawcett KA , Obeidat M , Melbourne CA , Shrine N , Guyatt AL , John C , Luan J , Richmond A , Moksnes MR , Granell R , Weiss S , Imboden M , May-Wilson S , Hysi P , Boutin TS , Portas L , Flexeder C , Harris SE , Wang CA , Lyytikäinen L , Palviainen T , Foong RE , Keidel D , Minelli C , Langenberg C , Bossé Y , van den Berge M , Sin D , Hao K , Campbell A , Porteous D , Padmanabhan S , Smith BH , Evans D , Ring S , Langhammer A , Hveem K , Willer C , Ewert R , Stubbe B , Pirastu N , Klaric L , Joshi PK , Patasova K , Massimo M , Polasek O , Starr JM , Rudan I , Rantanen T , Pietiläinen K , Kähönen M , Raitakari OT , Hall GL , Sly PD , Pennell CE , Kaprio J , Lehtimäki T , Vitart V , Deary IJ , Jarvis D , Wilson JF , Spector T , Probst-Hensch N , Wareham N , Völzke H , Henderson J , Strachan D , Brumpton BM , Hayward C , Hall IP , Tobin MD , Wain LV
Published: April 2019

Adult lung function is highly heritable and 279 genetic loci were recently reported as associated with spirometry-based measures of lung function. Though lung development and function differ between males and females throughout life, there has been no genome-wide study to identify genetic variants with differential effects on lung function in males and females. Here, we present the first genome-wide genotype-by-sex interaction study on four lung function traits in 303,612 participants from the UK Biobank. We detected five SNPs showing genome-wide significant (P<5 × 10−8) interactions with sex on lung function, as well as 21 suggestively significant interactions (P<1 × 10−6). The strongest sex interaction signal came from rs7697189 at 4:145436894 on forced expiratory volume in 1 second (FEV1) (P = 3.15 × 10−15), and was replicated (P = 0.016) in 75,696 individuals in the SpiroMeta consortium. Sex-stratified analyses demonstrated that the minor (C) allele of rs7697189 increased lung function to a greater extent in males than females (untransformed FEV1β = 0.028 [SE 0.0022] litres in males vs β = 0.009 [SE 0.0014] litres in females), and this effect was not accounted for by differential effects on height, smoking or age at puberty. This SNP resides upstream of the gene encoding hedgehog-interacting protein (HHIP) and has previously been reported for association with lung function andHHIPexpression in lung tissue. In our analyses, whileHHIPexpression in lung tissue was significantly different between the sexes with females having higher expression (most significant probeset P=6.90 × 10−6) after adjusting for age and smoking, rs7697189 did not demonstrate sex differential effects on expression. Establishing the mechanism by whichHHIPSNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases, such as chronic obstructive pulmonary disease (COPD), in both sexes.
Constitutive UPRERactivation sustains tumor cell differentiation
Authors: Doultsinos Dimitrios , McMahon Mari , Voutetakis Konstantinos , Obacz Joanna , Pineau Raphael , Le Reste Pierre-Jean , Obiedat Akram , Samal Juhi , Patterson John B. , Zheng Qingping , Samali Afshin , Pandit Abhay , Tirosh Boaz , Chatziioannou Aristotelis , Chevet Eric , Avril Tony
Published: April 2019

Endoplasmic Reticulum (ER) proteostasis control and the Unfolded Protein Response (UPRER) have been shown to contribute to tumor development and aggressiveness. As such, the UPRERsensor IRE1α (referred to as IRE1 hereafter) is a major regulator of glioblastoma (GBM) development and is an appealing therapeutic target. To document IRE1 suitability as an antineoplastic pharmacological target, we investigated how this protein contributed to GBM cell reprogramming, a property involved in treatment resistance and disease recurrence. Probing the IRE1 activity molecular signature on transcriptome datasets of human tumors, showed that high IRE1 activity correlated with low expression of the main GBM stemness transcription factors SOX2, SALL2, POU3F2 and OLIG2. Henceforth, this phenotype was pharmacologically and genetically recapitulated in immortalized and primary GBM cell lines as well as in mouse models. We demonstrated that constitutive activation of the IRE1/XBP1/miR148a signaling axis repressed the expression of SOX2 and led to maintenance of a differentiation phenotype in GBM cells. Our results describe a novel role for IRE1 signaling in maintaining differentiated tumor cell state and highlight opportunities of informed IRE1 modulation utility in GBM therapy.
Quantitative characterization of random partitioning in the evolution of plasmid-encoded traits
Authors: Halleran Andrew D. , Flores-Bautista Emanuel , Murray Richard M.
Published: April 2019

Plasmids are found across bacteria, archaea, and eukaryotes and play an important role in evolution. Plasmids exist at different copy numbers, the number of copies of the plasmid per cell, ranging from a single plasmid per cell to hundreds of plasmids per cell. This feature of a copy number greater than one can lead to a population of plasmids within a single cell that are not identical clones of one another, but rather have individual mutations that make a given plasmid unique. During cell division, this population of plasmids is partitioned into the two daughter cells, resulting in a random distribution of different plasmid variants in each daughter. In this study, we use stochastic simulations to investigate how random plasmid partitioning compares to a perfect partitioning model. Our simulation results demonstrate that random plasmid partitioning accelerates mutant allele fixation when the allele is beneficial and the selection is in an additive or recessive regime where increasing the copy number of the beneficial allele results in additional benefit for the host. This effect does not depend on the size of the benefit conferred or the mutation rate, but is magnified by increasing plasmid copy number.
Estimation of cell lineage trees by maximum-likelihood phylogenetics
Authors: Feng Jean , DeWitt William S , McKenna Aaron , Simon Noah , Willis Amy , Matsen Frederick A
Published: April 2019

CRISPR technology has enabled large-scale cell lineage tracing for complex multicellular organisms by mutating synthetic genomic barcodes during organismal development. However, these sophisticated biological tools currently use ad-hoc and outmoded computational methods to reconstruct the cell lineage tree from the mutated barcodes. Because these methods are agnostic to the biological mechanism, they are unable to take full advantage of the data’s structure. We propose a statistical model for the mutation process and develop a procedure to estimate the tree topology, branch lengths, and mutation parameters by iteratively applying penalized maximum likelihood estimation. In contrast to existing techniques, our method estimates time along each branch, rather than number of mutation events, thus providing a detailed account of tissue-type differentiation. Via simulations, we demonstrate that our method is substantially more accurate than existing approaches. Our reconstructed trees also better recapitulate known aspects of zebrafish development and reproduce similar results across fish replicates.
A DNA barcode reference library of the French Polynesian shore fishes
Authors: Delrieu-Trottin Erwan , Williams Jeffrey T. , Pitassy Diane , Driskell Amy , Hubert Nicolas , Viviani Jérémie , Cribb Thomas H. , Espiau Benoit , Galzin René , Kulbicki Michel , de Loma Thierry Lison , Meyer Christopher , Mourier Johann , Mou-Tham Gérard , Parravicini Valeriano , Plantard Patrick , Sasal Pierre , Siu Gilles , Tolou Nathalie , Veuille Michel , Weigt Lee , Planes Serge
Published: April 2019

The emergence of DNA barcoding and metabarcoding opened new ways to study biological diversity, however, the completion of DNA barcode libraries is fundamental for such approaches to succeed. This dataset is a DNA barcode reference library (fragment of Cytochrome Oxydase I gene) for 2,190 specimens representing at least 540 species of shore fishes collected over 10 years at 154 sites across the four volcanic archipelagos of French Polynesia; the Austral, Gambier, Marquesas and Society Islands, a 5,000,000 km2area. At present, 65% of the known shore fish species of these archipelagoes possess a DNA barcode associated with preserved, photographed, tissue sampled and cataloged specimens, and extensive collection locality data. This dataset represents one of the most comprehensive DNA barcoding efforts for a vertebrate fauna to date. Considering the challenges associated with the conservation of coral reef fishes and the difficulties of accurately identifying species using morphological characters, this publicly available library is expected to be helpful for both authorities and academics in various fields.
Primary pterygium was not associated with corneal endothelial cell decrease in a rural Chinese population
Authors: Hu Yijun , Li Li , Qi Wei , Liu Zhenhao , Liu Yingpeng , Yuan Ling
Published: April 2019

Purpose

To investigate the corneal endothelial cell density (ECD) in eyes with primary pterygium.

Methods

We first conducted a retrospective study to compare the ECD between 1670 eyes with primary pterygium and 4060 eyes without pterygium. Then we designed a prospective study to confirm the critical findings of the retrospective study in 95 patients with unilateral primary pterygium.

Results

In the retrospective study, the mean preoperative ECD in eyes with primary ptergyium (2453±306 cells/mm2) was statistically significantly lower than those in eyes without pterygium (2529±313 cells/mm2, P<0.0001). However, the difference was minor (76 cells/mm2, 3.1%). In the prospective study, the mean ECD in eyes with unilateral primary pterygium (2480±263 cells/mm2) was not significantly different from those in the contralateral eyes (2527±277 cells/mm2, P=0.20). The hexagonality (P=0.10) or coefficient of variation of size (P=0.15) of corneal endothelial cells was not significantly different between eyes with pterygium and the contralateral eyes.

Conclusion

Primary pterygium may not be associated with ECD decrease in our study cohort.
Suppression of transcytosis regulates zebrafish blood-brain barrier development
Authors: O’Brown Natasha M. , Megason Sean G. , Gu Chenghua
Published: April 2019

As an optically transparent model organism with an endothelial blood-brain barrier (BBB), zebrafish offer a powerful tool to study the vertebrate BBB. However, the precise developmental profile of functional zebrafish BBB acquisition and the subcellular and molecular mechanisms governing the zebrafish BBB remain poorly characterized. Here we find a spatiotemporal gradient of barrier acquisition. Moreover, we capture the dynamics of developmental BBB leakage using live imaging, revealing a combination of steady accumulation in the parenchyma and sporadic bursts of tracer leakage. Electron microscopy studies further reveal that this steady accumulation results from high levels of transcytosis that are eventually suppressed, sealing the BBB. Finally, we demonstrate a key mammalian BBB regulator Mfsd2a, which inhibits transcytosis, plays a conserved role in zebrafish. Mfsd2aa mutants display increased larval and adult BBB permeability due to increased transcytosis. Our findings indicate a conserved developmental program of barrier acquisition between zebrafish and mice.
Real-time integration of cell death mechanisms and proliferation kinetics at the single-cell and population-level using high-throughput live-cell imaging
Authors: Gelles Jesse D. , Mohammed Jarvier N. , Santos Luis C. , Legarda Diana , Ting Adrian T. , Chipuk Jerry E.
Published: April 2019

Quantifying cytostatic and cytotoxic outcomes are integral components of characterizing perturbagens used as research tools and/or in drug discovery pipelines. Furthermore, data-rich acquisition coupled with robust methods for analysis is required to properly assess the function and impact of these perturbagens. Here, we present a detailed and versatile method for Single-cell and Population-level Analyses using Real-time Kinetic Labeling (SPARKL). SPARKL integrates high-content live-cell imaging with automated detection and analysis of fluorescent reporters of cell death. We outline several examples of zero-handling, non-disruptive protocols for detailing cell death mechanisms and proliferation profiles. Additionally, we suggest several methods for mathematically analyzing these data to best utilize the collected kinetic data. Compared to traditional methods of detection and analysis, SPARKL is more sensitive, accurate, and high-throughput while substantially eliminating sample processing and providing richer data.
Modeling the demography of species providing extended parental care: A capture-recapture multievent model with a case study on Polar Bears (Ursus maritimus)
Authors: Cubaynes Sarah , Aars Jon , Yoccoz Nigel G. , Pradel Roger , Wiig Øystein , Ims Rolf A , Gimenez Olivier
Published: April 2019

In species providing extended parental care, one or both parents care for altricial young over a period including more than one breeding season. We expect large parental investment and long-term dependency within family units to cause high variability in life trajectories among individuals with complex consequences at the population level. So far, models for estimating demographic parameters in free-ranging animal populations mostly ignore extended parental care, thereby limiting our understanding of its consequences on parents and offspring life histories.

We designed a capture-recapture multi-event model for studying the demography of species providing extended parental care. It handles statistical multiple-year dependency among individual demographic parameters grouped within family units, variable litter size, and uncertainty on the timing at offspring independence. It allows to evaluate trade-offs among demographic parameters, the influence of past reproductive history on the caring parent survival status, breeding probability and litter size probability, while accounting for imperfect detection of family units. We assess the model performances using simulated data, and illustrate its use with a long-term dataset collected on the Svalbard polar bears (Ursus maritimus).

Our model performed well in terms of bias and mean square error and in estimating demographic parameters in all simulated scenarios, both when offspring departure probability from the family unit occurred at a constant rate or varied during the field season depending on the date of capture. For the polar bear case study, we provide estimates of adult and dependent offspring survival rates, breeding probability and litter size probability. Results showed that the outcome of the previous reproduction influenced breeding probability.

Overall, our results show the importance of accounting for i) the multiple-year statistical dependency within family units, ii) uncertainty on the timing at offspring independence, and iii) past reproductive history of the caring parent. If ignored, estimates obtained for breeding probability, litter size, and survival can be biased. This is of interest in terms of conservation because species providing extended parental care are often long-living mammals vulnerable or threatened with extinction.
Dynamics of inhibitory control during bilingual speech production: An electrophysiological study
Authors: Zheng Xiaochen , Roelofs Ardi , Erkan Hasan , Lemhöfer Kristin
Published: April 2019

Bilingual speakers have to control their languages to avoid interference, which may be achieved by enhancing the target language and/or inhibiting the nontarget language. Previous research has provided evidence that bilinguals may use inhibition (e.g., Jackson, Swainson, Cunnington, & Jackson, 2001), which is reflected in the N2 component of the event-related potential (ERP). In the current study, we investigated the dynamics of inhibitory control by measuring the N2 during language switching and repetition in picture naming. We recorded the EEG of 30 unbalanced Dutch-English bilinguals in a cued language-switching task. Participants had to name pictures in Dutch or English depending on the cue. A run of same-language trials could be short (two or three trials) or long (five or six trials). We assessed whether RTs and N2 changed over the course of same-language runs, and at a switch between languages. Results showed that speakers named pictures more quickly late as compared to early in a run of same-language trials. Moreover, they made a language switch more quickly after a long run than after a short run. In ERPs, we observed a widely distributed switch effect in the N2, which was larger after a short run than after a long run. The N2 was not modulated during a same-language run, challenging Kleinman and Gollan (2018), who maintained that inhibition accumulates over time. Our results suggests that speakers adjust the level of inhibitory control at a language switch, but not when repeatedly naming in the same language.
Prevalence and determinants of neonatal danger signs in northwest Ethiopia: a multilevel analysis
Authors: Nigatu Tariku , Gebeyehu Abebaw , Worku Alemayehu , Andargie Gashaw , Tigabu Zemene
Published: April 2019

Background

There is association between neonatal danger signs and neonatal deaths. Hence, understanding the factors associated with the occurrence of neonatal danger signs help reduce the stagnating neonatal mortality in countries like Ethiopia.

Method

A cross sectional community and facility linked study was conducted in 39 kebeles in Amhara region, North Gondar Zone of Ethiopia from March 3-18, 2016. A representative sample of 1,150 mother-newborn pairs were included in the study. Percentage was used to calculate the prevalence. Multilevel analysis was used to identify individual and kebele level characteristics associated with the occurrence of neonatal danger signs.

Result

The result showed that around a quarter, 286 (24.9%), of the newborns experienced one or more danger signs during the neonatal period. Significant differences were found between groups/kebeles in the occurrence of danger signs. At individual level, having low birth weight (AOR= 0.65; 95% CI: 0.48-0.88) and maternal danger signs during pregnancy and delivery (AOR= 1.93; 95% CI: 1.41-2.65) were found to be significantly associated with the occurrence of neonatal danger signs. At group/kebele level, antenatal care coverage (AOR= 0.35; 95% CI: 0.13-0.93) and year of health extension workers experience (AOR= 0.91; 95 % CI: 0.84-0.99) were significantly associated with the occurrence of neonatal danger signs.

Conclusion

The prevalence of neonatal danger signs is high. There areindividual and kebele level characteristics associated with occurrence of danger signs in newborns. Expanding maternal health services and strengthening the health extension program is critical.
Understanding the molecular mechanism of umami recognition by T1R1-T1R3 using molecular dynamics simulations
Authors: Liu Hai , Da Lin-Tai , Liu Yuan
Published: April 2019

Taste receptor T1R1-T1R3 can be activated by binding to several natural ligands, e.g., L-glutamate and 5’-ribonucleotides etc., thereby stimulating the umami taste. The molecular mechanism of umami recognition at an atomic level, however, remains elusive. Here, using homology modeling, molecular docking and molecular dynamics (MD) simulations, we investigate the effects of five natural umami ligands on the structural dynamics of T1R1-T1R3. Our work identifies the key residues that are directly involved in recognizing the binding ligands. In addition, two adjacent binding sites in T1R1 are determined for substrate binding, and depending on the molecular size and chemical properties of the incoming ligand, one or both these binding sites can be occupied. More interestingly, the binding of varied ligands can lead to either closing or opening of T1R1, based on which, we further classify the five ligands into two groups. This different binding effects are likely associated with the distinct umami signals stimulated by various ligands. This work warrants new experimental assays to further validate the theoretical model and provides guidance to design more effective umami ligands.

Author summary

Umami, as the fifth basic taste, is induced by umami substances from the natural food, such as L-glutamate, 5’-ribonucleotides, and peptides etc. These umami substances are widely added to foods as flavor enhancers to promote food quality. However, although extensive experimental and theoretical studies have been devoted to revealing the recognition mechanisms of the taste receptor T1R1-T1R3 to the umami ligands, the detailed molecular mechanism is still unknown, largely due to the lack of the receptor structure. Here, using a new template structure different from the former theoretical studies, we constructed a more accurate homology model of T1R1-T1R3. Based on this receptor model, combined with molecular docking and MD simulations, we investigate how different ligands with varied molecular size and chemical groups might affect the dynamics of T1R1. Our work provides the structural basis for relating the dynamics of umami receptor induced by varied ligands to the resulting umami signal.
Crystal structure of 4,5,6,7,8,8-hexachloro-2-(3,4-dimethoxyphenethyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione [+solvent]
Authors: Manohar R. , Harikrishna M. , Etti S. Harikrishna , Ramanathan C. , Gunasekaran K.
Published: April 2019

In the title compound, C19H15Cl6NO4 [+solvent], the six-membered ring of the norbornene moiety adopts a boat conformation and the two five-membered rings have envelope conformations. The pyrrolidine ring makes a dihedral angle of 14.83 (12)° with the 3,4-dimethoxyphenyl ring, which are attached to each other by an extended N—CH2—CH2—Car bridge. In the crystal, the structure features C—H...O intermolecular hydrogen bonds, an offset π–π interaction [intercentroid distance = 3.564 (1) Å] and a C—Cl...π interaction. The contribution of some disordered solvent to the scattering was removed using the SQUEEZE routine [Spek (2015). Acta Cryst. C71, 9–18] of PLATON. The solvent contribution was not included in the reported molecular weight and density.
Crystal engineering with short-chained amphiphiles: decasodium octa-n-butanesulfonate di-μ-chlorido-bis[dichloridopalladate(II)] tetrahydrate, a layered inorganic–organic hybrid material
Authors: Thoelen Felix , Frank Walter
Published: April 2019

In the course of crystal-engineering experiments, crystals of the hydrated title salt, Na10[Pd2Cl6](C4H9SO3)8·4H2O, were obtained from a water/2-propanol solution of sodium n-butanesulfonate and sodium tetrachloridopalladate(II). In the crystal, sodium n-butanesulfonate anions and water molecules are arranged in an amphiphilic inverse bilayered cationic array represented by the formula {[Na10(C4H9SO3)8(H2O)4]2+}
n
. Within this lamellar array: (i) a hydrophilic layer region parallel to the bc plane is established by the Na+ cations, the H2O molecules (as aqua ligands in κNa,κNa′-bridging coordination mode) and the O3S– groups of the sulfonate ions, and (ii) hydrophobic regions are present containing all the n-butyl groups in an almost parallel orientation, with the chain direction approximately perpendicular to the aforementioned hydrophilic layer. Unexpectedly, the flat centrosymmetric [Pd2Cl6]2− anion in the structure is placed between the butyl groups, within the hydrophobic regions, but due to its appropriate length primarily bonded to the hydrophilic `inorganic' layer regions above and below the hydrophobic area via Pd—Clt...Na- and Pd—Clt...H—O(H)—Na-type (Clt is terminal chloride) interactions. In addition to these hydrogen-bonding interactions, both aqua ligands are engaged in charge-supported S—O...H—O hydrogen bonds of a motif characterized by the D
4
3(9) graph-set descriptor within the hydrophilic region. The crystal structure of the title compound is the first reported for a metal n-butanesulfonate.
A triclinic polymorph of N-[5-(diphenylamino)penta-2,4-diyn-1-yl]benzamide
Authors: Ozaki Koji , Okuno Tsunehisa
Published: April 2019

The title compound, C24H18N2O, was been described previously in the space group P21/c with Z = 4 [Kawashima & Okuno (2017). IUCrData, 2, x170277]. The current P\overline{1} polymorph was obtained from a chloroform–ethanol solution. The molecular structure in this polymorph is slightly different from the previously reported structure, with different dihedral angles of the two N-phenyl groups to the ynamine plane; these are 79.99 (11) and 12.09 (11)° in the polymorph reported here. The molecules form dimers through four C—H...π interactions. Furthermore, in this polymorph, the molecules stack along the a axis to form a molecular arrangement that would be suitable to promote the solid-state polymerization of diacetylenes.
Dynamic stability analysis of a tracked mobile robot based on human–robot interaction
Authors: Zong Chengguo , Ji Zhijian , Yu Haisheng
Published: April 2019

Purpose

This paper aims to provide a theoretical principle for the stability control of robot climbing stairs, autonomously based on human–robot interaction. Through this research, tracked mobile robots with human-robot interaction will be extensively used in rescue in disaster, exploration on planetary, fighting in battle, and searching for survivors in collapsed buildings.

Design/methodology/approach

This paper introduces the tracked mobile robot, based on human–robot interaction, and its six moving postures. The dynamic process of climbing stairs is analyzed, and the dynamic model of the robot is proposed. The dynamic stability criterion is derived when the tracked mobile robot contacts the stairs steps in one, two and more points. A further conduction of simulation on the relationship of the traction force and bearing force vs the velocity and acceleration in the three cases was carried out.

Findings

This paper explains that the tracked mobile robot, based on human–robot interaction, can stably climb stairs so long as the velocity and acceleration satisfy the dynamic stability criterion as noted above. In addition, the experiment tests the correctness of dynamic stability analysis when the tracked mobile robot contacts the stair steps in one, two or more points.

Originality/value

This paper provides the mechanical structure and working principle of the tracked mobile robot based on human–robot interaction and proposes an identification method of dynamic stability criterion when the robot contacts the stairs steps in one, two and more points.
Dynamic framework transfer model for public–private partnerships
Authors: Bao Fengyu , Chen Chuan , Chan Albert P.C. , Martek Igor , Shrestha Asheem
Published: April 2019

Purpose

Public–private partnerships (PPPs) have emerged in developing countries, such as China, as a ubiquitous means by which government procures needed infrastructure. In this regard, they have been much studied. However, due to their long concession period, running into decades, few have run their full course into the transfer phase (TP) in which the PPP concession reverts from the private entity back to the public. In China, this is about to change as many PPPs approach their TP. Hence, the purpose of this paper is to comprehensively investigate the TP of PPPs in China.

Design/methodology/approach

A three-part methodology was undertaken to achieve the research purpose. Extensive literature review was first conducted to analyze the status quo of the transfer management regime in China, followed by the identification of critical challenges and the exploration of solutions via studying the TP of the Chengdu No. 6 Water Plant B Project – the first PPP in China’s water sector to reach the TP. Research procedures and outcomes were hierarchically visualized by using Integration DEFinition language 0 (IDEF0) method.

Findings

The current transfer management regime of PPPs in China’s water sector is deficient in many aspects. Based on the insight into the practice, a generic transfer process model with hierarchical structure process and sub-processes serving as a dynamic framework transfer model with self-evolving nature is developed to facilitate the successful transfer of the PPP utility.

Originality/value

To the authors’ best knowledge, this is the first attempt to systematically probe the TP of PPPs. Hopefully, the findings of this paper are to instruct government and PPP practitioners alike on mechanisms for smoothing the TP of further PPP projects ending their concession period.
Description–experience gap under imperfect information
Authors: Du Jing , Wang Qi , Shi Qian
Published: April 2019

Purpose

Capital project delivery, such as the delivery of transportation networks and industrial facilities, often suffers losses due to overly aggressive planning. Planners often are overly optimistic about the chance of success while underestimating risks. The purpose of this paper is to examine the hypothesis that these biases are from the difficulties most decision makers face when interpreting probabilistic information.

Design/methodology/approach

Three behavioral experiments were conducted to test the theoretical fitness of the paradigms proposed by the description–experience gap literature, namely, the sampling errors effect, the recency effect and statistical information format. College students were recruited to participate in a series of estimating tasks. And their estimating results were compared given different levels of information completeness.

Findings

It was found that the existing paradigms could predict risk decision making in the risk-averse estimating scenarios where test subjects were required to give a relatively conservative estimate, but they seemed to be less effective in predicting decisions in the risk-seeking estimating scenario, where test subjects were asked to give a relatively aggressive estimate.

Originality/value

Based on these findings, an integrative model is proposed to explain the observations pertaining to aggressive planning in capital projects. Two dimensions are deemed to be relevant: including risk-taking intentions, and an information uncertainty continuum that ranges from an implicit experience-based information representation to an explicit description-based information representation.