bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoacoustic pigment relocalization sensor
Authors: Lauri Antonella , Soliman Dominik , Omar Murad , Stelzl Anja , Ntziachristos Vasilis , Westmeyer Gil G.
Published: October 2018

Photoacoustic (optoacoustic) imaging can extract molecular information with deeper tissue penetration than possible by fluorescence microscopy techniques. However, there is currently still a lack of robust genetically controlled contrast agents and molecular sensors that can dynamically detect biological analytes of interest with photoacoustics. In this biomimetic approach, we took inspiration from cuttlefish who can change their color by relocalizing pigment-filled organelles in so-called chromatophore cells under neurohumoral control. Analogously, we tested the use of melanophore cells from Xenopus laevis, containing compartments (melanosomes) filled with strongly absorbing melanin, as whole-cell sensors for optoacoustic imaging. Our results show that pigment relocalization in these cells, which is dependent on binding of a ligand of interest to a specific G protein-coupled receptor (GPCR), can be monitored in vitro and in vivo using photoacoustic mesoscopy. In addition to changes in the photoacoustic signal amplitudes, we could furthermore detect the melanosome aggregation process by a change in the frequency content of the photoacoustic signals. Using bioinspired engineering, we thus introduce a photoacoustic pigment relocalization sensor (PaPiReS) for molecular photoacoustic imaging of GPCR-mediated signaling molecules.
Retinotopic maps of visual space in the human cerebellum
Authors: van Es D.M. , van der Zwaag W. , Knapen T.
Published: October 2018

While the cerebellum is instrumental for motor control, it is not traditionally implicated in vision. Here, we report the existence of 5 ipsilateral visual field maps in the human cerebellum. These maps are located within the oculomotor vermis and cerebellar nodes of the dorsal attention and visual networks. These findings imply that the cerebellum is closely involved in visuospatial cognition, and that its contributions are anchored in sensory coordinates.
The development of social interactions inCorydoras aeneuslarvae
Authors: Riley RJ , Roe T , Gillie ER , Boogert NJ , Manica A
Published: October 2018

Very young animals develop life skills as they mature, and for social animals this includes the acquisition of social abilities such as communication. Many animals exhibit changeable patterns of social behavior based on development, and social experience during the juvenile period can be vital for the development of necessary social behaviors in adulthood. We investigated the development of a distinctive tactile interaction behavior inCorydoras aeneus, the Bronze Cory catfish. Adults use this behavior to coordinate group activities during foraging and flight responses from predators, and the development of this behavior in larvae is of interest in investigating how communication and social behaviors develop as an individual matures, and which factors affect their development. We found that larvae respond to applied tactile stimulation with a flight response far less often as larvae matured, implying that larvae become less sensitive to tactile stimulation with age. Given that adults frequently interact with one another tactilely, this development is consistent with developing appropriate social behavior in adulthood. We also found that social exposure affects the development of the larval response to tactile interactions with conspecifics, and that isolation in the earliest larval stage leads to a greater likelihood of responding to a tactile interaction with a conspecific with a flight response. This suggests that social exposure is important for developing an appropriate response to tactile stimulation in social settings and underscores the particular importance of early life experiences in the development of sociality.
Novel insights into the genetic relationship between growth and disease resistance in Pacific salmon
Authors: Barría Agustin , Doeschl-Wilson Andrea. B. , Lhorente Jean P. , Houston Ross. D. , Yáñez José. M.
Published: October 2018

Background

Breeding for disease resistance has become a highly desirable strategy for mitigating infectious disease problems in aquaculture. However, knowledge of the genetic relationship between resistance and other economically important traits, such as growth, is important to assess prior to including disease resistance into the breeding goal. Our study assessed the genetic correlations between growth and survival traits in a large bacterial infection challenge experiment. A population of 2,606 coho salmon individuals from 107 full-sibling families were challenged with the bacteria Piscirickettsia salmonis. Growth was measured as average daily gain prior (ADG0) and during (ADGi) the experimental infection and as harvest weight (HW). Resistance was measured as Survival time (ST) and binary survival (BS). Furthermore, individual measures of bacterial load (BL) were assessed as new resistance phenotypes and to provide an indication of genetic variation in tolerance in salmonid species.

Results

Significant moderate heritabilities were estimated for ADG0 (0.30 ± 0.05), HW (0.38 ± 0.03), and for the survival traits ST (0.16 ± 0.03) and BS (0.18 ± 0.03). In contrast, heritabilities for ADGi and log-transformed BL were low (0.07 ± 0.02 (significant) and 0.04 ± 0.03, respectively), although these increased to moderate significant levels (0.20 ± 0.09 and 0.12 ± 0.05, respectively) when traits were assessed in survivors only. Significant and favorable genetic correlations were found between ADG0 and the growth traits ADGi (0.40 ± 0.16) and HW (0.64 ± 0.09), as well as with resistance as ST (0.43 ± 0.18), indicating that fish with higher genetic growth rate early on and prior to infection not only tend to maintain their genetic growth advantage until harvest, but also tend to grow faster and survive longer during infection. Furthermore, no robust unfavorable genetic correlations between ADG0 and any of the other traits considered in this study, in particular BL, was identified. Adding log BL as covariates into the models for growth under infection and survival provided an indication for genetic variation in tolerance.

Conclusions

These results suggest that selective breeding for early growth would be expected to simultaneously increase survival time and growth performance during an infection with Piscirickettsia salmonis after accounting for variation in bacterial load, and harvest weight in this coho salmon population, without negatively impacting on pathogen burden.
Bioinorganic Angiogenesis
Authors: Maillard Sophie , Charbonnier Baptiste , Sayed Omaer , Baradaran Aslan , Manga Harshdeep , Dallison Benjamin , Zhang Zishuai , Zhang Yu Ling , Hussain Sabah N.A. , Mayaki Dominique , Seitz Hermann , Harvey Edward J. , Gilardino Mirko , Gbureck Uwe , Makhoul Nicholas , Barralet Jake
Published: October 2018

Causing a large diameter blood vessel to sprout branches and a capillary network on demand to create a new angiosome is key to harnessing to potential of regenerative medicine and advancing reconstructive surgery. Currently this can only be achieved by connecting a vein graft to an artery by microsurgery, the arteriovenous loop technique (AVL). The arterial blood pressure in the thin-walled vein is thought to drive remodelling to create branches, however the surgical complexity limits the application of the technique. In this study we demonstrate that unexpectedly, a vessel density of luminal branches in excess of that achieved by the surgical AVL approach can be induced simply by placing a vein in contact with a microporous calcium phosphate. Only osteoinductive biomaterials have been reported previously, this is thought to be the first report of an angio-inductive material. Pilot studies indicated that the material type greatly affected the degree of luminal vascularization. Material contact with the vein is not a requirement for luminal angiogenesis of the vein and together these findings point to a bioinorganic effect, wherein the degradation of the material both releases a stimulatory ionic milieu and creates space for the developing angiosome.
Characterising Genetic Diversity in Cassava Brown Streak Virus
Authors: Crotty Stephen M , Rohrlach Adam B , Ndunguru Joseph , Boykin Laura M
Published: October 2018

Plant viruses represent a significant threat to food security for many global populations. Cassava Brown Streak Virus (CBSV) causes immense damage to cassava crops in Eastern, Central and Southern Africa. The eradication of CBSV is a difficult challenge, as it has been shown to be fast-evolving and it is transmitted by flying insects that are ubiquitous in cassava growing regions. In this paper we demonstrate the ability of two new developments in bioinformatics that can be used to increase our understanding of CBSV and ultimately inform strategies for its combat. We reconstruct the phylogeny of 29 whole-genome virus isolates using the GHOST model. This phylogeny identifies three distinct clades among the viruses and highlights a section of the genomes that is highly influential in their divergence. We also perform Multiple Correspondence Analysis on the alignment which is consistent in recovering the three clades, and offers insight on the significance of the influence of a variety of external variables on the evolution of the viruses. Knowledge and information from this analysis will be used as a base on which to formulate sustainable Cassava Brown Streak Disease (CBSD) management strategies in Africa.
Multi-SNP Mediation Intersection-Union Test
Authors: Zhong Wujuan , Spracklen Cassandra N. , Mohlke Karen L. , Zheng Xiaojing , Fine Jason , Li Yun
Published: October 2018

Tens of thousands of reproducibly identified GWAS (Genome-Wide Association Studies) variants, with the vast majority falling in non-coding regions resulting in no eventual protein products, call urgently for mechanistic interpretations. Although numerous methods exist, there are few, if any methods, for simultaneously testing the mediation effects of multiple correlated SNPs via some mediator (for example, the expression of a gene in the neighborhood) on phenotypic outcome. We propose SMUT, multi-SNPMediation intersection-UnionTest to fill in this methodological gap. Our extensive simulations demonstrate the validity of SMUT as well as substantial, up to 92%, power gains over alternative methods. In addition, SMUT confirmed known mediators in a real dataset of Finns for plasma adiponectin level, which were missed by many alternative methods. We believe SMUT will become a useful tool to generate mechanistic hypotheses underlying GWAS variants, facilitating functional follow-up. The R package SMUT is publicly available from CRAN athttps://CRAN.R-project.org/package=SMUT.
Reprogramming the antigen specificity of B cells using genomeediting technologies
Authors: Voss James E. , Gonzalez-Martin Alicia , Andrabi Raiees , Fuller Roberta P. , Murrell Ben , McCoy Laura E. , Porter Katelyn , Huang Deli , Li Wenjuan , Sok Devin , Le Khoa , Briney Bryan , Chateau Morgan , Rogers Geoffrey , Hangartner Lars , Feeney Ann J. , Nemazee David , Cannon Paula , Burton Dennis R.
Published: October 2018

We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repair strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV broadly neutralizing antibody, PG9. Our strategy is designed to function in cells that have undergone VDJ recombination using any combination of variable (V), diversity (D) and joining (J) genes. The modified locus expresses PG9 HC which pairs with native light chains resulting in the cell surface expression of HIV specific B cell receptors (BCRs). Endogenous activation-induced cytidine deaminase (AID) in engineered cells allowed for Ig class switching and generated BCR variants with improved anti-HIV neutralizing activity. Thus, BCRs engineered in this way retain the genetic flexibility normally required for affinity maturation during adaptive immune responses.
Phylodynamics of rapidly adapting pathogens: extinction and speciation of a Red Queen
Authors: Yan Le , Neher Richard A. , Shraiman Boris I.
Published: October 2018

Rapidly evolving pathogens like influenza viruses can persist by accumulating antigenic novelty fast enough to evade the adaptive immunity of the host population, yet without continuous accumulation of genetic diversity. This dynamical state is often compared to the Red Queen evolving as fast as it can just to maintain its foothold in the host population: Accumulation of antigenic novelty is balanced by the build-up of host immunity. Such Red Queen States (RQS) of continuous adaptation in large rapidly mutating populations are well understood in terms of Traveling Wave (TW) theories of population genetics. Here we shall make explicit the mapping of the established Multi-strain Susceptible-Infected-Recovered (SIR) model onto the TW theory and demonstrate that a pathogen can persist in RQS if cross-immunity is long-ranged and its population size is large populations allowing for rapid adaptation. We then investigate the stability of this state focusing on the rate of extinction and the rate of “speciation” defined as antigenic divergence of viral strains beyond the range of cross-inhibition. RQS states are transient, but in a certain range of evolutionary parameters can exist for the time long compared to the typical time to the most recent common ancestor (TMRCA). In this range the steady TW is unstable and the antigenic advance of the lead strains relative to the typical co-circulating viruses tends to oscillate. This results in large fluctuations in prevalence that facilitate extinction. We shall demonstrate that the rate of TW fission into antigenically uncoupled viral populations is related to fluctuations of TMRCA and construct a “phase diagram” identifying different regimes of viral phylodynamics as a function of evolutionary parameters.
Use of a corneal impression membrane for the detection of Herpes Simplex Virus type-1
Authors: Brunner Matthias , Somerville Tobi , Corless Caroline E , Myneni Jayavani , Rajhbeharrysingh Tara , Tiew Stephenie , Neal Timothy , Kaye Stephen B.
Published: October 2018

Purpose

To investigate the use of a corneal impression membrane (CIM) for the detection of Herpes Simplex Virus type 1 (HSV-1) in suspected Herpes Simplex Keratitis (HSK).

Materials and Methods

In the laboratory study, swabs and CIMs made from polytetrafluoroethylene were spiked with different concentrations of HSV-1. DNA was extracted and real time PCR undertaken using 2 sets of primers. In the clinical study consecutive patients presenting with suspected HSK were included. For each patient, samples were collected from corneal lesions with a swab and a CIM in random order. Clinical details were collected using a standardised clinical form and patients were categorized into probable, presumed and possible HSK.

Results

There was no difference in the performance of both primer sets for all HSV-1 dilutions (p=0.83) or between a CIM and a swab (p=0.18). 110 patients were included. Seventy-three patients (66.4%) had probable, 20 patients (18.2%) presumed, and 17 patients (15.5%) possible HSV-1 keratitis. The HSV-1 detection rate was significantly higher using a CIM (40/110, 36.4%) than a swab (28/110, 25.5%) (p=0.004). In the probable HSV keratitis group, the detection rate using a CIM was 43.8% compared to 27.4% for a swab (p=0.004). The Cp values obtained for the conjunctival swabs were higher than those obtained for the CIMs (p<0.001).

Conclusions

In suspected HSK, a CIM is a useful alternative to a swab and more likely to detect the presence of HSV-1.
A novel real-time PCR assay panel for detection of common respiratory pathogens in a convenient, strip-tube array format
Authors: Hasan Mohammad Rubayet , Mana Hassan Al , Young Virginia , Tang Patrick , Thomas Eva , Tan Rusung , Tilley Peter
Published: October 2018

Commercial multiplex assays, built on different chemistries and platforms are widely available for simultaneous detection of pathogens that cause respiratory infections. However, these tests are often difficult to implement in a resource limited setting because of high cost. In this study, we developed and validated a method for simultaneous testing of common respiratory pathogens (Respanel) by real-time PCR in a convenient, strip-tube array format. Primers and probes for sixteen PCR assays were selected from the literature or newly designed. Following optimization of individual PCR assays, strip-tube arrays were prepared by dispensing primer-probe mixes (PPM) into two sets of 8-tube strips. Nucleic acid extracts from specimens were mixed with PCR master mix, and dispensed column-wise into 2X8-wells of a 96-well plate. PPMs from strip-tubes were then added to the wells using a multichannel pipette for real-time PCR. Individual PCR assays were optimized using previously known specimens (n=397) with 91%-100% concordance with culture, DFA or PCR results. Respanel was then tested in a routine manner at two different sites using specimens (n=147) previously tested by Qiagen Resplex I&II or Fast-Track Diagnostics Respiratory Pathogens 21 assays. The sensitivity, specificity and accuracy of Respanel were 94%, 95% and 95%, respectively, against Resplex and 88%, 100% and 99%, respectively, against FTDRP21. Respanel detected 48% more pathogens (p<0.05) than Resplex but the rate of pathogen detection was not significantly different from FTDRP21. Respanel is a convenient and inexpensive assay that is more sensitive than Resplex and comparable to FTDRP21 for the detection of common respiratory pathogens.
Intra-Nuclear Tensile Strain Mediates Reorganization of Epigenetically Marked Chromatin During Cardiac Development and Disease
Authors: Seelbinder Benjamin , Ghosh Soham , Berman Alycia G. , Schneider Stephanie E. , Goergen Craig J. , Calve Sarah , Neu Corey P.
Published: October 2018

Environmental mechanical cues are critical to guide cell fate. Forces transmit to the nucleus through the Linker of Nucleo- and Cytoskeleton (LINC) complex and are thought to influence the organization of chromatin that is related to cell differentiation; however, the underlying mechanisms are unclear. Here, we investigated chromatin reorganization during murine cardiac development and found that cardiomyocytes establish a distinct architecture characterized by relocation of H3K9me3-modified chromatin from the nuclear interior to the periphery and co-localization to myofibrils. This effect was abrogated in stiff environments that inhibited cardiomyocyte contractility, or after LINC complex disruption, and resulted in the relocation of H3K27me3-modified chromatin instead. By generating high-resolution intra-nuclear strain maps during cardiomyocyte contraction, we discovered that the reorganization of H3K9me3-marked chromatin is influenced by tensile, but not compressive, nuclear strains. Our findings highlight a new role for nuclear mechanosensation in guiding cell fate through chromatin reorganization in response to environmental cues.
Drug-Target Interaction prediction using Multi Graph Regularized Nuclear Norm Minimization
Authors: Mongia Aanchal , Majumdar Angshul
Published: October 2018

The identification of interactions between drugs and target proteins is crucial in pharmaceutical sciences. The experimental validation of interactions in genomic drug discovery is laborious and expensive; hence, there is a need for efficient and accurate in-silico techniques which can predict potential drug-target interactions to narrow down the search space for experimental verification.

In this work, we propose a new framework, namely, Multi Graph Regularized Nuclear Norm Minimization, which predicts the interactions between drugs and proteins from three inputs: known drug-target interaction network, similarities over drugs and those over targets. The proposed method focuses on finding a low-rank interaction matrix that is structured by the proximities of drugs and targets encoded by graphs. Previous works on Drug Target Interaction (DTI) prediction have shown that incorporating drug and target similarities helps in learning the data manifold better by preserving the local geometries of the original data. But, there is no clear consensus on which kind and what combination of similarities would best assist the prediction task. Hence, we propose to use various multiple drug-drug similarities and target-target similarities as multiple graph Laplacian (over drugs/targets) regularization terms to capture the proximities exhaustively.

Extensive cross-validation experiments on four benchmark datasets using standard evaluation metrics (AUPR and AUC) show that the proposed algorithm improves the predictive performance and outperforms recent state-of-the-art computational methods by a large margin.

Author summary

This work introduces a computational approach, namely Multi-Graph Regularized Nuclear Norm Minimization (MGRNNM), to predict potential interactions between drugs and targets. The novelty of MGRNNM lies in structuring drug-target interactions by multiple proximities of drugs and targets. There have been previous works which have graph regularized Matrix factorization and Matrix completion algorithms to incorporate the standard chemical structure drug similarity and genomic sequence target protein similarity, respectively. We introduce multiple drug-graph laplacian and target-graph laplacian regularization terms to the standard matrix completion framework to predict the missing values in the interaction matrix. The graph Laplacian terms are constructed from various kinds and combinations of similarities over drugs and targets (computed from the interaction matrix itself). In addition to this, we further improve the prediction accuracy by sparsifying the drug and target similarity matrices, respectively. For performance evaluation, we conducted extensive experiments on four benchmark datasets. The experimental results demonstrated that MGRNNM clearly outperforms recent state-of-the-art methods under three different cross-validation settings, in terms of the area under the ROC curve (AUC) and the area under the precision-recall curve (AUPR).
An integrative machine learning approach for prediction of toxicity-related drug safety
Authors: Lysenko Artem , Sharma Alok , Boroevich Keith A , Tsunoda Tatsuhiko
Published: October 2018

Recent trends in drug development have been marked by diminishing returns of escalating costs and falling rate of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials as well as the leading cause of drug withdraws after release to market. Computational methods capable of predicting these failures can reduce waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity. We demonstrate that our method (TargeTox) can distinguish potentially idiosyncratically toxic drugs from safe drugs and is also suitable for speculative evaluation of different target sets to support the design of optimal low-toxicity combinations.

Summary blurb:

Prediction of toxicity-related drug clinical trial failures, withdrawals from market and idiosyncratic toxicity risk by combining biological network analysis with machine learning.
Altered BOLD signal variation in Alzheimer’s disease and frontotemporal dementia
Authors: Tuovinen Timo , Kananen Janne , Rytty Riikka , Moilanen Virpi , Elseoud Ahmed Abou , Remes Anne M , Kiviniemi Vesa ,   ADNI
Published: October 2018

Recently discovered glymphatic brain clearance mechanisms utilizing physiological pulsations have been shown to fail at removing waste materials such as amyloid and tau plaques in neurodegenerative diseases. Since cardiovascular pulsations are a main driving force of the clearance, this research investigates if commonly available blood oxygen level-dependent (BOLD) signals at 1.5 and 3 T could detect abnormal physiological pulsations in neurodegenerative diseases. Coefficient of variation in BOLD signal (CVBOLD) was used to estimate contribution of physiological signals in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). 17 AD patients and 18 bvFTD patients were compared to 24 control subjects imaged with a 1.5 T setup from a local institute. AD results were further verified with 3 T data from the Alzheimer’s disease neuroimaging initiative (ADNI) repository with 30 AD patients and 40 matched controls. Effect of motion and gray matter atrophy was evaluated and receiver operating characteristic (ROC) analyses was performed.

The CVBOLD was higher in both AD and bvFTD groups compared to controls (p < 0.0005). The difference was not explained by head motion or gray matter atrophy. In AD patients, the CVBOLD alterations were localized in overlapping structures in both 1.5 T and 3 T data. Localization of the CVBOLD alterations was different in AD than in bvFTD. Areas where CVBOLD is higher in patient groups than in control group involved periventricular white matter, basal ganglia and multiple cortical structures. Notably, a robust difference between AD and bvFTD groups was found in the CVBOLD of frontal poles. In the analysis of diagnostic accuracy, the CVBOLD metrics area under the ROC for detecting disease ranged 0.85 – 0.96.

Conclusions

The analysis of brain physiological pulsations measured using CVBOLD reveals disease-specific alterations in both AD and bvFTD.
Functionally Coherent Transcription Factor Target Networks Illuminate Control of Epithelial Remodelling
Authors: Overton Ian M. , Sims Andrew H. , Owen Jeremy A. , Heale Bret S. E. , Ford Matthew J. , Lubbock Alexander L. R. , Pairo-Castineira Erola , Essafi Abdelkader
Published: October 2018

Cell identity is governed by gene expression, regulated by Transcription Factor (TF) binding at cis-regulatory modules. We developed the NetNC software to decode the relationship between TF binding and the regulation of cognate target genes in cell decision-making; demonstrated on nine datasets for the Snail and Twist TFs, and also modENCODE ‘HOT’ regions. Results illuminated conserved molecular networks controlling development and disease, with implications for precision medicine. Predicted ‘neutral’ TF binding accounted for the majority (50% to ≥80%) of candidate target genes from statistically significant peaks and HOT regions had high functional coherence. Expression of orthologous functional TF targets discriminated breast cancer molecular subtypes and predicted novel tumour biology. We identified new gene functions and network modules including crosstalk with notch signalling and regulation of chromatin organisation, evidencing networks that reshape Waddington’s landscape during epithelial remodelling. Predicted invasion roleswere validated using a tractable cell model, supporting our computational approach.
TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation
Authors: Ferrari Roberto , de Llobet Cucalon Lara Isabel , Di Vona Chiara , Le Dilly François , Vidal Enrique , Lioutas Antonios , Oliete Javier Quilez , Jochem Laura , Cutts Erin , Dieci Giorgio , Vannini Alessandro , Teichmann Martin , de la Luna Susana , Beato Miguel
Published: October 2018

Summary paragraph

The mammalian genome is shaped by the expansion of repetitive elements that provide new regulatory networks for coordinated control of gene expression1 and genome folding2–4. Alu elements (AEs) are selectively retained close to the transcription start site of genes5, show protoenhancer functions6, correlate with the level of chromatin interactions7 and are recognized by transcription factor III (TFIIIC)8, but the relevance of all this is not clear. Here we report regulatory mechanisms that unveil a central role of AEs and TFIIIC in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of pre-marked AEs near cell cycle genes recruit TFIIIC to alter their chromatin accessibility via TFIIIC-mediated acetylation of histone H3 Lysine-18 (H3K18). This facilitates AEs contact with distant CTCF sites near other cell cycle genes promoters, which also become hyperacetylated at H3K18. These changes ensure basal transcription of crucial cell cycle genes, and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor adjusts 3D genome folding and gene expression. We anticipate that expansion of several families of repetitive elements during evolution might have served to generate new genomic cis-regulatory circuits enabling the coordinated regulation of a large set of genes relevant for cellular stress survival. As growth factor withdrawal is a situation relevant in cancer biology, our study identifies TFIIIC as a new potential target for clinical intervention.
Multipoint and large volume fiber photometry with a single tapered optical fiber implant
Authors: Pisano Filippo , Pisanello Marco , Maglie Emanuela , Balena Antonio , Sileo Leonardo , Spagnolo Barbara , Hyun Minsuk , De Vittorio Massimo , Sabatini Bernardo L. , Pisanello Ferruccio
Published: October 2018

Techniques to monitor functional fluorescence signal from the brain are increasingly popular in the neuroscience community. However, most implementations are based on flat cleaved optical fibers (FFs) that can only interface with shallow tissue volumes adjacent to the fiber opening. To circumvent this limitation, we exploit modal properties of tapered optical fibers (TFs) to structure light collection over the wide optically active area of the fiber taper, providing an approach to efficiently and selectively collect light from the region(s) of interest. While being less invasive than FFs, TF probes can uniformly collect light over up to 2 mm of tissue and allow for multisite photometry along the taper. Furthermore, by micro-structuring the non-planar surface of the fiber taper, collection volumes from TFs can also be engineered arbitrarily in both shape and size. Owing to the abilities offered by these probes, we envision that TFs can set a novel, powerful paradigm in optically targeting not only the deep brain, but, more in general, any biological system or organ where light collection from the deep tissues is beneficial but challenging because of tissue scattering and absorption.
Comparative analysis of cellular immune responses in conventional and SPF Baboons (Papio spp.)
Authors: Magden Elizabeth R , Nehete Bharti P. , Chitta Sriram , Williams Lawrence E. , Simmons Joe H , Abee Christian R. , Nehete Pramod N.
Published: October 2018

Baboons (papio spp.) have served as a successful model of human disease such as cardiac and respiratory, infectious, diabetes, genetics, immunology, aging, and xenotransplantation. The development of an immunologically defined specific-pathogen free (SPF) baboon model has further advanced research, especially with studies involving the immune system and immunosuppression. In this study, we compare normal immunological changes of peripheral blood mononuclear cell (PBMC) subsets, and their function in age-matched conventional and SPF baboons. Our results demonstrate that both groups have comparable numbers of different lymphocyte subsets, but there are phenotypic differences in central and effector memory T cells subsets that are more pronounced in the CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboon groups, PBMC show higher proliferative responses to mitogens PHA and PWM and higher IFN-γ producing cells to Con A and PWM in the conventional group. Plasma levels of the inflammatory cytokine TNF-α were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll like ligands (TLR ligands) TLR-3, TLR-4 and TLR-8 show higher IFN-γ producing cells while PBMC from SPF baboons stimulated with TLR-5 and TLR-6 ligand show higher IFN-γ producing cells. These findings suggest that while the lymphocyte subsets in conventional and SPF baboons share many phenotypic and functional similarities, specific differences exist in immune function of lymphocytes which could impact the quality and quantity of innate and adaptive immune responses. These differences should be considered for better experimental outcomes, specifically in studies measuring immunological endpoints.
Salivary and plasma levels of matrix metalloproteinase-9 and myeloperoxidase at rest and after acute physical exercise in patients with coronary artery disease
Authors: Mahmood Zeid , Enocsson Helena , Bäck Maria , Lundberg Anna K , Jonasson Lena
Published: October 2018

Background

Low-grade systemic inflammation is a predictor of recurrent cardiac events in patients with coronary artery disease (CAD). Plasma proteins such as matrix metalloproteinase (MMP)-9 and myeloperoxidase (MPO) have been shown to reflect basal as well as stress-induced inflammation in CAD. Measurements of MMP-9 and MPO in saliva might pose several advantages. Therefore, we investigated whether salivary levels of MMP-9 and MPO corresponded to plasma levels in patients with CAD, both at rest and after acute physical exercise.

Methods

An acute bout of physical exercise on a bicycle ergometer was used as a model for stress-induced inflammation. Twenty-three CAD patients performed the test on two occasions 3-6 months apart. Whole unstimulated saliva was collected before, directly after and 30 min after exercise while plasma was collected before and after 30 min. MMP-9 and MPO in saliva and plasma were determined by Luminex.

Results

MMP-9 and MPO levels were 2- to 4-fold higher in saliva than in plasma. Within the saliva compartment, and also to a great extent within the plasma compartments, MMP-9 and MPO showed strong intercorrelations at all time points. However, there were no (or weak) correlations between salivary and plasma MMP-9 and none between salivary and plasma MPO.

Conclusion

We conclude that salivary diagnostics cannot be used to assess systemic levels of MMP-9 and MPO in CAD patients, neither at rest nor after acute physical exercise.
Patterns of fish utilisation in a tropical Indo-Pacific mangrove-coral seascape, New Caledonia
Authors: Dubuc A , Waltham N. , Baker R. , Marchand C. , Sheaves M.
Published: October 2018

Mangrove forests are important habitats for fish. However, their utilisation by fish, and the specific values they confer, are still not fully understood. This study describes how fish use mangrove forests in an Indo-Pacific mangrove-coral reef seascape. Sampling was conducted using underwater video cameras (UVCs) to describe spatial and temporal variations in fish assemblages across a small-scale (~ 2.5 km2) system, and over the tidal and lunar cycle. UVCs were deployed in the two main component habitats of mangrove forests: at the mangrove forest edge, and inside the forest (5 m from the forest edge), to establish patterns of utilisation of fish across the tidal and lunar cycle. Proximity to coral reefs had a strong influence on the mangrove fish community, as most fish recorded were reef-associated. Juveniles of 12 reef species were observed, including two species classified as vulnerable on the IUCN list, and one endemic species. Fish assemblages on the mangrove edge differed significantly from those inside the forest. Most fish utilised the forest edge, with few species making regular use of in-forest habitats, supporting the contention that most fish species remain on the edge and potentially retreat into the forest for opportunistic feeding, or when threatened by larger predators. Species-specific patterns of utilisation varied across the tidal and lunar cycle. Small differences in depth profiles and substrate across the small-scale system had a significant effect on fish assemblages, highlighting the importance of accounting for spatial heterogeneity in these factors. These data provide important information for managers to implement adequate conservation strategies that include broader interconnected habitat mosaics.
Preclinical Modeling of Exposure to a Global Marine Bio-Contaminant: Effects of In Utero Domoic Acid Exposure on Neonatal Behavior and Infant Memory
Authors: Grant Kimberly S. , Crouthamel Brenda , Kenney Caroline , McKain Noelle , Petroff Rebekah , Shum Sara , Jing Jing , Isoherranen Nina , Burbacher Thomas M.
Published: October 2018

Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the recognition memory assessment, given between 1-2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential visual attention to novel test stimuli. This finding suggests subtle but significant impairment in recognition memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.
Deep Consensus, a deep learning-based approach for particle pruning in cryo-electron microscopy
Authors: Sanchez-Garcia Ruben , Segura Joan , Maluenda David , Carazo Jose Maria , Sorzano Carlos Oscar S.
Published: October 2018

Single-particle cryo-electron microscopy (cryo-EM) has recently become a mainstream technique for the structural determination of macromolecules. Typical cryo-EM workflows collect hundreds of thousands of single-particle projections from thousands of micrographs using particle-picking algorithms. However, the number of false positives selected by these algorithms is large, so that a number of different `cleaning steps' are necessary to decrease the false-positive ratio. Most commonly employed techniques for the pruning of false-positive particles are time-consuming and require user intervention. In order to overcome these limitations, a deep learning-based algorithm named Deep Consensus is presented in this work. Deep Consensus works by computing a smart consensus over the output of different particle-picking algorithms, resulting in a set of particles with a lower false-positive ratio than the initial set obtained by the pickers. Deep Consensus is based on a deep convolutional neural network that is trained on a semi-automatically generated data set. The performance of Deep Consensus has been assessed on two well known experimental data sets, virtually eliminating user intervention for pruning, and enhances the reproducibility and objectivity of the whole process while achieving precision and recall figures above 90%.
CAB: a cyclic automatic model-building procedure
Authors: Burla Maria Cristina , Carrozzini Benedetta , Cascarano Giovanni Luca , Polidori Giampiero , Giacovazzo Carmelo
Published: October 2018

The program Buccaneer, a well known fast and efficient automatic model-building program, is also a tool for phase refinement: indeed, input phases are used to calculate electron-density maps that are interpreted in terms of a molecular model, from which new phase estimates may be obtained. This specific property is shared by all other automatic model-building programs and allows their cyclic use, as is usually performed in other phase-refinement methods (for example electron-density modification techniques). Buccaneer has been included in a cyclic procedure, called CAB, aimed at increasing the rate of success of Buccaneer and the quality of the molecular models provided. CAB has been tested on 81 protein structures that were solved via molecular-replacement, anomalous dispersion and ab initio methods. The corresponding phases were submitted to a phase-refinement process that synergically combines current phase-refinement techniques and out-of-mainstream refinement methods [Burla et al. (2017), Acta Cryst. D73, 877–888]. The phases thus obtained were used as input for CAB. The experimental results were compared with those obtained by the sole use of Buccaneer: it is shown that CAB improves the Buccaneer results, both in completeness and in accuracy.
Do consumers want mobile commerce? A closer look at M-shopping and technology adoption in Malaysia
Authors: Ghazali Ezlika M. , Mutum Dilip S. , Chong Jiu Hui , Nguyen Bang
Published: October 2018

Purpose

Mobile shopping is expected to emerge as a new way of shopping as the Asia Pacific region moves towards the digital era. It is important to understand factors that influence consumers’ intentions to adopt this new shopping channel, especially in developing countries such as Malaysia where it has the fastest growing mobile penetration rate in the world. The purpose of this paper is to integrate the Technology Acceptance Model (TAM) and the Theory of Planned Behaviour (TPB), and includes additional variables such as personal innovativeness (PI) and trust.

Design/methodology/approach

Empirical data from 453 consumers were tested against a proposed model using partial least squares structural equation modelling.

Findings

Findings suggest that most of the constructs in the model (i.e. trust, perceived ease of use, perceived usefulness, attitudes, PI and perceived behavioural control) influence a shopper’s intentions towards adopting mobile shopping. For example, consumers’ attitudes towards M-shopping adoption is higher if a system is not complex and easy to use; if consumers can easily pull out their mobile devices from their pockets to browse or shop by using just one finger, without a complicated process, they tend to use M-shopping channels. In addition, when mobile technology is user-friendly and free from mental effort, it creates positive perceptions that the system is useful, developing stronger intentions for consumers to adopt this alternative.

Originality/value

Since M-shopping is a personalised activity that involves money transactions, consumers are more cautious with adoption intentions, and do not follow social norms blindly. Thus, the empirical evidence from Malaysian consumers contributes to literature with insights into their specific m-shopping behaviour in this emerging market. In addition, from a theoretical perspective, the research model in this study integrates both TAM and TPB to provide a holistic view of consumers’ M-shopping adoption intentions in an emerging market, incorporating user-centric factors (i.e. trust and PI). An important finding which differs from other studies is that the relationship between subjective norms and behavioural intention to use M-shopping was not significant, which is contrary to the findings of previous studies. Moreover, attitude was found to mediate the effect of PEOU and PU on consumer’s intention towards mobile shopping adoption. The validated instrument would serve as a useful guideline for researchers during development and refinement of studies on M-shopping.
Why are experienced users of WeChat likely to continue using the app?
Authors: Gong Xiuyuan , Liu Zhiying , Zheng Xiabing , Wu Tailai
Published: October 2018

Purpose

Mobile social apps permeate every facet of daily life through the pervasive use of smartphones. Customer retention with mobile social apps has become extremely important for app-related companies. The purpose of this paper is to explore why experienced users in mobile social apps (e.g. WeChat) are likely to continue using the app.

Design/methodology/approach

This study proposed a conceptual model to identify key determinants of continuance intention of WeChat users and highlight the effects of individual experience. Data were collected from WeChat users, which is one of the most popular mobile social apps in China. The study employed partial least squares regression to test the research model based on a survey of 295 valid responses.

Findings

Results showed that trust, which was driven by user satisfaction and perceived critical mass, played a critical role in influencing the continuance intention of WeChat users. Moreover, tie strength exerted a negative moderating effect on the relationship between trust and continuance intention. Specifically, tie strength and perceived critical mass had strong impacts on the continuance intention of low-experience users. In addition, the effect of frequency was closely associated with the continuance intention of high-experience users.

Research limitations/implications

This study addressed the issue of mobile social app continuance intention by providing an innovative means to explore the key antecedents of user continuance intention from the experience perspective. The findings not only prove that trust plays a central role in influencing the continuance intention of experienced users but also reveal that the determinants of continuance intention vary among users with different experience. The results provide insights into the key antecedents of experienced WeChat user continuance intention and contribute to the literature on mobile social apps and individual differences.

Practical implications

The results provide suggestions for mobile social app practitioners to effectively plan mobile social app retention practices and to set up appropriate incentive mechanisms for retaining users with different experiences.

Originality/value

Although abundant studies have focused on the adoption of media users, few studies have investigated the post-adoption behavior of experienced users in the context of mobile social apps. This study revealed the key determinants of the continuance intention of WeChat users and pinpointed the different impacts of these antecedents on users with different levels of experience. It also provides useful guidelines for practitioners to effectively retain users with different levels of experience.