bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physics of growing biological tissues: the complex cross-talk between cell activity, growth and resistance
Authors: Ben Amar Martine , Nassoy Pierre , LeGoff Loic 
Published: March 2019

For many organisms, shapes emerge from growth, which generates stresses, which in turn can feedback on growth. In this review, theoretical methods to analyse various aspects of morphogenesis are discussed with the aim to determine the most adapted method for tissue mechanics. We discuss the need to work at scales intermediate between cells and tissues and emphasize the use of finite elasticity for this. We detail the application of these ideas to four systems: active cells embedded in tissues, brain cortical convolutions, the cortex ofCaenorhabditis elegansduring elongation and finally the proliferation of epithelia on extracellular matrix. Numerical models well adapted to inhomogeneities are also presented.This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
An Eulerian formulation of inelasticity: from metal plasticity to growth of biological tissues
Authors: Rubin M. B. 
Published: March 2019

The purpose of this paper is to review and contrast the Lagrangian and Eulerian formulations of inelasticity as they apply to metal plasticity and growth of biological tissues. In contrast with the Lagrangian formulation of inelasticity, the Eulerian formulation is unaffected by arbitrary choices of the reference configuration, an intermediate configuration, a total deformation measure and an inelastic deformation measure. Although the Eulerian formulation for growth of biological tissues includes a rate of mass supply and can be used to understand the mechanics of growth, it does not yet model essential mechanobiological processes that control growth. Much research is needed before this theory can help design medical treatments for growth related disease.
This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
A microstructural model of cross-link interaction between collagen fibrils in the human cornea
Authors: Pandolfi A. , Gizzi A. , Vasta M. 
Published: March 2019

We propose a simplified micromechanical model of the fibrous reinforcement of the corneal tissue. We restrict our consideration to the structural function of the collagen fibrils located in the stroma and disregard the other all-important components of the cornea. The reinforcing structure is modelled with two sets of parallel fibrils, connected by transversal bonds within the single fibril family (inter-cross-link) and across the two families (intra-cross-link). The particular design chosen for this ideal structure relies on the fact that its ability to sustain loads is dependent on the degree of the cross-link and, therefore, on the density and stiffness of the bonds. We analyse the mechanical response of the system according to the type of interlacing and on the stiffness of fibres and bonds. Results show that the weakening of transversal bonds is associated with a marked increase of the deformability of the system. In particular, the deterioration of transversal bonds due to mechanical, chemical or enzymatic reasons can justify the loss of stiffness of the stromal tissue resulting in localized thinning and bulging typically observed in keratoconus corneas.This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Overt and covert paths for sound in the auditory system of mammals
Authors: Auriol B. , Auriol B. , Béard J. , Bibé B. , Broto J.-M. , Descouens D.F. , Durand L.J.S. , Florens J.-P. , Garcia F. , Gillieaux C. , Joiner E.G. , Libes B. , Pergent P. , Ruiz R. , Thalamas C. 
Published: March 2019

AbstractCurrent scientific consensus holds that sound is transmitted, solely mechanically, from the tympanum to the cochlea via ossicles.But this theory does not explain the hearing extreme quality regarding high frequencies in mammals. So, we propose a bioelectronic pathway (the covert path) that is complementary to the overt path.We demonstrate experimentally that the tympanum produces piezoelectric potentials isochronous to acoustic vibrations thanks to its collagen fibers and that their amplitude increases along with the frequency and level of the vibrations. This finding supports the existence of an electrical pathway, specialized in transmitting high-frequency sounds, that works in unison with the mechanical pathway. A bio-organic triode, similar to a field effect transistor, is the key mechanism of our hypothesized pathway. We present evidence that any deficiency along this pathway produces hearing impairment. By augmenting the classical theory of sound transmission, our discovery offers new perspectives for research into both normal and pathological audition and may contribute to an understanding of genetic and physiological problems of hearing.
Vaccine blunts fentanyl potency in male rhesus monkeys
Authors: Tenney Rebekah D. , Blake Steven , Bremer Paul T. , Zhou Bin , Hwang Candy S. , Poklis Justin L. , Janda Kim D. , Banks Matthew L. 
Published: March 2019

AbstractOne proposed factor contributing to the increased opioid overdose deaths is the increased frequency of synthetic opioids, including fentanyl and fentanyl analogs. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dissimilar mu-opioid agonist oxycodone in male rhesus monkeys (n=3-4). Fentanyl and oxycodone produced dose-dependent suppression of behavior in an assay of schedule-controlled responding and antinociception in an assay of thermal nociception (50°C). Acute naltrexone (0.032 mg/kg) produced an approximate 10-fold potency shift for fentanyl to decrease operant responding. The fentanyl vaccine was administered at weeks 0, 2, 4, 9, 19, and 44 and fentanyl or oxycodone potencies in both behavioral assays were redetermined over the course of 49 weeks. The vaccine significantly and selectively shifted fentanyl potency at least 10-fold in both assays at several time points over the entire experimental period. Mid-point titer levels were significantly correlated with fentanyl antinociceptive potency shifts. Antibody affinity for fentanyl as measured by a competitive binding assay increased over time to around 3-4 nM. The fentanyl vaccine also significantly increased fentanyl plasma levels approximately 6-fold consistent with the hypothesis that the vaccine sequesters fentanyl in the blood. Overall, these results support the continued development and evaluation of this fentanyl vaccine to address the ongoing opioid crisis.HighlightsVaccine blunted fentanyl rate-suppression potency ∼ 10-foldVaccine blunted fentanyl antinociceptive potency ∼25-foldFentanyl vaccine was as effective as acute 0.032 mg/kg naltrexoneVaccine was selective for fentanyl and not oxycodoneAntibody immune response ∼ 3 nM affinity for fentanyl
Shared risk alleles with discordant polygenic effects: Disentangling the genetic overlap between ASD and ADHD
Authors: Verhoef Ellen , Grove Jakob , Shapland Chin Yang , Demontis Ditte , Burgess Stephen , Rai Dheeraj , Børglum Anders D. , St Pourcain Beate 
Published: March 2019

AbstractInsight into shared polygenetic architectures affects our understanding of neurodevelopmental disorders. Here, we investigate evidence for pleiotropic mechanisms that may explain the comorbidity between Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). These complex neurodevelopmental conditions often co-occur, but differ in their polygenetic association patterns, especially with educational attainment (EA), showing discordant association effects. Using multivariable regression analyses and existing genome-wide summary statistics based on 10,610 to 766,345 individuals, we demonstrate that EA-related polygenic variation is shared between ASD and ADHD. We show that different combinations of the same ASD and ADHD risk-increasing alleles can simultaneously re-capture known ASD-related positive and ADHD-related negative associations with EA. Such patterns, although to a lesser degree, were also present for combinations of other psychiatric disorders. These findings suggest pleiotropic mechanisms, where the same polygenic sites can encode multiple independent, even discordant, association patterns without involving distinct loci, and have implications for cross-disorder investigations.
Visualization of Loki- and Heimdallarchaeia (Asgardarchaeota) by fluorescence in situ hybridization and catalyzed reporter deposition (CARD-FISH)
Authors: Salcher Michaela M. , Andrei Adrian-Ştefan , Bulzu Paul-Adrian , Keresztes Zsolt G. , Banciu Horia L. , Ghai Rohit 
Published: March 2019

AbstractMetagenome-assembled genomes (MAGs) of Asgardarchaeota are starting to be recovered from a variety of habitats, broadening their environmental distribution and providing access to the genetic makeup of this archaeal lineage. Despite their singular phylogenetic position at the base of the eukaryotic tree of life, the morphology of these bewildering organisms remains a mystery. In order to visualize this elusive group, we applied a combination of CARD-FISH and epifluorescence microscopy on coastal hypersaline sediment samples, using specifically designed CARD-FISH probes for Heimdallarchaeia and Lokiarchaeia lineages and provide the first visual evidence for both these groups. Here, we show that while Heimdallarchaeia are characterized by a uniform cellular morphology typified by central DNA localization, Lokiarchaeia display a plethora of shapes and sizes that likely reflect their broad phylogenetic diversity and ecological distribution.
Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition
Authors: Wasnick RM , Korfei M , Piskulak K , Henneke I , Wilhelm J , Mahavadi P , von der Beck D , Koch M , Shalashova I , Klymenko O , Fink L , Witt H , Hackstein H , El Agha E , Bellusci S , Klepetko W , Königshoff M , Eickelberg O , Braun T , Seeger W , Ruppert C , Guenther A 
Published: March 2019

AbstractAlveolar epithelial cell type II (AEC2) injury underlies idiopathic pulmonary fibrosis (IPF). Here we show increased Notch1 signaling in AEC2s in human IPF and IPF models, causing enhanced proliferation and de-differentiation of AEC2s. As a result, we observed defective surfactant protein (SP)-B/C processing, elevated alveolar surface tension, repetitive alveolar collapse and development of lung fibrosis. Similar changes were encountered upon pharmacological inhibition of SP-B/C processing in vivo by pepstatin A. Inhibition of Notch signaling in cultured human IPF precision cut lung slices improved surfactant processing capacity of AEC2s and reversed fibrosis. Notch1 therefore offers as novel therapeutic target.One sentence summaryNotch1 inhibition restores alveolar epithelial differentiation and surface tension and reverses matrix deposition in lung fibrosis
Differential Expression of N- and O-glycans on HeLa Cells-Revealed by Direct Fluorescent Glycan Labeling with Recombinant Sialyltransferases
Authors: Wu Zhengliang L , Person Anthony D , Burton Andrew J. , Singh Ravinder , Burroughs Barbara , Fryxell Dan , Tatge Timothy J. , Manning Timothy , Wu Guoping , Swift Karl A.D. , Kalabokis Vassili 
Published: March 2019

AbstractCells are covered with glycans. The expression and distribution of specific glycans on cell surface are important for various cellular functions. Imaging these glycans is essential to elucidate their biological roles. Here, utilizing enzymatic incorporation of fluorophore-conjugated sialic acids, dubbed asdirectfluorescentglycanlabeling (DFGL), we report the imaging of N- and O-glycans and particularly tumor specific sialyl T antigen on HeLa cells. It is found that while Core-1 O-glycans are relatively evenly distributed on cells, the expression of N-glycans tend to be more peripheral. More interestingly, the expression of sialyl T antigen displays random and sporadic patterns. In technique side, DFGL allows convenient labeling or imaging of various glycans on intact glycoproteins or cell surfaces with variety of fluorescent dyes.
PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions
Authors: Grebeňová D. , Holoubek A. , Röselová P. , Obr A. , Brodská B. , Kuželová K. 
Published: March 2019

AbstractP21-activated kinases (PAK) are key effectors of the small GTPases Rac1 and Cdc42, as well as of Src family kinases. In particular, PAK1 has several well-documented roles, both kinase-dependent and kinase-independent, in cancer-related processes, such as cell proliferation, adhesion, and migration. However, PAK1 properties and functions have not been attributed to individual PAK1 isoforms: besides the full-length kinase (PAK1-full), a splicing variant lacking the exon 15 (PAK1Δ15) is annotated in protein databases. In addition, it is not clear if PAK1 and PAK2 are functionally overlapping. Using fluorescently tagged forms of human PAK1-full, PAK1Δ15, and PAK2, we analyzed their intracellular localization and mutual interactions. Effects of PAK inhibition or depletion on cell-surface adhesion were monitored by real-time microimpedance measurement. We show that PAK1Δ15 is in many aspects similar to PAK2, rather than to PAK1-full. Both PAK1Δ15 and PAK2, but not PAK1-full, were enriched in focal adhesions, indicating that the C-terminus might be important for PAK intracellular localization. Using immunoprecipitation, we documented direct interactions among the studied PAK group I members: PAK1 and PAK2 form homodimers, but all possible heterodimers were also detected. Our results indicate that PAK1 and PAK2 have distinct roles in cell adhesion and mutually affect their function. PAK1-full is required for formation of membrane protrusions, whereas PAK2 is involved in focal adhesion assembly. We have also noted that PAK inhibition was associated with a large reduction of the cell glycolytic rate. Altogether, our data suggest a complex interplay among different PAK group I members, which have largely non-redundant functions.
Asymmetric sampling in human auditory cortex reveals spectral processing hierarchy
Authors: Giroud Jérémy , Trébuchon Agnès , Schön Daniele , Marquis Patrick , Liegeois-Chauvel Catherine , Poeppel David , Morillon Benjamin 
Published: March 2019

AbstractSpeech perception is mediated by both left and right auditory cortices, but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex. We presented short acoustic transients to reveal the stereotyped spectro-spatial oscillatory response profile of the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with preferred processing modes in the theta (∼4-8 Hz) and low gamma (∼25-50 Hz) ranges. These results highlight that the human auditory system employs a two-timescale processing mode. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (∼3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (∼6/40 Hz) activity in the left. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the two hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.Author summarySpeech processing is now known to be distributed across the two hemispheres, but the origin and function of lateralization continues to be vigorously debated. The asymmetric sampling in time (AST) hypothesis predicts that (1) the auditory system employs a two-timescales processing mode, (2) present in both hemispheres but with a different ratio of fast and slow timescales, (3) that emerges outside of primary cortical regions. Capitalizing on intracranial data from 96 epileptic patients we sensitively validated each of these predictions and provide a precise estimate of the processing timescales. In particular, we reveal that asymmetric sampling in associative areas is subtended by distinct two-timescales processing modes. Overall, our results shed light on the neurofunctional architecture of cortical auditory processing.
Sign-tracking behavior is difficult to extinguish and resistant to multiple cognitive enhancers
Authors: Fitzpatrick Christopher J. , Geary Trevor , Creeden Justin F. , Morrow Jonathan D. 
Published: March 2019

AbstractThe attribution of incentive-motivational value to drug-related cues underlies relapse and craving in drug addiction. One method of addiction treatment, cue-exposure therapy, utilizes repeated presentations of drug-related cues in the absence of drug (i.e., extinction learning); however, its efficacy has been limited due to an incomplete understanding of extinction and relapse processes after cues have been imbued with incentive-motivational value. To investigate this, we used a Pavlovian conditioned approach procedure to screen for rats that attribute incentive-motivational value to reward-related cues (sign-trackers; STs) or those that do not (goal-trackers; GTs). In Experiment 1, rats underwent Pavlovian extinction followed by reinstatement and spontaneous recovery tests. For comparison, a separate group of rats underwent PCA training followed by operant conditioning, extinction, and tests of reinstatement and spontaneous recovery. In Experiment 2, three cognitive enhancers (sodium butyrate, D-cycloserine, and fibroblast growth factor 2) were administered following extinction training to facilitate extinction learning. STs but not GTs displayed enduring resistance to Pavlovian, but not operant, extinction and were more susceptible to spontaneous recovery. In addition, none of the cognitive enhancers tested affected extinction learning. These results expand our understanding of extinction learning by demonstrating that there is individual variation in extinction and relapse processes and highlight potential difficulties in applying extinction-based therapies to drug addiction treatment in the clinic.
Performance investigation of an advanced diagnostic method for SSTPI-fed IM drives under single and multiple open IGBT faults
Authors: Zdiri Mohamed Ali , Bouzidi Badii , Hadj Abdallah Hsan 
Published: March 2019

Purpose
This paper aims to analyze and investigate the performance of an improved fault detection and identification (FDI) method based on multiple criteria, applied to six-switch three-phase inverter (SSTPI)-fed induction motor (IM) drives under both single and multiple open insulated-gate bipolar transistors(IGBT) faults.

Design/methodology/approach
This paper proposes an advanced diagnostic method for both single and multiple open IGBT faults dedicated to SSTPI-fed IM drives considering five distinct faulty operating conditions as follows: a single IGBT open-circuit fault, a single-phase open-circuit fault, a non-crossed double fault in two different legs, a crossed double fault in two different legs and a three-IGBT open-circuit fault. This is achieved because of the introduction of a new diagnosis variable provided using the information of the slope of the current vector in (α-β) frame. The proposed FDI method is based on the synthesis and the analysis, under both healthy and faulty operations, of the behaviors of the introduced diagnosis variable, the three motor phase currents and their normalized average values. Doing so, the developed FDI method allows a best compromise of fast detection and precision localization of IGBT open-circuit fault of the inverter.

Findings
Simulation works, carried out considering the implementation of the direct rotor flux oriented control in an IM fed by the conventional SSTPI, have proved the high performance of the advanced FDI method in terms of fast fault detection associated with a high robustness against false alarms, against speed and load torque fast variations and against the oscillations of the DC-bus voltage in the case of both healthy and faulty operations.

Research limitations/implications
This work should be extended considering the validation of the obtained simulation results through experiments.

Originality/value
Different from other FDI methods, which suffer from a low diagnostic effectiveness for low load levels and false alarms during transient operation, this method offers the potentialities to overcome these drawbacks because of the introduction of the new diagnosis variable. This latter, combined with the information provided from the three motor phase currents and their normalized average values allow a more efficient detection and identification of IGBT open-circuit fault.
Nuances of microalgal technology in food and nutraceuticals: a review
Authors: Sahni Prashant , Aggarwal Poonam , Sharma Savita , Singh Baljit 
Published: March 2019

PurposeThe purpose of this paper is to acquaint the readers with the insights regarding the interventions of microalgal technology for production of metabolites and functional ingredients from microalgae for food and nutraceutical application and exploration of microalgae biomass for food application.Design/methodology/approachVarious information databases such as journals, library catalogues and professional websites were used to collect information pertaining to application of microalgae in food and nutraceutical sector. Systematic review was made with recent studies covering the vital aspects of art of microalgae cultivation for metabolite production, functional ingredients from microalgae, market scenario and utilisation of microalgae biomass for the valorisation of the food products. Key points have been discussed after every section to highlight the practical implications to make this review more insightful for the readers.FindingsMicroalgal technology provides sustainable solution for its application in food and nutraceutical sector. The heart of metabolite production lies in the optimisation of cultivation conditions of microalgae. Wide array of functional components are obtained from microalgae. Microalgae offer an alternative source for omega-3 fatty acids. Microalgae is widely exploited for production of pigments, namely, ß-carotene, astaxanthin, lutein, phycocyanin and chlorophyll, that have important implication as natural colourants and nutraceuticals in food. Larger diversity of sterols found in microalgae confers bioactivity. Microalgae is finding its place in market shelves as nutraceuticals where its functional ingredients are in the form of powder, tablets, extract and beverages and in innovative products such as microalgae protein and fat, culinary algae oil and butter. Sprulina and Chlorella are popular choice for the supplementation of food products with microalgae biomass.Originality/valueThis is a comprehensive review that highlights the application of microalgal technology for the development of healthy food products and presents holistic intervention in food and nutraceutical sector.