bluuebunny/crossref_metadata_2025 huggingface dataset:
The Progressive Nature of Menière's Disease: Stress Projections and Lesion Analysis
Authors: Pender Daniel J.
Published: January 2018

Hypothesis:

An engineering model of the labyrinth can provide a mechanism that accounts for the pattern of lesion development observed in Menière's disease.

Background:

Membrane lesions in Menière's disease can occur in virtually every part of the membranous labyrinth. How these lesions are induced is unclear and their mode of distribution uncertain. Pressure induced stress in the membranous labyrinth may play a mechanistic role in lesion formation and distribution.

Methods:

An engineering model of the labyrinth was used to provide membrane stress formulations and projections for lesion induction in the several chambers using membrane theory. These were compared with an analysis of actual lesions observed in Menière's disease to evaluate the model's accuracy.

Results:

The model projects that lesions in the membranous labyrinth will be induced progressively because of stress differentials among the chambers, with a chain of lesion pattern that follows the serial anatomic order and occurs with a frequency commensurate with chamber stress level. An analysis of lesions observed in actual cases of Menière's disease reveals a pattern of lesion development that is progressive, sequential, commensurate, and concordant with the model's stress projections.

Conclusions:

The concordance between the stress projections and the lesion analysis strengthens the hypothesis that Menière's is a progressive disease that follows a chain of lesions paradigm based on pressure-induced stress differentials in the variously configured chambers of the membranous labyrinth.
Ultra Long-Term Audiometric Outcomes in the Treatment of Vestibular Schwannoma With the Middle Cranial Fossa Approach
Authors: Roche Joseph P. , Woodson Erika A. , Hansen Marlan R. , Gantz Bruce J.
Published: January 2018

Objective:

Define the long-term audiometric outcomes of vestibular schwannomas treated using the middle cranial fossa (MCF) approach.

Study Design:

Retrospective records review.

Setting:

University-based tertiary referral center.

Patients:

Patients undergoing treatment of small vestibular schwannomas using the MCF approach.

Intervention(s):

MCF exposure and treatment of small vestibular schwannomas.

Main Outcome Measure(s):

Demographic and audiometric variables were assessed.

Results:

Thirteen subjects demonstrated audiometric data for review. The average time between surgery and the most recent audiometric testing was 14 years (range 10–18 yr). The mean baseline pure-tone average (PTA) was 36 dB HL and the most recent PTA was 59 dB HL in the operated ear. The mean baseline PTA was 16 dB HL and the most recent PTA was 37 dB HL in the nonoperated ear. The mean change from baseline to most recent follow-up was a threshold elevation of 22 and 19 dB HL in the operated and nonoperated ears, respectively. The mean baseline speech discrimination score (SDS) was 83% and the most recent SDS was 73% in the operated ear. The mean baseline SDS was 98% and the most recent SDS was 94% in the nonoperated ear. The mean changes from baseline to most recent follow-up were 10 and 0% SDS depression in the operated and nonoperated ears, respectively. The rates of changes in PTA and SDS were not statistically different between the operated and nonoperated ears.

Conclusions:

Surgically preserved hearing is maintained in the majority of patients more than 10 years following surgery. PTA and SDS changes were similar between the ipsilateral and contralateral ears.
Middle Fossa Approach for Cochlear Implantation
Authors: Gawęcki Wojciech , Karlik Michał , Borucki Łukasz , Wróbel Maciej , Stieler Olgierd Maciej , Szyfter Witold
Published: January 2018

Objective:

To present qualification criteria, surgery, and results of cochlear implantation via the middle fossa approach.

Study Design:

A retrospective analysis of medical charts of patients.

Setting:

Cochlear implant program in academic medical center.

Patients:

Six adults after middle ear surgery due to chronic otitis media with bilateral deafness or profound hearing loss.

Intervention:

Analysis aimed to identify patients qualified for cochlear implantation via middle fossa approach and to present surgery and result.

Main Outcome Measure:

Qualification criteria, details of surgery and surgical, functional and audiological results.

Results:

Surgery was completed in four patients and in the remaining two it was stopped because of adhesions and bleeding from the dura. In three patients, there were no postoperative complications and in one individual intracranial hematoma occurred. Postoperative computed tomography showed the intracochlear position of the electrode in all the implanted patients. All of the patients use their implant for 14 to 16 hours daily. One year after the implantation, they had hearing thresholds in the sound-free field of between 25 and 45 dB sound pressure level, number recognition scores between 80 and 100% and monosyllabic words recognition between 30 and 90%.

Conclusion:

Successful cochlear implantation via middle fossa approach results in satisfactory hearing, bringing deaf people into a hearing environment. However, this approach is technically difficult and provides the risk of intracranial complications. In our opinion this approach should be used in special cases only (e.g., postmeningitis or otosclerotis patients with obliteration of basal turn of cochlea). In analysed group it should not be considered the primary solution.
Bleeding risk of variceal band ligation in extrahepatic portal vein obstruction is not increased by oral anticoagulation
Authors: Guillaume Maeva , Christol Camille , Plessier Aurélie , Corbic Michèle , Péron Jean-Marie , Sommet Agnès , Rautou Pierre-Emmanuel , Consigny Yann , Vinel Jean-Pierre , Valla Charles-Dominique , Bureau Christophe
Published: January 2018

Background and objectives

Noncirrhotic nontumoral extrahepatic portal vein obstruction (EHPVO) is the second leading cause of portal hypertension (PHT) and is mainly related to prothrombotic disorders. Patients with EHPVO often require prolonged oral anticoagulation therapy (OAT) together with variceal band ligation (VBL) to prevent thrombosis recurrence and PHT-related bleeding, respectively. The benefit–risk balance of VBL in this context remains unknown. We aimed to assess upper gastrointestinal bleeding (UGB) risk and variceal eradication efficacy in EHPVO patients undergoing a VBL program without stopping OAT.

Patients and methods

All patients with EHPVO treated (group A) or not (group B) with OAT and undergoing the VBL program were included between 2001 and 2010 in two tertiary French liver centers. We compared the incidence, source, and severity of UGB and variceal eradication efficacy. All EHPVO patients were then matched 1 : 1 with compensated cirrhotic patients with PHT not receiving OAT (group C) to compare UGB incidence and VBL efficacy.

Results

Forty-three EHPVO patients (30 with and 13 without OAT) and 43 cirrhotic patients were included for a total of 471 VBL sessions. The incidence of UGB was similar between group A (nine episodes/121 sessions) and group B (6/130), and tended to be higher in EHPVO patients (group A and B) than in cirrhotic patients (2/220). There was no difference between groups when considering bleeding source or severity and variceal eradication efficacy (84%).

Conclusion

VBL can be performed safely and efficiently without stopping anticoagulation therapy in EHPVO patients.
Travelling-wave amplitudes as solutions of the phase-field crystal equation
Authors: Nizovtseva I. G. , Galenko P. K.
Published: January 2018

The dynamics of the diffuse interface between liquid and solid states is analysed. The diffuse interface is considered as an envelope of atomic density amplitudes as predicted by the phase-field crystal model (Elder
et al.
2004
Phys. Rev. E
70
, 051605 (
doi:10.1103/PhysRevE.70.051605
); Elder
et al.
2007
Phys. Rev. B
75
, 064107 (
doi:10.1103/PhysRevB.75.064107
)). The propagation of crystalline amplitudes into metastable liquid is described by the hyperbolic equation of an extended Allen–Cahn type (Galenko & Jou 2005
Phys. Rev. E
71
, 046125 (
doi:10.1103/PhysRevE.71.046125
)) for which the complete set of analytical travelling-wave solutions is obtained by the

method (Malfliet & Hereman 1996
Phys. Scr.
15
, 563–568 (
doi:10.1088/0031-8949/54/6/003
); Wazwaz 2004
Appl. Math. Comput.
154
, 713–723 (
doi:10.1016/S0096-3003(03)00745-8
)). The general

solution of travelling waves is based on the function of hyperbolic tangent. Together with its set of particular solutions, the general

solution is analysed within an example of specific task about the crystal front invading metastable liquid (Galenko
et al.
2015
Phys. D
308
, 1–10 (
doi:10.1016/j.physd.2015.06.002
)). The influence of the driving force on the phase-field profile, amplitude velocity and correlation length is investigated for various relaxation times of the gradient flow.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Coarse-graining for fast dynamics of order parameters in the phase-field model
Authors: Jou D. , Galenko P. K.
Published: January 2018

In standard descriptions, the master equation can be obtained by coarse-graining with the application of the hypothesis of full local thermalization that is equivalent to the local thermodynamic equilibrium. By contrast, fast transformations proceed in the absence of local equilibrium and the master equation must be obtained with the absence of thermalization. In the present work, a non-Markovian master equation leading, in specific cases of relaxation to local thermodynamic equilibrium, to hyperbolic evolution equations for a binary alloy, is derived for a system with two order parameters. One of them is a conserved order parameter related to the atomistic composition, and the other one is a non-conserved order parameter, which is related to phase field. A microscopic basis for phenomenological phase-field models of fast phase transitions, when the transition is so fast that there is not sufficient time to achieve local thermalization between two successive elementary processes in the system, is provided. In a particular case, when the relaxation to local thermalization proceeds by the exponential law, the obtained coarse-grained equations are related to the hyperbolic phase-field model. The solution of the model equations is obtained to demonstrate non-equilibrium phenomenon of solute trapping which appears in rapid growth of dendritic crystals.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics
Authors: Shur Vladimir Ya. , Akhmatkhanov Andrey R.
Published: January 2018

The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Crystal growth kinetics in undercooled melts of pure Ge, Si and Ge–Si alloys
Authors: Herlach Dieter M. , Simons Daniel , Pichon Pierre-Yves
Published: January 2018

We report on measurements of crystal growth dynamics in semiconducting pure Ge and pure Si melts and in Ge

100−
x

Si

x

(
x
 = 25, 50, 75) alloy melts as a function of undercooling. Electromagnetic levitation techniques are applied to undercool the samples in a containerless way. The growth velocity is measured by the utilization of a high-speed camera technique over an extended range of undercooling. Solidified samples are examined with respect to their microstructure by scanning electron microscopic investigations. We analyse the experimental results of crystal growth kinetics as a function of undercooling within the sharp interface theory developed by Peter Galenko. Transitions of the atomic attachment kinetics are found at large undercoolings, from faceted growth to dendrite growth.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
A model for free growth of a lamellar eutectic dendrite with an incident flow
Authors: Gao Jianrong
Published: January 2018

A model for free growth of a lamellar eutectic dendrite with an incident flow was proposed for the breakdown of a planar solid/liquid interface into a dendritic contour due to a negative thermal gradient in an undercooled liquid. The model was used to predict the growth kinetics of an
α
-Ni/Ni
3
Sn eutectic dendrite with and without an incident flow in the growth direction. The modelling showed that free eutectic growth is not sensitive to the tip selection parameter of the eutectic dendrite, but is sensitive to incident flow of magnitude larger than eutectic growth velocities. While the larger incident flow increases the eutectic growth velocities generally, it has opposing effects on the interlamellar spacings depending on undercooling. The prediction of the model awaits experimental validation.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
From atomistic interfaces to dendritic patterns
Authors: Galenko P. K. , Alexandrov D. V.
Published: January 2018

Transport processes around phase interfaces, together with thermodynamic properties and kinetic phenomena, control the formation of dendritic patterns. Using the thermodynamic and kinetic data of phase interfaces obtained on the atomic scale, one can analyse the formation of a single dendrite and the growth of a dendritic ensemble. This is the result of recent progress in theoretical methods and computational algorithms calculated using powerful computer clusters. Great benefits can be attained from the development of micro-, meso- and macro-levels of analysis when investigating the dynamics of interfaces, interpreting experimental data and designing the macrostructure of samples. The review and research articles in this theme issue cover the spectrum of scales (from nano- to macro-length scales) in order to exhibit recently developing trends in the theoretical analysis and computational modelling of dendrite pattern formation. Atomistic modelling, the flow effect on interface dynamics, the transition from diffusion-limited to thermally controlled growth existing at a considerable driving force, two-phase (mushy) layer formation, the growth of eutectic dendrites, the formation of a secondary dendritic network due to coalescence, computational methods, including boundary integral and phase-field methods, and experimental tests for theoretical models—all these themes are highlighted in the present issue.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
A phase-field-crystal alloy model for late-stage solidification studies involving the interaction of solid, liquid and gas phases
Authors: Wang Nan , Kocher Gabriel , Provatas Nikolas
Published: January 2018

We present a multiphase binary alloy phase-field-crystal model. By introducing density difference between solid and liquid into a previous alloy model, this new fusion leads to a practical tool that can be used to investigate formation of defects in late-stage alloy solidification. It is shown that this model can qualitatively capture the liquid pressure drop due to solidification shrinkage in confined geometry. With an inherited gas phase from a previous multiphase model, cavitation of liquid from shrinkage-induced pressure is also included in this framework. As a unique model that has both solute concentration and pressure-induced liquid cavitation, it also captures a modified Scheil–Gulliver-type segregation behaviour due to cavitation. Simulation of inter-dendritic channel solidification using this model demonstrates a strong cooling rate dependence of the resulting microstructure.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Dendrite fragmentation: an experiment-driven simulation
Authors: Cool T. , Voorhees P. W.
Published: January 2018

The processes leading to the fragmentation of secondary dendrite arms are studied using a three-dimensional Sn dendritic structure that was measured experimentally as an initial condition in a phase-field simulation. The phase-field model replicates the kinetics of the coarsening process seen experimentally. Consistent with the experiment, the simulations of the Sn-rich dendrite show that secondary dendrite arm coalescence is prevalent and that fragmentation is not. The lack of fragmentation is due to the non-axisymmetric morphology and comparatively small spacing of the dendrite arms. A model for the coalescence process is proposed, and, consistent with the model, the radius of the contact region following coalescence increases ast1/3. We find that small changes in the width and spacing of the dendrite arms can lead to a very different fragmentation-dominated coarsening process. Thus, the alloy system and growth conditions of the dendrite can have a major impact on the fragmentation process.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
Analytical solutions of mushy layer equations describing directional solidification in the presence of nucleation
Authors: Alexandrov Dmitri V. , Ivanov Alexander A. , Alexandrova Irina V.
Published: January 2018

The processes of particle nucleation and their evolution in a moving metastable layer of phase transition (supercooled liquid or supersaturated solution) are studied analytically. The transient integro-differential model for the density distribution function and metastability level is solved for the kinetic and diffusionally controlled regimes of crystal growth. The Weber–Volmer–Frenkel–Zel’dovich and Meirs mechanisms for nucleation kinetics are used. We demonstrate that the phase transition boundary lying between the mushy and pure liquid layers evolves with time according to the following power dynamic law:

, where
Z
1
(
t
)=
βt
7/2
and
Z
1
(
t
)=
βt
2
in cases of kinetic and diffusionally controlled scenarios. The growth rate parameters
α
,
β
and
ε
are determined analytically. We show that the phase transition interface in the presence of crystal nucleation and evolution propagates slower than in the absence of their nucleation.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
The boundary integral theory for slow and rapid curved solid/liquid interfaces propagating into binary systems
Authors: Galenko Peter K. , Alexandrov Dmitri V. , Titova Ekaterina A.
Published: January 2018

The boundary integral method for propagating solid/liquid interfaces is detailed with allowance for the thermo-solutal Stefan-type models. Two types of mass transfer mechanisms corresponding to the local equilibrium (parabolic-type equation) and local non-equilibrium (hyperbolic-type equation) solidification conditions are considered. A unified integro-differential equation for the curved interface is derived. This equation contains the steady-state conditions of solidification as a special case. The boundary integral analysis demonstrates how to derive the quasi-stationary Ivantsov and Horvay–Cahn solutions that, respectively, define the paraboloidal and elliptical crystal shapes. In the limit of highest Péclet numbers, these quasi-stationary solutions describe the shape of the area around the dendritic tip in the form of a smooth sphere in the isotropic case and a deformed sphere along the directions of anisotropy strength in the anisotropic case. A thermo-solutal selection criterion of the quasi-stationary growth mode of dendrites which includes arbitrary Péclet numbers is obtained. To demonstrate the selection of patterns, computational modelling of the quasi-stationary growth of crystals in a binary mixture is carried out. The modelling makes it possible to obtain selected structures in the form of dendritic, fractal or planar crystals.

This article is part of the theme issue ‘From atomistic interfaces to dendritic patterns’.
First confirmed case of nasal pythiosis in a horse in Thailand
Authors: Tonpitak Walaiporn , Pathomsakulwong Watcharapol , Sornklien Chulabha , Krajaejun Theerapong , Wutthiwithayaphong Suppathat
Published: January 2018

Introduction. Pythiosis is caused by Pythium insidiosum, a fungus-like organism in the class Oomycetes. It can infect humans and a variety of animal species in tropical, subtropical and some temperate regions. Cases of animal pythiosis have occurred predominantly in horses in the skin and subcutaneous tissue at the limbs and in the ventral portion of thoracoabdominal wall - lesions in the nasal region are rarely reported. Moreover, although many human pythiosis cases have been reported in Thailand, no cases of animal pythiosis in Thailand have been reported.

Case presentation. We report a case of pythiosis in a horse infected at the nasal cavity. Diagnosis was performed by zoospore formation by bait technique, immunohistochemical stain, immunochromatography and sequence analysis.

Conclusion. The sequences of rDNA were 99 % and 96 to 99 % identical to GenBank isolates of Pythium insidiosum from two Thai human patients and horses from various countries, respectively. This represents the first confirmed report of nasal equine pythiosis in Thailand.
Genome-wide association analysis of lifetime cannabis use (N=184,765) identifies new risk loci, genetic overlap with mental health, and a causal influence of schizophrenia on cannabis use
Authors: Pasman Joëlle A. , Verweij Karin J.H. , Gerring Zachary , Stringer Sven , Sanchez-Roige Sandra , Treur Jorien L. , Abdellaoui Abdel , Nivard Michel G. , Baselmans Bart M.L. , Ong Jue-Sheng , Ip Hill F. , van der Zee Matthijs D. , Bartels Meike , Day Felix R. , Fontanillas Pierre , Elson Sarah L. ,   the 23andMe Research Team, de Wit Harriet , Davis Lea K. , MacKillop James ,   International Cannabis Consortium, Derringer Jaime L. , Branje Susan J.T. , Hartman Catharina A. , Heath Andrew C. , van Lier Pol A.C. , Madden Pamela A.F. , Mägi Reedik , Meeus Wim , Montgomery Grant W. , Oldehinkel A.J. , Pausova Zdenka , Ramos-Quiroga Josep A. , Paus Tomas , Ribases Marta , Kaprio Jaakko , Boks Marco P.M. , Bell Jordana T. , Spector Tim D. , Gelernter Joel , Boomsma Dorret I. , Martin Nicholas G. , MacGregor Stuart , Perry John R.B. , Palmer Abraham A. , Posthuma Danielle , Munafò Marcus R. , Gillespie Nathan A. , Derks Eske M. , Vink Jacqueline M.
Published: January 2018

Cannabis use is a heritable trait [1] that has been associated with adverse mental health outcomes. To identify risk variants and improve our knowledge of the genetic etiology of cannabis use, we performed the largest genome-wide association study (GWAS) meta-analysis for lifetime cannabis use (N=184,765) to date. We identified 4 independent loci containing genome-wide significant SNP associations. Gene-based tests revealed 29 genome-wide significant genes located in these 4 loci and 8 additional regions. All SNPs combined explained 10% of the variance in lifetime cannabis use. The most significantly associated gene, CADM2, has previously been associated with substance use and risk-taking phenotypes [2–4]. We used S-PrediXcan to explore gene expression levels and found 11 unique eGenes. LD-score regression uncovered genetic correlations with smoking, alcohol use and mental health outcomes, including schizophrenia and bipolar disorder. Mendelian randomisation analysis provided evidence for a causal positive influence of schizophrenia risk on lifetime cannabis use.
Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms
Authors: Liu Tsung-Li , Upadhyayula Srigokul , Milkie Daniel E. , Singh Ved , Wang Kai , Swinburne Ian A. , Mosaliganti Kishore R. , Collins Zach M. , Hiscock Tom W. , Shea Jamien , Kohrman Abraham Q. , Medwig Taylor N. , Dambournet Daphne , Forster Ryan , Cunniff Brian , Ruan Yuan , Yashiro Hanako , Scholpp Steffen , Meyerowitz Elliot M. , Hockemeyer Dirk , Drubin David G. , Martin Benjamin L. , Matus David Q. , Koyama Minoru , Megason Sean G. , Kirchhausen Tom , Betzig Eric
Published: January 2018

True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages, and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.

One Sentence Summary

Combining lattice light sheet microscopy with adaptive optics enables high speed, high resolution in vivo 3D imaging of dynamic processes inside cells under physiological conditions within their parent organisms.
Radial glial lineage progression and differential intermediate progenitor amplification underlie striatal compartments and circuit organization
Authors: Kelly Sean M. , Raudales Ricardo , He Miao , Lee Jannifer , Kim Yongsoo , Gibb Leif G. , Wu Priscilla , Matho Katie , Osten Pavel , Graybiel Ann M. , Huang Z. Josh
Published: January 2018

The circuitry of the striatum is characterized by two organizational plans: the division into striosome and matrix compartments, thought to mediate evaluation and action, and the direct and indirect pathways, thought to promote or suppress behavior. The developmental origins of and relationships between these organizations are unknown, leaving a conceptual gap in understanding the cortico-basal ganglia system. Through genetic fate mapping, we demonstrate that striosome-matrix compartmentalization arises from a lineage program embedded in lateral ganglionic eminence radial glial progenitors mediating neurogenesis through two distinct types of intermediate progenitors (IPs). The early phase of this program produces striosomal spiny projection neurons (SPNs) through fate-restricted apical IPs (aIPSs) with limited capacity; the late phase produces matrix SPNs through fate-restricted basal IPs (bIPMs) with expanded capacity. Remarkably, direct and indirect pathway SPNs arise within both aIPSand bIPMpools, suggesting that striosome-matrix architecture is the fundamental organizational plan of basal ganglia circuitry organization.
Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue
Authors: Haridas Parvathi , Browning Alexander P. , McGovern Jacqui A. , McElwain D.L. Sean , Simpson Matthew J.
Published: January 2018

Background

Melanoma can be diagnosed by identifying nests of cells on the skin surface. Understanding the processes that drive nest formation is important as these processes could be potential targets for new cancer drugs. Cell proliferation and cell migration are two potential mechanisms that could conceivably drive melanoma nest formation. However, it is unclear which one of these two putative mechanisms plays a dominant role in driving nest formation.

Results

We use a suite of three-dimensional (3D) experiments in human skin tissue and a parallel series of 3D individual-based simulations to explore whether cell migration or cell proliferation plays a dominant role in nest formation. In the experiments we measure nest formation in populations of irradiated (non-proliferative) and non-irradiated (proliferative) melanoma cells, cultured together with primary keratinocyte and fibroblast cells on a 3D experimental human skin model. Results show that nest size depends on initial cell number and is driven primarily by cell proliferation rather than cell migration.

Conclusions

We find that nest size depends on initial cell number, and is driven primarily by cell proliferation rather than cell migration. All experimental results are consistent with simulation data from a 3D individual based model (IBM) of cell migration and cell proliferation.
The Smallest Intestine (TSI) – a low volumein vitromodel of the small intestine with increased throughput
Authors: Cieplak T. , Wiese M. , Nielsen S. , Van de Wiele T. , van den Berg F. , Nielsen D.S.
Published: January 2018

Aims

To develop a low volumein vitromodel with increased throughput simulating the human small intestine, incorporating the presence of ileal microbiota, to study microbial behaviour in the small intestine.

Methods and Results

The Smallest Intestinein vitromodel (TSI) was developed. During the simulated passage of the small intestine bile is absorbed by dialysis and pH adjusted to physiologically relevant level. A consortium of seven representative bacterial members of the ileum microbiota is included in the ileal stage of the model. It was found that the model can be applied for the testing of survival of probiotic bacteria in upper intestine. Moreover, it was found, that the presence of the ileal microbiota significantly impacted probiotic survival.

Conclusions

TSI allows testing a substantial number of samples, at low cost and short time, and is thus suitable as anin vitroscreening platform. Multiples of five reactors can be added to increase the number of biological and technical replicates.

Significance and Impact of the Study

TSI serves as an alternative for costly and low throughputin vitromodels currently existing on the market. Above that, significance of small intestine bacteria presence on survival of probiotic bacteria in the upper intestine was proved.
Dynamic compartmentalization in neurons enables branch-specific learning
Authors: Wybo Willem A.M. , Torben-Nielsen Benjamin , Gewaltig Marc-Oliver
Published: January 2018

The dendritic trees of neurons play an important role in the information processing in the brain. While it is tacitly assumed that dendrites require independent compartments to perform most of their computational functions, it is still not understood how they compartmentalize into functional subunits. Here we show how these subunits can be deduced from the structural and electrical properties of dendrites. We devised a mathematical formalism that links the dendritic arborization to an impedance-based tree-graph and show how the topology of this tree-graph reveals independent dendritic compartments. This analysis reveals that coopera-tivity between synapses decreases less than depolarization with increasing electrical separation, and thus that surprisingly few independent subunits coexist on dendritic trees. We nevertheless find that balanced inputs or shunting inhibition can modify this topology and increase the number and size of compartments in a context-dependent, temporal manner. We also find that this dynamic recompartmentalization can enable branch-specific learning of stimulus features.
Neuron-specific cTag-CLIP reveals cell-specific diversity of functional RNA regulation in the brain
Authors: Saito Yuhki , Yuan Yuan , Zucker-Scharff Ilana , Fak John J. , Tajima Yoko , Licatalosi Donny D. , Darnell Robert B.
Published: January 2018

RNA-binding proteins (RBPs) regulate genetic diversity, but the degree to which they do so in individual cell-typesin vivois unknown. We employed NOVA2 cTag-CLIP to generate functional RBP-RNA maps from single neuronal populations in the mouse brain. Combining cell-type specific data fromNova2-cTagandNova2conditional knock-out mice revealed differential NOVA2 regulatory actions (e.g. alternative splicing) on the same transcripts in different neurons, including in cerebellar Purkinje cells, where NOVA2 acts as an essential factor for proper motor coordination and synapse formation. This also led to the discovery of a mechanism by which NOVA2 action leads to different outcomes in different cells on the same transcripts: NOVA2 is able to regulate retained introns, which subsequently serve as scaffolds for anothertrans-actingsplicing factor, PTBP2. Our results describe differential roles and mechanisms by which RBPs mediate RNA diversity in different neurons and consequent functional outcomes within the brain.
Galleria mellonella as an Insect Model for P. destructans, the Cause of White-Nose Syndrome in Bats
Authors: Beekman Chapman , Meckler Lauren , Kim Eleanor , Bennett Richard J.
Published: January 2018

Pseudogymnoascus destructans is the fungal pathogen responsible for White-nose Syndrome (WNS), a disease that has killed millions of bats in North America over the last decade. A major obstacle to research on P. destructans has been the lack of a tractable infection model for monitoring virulence. Here, we establish a high-throughput model of infection using larvae of Galleria mellonella, an invertebrate used to study host-pathogen interactions for a wide range of microbial species. We demonstrate that P. destructans can kill G. mellonella larvae in an inoculum-dependent manner when infected larvae are housed at 13°C or 18°C. Larval killing is an active process, as heat-killed P. destructans spores caused significantly decreased levels of larval death compared to live spores. We also show that fungal spores that were germinated prior to inoculation were able to kill larvae 3–4 times faster than non-germinated spores. Lastly, we identified chemical inhibitors of P. destructans and used G. mellonella to evaluate these inhibitors for their ability to reduce virulence. We demonstrate that two chemicals, trifluoperazine and amphotericin B, can effectively block larval killing by P. destructans and thereby establish that this infection model can be used to screen biocontrol agents against this fungal pathogen.
Conflicting Auxin-Phosphate Signals Impact on RSL2 Expression and ROS-Homeostasis Linked to Root Hair Growth in Arabidopsis
Authors: Mangano Silvina , Denita-Juarez Silvina Paola , Marzol Eliana , Borassi Cecilia , Estevez José M.
Published: January 2018

Here, we examined by which mechanism root hairs integrate conflicting growth-signals like the repressive high Pi-level clue and a concomitant high auxin exposure that should promote growth and questioned if these complex signals might activate known molecular players in polar growth.
Prohlatype: A Probabilistic Framework for HLA Typing
Authors: Rozenberg Leonid , Hammerbacher Jeff
Published: January 2018

HLA typing from sequencing data is considered as a classical probabilistic inference problem and Profile Hidden Markov Models (PHMM) are motivated for the likelihood calculation. Their generative property makes them a natural and highly discernible method; at the cost of considerable computation. We discuss ways to ameliorate this burden, and present an implementation https://github.com/hammerlab/prohlatype.
Neural responses in the pain matrix when observing pain of others are unaffected by testosterone administration
Authors: Heany Sarah J. , Terburg David , Stein Dan J. , van Honk Jack , Bos Peter A.
Published: January 2018

There is evidence of testosterone having deteriorating effects on cognitive and affective empathy. However, whether testosterone influences core affective empathy, that is empathy for pain, has not yet been investigated. Therefore, we tested neural responses to witnessing others in pain in a within-subject placebo controlled testosterone administration study. Using functional magnetic resonance imaging we provide affirming evidence that the empathy inducing paradigm causes changes in the activity throughout the pain circuitry, including the bilateral insula and anterior cingulate cortex. Administration of testosterone however did not influence these activation patterns in the pain matrix. Testosterone has thus downregulating effects on aspects of empathic behaviour, but based on these data does not seem to influence neural responses during core empathy for pain. This finding gives more insight into the role of testosterone in human empathy.
PET Brain imaging of α7-nAChR with [18F]ASEM
Authors: Wong Dean F. , Kuwabara Hiroto , Horti Andrew G. , Roberts Joshua M. , Nandi Ayon , Casella Nicola , Brasic James , Weerts Elise M. , Kitzmiller Kelly , Phan Jenny A. , Gapasin Lorena , Sawa Akira , Valentine Heather , Wand Gary , George Noble , McDonald Michael , Kem William , Freedman Robert , Gjedde Albert
Published: January 2018

The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The a7-nAChR primarily is located in cerebral cortex and sub-cortical regions, compared to the α4β2 nAChR subtype that has a more subcortical distribution. The highly cortical distribution suggests a role of a7-nAChR in cognition. We expanded the first-in-human PET imaging of α7-nAChR with [18F]ASEM from five to 21 healthy non-smoking volunteers and added preliminary evidence of binding in six male patients with schizophrenia. Study aims included 1) confirmation of test-retest reproducibility of [18F]ASEM binding in normal volunteers, 2) demonstration of specificity of [18F]ASEM binding by competition with DMXB-A, an α7-nAChR partial agonist previously tested in clinical trials of patients with schizophrenia, 3) estimation of [18F]ASEM binding potentials and α7-nAChR density in vivo in humans, and 4) α7-nAChR binding in patients with schizophrenia compared to healthy volunteers.

Test-retest PET confirmed reproducibility (>90%) (variability ≤ 7%) of [18F]ASEM volume of distribution (Vt) estimates in healthy volunteers. Repeated sessions of PET in five healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of α7-nAChR by DMXB-A at 17-49% for plasma concentrations at 60-200 nM DMXB-A. In agreement with evidence post-mortem, α7-nAChR density (Bmax) averaged 0.67-0.82 nM and inhibitor affinity constant (Ki) averaged 170-385 nM. Median Vt in a feasibility study of six patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus. Mann-Whitney test identified cingulate cortex and hippocampus as regions with significantly lower median Vt in patients than in healthy volunteers when a single outlier patient was excluded from analysis (P = 0.02, corrected for multiple comparisons).
Visualization of PRC2-Dinucleosome Interactions Leading to Epigenetic Repression
Authors: Poepsel Simon , Kasinath Vignesh , Nogales Eva
Published: January 2018

Epigenetic regulation is mediated by protein complexes that couple recognition of chromatin marks to activity or recruitment of chromatin-modifying enzymes. Polycomb repressive complex 2 (PRC2), a gene silencer that methylates lysine 27 of histone H3, is stimulated upon recognition of its own catalytic product, and has been shown to be more active on dinucleosomes than H3 tails or single nucleosomes. These properties likely facilitate local H3K27me2/3 spreading causing heterochromatin formation and gene repression. Here, cryo-EM reconstructions of human PRC2 bound to dinucleosomes show how a single PRC2, interacting with nucleosomal DNA, precisely positions the H3 tails to recognize a H3K27me3 mark in one nucleosome and is stimulated to modify a neighboring nucleosome. The geometry of the PRC2-DNA interactions allow PRC2 to tolerate different dinucleosome geometries due to varying lengths of the linker DNA. Our structures are the first to illustrate how an epigenetic regulator engages with a complex chromatin substrate.
Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics
Authors: Foster Charles T. , Gualdrini Francesco , Treisman Richard
Published: January 2018

Both the MRTF–SRF and the YAP–TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF–SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF–SRF and YAP–TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF–SRF genomic targets is also dependent on YAP–TEAD activity, and, conversely, YAP–TEAD target gene expression is also dependent on MRTF–SRF signaling. In normal fibroblasts, expression of activated MRTF derivatives activates YAP, while activated YAP derivatives activate MRTF. Cross-talk between the pathways requires recruitment of MRTF and YAP to DNA via their respective DNA-binding partners (SRF and TEAD) and is therefore indirect, arising as a consequence of activation of their target genes. In both CAFs and normal fibroblasts, we found that YAP–TEAD activity is sensitive to MRTF–SRF-induced contractility, while MRTF–SRF signaling responds to YAP–TEAD-dependent TGFβ signaling. Thus, the MRF–SRF and YAP–TEAD pathways interact indirectly through their ability to control cytoskeletal dynamics.
Reconstructing differentiation networks and their regulation from time series single-cell expression data
Authors: Ding Jun , Aronow Bruce J. , Kaminski Naftali , Kitzmiller Joseph , Whitsett Jeffrey A. , Bar-Joseph Ziv
Published: January 2018

Generating detailed and accurate organogenesis models using single-cell RNA-seq data remains a major challenge. Current methods have relied primarily on the assumption that descendant cells are similar to their parents in terms of gene expression levels. These assumptions do not always hold for in vivo studies, which often include infrequently sampled, unsynchronized, and diverse cell populations. Thus, additional information may be needed to determine the correct ordering and branching of progenitor cells and the set of transcription factors (TFs) that are active during advancing stages of organogenesis. To enable such modeling, we have developed a method that learns a probabilistic model that integrates expression similarity with regulatory information to reconstruct the dynamic developmental cell trajectories. When applied to mouse lung developmental data, the method accurately distinguished different cell types and lineages. Existing and new experimental data validated the ability of the method to identify key regulators of cell fate.
Microporous crystal structure of labuntsovite-Fe and high-pressure behavior up to 23 GPa
Authors: Aksenov Sergey M. , Bykova Elena A. , Rastsvetaeva Ramiza K. , Chukanov Nikita V. , Makarova Irina P. , Hanfland Michael , Dubrovinsky Leonid
Published: January 2018

Labuntsovite-Fe, an Fe-dominant member of the labuntsovite subgroup, was first discovered in the Khibiny alkaline massif on Mt Kukisvumchorr [Khomyakov et al. (2001). Zap. Vseross. Mineral. Oba,
130, 36–45]. However, no data are published about the crystal structure of this mineral. Labuntsovite-Fe from a peralkaline pegmatite located on Mt Nyorkpakhk, in the Khibiny alkaline complex, Kola Peninsula, Russia, has been investigated by means of electron microprobe analyses, single-crystal X-ray structure refinement, and IR and Raman spectroscopies. Monoclinic unit-cell parameters of labuntsovite-Fe are: a = 14.2584 (4), b = 13.7541 (6), c = 7.7770 (2) Å, β = 116.893 (3)°; V = 1360.22 (9) Å3; space group C2/m. The structure was refined to final R
1 = 0.0467, wR
2 = 0.0715 for 3202 reflections [I > 3σ(I)]. The refined crystal chemical formula is (Z = 2): Na2K2Ba0.7[(Fe0.5Ti0.1Mg0.05)(H2O)1.3]{[Ti2(Ti1.9Nb0.1)(O,OH)4][Si4O12]2}·4H2O. The high-pressure in situ single-crystal X-ray diffraction study of the labuntsovite-Fe has been carried out in a diamond anvil cell. The labuntsovite-type structure is stable up to 23 GPa and phase transitions are not observed. Calculations using the BM3 equation of state resulted in the bulk modulus K = 72 (2) GPa, K′0 = 3.7 (2) and V
0 = 1363 (2) Å3. Compressing of the heteropolyhedral zeolite-like framework leads to the deformation of main structural units. Octahedral rods show the gradual increase of distortion and the wave-like character of rods becomes more distinct. Rod deformations result in the distortion of the silicon–oxygen ring which is not equal in different directions. Structural channels are characterized by a different ellipticity–pressure relationship: the cross-section of the largest channel I and channel II demonstrates the stability of the geometrical characteristics which practically do not depend on pressure: ∊channel I ≃ 0.85 (4) (cross-section is rather regular) and ∊channel II ≃ 0.52 (2) within the whole pressure range. However, channel III is characterized by the increasing of ellipticity with pressure (∊ = 0.40 → 0.10).
X-ray, dielectric, piezoelectric and optical analyses of a new nonlinear optical 8-hydroxyquinolinium hydrogen squarate crystal
Authors: Goel Sahil , Yadav Harsh , Sinha Nidhi , Singh Budhendra , Bdikin Igor , Kumar Binay
Published: January 2018

The 1:1 complex of 8-hydroxyquinoline with squaric acid has been characterized using single-crystal X-ray diffraction, UV–vis spectroscopy, density functional theory (DFT) calculations, and photoluminescence, dielectric, piezoelectric and second-harmonic generation (SHG) studies. The title compound (8-hydroxyquinolinium hydrogen squarate; HQS) contains one protonated 8-hydroxyquinoline cation (C9H8NO+) and one hydrogen squarate mono-anion (C4HO4
−). All the intermolecular hydrogen-bonding interactions present in the HQS crystal structure are analyzed by three-dimensional molecular Hirshfeld surface analysis and their relative contributions are determined from two-dimensional fingerprint plots. The structure of C9H8NO+·C4HO4
− molecular complex has been optimized at the DFT/B3LYP/6-31G(d,p) level. The UV–vis spectroscopic data calculated by time-dependent density functional theory are compared with the experimental data. The LUMO+1, LUMO, HOMO and HOMO−1 energy values, their shapes and energy gaps are calculated using the B3LYP/6-31G(d,p) level of theory. The HQS material exhibits high SHG output (2.6 times of that of potassium dihydrogen phosphate), high photoluminescence emission centred at 474 nm and a piezoelectric charge coefficient of 3 pC N−1. Henceforth, HQS can serve as an alternative potential candidate for multifunctional nonlinear optically active and piezoelectric crystals.
Crystal structures of 2,4,6-triiodobenzonitrile and 2,4,6-triiodophenyl isocyanide
Authors: Noland Wayland E. , Britton Doyle , Sutton Gregory K. , Schneerer Andrew K. , Tritch Kenneth J.
Published: January 2018

The title crystals, C7H2I3N, are isomorphous. Both molecules lie across two crystallographic mirror planes and a twofold axis. The principal supramolecular interaction is centric R
2
2(10) CN/NC...I short contacts involving both ortho I atoms, with two contacts bisecting each cyano and isocyano group. These form ribbons along [010] and give rise to a planar sheet structure parallel to (100). All pairs of adjacent sheets have centric stacking, a mode not previously reported for sheets of this type. This study completes the series of homo-2,4,6-trihalobenzonitriles, in which I atoms give the strongest CN...X and NC...X interactions (X = F, Cl, Br, I).
Ethyl 1-phenyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylate
Authors: El-Hiti Gamal A. , Mohamed Hanan A. , Abdel-Wahab Bakr F. , Alotaibi Mohammad Hayal , Hegazy Amany S. , Kariuki Benson M.
Published: January 2018

The non-H atoms of the title molecule, C19H16N2O2, are almost coplanar (r.m.s. deviation = 0.019 Å), apart from the phenyl group, which is disordered with two components of almost equal occupancy: the dihedral angle between them is 78.9 (3)°. In the crystal, weak C—H...N hydrogen bonds link the molecules into [001] chains and aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.747 (2) Å] form columns parallel to the c-axis direction.