bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of calcineurin from GFAP-expressing astrocytes impairs excitability of cerebellar and hippocampal neurons through astroglial Na+/K+ATPase
Authors: Tapella Laura , Soda Teresa , Mapelli Lisa , Bortolotto Valeria , Bondi Heather , Ruffinatti Federico A , Dematteis Giulia , Stevano Alessio , Dionisi Marianna , Ummarino Simone , Ruscio Annalisa Di , Distasi Carla , Grilli Mariagrazia , Genazzani Armando A , D’Angelo Egidio , Moccia Francesco , Lim Dmitry 
Published: August 2019

ABSTRACTAstrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although the regulatory mechanisms are currently poorly understood. The astrocytic Ca2+/calmodulin-activated phosphatase calcineurin (CaN) is implicated in the development of reactive gliosis and neuroinflammation, but its roles, including the control of neuronal excitability, in healthy brain is unknown. We have generated a mouse line with conditional knockout (KO) of CaN B1 (CaNB1) in glial fibrillary acidic protein (GFAP)-expressing astrocytes (astroglialcalcineurinknock-out, ACN-KO). Here we report that postnatal and astrocyte-specific ablation of CaNB1 did not alter normal growth and development as well as adult neurogenesis. Yet, we found that specific deletion of astrocytic CaN selectively impairs intrinsic neuronal excitability in hippocampal CA1 pyramidal neurons and cerebellar granule cells (CGCs). This impairment was associated with a decrease in after-hyperpolarization in CGC, while passive properties were unchanged, suggesting impairment of K+homeostasis. Indeed, blockade of Na+/K+-ATPase (NKA) with ouabain phenocopied the electrophysiological alterations observed in ACN-KO CGCs. In addition, NKA activity was significantly lower in cerebellar and hippocampal lysates and in pure astrocytic cultures from ACN-KO mice. While no changes were found in protein levels, NKA activity was inhibited by the specific CaN inhibitor FK506 in both cerebellar lysates and primary astroglia from control mice, suggesting that CaN directly modulates NKA activity and in this manner controls neuronal excitability. In summary, our data provide formal evidence for the notion that astroglia is fundamental for controlling basic neuronal functions and place CaN center-stage as an astrocytic Ca2+-sensitive switch.
A cross-species neural integration of gravity for motor optimisation
Authors: Gaveau Jeremie , Grospretre Sidney , Angelaki Dora , Papaxanthis Charalambos 
Published: August 2019

AbstractRecent kinematic results, combined with model simulations, have provided support for the hypothesis that the human brain uses an internal model of gravity to shape motor patterns that minimise muscle effort. Because many different muscular activation patterns can give rise to the same trajectory, here we analyse muscular activation patterns during single-degree-of-freedom arm movements in various directions, which allow to specifically investigating gravity-related movement properties. Using a well-known decomposition method of tonic and phasic electromyographic activities, we demonstrate that phasic EMGs present systematic negative phases. This negativity demonstrates that gravity effects are harvested to save muscle effort and reveals that the brain implements an optimal motor plan using gravity to accelerate downward and decelerate upward movements. Furthermore, for the first time, we compare experimental findings in humans to monkeys, thereby generalising the Effort-optimization strategy across species.
Estrogen mediates acute elastic fibre homeostasis in skin
Authors: Saville Charis R , Holmes David F , Swift Joe , Derby Brian , Emmerson Elaine , Hardman Matthew J , Sherratt Michael J 
Published: August 2019

ABSTRACTRemodelling of the dermal extracellular matrix makes a major contribution to skin fragility in the elderly. The peri-menopausal period in females is also associated with an age-like phenotype which can be reversed by hormone replacement therapy. This suggests a direct link between circulating hormone levels and tissue ageing. Despite work investigating the role of estrogen as a regulator of collagen fibril abundance and structure, the influence of estrogen on the elastic fibre system remains poorly defined. Here we used an ovariectomised (Ovx) mouse surgical menopause model to show that just 7 weeks of acute hormone deficiency significantly decreased skin tensile strength and elasticity. Systemic replacement of 17β-estradiol to physiological levels protected against these changes to the skin mechanical properties. Moreover, acute hormone deficiency differentially influenced dermal structural networks, significantly decreasing dermal elastic fibre abundance without discernible effect on collagen fibril organisation or abundance. We suggest that this specific elastic fibre proteolysis may be driven by extracellular protease activity, or be a consequence of significant adipocyte hypertrophy. 17β-estradiol supplementation in Ovx micein vivoprotected the elastic fibre system. Treatment of human dermal fibroblasts with 17β-estradiolin vitroinduced the selective upregulation of tropoelastin, fibrillin-1 and associated elastic fibre-associated proteins (including EMILINs and fibulins). In summary, these data show that the elastic fibre system is significantly perturbed by estrogen deprivation. Thus, pharmacological intervention may slow the acute effects of menopause and potentially the chronic effects of ageing in skin.
Feedback control of a two-component signaling system by an Fe-S-binding receiver domain
Authors: Stein Benjamin J. , Fiebig Aretha , Crosson Sean 
Published: August 2019

AbstractTwo-component signaling systems (TCSs) function to detect environmental cues and transduce this information into a change in transcription. In its simplest form, TCS-dependent regulation of transcription entails phosphoryl-transfer from a sensory histidine kinase to its cognate DNA-binding receiver protein. However, in certain cases, auxiliary proteins may modulate TCSs in response to secondary environmental cues.Caulobacter crescentusFixT is one such auxiliary regulator. FixT is composed of a single receiver domain and functions as a feedback inhibitor of the FixL-FixJ (FixLJ) TCS, which regulates the transcription of genes involved in adaptation to microaerobiosis. We sought to define the impact offixTonCaulobactercell physiology and to understand the molecular mechanism by which FixT represses FixLJ signaling.fixTdeletion results in excess production of porphyrins and premature entry into stationary phase, demonstrating the importance of feedback inhibition of the FixLJ signaling system. Although FixT is a receiver domain, it does not affect dephosphorylation of the oxygen-sensor kinase FixL or phosphoryltransfer from FixL to its cognate receiver FixJ. Rather, FixT represses FixLJ signaling by inhibiting the FixL autophosphorylation reaction. We have further identified a 4-cysteine motif inCaulobacterFixT that binds an Fe-S cluster and protects the protein from degradation by the Lon protease. Our data support a model in which oxidation of this Fe-S cluster promotes degradation of FixTin vivo. This proteolytic mechanism facilitates clearance the of the FixT feedback inhibitor from the cell under normoxia and resets the FixLJ system for a future microaerobic signaling event.ImportanceTwo-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components: a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that a single-domain receiver protein, FixT, binds an Fe-S cluster and controlsCaulobacterheme homeostasis though its function as a negative feedback regulator of the oxygen-sensor kinase, FixL. We provide evidence that the Fe-S cluster protects FixT from Lon-dependent proteolysis in the cell and endows FixT with the ability to function as a second, autonomous oxygen/redox sensor in the FixL-FixJ signaling pathway. This study introduces a novel mechanism of regulated TCS feedback control by an Fe-S-binding receiver domain.
Six-state amino acid recoding is not an effective strategy to offset the effects of compositional heterogeneity and saturation in phylogenetic analyses
Authors: Hernandez Alexandra M. , Ryan Joseph F. 
Published: August 2019

AbstractSix-state amino acid recoding strategies are commonly applied to combat the effects of compositional heterogeneity and substitution saturation in phylogenetic analyses. While these methods have been endorsed from a theoretical perspective, their performance has never been extensively tested. Here, we test the effectiveness of 6-state recoding approaches by comparing the performance of analyses on recoded and non-recoded datasets that have been simulated under gradients of compositional heterogeneity or saturation. In all of our simulation analyses, non-recoding approaches greatly outperformed 6-state recoding approaches. Our results suggest that 6-state recoding strategies are not effective in the face of high saturation. Further, while recoding strategies do buffer the effects of compositional heterogeneity, the loss of information that accompanies 6-state recoding outweighs its benefits, even in the most compositionally heterogeneous datasets. In addition, we evaluate recoding schemes with 9, 12, 15, and 18 states and show that these all outperform 6-state recoding. Our results have important implications for the more than 70 published papers that have incorporated 6-state recoding, many of which have significant bearing on relationships across the tree of life.
Vasoactive intestinal peptide confers anticipatory mucosal immunity by regulating ILC3 activity
Authors: Seillet Cyril , Luong Kylie , Tellier Julie , Jacquelot Nicolas , Shen Rui Dong , Hickey Peter , Wimmer Verena C. , Whitehead Lachlan , Rogers Kelly , Smyth Gordon K. , Garnham Alexandra L. , Ritchie Matthew , Belz Gabrielle T. 
Published: August 2019

AbstractILC3-mediated IL-22 cytokine production is critical for the maintenance of immune homeostasis in the gastrointestinal tract. Here, we show that group 3 ILC (ILC3) constitutive function is not constant across the day but instead oscilliates between active and resting phases. Coordinate responsiveness of ILC3 in the intestine depended on food-induced expression of the neuronal hormone vasoactive intestinal peptide (VIP). Intestinal ILC3 expressed high levels of the G protein-coupled receptor, VIPR2, and activation via enteric neuronal VIP markedly enhanced IL-22 production and conferred gut protection. Conversely, deficiency of VIPR2 signalling led to impaired production of IL-22 by ILC3 and increased susceptibility to inflammatory gut disease. As such, intrinsic cellular rhythms synergise with the cyclic patterns of food intake to drive IL-22 thereby syncronizing intestinal epithelial protection via the ILC3 VIP-VIPR2 pathway.
Revisiting the Natural History of Pulmonary Tuberculosis: a Bayesian Estimation of Natural Recovery and Mortality rates
Authors: Ragonnet Romain , Flegg Jennifer A. , Brilleman Samuel L. , Tiemersma Edine , Melsew Yayehirad A. , McBryde Emma S. , Trauer James M. 
Published: August 2019

AbstractBackgroundTuberculosis (TB) natural history remains poorly characterised and new investigations are impossible as it would be unethical to follow up TB patients without treating them. Estimates of TB burden and mortality rely heavily on TB self-recovery and mortality rates, as around 40% of individuals with TB are never detected, making their prognosis entirely dependent on the disease natural history.MethodsWe considered the reports identified in a previous systematic review of studies from the prechemotherapy era, and extracted detailed data on mortality over time. We used a continuous-time Markov model in a Bayesian framework to estimate the rates of TB-induced mortality and self-cure. A hierarchical model was employed to allow estimates to vary by cohort. Inference was performed separately for smear-positive TB (SP-TB) and smear-negative TB (SN-TB).ResultsWe included 41 cohorts of SP-TB patients and 19 cohorts of pulmonary SN-TB patients in the analysis. No data were available on extrapulmonary TB. The posterior median estimates of the TB-specific mortality rates were 0.390 year−1 (0.329-0.452, 95% credible interval) and 0.025 year−1 (0.016-0.036) for SP-TB and SN-TB patients, respectively. The estimates for self-recovery rates were 0.233 year−1 (0.179-0.293) and 0.147 year−1 (0.087-0.248) for SP-TB and SN-TB patients, respectively. These rates correspond to average durations of untreated TB of 1.57 years (1.37-1.81) and 5.35 years (3.42-8.23) for SP-TB and SN-TB, respectively, when assuming a natural mortality rate of 0.014 year−1 (i.e. a 70-year life expectancy).ConclusionsTB-specific mortality rates are around 15 times higher for SP-TB than for SN-TB patients. This difference was underestimated dramatically in previous TB modelling studies that parameterised models based on the ratio of 3.3 between the 10-year case fatality of SP-TB and SN-TB. Our findings raise important concerns about the accuracy of past and current estimates of TB mortality and predicted impact of control interventions on TB mortality.
Microbial community and geochemical analyses of trans-trench sediments for understanding the roles of hadal environments
Authors: Hiraoka Satoshi , Hirai Miho , Matsui Yohei , Makabe Akiko , Minegishi Hiroaki , Tsuda Miwako , Juliarni  , Rastelli Eugenio , Danovaro Roberto , Corinaldesi Cinzia , Kitahashi Tomo , Tasumi Eiji , Nishizawa Manabu , Takai Ken , Nomaki Hidetaka , Nunoura Takuro 
Published: August 2019

AbstractHadal trench bottom (>6,000 m below sea level) sediments harbor higher microbial cell abundance compared to adjacent abyssal plain sediments. This is supported by the accumulation of sedimentary organic matter (OM), facilitated by trench topography. However, the distribution of benthic microbes in different trench systems has not been explored yet. Here, we carried out small subunit ribosomal RNA gene tag sequencing for 92 sediment subsamples of seven abyssal and seven hadal sediment cores collected from three trench regions in the northwest Pacific Ocean: the Japan, Izu-Ogasawara, and Mariana Trenches. Tag-sequencing analyses showed specific distribution patterns of several phyla associated with oxygen and nitrate. The community structure was distinct between abyssal and hadal sediments, following geographic locations and factors represented by sediment depth. Co-occurrence network revealed six potential prokaryotic consortiums that covaried across regions. Our results further support that the endogenous OM cycle is driven by hadal currents and/or rapid burial shapes microbial community structures at trench bottom sites, in addition to vertical deposition from the surface ocean. Our trans-trench analysis highlights intra- and inter-trench distributions of microbial assemblages and geochemistry in surface seafloor sediments, providing novel insights into ultra-deep-sea microbial ecology, one of the last frontiers on our planet.
Decreasing human body temperature in the United States since the Industrial Revolution
Authors: Protsiv Myroslava , Ley Catherine , Lankester Joanna , Hastie Trevor , Parsonnet Julie 
Published: August 2019

ABSTRACTIn the US, the normal, oral temperature of adults is, on average, lower than the canonical 37°C established in the 19th century. We postulated that body temperature has decreased over time. Using measurements from three cohorts--the Union Army Veterans of the Civil War (N=23,710; measurement years 1860-1940), the National Health and Nutrition Examination Survey I (N=15,301; 1971-1975), and the Stanford Translational Research Integrated Database Environment (N=150,280; 2007-2017)--we determined that mean body temperature in men and women, after adjusting for age, height, weight and, in some models date and time of day, has decreased monotonically by 0.03°C per birth decade. A similar decline within the Union Army cohort as between cohorts, makes measurement error an unlikely explanation. This substantive and continuing shift in body temperature—a marker for metabolic rate—provides a framework for understanding changes in body habitus and human longevity over the last 200 years.
Economic inequality: problems and perspectives for interdisciplinary accounting research
Authors: Tweedie Dale , Hazelton James 
Published: August 2019

Purpose
The purpose of this paper is to encourage and advance interdisciplinary accounting research on economic inequality.

Design/methodology/approach
The authors review prior research into economic inequality, including two new papers in this issue, to identify topics where economic inequality and accounting research intersect. The authors then draw on prior accounting research to identify frameworks accounting scholars already use apposite to analysing these topics.

Findings
Economic inequality cuts across major accounting topics, including measurement, reporting and tax. Inequality also bears on an influential agenda in interdisciplinary accounting research to hold corporations and states accountable for their impacts. Four prior research frameworks accounting scholars might apply to this agenda are: critical Marxian or post-Marxian; accounting ethics; advocacy; and disclosure studies.

Social implications
A growing body of social scientific research, as well as influential global institutions, social movements and political debates, raise concerns over inequitable global distributions of wealth and income. The authors explore ways accounting scholars can help redress these inequities.

Originality/value
While economic inequality affects billions of people, accounting scholarship is yet to give these inequities the attention their scale and social impact merits. The authors suggest ways accounting researchers can make substantive contributions to addressing this issue.
Who gets all the PIE? Regulation of the statutory audit for private UK companies
Authors: Clacher Iain , Duboisée de Ricquebourg Alan , May Amy 
Published: August 2019

Purpose
While recently introduced EU regulation on the statutory audit of public interest entities (PIEs) aims to improve audit competition and quality, its success and impact depends on the definition of a PIE applied across the various EU Member States. In the UK, even though little is known about their auditing choices, these changes will not apply to most private companies despite their importance to the wider economy. The purpose of this paper is to provide an in-depth analysis of the private company audit market and examine the lobbying behaviour of the accounting profession around the definition of a PIE in the UK.

Design/methodology/approach
Using a large panel of independent private company audits in the UK and a textual analysis of submitted comment letters to a government consultation on the new regulation, this paper presents a comprehensive analysis of the audit market for private companies by measuring supplier concentration using four different measures of market share, and of the lobbying behaviour of the accounting profession.

Findings
There are two main findings. First, the private company audit market is characterised by low auditor switching rates along with a tight oligopoly of the largest independent private company audits maintained by the Big Four audit firms. Second, the lobbying behaviour of accounting and audit firms sought, and succeeded, to limit the scope of the definition of a PIE in the UK, consistent with the theoretical predictions of monopoly capitalism and the theory of professions.

Originality/value
The paper shows that the definition and scope of a PIE needs revisiting both within the UK and across all EU Member States, with a view to including more of these economically important private companies and highlights the policy challenge of increasing competition and choice in a concentrated audit market.
Modelling the penetration of magnetic flux in thin superconducting films with shell transformations
Authors: Burger Loïc , Geuzaine Christophe , Henrotte Francois , Vanderheyden Benoît 
Published: August 2019

Purpose
Finite element (FE) models are considered for the penetration of magnetic flux in type-II superconductor films. A shell transformation allows boundary conditions to be applied at infinity with no truncation approximation. This paper aims to determine the accuracy and efficiency of shell transformation techniques in such non-linear eddy current problems.

Design/methodology/approach
A three-dimensional H – ϕ formulation is considered, where the reaction field is calculated in the presence of a uniform applied field. The shell transformation is used in the far-field region, and the uniform applied field is introduced through surface terms, so as to avoid infinite energy terms. The resulting field distributions are compared against known solutions for different geometries (thin disks and thin strips in the critical state, square thin films). The influence of the shape, size and mesh quality of the far-field regions are discussed.

Findings
The formulation is shown to provide accurate results for a number of film geometries and shell transformation shapes. The size of the far-field region has to be chosen in such a way to properly capture the asymptotic decay of the fields, and a practical procedure to determine this size is provided.

Originality/value
The importance of the size of the far-field region in a shell transformation and its proximity to the conducting domains are both highlighted. This paper also provides a numerical way to apply a constant magnetic field in a given region, while the source, on which only the far-field behaviour of the applied field depends, is excluded from the model.
Comparison of different vector Preisach models for the simulation of ferromagnetic materials
Authors: Nierla Michael , Loeffler Michael , Kaltenbacher Manfred , Rupitsch Stefan Johann 
Published: August 2019

Purpose
The numerical computation of magnetization processes in moving and rotating assemblies requires the usage of vector hysteresis models. A commonly used model is the so-called Mayergoyz vector Preisach model, which applies the scalar Preisach model into multiple angles of the halfspace. The usage of several scalar models, which are optionally weighted differently, enables the description of isotropic as well as anisotropic materials. The flexibility is achieved, however, at the cost of multiple scalar model evaluations. For solely isotropic materials, two vector Preisach models, based on an extra rotational operator, might offer a lightweight alternative in terms of evaluation cost. The study aims at comparing the three mentioned models with respect to computational efficiency and practical applicability.

Design/methodology/approach
The three mentioned vector Preisach models are compared with respect to their computational costs and their representation of magnetic polarization curves measured by a vector vibrating sample magnetometer.

Findings
The results prove the applicability of all three models to practical scenarios and show the higher efficiency of the vector models based on rotational operators in terms of computational time.

Originality/value
Although the two vector Preisach models, based on an extra rotational operator, have been proposed in 2012 and 2015, their practical application and inversion has not been tested yet. This paper not only shows the usability of these particular vector Preisach models but also proves the efficiency of a special stageless evaluation approach that was proposed in a former contribution.