bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmural Myocardial Scar Assessed by Cardiac Computed Tomography: Predictor of Echocardiographic Versus Clinical Response to Cardiac Resynchronization Therapy?
Authors: Fyenbo Daniel Benjamin , Sommer Anders , Kühl J. Tobias , Kofoed Klaus F. , Nørgaard Bjarne L. , Kronborg Mads B. , Bouchelouche Kirsten , Nielsen Jens C.
Published: November 2018

Objectives

Before cardiac resynchronization therapy (CRT) implantation, cardiac computed tomography (CT) can provide assessment of cardiac venous anatomy and visualize left ventricular (LV) myocardial scar. We hypothesized that localization and burden of transmural myocardial scar verified by cardiac CT are associated with echocardiographic and clinical response to CRT.

Methods

We prospectively included 140 CRT recipients undergoing preimplant cardiac CT. We assessed transmural scar, defined as hypoperfusion involving more than one-half of the myocardial wall in each LV segment using a 17-segment model. Echocardiographic nonresponse was defined as less than 5% absolute improvement in LV ejection fraction at 6 months' follow-up. Clinical nonresponse was defined as 1 or more of the following at 6 months' follow-up: death, heart failure hospitalization, or no improvement in New York Heart Association class and less than 10% increase in 6-minute walk-test distance.

Results

Higher burden of myocardial scar was associated with echocardiographic nonresponse (adjusted odds ratio, 3.02; 95% confidence interval, 1.03–8.91; P = 0.045). Scar concordant or adjacent to LV pacing site was associated with echocardiographic nonresponse (adjusted odds ratio, 8.2; 95% confidence interval, 1.51–44.27; P = 0.015). No association between scar and clinical nonresponse was demonstrated.

Conclusions

Higher scar burden and scar in proximity to the LV pacing site assessed by cardiac CT are associated with echocardiographic nonresponse to CRT. Burden and location of scar were not associated with clinical nonresponse. Further large-scale studies are needed to assess the potential association between myocardial scar detected by cardiac CT and clinical CRT outcome.
Cardiac Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine
Authors: Datzmann Thomas , Wepler Martin , Wachter Ulrich , Vogt Josef A. , McCook Oscar , Merz Tamara , Calzia Enrico , Gröger Michael , Hartmann Clair , Asfar Pierre , Radermacher Peter , Nussbaum Benedikt Lukas
Published: November 2018

Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular comorbidity.

After 3 h of hemorrhage (removal of 30% of the calculated blood volume and subsequent titration of mean arterial pressure to 40 mm Hg) 19 anesthetized, mechanically ventilated, and instrumented pigs received FIO2 = 0.3(control) or hyperoxia(FIO2 = 1.0) during the first 24 h. Before, at the end of and every 12 h after shock, hemodynamics, blood gases, metabolism, cytokines, and cardiac function (pulmonary artery thermodilution, left ventricular pressure-conductance catheterization) were recorded. At 48 h, cardiac tissue was harvested for western blotting, immunohistochemistry, and mitochondrial respiration.

Except for higher left ventricular end-diastolic pressures at 24 h (hyperoxia 21 (17;24), control 17 (15;18) mm Hg; P = 0.046), hyperoxia affected neither left ventricular function cardiac injury (max. Troponin I at 12 h: hyperoxia:9 (6;23), control:17 (11;24) ng mL−1; P = 0.395), nor plasma cytokines (except for interleukin-1β: hyperoxia 10 (10;10) and 10 (10;10)/control 14 (10;22), 12 (10;15) pg mL−1, P = 0.023 and 0.021 at 12 and 24 h, respectively), oxidation and nitrosative stress, and mitochondrial respiration. However, hyperoxia decreased cardiac tissue three-nitrotyrosine formation (P < 0.001) and inducible nitric oxide synthase expression (P = 0.016). Ultimately, survival did not differ significantly either.

In conclusion, in contrast to our previous study in swine with coronary artery disease, hyperoxia did not beneficially affect cardiac function or tissue injury in healthy swine, but was devoid of deleterious side effects.
Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock
Authors: Hofmann Nikolaus , Zipperle Johannes , Brettner Florian , Jafarmadar Mohammad , Ashmwe Mostafa , Keibl Claudia , Ponschab Martin , Kipman Ulrike , Bahrami Arian , Redl Heinz , Bahrami Soheyl , Fuhrmann Valentin , Schöchl Herbert
Published: November 2018

Background:

Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS.

Methods:

Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30–35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1).

Results:

Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL).

Conclusion:

The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential.

Level of evidence:

V

Experimental in vivo study.
Reproductive resilience of an estuarine fish in the eye of a hurricane
Authors: Biggs Christopher R. , Lowerre-Barbieri Susan K. , Erisman Brad
Published: November 2018

Spatial and temporal patterns of spawning activity are important measures of resilience in fishes that directly link environmental disturbances with reproductive success. We acoustically monitored spawning in spotted seatrout (
Cynoscion nebulosus
) from April through September 2017 at 15 sites near Port Aransas, Texas, which coincided with the landfall of a category 4 hurricane (Harvey) on 25 August. Spawning sounds were recorded every day of the study across all sites and were also confirmed during the hurricane at two sites located within the eye of the storm. Daily spawning continued after the hurricane, but the onset of spawning shifted 2.12 h earlier for 5 days, after which it returned to the pre-storm schedule. These results illustrate the resilience of seatrout to intense, episodic disturbances and offer insights on the phenotypic plasticity of estuarine fishes to cope with projected increases in environmental variability.
Social eavesdropping allows for a more risky gliding strategy by thermal-soaring birds
Authors: Williams Hannah J. , King Andrew J. , Duriez Olivier , Börger Luca , Shepard Emily L. C.
Published: November 2018

Vultures are thought to form networks in the sky, with individuals monitoring the movements of others to gain up-to-date information on resource availability. While it is recognized that social information facilitates the search for carrion, how this facilitates the search for updrafts, another critical resource, remains unknown. In theory, birds could use information on updraft availability to modulate their flight speed, increasing their airspeed when informed on updraft location. In addition, the stylized circling behaviour associated with thermal soaring is likely to provide social cues on updraft availability for any bird operating in the surrounding area. We equipped fiveGypsvultures with GPS and airspeed loggers to quantify the movements of birds flying in the same airspace. Birds that were socially informed on updraft availability immediately adopted higher airspeeds on entering the inter-thermal glide; a strategy that would be risky if birds were relying on personal information alone. This was embedded within a broader pattern of a reduction in airspeed (approx. 3 m s−1) through the glide, likely reflecting the need for low speed to sense and turn into the next thermal. Overall, this demonstrates (i) the complexity of factors affecting speed selection over fine temporal scales and (ii) thatGypsvultures respond to social information on the occurrence of energy in the aerial environment, which may reduce uncertainty in their movement decisions.
Phosphorylation of Parkin at serine 65 is essential for its activationin vivo
Authors: McWilliams Thomas G. , Barini Erica , Pohjolan-Pirhonen Risto , Brooks Simon P. , Singh François , Burel Sophie , Balk Kristin , Kumar Atul , Montava-Garriga Lambert , Prescott Alan R. , Hassoun Sidi Mohamed , Mouton-Liger François , Ball Graeme , Hills Rachel , Knebel Axel , Ulusoy Ayse , Di Monte Donato A. , Tamjar Jevgenia , Antico Odetta , Fears Kyle , Smith Laura , Brambilla Riccardo , Palin Eino , Valori Miko , Eerola-Rautio Johanna , Tienari Pentti , Corti Olga , Dunnett Stephen B. , Ganley Ian G. , Suomalainen Anu , Muqit Miratul M. K.
Published: November 2018

Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture andin vitrostudies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination of damaged mitochondria via mitophagy. PINK1 phosphorylates ubiquitin at serine 65 (Ser65) and Parkin at an equivalent Ser65 residue located within its N-terminal ubiquitin-like domain, resulting in activation; however, the physiological significance of Parkin Ser65 phosphorylationin vivoin mammals remains unknown. To address this, we generated aParkinSer65Ala (S65A) knock-in mouse model. We observe endogenous Parkin Ser65 phosphorylation and activation in mature primary neurons following mitochondrial depolarization and reveal this is disrupted inParkinS65A/S65Aneurons. Phenotypically,ParkinS65A/S65Amice exhibit selective motor dysfunction in the absence of any overt neurodegeneration or alterations in nigrostriatal mitophagy. The clinical relevance of our findings is substantiated by the discovery of homozygous PARKIN (PARK2) p.S65N mutations in two unrelated patients with PD. Moreover, biochemical and structural analysis demonstrates that the ParkinS65N/S65Nmutant is pathogenic and cannot be activated by PINK1. Our findings highlight the central role of Parkin Ser65 phosphorylation in health and disease.
The recovery of North Atlantic right whales,Eubalaena glacialis, has been constrained by human-caused mortality
Authors: Corkeron Peter , Hamilton Philip , Bannister John , Best Peter , Charlton Claire , Groch Karina R. , Findlay Ken , Rowntree Victoria , Vermeulen Els , Pace Richard M.
Published: November 2018

North Atlantic right whales (NARW),Eubalaena glacialis, were nearly exterminated by historical whaling. Their abundance slowly increased up until 2010, to a maximum of fewer than 500 whales, and since then they have been in decline. We assessed the extent to which the relatively slow increase demonstrated by NARW was intrinsic, and how much could be due to anthropogenic impacts. In order to do so, we first compared calf counts of three populations of Southern right whales (SRW),E. australis, with that of NARW, over the period 1992–2016. By this index, the annual rate of increase of NARW was approximately one-third of that of SRW. Next we constructed a population projection model for female NARW, using the highest annual survival estimates available from recent mark–resight analysis, and assuming a four-year calving interval. The model results indicated an intrinsic rate of increase of 4% per year, approximately twice that observed, and that adult female mortality is the main factor influencing this rate. Necropsy records demonstrate that anthropogenic mortality is the primary cause of known mortality of NARW. Anthropogenic mortality and morbidity has limited the recovery of NARW, and baseline conditions prior to their recent decline were already jeopardizing NARW recovery.
The research progress of p53 tumour suppressor activity controlled by Numb in triple-negative breast cancer
Authors: Xian Jie , Cheng Yu , Qin Xue , Luo Yequn , Cao Yijia , Cao Youde
Published: November 2018

Numb is known as a cell fate determinant as it determines the direction of cell differentiation by asymmetrically partitioning at mitosis. It has been shown to be a tumor suppressor, and there is frequent loss of Numb expression in breast cancer. Numb enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. The aim of this study was to investigate the expression and migration of Numb, HDM2 and p53 proteins in the membrane, cytoplasmic and nuclear fractions of MCF-10A cells and MDA-MB-231 cells. We extracted the cell fractions to detect changes of these three protein levels after re-expression of NUMB in the basal-like triple-negative cell line MDA-MB-231 and knocking down NUMB in the normal mammary epithelial cell line MCF-10A. Our results show that Numb protein can migrate from cytoplasm to nucleus of the MDA-MB-231 cells. Numb protein regulates p53 levels in nucleus of MCF-10A cells and MDA-MB-231 cells, and the Numb levels is positively correlated with p53 levels. We have a finding on HDM2 protein that after knocking down NUMB in MCF-10A cells, it was remarkably reduced in the membrane fraction of NUMB knockdown cells, but its mRNA levels was significantly increased. We also examined the Numb expression in 125 patients with triple-negative breast cancer, 61(48.8%) displayed deficient or reduced expression of Numb. The percent of Ki67>14% in retained Numb group was significantly lower than that in the reduced and deficient Numb group (86.00% vs. 98.40%, P=0.0171).
Plum is a novel regulator of synaptic function and muscle size inD. melanogaster
Authors: Augustin Hrvoje , Spiers Jereme G. , Woodling Nathaniel S. , Steinert Joern R. , Partridge Linda
Published: November 2018

Alterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), theDrosophilahomolog of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction (NMJ), and a negative regulator of body weight and muscle size and function in flies. Here, we identified Plum, a cell surface immunoglobulin homologous to mammalian developmental regulators Protogenin and Nope, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum specifically in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function, likely by de-sequestrating the remaining MYO. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions.
Characterization of glutamatergic VTA neural population responses to aversive and rewarding conditioning in freely-moving mice
Authors: Montardy Quentin , Zhou Zheng , Lei Zhuogui , Liu Xuemei , Zeng Pengyu , Chen Chen , Liu Yuanming , Sanz-Leon Paula , Huang Kang , Wang Liping
Published: November 2018

The Ventral Tegmental Area (VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, a function involving VTA Dopaminergic and GABAergic neurons. VTA also contains a less known population: glutamatergic (VGluT2) neurons. Direct activation of VGluT2 soma evokes rewarding behaviors, while stimulation of their axonal projections to the Nucleus Accumbens (NAc) and the Lateral Habenula (LHb) evokes aversive behaviors. Here, a systematic investigation of the VTAVGluT2+ population response to aversive or rewarding conditioning facilitated our understanding these conflicting properties. We recorded calcium signals from VTA glutamatergic population neurons using fiber photometry in VGluT2-cre mice to investigate how the VTA glutamatergic neuronal population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+ neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. The inputs and outputs of VTAVGluT2+ neurons were then investigated using Cholera Toxin B (CTB) and rabies virus, and we propose based on all results that VTAVGluT2+ neurons specialized function may be partially due to their connectivity.
Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner
Authors: Sepahi Ali , Kraus Aurora , Johnston Christopher A , Galindo-Villegas Jorge , Kelly Cecelia , García-Moreno Diana , Muñoz Pilar , Mulero Victoriano , Huertas Mar , Salinas Irene
Published: November 2018

The nervous system is known to regulate host immune responses. However, the ability of neurons to detect danger and initiate immune responses at barrier tissues is unclear. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with the external environment and therefore directly exposed to pathogens. Here, we report that nasal delivery of rhadboviruses induced apoptosis in crypt OSNs in rainbow trout olfactory organ (OO) via the interaction of the OSN TrkA receptor with viral glycoprotein. This signal resulted in pro-inflammatory responses in the OO and dampened inflammation in the olfactory bulb (OB). CD8α+cells infiltrated the OO within minutes of nasal viral delivery and this response was abrogated when TrkA was blocked. Infiltrating CD8α+cells originated from the microvasculature surrounding the OB and not the periphery. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviral challenge. Our results, therefore, indicate a novel function for OSNs as a first layer of pathogen detection in vertebrates.
NCLX prevents cell death during adrenergic activation of the brown adipose tissue
Authors: Assali Essam A. , Jones Anthony E. , Veliova Michaela , Taha Mahmoud , Miller Nathanael , Shum Michaël , Oliveira Marcus F. , Las Guy , Liesa Marc , Sekler Israel , Shirihai Orian S.
Published: November 2018

A sharp increase in mitochondrial Ca2+marks the activation of the brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca2+deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca2+extrusion via the mitochondrial Na+/Ca2+exchanger, NCLX. Adrenergic stimulation of NCLX-ablated brown adipocytes (BA) induces a profound mitochondrial Ca2+overload and impaired uncoupled respiration. Core body temperature, PET imaging and VO2 measurements confirm a BAT specific thermogenic defect in NCLX-null mice.

We show that mitochondrial Ca2+overload induced by adrenergic stimulation of NCLX-null BAT, triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to remarkable mitochondrial swelling, Cytochromecrelease and cell death in BAT. However, treatment with mPTP inhibitors rescue mitochondrial respiratory function and thermogenesis in NCLX-null BA,in vitroandin vivo.

Our findings identify a novel pathway enabling non-lethal mitochondrial Ca2+elevation during adrenergic stimulation of uncoupled respiration. Deletion of NCLX transforms the adrenergic pathway responsible for the stimulation of thermogenesis into a death pathway.
Bacteria in Paper, a versatile platform to study bacterial ecology
Authors: Hol Felix JH , Whitesides George M , Dekker Cees
Published: November 2018

Habitat spatial structure has a profound influence on bacterial life, yet there currently are no low-cost equipment-free laboratory techniques to reproduce the intricate structure of natural bacterial habitats. Here, we demonstrate the use of paper scaffolds to create landscapes spatially structured at the scales relevant to bacterial ecology. In paper scaffolds, planktonic bacteria migrate through liquid filled pores, while the paper’s cellulose fibers serve as anchor points for sessile colonies (biofilms). Using this novel approach we explore bacterial colonization dynamics in different landscape topographies, and characterize the community composition of Escherichia coli strains undergoing centimeter-scale range expansions in habitats structured at the micrometer scale. The bacteria-in-paper platform enables quantitative assessment of bacterial community dynamics in complex environments using everyday materials.
Unlocking HDR-mediated Nucleotide Editing by identifying high-efficiency target sites using machine learning
Authors: O’Brien Aidan R. , Wilson Laurence O.W. , Burgio Gaetan , Bauer Denis C.
Published: November 2018

Editing individual nucleotides is a crucial component for validating genomic disease association. It currently is hampered by CRISPR-Cas-mediated “base editing” being limited to certain nucleotide changes, and only achievable within a small window around CRISPR-Cas target sites. The more versatile alternative, HDR (homology directed repair), has a 4-fold lower efficiency with known optimization factors being largely immutable in experiments. Here, we investigated the variable efficiency-governing factors on a novel mouse dataset using machine learning. We found the sequence composition of the repair template (ssODN) to be a governing factor, where different regions of the ssODN have variable influence, which reflects the underlying biophysical mechanism. Our model improves HDR efficiency by 83% compared to traditionally chosen targets. Using our findings, we develop CUNE (Computational Universal Nucleotide Editor), which enables users to identify and design the optimal targeting strategy using traditional base editing or – for-the-first-time – HDR-mediated nucleotide changes.

CUNE can be run via the web at:https://gt-scan.net/cune
L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks
Authors: Plumbly William , Brandon Nicholas J. , Deeb Tarek Z. , Hall Jeremy , Harwood Adrian J.
Published: November 2018

The combination of in vitro multi-electrode arrays (MEAs) and the neuronal differentiation of stem cells offers the capability to study human neuronal networks from patient or engineered human cell lines. Here, we use MEA-based assays to probe synaptic function and network interactions of hiPSC-derived neurons. Neuronal network behaviour first emerges at approximately 30 days of culture and is driven by glutamate neurotransmission. Over a further 30 days, inhibitory GABergic signalling shapes network behaviour into a synchronous regular pattern of burst firing activity and low activity periods. Gene mutations in L-type voltage gated calcium channel subunit genes are strongly implicated as genetic risk factors for the development of schizophrenia and bipolar disorder. We find that, although basal neuronal firing rate is unaffected, there is a dose-dependent effect of L-type voltage gated calcium channel inhibitors on synchronous firing patterns of our hiPSC-derived neural networks. This demonstrates that MEA assays have sufficient sensitivity to detect changes in patterns of neuronal interaction that may arise from hypo-function of psychiatric risk genes. Our study highlights the utility of in vitro MEA based platforms for the study of hiPSC neural network activity and their potential use in novel compound screening.
Inferring B cell specificity for vaccines using a mixture model
Authors: Fowler Anna , Galson Jacob D. , Trück Johannes , Kelly Dominic F. , Lunter Gerton
Published: November 2018

Vaccines have greatly reduced the burden of infectious disease, ranking in their impact on global health second only after clean water. Most vaccines confer protection by the production of antibodies with binding affinity for the antigen, which is the main effector function of B cells. This results in short term changes in the B Cell receptor (BCR) repertoire when an immune response is launched, and long term changes when immunity is conferred. Analysis of antibodies in the serum is usually used to evaluate vaccine response, however this is limited and therefore the investigation of the BCR repertoire provides far more detail for the analysis of vaccine response. Here, we introduce a novel Bayesian model to describe the observed distribution of BCR sequences and the pattern of sharing across time and between individuals, with the goal to identify vaccine-specific BCR sequences. We use data from two studies to assess the model and estimate that we can identify vaccine-specific sequences with 69% sensitivity.
Probiotic Associated Therapeutic Curli Hybrids (PATCH)
Authors: Praveschotinunt Pichet , Duraj-Thatte Anna M. , Gelfat Ilia , Bahl Franziska , Chou David B. , Joshi Neel S.
Published: November 2018

There is an unmet need for new treatment methods for inflammatory bowel disease (IBD) that can reliably maintain remission without leading to detrimental side effects. Beneficial bacteria have been utilized as an alternative treatment for IBD albeit with low efficacy. We genetically engineered Escherichia coli Nissle 1917 (EcN) to create an anti-inflammatory fibrous matrix in situ. This matrix consists of EcN-produced curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirmed that engineered EcN was able to secrete the curli-fused TFFs in vitro and in vivo, and was non-pathogenic. We observed an enhanced protective effect of engineered EcN against dextran sodium sulfate induced colitis in mice, associated with barrier function reinforcement and immunomodulation. This work sets the foundation for the development of a novel therapeutic platform in which the in situ production of a therapeutic protein matrix from beneficial bacteria can be exploited.
Real estate advertising campaigns in the context of natural hazards
Authors: Yin Long , Wang Lin , Huang Lifang , Wang Jinxiu , Xu Hui , Deng Milan
Published: November 2018

Purpose

The purpose of this paper is to examine how advertising is used by real estate companies as an instrument for managing the adverse effects of a catastrophe.

Design/methodology/approach

Through a theoretical analysis, types of post-disaster advertising messages were identified. On the basis of the likely variations in post-disaster advertising, a content analysis was conducted of a sample of 4,150 property print advertisements to identify advertising messages related to the earthquake. Finally, the message changes in these earthquake-related advertisements were evaluated and compared with the dimension of time to explore the development of advertising strategies.

Findings

The authors found that 12 types of advertising messages were used by developers in response to the Wenchuan earthquake. The initial advertising strategy was mainly to manage public relations, then the strategy was to reduce or compensate for the increased earthquake risk perceptions of buyers.

Practical implications

The findings provide valuable references for helping enterprises adopt effective advertising messages and strategies to reduce the negative effects of disasters.

Originality/value

There are only a few studies on advertising campaigns, especially in the real estate industry, that have been conducted in the wake of catastrophes. This study sought to expand upon the scarce findings in this particular field.
Does the composition of government expenditure matter for Eastern Caribbean economies’ long-run sectoral output growth?
Authors: Scott-Joseph Ankie , Turner Treshauna Felecia
Published: November 2018

Purpose

This study takes a disaggregated approach to investigate the impacts of long-run GDP on changes in total government expenditure in the Eastern Caribbean Currency Union (ECCU) economies. An understanding of the relationship between changes in total government expenditure and GDP (by sector categories) is expected to provide a working tool to understand the growth debt nexus of Caribbean countries. The purpose of the paper is to use an auto regressive distributed lag (ARDL) and error correction model (ECM) to examine and analyse short- and long-run dynamics of disaggregated approach to both output and government expenditure in a dynamic model to identify the growth in the Eastern Caribbean Countries.

Design/methodology/approach

In an attempt to examine the long-run dynamics, data for the period 1970-2015 were used in an ARDL and ECM framework. The authors examine the long-run GDP impacts of changes in total government expenditure and in the shares of different spending categories for the ECCU countries to establish and analyse short and long-run dynamics.

Findings

The results suggest that total fiscal expenditure and disaggregated expenditure including debt services have both positively and negatively contributed to economic growth in the agriculture, manufacturing and mining sectors. Among others, the study found that high national debt in the region resulted primarily from increases in government expenses and diminishing income sources.

Originality/value

This paper is the first to take a disaggregated approach to investigate the relationship between economic growth and government expenditure in the Eastern Caribbean States. The authors’ empirical results suggest that debt servicing reduces economic growth both in the short and long run. The greatest impact being felt in the mining and manufacturing sectors, namely, 1 per cent increase in debt service will bring about 7.90 and 1.67 per cent decrease in economic growth. These results offer fairly strong support to the view that expenditure share variables can weaken sectoral growth, and hence force the overall growth to decline.
NGOs management: a roadmap to effective practices
Authors: Aboramadan Mohammed
Published: November 2018

Purpose

From one year to another, more researchers join in the ever-growing field of interest of non-governmental organizations (NGOs). Nevertheless, the literature on NGOs management is not as rich as what has been developed for private companies and bodies in the business world. The purpose of this paper is to propose a framework for managing NGOs effectively.

Design/methodology/approach

Reviewing the literature on NGOs management from different areas, the paper proposes a conceptual framework.

Findings

The paper provides a conceptual framework on how different management functions are involved in a mutual framework for managing NGOs.

Research limitations/implications

The author needs to empirically test the suggested framework using qualitative and qualitative techniques.

Originality/value

The author’s perspective on NGOs management is a subject of great interest for different NGOs stakeholders including: donors, communities, volunteers, managers and policy-makers.
Modelling the strengthening factors for competitive position of apparel retailing in India
Authors: Singh Abhishek Kumar , Samuel Cherian
Published: November 2018

Purpose

The aim of this paper is, first, the desire to present the issue of retail sector competitiveness with the simultaneous determination of factors having an impact on competitiveness and their development. The main aim is to identify the factors and relationships among those factors to strengthen the competitive positioning of apparel retail stores.

Design/methodology/approach

The literature review and experts’ opinion helped to identify the key factors. The relationships among the factors were obtained by using interpretive structural modelling (ISM). Experts’ opinions were collected again for the fuzzy direct relationship matrix. Factors were further classified by driver and dependence power using the fuzzy matrix of cross-impact multiplications applied to classification (FMICMAC) analysis.

Findings

Total nine strengthening factors (SFs) identified here, and developed an integrated model using ISM and classified it into four clusters with the help of driver and dependence power. The model hierarchy shows the interrelationships among these SFs. The retail environment, Information and Communication Technology, technology adoption and human resource management were found to be the most significant factors needing some spotlight by the top-level authority.

Research limitations/implications

The study will help managers to understand the variables and their relationships and to select the right factors to achieve a potential competitive position. Relationships among the factors were obtained through the opinions of experts and academicians. Expert opinion is a subjective judgement, and biasing in judgement might affect the result.

Originality/value

The research presents the first kind of an integrated model using ISM and FMICMAC to identify nine factors and classify them by their driving and dependence power. The developed model helps in the identification, classification and selection of factors as per requirement. This study will assist managers to understand the variables and their relationships and to select right factors to achieve a potential competitive position.
Expression of T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain on CD4+ T cells in patients with atopic dermatitis
Authors: Kurita Miki , Yoshihara Yuki , Ishiuji Yozo , Chihara Mami , Ishiji Takaoki , Asahina Akihiko , Yanaba Koichi
Published: November 2018

The T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is a co‐inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation‐regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway‐based therapeutic approach for AD.
“Wonder Nuns:” Sor Patrocinio, the Politics of the Supernatural, and Republican Caricature
Authors: Graus Andrea
Published: November 2018

This paper examines the relationship between politics and the supernatural in nineteenth‐century Spain through the figure of Sor Patrocinio: a stigmatized nun and advisor to Queen Isabel II of Spain. I introduce Sor Patrocinio as an example of a “wonder nun:” a type of ultra‐charismatic, supposedly supernaturally gifted religious woman who influenced her country's political agenda. During Sor Patrocinio's rise to fame, she lost control of her public image. In their efforts to dethrone Isabel II, Spanish republicans transformed Sor Patrocinio into a politico‐religious symbol, a living reminder of the anti‐liberal and neo‐Catholic tendencies attributed to Isabel II and her clique. On the one hand, her case exemplifies the struggle of liberalism to form modern nations in Europe. On the other, it shows how some religious women obtained power through their experience of the supernatural during the “culture wars” of the period, reflecting how such experience was shaped by political affairs.
Association of dietary inflammatory index with metabolic profile in metabolically healthy and unhealthy obese people
Authors: Abdurahman Ahmed A. , Azadbakhat Leila , Rasouli Mahkameh , Chamari Maryam , Qorbani Mostafa , Dorosty Ahmed R.
Published: November 2018

Aim

Obesity is an emerging public health problem, with its incidence on the rise. An abnormal metabolic profile is a risk factor for developing obesity. Dietary factors play a central role in the regulation of inflammation and obesity. The aim of the present study was to determine the prevalence of metabolically healthy obese and metabolically unhealthy obese (MUO) phenotypes, and their association with dietary inflammatory index (DII) among obese Iranian people.

Methods

A cross‐sectional study was conducted from July to October 2017 among 300 obese participants in southern Tehran. DII scores were computed based on the overall inflammatory properties of 32 dietary components using dietary intake assessed by food frequency questionnaire. MUO phenotype was defined as having three or more of these metabolic abnormalities: high blood glucose, high triglycerides, low high‐density lipoprotein cholesterol, elevated blood pressure or abdominal obesity. The association was determined using logistic regression analysis.

Results

The MUO phenotype (n = 176) was found in 63.5% of obese participants. Compared with participants in the first quartile, those in the fourth quartile of DII score (more pro‐inflammatory diet) had higher odds of MUO phenotype (odds ratio, OR: 2.58 (95% CI: 1.19–5.59), P = 0.04), and there was a significant association between the continuous form of DII score and the odds of MUO phenotype (OR: 1.18 (95% CI: 1.01–1.37)) after adjusting for potential confounders.

Conclusions

Higher DII scores were positively associated with the MUO phenotype. A more pro‐inflammatory diet is a potential risk factor for MUO phenotype.
Affective Battlefields: Royal Gender Hybridity and the Cultural Afterlife of Friedrich II
Authors: Maurer Kathrin
Published: November 2018

This article engages with a case of royal ‘gender trouble’, namely, the representation of Friedrich II in a popular history book: Franz Kugler and Adolph Menzel's History of Frederick the Great (1842). The article offers a brief overview of the political instrumentalisation of Friedrich II's body, and then engages with the representation of ‘affective battlefields.’ The analysis shows how these ‘affective battlefields’ become a stage on which writers and artists could display Friedrich's hybrid gendering. This hybridisation is finally discussed with reference to the book's political agenda, and, more broadly, representations of war, kings and power during the long eighteenth century.
Fc‐gamma receptor expression profile in a North‐Indian cohort of pediatric‐onset systemic lupus erythematosus: An observational study
Authors: Williams Vijai , Rawat Amit , Vignesh Pandiarajan , Shandilya Jitendra Kumar , Gupta Anju , Singh Surjit
Published: November 2018

Background

Polymorphisms in the Fcγ‐receptor (FcγR) have been associated with increased susceptibility to systemic lupus erythematosus (SLE). There is a paucity of data on FcγR expression pattern in pediatric subjects with SLE. The aim of the study was to assess the expression of various FcγRs by flow cytometry in children with pediatric‐onset SLE (pSLE).

Methods

Thirty‐one children aged 0‐15 years fulfilling 2012 Systemic Lupus International Collaborating Clinics Classification Criteria for SLE were enrolled. Disease‐active (n = 14) and the inactive group were delineated using the SLE Disease Activity Index (SLEDAI). Thirteen age‐ and sex‐matched controls were also enrolled. Blood samples of cases and controls were assessed for CD64, CD32B and CD16 expression on B lymphocytes, neutrophils and monocytes by flow cytometry using standard techniques. Median fluorescence intensity (MFI) and percentage expression were calculated using the FACS DIVA software and Kaluza software.

Results

Median fluorescence intensity and percentage expression of CD64 on monocytes (MFI: 1.71 vs 1.51, P = 0.86) and neutrophils (MFI: 0.42 vs 0.64, P = 0.3) were comparable between patients and controls. MFIs of CD16 expression on neutrophils (3.47 vs 11.4, P = 0.05) and monocytes (1.28 vs 3.45, P = 0.07) were lower in patients compared to controls. CD32B expression on lymphocytes (MFI: 0.56 vs 1.37; % expression:18.3% vs 12.32%) was also comparable between cases and controls. Expression of CD64, CD16, and CD32B were also comparable between patients with active and inactive disease.

Conclusion

No significant differences were observed in FcγR expression between patients and controls. However, the overall trends of FcγR expression and decreased CD16 on monocytes and neutrophils are in consonance with data from larger cohorts of adult SLE patients.
Indian Monetary Policy in the Time of Inflation Targeting and Demonetization
Authors: Mohan Rakesh , Ray Partha
Published: November 2018

This paper provides a narrative of Indian monetary policy since the North Atlantic Financial Crisis (NAFC) in the mid‐2008 till the current period. The period 2009–2013 was dominated by the joint monetary and fiscal stimuli of the Indian authorities prompted by the NAFC. These, along with some structural shocks and a hands‐off attitude in forex market intervention, could have had their role in rising inflation and external account instability (leading up to the taper tantrum episode). In such a backdrop, after considerable discussion during 2013–2014, a Monetary Policy Framework Agreement was signed between the Government of India and the Reserve Bank of India on February 20, 2015 that formally adopted flexible inflation targeting (IT) in India. While the IT regime so far has coincided with significant reduction in inflation in India, the atmosphere has been benign. Now that fuel prices have started moving in the north‐east direction, the government has proposed a revised framework for the minimum support price in the Union Budget for 2018–2019 and fiscal slippages have started happening, it remains to be seen whether IT can wither more rough weather in the days to come. Finally, in recent years, Indian monetary policy has been dominated by two significant events: the emergence of significant deterioration of Indian public sector balance sheets, and the demonetization episode in November 2016. Monetary policy in both of these periods wrestled with fashioning an appropriate strategy for managing the impossible trinity.
Informality, Micro and Small Enterprises, and the 2016 Demonetisation Policy in India
Authors: Kurosaki Takashi
Published: November 2018

Using a panel dataset collected in 2014–2017, we examine small and micro entrepreneurs in Delhi, India, distinguishing registered (more formal) and unregistered (more informal) enterprises. The dataset contains not only information on the characteristics of entrepreneurs and firms, but also General Social Survey trust information. Quantitative analysis comparing the two types of entrepreneurs reveals that their social backgrounds and trust were different, and that the difference is correlated with firm performance. In the micro and small enterprise sector in Delhi, registered and unregistered firms coexist with different kinds of superiority, but the business transactions of both types of firms remain highly cash‐dependent even after the 2016 Demonetisation shock.
Vectorcardiogram in athletes: The Sun Valley Ski Study
Authors: Thomas Jason A. , A. Perez‐Alday Erick , Junell Allison , Newton Kelley , Hamilton Christopher , Li‐Pershing Yin , German David , Bender Aron , Tereshchenko Larisa G.
Published: November 2018

Background

Global electrical heterogeneity (GEH) is associated with sudden cardiac death (SCD) in adults of 45 years and above. However, GEH has not been previously measured in young athletes. The goal of this study was to establish a reference for vectorcardiograpic (VCG) metrics in male and female athletes.

Methods

Skiers (n = 140; mean age 19.2 ± 3.5 years; 66% male, 94% white; 53% professional athletes) were enrolled in a prospective cohort. Resting 12‐lead ECGs were interpreted per the International ECG criteria. Associations of age, sex, and athletic performance with GEH were studied.

Results

In age and training level‐adjusted analyses, male sex was associated with a larger T vector [T peak magnitude +186 (95% CI 106–266) µV] and a wider spatial QRS‐T angle [+28.2 (17.3–39.2)°] as compared to women. Spatial QRS‐T angle in the ECG left ventricular hypertrophy (LVH) voltage group (n = 21; 15%) and normal ECG group did not differ (67.7 ± 25.0 vs. 66.8 ± 28.2; p = 0.914), suggesting that ECG LVH voltage in athletes reflects physiological remodeling. In contrast, skiers with right ventricular hypertrophy (RVH) voltage (n = 26, 18.6%) had wider QRS‐T angle (92.7 ± 29.6 vs. 66.8 ± 28.2°; p = 0.001), larger SAI QRST (194.9 ± 30.2 vs. 157.8 ± 42.6 mV × ms; p < 0.0001), but similar peak SVG vector magnitude (1976 ± 548 vs. 1939 ± 395 µV; p = 0.775) as compared to the normal ECG group. Better athletic performance was associated with the narrower QRS‐T angle. Each 10% worsening in an athlete's Federation Internationale de’ Ski downhill ranking percentile was associated with an increase in spatial QRS‐T angle by 2.1 (95% CI 0.3–3.9) degrees (p = 0.013).

Conclusion

Vectorcardiograpic adds nuances to ECG phenomena in athletes.