bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of microbial diversity and body site heterogeneity in individuals with Hidradenitis Suppurativa
Authors: Schneider Andrea M. , Cook Lauren C. , Zhan Xiang , Banerjee Kalins , Cong Zhaoyuan , Imamura-Kawasawa Yuka , Gettle Samantha L. , Longenecker Amy L. , Kirby Joslyn S. , Nelson Amanda M.
Published: April 2019

Hidradenitis Suppurativa (HS) is a chronic, scarring, inflammatory skin disease affecting hair follicles in axillae, inguinal, and anogenital regions. Dysbiosis in HS patients compared to healthy subjects is documented. However, whether dysbiosis is specific to particular body sites or skin niches is unknown. We investigated the follicular and skin surface microbiome of the axilla and groin of HS patients (n=11) and healthy individuals (n=10) using 16S rRNA gene sequencing (V3-V4). We sampled non-lesional (HSN) and lesional skin (HSL) of HS patients. β-diversity was significantly decreased (p<0.05) in HSN and HSL skin compared to normal skin with loss of body site and skin niche heterogeneity in HS samples. The relative bacterial abundance of specific microbes was also significantly different between normal and HSN (15 genera) or HSL (21 genera) skin. Smoking and alcohol use influenced the β-diversity (p<0.08) in HS skin. We investigated metabolic profiles of bacterial communities in HS and normal skin using a computational approach.Metabolism, Genetic Information Processing, andEnvironmental Information Processingwere significantly different between normal and HS samples. Altered metabolic pathways associated with dysbiosis of HS skin suggest mechanisms underlying the disease pathology and information about treatment with drugs targeting those pathways.
A novel reporter gene assay for pyrogen detection
Authors: He Qing , Yu Chuan-fei , Wang Lang , Ni Yong-bo , Zhang Heng , Du Ying , Gao Hua , Wang Jun-zhi
Published: April 2019

Fever is a systemic inflammatory response of the body to pyrogens. Nuclear factor κB (NF-κB) is a central signalling molecule that causes the excessive secretion of various proinflammatory factors induced by pyrogens. This study explored the feasibility of a novel reporter gene assay (RGA) for pyrogen detection using RAW 264.7 cells stably transfected with the NF-κB reporter gene as a pyrogenic marker. Pyrogen was incubated with the transgenic cells, and the intensity of the fluorescence signal generated by luciferase secreted by the reporter gene was used to reflect the degree of activation of NF-κB, so as to quantitatively detect the pyrogens. The RGA could detect different types of pyrogens, including the lipopolysaccharide (LPS) of gram-negative bacteria, the lipoteichoic acid (LTA) of gram-positive bacteria, and the zymosan of fungi, and a good dose-effect relationship was observed in terms of NF-κB activity. The limits of detection of the RGA to those pyrogens were 0.03 EU/ml, 0.001 μg/ml, and 1 μg/ml, respectively. The method had good precision and accuracy and could be applied to many biological products (e.g., nivolumab, rituximab, bevacizumab, etanercept, basiliximab, haemophilus influenzae type b conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine, and group A and group C meningococcal conjugate vaccine). The results of this study suggest that the novel RGA has a wide pyrogen detection spectrum and is sufficiently sensitive, stable, and accurate for various applications.

Importance

Pyrogen testing is mandatory and a critical method to ensure the safety of parenteral products including vaccines.

Currently, only two pharmacological tests, including the rabbit pyrogen test and the bacterial endotoxins test (BET), are applied to evaluate pyrogenic contamination in parenteral pharmaceuticals by most of state pharmacopoeias. Although generally reliable, both of these assays have shortcomings. The rabbit test is not quantitative but is expensive and involves the use of animals. It can also produce varying responses depending on the strain, age and housing conditions of the rabbits. The BET, however, does not detect pyrogens other than gram-negative bacterial endotoxins and is often problematic when used to test solutions with a high protein content.

To overcome these shortcomings and satisfy the growing need for new methods prompted by the constantly increasing production of biological compounds, it is necessary to develop the novel assay for pyrogen detection.

Highlights

This novel reporter gene assay can detect different types of pyrogens, including the lipopolysaccharide of gram-negative bacteria, the lipoteichoic acid of gram-positive bacteria, and the zymosan of fungi.

The novel reporter gene assay is sufficiently sensitive, stable, and accurate for various applications.
The molecular mechanism of Hsp90-induced oligomerization of Tau
Authors: Weickert Sabrina , Wawrzyniuk Magdalena , John Laura , Rüdiger Stefan G. D. , Drescher Malte
Published: April 2019

Aggregation of the microtubule-associated protein Tau is a hallmark of Alzheimer’s disease with Tau oligomers suspected as the most toxic agent. Tau is a client of Hsp90, though it is unclear whether and how the chaperone massages the structure of intrinsically disordered Tau. Using electron paramagnetic resonance, we extract structural information from the very broad conformational ensemble of Tau: Tau in solution is highly dynamic and polymorphic, though ‘paper-clip’-shaped by long-range contacts. Interaction with Hsp90 promotes an open Tau conformation, which we identify as the molecular basis for the formation of small Tau oligomers by exposure of the aggregation-prone repeat domain to other Tau molecules. At the same time, formation of Tau fibrils is inhibited. We therefore provide the nanometer-scale zoom into chaperoning an amyloid client, highlighting formation of oligomers as the consequence of this biologically relevant interaction.
Macrophage plasticity is Rac signalling and MMP9 dependant
Authors: Travnickova Jana , Nhim Sandra , Abdellaoui Naoill , Djouad Farida , Nguyen-Chi Maï , Parmeggiani Andrea , Kissa Karima
Published: April 2019

In vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilisation haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Live imaging revealed that macrophages successively adopt all four shapes as they migrate through ECM. Treatment with inhibitors of MMPs or Rac GTPase to abolish mesenchymal migration, suppresses both ECM degradation and HSPC mobilisation while differently affecting macrophage behaviour. This study depicts real time macrophage behaviour in a physiological context and reveals extreme reactivity of these cells constantly adapting and switching migratory shapes to achieve HSPCs proper mobilisation.
Threat-Induced Anxiety During Goal Pursuit Disrupts Amygdala-Prefrontal Cortex Connectivity in Posttraumatic Stress Disorder
Authors: Sun Delin , Gold Andrea L. , Swanson Chelsea A. , Haswell Courtney C. , Brown Vanessa M. , Stjepanovic Daniel ,   VA Mid-Atlantic MIRECC Workgroup, LaBar Kevin S. , Morey Rajendra A.
Published: April 2019

To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n=25) versus trauma-exposed Control (n=25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts – one involving exposure to unpredictable, task-irrelevant threat by randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat than nonthreat contexts was associated with stronger left amygdala-vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala-vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala-vmPFC functional connectivity and greater localized vmPFC processing under threat-modulation of goal-directed behavior, specifically related to successful task performance while avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD rely on stronger threat-modulated left amygdala-vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.
Creating reproducible pharmacogenomic analysis pipelines
Authors: Mammoliti Anthony , Smirnov Petr , Safikhani Zhaleh , Ba-Alawi Wail , Haibe-Kains Benjamin
Published: April 2019

The field of Pharmacogenomics presents great challenges for researchers that are willing to make their studies reproducible and shareable. This is attributed to the generation of large volumes of high-throughput multimodal data, and the lack of standardized workflows that are robust, scalable, and flexible to perform large-scale analyses. To address this issue, we developed pharmacogenomic workflows in the Common Workflow Language to process two breast cancer datasets in a reproducible and transparent manner. Our pipelines combine both pharmacological and molecular profiles into a portable data object that can be used for future analyses in cancer research. Our data objects and workflows are shared on Harvard Dataverse and Code Ocean where they have been assigned a unique Digital Object Identifier, providing a level of data provenance and a persistent location to access and share our data with the community.
Small molecule inhibitors of a human recombination-associated ATPase, RAD54
Authors: Ehmsen Kirk T. , Ang Kenny K.H. , Wright William D. , Davies Julia L. , Younis Yassir , Birman Yuliya , Bryant Clifford , Gallardo-Godoy Alejandra , Renslo Adam R. , Neitz R. Jeffrey , Arkin Michelle R. , Heyer Wolf-Dietrich
Published: April 2019

Homologous recombination (HR) is a principal support pathway for DNA replication and for recovery from DNA breaks and interstrand crosslinks, making it a rational target for inhibition in cancer therapy. The ATPase RAD54 functions in molecular events that promote DNA sequence-preservation during HR-mediated damage repair, including homology search, DNA strand exchange, and transition to DNA repair synthesis within a displacement loop intermediate. We developed a high-throughput biochemical screen to identify small-molecule inhibitors of human RAD54, using a phosphate detection assay to monitor RAD54 ATPase activity in the presence of double-stranded DNA (dsDNA). After filtering potential DNA intercalators and ‘frequent hitters,’ we identified two chemotypes that reproducibly inhibited RAD54 ATPase in vitro. We evaluated these chemotypes for inhibition of RAD54-dsDNA binding and cancer cell survival. A halogenated carbazole/dihydroacridine scaffold inhibited a panel of SWI2/SNF2-related ATPases but not VCP/p97, an unrelated ATPase. Small molecules that interfere with key steps in HR— such as inhibitors of RAD54—may expose DNA repair-dependent vulnerabilities in cancer cells.
Radiator: a cloud-based framework for deploying re-usable bioinformatics tools
Authors: Lo Emily K.W. , Schwab Remy M. , Burke Zak , Cahan Patrick
Published: April 2019

Accessibility and usability of compute-intensive bioinformatics tools can be increased with simplified web-based graphic user interfaces. However, deploying such tools as web applications presents additional barriers, including the complexity of developing a usable interface, network latency in transferring large datasets, and cost, which we encountered in developing a web-based version of our command-line tool CellNet. Learning and generalizing from this experience, we have devised a lightweight framework, Radiator, to facilitate deploying bioinformatics tools as web applications. To achieve reproducibility, usability, consistent accessibility, throughput, and cost-efficiency, Radiator is designed to be deployed on the cloud. Here, we describe the internals of Radiator and how to use it.

Availability and Implementation

Code for Radiator and the CellNet Web Application are freely available at https://github.com/pcahan1 under the MIT license. The CellNet WebApp, Radiator, and Radiator-derived applications can be launched through public Amazon Machine Images from the cloud provider Amazon Web Services (AWS) (https://aws.amazon.com/).
Broken force dispersal network in tip-links by the mutations induces hearing-loss
Authors: Hazra Jagadish P. , Sagar Amin , Arora Nisha , Deb Debadutta , Kaur Simerpreet , Rakshit Sabyasachi
Published: April 2019

Tip-link as force-sensor in the hearing conveys the mechanical force originating from sound to ion-channels while maintaining the integrity of the entire sensory assembly in inner-ear. This delicate balance between structure and function of tip-links is regulated by Ca2+-ions present in endolymph. Mutations at the Ca2+-binding sites of tip-links often lead to congenital deafness, sometimes syndromic defects impairing vision along with hearing. Although such mutations are already identified, it is still not clear how the mutants alter the structure-function properties of the force-sensors associated with diseases. With an aim to decipher the differences in force-conveying properties of the force-sensors in molecular details, we identified the conformational variability of mutant and wild-type tip-links at the single-molecule level using FRET at the endolymphatic Ca2+ concentrations and subsequently measured the force-responsive behavior using single-molecule force spectroscopy with an AFM. AFM allowed us to mimic the high and wide range of force ramps (103 - 106 pN.s−1) as experienced in the inner ear. We performed in silico network analyses to learn that alterations in the conformations of the mutants interrupt the natural force-propagation paths through the sensors and make the mutant tip-links vulnerable to input forces from sound stimuli. We also demonstrated that a Ca2+ rich environment can restore the force-response of the mutant tip-links which may eventually facilitate the designing of better therapeutic strategies to the hearing loss.

Significance Statement

Force-sensors in inner ear are the key components in the hearing. Mutations in force-sensors often lead to congenital hearing loss. Loss of hearing has become a threat to humanity, with over 5% of world population suffering from deafness and 40% of which is congenital, primarily due to mutations in the sensory machinery in inner-ear. A better understanding of the molecular mechanism of the underlined hearing loss due to mutations is, therefore, necessary for better therapeutics to deaf. Here with a zoomed region of the force-sensors, we pointed out the differences in the force-propagation properties of the mutant and wild-type force-sensors. Our observation on restoring of functions of mutants in Ca2+-rich buffer indicates methods of developing low-cost therapeutic strategies against deafness.
A Plant-Specific Polarity Module Establishes Cell Fate Asymmetry in the Arabidopsis Stomatal Lineage
Authors: Rowe Matthew H. , Dong Juan , Weimer Annika K. , Bergmann Dominique C.
Published: April 2019

Generating cell polarity in anticipation of asymmetric cell division is required in many developmental contexts across a diverse range of species. Physical and genetic diversity among major multicellular taxa, however, demand different molecular solutions to this problem. The Arabidopsis stomatal lineage displays asymmetric, stem cell-like and oriented cell divisions, which require the activity of the polarly localized protein, BASL. Here we identify the plant-specific BREVIS RADIX (BRX) family as localization and activity partners of BASL. We show that members of the BRX family are polarly localized to peripheral domains in stomatal lineage cells and that their collective activity is required for asymmetric cell divisions. We further demonstrate a mechanism for these behaviors by uncovering mutual, yet unequal dependencies of BASL and the BRX family for each other’s localization and segregation at the periphery of stomatal lineage cells.
Functional promoter polymorphisms govern the differential expression of HMG-CoA Reductase gene in rat models of essential hypertension
Authors: Khan Abrar A. , Sundar Poovitha , Gupta Vinayak , Arige Vikas , Reddy S. Santosh , Dikshit Madhu , Barthwal Manoj K. , Mahapatra Nitish R.
Published: April 2019

3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encoding the rate-limiting enzyme in the cholesterol biosynthesis pathway is a candidate gene for essential hypertension (EH). However, the regulation ofHmgcrin rat models of hypertension (viz. Spontaneously Hypertensive Rats [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unknown. Here, we show that Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. Consistently, a number of other rat models of hypertension display diminished cholesterol levels as compared to corresponding control strains. Sequencing of theHmgcrpromoter in SHR/WKY reveals three variations: A-405G, C-62T and a 11 bp insertion (-393_-382insTGCGGTCCTCC) in SHR. Moreover, SHR-Hmgcrpromoter displays higher activity than WKY-Hmgcrpromoter in various cell lines. Transient transfections ofHmgcr-promoter mutants andin silicoanalysis suggest altered binding of Runx3 and Srebf1 across A-405G and -393_-382insTGCGGTCCTCC sites. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3/Srebf1 toHmgcrpromoter leading to diminished expression ofHmgcrin SHR as compared to WKY under basal/cholesterol-modulated conditions. Taken together, this study provides mechanistic insights for the alteredHmgcrexpression in these models of EH, thereby unravelling the links of this gene to hypertension and associated cardiovascular disease states.
Experience-dependent development and maintenance of binocular neurons in the mouse visual cortex
Authors: Jenks Kyle R. , Shepherd Jason D.
Published: April 2019

The normal development of neuronal circuits requires both hard-wired gene expression and experience. Sensory processing, such as vision, is especially sensitive to perturbations in experience. However, the exact contribution of experience to neuronal visual response properties and binocular vision remains unknown. To determine how visual response properties developin vivo, we used single cell resolution two-photon calcium imaging of mouse binocular visual cortex at multiple time-points after eye opening. Few neurons are binocularly responsive immediately after eye opening and respond solely to either the contralateral or ipsilateral eye. Binocular neurons emerge during development, which requires visual experience, and show specific tuning of visual response properties. As binocular neurons emerge, activity between the two eyes becomes more correlated in the neuropil. Since experience-dependent plasticity requires the expression of activity-dependent genes, we determined whether the plasticity geneArcmediates the development of normal visual response properties. Surprisingly, rather than mirroring the effects of visual deprivation, mice that lackArcshow increased numbers of binocular neurons during development. Strikingly, removingArcin adult binocular visual cortex increases the numbers of binocular neurons and recapitulates the developmental phenotype, suggesting cortical circuits that mediate visual processing require ongoing experience-dependent plasticity. Thus, experience is critical for the normal development and maintenance of circuits required to process binocular vision.
Are agri‐environment schemes successful in delivering conservation grazing management on saltmarsh?
Authors: Mason Lucy R. , Feather Alastair , Godden Nick , Vreugdenhil Chris C. , Smart Jennifer
Published: April 2019

Grasslands occur around the globe and, in temperate regions, their natural management by fire, drought and wild herbivores has largely been replaced by grazing with domestic livestock. Successful management for agriculture is not always suitable for conservation and can have a detrimental effect on biodiversity. Conservation grazing of saltmarshes, delivered through agri‐environment schemes, may provide a solution to counteract biodiversity loss by providing farmers with financial incentives to graze these internationally important coastal wetlands more sensitively.

To assess whether conservation grazing is being achieved and whether agri‐environment schemes are effective in delivering this management, we conducted a national survey on English saltmarshes, scoring the management on each site as optimal, suboptimal or detrimental in terms of suitability for achieving conservation aims for five aspects of grazing: presence, stock type, intensity, timing and habitat impact.

Although most saltmarshes suitable for grazing in England were grazed, conservation grazing was not being achieved. Sites under agri‐environment management for longer did score higher and approached optimal levels in terms of grazing intensity in one region, but sites with agri‐environment agreements were no more likely to be grazed at optimal conservation levels than sites without them overall, indicating that agri‐environment schemes, in their current form, are an ineffective delivery mechanism for conservation grazing on saltmarsh.

The low specificity of agri‐environment prescription wording may contribute to this failure, with prescriptions either being vague or specifying suboptimal or detrimental management objectives, particularly for grazing intensity, timing and stock type. These objectives are often set too high or too low, during unsuitable periods or using stock types inappropriate for achieving conservation aims.

Synthesis and applications. Our national survey indicates that agri‐environment schemes are not currently delivering conservation grazing on English saltmarshes. Agri‐environment schemes are the only mechanism through which such grazing can be implemented on a national scale, so improving their effectiveness is a priority. Policymakers, researchers and managers need to work together to ensure better translation of conservation guidelines into schemes, increasing the specificity of management prescriptions and improving understanding of the need for management measures. A more detailed and reliable system of auditing to ensure that management activities are taking place would be beneficial or alternatively moving to a results‐based scheme where payments are made on desirable outcomes rather than on evidence of management.
The pathophysiology of the septate uterus: a systematic review
Authors: Rikken JFW , Leeuwis‐Fedorovich NE , Letteboer S , Emanuel MH , Limpens J , van der Veen F , Goddijn M , van Wely M
Published: April 2019

Background

Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus.

Objectives

We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects.

Search strategy

We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018.

Selection criteria

We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded.

Data collection and analysis

Two reviewers independently evaluated potentially eligible papers.

Main results

Thirty‐eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall.

Conclusions

We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum.

Tweetable abstract

In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.
High accruals momentum
Authors: Hao Xiaoting , Jang Juwon , Lee Eunju
Published: April 2019

We examine the information content of high accruals momentum defined as a string of high discretionary accruals for four consecutive years. We find that firms that consistently report high levels of discretionary accruals experience low subsequent returns. The results are robust after we control for annual levels of discretionary accruals for the estimation period of high accruals momentum. Furthermore, the predictive power of the high accruals momentum for future returns is strongly persistent even after the existing accruals anomaly disappears. Our results also show that the high accruals momentum impact is more pronounced for low growth firms, suggesting that the overpricing of stocks with high accruals momentum is driven by managerial discretion to manage earnings.
Population reinforcement accelerates subadult recruitment rates in an endangered freshwater turtle
Authors: Carstairs S. , Paterson J. E. , Jager K. L. , Gasbarrini D. , Mui A. B. , Davy C. M.
Published: April 2019

Wildlife diversity and abundance are declining globally and population reinforcement with captive‐reared animals is a common intervention used to prevent extinctions. Released captive‐reared individuals may undergo an acclimation period before their behavior and success is comparable to wild‐reared individuals because they lack experience with predators, complex habitats and variable environmental conditions. Quantifying post‐release acclimation effects on fitness and behavior is important for maximizing the success of reintroduction programs and for predicting the number of captive‐reared animals required for release. Endangered Blanding's turtles Emydoidea blandingii exhibit low recruitment and may benefit from population reinforcement with captive‐reared, ‘headstarted’ individuals (headstarts). We used 6 years of data to compare survival, growth, habitat use and movement ecology between wild‐hatched juvenile turtles and headstarts reared from eggs rescued from injured females. We found strong evidence of an acclimation effect in headstarts, with lower movement, growth, and survival during the first one to two years post‐release. Following this acclimation period, headstarts had movement, growth and survival similar to wild‐hatched juveniles. Habitat use did not differ between headstarts and wild‐hatched juveniles. We hypothesize that the acclimation period occurred because headstarts were introduced directly into the wild (i.e. ‘hard release’) and that providing additional support before or after release may improve the success of headstarts. Headstarts had a monthly survival probability of 0.89 in the first year post‐release, and 0.98 after the first year post‐release. We estimated that headstarts at our sites have approximately three times higher probability of surviving to 10 years of age, compared to wild‐hatched individuals at other sites. Our results highlight that headstarts should be released into habitat individually rather than in clusters, and highlight the need to investigate whether post‐release mortality of captive‐reared animals could be mitigated by increased acclimation to wild conditions, for example through prerelease periods in outdoor pens.
Spatio‐temporal gradients in food supply help explain the short‐term colonisation dynamics of the critically endangered central rock‐rat (Zyzomys pedunculatus)
Authors: Nano Catherine E. M. , Randall Debbie J. , Stewart Alistair J. , Pavey Chris R. , McDonald Peter J.
Published: April 2019

Currently, the impact of introduced predators on small mammal population decline is a focal research direction in the Australian desert literature. In all likelihood though, single‐factor explanation of population dynamics is inadequate, leaving gaps in our knowledge of the multitude of potential influences on small mammal abundance and occupancy patterns in time and space. Here, we investigated floristic gradients across four potential refuge sites of the central rock‐rat, Zyzomys pedunculatus, a granivore rodent (50–120 g) that is endemic to central Australia and is categorised as critically endangered. The study took place in Tjoritja/West MacDonnell National Park in the MacDonnell Ranges bioregion. Floristic sampling was allocated across the four sites, the locations of which were predetermined by an established monitoring and management programme for the central rock‐rat. Our aim was to examine the relationship between environmental gradients and floristic composition across the four sites, and thereby test the extent to which the patterns of food type and food availability can inform central rock‐rat spatio‐temporal dynamics. We found high site‐scale floristic patterning that related foremost to elevation and then to antecedent rainfall and time‐since‐fire and fire‐severity effects. To interpret these results, we applied the principles of refuge theory and we described a gradient from core refuge habitat to intermittent and then marginal habitat within the current central rock‐rat stronghold area. Overall, our results implied a strong floristic basis to central rock‐rat site occurrence, and they thus compel us to take explicit account of spatial (elevation) and temporal (rainfall–productivity and fire‐disturbance) influences on the food axis of potential refuge sites of this critically endangered species.
Retracted: Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats
Authors: Toral Marta , Robles‐Vera Iñaki , de la Visitación Néstor , Romero Miguel , Sánchez Manuel , Gómez‐Guzmán Manuel , Rodriguez‐Nogales Alba , Yang Tao , Jiménez Rosario , Algieri Francesca , Gálvez Julio , Raizada Mohan K , Duarte Juan
Published: April 2019

Aim

High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) alter the gut‐immune system interaction inducing changes in vascular function and BP.

Methods

Twenty‐week‐old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7‐dependent costimulation with CTLA4‐Ig or blockade of IL‐17 with IL‐17‐neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.

Results

Correlation analyses identified the bacterial abundance of Turicibacter and S24‐7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7‐dependent costimulation with CTLA4‐Ig. IL‐17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.

Conclusion

Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T‐cell activation in gut immune system and vascular T‐cells accumulation.
Examining family and school factors as predictors of delinquency: A study of juvenile offenders, at‐risk students, and low‐risk students in Malaysia
Authors: Tan Bee Piang , Zuraini Jamil @ Osman , Noor Banu Mahadir Naidu
Published: April 2019

This study aims to examine family and school factors as predictors of delinquency among adolescents in Malaysia. A total of 101 juvenile offenders, 86 at‐risk students, and 92 low‐risk students were involved in this study. Multinomial logistic regression was used to predict the likelihood of an adolescent being in a group of juvenile offenders or of being an at‐risk or low‐risk student, based on four predictor variables: family structure, family relationships, school relationships, and commitment to learning. The results show that family relations, school relations, and commitment to learning have different predictive effects on the likelihood of different levels of delinquent behavior. However, family structure is not found to be a significant predictor in the logistic regression in this study. The findings of the study suggest that keeping young people in school can serve as a strong protective factor that serves to prevent at‐risk students from moving along the trajectory of serious delinquent behaviors.
Agitated depression in bipolar disorder
Authors: Serra Francesca , Gordon‐Smith Katherine , Perry Amy , Fraser Christine , Di Florio Arianna , Craddock Nick , Jones Ian , Jones Lisa
Published: April 2019

Objectives

It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well‐characterized bipolar disorder sample.

Method

The prevalence of agitation, based on semi‐structured interview and medical case‐notes, in the most severe depressive episode was estimated in 2925 individuals with DSM‐IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models.

Results

32.3% (n = 946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P < 0.001), poor concentration (OR 1.966, P = 0.027), decreased libido (OR 1.960, P < 0.001), suicidal ideation (OR 1.861, P < 0.001), slowed activity (OR 1.504, P = 0.001), and poor appetite (OR 1.297, P = 0.029). Over the lifetime illness course, co‐morbid panic disorder (OR 2.000, P < 0.001), suicide attempt (OR 1.399, P = 0.007), and dysphoric mania (OR 1.354, P = 0.017) were significantly associated with AD.

Conclusions

Agitation accompanied bipolar depression in at least one‐third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.
Empirical-Likelihood-Based Criteria for Model Selection on Marginal Analysis of Longitudinal Data With Dropout Missingness
Authors: Chen Chixiang , Shen Biyi , Zhang Lijun , Xue Yuan , Wang Ming
Published: April 2019

Longitudinal data are common in clinical trials and observational studies, where missing outcomes due to dropouts are always encountered. Under such context with the assumption of missing at random, the weighted generalized estimating equation (WGEE) approach is widely adopted for marginal analysis. Model selection on marginal mean regression is a crucial aspect of data analysis, and identifying an appropriate correlation structure for model fitting may also be of interest and importance. However, the existing information criteria for model selection in WGEE have limitations, such as separate criteria for the selection of marginal mean and correlation structures, unsatisfactory selection performance in small-sample setups, and so forth. In particular, there are few studies to develop joint information criteria for selection of both marginal mean and correlation structures. In this work, by embedding empirical likelihood into the WGEE framework, we propose two innovative information criteria named a joint empirical Akaike information criterion and a joint empirical Bayesian information criterion, which can simultaneously select the variables for marginal mean regression and also correlation structure. Through extensive simulation studies, these empirical-likelihood-based criteria exhibit robustness, flexibility, and outperformance compared to the other criteria including the weighted quasi-likelihood under the independence model criterion, the missing longitudinal information criterion, and the joint longitudinal information criterion. In addition, we provide a theoretical justification of our proposed criteria, and present two real data examples in practice for further illustration.
Empathy for others’ pain is disrupted at the neurophysiological level in schizophrenia
Authors: Varcin Kandice J. , Grainger Sarah A. , Bailey Phoebe E. , Richmond Jenny L. , Henry Julie D.
Published: April 2019

Objective

Previous research has shown that empathy for pain is disrupted at the neural level in people with schizophrenia. However, many of these studies have failed to assess key background contextual variables that have previously been linked to neurophysiological responding. Moreover, no study to date has examined the potential influence of schizotypal characteristics on neurophysiological responding in non‐clinical individuals.

Methods

People with schizophrenia (N = 17) were compared to demographically matched controls (N = 19) on an event‐related potential (ERP) empathy for pain paradigm. The control group also completed a measure of schizotypal personality traits.

Results

People with schizophrenia exhibited atypical neural responding at early, emotion‐sharing (frontal N110), and late, cognitive (central late positive potential [LPP]) processing stages of pain empathy, relative to controls. In the control group, positive schizotypy traits were significantly negatively related to reduced ERP amplitude in the late, cognitive (central LPP) processing stage of empathy.

Conclusions

These data cross‐validate previous studies that have shown that schizophrenia is associated with atypicalities in bottom‐up automatic resonance processes that likely contribute to empathic and socio‐emotional processing deficits, and indicate that these findings cannot be easily attributed to background contextual differences between the two groups. The results also point to a potential relationship between positive schizotypal characteristics and neurophysiological responding. Implications for simulation theories of empathy and social functioning in schizophrenia are discussed.

Practitioner points

Empathic processing has been consistently linked to well‐being and mental health in many groups, including people with schizophrenia.

Previous research has shown that, relative to controls, people with schizophrenia exhibit abnormalities in their neurophysiological empathic response, but in these prior studies, the two groups also differed in a number of potentially important background contextual variables.

The current study shows that, when closely matched on background contextual variables, abnormal neural responding is still evident.

These data suggest that empathy for pain is disrupted at the neurophysiological level in schizophrenia.
Similarity attracts: The role of personality in similarity perceptions and children's attitudes towards refugees
Authors: Reches Leyla H. L. , Feddes Allard R.
Published: April 2019

Previous research has shown that children's intergroup similarity judgements are based not only on ethnicity but also on other dimensions such as sports interest. The present research investigates the role of personality in perceived similarity between ingroup children and refugee outgroup children. A study was conducted among 9‐ to 12‐year‐old children (N = 124) at two elementary schools in the Netherlands. It was predicted and found that children take into account ethnicity as well as personality (whether a child is introverted or extraverted) when judging similarity of ingroup (Dutch) and outgroup (refugee) children. Furthermore, we predicted and found that greater perceived similarity between Dutch children and refugee children was associated with more positive attitudes towards refugee children. Finally, children felt lower levels of anxiety towards an extraverted compared to an introverted refugee child. Lower anxiety, in turn, was associated with more positive attitudes towards refugee children. Theoretical and practical implications are discussed.

Statement of contribution

What is already known?

McGlothlin et al. (2005, British Journal of Developmental Psychology, 23, 227) found that similarity ratings are based not only on ethnicity but also on sports interest.

Studies among adults show that extraversion is negatively related to anxiety and positively to cross‐group friendships.

What does this study add?

The present study shows that children also base similarity ratings on the personality trait extraversion.

Higher similarity between self/ingroup and refugee children is related to positive outgroup attitudes.

This study shows that extraverted children feel less anxiety to an extraverted refugee child.

Lower anxiety in children is related to more positive attitudes to refugee children in general.
On the complementarity of holistic and analytic approaches to performance assessment scoring
Authors: Zlatkin‐Troitschanskaia Olga , Shavelson Richard J. , Schmidt Susanne , Beck Klaus
Published: April 2019

Background

A holistic approach to performance assessment recognizes the theoretical complexity of multifaceted critical thinking (CT), a key objective of higher education. However, issues related to reliability, interpretation, and use arise with this approach.

Aims and Method

Therefore, we take an analytic approach to scoring students’ written responses on a performance assessment. We focus on the complementarity of holistic and analytic approaches and on whether theoretically developed analytical scoring rubrics can produce sub‐scores that may measure the ‘whole’ performance in a holistic assessment.

Sample

We use data from the Wind Turbines performance assessment, developed in the iPAL project this study where 55 students at a German university participated.

Results

The (sub)scores generated from the scoring scheme empirically reproduced the theoretically assumed structure of CT, with valid and reliable scores in a three‐dimensional model. The proposed interpretation of CT as assessed with a performance assessment and measured by the rating scheme was supported preliminarily.

Conclusion

Our results support the complementarity of holistic and analytic approaches to assessing CT. When combined, they provide interpretable scores for a complex, multifaceted construct useful in diagnostic contexts.
Early parental positive personality and stress: Longitudinal associations with children's sleep
Authors: Miadich Samantha A. , Doane Leah D. , Davis Mary C. , Lemery‐Chalfant Kathryn
Published: April 2019

Objectives

The current study examined the influence of early parental stress and positive parent personality during infancy on sleep in middle childhood. Further, the role of positive parent personality as a buffer of the association between parental stress and sleep was considered.

Methods

Participants included 381 twins and their primary caregivers who were recruited from birth records in the United States. Primary caregivers completed survey assessments via phone when twins were 12 and 30 months of age to assess multiple dimensions of parental stress and positive parent personality. Approximately 6 years later (M = 5.78, SD = 0.42), twins participated in an intensive assessment that included wearing actigraph watches to provide an objective measurement of sleep, while primary caregivers completed daily diaries regarding twins' sleep.

Results

Positive parent personality was associated prospectively with longer actigraphy sleep duration and higher parent‐reported sleep quality/daytime functioning. Parental stress was associated prospectively with greater variability in sleep duration. Positive parent personality moderated the parental stress – sleep‐timing relation, such that greater parental stress was associated with a later midpoint of the sleep period only for children with parents low on positive personality (e.g., low optimism). All other findings were non‐significant.

Conclusions

Findings suggest that both positive attributes and stress may influence sleep in middle childhood and that low parent positive personality may exacerbate associations between parental stress and later timing of sleep periods in children. Early interventions to promote healthy sleeping may consider focusing on decreasing parental stress and increasing parental empathy and optimism as early as infancy.

Statement of contribution

What is already known on this subject?

Early‐life experiences, especially adversity, have been related to health outcomes among adults and children, such that negative experiences are associated with poor health outcomes.

Poor sleep (e.g., short duration, poor quality) among children is associated with negative outcomes including poorer cognitive performance and higher adiposity.

What does this study add?

This study used a prospective design to understand relations between early parent‐related factors and child sleep.

Early parental stress and positive parent personality were associated with objective sleep quality.

Positive parent personality during infancy may have promotive/protective influences on sleep later in childhood.
The importance of the relational needs of people with learning disabilities in the promotion of self‐determination
Authors: Cudré‐Mauroux Annick , Piérart Geneviève , Vaucher Carla
Published: April 2019

Accessible summary

People with learning disabilities may need to receive support from social care professionals to make choices and to change things in their life.

They may need to receive advice, but sometimes they prefer not to receive advice.

Professionals must trust them when they try something new.

It is important that professionals know what people with learning disabilities want and need to support them in a better way. It is important that they become aware of the importance to express what they want and what they need.

Background: Intervention to increase self‐determination of people with learning disabilities is a major issue for social care practices. This study examines relational needs of people with learning disabilities regarding self‐determination in the context of the relationships they share with social care professionals. Method: We held focus group discussions to explore the relational needs of 10 residents and 10 educators at three facilities for people with learning disabilities located in the French part of Switzerland. Results: Relational needs expressed by participants with learning disabilities concern three distinct stages of the self‐determination process (pre‐choice, post‐choice and goal achievement).

Conclusion

They suggest the importance of the relational quality of interventions aimed to enhance self‐determination of people with learning disabilities.