bluuebunny/crossref_metadata_2025 huggingface dataset:
Zebrafish embryonic tissue differentiation is marked by concurrent cell cycle dynamic and gene promoter regulatory changes
Authors: Wragg Joseph W , Roos Leonie , Vucenovic Dunja , Cvetesic Nevena , Lenhard Boris , Müller Ferenc
Published: December 2019

The core promoter, a stretch of DNA surrounding the transcription start site (TSS) is a major integration point for regulatory signals controlling gene transcription. The process of cell differentiation is accompanied by a marked divergence in transcriptional repertoire between cells of different fates, accompanied by changes in cellular behaviour, in particular their proliferative activity. Investigation of divergent core promoter architectures suggest distinct regulatory networks act on the core promoter, modulating cell behavior through transcriptional profile changes, which ultimately drives key transitions in cellular behaviour during embryonic development. The role that promoter-associated gene regulatory networks play in development associated transitions in cell cycle dynamics (e.g. during differentiation) however, is poorly understood. In this study we demonstrate in a developingin vivomodel, how core promoter variations play a key role in defining transcriptional output in cells transitioning from a proliferative to cell-lineage specifying phenotype. The FUCCI transgenic system, differentially marks cells in G1 and S/G2/M phases of the cell cycle and can therefore be used to separate rapidly and slowly cycling cellsin vivo, by virtue of the cell cycle stage they primarily inhabit. Longitudinal assessment of cell proliferation rate during zebrafish embryo development, using this system, revealed a spatial and lineage-specific separation in cell cycling behaviour across post-gastrulation embryos. In order to investigate the role differential promoter usage plays in this process, cap analysis of gene expression (CAGE) was performed on fluorescent associated cell sorted (FACS) FUCCI zebrafish embryos going through somitogenesis, separating cells in accordance with the rate of their cell cycling. This analysis revealed a dramatic increase in lineage and tissue-specific gene expression, concurrent with a slowing of their cell cycling. Core promoters associated with rapidly cycling cells, showed broad distribution of transcription start site usage, featuring positionally constrained CCAAT-box, while slowly cycling cells favoured sharp TSS usage coupled with canonical TATA-box utilisation and enrichment of Sp1 binding sites. These results demonstrate the regulatory role of core promoters in cell cycle-dependent transcription regulation, during somitogenesis stages of embryo development.
Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
Authors: Saiz Néstor , Mora-Bitria Laura , Rahman Shahadat , George Hannah , Herder Jeremy P , García-Ojalvo Jordi , Hadjantonakis Anna-Katerina
Published: December 2019

Precise control and maintenance of the size of cell populations is fundamental for organismal development and homeostasis. The three cell types that comprise the mammalian blastocyst-stage embryo are generated in precise proportions and over a short time, suggesting a size control mechanism ensures a reproducible outcome. Guided by experimental observations, we developed a minimal mathematical model that shows growth factor signaling is sufficient to guarantee this robustness. The model anticipates, without additional parameter fitting, the response of the embryo to perturbations in its lineage composition. We experimentally added lineage-restricted cells to the epiblast bothin vivoandin silico, which resulted in a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biased the specification of progenitors towards the targeted cell type. Finally, we show that FGF4 couples cell fate decisions to lineage composition through changes in local concentration of the growth factor. Our results provide a basis for the regulative abilities of the mammalian embryo and reveal how, in a self-organizing system, individual cell fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.
Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits
Authors: Zhang Wen , Voloudakis Georgios , Rajagopal Veera M. , Reahead Ben , Dudley Joel T. , Schadt Eric E. , Björkegren Johan L.M. , Kim Yungil , Fullard John F. , Hoffman Gabriel E. , Roussos Panos
Published: December 2019

Transcriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we improve the accuracy of transcriptome prediction and the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge to biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify known and novel compounds that mimic or reverse trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.
Exosomal miR‐103a‐3p ameliorates lipopolysaccharide‐induced immune response in BEAS‐2B cells via NF‐κB pathway by targeting transducin β‐like 1X related protein 1
Authors: Li Ruina , Liang Pengbo , Yuan Juan , He Fangzhi
Published: December 2019

Abnormal immune response contributes to pathophysiology of pneumonia and is recognized as a main factor for high incidence rate in children. The association between exosomes and inflammation has been reported in diverse cell types and diseases. The current study focuses on exploring the effects of exosomal miR‐103a‐3p on lipopolysaccharide (LPS)‐induced inflammation, and investigates the underlying mechanisms. We proved that miR‐103a‐3p was lowly expressed in blood samples of pneumonia patients and LPS‐induced lung cells, and overexpression of miR‐103a‐3p weaken the LPS‐induced inflammation. Using luciferase reporter assay and immunoprecipitation assay, we demonstrated that miR‐103a‐3p directly binds to a specific region of transducin β‐like 1X related protein 1 (TBL1XR1), mediating the NF‐κB signalling pathway, thus regulating immune response. Taken together, our data revealed that miR‐103a‐3p functions as an anti‐inflammatory gene in childhood pneumonia and can be applied as therapeutic targets for the treatment of childhood pneumonia in the future.
Economic vulnerability and regional implications of a low carbon emissions future
Authors: Fleming‐Muñoz David A. , Poruschi Lavinia , Measham Thomas , Meyers Jacqui , Moglia Magnus
Published: December 2019

Climate change, as well as associated mitigation efforts, will substantially disrupt some economies. Seemingly inevitable market and policy changes will push economies to transition away from reliance on industries with higher carbon emissions and bring transient economic impacts, especially in regions that are currently heavily reliant on such industries. This situation is not unusual in a global context. To underpin better‐informed decisions that enable a smoother economic transition to a low‐emissions future, we developed a ‘latent economic vulnerability to emissions reduction’ (LEVER) index, which maps and explores regions that are more likely to be economically impacted from climate change mitigation. Thus, this paper provides an analysis and discussion of the potential regional implications of a future low‐emissions economy, with the analysis contextualised for the state of Queensland, Australia. Given this case study, the economic impacts and future of coal‐fired power stations, coal mining and renewable energy are discussed.  The LEVER index weighs the risk of high carbon economic exposure against the variability in carbon economic resilience from employment in low‐emission sectors across local economies. We find that between 3 and 6 per cent of Queensland regions are assessed as having a very high latent economic vulnerability to increased decarbonisation of industrial activities. To promote a smoother transition, these regions will require targeted investments and strategies to enable their transition towards lower carbon‐intensive systems, while maximising economic and social outcomes.
Snakes and ladders: legal coercion, housing precarity, and home‐making aspirations in southern England
Authors: Davey Ryan
Published: December 2019

The potential for eviction is an ordinary condition of domestic life for many in Europe and North America. This poses a challenge to anthropological theories of the state's presence in ordinary homes, which have accounted for public housing and mass displacement, but not liberalized settings where the state has ostensibly withdrawn from the home. Studies of housing precarity identify state policy and capitalist transformation among its sources, but the consequences of housing precarity for domesticity itself have not been fully explored. Private renters on a housing estate in southern England responded to the bleak prospect of eviction with home‐making pursuits that would instil a sense of optimism in their homes, including mortgage‐based ownership and immersive home entertainment technology. By examining the interplay between fears of eviction and home‐making aspirations, this article argues that the British state's organization of legitimate coercion has a subtle but significant influence on tenants’ ethical visions of what constitutes a good home.
The role of primary school teachers’ attitudes and self‐efficacy beliefs for everyday practices in inclusive classrooms – a study on the verification of the ‘Theory of Planned Behaviour’
Authors: Hellmich Frank , Löper Marwin F. , Görel Gamze
Published: December 2019

Within the framework of implementing inclusive education in primary schools, various questions arise concerning the role of teachers’ personal resources in their everyday practices in heterogeneous classrooms. Teachers’ professional personalities as well as their intentions concerning inclusive teaching are considered to be important prerequisites for successful learning environments. Therefore, we examined the relevance of primary school teachers’ personal resources, such as their attitudes towards inclusion and their perceived collective self‐efficacy beliefs concerning inclusive teaching, in terms of their everyday practices in heterogeneous classrooms on the basis of the ‘Theory of Planned Behaviour’. We investigated N = 290 primary school teachers’ everyday practices according to their attitudes towards inclusion, their collective self‐efficacy beliefs concerning inclusive education, their perceptions of school management’s expectations and their intentions regarding inclusive education. The results of our study indicate that primary school teachers’ everyday practices in heterogeneous classrooms are significantly predicted by their intentions regarding the implementation of inclusive education and by their attitudes towards inclusive education but not by their collective self‐efficacy beliefs or by their perceptions of school management’s expectations. Specifically, the effect of teachers’ attitudes on their everyday practices in heterogeneous classrooms is significantly mediated by their intentions regarding the implementation of inclusive education.
Subcutaneous granuloma caused by Kodamaea ohmeri in an immunocompromised patient in China
Authors: Yu Qian , Yan Jianna , Gao Zhiqin , Yang Hong , Tang Yichen , Yang Lianjuan
Published: December 2019

We present a case of subcutaneous granuloma caused by Kodamaea ohmeri and describe the histopathological characteristics and skin lesions caused by this pathogen. A 55‐year‐old woman, with a history of rheumatoid arthritis, presented with red, painless plaque on her forehead, persistent for 3 months; based on the histopathological and mycological findings and gene sequencing, the patient was diagnosed with subcutaneous granuloma caused by K. ohmeri. This report highlights that early identification and diagnosis and optimal regimens are vital in the management of this intractable infection.
The anatomic distribution of cutaneous melanoma: A detailed study of 5141 lesions
Authors: Wee Edmund , Wolfe Rory , Mclean Catriona , Kelly John W. , Pan Yan
Published: December 2019

Background/Objectives

There is evidence that cutaneous melanomas at different anatomic sites present with distinctive clinicopathologic features. We examined the anatomic distribution of cutaneous melanoma and its variation by patient characteristics, subtype and Breslow thickness, using high‐resolution anatomic site data.

Methods

A cross‐sectional study was performed of all primary cutaneous melanoma cases managed at a tertiary referral centre, analysing prospectively collected clinical data across 50 anatomic subsites.

Results

The study included 5141 in situ or invasive melanomas; most were invasive (76.2%), and the median Breslow thickness of invasive lesions was 1.0 mm. Superficial spreading (57.2%), lentigo maligna (20.8%) and nodular (12.2%) were the most common histopathological subtypes. Sun‐exposed sites such as the female nose and cheek, the male ear, as well as the upper back in both sexes had the highest incidence of melanoma per unit area. When compared to the posterior forearm, the scalp, ear, preauricular, perioral, subungual and plantar sites had thicker invasive melanomas (each P < 0.05). The peri‐auricular, ear and cheek had the highest incidence of nodular melanoma per unit area. There were subtype‐, age‐ and sex‐specific differences in melanoma anatomic distribution.

Conclusion

Melanoma most commonly arises in sun‐exposed facial areas, as well as the upper back. Increased thickness is found for melanoma in acral and many head and neck sites. Nodular melanoma is more likely to occur in head and neck sites including the peri‐auricular area, ear and cheek. Clinicians should carefully assess these sites during skin examinations.
Letter: Helicobacter pylori in proton pump inhibitor‐associated biliary disease
Authors: Papaefthymiou Apostolis , Doulberis Michael , Polyzos Stergios A. , Katsinelos Panagiotis , Liatsos Christos , Koffas Apostolos , Kazakos Evangelos , Deretzi Georgia , Srivastava David S. , Kountouras Jannis
Published: December 2019

LINKED CONTENT

This article is linked to Min et al paper. To view this article, visit https://doi.org/10.1111/apt.15466.
Macular oedema and changes in macular thickness in multiple sclerosis patients treated with fingolimod
Authors: Nørgaard Thomas Lohne , Andersen Carl Uggerhøj , Hilt Claudia , Andersen Charlotte Uggerhøj
Published: December 2019

Macular oedema is a known side effect to fingolimod, but changes in specific areas of the retina are only sparsely described. Our aim was to investigate the prevalence of macular oedema and characterize macular changes after initiation of fingolimod based on routine ophthalmological examinations in all consecutive patients treated at our hospital. We evaluated macular thickness change from baseline to 3‐4 months after initiation of treatment. Central retinal thickness, total macular volume, total macular thickness, average thickness and inner‐/outer macular thickness were automatically measured using optical coherence tomography (OCT). A total of 190 eyes completed the study, and none of those developed visible macular oedema. All macular areas showed a small, but statistically significant increase in thickness. Total macular volume increased by a mean of 0.05 mm3 (P = <.001). Mean best‐corrected visual acuity only changed by .03 (P = .074). We observed a minimal change in macular thickness and no clinically relevant affection on visual acuity after 3‐4 months of fingolimod treatment. Thus, our results do not underpin the need for routine screening for macular oedema in asymptomatic MS patients without diabetes or uveitis receiving 0.5 mg fingolimod daily.
Health and health belief factors associated with screening and help‐seeking behaviours for breast cancer: A systematic review and meta‐analysis of the European evidence
Authors: Grimley Catherine E. , Kato Pamela M. , Grunfeld Elizabeth A.
Published: December 2019

Purpose

The aim of this systematic review was to identify health or health belief factors associated with mammography attendance or with self‐initiated medical help‐seeking for breast cancer symptoms among women in Europe.

Methods

Five databases were searched for articles published between 2005 and 2018. Meta‐analyses were conducted for 13 factors related to screening attendance and two factors associated with help‐seeking behaviour. Where there were too few studies to include in the meta‐analysis, a narrative synthesis was undertaken.

Results

Sixty‐five studies were included. Never having had cervical screening (d = −.72,p < .001) and higher perceived barriers to mammography (d = −.40,p < .001) were associated with lower levels of screening attendance. Possessing health insurance (d = .49,p < .001), greater perceived benefits (d = .31,p < .001) and motivation (d = .36,p = .003) towards screening, and higher perceived seriousness (d = .24,p = .019) and susceptibility (d = .20,p = .024) towards breast cancer were associated with a higher level of screening attendance. Presenting with a non‐lump symptom was associated with a longer time to presentation (d = .32,p < .001). The narrative synthesis revealed that previous benign breast disease was associated with a higher level of screening attendance but with a longer time to presentation.

Conclusions

The review identified key similarities in factors associated with screening and help‐seeking behaviours which offer scope for combined interventions aimed at women that target both behaviours. Furthermore, the review highlighted that fewer studies have focused on help‐seeking behaviour, despite two thirds of breast cancer cases being self‐detected. Future research should further examine predictors of help‐seeking behaviour including a focus on modifiable factors, such as BMI, and physical activity.
Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB1/CB2 versus GPR55 receptors
Authors: Wang Xiao‐Fei , Galaj Ewa , Bi Guo‐Hua , Zhang Cindy , He Yi , Zhan Jia , Bauman Michael H. , Gardner Eliot L. , Xi Zheng‐Xiong
Published: December 2019

Background and Purpose

Cannabis or cannabinoids produce characteristic tetrad effects—analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action.

Experimental Approach

We compared Δ9‐tetrahydrocannabinol (Δ9‐THC)‐, WIN55212‐2‐, or XLR11‐induced tetrad effects between wild‐type (WT) and each genotype of CB1‐, CB2‐ or GPR55‐knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice.

Key Results

Systemic administration of Δ9‐THC, WIN55212‐2 or XLR11 produced dose‐dependent tetrad effects in WT mice. Genetic deletion or pharmacological blockade of CB1 receptors abolished the tetrad effects produced by all three cannabinoids. Unexpectedly, genetic deletion of CB2 receptor abolished analgesia and catalepsy produced by Δ9‐THC or WIN55212‐2, but not by XLR11. Microinjections of Δ9‐THC into the lateral ventricles also produced tetrad effects in WT, but not in CB1‐KO mice. CB2‐KO mice displayed a reduction in intraventricular Δ9‐THC‐induced analgesia and catalepsy. In contrast to CB1 and CB2 receptors, genetic deletion of GPR55 receptors caused enhanced responses to Δ9‐THC or WIN55212‐2. Antagonisim of CB1, CB2 or GPR55 receptors produced alterations similar to those observed in each genotype mouse line.

Conclusions and Implications

These findings suggest that in addition to CB1, both CB2 and GPR55 receptors are also involved in some pharmacological effects produced by cannabinoids. CB1/CB2, in contrast to GPR55, receptors appears to play opposite roles in cannabinoid action.
Cell‐permeable high‐affinity tracers for Gq proteins provide structural insights, reveal distinct binding kinetics and identify small molecule inhibitors
Authors: Kuschak Markus , Namasivayam Vigneshwaran , Rafehi Muhammad , Voss Jan H. , Garg Jaspal , Schlegel Jonathan G. , Abdelrahman Aliaa , Kehraus Stefan , Reher Raphael , Küppers Jim , Sylvester Katharina , Hinz Sonja , Matthey Michaela , Wenzel Daniela , Fleischmann Bernd K. , Pfeifer Alexander , Inoue Asuka , Gütschow Michael , König Gabriele M. , Müller Christa E.
Published: December 2019

Background and Purpose

G proteins are intracellular switches that transduce and amplify extracellular signals from GPCRs. The Gq protein subtypes, which are coupled to PLC activation, can act as oncogenes, and their expression was reported to be up‐regulated in cancer and inflammatory diseases. Gq inhibition may be an efficient therapeutic strategy constituting a new level of intervention. However, diagnostic tools and therapeutic drugs for Gq proteins are lacking.

Experimental Approach

We have now developed Gq‐specific, cell‐permeable 3H‐labelled high‐affinity probes based on the macrocyclic depsipeptides FR900359 (FR) and YM‐254890 (YM). The tracers served to specifically label and quantify Gq proteins in their native conformation in cells and tissues with high accuracy.

Key Results

FR and YM displayed low nanomolar affinity for Gαq, Gα11 and Gα14 expressed in CRISPR/Cas9 Gαq‐knockout cells, but not for Gα15. The two structurally very similar tracers showed strikingly different dissociation kinetics, which is predicted to result in divergent biological effects. Computational studies suggested a “dowel” effect of the pseudoirreversibly binding FR. A high‐throughput binding assay led to the discovery of novel Gq inhibitors, which inhibited Gq signalling in recombinant cells and primary murine brown adipocytes, resulting in enhanced differentiation.

Conclusions and Implications

The Gq protein inhibitors YM and FR are pharmacologically different despite similar structures. The new versatile tools and powerful assays will contribute to the advancement of the rising field of G protein research.
Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway
Authors: Wan Xiao‐Qin , Zeng Fan , Huang Xu‐Feng , Yang He‐Qin , Wang Lan , Shi Yan‐Chuan , Zhang Zhi‐Hui , Lin Shu
Published: December 2019

Aims

Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated.

Methods

Twenty‐four C57BL/6J mice were divided into four groups: a control group; a risperidone‐treated group; a lorcaserin‐treated group; and a combined risperidone + lorcaserin‐treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post‐treatment for determination of c‐fos activity. In addition, brains of NPY‐GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c‐fos, as well as NPY and 5‐HT2c receptor using immunohistochemistry.

Results

There was significantly elevated c‐fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone‐treated mice. More than 68% c‐fos‐positive neurons were NPY‐expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone‐treated group compared with control group. Moreover, we identified that 95% 5‐HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5‐HT2c receptor agonist.

Conclusion

Our findings provide critical insight into the mechanisms underlying antipsychotic‐induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.
Leveraging active learning to reduce human effort in the generation of ground‐truth for entity resolution
Authors: Fernandes de Araújo Diego , Santos Pires Carlos Eduardo , Cassimiro Nascimento Dimas
Published: December 2019

Several methods of entity resolution (ER) have been developed in academia and industry over the years, with the intention to identify duplicate entities (eg, records) in datasets. To evaluate the efficacy of such methods, it is necessary to compare their results with a ground‐truth, which consists of a document containing all known duplicate record pairs in a dataset. In general, the generation of ground‐truths for real datasets is performed manually from the inspection of all combinations of pairs of records in a dataset. This is subject to error and presents quadratic complexity, with respect to the size(s) of the dataset(s), requiring a long time to be performed. In this context, some works present (semi)automatic approaches for the generation of ground‐truths for the ER task. However, such approaches are either not applicable to several domains or still present a considerable manual effort. In this work, we propose GTGenERAL, a semiautomatic approach that combines results from multiple algorithms of ER together with active learning to generate accurate ground‐truths employing reduced manual effort. Experiments using real datasets show that, with great manual effort reduction, GTGenERAL is able to generate ground‐truths close to those generated by the state‐of‐the‐art approach.
Long‐term monitoring reveals forest tree community change driven by atmospheric sulphate pollution and contemporary climate change
Authors: Verrico Brittany M. , Weiland Jeremy , Perkins Timothy D. , Beckage Brian , Keller Stephen R.
Published: December 2019

Aim

Montane environments are sentinels of global change, providing unique opportunities to assess impacts on species diversity. Multiple anthropogenic stressors such as climate change and atmospheric pollution may act concurrently or synergistically in restructuring communities. Thus, a major challenge for conservation is untangling the relative importance of different stressors. Here, we combine long‐term monitoring with multivariate community modelling to estimate the anthropogenic drivers shaping forest tree diversity along an elevational gradient.

Location

Camels Hump Mountain, Vermont, USA.

Methods

We used Generalized Dissimilarity Modelling (GDM) to model spatial and temporal turnover in beta diversity along an elevational gradient over a 50‐year period and tested for spatiotemporal shifts in density and elevational distribution of individual species. GDMs were used to predict community turnover as nonlinear functions of changes in elevation, climate and atmospheric pollution.

Results

We observed significant shifts in elevational range and density of individual species, which contributed to an overall reduction in the elevational gradient in beta diversity through time. GDMs showed the combined effects of sulphate deposition and temperature as drivers of this temporal reduction in beta diversity. Spatiotemporal changes differed among species, with shifts observed both up‐ and downslope. For example, in a reversal of a previous upslope range contraction, red spruce (Picea rubens Sarg.) increased in density and shifted downslope since the 1990s, occupying warmer, drier climates.

Main conclusion

Our results demonstrate that global change is impacting the stratification of forest tree diversity along elevational gradients, but the responses of individual species are complex and variable in direction. We suggest abiotic drivers may directly impact individual species while also indirectly altering species interactions along elevational gradients. Our approach modelling the drivers of compositional turnover quantifies the rate and amount of change in beta diversity along environmental gradients and serves as a powerful complement to studying species‐specific responses.
Human footprint differentially impacts genetic connectivity of four wide‐ranging mammals in a fragmented landscape
Authors: Thatte Prachi , Chandramouli Anuradha , Tyagi Abhinav , Patel Kaushal , Baro Phulmani , Chhattani Himanshu , Ramakrishnan Uma
Published: December 2019

Aim

Maintaining connectivity is critical for long‐term persistence of wild carnivores in landscapes fragmented due to anthropogenic activity. We examined spatial genetic structure and the impact of landscape features on genetic structure in four widespread species—jungle cat (Felis chaus), leopard (Panthera pardus), sloth bear (Melursus ursinus) and tiger (Panthera tigris).

Location

Our study was carried out in the central Indian landscape, a stronghold in terms of distribution and abundance of large mammals. The landscape comprises fragmented forests embedded in a heterogeneous matrix of multiple land use types.

Methods

Microsatellite data from non‐invasively sampled individuals (90 jungle cats, 82 leopards, 104 sloth bears and 117 tigers) were used to investigate genetic differentiation. Impact of landscape features on genetic structure was inferred using a multimodel landscape resistance optimization approach.

Results

All four study species revealed significant isolation by distance (IBD). The correlation between genetic and geographic distance was significant only over a short distance for jungle cat, followed by longer distances for sloth bear, leopard and tiger. Overall, human footprint had a high negative impact on gene flow in tigers, followed by leopards, sloth bears and the least on jungle cats. Individual landscape variables—land use, human population density, density of linear features and roads—impacted the study species differently. Although land use was found to be an important variable explaining genetic structure for all four species, the amount of variation explained, and the optimum spatial resolution and the resistance values of different land use classes varied.

Main conclusions

As expected from theory, but rarely demonstrated using empirical data, the pattern of spatial autocorrelation of genetic variation scaled with dispersal ability and density of the study species. Landscape genetic analyses revealed species‐specific impact of landscape features and provided insights into interactions between species biology and landscape structure. Our results emphasize the need for incorporating functional connectivity data from multiple species for landscape‐level conservation planning.
Sleep architecture and homeostasis in children with epilepsy: a neurodevelopmental perspective
Authors: Chan Samantha Yuen‐Sum
Published: December 2019

Although the influence of sleep on epilepsy has long been recognized, this relationship has yet to be fully exploited to benefit patients. The past decade has seen significant advances in understanding paediatric sleep, providing a framework by which to properly evaluate the sleep of children with epilepsy, which itself has been subject to increasing scrutiny. The role of sleep in learning and the potential for interictal discharges to disrupt sleep‐related memory consolidation provide a novel perspective for understanding the association of childhood epilepsy with a high rate of intellectual disability. In this review, I outline the evolution of sleep duration, architecture, and homeostasis across childhood, relating this to the development of cognitive functions. I describe how these may be disrupted or preserved in children with epilepsy; in particular, collating data from polysomnography. Finally, I explore how sleep may, in the future, be modulated to improve cognitive outcome in these patients.

What this paper adds

Children with epilepsy have less rapid eye movement sleep than controls, but this improves with seizure cessation.

Deep or slow‐wave sleep is highly conserved in children with epilepsy.

Sleep homeostasis may be disrupted either at a local or global level by the presence of interictal epileptiform discharges.
Incidence of falls among adults with cerebral palsy: a cohort study using primary care data
Authors: Ryan Jennifer M , Cameron Michelle H , Liverani Silvia , Smith Kimberley J , O'connell Neil , Peterson Mark D , Anokye Nana , Victor Christina , Boland Fiona
Published: December 2019

Aim

To compare the rate of falls between adults with and without cerebral palsy (CP).

Method

We used primary care data on 1705 adults with CP and 5115 adults without CP matched for age, sex, and general practice attended. We compared odds of experiencing a fall between adults with and without CP using conditional logistic regression. We compared the rate of falls using a negative binomial model.

Results

Participants were 3628 males (53%) and 3192 females (47%) (median age 29y, interquartile range 20–42y) at the start of follow‐up. Follow‐up was 14 617 person‐years for adults with CP and 56 816 person‐years for adults without CP. Of adults with CP, 15.3% experienced at least one fall compared to 5.7% of adults without CP. Adults with CP had 3.64 times (95% confidence interval [CI] 2.98–4.45) the odds of experiencing a fall compared to adults without CP. The rate of falls was 30.5 per 1000 person‐years and 6.7 per 1000 person‐years for adults with and without CP respectively (rate ratio 5.83, 95% CI 4.84–7.02)

Interpretation

Adults with CP are more likely to fall, and fall more often, than adults without CP. The causes and consequences of falls in adults with CP need examination.

What this paper adds

Twenty adults with CP and 5.3 adults without CP experienced at least one fall per 1000 person‐years.

Adults with CP experienced 30.5 falls per 1000 person‐years compared to 6.7 falls per 1000 person‐years among adults without CP.

Adults with CP had 3.64 times the odds of experiencing a fall compared to adults without CP.

Adults with CP experienced 5.83 times more falls than adults without CP.
Proportion of young people in the general population consulting general practitioners: Potential for mental health screening and prevention
Authors: Solmi Marco , Durbaba Stevo , Ashworth Mark , Fusar‐Poli Paolo
Published: December 2019

Aim

One of the main obstacles with prevention in psychiatry is low detection of young subjects at risk for psychosis. The aim of the present work is to test whether general practitioners' (GP) offices are a possible setting for prevention of mental illness.

Methods

We used an Electronic Health Record database (Datanet) representing South‐London (Lambeth), where frequency of GP visits were available for each registered subject.

Results

We show that in 2018 out of almost 175 000 subjects aged 12 to 35, almost six out of ten people were seen by their General practitioner at least once in 2018, and considering those subjects with at least one medical condition, around nine subjects out of ten did the same.

Conclusions

A high proportion of adolescents and young adults are seen by GPs at least once per year. GP offices should be tested as possible setting for detection of subjects at risk for mental illness, in particular in subjects with risk factors for mental illness.
Age–period–cohort analysis of trends in toothache prevalence among 15‐ to 64‐yr‐old Finns over a 25‐yr period
Authors: Raittio Eero , Helakorpi Satu , Suominen Anna L.
Published: December 2019

Information on long‐term trends in toothache prevalence is scarce. The aim of this study was to assess age‐, period‐, and cohort‐related changes in toothache prevalence among 15‐ to 64‐yr‐old adults in Finland between 1990 and 2014 by using annual, representative postal surveys, albeit with decreasing response rates from 76% (n = 3,812) to 53% (n = 2,630). Age–period–cohort analysis of toothache prevalence during the past month was performed. Logistic regression analyses were conducted to account for other factors contributing to toothache. Toothache prevalence increased from 7% to 12% during the time period 1990 to 2014. Age–period–cohort analysis revealed that toothache prevalence increased from cohort to cohort, especially from the 1960 birth cohorts onwards (cohort effect). Adults under 30 yr of age had the highest toothache prevalence (~17%), while, in those over 30 yr of age, toothache prevalence decreased steadily according to age (to ~5% at age 64 yr, age effect). Toothache prevalence peaked at ~ 11% in the mid‐2000s (period effect). Toothache was strongly associated with poorer perceived health and lower toothbrushing frequency and less strongly associated with higher educational level, a higher number of missing teeth, history of smoking, being single, separated, or divorced, and female gender. The increase in toothache prevalence occurred especially from 1990 to the mid‐2000s, and mainly among younger age groups and more recent cohorts.
Electromagnetic optimization‐based clustering algorithm
Authors: Kushwaha Neetu , Pant Millie , Sharma Sugam
Published: December 2019

This paper introduces the electromagnetic clustering algorithm (ELMC), an enhanced variant of electromagnetic field optimization (EFO), for clustering. The motivation behind ELMC is to overcome the shortcomings of traditional k‐means clustering algorithm. The performance of k‐means primarily depends upon the initial choice of centroids, which can lead the algorithm towards an undesirable local optimum, if chosen incorrectly or inefficiently. The ELMC utilizes the attraction–repulsion concept of the EFO algorithm to maintain the diversity of the population, making it less vulnerable towards the initial choice of centroids. The performance of ELMC is validated on a set of benchmark problems, and the results are compared with other state‐of‐the‐art algorithms. Numerical and graphical results indicate the competence of the proposed ELMC algorithm.
A Na+ A1AO ATP synthase with a V‐type c subunit in a mesophilic bacterium
Authors: Litty Dennis , Müller Volker
Published: December 2019

A1AO ATP synthases with a V‐type c subunit have only been found in hyperthermophilic archaea which makes bioenergetic analyses impossible due to the instability of liposomes at high temperatures. A search for a potential archaeal A1AO ATP synthase with a V‐type c subunit in a mesophilic organism revealed an A1AO ATP synthase cluster in the anaerobic, acetogenic bacterium Eubacterium limosum KIST612. The enzyme was purified to apparent homogeneity from cells grown on methanol to a specific activity of 1.2 U·mg−1 with a yield of 12%. The enzyme contained subunits A, B, C, D, E, F, H, a, and c. Subunit c is predicted to be a typical V‐type c subunit with only one ion (Na+)‐binding site. Indeed, ATP hydrolysis was strictly Na+‐dependent. N,N′‐dicyclohexylcarbodiimide (DCCD) inhibited ATP hydrolysis, but inhibition was relieved by addition of Na+. Na+ was shown directly to abolish binding of the fluorescence DCCD derivative, NCD‐4, to subunit c, demonstrating a competition of Na+ and DCCD/NCD‐4 for a common binding site. After incorporation of the A1AO ATP synthase into liposomes, ATP‐dependent primary transport of 22Na+ as well as ΔµNa+‐driven ATP synthesis could be demonstrated. The Na+ A1AO ATP synthase from E. limosum is the first ATP synthase with a V‐type c subunit from a mesophilic organism. This will enable future bioenergetic analysis of these unique ATP synthases.
Restoring Halite Fluid Inclusions as an Accurate Palaeothermometer: Brillouin Thermometry Versus Microthermometry
Authors: Guillerm Emmanuel , Gardien Véronique , Ariztegui Daniel , Caupin Frédéric
Published: December 2019

Halite traps inclusions of the mother fluid when precipitating. When unchanged, the density of these fluid inclusions (FIs) records the water temperature Tf at the time of crystal formation. As halite is ubiquitous on Earth and geological time, its FIs possess a high potential as temperature archives. However, the use of FIs in halite as an accurate palaeothermometer has been hampered due to limitations of microthermometry, the most commonly used analytical method. Here, we show how Brillouin spectroscopy in halite FIs bypasses these limitations and allows recovering Tf to within 1 °C or less. To demonstrate this, we measured samples synthesised at 24.6 ± 0.5 °C and 33 ± 1 °C, and obtained 24.8 ± 0.4 °C and 31.9 ± 0.4 °C, respectively. This novel approach thus provides an accurate palaeothermometer for lacustrine and marine environments. Moreover, Brillouin spectroscopy solves the long‐standing debate on damage of halite fluid inclusions through quantifying the acceptable temperature excursion for preserving elastic behaviour: [l/(1 µm)]−0.64 × (90 °C), where l is the FI size. This threshold is lower for FIs close to the surface of the host crystal or to another FI. We also list ‘best practices’ for applying both microthermometry and Brillouin thermometry.
Mucoid and coccoid Helicobacter pylori with fast growth and antibiotic resistance
Authors: Kadkhodaei Sara , Siavoshi Farideh , Akbari Noghabi Kambiz
Published: December 2019

Background

In this study, one Helicobacter pylori isolate, from gastric biopsy of a dyspeptic patient that turned into mucoid‐coccoid (MC) form upon consecutive subcultures, was identified. The culturability, antibiotic resistance, and lipid contents of MC were compared with those of non‐mucoid (NM) spiral H pylori.

Materials and Methods

Mucoid‐coccoid and NM H pylori were subcultured on Brucella blood agar (BBA) and incubated under aerobic and microaerobic atmospheres at 37°C. Cultures were examined for colony characteristics and bacterial morphology after 1‐3 days. The isolates were identified by biochemical tests and detection of H pylori‐16S rDNA. Antibiogram was performed with currently used antibiotics for H pylori eradication. Cellular lipid contents were extracted and analyzed by gas chromatography.

Results

Compared with pin‐pointed and glistening colonies of NM H pylori that appeared under microaerobic conditions, MC H pylori grew well in consecutive subcultures under aerobic and microaerobic atmospheres and produced white patches of mucoid colonies. MC exhibited coccoid and NM spiral morphology. Both isolates were catalase, oxidase, and urease positive and contained 16S rDNA. Compared with NM that was susceptible to almost all the antibiotics, MC was resistant to all the antibiotics. Lipid analyses showed high frequency of unsaturated fatty acids and cholesterol in MC.

Conclusions

Coccoid forms with high fatty acid and cholesterol contents that show resistance to antibiotics might resist against other stressful conditions such as gastric acidity and immune response. Moreover, mucoid property may enhance resistance of coccoids to stresses. With mucoid‐coccoid lifestyle, H pylori may establish a chronic infection refractory to antimicrobial therapy.
PROTECT: Relational safety based suicide prevention training frameworks
Authors: Kar Ray Manaan , Wyder Marianne , Crompton David , Kousoulis Antonis A. , Arensman Ella , Hafizi Sepehr , Van Bortel Tine , Lombardo Chiara
Published: December 2019

Preventing suicide is a global priority, and staff training is a core prevention strategy. However, frontline pressures make translating training into better care and better outcomes difficult. The aim of the paper was to highlight challenges in suicide risk assessment and management and introduce training frameworks to assist with mindful practice so professionals can strike a balance between risk and recovery. We combined the scientific literature with contemporary practice from two successful initiatives from Cambridgeshire, UK: 333 – a recovery‐oriented model of inpatient/community crisis care and PROMISE – a programme to reduce coercion in care by enhancing patient experience. The resulting PROTECT (PROactive deTECTion) frameworks operationalize ongoing practice of relational safety in these programmes. PROTECT is a combination of novel concepts and adaptations of well‐established therapeutic approaches. It has four training frameworks: AWARE for reflection on clinical decisions; DESPAIR for assessment; ASPIRE for management; and NOTES for documentation. PROTECT aims to improve self‐awareness of mental shortcuts and risk‐taking thresholds and increase rigour through time‐efficient cross‐checks. The training frameworks should support a relational approach to self‐harm/suicide risk detection, mitigation, and documentation, making care safer and person‐centred. The goal is to enthuse practitioners with recovery‐oriented practice that draws on the strengths of the person in distress and their natural circle of support. It will provide the confidence to engage in participatory approaches to seek out unique individualized solutions to the overwhelming psychological pain of suicidal distress. Future collaborative research with people with lived and carer experience is needed for fine‐tuning.
Controlled trial of an mHealth intervention to promote healthy behaviours in adolescence (TeenPower): Effectiveness analysis
Authors: Sousa Pedro , Martinho Ricardo , Reis Catarina I. , Dias Sara S. , Gaspar Pedro J. S. , Dixe Maria dos Anjos , Luis Luis S. , Ferreira Regina
Published: December 2019

Aim

To evaluate the effectiveness on lifestyle change of an mHealth intervention to promote healthy behaviours in adolescence (TeenPower) and to analyse the predictors of the mHealth intervention effectiveness.

Design

This study is designed as a non‐randomized controlled trial with a two‐arm structure.

Methods

Adolescents of 12–16‐year old were recruited from three school districts, with access to the Internet and smartphone/tablet devices. The intervention group was invited to engage in the mHealth intervention (TeenPower) for 6 months in addition to a school‐based intervention. The control group only followed the school‐based intervention. A repeated measures factorial ANOVA was used and the main effectiveness outcome was the lifestyle change measured by the adolescent lifestyle profile.

Results

The outcomes of the mHealth intervention (TeenPower) show a significant effect on nutrition (ƞ2p = 0.03, p = .03), positive life perspective (ƞ2p = 0.04, p = .01), and global lifestyle (ƞ2p = 0.02, p = .05), with a dropout rate of 62.1%. The analysis of the effectiveness predictors of the mHealth intervention suggested that older adolescents tended to show a significant increase in the rates of stress management (r = .40; p < .05).

Conclusions

Although the considerable dropout rate, the mHealth intervention presented significant impact on multiple lifestyle domains, providing support for the effectiveness of mHealth interventions for health promotion as an add‐on to standard interdisciplinary interventions.

Impact

Adolescents must have the necessary and appropriate knowledge for the correct and responsible decision‐making regarding their health and lifestyle. Innovative strategies (mHealth intervention) were used to promote healthy behaviours. This study evaluates the effectiveness of an mHealth intervention (TeenPower) specifically designed for adolescents. We found a significant impact in several lifestyle domains such as health responsibility, nutrition, positive life perspective, and global lifestyle.