bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalable probabilistic PCA for large-scale genetic variation data
Authors: Agrawal Aman , Chiu Alec M. , Le Minh , Halperin Eran , Sankararaman Sriram
Published: August 2019

Principal component analysis (PCA) is a key tool for understanding population structure and controlling for population stratification in genome-wide association studies (GWAS). With the advent of large-scale datasets of genetic variation, there is a need for methods that can compute principal components (PCs) with scalable computational and memory requirements. We present ProPCA, a highly scalable method based on a probabilistic generative model, which computes the top PCs on genetic variation data efficiently. We applied ProPCA to compute the top five PCs on genotype data from the UK Biobank, consisting of 488,363 individuals and 146,671 SNPs, in less than thirty minutes. Leveraging the population structure inferred by ProPCA within the White British individuals in the UK Biobank, we scanned for SNPs that are not well-explained by the PCs to identify several novel genome-wide signals of recent putative selection including missense mutations in RPGRIP1L and TLR4.

Author Summary

Principal component analysis is a commonly used technique for understanding population structure and genetic variation. With the advent of large-scale datasets that contain the genetic information of hundreds of thousands of individuals, there is a need for methods that can compute principal components (PCs) with scalable computational and memory requirements. In this study, we present ProPCA, a highly scalable statistical method to compute genetic PCs efficiently. We systematically evaluate the accuracy and robustness of our method on large-scale simulated data and apply it to the UK Biobank. Leveraging the population structure inferred by ProPCA within the White British individuals in the UK Biobank, we identify several novel signals of putative recent selection.
Environmental influences on placental programming and offspring outcomes following maternal immune activation
Authors: Núñez Estevez Karen J. , Rondón-Ortiz Alejandro N. , Nguyen Jenny Q.T. , Kentner Amanda C.
Published: August 2019

Adverse experiences during pregnancy induce placental programming, affecting the fetus and its developmental trajectory. However, the influence of ‘positive’ maternal experiences on the placenta and fetus remain unclear. In animal models of early life stress, environmental enrichment (EE) has ameliorated and even prevented associated impairments in brain and behavior. Here, using a maternal immune activation (MIA) model in rats, we test whether EE attenuates maternal, placental and/or fetal responses to an inflammatory challenge, thereby offering a mechanism by which fetal programming may be prevented. Moreover, we evaluate life-long EE exposure on offspring development and examine a constellation of genes and epigenetic writers that may protect against MIA challenges. In our model, maternal plasma corticosterone and interleukin-1β were elevated 3 h after MIA, validating the maternal inflammatory response. Evidence for developmental programming was demonstrated by a simultaneous decrease in the placental enzymes Hsd11b2 and Hsd11b2/Hsd11b1, suggesting disturbances in glucocorticoid metabolism. Reductions of Hsd11b2 in response to challenge is thought to result in excess glucocorticoid exposure to the fetus and altered glucocorticoid receptor expression, increasing susceptibility to behavioral impairments later in life. The placental, but not maternal, glucocorticoid implications of MIA were attenuated by EE. There were also sustained changes in epigenetic writers in both placenta and fetal brain as a consequence of environmental experience and sex. Following MIA, both male and female juvenile animals were impaired in social discrimination ability. Life-long EE mitigated these impairments, in addition to the sex specific MIA associated disruptions in central Fkbp5 and Oprm1. These data provide the first evidence that EE protects placental functioning during stressor exposure, underscoring the importance of addressing maternal health and well-being throughout pregnancy. Future work must evaluate critical periods of EE use to determine if postnatal EE experience is necessary, or if prenatal exposure alone is sufficient to confer protection.
Herpes simplex virus-1 pUL56 degrades GOPC to alter the plasma membrane proteome
Authors: Soh Timothy K. , Davies Colin T. R. , Muenzner Julia , Connor Viv , Bouton Clément R. , Barrow Henry G. , Smith Cameron , Emmott Edward , Antrobus Robin , Graham Stephen C. , Weekes Michael P. , Crump Colin M.
Published: August 2019

Herpesviruses are ubiquitous in the human population and they extensively remodel the cellular environment during infection. Multiplexed quantitative proteomic analysis over a whole time-course of herpes simplex virus (HSV)-1 infection was used to characterize changes in the host-cell proteome and to probe the kinetics of viral protein production. Several host-cell proteins were targeted for rapid degradation by HSV-1, including the cellular trafficking factor GOPC. We identify that the poorly-characterized HSV-1 protein pUL56 binds directly to GOPC, stimulating its ubiquitination and proteasomal degradation. Plasma membrane profiling revealed that pUL56 mediates specific changes to the surface proteome of infected cells, including loss of IL18 receptor and Toll-like receptor 2, and delivery of Toll-like receptor 2 to the cell-surface requires GOPC. Our study highlights an unanticipated and efficient mechanism whereby a single virus protein targets a cellular trafficking factor to modify the abundance of multiple signaling molecules at the surface of infected cells.
Absence of pathogenic Short Tandem Repeat expansions in Systemic Lupus Erythematosus disease-associated genes
Authors: Lee Audrey , Cho Vicky , Andrews T. Daniel
Published: August 2019

Short tandem repeat (STR) expansions have been shown to be pathogenic in human neurological diseases, such as Huntington disease. Yet, the potential role of STRs in non-neurological diseases has yet to be fully investigated. In this study, the potential role of STR expansions in the pathogenesis of systemic lupus erythematosus (SLE) was investigated using patient genomic data and two computational tools, HipSTR and exSTRa. The length variability of STRs in 76 SLE-associated genes was compared using exome data from 271 SLE affected individuals and 158 of their unaffected relatives. We conclude that no large STR expansions associated with SLE were present in these affected individuals within the 76 genes investigated. Lack of evidence does not negate a pathogenic role for STR expansions in SLE, yet given the number of individuals included in this study, we expect that this is not a common source of pathogenesis in SLE.

Significance statement

The increasing availability and decreasing cost of sequencing genomes lends itself to computational analysis, extracting information to aid diagnosis, guide treatment or discover disease mechanisms and new treatments. Computational tools have been developed to look for various types of mutations, including short tandem repeats (STRs), which has been shown to cause diseases such as Huntington disease. Limited research on the possible role of STR expansions in systemic lupus erythematosus (SLE) has been done. Here we use computational tools to compare the length of STRs in 76 SLE-associated genes in patients and their unaffected relatives. Our results did not identify any large STR expansions associated with SLE, and further research is required to gain a better understanding of this complex disease.
Assessment of human diploid genome assembly with 10x Linked-Reads data
Authors: Zhang Lu , Zhou Xin , Weng Ziming , Sidow Arend
Published: August 2019

Background

Producing cost-effective haplotype-resolved personal genomes remains challenging. 10x Linked-Read sequencing, with its high base quality and long-range information, has been demonstrated to facilitate de novo assembly of human genomes and variant detection. In this study, we investigate in depth how the parameter space of 10x library preparation and sequencing affects assembly quality, on the basis of both simulated and real libraries.

Findings

We prepared and sequenced eight 10x libraries with a diverse set of parameters from standard cell lines NA12878 and NA24385 and performed whole genome assembly on the data. We also developed the simulator LRTK-SIM to follow the workflow of 10x data generation and produce realistic simulated Linked-Read data sets. We found that assembly quality could be improved by increasing the total sequencing coverage (C) and keeping physical coverage of DNA fragments (CF) or read coverage per fragment (CR) within broad ranges. The optimal physical coverage was between 332X and 823X and assembly quality worsened if it increased to greater than 1,000X for a given C. Long DNA fragments could significantly extend phase blocks, but decreased contig contiguity. The optimal length-weighted fragment length (WμFL) was around 50 – 150kb. When broadly optimal parameters were used for library preparation and sequencing, ca. 80% of the genome was assembled in a diploid state.

Conclusion

The Linked-Read libraries we generated and the parameter space we identified provide theoretical considerations and practical guidelines for personal genome assemblies based on 10x Linked-Read sequencing.
Direct detection of mRNA expression in microbial cells by fluorescencein situhybridization using RNase H-assisted rolling circle amplification
Authors: Takahashi Hirokazu , Horio Kyohei , Kato Setsu , Kobori Toshiro , Watanabe Kenshi , Aki Tsunehiro , Nakashimada Yutaka , Okamura Yoshiko
Published: August 2019

Meta-analyses using next generation sequencing is a powerful strategy for studying microbiota; however, it cannot clarify the role of individual microbes within microbiota. To know which cell expresses what gene is important for elucidation of the individual cell’s function in microbiota. In this report, we developed novel fluorescencein situhybridization (FISH) procedure using RNase-H-assisted rolling circle amplification to visualize mRNA of interest in microbial cells without reverse transcription. Our results show that this method is applicable to both gram-negative and gram-positive microbes without any noise from DNA, and it is possible to visualize the target mRNA expression directly at the single-cell level. Therefore, our procedure, when combined with data of meta-analyses, can help to understand the role of individual microbes in the microbiota.
High Fat Diet-Induced Obesity Negatively Affects Whole Bone Bending Strength but not Cortical Structure in the Femur
Authors: Hanne Nicholas J. , Steward Andrew J. , Cox Jason M. , Easter Elizabeth D. , Thornburg Hannah L. , Sessions Marci R. , Pinnamaraju Sriharsha V. , Cole Jacqueline H.
Published: August 2019

Although body mass index is positively associated with bone mineral density, suggesting obesity is protective against fracture, elderly obese individuals experience greater fracture risk at certain sites than non-obese peers, suggesting bone structural or material changes contribute to fragility. Diet-induced obesity rodent studies have reported detrimental changes to bone microstructure and some apparent-level material properties, but tissue-level material changes are not well understood. Because adipose tissue is highly vascularized, and bone remodeling depends critically on functional vascular supply, concurrent effects on osteovascular perfusion and structure may provide insight about obesity-related bone fragility. This study aimed to determine the effects of obesity on both tissue-level bone properties and osteovascular properties that could negatively impact bone strength. Five-week-old male C57Bl/6J mice were fed either high fat diet (HFD) or control fat diet (CFD) for 17 weeks and received daily treadmill exercise or remained sedentary for eight weeks at ages 14-22 weeks. HFD negatively affected femur bending strength, with 18% lower yield load than CFD. Although HFD negatively altered cancellous microstructure in the distal femur, with 32% lower bone volume fraction than CFD, it did not affect cortical bone geometry in the femoral metaphysis or diaphysis. HFD caused increased carbonate substitution but had no effect on other composition metrics or apparent- or tissue-level material properties in the femoral diaphysis. Exercise did not affect bone strength or microstructure but increased endosteal mineralizing surface in the tibial diaphysis, mineral crystallinity and mineral-to-matrix ratio in the femur, and blood supply to the proximal tibial metaphysis. HFD did not affect blood supply in the tibia or 2D osteovascular structure in the distal femoral metaphysis, indicating that HFD negatively affects cancellous bone without affecting osteovasculature. This study reveals that HFD negatively affected cancellous microstructure without affecting osteovascular structure, and whole-bone strength without altering cortical geometry or material properties.
Ischemic Stroke Reduces Bone Perfusion and Alters Osteovascular Structure
Authors: Hanne Nicholas J. , Steward Andrew J. , Geeroms Carla , Easter Elizabeth D. , Thornburg Hannah L. , Kerckhofs Greet , Parac-Vogt Tatjana , Sheng Huaxin , Cole Jacqueline H.
Published: August 2019

Rationale

Stroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown.

Objective

To characterize changes to osteovascular function, structure, and composition following mild-to-moderate-severity ischemic stroke in mice, both with and without exercise therapy.

Methods and Results

Twelve-week-old male mice (n=27) received either a stroke (middle cerebral artery occlusion) or sham procedure, followed by four weeks of daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis, was reduced by stroke for two weeks. In the second week of recovery, exercise nearly restored perfusion to sham levels, and perfusion tended to be lower in the stroke-affected limb. At the conclusion of the study, osteovascular structure was assessed with contrast-enhanced computed tomography in the distal femoral metaphysis. Stroke significantly increased osteovascular volume and branching but reduced the relative number of blood vessels close to bone surfaces (6-22 µm away) and increased the relative number more than 52 µm away. These differences in vessel proximity to bone were driven by changes in the stroke-exercise group, indicating compounded effects of stroke and exercise. Exercise, but not stroke, nearly reduced the amount of osteogenic Type H blood vessels in the proximal tibial metaphysis, quantified with immunofluorescence microscopy.

Conclusions

This study is the first to examine the effects of stroke on osteovasculature. Stroke increased the amount of osteovasculature, but since blood vessels close to bone are associated with bone remodeling, the shift in osteovascular structure could play a role in bone loss following stroke. The exercise-induced reduction in the amount of Type H vessels and the stroke-exercise effect on osteovascular structure suggest moderate aerobic activity may have detrimental effects on bone remodeling during early stroke recovery.
Synchrony and complexity in state-related EEG networks: an application of spectral graph theory
Authors: Ghaderi Amir Hossein , Baltaretu Bianca R. , Andevari Masood Nemati , Bharmauria Vishal , Balci Fuat
Published: August 2019

To characterize differences between different state-related brain networks, statistical graph theory approaches have been employed to identify informative, topological properties. However, dynamical properties have been studied little in this regard. Our goal here was to introduce spectral graph theory as a reliable approach to determine dynamic properties of functional brain networks and to find how topological versus dynamical features differentiate between such networks. To this goal, 45 participants performed no task with eyes open (EO) or closed (EC) while electroencephalography data were recorded. These data were used to create weighted adjacency matrices for each condition (rest state EO and rest state EC). Then, using the spectral graph theory approach and Shannon entropy, we identified dynamical properties for weighted graphs, and we compared these features with topological aspects of graphs. The results showed that spectral graph theory can distinguish different state-dependent neural networks with different synchronies. On the other hand, correlation analysis indicated that although dynamical and topological properties of random networks are completely independent, these network features can be related in the case of brain generated graphs. In conclusion, the spectral graph theory approach can be used to make inferences about various state-related brain networks, for healthy and clinical populations.

Author Summery

By considering functional communications across different brain regions, a complex network is achieved that is known as functional brain network. Topologically, this network is constructed by different nodes (activity of brain regions or signals over recording electrodes) and different edges (similarity, correlation or phase difference between nodes). Paths, clusters, hubs, and centrality of nodes are examples of topological properties of these networks. However, synchrony and stability of functional brain networks can not be revealed by consideration of topological properties. Alternatively, spectral graph theory (SGT) can demonstrate the dynamic, synchrony and stability of graphs. But this approach has been studied little in brain network analysis. Here, we employed SGT, as well as topological methods, to investigate which approaches are more reliable to find differences between distinct state-related brain networks. On the other hand, we investigated correlations between topology and dynamic in different type of networks (brain generated and random networks). We found that SGT measures can clearly distinguish between distinct state-related brain networks and it can reveal synchrony and complexity of these networks. Also, results show that although dynamic and topology of random-generated graph are completely independent, these properties exhibit several correlations in the case of functional brain networks.
Reconstructing the invasion route of DNA transposons using extant population samples
Authors: Weilguny Lukas , Vlachos Christos , Selvaraju Divya , Kofler Robert
Published: August 2019

Reconstructing invasion routes of transposable elements (TEs), so far, required capturing an ongoing invasion with population samples from different geographic regions and time points. Here, we propose a more accessible approach. Abundantly occurring internal deletions of DNA transposons allow to trace the direction as well as the path of an invasion, even hundreds of generations after the spread of a TE. We validated this hypothesis with computer simulations and by accurately reproducing the route of the P-element invasion inDrosophila melanogaster. Finally, we used our method to shed light on the controversial hobo invasion inD. melanogaster. Our approach solely requires sequenced samples from extant populations and sequences of TEs of interest. Hence, DNA transposons in a wide range of model and non-model organisms may be analyzed. Our approach will further our understanding of TE dynamics, migration patterns, and the ecology of species.
Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields
Authors: Agnes Everton J. , Luppi Andrea I. , Vogels Tim P.
Published: August 2019

Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.
A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair
Authors: Marnef Aline , Finoux Anne-Laure , Arnould Coline , Guillou Emmanuelle , Daburon Virginie , Rocher Vincent , Mangeat Thomas , Mangeot Philippe E. , Ricci Emiliano P. , Legube Gaëlle
Published: August 2019

The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. DNA double-strand breaks (DSBs) within rDNA induce both rDNA transcriptional repression and nucleolar segregation, but the link between the two events remains unclear. Here we found that DSBs induced on rDNA trigger transcriptional repression in a cohesin- and HUSH (human silencing hub) complex-dependent manner throughout the cell cycle. In S/G2 cells, transcriptional repression is further followed by extended resection within the interior of the nucleolus, DSB mobilization at the nucleolar periphery within nucleolar caps, and repair by homologous recombination. We showed that nuclear envelope invaginations frequently connect the nucleolus and that rDNA DSB mobilization, but not transcriptional repression, involves the nuclear envelope-associated LINC complex and the actin pathway. Altogether, our data indicate that rDNA break localization at the nucleolar periphery is not a direct consequence of transcriptional repression but rather is an active process that shares features with the mobilization of persistent DSB in active genes and heterochromatin.
Maxdeletion destabilizes MYC protein and abrogates Eµ-Myclymphomagenesis
Authors: Mathsyaraja Haritha , Freie Brian , Cheng Pei-Feng , Babaeva Ekaterina , Catchpole Jonathen T. , Janssens Derek , Henikoff Steven , Eisenman Robert N.
Published: August 2019

Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion ofMaxhas a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. WhileMaxloss affects only a few hundred genes in normal B cells, it leads to the global down-regulation ofMyc-activated genes in premalignant Eµ-Myccells. We show that the balance between MYC–MAX and MNT–MAX interactions in B cells shifts in premalignant B cells toward a MYC-driven transcriptional program. Moreover, we found that MAX loss leads to a significant reduction in MYC protein levels and down-regulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC–MAX dimerization inhibitors. Our work uncovers a layer ofMycautoregulation critical for lymphomagenesis yet partly dispensable for normal development.
Influence of inclined Lorentz forces through a porous media on squeezing Cu-H2o nanofluid in the presence of heat source/sink
Authors: Mousavisani Seyedmohammad , Khalesi Javad , Golbaharan Hossein , Sepehr Mohammad , Ganji D.D.
Published: August 2019

Purpose

The purpose of this paper is to find the approximate solutions of unsteady squeezing nanofluid flow and heat transfer between two parallel plates in the presence of variable heat source, viscous dissipation and inclined magnetic field using collocation method (CM).

Design/methodology/approach

The partial governing equations are reduced to nonlinear ordinary differential equations by using appropriate transformations and then are solved analytically by using the CM.

Findings

It is observed that the enhancing values of aligned angle of the magnetic causes a reduction in temperature distribution. It is also seen that the effect of nanoparticle volume fraction is significant on the temperature but negligible on the velocity profile.

Originality/value

To the best of the authors’ knowledge, no research has been carried out considering the combined effects of inclined Lorentz forces and variable heat source on squeezing flow and heat transfer of nanofluid between the infinite parallel plates.
Nonlinear radiative flow of nanofluid in presence of gyrotactic microorganisms and magnetohydrodynamic
Authors: Hayat Tasawar , Bashir Zeenat , Qayyum Sumaira , Alsaedi Ahmed
Published: August 2019

Purpose

This paper aims to explore the study of magnetohydrodynamic viscous fluid flow past on a stretching cylinder with nonlinear thermal radiation having gyrotactic microorganisms.

Design/methodology/approach

Appropriate transformations reduce the nonlinear partial differential equation to ordinary ones. Subsequent nonlinear equations are calculated to get convergent series solutions.

Findings

Fluid velocity declines for elevating values of magnetic field parameter. For larger values of curvature parameter near the cylinder temperature reduces.

Originality/value

To the best of the authors’ knowledge, magnetohydrodynamic boundary layer flow of viscous fluid by nonlinear stretching cylinder with nonlinear thermal radiation having gyrotatic microorganisms is not studied yet. The purpose is to study this.
Shared amenities’ impacts on condominium resale values
Authors: Tajima Kayo
Published: August 2019

Purpose

This study aims to analyze whether and how condominium shared utilities and facilities (e.g. community spaces), of which buyers assume a share of the ownership upon acquisition of a residential unit, affect the condominium unit price over time.

Design/methodology/approach

The transaction price of each unit reflects the quality of the residential unit and the properties of the shared facilities. Based on the hedonic pricing method, this study assesses the impact of shared amenities on unit resale prices, using an original data set on condominium unit resale transactions and the status of housing characteristics for both condominium units and condominium buildings.

Findings

Results show that holding other conditions constant, a meeting room and an external space that can host events increase the unit resale price by approximately 7 and 16 per cent, respectively. Some community amenities such as a meeting room may increase its impact later in the condominium’s lifetime.

Research limitations/implications

Because of the proprietary nature of data, the analysis focuses on high-end condominium properties in central Tokyo. Although it is difficult to single out the shared amenities’ effects on condominium resale prices from potentially confounding factors, this study partially overcomes this issue by including explanatory geographical variables (e.g. ground heights).

Practical implications

The results suggest that a shared facility that hosts social interactions among residents significantly affects the resale market value of housing units and that their magnitudes may change over time.

Originality/value

To the best of the author’s knowledge, this study provides the first empirical evidence of the impacts of shared structures on condominium unit sales using micro-level transaction data in Japan.
Sustainability in Brazilian HEI: practices overview
Authors: Moura Manoela Maria Caron , Frankenberger Fernanda , Tortato Ubiratã
Published: August 2019

Purpose

The purpose of this paper is to verify how Brazilian HEIs apply sustainability practices, as means to improve their effects towards society, making clear to the public, including current and future students, what the university is doing and how it is concerned with sustainability.

Design/methodology/approach

Based on the Brazilian Education Ministry evaluation, 123 HEIs were selected as sample for the study. The websites of these HEI were verified to check for sustainability practices.

Findings

In general, the HEI focuses on helping people who live around the campus with social projects, health and work preparation. Further practices areas are new forms of energy, selective collection and new standards of plastic consumption. HEI with higher evaluations from the Education Ministry focuses mainly on educational programs and projects to improve sustainability inside and outside the campus.

Research limitations/implications

With the methodology used, not all HEIs in Brazil were analyzed, which gives a great opportunity for further studies.

Practical implications

HEIs may use the findings of this research to develop their sustainability practices, either in the curriculum, projects, strategic plans or even organizational structure.

Social implications

Communities are positively supported by universities applying sustainability practices. Such support includes education, health, guidance and provision of services to the community, financial aid and social well-being.

Originality/value

Focusing on sustainability practices of HEI located in Brazil, the research finds, besides the practices, gaps in several of the researched universities.
Who benefits from university–industry collaboration for environmental sustainability?
Authors: Di Maria Eleonora , De Marchi Valentina , Spraul Katharina
Published: August 2019

Purpose

This paper aims to analyze the characteristics and performance of university–industry (U-I) collaboration for knowledge transfer in relation to environmental sustainability, considering for both parties of the collaborations.

Design/methodology/approach

The study is explorative in nature, based on an original data set of more than 350 U-I research and consultancy contracts signed by more than 70 professors specializing in environmental sustainability-related academic disciplines at the University of Padova (Italy) for the period 2008-2012. A mixed-method approach is adopted. Social network analysis and regressions are used to explore the impact of U-I on performance considering for characteristics of the firms, the professors and the collaboration. Interviews with key informants at University of Padova is used to complement and validate the emerging evidence.

Findings

Results suggest that U-I positively impacts the performance of firms, but not of professors. Indeed, the hypothesis that professors’ performance (measures in terms of academic publications) is positively associated with academic engagement is not supported. On the contrary, firms’ financial performance is positively associated with U-I collaboration focused on knowledge transfer for environmental innovation; the higher the contracts activated the better the economic performance.

Originality/value

While most previous research has focused either on the university or the firm side of U-I, this study looks at both sides and focuses specifically on engagement in green contracts. The analysis of the geographical scope of U-I collaborations contributes to the growing body of literature by outlining geography’s role in U-I collaborations related to sustainability.
How mindfulness training cultivates introspection and competence development for sustainable consumption
Authors: Frank Pascal , Sundermann Anna , Fischer Daniel
Published: August 2019

Purpose

This paper aims to explore the relationship between introspection and key competencies for sustainable consumption (KCSCs). It investigates whether mindfulness training can cultivate the ability to introspect and stimulate the development of KCSCs.

Design/methodology/approach

Two independent studies were analyzed. Data were retrieved from interviews with participants of a consumer-focused mindfulness training (Study 1, 11 participants), as well as from diaries of students attending a university seminar with mindfulness training (Study 2, 13 students), and made subject to qualitative content analysis.

Findings

Both studies show a clear intersection between both constructs and suggest that mindfulness training can contribute to the development of KCSCs and learners’ ability to introspect. The studies also demonstrated that introspection is not equally related to all competencies and that KCSCs must not be reduced to introspection.

Research limitations/implications

Both KCSCs and introspection are complex and latent constructs and hence challenging to observe. The research understands itself as a first exploratory approach for empirically investigating this complex relation.

Originality/value

While increasing (self-)reflectivity is at the core of competence-based education, a systematic engagement with the practice of introspection as a means to enhancing reflectivity is surprisingly lacking. Mindfulness training could be a promising way to cultivate introspective abilities and thus facilitate learning processes that are conducive to competence development.
Building a typology of the 100 smart cities in India
Authors: Praharaj Sarbeswar , Han Hoon
Published: August 2019

Purpose

The Smart Cities Mission (SCM) in India is generating significant interest among researchers and policymakers globally. Cities under the SCM, irrespective of their locations, size, capacities or local needs, are heavily investing in technological solutions to improve civic conditions. The purpose of this paper is to build a typology and urban classification system of these 100 smart cities using a series of key performance indicators (KPIs) around urban development and access to public services. The paper also systematically recognises the diversity of challenges facing these cities and assess whether a generic technology-based approach is adequate to address them.

Design/methodology/approach

A two-stage statistical process is employed in this typology building exercise – first, a cluster analysis is conducted to classify the selected cities, then a multiple discriminant analysis is used to characterise each classified city.

Findings

The urban typology analysis finds that vast disparities remain across India’s urban centres, located in different geographical regions, in terms of access to social capital and physical infrastructure. The KPIs around education, health and social services emerged from the analysis as the most significant drivers in the urban typology building process. The lack of basic community infrastructure, especially in the small-to-medium-sized cities in India, exposes the shortcomings of a one-size-fits-all technocratic smart city development strategy that assumes foundational infrastructure is already in place for technology to take effect.

Originality/value

The research methodologies developed in this paper offers a novel planning approach for smart city policymakers to devise place-based smart city interventions, acknowledging diverse cultures and specific community needs.
Family of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis caused by a novel FAM111B mutation
Authors: Zhang Zhen , Zhang Jia , Chen Fuying , Zheng Luyao , Li Huaguo , Liu Ming , Li Ming , Yao Zhirong
Published: August 2019

Hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP) is a recently identified autosomal dominant genetic syndrome with mutations in FAM111B. Herein, we report a 14‐month‐old girl who presented with progressive poikiloderma on the face. Her 24‐year‐old mother had an identical facial poikiloderma, hyperpigmentation, mottling and Blaschko line hypopigmentation on the trunk and limbs, as well as severe tendon contractures. Next‐generation sequencing based on a targeted gene capture panel revealed a missense mutation in the FAM111B gene p.Phe416Ser (c.1247T>C). Her mother had the same mutation as the proband. Moreover, this mutation was absent in the unaffected father and maternal grandparents. Based on the clinical manifestations and genetic analysis, the proband and her mother were diagnosed with POIKTMP. Protein modeling indicated that the mutation p.Phe416Ser dramatically changed the protein structure, especially its structural stability, and affected the protein function. This is the first report of POIKTMP in a Chinese family due to a novel FAM111B mutation. Furthermore, we have reviewed the genotype–phenotype correlation, differential diagnoses and management of POIKTMP.
Ascoma genotyping and mating type analyses of mycorrhizas and soil mycelia of Tuber borchii in a truffle orchard established by mycelial inoculated plants
Authors: Leonardi Pamela , Murat Claude , Puliga Federico , Iotti Mirco , Zambonelli Alessandra
Published: August 2019

Tuber borchii (the Bianchetto truffle) is a heterothallic Ascomycete living in symbiotic association with trees and shrubs. Maternal and paternal genotype dynamics have already been studied for the black truffles Tuber melanosporum and Tuber aestivum but not yet for T. borchii. In this study, we analysed maternal and paternal genotypes in the first truffle orchard realized with plants inoculated with five different T. borchii mycelia. Our aims were to test the persistence of the inoculated mycelia, if maternal and/or paternal genotypes correspond to inoculated mycelia and to assess the hermaphroditism of T. borchii. The mating type of each isolate as well as those of mycorrhizas, ascomata and extraradical soil mycelia was determined. Moreover, simple sequence repeat (SSR) profiles of maternal and paternal genotypes were assessed in 18 fruiting bodies to investigate the sexual behaviour of this truffle. The maternal genotypes of the fruiting bodies corresponded to those of the inoculated mycelia with only two exceptions. This confirmed that the inoculated mycelia persisted 9 years after plantation. As regards paternal partner, only two had the same genotype as those of the inoculated mycelia, suggesting hermaphroditism. Most of the new paternal genotypes originated from a recombination of those of inoculated mycelia.
Reproducibility of Artificial Cut on Heel Area of Rubber Outsole
Authors: Liu Luoxi , Wu Jian , Luo Yaping , Lin Sheng
Published: August 2019

Randomly acquired characteristics (RAC) are seldom used for exclusion in footwear examinations because they can disappear owing to wear. To help examiners explain discrepancies in RAC, this study investigated the reproducibility of cuts. One cut was made on the heel area of each shoe outsole and then measured. Changes in cuts were statistically evaluated, correlations between their variations and the weight/height of the subject were assessed, and the Support Vector Machine was used for the first time to study their discrimination probability. Most cuts became larger at first and then became smaller. The solidities of most cuts increased after 21 days, and the variation in the cut and the subject's weight/height were negatively correlated. Although the discrimination probability declined as the cut aged, 77% of the same‐source and 96.88% of the different‐source cuts could be identified correctly after 6 months, indicating that cuts on the heel area are relatively reliable.
Is the global prevalence rate of adult mental illness increasing? Systematic review and meta‐analysis
Authors: Richter D. , Wall A. , Bruen A. , Whittington R.
Published: August 2019

Objectives

The question whether mental illness prevalence rates are increasing is a controversially debated topic. Epidemiological articles and review publications that look into this research issue are often compromised by methodological problems. The present study aimed at using a meta‐analysis technique that is usually applied for the analysis of intervention studies to achieve more transparency and statistical precision.

Methods

We searched PubMed, PsycINFO, CINAHL, Google Scholar and reference lists for repeated cross‐sectional population studies on prevalence rates of adult mental illness based on ICD‐ or DSM‐based diagnoses, symptom scales and distress scales that used the same methodological approach at least twice in the same geographical region. The study is registered with PROSPERO (CRD42018090959).

Results

We included 44 samples from 42 publications, representing 1 035 697 primary observations for the first time point and 783 897 primary observations for the second and last time point. Studies were conducted between 1978 and 2015. Controlling for a hierarchical data structure, we found an overall global prevalence increase in odds ratio of 1.179 (95%‐CI: 1.065–1.305). A multivariate meta‐regression suggested relevant associations with methodological characteristics of included studies.

Conclusions

We conclude that the prevalence increase in adult mental illness is small, and we assume that this increase is mainly related to demographic changes.
Modulation of the functions of myeloid‐derived suppressor cells : a new strategy of hydrogen sulfide anti‐cancer effects
Authors: De Cicco Paola , Ercolano Giuseppe , Rubino Valentina , Terrazzano Giuseppe , Ruggiero Giuseppina , Cirino Giuseppe , Ianaro Angela
Published: August 2019

Background and Purpose

Myeloid‐derived suppressor cells (MDSCs) represent a major obstacle to cancer treatment, as they negatively regulate anti‐tumour immunity through the suppression of tumour‐specific T lymphocytes. Thus, the efficacy of immunotherapies may be improved by targeting MDSCs. In this study, we assessed the ability of hydrogen sulfide (H2S), a gasotransmitter whose anti‐cancer effects are well known, to inhibit the accumulation and immunosuppressive functions of MDSCs in melanoma.

Experimental Approach

Effects of H2S on the host immune response to cancer were evaluated using an in vivo syngeneic model of murine melanoma. B16F10‐melanoma‐bearing mice were treated with the H2S donor, diallyl trisulfide (DATS) and analysed for content of MDSCs, dendritic cells (DCs) and T cells. Effects of H2S on expression of immunosuppressive genes in MDSCs and on T cell proliferation were evaluated.

Key Results

In melanoma‐bearing mice, DATS inhibited tumour growth, and this effect was associated with a reduction in the frequency of MDSCs in the spleen, in the blood as well as in the tumour micro‐environment. In addition, we found that CD8+ T cells and DCs were increased. Furthermore, DATS reduced the immuno‐suppressive activity of MDSCs, restoring T cell proliferation.

Conclusions and Implications

The H2S donor compound, DATS, inhibited the expansion and the suppressive functions of MDSCs, suggesting a novel role for H2S as a modulator of MDSCs in cancer. Therefore, H2S donors may provide a novel approach for enhancing the efficacy of melanoma immunotherapy.

Linked Articles

This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc
Geographic accessibility to primary care providers: Comparing rural and urban areas in Southwestern Ontario
Authors: Shah Tayyab I. , Clark Andrew F. , Seabrook Jamie A. , Sibbald Shannon , Gilliland Jason A.
Published: August 2019

This research examines geographical accessibility to primary care providers (PCPs) across urban and rural areas of Southwestern Ontario and examines variations in the distribution of PCPs in relation to the senior population (aged 65 years and older). Information about PCP practices was provided by the HealthForceOntario Marketing and Recruitment Agency. Population data were obtained from the 2016 Census of Canada. To calculate scores for accessibility to PCPs (i.e., PCPs/10,000 population), we applied the enhanced 2‐step floating catchment area method with distance decay effect within a global service catchment of 30‐minute drive time. A geospatial mapping approach revealed disparities in the distribution of PCPs with a pattern of higher spatial accessibility in or around major urban areas in Southwestern Ontario. Comparative analyses were performed in association with the seniors’ population to identify how accessibility scores were mismatched with the population needs. The outcome of this study will assist researchers and health service planners to better understand the distribution of existing PCPs to address inequalities, particularly in rural areas.
Identification of potential drug–targets by combining evolutionary information extracted from frequency profiles and molecular topological structures
Authors: Wang Lei , You Zhu‐Hong , Li Li‐Ping , Yan Xin , Zhang Wei , Song Ke‐Jian , Song Chuan‐Dong
Published: August 2019

Identifying interactions among drug compounds and target proteins is the basis of drug research and plays a crucial role in drug discovery. However, determining drug–target interactions (DTIs) and potential protein–compound interactions by biological experiment‐based method alone is a very complicated, expensive, and time‐consuming process. Hence, there is an intense motivation to design in silico prediction methods to overcome these obstacles. In this work, we designed a novel in silico strategy to predict proteome‐scale DTIs based on the assumption that DTI pairs can be expressed through the evolutionary information derived from frequency profiles and drugs’ structural properties. To achieve this, drug molecules are encoded into the substructure fingerprints to represent certain fragments; target proteins are first converted into position‐specific scoring matrix (PSSM) and then encoded as 2‐dimensional principal component analysis (2DPCA) descriptors. In the prediction phase, the feature weighted rotation forest (RF) classifier is used to estimate whether drug and target interact with each other on four benchmark datasets,includingEnzymes, Ion Channels, GPCRs, andNuclear Receptors. The prediction accuracy of cross‐validation on the four datasets is 95.40%, 88.82%, 85.67%, and 82.22%, respectively. In order to have a clearer assessment of the proposed approach, we compared it with the discrete cosine transform (DCT) descriptor model, support vector machine (SVM) classifier model, and existing excellent approaches, including DBSI, NetCBP, KBMF2K, SIMCOMP, and RFDT. The excellent results of the experiment indicated that the proposed approach can effectively improve the DTI prediction accuracy and can be used as a practical tool for the research and design of new drugs.
Prediction of hERG K+ channel blockage using deep neural networks
Authors: Zhang Yanmin , Zhao Junnan , Wang Yuchen , Fan Yuanrong , Zhu Lu , Yang Yan , Chen Xingye , Lu Tao , Chen Yadong , Liu Haichun
Published: August 2019

Human ether‐a‐go‐go‐related gene (hERG) K+ channel blockage may cause severe cardiac side‐effects and has become a serious issue in safety evaluation of drug candidates. Therefore, improving the ability to avoid undesirable hERG activity in the early stage of drug discovery is of significant importance. The purpose of this study was to build predictive models of hERG activity by deep neural networks. For each combination of sampling methods and descriptors, deep neural networks with different architectures were implemented to build classification models. The optimal model M15 with three hidden layers, undersampling method, and 2D descriptors yielded the prediction accuracy of 0.78 and F1 score of 0.75 on the test set as well as accuracy of 0.77 and F1 score of 0.34 on the external validation set, outperforming the other 35 models including 9 random forest models. Particularly, the optimal model M15 achieved the highest F1 score and the second highest accuracy when compared with other five methods from four groups using different machine learning algorithms with the same external validation set. It can be believed that this model has powerful capability on prediction of hERG toxicity, which is of great benefit for developing novel drug candidates.