bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Engineering and Regenerative Medicine in Craniofacial Reconstruction and Facial Aesthetics
Authors: Borrelli Mimi R. , Hu Michael S. , Longaker Michael T. , Lorenz Hermann Peter
Published: August 2019

The craniofacial region is anatomically complex and is of critical functional and cosmetic importance, making reconstruction challenging. The limitations of current surgical options highlight the importance of developing new strategies to restore the form, function, and esthetics of missing or damaged soft tissue and skeletal tissue in the face and cranium. Regenerative medicine (RM) is an expanding field which combines the principles of tissue engineering (TE) and self-healing in the regeneration of cells, tissues, and organs, to restore their impaired function. RM offers many advantages over current treatments as tissue can be engineered for specific defects, using an unlimited supply of bioengineered resources, and does not require immunosuppression. In the craniofacial region, TE and RM are being increasingly used in preclinical and clinical studies to reconstruct bone, cartilage, soft tissue, nerves, and blood vessels. This review outlines the current progress that has been made toward the engineering of these tissues for craniofacial reconstruction and facial esthetics.
Trends, Determinants, and Impact on Survival of Post-Lung Transplant Weight Changes: A Single-center Longitudinal Retrospective Study
Authors: Jomphe Valérie , Nguyen Cécile , Durette Gabrielle , Chagnon Miguel , Nasir Basil , Poirier Charles , Ferraro Pasquale , Lands Larry C. , Mailhot Geneviève
Published: August 2019

Background.

Weight gain is commonly seen in lung transplant (LTx) recipients. Although previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality.

Methods.

Retrospective cohort study of LTx recipients between January 1, 2000, and November 30, 2016 (n = 502). Absolute weight changes from transplant were calculated at fixed time periods (6 mo, 1, 2, 5, 10, and 15 y), and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis.

Results.

LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all time points, whereas transplant body mass index categories were significant predictors at earlier time points. Patients with a weight gain of >10% at 5 years had a better survival (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.20-0.66), whereas a 10% weight loss at earlier time points was associated with worse survival (1 y: HR, 2.04; 95% CI, 1.22-3.41 and 2 y: HR, 2.37; 95% CI, 1.22-4.58).

Conclusions.

Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors, and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant.
Classification of idiopathic inflammatory myopathies: pathology perspectives
Authors: Tanboon Jantima , Nishino Ichizo
Published: August 2019

Purpose of review

Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering various combinations of clinical, serological, and pathological information have been proposed. This review summarizes recent clinicoseropathological development in major subgroups of IIM.

Recent findings

Considering clinicoseropathological features, IIM are suggestively classified into four major subgroups: dermatomyositis, immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM). Many historically diagnosed polymyositis have been mainly reclassified as IBM, IMNM, and ASS. Different types of myositis-specific antibodies (MSA) suggest distinct clinicopathological subsets of IIM. Excluding IBM, at least one-third of the IIMs have no known associated MSA.

MSA are crucial for IIM classification but can be negative. Thus, IIM should be universally classified using stepwise or integrated information on clinical, serological, and pathological findings.
EZH2 inhibition results in genome-wide PRC2 redistribution
Authors: Yuan Chih-Chi , Jeon Ah Jung , Tucker-Kellogg Greg , Bryant Barbara , Trojer Patrick
Published: August 2019

Histone methyltransferase polycomb repressive complex 2 (PRC2) plays a critical role in cell fate determination, and its catalytic subunit EZH2 is a key oncogenic driver in GCB-DLBCL. EZH2 inhibition in some GCB-DLBCL cell models leads to a global loss of H3K27me3, the derepression of a subset of silenced PRC2 target genes, and ultimately cell death. Here we show that EZH2 inhibition causes global redistribution of PRC2 components. We observe a reduction in the already-low levels of PRC2 at active genes. On the other hand, focal PRC2 accumulation and concomitant H3K27me3 retention occur at many canonical embryonic stem cell PRC2 nucleation sites. PRC2 accumulation is also enriched in plasma/memory cell genes repressed by PRC2 activity in the germinal center. We see PRC2 redistribution to, and H3K27me3 retention at, differentiation-related genes not only in cell lines that are insensitive to killing by EZH2 inhibition, but also in sensitive cell lines. Thus, PRC2 redistribution to B cell differentiation genes is not sufficient to explain the resistance to EZH2 inhibitors in some DLBCL cell lines.
MesenchymalIgf2is a major paracrine regulator of pancreatic growth and function
Authors: Hammerle Constanze M. , Sandovici Ionel , Brierley Gemma V. , Smith Nicola M. , Zimmer Warren E. , Zvetkova Ilona , Prosser Haydn M. , Sekita Yoichi , Lam Brian Y.H. , Ma Marcella , Cooper Wendy N. , Vidal-Puig Antonio , Ozanne Susan E. , Medina-Gómez Gema , Constância Miguel
Published: August 2019

The genetic mechanisms that determine the size of the adult pancreas are poorly understood. Here we demonstrate that many imprinted genes are highly expressed in the pancreatic mesenchyme, and explore the role ofIgf2 in-vivo. Mesenchyme-specificIgf2deletion results in acinar and beta-cell hypoplasia, postnatal whole-body growth restriction and maternal glucose intolerance during pregnancy. Surprisingly, mesenchymal mass is unaffected, suggesting that the mesenchyme is a developmental reservoir of IGF2 used for paracrine signalling. The unique actions of mesenchymal IGF2 are demonstrated by the absence of phenotypes uponIgf2deletion in the developing pancreatic epithelium. Furthermore, increased IGF2 activity specifically in the mesenchyme, throughIgf2loss-of-imprinting orIgf2rdeletion, leads to pancreatic acinar overgrowth.Ex-vivoexposure of primary acinar cells to exogenous IGF2 increases cell proliferation and amylase production through AKT signalling. We propose that mesenchymalIgf2, and perhaps other imprinted genes, are key developmental regulators of adult pancreas size and function.
A scalable culturing system for the marine annelid Platynereis dumerilii
Authors: Kuehn Emily , Stockinger Alexander W. , Girard Jerome , Raible Florian , Özpolat B. Duygu
Published: August 2019

Platynereis dumerilii is a marine segmented worm (annelid) with externally fertilized embryos and it can be cultured for the full life cycle in the laboratory. The accessibility of embryos and larvae combined with the breadth of the established molecular and functional techniques has made P. dumerilii an attractive model for studying development, cell lineages, cell type evolution, reproduction, regeneration, the nervous system, and behavior. Traditionally, these worms have been kept in rooms dedicated for their culture. This allows for the regulation of temperature and light cycles, which is critical to synchronizing sexual maturation. However, regulating the conditions of a whole room present limitations, especially if experiments require being able to change culturing conditions. Here we present scalable and flexible culture methods that provide ability to control the environmental conditions, and have a multi-purpose culture space. We provide a closed setup shelving design with proper light conditions necessary for P. dumerilii to mature. We also implemented a standardized method of feeding P. dumerilii cultures with powdered spirulina which relieves the ambiguity associated with using frozen spinach, and helps standardize nutrition conditions across experiments and across different labs. By using these methods, we were able to raise mature P. dumerilii, capable of spawning and producing viable embryos for experimentation and replenishing culture populations. These methods will allow for the further accessibility of P. dumerilii as a model system, and they can be adapted for other aquatic organisms.
Phylogenies of extant species are consistent with an infinite array of diversification histories
Authors: Louca Stilianos , Pennell Matthew W.
Published: August 2019

Time-calibrated molecular phylogenies of extant species ("extant timetrees") are widely used for estimating the dynamics of diversification rates (1–6) and testing for associations between these rates and environmental factors (5, 7) or species traits (8). However, there has been considerable debate surrounding the reliability of these inferences in the absence of fossil data (9–13), and to date this critical question remains unresolved. Here we mathematically clarify the precise information that can be extracted from extant timetrees under the generalized birth-death model, which underlies the majority of existing estimation methods. We prove that for a given extant timetree and a candidate diversification scenario, there exists an infinite number of alternative diversification scenarios that are equally likely to have generated a given tree. These “congruent” scenarios cannot possibly be distinguished using extant timetrees alone, even in the presence of infinite data. Importantly, congruent diversification scenarios can exhibit markedly different and yet plausible diversification dynamics, suggesting that many previous studies may have over-interpreted phylogenetic evidence. We show that sets of congruent models can be uniquely described using composite variables, which contain all available information about past dynamics of diversification (14); this suggests an alternative paradigm for learning about the past from extant timetrees.
A neural network for information seeking
Authors: White J. Kael , Bromberg-Martin Ethan S. , Heilbronner Sarah R. , Zhang Kaining , Pai Julia , Haber Suzanne N. , Monosov Ilya E.
Published: August 2019

Humans and other animals often show a strong desire to know the uncertain rewards their future has in store, even when they cannot use this information to influence the outcome. However, it is unknown how the brain predicts opportunities to gain information and motivates this information seeking behavior. Here we show that neurons in a network of interconnected subregions of primate anterior cingulate cortex and basal ganglia predict the moment of gaining information about uncertain rewards. Spontaneous increases in their information prediction signals are followed by gaze shifts toward objects associated with resolving uncertainty, and pharmacologically disrupting this network reduces the motivation to seek information. These findings demonstrate a cortico-basal ganglia mechanism responsible for motivating actions to resolve uncertainty by seeking knowledge about the future.
Telomeric chromosome ends are highly mobile and behave like free double-strand DNA breaks
Authors: Toulouze Mathias , Amitai Assaf , Shukron Ofir , Holcman David , Dubrana Karine
Published: August 2019

Chromosome organization and dynamics are critical for DNA transactions, including gene expression, replication, and DNA repair. In yeast, the chromosomes are anchored through their centromeres to the spindle pole body, and their telomeres are grouped into clusters at the nuclear periphery, constraining chromosome mobility. Here, we have used experimental and computational approaches to study the effects of chromosome-nuclear envelope (NE) attachments on the dynamics ofS. cerevisiaechromosomes. We found that although centromere proximal loci were, as predicted, more dynamically constrained than distal loci, telomeres were highly mobile, even when positioned at the nuclear periphery. Polymer modeling indicated that polymer ends are intrinsically more mobile than internal sites. We tested this model by measuring the mobility of a double strand break (DSB) end within a chromosome arm. Upon separation of the DSB ends, their mobility significantly increased. Altogether, our results reveal that telomeres behave as highly mobile polymer ends, despite interactions with the nuclear membrane.
Genetic control of tracheid properties in Norway spruce wood
Authors: Baison J , Zhou Linghua , Forsberg Nils , Mörling Tommy , Grahn Thomas , Olsson Lars , Karlsson Bo , Wu Harry X , Mellerowicz Ewa J. , Lundqvist Sven-Olof , García-Gil María Rosario
Published: August 2019

➢ Through the use of genome-wide association (GWAS) mapping it is possible to establish the genetic basis of phenotypic trait variation. Our GWAS study presents the first such an effort in Norway spruce (Picea abies(L). Karst.) for the traits related to wood tracheid characteristics.

➢ The study employed an exome capture genotyping approach that generated 178 101 high quality Single Nucleotide Polymorphisms (SNPs) from 40 018 probes within a population of 517 Norway spruce mother trees. We applied a LASSO based association mapping method using a functional multi-locus mapping approach that utilizes latent traits, with a stability selection probability method as the hypothesis testing approach to determine significant Quantitative Trait Loci (QTLs). Expression of the identified candidate genes was examined using publicly available spruce databases.

➢ The analysis have provided 31 loci and 26 mostly novel candidate genes, majority of which showing specific expression in wood-forming tissues or high ubiquitous expression, potentially controlling tracheids dimensions, their cell wall thickness and microfibril angle. Among most promising candidates, the analysis identifiedPicea abies BIG GRAIN 2(PabBG2) with predicted function in auxin transport and sensitivity, andMA_373300g0010- similar to wall-associated receptor kinases (WAKs), both associated to cell wall thickness.

➢ The results demonstrate feasibility of GWAS to identify novel candidate genes controlling industrially-relevant tracheid traits in Norway spruce. The presence of many traits with several significant QTLs supports the notion that the majority of these traits are polygenic in nature.
Anti-inflammatory role of curcumin in Lipopolysaccharide treated A549 cells at global proteome level and on mycobacterial infection
Authors: Singh Suchita , Arya Rakesh , Bargaje Rhishikesh R , Das Mrinal Kumar , Akram Subia , Faruquee Hossain Md. , Behera Rajendra Kumar , Nanda Ranjan Kumar , Agrawal Anurag
Published: August 2019

A diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) is yet to be explored. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated with curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected withMycobacterium tuberculosisH37Rv strain to monitor bacterial load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway were deregulated in curcumin treated cells. Higher mitochondria intensity was observed in curcumin treated A549 cells than LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Curcumin and/or LPS pretreated A549 cells infected with H37Rv, showed successful bacterial internalization. LPS treated A549 cells after infection showed increased bacterial load than curcumin compared to non-treated infected cells. However, simultaneous treatment of curcumin and LPS neutralized the effect of LPS. This study generated molecular evidence to deepen our understanding of the anti-inflammatory role of curcumin and may be useful to identify molecular targets for drug discovery.
A comparison of pedigree, genetic, and genomic estimates of relatedness for informing pairing decisions in two critically endangered birds
Authors: Galla Stephanie , Moraga Roger , Brown Liz , Cleland Simone , Hoeppner Marc P. , Maloney Richard , Richardson Anne , Slater Lyndon , Santure Anna W. , Steeves Tammy
Published: August 2019

Conservation management strategies for many highly threatened species include conservation breeding to prevent extinction and enhance recovery. Pairing decisions for these conservation breeding programmes can be informed by pedigree data to minimise relatedness between individuals in an effort to avoid inbreeding, maximise diversity, and maintain evolutionary potential. However, conservation breeding programmes struggle to use this approach when pedigrees are shallow or incomplete. While genetic data (i.e., microsatellites) can be used to estimate relatedness to inform pairing decisions, emerging evidence indicates this approach lacks precision in genetically depauperate species, and more effective estimates will likely be obtained from genomic data (i.e., thousands of genome-wide single nucleotide polymorphisms, or SNPs). Here, we compare relatedness estimates using pedigree-, genetic-, and genomic-based approaches for making pairing decisions in two critically endangered birds endemic to New Zealand: kakī/black stilt (Himantopus novaezelandiae) and kākāriki karaka/orange-fronted parakeet (Cyanoramphus malherbi). Our findings indicate genetic-based estimates of relatedness are indeed the least precise when assessing known parent-offspring and full sibling relationships. Furthermore, our results show that relatedness estimates and subsequent pairing recommendations using PMx are most similar between pedigree- and genomic-based approaches. These combined results indicate that in lieu of robust pedigrees, SNPs are an effective tool for informing pairing decisions, which has exciting implications for many poorly pedigreed conservation breeding programmes worldwide.
Neuroanatomical Risk Factors for Post Traumatic Stress Disorder (PTSD) in Recent Trauma Survivors
Authors: Ben-Zion Ziv , Artzi Moran , Niry Dana , Keynan Nimrod Jackob , Zeevi Yoav , Admon Roee , Sharon Haggai , Halpern Pinchas , Liberzon Israel , Shalev Arieh Y. , Hendler Talma
Published: August 2019

Background

Low hippocampal volume could serve as an early risk factor for Post-traumatic Stress Disorder (PTSD) in interaction with other brain anomalies of developmental origin. One such anomaly may well be a presence of large Cavum Septum Pellucidum (CSP), which has been loosely associated with PTSD. Here, we performed a longitudinal prospective study of recent trauma survivors. We hypothesized that at one-month after trauma exposure, the relation between hippocampal volume and PTSD symptom severity will be moderated by CSP volume, and that this early interaction will account for persistent PTSD symptoms at subsequent time-points.

Methods

171 adults (87 females, average age=34.22, range=18-65) admitted to a general hospital’s emergency department following a traumatic event, underwent clinical assessment and structural MRI within one-month after trauma. Follow-up clinical evaluations were conducted at six (n=97) and fourteen (n=78) months after trauma. Hippocampus and CSP volumes were measured automatically by FreeSurfer software and verified manually by a neuroradiologist.

Results

At one-month following trauma, CSP volume significantly moderated the relation between hippocampal volume and PTSD severity (p=0.026), and this interaction further predicted symptom severity at fourteen months post-trauma (p=0.018). Specifically, individuals with smaller hippocampus and larger CSP at one-month post-trauma, showed more severe symptoms at one-and fourteen months following trauma exposure.

Conclusions

Our study provides evidence for an early neuroanatomical risk factors for PTSD, which could also predict the progression of the disorder in the year following trauma exposure. Such a simple-to-acquire neuroanatomical signature for PTSD could guide early management, as well as long-term monitoring.

Trial Registration

Neurobehavioral Moderators of Post-traumatic Disease Trajectories. ClinicalTrials.gov registration:NCT03756545.https://clinicaltrials.gov/ct2/show/NCT03756545
Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors
Authors: Dembny Paul , Newman Andrew G. , Singh Manvendra , Hinz Michael , Szczepek Michal , Krüger Christina , Adalbert Robert , al-Dzaye Omar , Trimbuch Thorsten , Wallach Thomas , Kleinau Gunnar , Derkow Katja , Richard Bernhard C. , Schipke Carola , Scheidereit Claus , Golenbock Douglas , Peters Oliver , Coleman Michael , Heppner Frank L. , Scheerer Patrick , Tarabykin Victor , Ruprecht Klemens , Izsvák Zsuzsanna , Mayer Jens , Lehnardt Seija
Published: August 2019

Although human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs have been suggested to be involved in neurological disorders, little is known about their biological function and pathophysiological relevance. HERV-K(HML-2) comprises evolutionarily young proviruses transcribed in the brain. We report that RNA derived from an HERV-K(HML-2) env gene region binds to the human RNA-sensing Toll-like receptor (TLR) 8, activates human TLR8, as well as murine Tlr7, and causes neurodegeneration through TLR8 and Tlr7 in neurons and microglia. HERV-K(HML-2) RNA introduced extracellularly into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer’s disease (AD), resulted in neurodegeneration. Tlr7-deficient mice were protected against neurodegenerative effects, but were re-sensitized towards HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Accordingly, transcriptome datasets of human brain samples from AD patients revealed a specific correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from AD individuals compared to controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for human TLR8 and murine Tlr7 and imply a functional contribution of specific human endogenous retroviral transcripts to neurodegenerative processes such as AD.
Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease
Authors: Atlasy Nader , Bujko Anna , Brazda Peter B , Janssen-Megens Eva , Bækkevold Espen S. , Jahnsen Jørgen , Jahnsen Frode L. , Stunnenberg Hendrik G.
Published: August 2019

Celiac disease (CeD) is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine1,2. The CeD lesion is characterized by crypt hyperplasia, villous atrophy and chronic inflammation with accumulation of leukocytes both in the lamina propria (LP) and in the epithelium3, which eventually leads to destruction of the intestinal epithelium1 and subsequent digestive complications and higher risk of non-hodgkin lymphoma4. A lifetime gluten-free diet is currently the only available treatment5. Gluten-specific LP CD4 T cells and cytotoxic intraepithelial CD8+ T cells are thought to be central in disease pathology1,6-8, however, CeD is a complex immune-mediated disorder and to date the findings are mostly based on analysis of heterogeneous cell populations and on animal models. Here, we comprehensively explore the cellular heterogeneity of CD45+ immune cells in human small intestine using index-sorting single-cell RNA-sequencing9,10. We find that myeloid and mast cell transcriptomes are reshaped in CeD. We observe extensive changes in the proportion and transcriptomes of CD4+ and CD8+ T cells and define a CD3zeta expressing NK-T-like cell population present in the control LP and epithelial layers that is absent and replaced in CeD. Our findings show that the immune landscape is dramatically changed in active CeD which provide new insights and considerably extend the current knowledge of CeD immunopathology.
Comprehensive scanning mutagenesis of human retrotransposon LINE-1 identifies motifs essential for function
Authors: Adney Emily M. , Ochmann Matthias T. , Sil Srinjoy , Truong David M. , Mita Paolo , Wang Xuya , Kahler David J. , Fenyö David , Holt Liam J. , Boeke Jef D.
Published: August 2019

Long Interspersed Nuclear Element-1 (LINE-1, L1) is the only autonomous active transposable element in the human genome. The L1-encoded proteins ORF1p and ORF2p enable the element to jump from one locus to another via a “copy and paste” mechanism. ORF1p is an RNA-binding protein and ORF2p has endonuclease and reverse transcriptase activities. The huge number of truncated L1 remnants in the human genome suggests that the host has likely evolved mechanisms to prevent full L1 replication and thereby decrease the proliferation of active elements and reduce the mutagenic potential of L1. In turn, L1 appears to have a minimized length to increase the probability of successful full-length replication. This streamlining would be expected to lead to high information density. Here, we describe the construction and initial characterization of a library of 538 consecutive trialanine substitutions that scan along ORF1p and ORF2p to identify functionally important regions. In accordance with the streamlining hypothesis, retrotransposition was overall very sensitive to mutations in ORF1p and ORF2p, only 16% of trialanine mutants retained near-wild-type activity. All ORF1p mutants formed near-wild-type levels of mRNA transcripts and seventy-five percent formed near-wild-type levels of protein. Two ORF1p mutants present a unique nucleolar-relocalization phenotype. Regions of ORF2p that are sensitive to mutagenesis, but lack phylogenetic conservation were also identified. We provide comprehensive information on the regions most critical to retrotransposition. This resource will guide future studies of intermolecular interactions that form with RNA, proteins and target DNA throughout the L1 life cycle.
Transcriptome association studies of neuropsychiatric traits in African Americans implicatePRMT7in schizophrenia
Authors: Fiorica Peter N. , Wheeler Heather E.
Published: August 2019

In the past fifteen years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than two percent of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n=2,256) and bipolar disorder (n=1,019) in African American cohorts. In our PrediXcan analyses, we identifiedPRMT7(P= 5.5 × 10−6, local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to thePRMT7association with schizophrenia, we identified rs10168049 (P= 1.0 × 10−6) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.
Anthropocene refugia: integrating history and predictive modelling to assess the space available for biodiversity in a human-dominated world
Authors: Monsarrat Sophie , Jarvie Scott , Svenning Jens-Christian
Published: August 2019

1.

During periods of strong environmental change, some areas may serve as refugia, where components of biodiversity can find protection, persist and potentially expand from should conditions again become favourable. The refugia concept has previously been used in the context of climatic change, to describe climatically stable areas in which taxa survived past Quaternary glacial-interglacial oscillations, or where they might persist in the future under anthropogenic climate change. However, with the recognition that Earth has entered the Anthropocene, an era in which human activities are the dominant driving force on ecosystems, it is critical to also consider human pressures on the environment as factors limiting species distributions. Here, we present a novel concept, Anthropocene refugia, to refer to areas that provide spatial and temporal protection from human activities and that will remain suitable for a given taxonomic unit in the long-term. It integrates a deep-time perspective on species biogeography that provides information on the natural rather than current-day relictual distribution of species, with spatial information on modern and future anthropogenic threats. We define the concept and propose a methodology to effectively identify and map realised and potential current and future refugia, using examples for two megafauna species as a proof of concept. We argue that identifying Anthropocene refugia will improve biodiversity conservation and restoration by allowing better prediction of key areas for conservation and potential for re-expansions today and in the future. More generally, it forms a new conceptual framework to assess and manage the impact of anthropogenic activities on past, current and future patterns of species distributions.
CRISPR/Cas9-mediated integration of large transgene into pig potential safe harbor
Authors: Li Guoling , Zhang Xianwei , Wang Haoqiang , Mo Jianxin , Zhong Cuili , Shi Junsong , Zhou Rong , Li Zicong , Yang Huaqiang , Wu Zhenfang , liu Dewu
Published: August 2019

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (Cas9) is a precise genome manipulating tool which can produce targeted gene mutations in various cells and organisms. Although CRISPR/Cas9 can efficiently generate gene knock-out, the gene knock-in efficiency mediated by homology-directed repair (HDR) remains low, especially for large fragment integration. In this study, we established an efficient method for CRISPR/Cas9-mediated integration of large transgene cassette carrying salivary gland-expressing multiple digestion enzymes (≈ 20 kbp) in CEP112 locus in pig fetal fibroblasts. Our results showed that using homologous donor with a short left arm and a long right arm yielded the best CRISPR/Cas9-mediated knock-in efficiency, and the targeting efficiency in potential safe harbor CEP112 locus are higher than ROSA26 locus. The CEP112 knock-in cell lines were used as nuclear donors for somatic cell nuclear transfer to create genetically modified pigs. We found that knock-in pig (705) successfully expressed three microbial enzymes (β-glucanase, xylanase, and phytase) in salivary gland, suggesting potential safe harbor CEP112 locus supports exogenous genes expression by a tissue-specific promoter. In summary, we successfully targeted CEP112 locus using our optimal homology arm system for precise modification of pigs, and established a modified pig model for foreign digestion enzyme expression in saliva.
Evolutionary constraints in regulatory networks defined by partial order between phenotypes
Authors: Kogenaru Manjunatha , Nghe Philippe , Poelwijk Frank J. , Tans Sander J.
Published: August 2019

Gene regulation networks allow organisms to adapt to diverse environmental niches. However, the constraints underlying the evolution of regulatory phenotypes remain ill-defined both theoretically and experimentally. Here, we show that the concept of partial order identifies such constraints, and test the predictions by experimentally evolving an engineered signal-integrating network in multiple environments. We find that populations: 1) expand in fitness space along the Pareto-optimal front predicted by conflicts in regulatory demands, by fine-tuning binding affinities within the network, 2) expand beyond this constraint by changes in the network structure, thus allowing access to new fitness domains. Strikingly, the constraint predictions are based on whether the network output increases or decreases in response to the different signals, and do not require information on the network architecture or underlying genetics. Overall, our findings show that limited knowledge on current regulatory phenotypes can provide predictions on future evolutionary constraints.
The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1
Authors: Welte Thomas , Tuck Alex C. , Papasaikas Panagiotis , Carl Sarah H. , Flemr Matyas , Knuckles Philip , Rankova Aneliya , Bühler Marc , Großhans Helge
Published: August 2019

TRIM71/LIN-41, a phylogenetically conserved regulator of development, controls stem cell fates. Mammalian TRIM71 exhibits both RNA-binding and protein ubiquitylation activities, but the functional contribution of either activity and relevant primary targets remain poorly understood. Here, we demonstrate that TRIM71 shapes the transcriptome of mouse embryonic stem cells (mESCs) predominantly through its RNA-binding activity. We reveal that TRIM71 binds targets through 3′ untranslated region (UTR) hairpin motifs and that it acts predominantly by target degradation. TRIM71 mutations implicated in etiogenesis of human congenital hydrocephalus impair target silencing. We identify a set of primary targets consistently regulated in various human and mouse cell lines, including MBNL1 (Muscleblind-like protein 1). MBNL1 promotes cell differentiation through regulation of alternative splicing, and we demonstrate that TRIM71 promotes embryonic splicing patterns through MBNL1 repression. Hence, repression of MBNL1-dependent alternative splicing may contribute to TRIM71's function in regulating stem cell fates.
Exploring the rationale for integrated report assurance
Authors: Maroun Warren
Published: August 2019

Purpose

The purpose of this paper is to examine why companies assure some of the information found in their integrated reports, possible changes required to existing assurance practices and the motivation for either seeking to expand current technologies of assurance or to maintain the status quo.

Design/methodology/approach

The research is exploratory/interpretive. Data are collected from detailed interviews with preparers and assurance experts. Framing theory provides the data analysis framework.

Findings

Three broad views on assurance are identified. An expectation management perspective focusses on the role of assurance as a legitimisation tool and requires no changes to existing assurance standards. A value-adding perspective emphasises the role of assurance in improving the usefulness of information being reported to stakeholders and its function as part of a broader corporate governance system. This can evolve into a change-potential outlook in terms of which assurance is used to promote positive organisational change, something which may require the development of new standards/guidelines for assuring integrated reports.

Research limitations/implications

Only preparers and assurance experts are engaged to explore the rationale for seeking to have parts of an integrated report assured. The views of the broader stakeholder community are not taken into account. The study is also limited to a single jurisdiction where integrated reporting practices are relatively well established.

Practical implications

Assurance of non-financial information cannot be understood only in terms of broad drivers such as firm size, environmental impact or listing status. It is inextricably linked with the perceived relevance of integrated (or sustainability) reporting and the value which assurance provides to an organisation and its stakeholders.

Originality/value

The study complements the mainly quantitative research on determinants of assurance of environmental or social disclosures. It is one of the few to provide primary evidence on the reasons for having these types of disclosures assured and how this informs the need for changes to existing assurance practices. The paper is also one of the first to deal with the assurance of environmental or social information in an integrated reporting context.
“Palm oil free” vs “sustainable palm oil”: the impact of claims on consumer perception
Authors: Vergura Donata Tania , Zerbini Cristina , Luceri Beatrice
Published: August 2019

Purpose

The palm oil debate has become highly polarised in recent years and is of crucial importance for multinationals and their policies. The purpose of this paper is to investigate the consumers’ response towards product packs communicating this food ingredient in different ways: through “palm oil free” and “with sustainable palm oil” claims or without mentioning it.

Design/methodology/approach

A mail survey with a sample of 191 consumers was conducted. Respondents were equally and randomly distributed among the experimental conditions. The hypotheses were tested by a between-subjects factorial design.

Findings

Results revealed that consumer exposed to the “palm oil free” products showed a lower risk perception compared to those exposed to the “with sustainable palm oil” products and to products without claim. Moreover, the product evaluation was better in the “palm oil free” condition compared to the “with sustainable palm oil” condition. No differences emerged in attitude, expected tastiness and willingness to pay.

Research limitations/implications

The study sheds light on the consumer valuation of palm oil products and provides some useful managerial implications to manufacturers and product managers.

Originality/value

Results enrich the literature on food claims on pre-packaged foods as the source of information and on consumers’ perception towards palm oil.
Typology of contemporary corporate communication channels
Authors: Oltarzhevskyi Dmytro Olehovych
Published: August 2019

Purpose

The purpose of this paper is to distinguish the corporate communication channels by typology, by the designation of their characteristics and features of application, as well as to institutionalize the concept of corporate media.

Design/methodology/approach

In the theoretical part, with the help of general review, critical analysis, systematization and generalization, the main scientific works devoted to corporate communications have been studied. In practical part, the method of typology there has been used and descriptive analysis of types of communication channels has been carried out.

Findings

The research distinguishes the types of channels used in modern corporate communication. It reveals that corporate communication channels can be divided into two main types according to the criteria of relation to the company: outsiders and insiders. Then the channels can be divided into broad functional subtypes: events, advertising, media and a specific category – social media. The typological separation also can be based on the auditorium and communication technologies indications.

Originality/value

This study makes a significant contribution to the development of studies of corporate communication through structuring communication channels. The establishment of types, features and prospects for the development of communication channels, in particular such specific ones as corporate and social media, contribute to a more systematic approach to the methods of their use. From a practical point of view, companies can be guided by the results of this research during the formation of a mix of corporate communication.
Design thinking for improving employee experience: a case of a food tech company
Authors: Sinha Anamika , Varkkey Biju , Meenakshi N.
Published: August 2019

Purpose

The purpose of this paper is to demonstrate applicability of design thinking in creating employee centric HR solutions. This application is studied in the context of a food tech company. A design thinking process for arriving at an HR solution for employee experience management is proposed.

Design/methodology/approach

The study uses a single case study method. The HR professionals of a food tech company were interviewed to relate their narratives with the existing conceptual framework on design thinking.

Findings

It was found that the firm focused on the technological supremacy as well as developed an engaged and motivated team of delivery boys. This provided the required competitive advantage and growth. The first step in implementing the HR solution was to collect primary data for insights into the pain and gain points in employee’s day to day routine. Using the lens of empathy, multiple touch points through incentive policies, rewards, work engagement tools, feedback, inclusive decision making, and technology enabled learning solutions were designed. These signaled a caring and employee centric leadership and built future orientation and engaged the employees.

Practical implications

By demonstrating the applicability of design thinking and linking it to the HR solutions, a conceptual model relevant to the Food Tech industry was proposed. By integrating the process used to reach the solution, a modified model can be developed by other HR professionals working in any other Food tech company, aggregator/ service providers or logistics companies.

Originality/value

The study is among the initial studies to approach design thinking for HR solutions in a food tech industry.
The efficacy of trust for the governance of uncertainty and opportunism in megaprojects
Authors: Wang Dedong , Fu Hongwei , Fang Shaoze
Published: August 2019

Purpose

The low success rate of megaprojects stems from the opportunism triggered by uncertainty. Developing trust between participants is an effective means to reduce uncertainty, but this process is inevitably affected by contracts. The purpose of this paper is to examine the impact of uncertainty on participants’ opportunism in megaprojects and the effect of trust on reducing uncertainty. At the same time, the moderating effects of contractual control are tested.

Design/methodology/approach

This research classifies trust into competence-based trust and goodwill-based trust and categorizes uncertainty into environmental uncertainty and behavioral uncertainty. Partial least squares structural equation modeling is used to test the hypotheses based on data collected from 172 respondents.

Findings

The results show a positive correlation between the two types of uncertainty and opportunism. For the governance of uncertainty, competence-based trust can reduce environmental uncertainty, but it is ineffective for behavioral uncertainty, and goodwill-based trust has a significant effect on both types of uncertainty. The test of moderating effects shows that contractual control strengthens the effect of competence-based trust but weakens the effect of goodwill-based trust, which means that contractual control complements competence-based trust and substitutes for goodwill-based trust.

Research limitations/implications

This research enriches the theory of megaproject management. First, it validates the role of competence-based trust and goodwill-based trust in reducing the different types of uncertainty in megaprojects. Second, this study clarifies the substitution or complementarity between contractual control and different dimensions of trust in the context of high uncertainty, which provides a comprehensive answer to prior research inconsistencies on contractual control and trust.

Practical implications

For practice, this research provides some implications for megaproject management. First, project managers should recognize that the match between trust and project uncertainty is key to the success of megaproject governance. For example, some megaprojects involve many organizations, and there are many difficulties in behavioral supervision and performance appraisal. Therefore, developing goodwill-based trust between participants through positive interactions is an effective means to reduce the behavioral uncertainty of all participants and to curb opportunistic behaviors.

Originality/value

This research validated the role of competence-based trust and goodwill-based trust in reducing the different types of uncertainty in megaprojects. Furthermore, it clarifies the substitution or complementarity between contractual control and different dimensions of trust in the context of high uncertainty, which provides a comprehensive answer to prior research inconsistencies on contractual control and trust.
Barriers to the use of integrated project delivery (IPD): a quantified model for Malaysia
Authors: Durdyev Serdar , Hosseini M. Reza , Martek Igor , Ismail Syuhaida , Arashpour Mehrdad
Published: August 2019

Purpose

The purpose of this paper is to quantify the barriers to the use of integrated project delivery (IPD), as assessed by 115 construction professionals in Malaysia.

Design/methodology/approach

Barriers recording highest citation amongst researchers worldwide were collated in the form of a conceptual model. This model was validated via a partial least squares structural equation modelling technique.

Findings

Findings advance the body of knowledge on IPD by providing original insights into the nature of key barriers, quantifying the relative importance of each barrier.

Research limitations/implications

Despite the above-mentioned contributions, and before drawing any conclusion, it is prudent to acknowledge limitations, particularly the chosen research approach in focusing on the Malaysian context. Therefore, caution must be exercised in direct application of findings to other contexts; research findings should be seen through the lens of moderatum generalisations (see Payne and Williams, 2005).

Practical implications

Apart from contributions to the body of knowledge, for the world of practice, conditions impacting a transition to IPD are discussed, with a recommendation for change management through a tested mechanism like the European Corporate Sustainability Framework.

Originality/value

Being the first empirical study undertaken to quantify the relationship among the identified barriers and IPD, the present study contributes to the field by addressing the gap in IPD research in Malaysia, as an exemplar of a developing country; it creates knowledge to inform further improvements in project performance through facilitating IPD use. The study also offers insight to construction stakeholders in other developing countries for tackling issues that hinder the adoption of an IPD approach, and it also points to major barriers such that resources for tackling barriers may be allocated properly.