bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptations of energy metabolism in cetaceans have consequences for their response to foraging disruption
Authors: Derous Davina , Sahu Jagajjit , Douglas Alex , Lusseau David , Wenzel Marius
Published: July 2019

Cetaceans have varied their anatomical structure, physiology and metabolism to adapt to the challenges of aquatic life. Key to this change is the deposition of blubber. This adipose tissue plays a significant regulatory and signaling role in mammalian metabolism. As foraging disruption by human activities is emerging as a key conservation threat for cetaceans, we need to understand how selection for aquatic life might have altered key nutrient sensing pathways associated with adipose signaling. We compared selection pressure on those energy metabolism biological pathways by contrasting the rate of substitution observed in genes associated with them in cetacean and artiodactyl genomes. We then estimated the likely consequence of these selection pressures for pathway functions. Here we show that genes involved in the insulin, mTOR, SIRT and NF-κB pathways were under significant positive selection in cetaceans compared to their terrestrial sister taxon. Our results suggest these genes may have been positively selected to adapt to a glucose-poor diet and it is unlikely that fat depots signaling function in the same manner as in terrestrial mammals. Secondary adaptation to life in water significantly affected functions in nutrient sensing pathways in cetaceans. Insulin is not likely to play the same role in energy balance as it does in terrestrial mammals and adiposity is not likely to have the deleterious health consequences it has in terrestrial mammals. The physiological ecology of cetacean fat deposition, and therefore its value as a condition index, needs to be interpreted in this evolutionary context.
Intranasal inoculation ofCryptococcus neoformansin mice produces nasal infection with rapid brain dissemination
Authors: Coelho Carolina , Camacho Emma , Salas Antonio , Alanio Alexandre , Casadevall Arturo
Published: July 2019

Cryptococcus neoformansis an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination ofC. neoformansis thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via the bloodstream, either by free yeast cells in bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal. All three modes of infection resulted in dissemination ofC. neoformansto the brain in under 3 hours. Further,C. neoformanswas detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery but our findings show that instillation ofC. neoformansproduces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume the initial sites of infection of infection are brain, lung and upper respiratory tract, including the nasal airways.

Importance

Cryptococcus neoformanscauses an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS.C. neoformanshas a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources and the fungus lays dormant within the human body. Upon immunosuppression, such as AIDS or therapy-induced as required by organ transplant recipients or autoimmune disease patients, cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study has detected that upon contact with the host,C. neoformanscan quickly (a few hours) reach the host brain and will also colonize the nose of infected animals. Therefore, this work paves the way to better knowledge of howC. neoformanstravels through the host body. Understanding howC. neoformansinfects, disseminates and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.
An Out-of-Patagonia dispersal explains most of the worldwide genetic distribution in Saccharomyces eubayanus
Authors: Nespolo Roberto F. , Villarroel Carlos A. , Oporto Christian I. , Tapia Sebastián M. , Vega Franco , Urbina Kamila , De Chiara Matteo , Mozzachiodi Simone , Mikhalev Ekaterina , Thompson Dawn , Saenz-Agudelo Pablo , Liti Gianni , Cubillos Francisco A.
Published: July 2019

Saccharomyces eubayanus represents missing cryotolerant ancestor of lager yeast hybrid and can be found in Patagonia in association with Nothofagus forests. The limited number of isolates and associated genomes available has prevented to resolve the S. eubayanus origin and evolution. Here, we present a sampling effort at an unprecedented scale and report the isolation of 160 strains from ten sampling sites along 2,000 km distance in South America. We sequenced the genome of 82 strains and, together with other 25 available genomes, performed comprehensive phylogenetic analysis. Our results revealed the presence of three main Patagonia-B lineages together with dozens of admixed strains distributed in three mosaic clusters. The PB-1 lineage isolated from Tierra del Fuego exhibited the highest genetic diversity, lowest LD blocks and highest Fis values compared to the other lineages, suggesting a successful adaptation to cold temperatures in extreme environments and greater inbreeding rates in Tierra del Fuego. Differences between lineages and strains were found in terms of aneuploidy and pangenome content, evidencing a lateral gene transfer event in PB-2 strains from an unknown donor species. Overall, the Patagonian lineages, particularly southern populations, showed a greater global genetic diversity compared to Holarctic and Chinese lineages, supporting the scenario of a S. eubayanus colonization from Patagonia and then spread towards northern and western regions, including the Holarctic (North America and China) and New Zealand. Interestingly, fermentative capacity and maltose consumption resulted negatively correlated with latitude, indicating a better fermentative performance in norther populations. Our genome analysis together with previous reports in the sister species S. uvarum strongly suggests that the S. eubayanus ancestor could have originated in Patagonia or the Southern Hemisphere, rather than China, yet further studies are needed to resolve this conflicting scenario. Understanding S. eubayanus evolutionary history is crucial to resolve the unknown origin of the lager yeast and might open new avenues for biotechnological applications.
Genome diversity and species richness in mammals
Authors: Herrick John , Sclavi Bianca
Published: July 2019

Evolutionary changes in karyotype have long been implicated in speciation events; however, the phylogenetic relationship between karyotype diversity and species richness in closely and distantly related mammalian lineages remains to be fully elucidated. Here we examine the association between genome diversity and species diversity across the class Mammalia. We tested five different metrics of genome diversity: clade-average genome size, standard deviation of genome size, diploid and fundamental numbers (karyotype diversity), sub-chromosomal rearrangements and percent synteny block conservation. We found a significant association between species richness (phylogenetic clade diversity) and genome diversity at both order and family level clades. Karyotype diversity provided the strongest support for a relationship between genome diversity and species diversity. Our results suggest that lineage specific variations in genome and karyotype stability can account for different levels of species diversity in mammals.
Fxr1 regulates sleep and synaptic homeostasis
Authors: Khlghatyan Jivan , Evstratova Alesya , Bozoyan Lusine , Chamberland Simon , Marakhovskaia Aleksandra , Silva Tiago Soares , Toth Katalin , Mongrain Valerie , Beaulieu Jean-Martin
Published: July 2019

The fragile X autosomal homolog 1 (Fxr1) has been GWAS-associated to schizophrenia and insomnia but its contributions to brain functions are unclear. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and engages both global and cell autonomous level processes. We used Crispr/Cas9-mediated somatic knockouts, overexpression, neuronal activity recordings and translatome sequencing, to examine the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and global-level sleep homeostasis. Our findings indicate that Fxr1 is downregulated during scaling and sleep deprivation via a Gsk3β dependent mechanism. In both conditions, downregulation of Fxr1 is essential for the homeostatic modulation of synaptic strength. Furthermore, overexpression of Fxr1 during sleep deprivation results in altered EEG signatures and reverts changes of translatome profiles. These findings indicate that Fxr1 represents a shared signaling hub linking cell autonomous homeostatic plasticity and system level sleep homeostasis with potential implications for neuropsychiatric illnesses.
An ABBA-BABA Test for Introgression Using Retroposon Insertion Data
Authors: Springer Mark S. , Gatesy John
Published: July 2019

DNA sequence alignments provide the majority of data for inferring phylogenetic relationships with both concatenation and coalescence methods. However, DNA sequences are susceptible to extensive homoplasy, especially for deep divergences in the Tree of Life. Retroposon insertions have emerged as a powerful alternative to sequences for deciphering evolutionary relationships because these data are nearly homoplasy-free. In addition, retroposon insertions satisfy the ‘no intralocus recombination’ assumption of summary coalescence methods because they are singular events and better approximate neutrality relative to DNA sequences commonly applied in phylogenomic work. Retroposons have traditionally been analyzed with phylogenetic methods that ignore incomplete lineage sorting (ILS). Here, we analyze three retroposon data sets for mammals (Placentalia, Laurasiatheria, Balaenopteroidea) with two different ILS-aware methods. The first approach constructs a species tree from retroposon bipartitions with ASTRAL, and the second is a modification of SVD-Quartets. We also develop a χ2 Quartet-Asymmetry Test to detect hybridization using retroposon data. Both coalescence methods recovered the same topology for each of the three data sets. The ASTRAL species tree for Laurasiatheria has consecutive short branch lengths that are consistent with an anomaly zone situation. For the Balaenopteroidea data set, which includes rorquals (Balaenopteridae) and gray whale (Eschrichtiidae), both coalescence methods recovered a topology that supports the paraphyly of Balaenopteridae. Application of the χ2 Quartet-Asymmetry Test to this data set detected 16 different quartets of species for which historical hybridization may be inferred, but significant asymmetry was not detected in the placental root and Laurasiatheria analyses.
The viral SUMO-targeted Ubiquitin Ligase ICP0 is phosphorylated and activated by host kinase Chk2
Authors: Hembram Dambarudhar SS , Negi Hitendra , Biswas Poulomi , Tripathi Vasvi , Bhushan Lokesh , Shet Divya , Kumar Vikas , Das Ranabir
Published: July 2019

When the Herpes Simplex virus (HSV) genome enters the nucleus for replication and transcription, phase-segregated nuclear protein bodies called PML Nuclear Bodies (PML NBs) colocalize with the genome and repress it. HSV encodes a SUMO-targeted Ubiquitin ligase ICP0 that degrades PML NBs to alleviate the repression. The molecular mechanism used by ICP0 to target PML NBs is unclear. For reasons unknown, the growth of HSV is dependent on the ATM/Chk2 pathway. Here we identify a bonafide SUMO-Interacting motif in ICP0 (SLS4) that is essential and sufficient to target SUMOylated proteins in PML NBs like PML and Sp100. Phosphorylation of SLS4 creates new salt-bridges between SUMO and SLS4, increases the SUMO/SLS4 affinity and switches ICP0 into a potent STUbL. We also report that ICP0 exploits the kinase Chk2 to phosphorylate SLS4 and enhance its STUbL activity. Our results uncover how a viral STUbL counters antiviral response by exploiting an unprecedented mechanism involving three post-translational modifications; ubiquitination, SUMOylation, and phosphorylation.
Core spliceosomal Sm proteins as constituents of cytoplasmic mRNPs in plants
Authors: Hyjek-Składanowska Malwina , Bajczyk Mateusz , Gołębiewski Marcin , Nuc Przemysław , Kołowerzo-Lubnau Agnieszka , Jarmołowski Artur , Smoliński Dariusz Jan
Published: July 2019

In light of recent studies, many of the cytoplasmic posttranscriptional mRNA processing steps take place in highly specialized microdomains referred to as cytoplasmic bodies. These evolutionarily conserved microdomains are sites of regulation for both mRNA translation and degradation. It has been shown that in the larch microsporocyte cytoplasm, there is a significant pool of Sm proteins not related to snRNP complexes. These Sm proteins accumulate within distinct cytoplasmic bodies (S-bodies) that also contain mRNA. Sm proteins constitute an evolutionarily ancient family of small RNA-binding proteins. In eukaryotic cells, these molecules are involved in pre-mRNA splicing. The latest research indicates that in addition to this well-known function, Sm proteins could also have an impact on mRNA at subsequent stages of its life cycle. The aim of this work was to verify the hypothesis that canonical Sm proteins are part of the cytoplasmic mRNP complex and thus function in the posttranscriptional regulation of gene expression in plants.
Design principles of selective transport through biopolymer barriers
Authors: Maguire Laura , Stefferson Michael , Betterton Meredith D. , Hough Loren E.
Published: July 2019

In biological systems, polymeric materials block the movement of some macromolecules while allowing the selective passage of others. In some cases, binding enables selective transport, while in others the most inert particles appear to transit most rapidly. To study the general principles of filtering, we develop a model motivated by features of the nuclear pore complex (NPC) which are highly conserved and could potentially be applied to other biological systems. The NPC allows selective transport of proteins called transport factors which transiently bind to disordered, flexible proteins called FG Nups. While the NPC is tuned for transport factors and their cargo, we show that a single feature is sufficient for selective transport: the bound-state motion resulting from transient binding to flexible filaments. Interchain transfer without unbinding can further improve selectivity, especially for crosslinked chains. We generalize this observation to model nanoparticle transport through mucus and show that bound-state motion accelerates transport of transient nanoparticle application, even with clearance by mucus flow. Our model provides a framework to control binding-induced selective transport in bipolymeric materials.
pyBedGraph: a Python package for fast operations on 1-dimensional genomic signal tracks
Authors: Zhang Henry B. , Kim Minji , Chuang Jeffrey H. , Ruan Yijun
Published: July 2019

Motivation

Modern genomic research relies heavily on next-generation sequencing experiments such as ChIP-seq and ChIA-PET that generate coverage files for transcription factor binding, as well as DHS and ATAC-seq that yield coverage files for chromatin accessibility. Such files are in a bedGraph text format or a bigWig binary format. Obtaining summary statistics in a given region is a fundamental task in analyzing protein binding intensity or chromatin accessibility. However, the existing Python package for operating on coverage files is not optimized for speed.

Results

We developed pyBedGraph, a Python package to quickly obtain summary statistics for a given interval in a bedGraph file. When tested on 8 ChIP-seq and ATAC-seq datasets, pyBedGraph is on average 245 times faster than the existing program. Notably, pyBedGraph can look up the exact mean signal of 1 million regions in ~0.26 second on a conventional laptop. An approximate mean for 10,000 regions can be computed in ~0.0012 second with an error rate of less than 5 percent.

Availability

pyBedGraph is publicly available at https://github.com/TheJacksonLaboratory/pyBedGraph under the MIT license.
A Hybrid Stochastic Model of the Budding Yeast Cell Cycle
Authors: Ahmadian Mansooreh , Tyson John J. , Peccoud Jean , Cao Yang
Published: July 2019

The growth and division of eukaryotic cells are regulated by complex, multi-scale networks. In this process, the mechanism controlling cell cycle progression has to be robust against inherent noise in the system. In this paper, a hybrid stochastic model is developed to study the effects of noise on the control mechanism of the budding yeast cell cycle. The modeling approach leverages, in a single multi-scale model, the advantages of two regimes: 1) the computational efficiency of a deterministic approach, and 2) the accuracy of stochastic simulations. Our results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements.
Large cities and the loss of green areas exclude migrant birds: a global analysis
Authors: Leveau Lucas M.
Published: July 2019

Several studies around the world have shown that the proportion of migrant species in bird communities increases toward the poles as a result of greater climatic seasonality and a considerable annual variation of resources. In this context, urban areas may impose a barrier to bird migrants given their buffered seasonality of resources and human disturbance. The aim of this study is to analyze the global pattern of migrant species proportion in urban green areas, considering the effects of climatic seasonality as well as the effects of urbanization. Data of bird communities in urban green areas were gathered through a search of scientific articles, book chapters, and thesis. Datasets that included a list of observed species, the numbers of parks surveyed and other methodological characteristics were considered for the analysis. Then, generalized linear models were used to relate the proportion of migratory species in each dataset to environmental and methodological variables that controlled for different sampling effort among studies. A total of 32 cities from four continents were analyzed. As expected, the migrant proportion increased with the annual range of temperature and precipitation and was higher in the Northern Hemisphere. However, the proportion of migrants decreased with the population size of cities but increased in those datasets with the highest maximum size of green areas surveyed. Although the global pattern of migrant proportion in urban green areas follows a similar pattern than those found in natural areas, the results obtained suggest that urbanization have a negative impact on this global pattern by reducing the proportion of migrant species in large cities. Moreover, green area loss in cities may impact negatively the proportion of migrant species.
Reverse Engineering Gene Networks Using Global-Local Shrinkage Rules
Authors: Panchal Viral , Linder Daniel
Published: July 2019

Inferring gene regulatory networks from high-throughput ‘omics’ data has proven to be a computationally demanding task of critical importance. Frequently the classical methods breakdown due to the curse of dimensionality, and popular strategies to overcome this are typically based on regularized versions of the classical methods. However, these approaches rely on loss functions that may not be robust and usually do not allow for the incorporation of prior information in a straightforward way. Fully Bayesian methods are equipped to handle both of these shortcomings quite naturally, and they offer potential for improvements in network structure learning. We propose a Bayesian hierarchical model to reconstruct gene regulatory networks from time series gene expression data, such as those common in perturbation experiments of biological systems. The proposed methodology utilizes global-local shrinkage priors for posterior selection of regulatory edges and relaxes the common normal likelihood assumption in order to allow for heavy-tailed data, which was shown in several of the cited references to severely impact network inference. We provide a sufficient condition for posterior propriety and derive an efficient MCMC via Gibbs sampling in the Appendix. We describe a novel way to detect multiple scales based on the corresponding posterior quantities. Finally, we demonstrate the performance of our approach in a simulation study and compare it with existing methods on real data from a T-cell activation study.
Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor
Authors: Li Jiarong , Gu Jinyan , Wang Shengnan , Lin Cui , Zhou Jianwei , Lei Jin , Zhou Jiyong
Published: July 2019

Circovirus, comprising one capsid protein, is the smallest nonenveloped virus and induces lymphopenia. Circovirus can be used to explore the cell adhesion mechanism of nonenveloped viruses. We developed a single-molecule fluorescence resonance energy transfer (smFRET) assay to directly visualize the capsid’s conformational feature. The capsid underwent reversible dynamic transformation between three conformations. The cell surface receptor heparan sulfate (HS) altered the dynamic equilibrium of the capsid to the high-FRET state, revealing the HS binding region. Neutralizing antibodies restricted capsid transition to a low-FRET state, masking the HS binding domain. The lack of positively charged amino acids in the HS binding site reduced cell surface affinity and attenuated virus infectivity via conformational changes. These intrinsic characteristics of the capsid suggested that conformational dynamics is critical for the structural changes occurring upon cell surface receptor binding, supporting a dynamics-based mechanism of receptor binding.

Importance

Viral proteins were commom working as ligand to interacte with cell surface glycosaminoglycan receptors to achieve the virus attachment, during which the conformational dynamics of the protein ligand are also vital for the binding properties. In this study, PCV2 capsid and heparin sulfate were used to study the protein conformational dynamics of nonenveloped and icosahedral circovirus capsid during triggering to cell surface receptor. we demonstrated the PCV2 capsid could acts as a dynamic machine, spontaneously adopting multiple conformations with reversible interconversion and intrinsic conformational features could be regulated by glycosaminoglycan receptors and neutralizing antibodies. These increased our understanding of the mechanism by which nonenveloped virus attach to cells.
The structure of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR-fold
Authors: Reichhardt Martin P. , Loimaranta Vuokko , Lea Susan M. , Johnson Steven
Published: July 2019

The scavenger receptor cysteine-rich (SRCR) family of proteins comprise more than 20 membrane-associated and secreted molecules. Characterised by the presence of one or more copies of the ~110 amino acid SRCR domain, this class of proteins have widespread functions as anti-microbial molecules, scavenger- and signalling-receptors. Despite the high level of structural conservation of SRCR domains, no molecular basis for ligand interaction has been described. The SRCR protein SALSA, also known as dmbt1/gp340, is a key player in mucosal immunology. Based on detailed structures of the SALSA SRCR domains 1 and 8, we here reveal a novel universal ligand binding mechanism for SALSA ligands. The binding interface incorporates a dual cation binding site, which is highly conserved across the SRCR super family. Along with the well-described cation dependency on most SRCR domain-ligand interactions, our data suggest that the binding mechanism described for the SALSA SRCR domains is applicable to all SRCR domains. We thus propose to have identified in SALSA a conserved functional mechanism for ligand recognition by the SRCR class of proteins.
The structural basis for distinct binding avidity of Pertuzumab and Trastuzumab IgM towards HER2
Authors: Samsudin Firdaus , Yeo Joshua Yi , Gan Samuel Ken-En , Bond Peter J.
Published: July 2019

Harnessing the therapeutic potential of immunoglobulin M (IgM) is of considerable interest in immunotherapy due to its complement-activating and cell-agglutinating abilities. Pertuzumab and Trastuzumab are monoclonal antibody drugs used in therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer but exhibit significantly different binding affinities as IgM when compared to the original IgG1 form. While the affinity of Pertuzumab IgM to the HER2 extracellular domain is about one order of magnitude higher than IgG1 in experiments, it was recently reported that Trastuzumab IgM and IgG have similar equilibrium dissociation constants to one another. We now perform an integrative multiscale simulation study in order to understand the structural basis for the differences in behavior between the two antibodies, based on complete antibody assemblies. We show that Pertuzumab IgM is able to utilize all of its V-regions to engage HER2 in a more stable mode than Trastuzumab IgM due to steric clashes between the large globular HER2 domains when bound to Trastuzumab. This is subsequently validated by confirming that Pertuzumab IgM inhibits proliferation in HER2 over-expressing live cells more effectively than its IgG1 counterpart. Given the widespread clinical use of Trastuzumab and Pertuzumab, elucidating the molecular details of antibody-antigen interaction may help guide the choice of epitopes for future design and selection of improved therapeutic antibody isotypes.
A massively parallel algorithm for finding non-existing sequences in genomes
Authors: Falda Marco
Published: July 2019

We discuss a method for producing a set of absent words in a reference genome with a guaranteed Hamming distance along all positions and additional information about the number of mismatches, their location and the position of the best match. We implemented it exploiting the massively parallelism of modern GPUs hardware: the code is available at https://bitbucket.org/mfalda/cuda_keeseek/.
Endoplasmic reticulum associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity
Authors: Liu Lu , Inoki Ayaka , Fan Kelly , Mao Fengbiao , Shi Guojun , Jin Xi , Zhao Meiling , Ney Gina , Sun Shengyi , Dou Yali , Inoki Ken , Qi Ling , Li Qing
Published: July 2019

Many tissue-specific stem cells require quiescence to sustain stem cell pool and maintain lifelong tissue integrity. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis and metabolic activities are significantly reduced. Here, we report that endoplasmic reticulum associated degradation (ERAD) is required to preserve the function of quiescent hematopoietic stem cells (HSC). The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyper-proliferation which leads to reduced self-renewal and HSC depletion. ERAD deficiency induces a non-apoptotic ER stress and activates unfolded protein response (UPR). Furthermore, Sel1L knockout leads to mTOR activation, and mTOR inhibition rescues the HSC defects in Sel1L knockout mice. Protein quality control is, therefore, tightly regulated and actively engaged in quiescent HSCs. Sel1L/Hrd1 ERAD maintains HSC quiescence and self-renewal via restricting mTOR activity.
Roraregulates activated T helper cells during inflammation
Authors: Haim-Vilmovsky Liora , Henriksson Johan , Walker Jennifer A , Miao Zhichao , Natan Eviatar , Kar Gozde , Clare Simon , Barlow Jillian L , Charidemou Evelina , Mamanova Lira , Chen Xi , Proserpio Valentina , Pramanik Jhuma , Woodhouse Steven , Protasio Anna V , Efremova Mirjana , Griffin Julian L. , Berriman Matt , Dougan Gordon , Fisher Jasmin , Marioni John C , McKenzie Andrew NJ , Teichmann Sarah A
Published: July 2019

The transcription factorRorahas been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role ofRoraacross CD4+ T cells, bothin vitroas well as in the context of severalin vivotype 2 infection models. We dissect the function ofRorausing overexpression and a CD4-conditionalRora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance ofRorain CD4+ T cells for controlling lung inflammation induced byNippostrongylus brasiliensisinfection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators ofRora, most importantly IL-33 and CCL7. Our data suggest thatRorais a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment.
A Willow Sex Chromosome Reveals Convergent Evolution of Complex Palindromic Repeats
Authors: Zhou Ran , Macaya-Sanz David , Carlson Craig H. , Schmutz Jeremy , Jenkins Jerry W. , Kudrna David , Sharma Aditi , Sandor Laura , Shu Shengqiang , Barry Kerrie , Tuskan Gerald A. , Ma Tao , Liu Jianquan , Olson Matthew , Smart Lawrence B. , DiFazio Stephen P.
Published: July 2019

Background

Sex chromosomes in a wide variety of species share common characteristics, including the presence of suppressed recombination surrounding sex determination loci. They have arisen independently in numerous lineages, providing a conclusive example of convergent evolution. Mammalian sex chromosomes contain multiple palindromic repeats across the non-recombining region that facilitate sequence conservation through gene conversion, and contain genes that are crucial for sexual reproduction. Plant sex chromosomes are less well understood, and in particular it is not clear how coding sequence conservation is maintained in the absence of homologous recombination.

Results

Here we present the first evidence of large palindromic structures in a plant sex chromosome, based on a highly contiguous assembly of the W chromosome of the dioecious shrubSalix purpurea. Two consecutive palindromes span over a region of 200 kb, with conspicuous 20 kb stretches of highly conserved sequences among the four arms. The closely-related speciesS. suchowensisalso has two copies of a portion of the palindrome arm and provides strong evidence for gene conversion. Four genes in the palindrome are homologous to genes in the SDR of the closely-related genusPopulus, which is located on a different chromosome. These genes show distinct, floral-biased expression patterns compared to paralogous copies on autosomes.

Conclusion

The presence of palindromic structures in sex chromosomes of mammals and plants highlights the intrinsic importance of these features in adaptive evolution in the absence of recombination. Convergent evolution is driving both the independent establishment of sex chromosomes as well as their fine-scale sequence structure.
Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq)
Authors: Reiner Benjamin C. , Doyle Glenn A. , Weller Andrew E. , Levinson Rachel N. , Namoglu Esin , Pigeon Alicia , Arauco-Shapiro Gabriella , Dávila Perea Emilie , Weickert Cyndi Shannon , Turecki Gustavo , Mash Deborah C. , Crist Richard C. , Berrettini Wade H.
Published: July 2019

Long interspersed element-1 retrotransposons (LINE-1 or L1) are ~6 kb mobile DNA elements implicated in the origins of many Mendelian and complex diseases. The actively retrotransposing L1s are mostly limited to the L1 human specific Ta subfamily. In this manuscript, we present REBELseq as a method for the construction of differentially amplified next-generation sequencing libraries and bioinformatic identification of Ta subfamily long interspersed element-1 human specific elements. REBELseq was performed on DNA isolated from NeuN+ neuronal nuclei from postmortem brain samples of 177 individuals and empirically-driven bioinformatic and experimental cutoffs were established. REBELseq reliably identified both known and novel Ta subfamily L1 insertions distributed throughout the genome. Differences in the proportion of individuals possessing a given reference or non-reference retrotransposon insertion were identified. We conclude that REBELseq is an unbiased, whole genome approach to the amplification and detection of Ta subfamily L1 retrotransposons.
p75NTR and DR6 regulate distinct phases of axon degeneration demarcated by spheroid rupture
Authors: Yong Yu , Gamage Kanchana , Cheng Irene , Barford Kelly , Spano Anthony , Winckler Bettina , Deppmann Christopher
Published: July 2019

The regressive events associated with trophic deprivation are critical for sculpting a functional nervous system. After nerve growth factor withdrawal, sympathetic axons maintain their structural integrity for roughly 18 hours (latent phase) followed by a rapid and near unison disassembly of axons over the next 3 hours (catastrophic phase). Here we examine the molecular basis by which axons transition from latent to catastrophic phases of degeneration following trophic withdrawal. Prior to catastrophic degeneration, we observed an increase in intra-axonal calcium. This calcium flux is accompanied by p75 neurotrophic factor receptor (NTR)-Rho-actin dependent expansion of calcium rich axonal spheroids that eventually rupture, releasing their contents to the extracellular space. Conditioned media derived from degenerating axons is capable of hastening transition into the catastrophic phase of degeneration. We also found that death receptor 6 (DR6) but not p75NTR is required for transition into the catastrophic phase in response to conditioned media but not for the intra-axonal calcium flux, spheroid formation, or rupture that occurs toward the end of latency. Our results support the existence of an inter-axonal degenerative signal that promotes catastrophic degeneration among trophically deprived axons.
Quantitative proximity proteomics resolves the epithelial apical-lateral border and uncovers a vertebrate marginal zone defined by the polarity protein Pals1
Authors: Tan Benedict , Peng Suat , Sandin Sara , Gunaratne Jayantha , Hunziker Walter , Ludwig Alexander
Published: July 2019

Epithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are still not well defined. Here we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to generate a nanometer-scale spatio-molecular map of the apical-lateral border in fully polarized MDCK-II cells. Using Par3 and Pals1 as surrogates for QPP we present a spatially resolved network of ∼800 junction-associated proteins. The network dissects TJ and AJ components and provides strong evidence that TJ are composed of distinct apical and basal subdomains. Moreover, we find that Pals1 and its binding partners PatJ, Lin7c and Crumbs3 define a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). The VMZ is physically associated with HOMER scaffolding proteins, regulators of apical exocytosis, and membrane-proximal HIPPO pathway proteins. Taken together our work defines the spatial and molecular organization of the apical-lateral border in fully polarized mammalian epithelial cells, reveals an intriguing molecular and spatial conservation of invertebrate and vertebrate cell polarity protein domains, and provides a comprehensive resource of potentially novel regulators of cell polarity and the mammalian AJC.
RSVdb: A comprehensive database of transcriptome RNA structure
Authors: Yu Haopeng , Zhang Yi , Sun Qing , Gao Huijie , Tao Shiheng
Published: July 2019

RNA fulfills a crucial regulatory role in cells by folding into a complex RNA structure. To date, a chemical compound, dimethyl sulfate (DMS), has been developed to effectively probe the RNA structure at the transcriptome level. We proposed a database, RSVdb (https://taolab.nwafu.edu.cn/rsvdb/), for the browsing and visualization of transcriptome RNA structures. RSVdb, including 626,225 RNAs with validated DMS reactivity from 178 samples in 8 species, supports four main functions: information retrieval, research overview, structure prediction, and resource download. Users can search for species, studies, transcripts and genes of interest; browse the quality control of sequencing data and statistical charts of RNA structure information; preview and perform online prediction of RNA structures in silico and under DMS restraint of different experimental treatments; and download RNA structure data for species and studies. Together, RSVdb provides a reference for RNA structure and will support future research on the function of RNA structure at the transcriptome level.
Household food waste management: socio-ecological dimensions
Authors: Aitsidou Vasiliki , Michailidis Anastasios , Partalidou Maria , Iakovidou Olga
Published: July 2019

Purpose

The purpose of this paper is to estimate respondents’ socio-ecological consciousness (SEC) (knowledge, perceptions, behaviour, habits and feelings) concerning household food waste (HFW) and to identify factors that influence attitude concerning HFW.

Design/methodology/approach

Data were collected through a questionnaire survey addressing to 279 residents in Western Macedonia, Greece. A principal component analysis was primarily applied to provide a manageable set of variables relevant to SEC. These variables were analyzed according to their positive/negative influence in SEC through descriptive statistics. Independent samples t-test analysis was employed to examine factors that influence HFW.

Findings

Results show that SEC is formed by three main activities: knowledge, perception and attitude. The survey reveals an inconsistency between existing knowledge and problematic perceptions, while the attitude includes neither harmful nor harmless HFW-related activities. A significant finding is that respondents’ age affects food rejection in different consumption stages in a household.

Research limitations/implications

Reliance on self-reported data for HFW that concerns a Greek case study does not allow a generalization of results.

Practical implications

The authors suggest a campaign plan for local bodies. The aim is to enhance respondents’ perceptual abilities and attitude concerning HFW. In order to raise awareness of students and individuals/households, related campaigns could be implemented by educational institutions and other policymakers.

Originality/value

The survey provides information for HFW, a topic not widely examined in Greece, and it is analyzed for the first time on the basis of SEC theory.
Moving towards a healthier assortment in secondary and vocational school food environments
Authors: van Kleef Ellen , Meeuwsen Tanja , Rigterink Jetteke , Van Trijp Hans
Published: July 2019

Purpose

In many countries, schools move toward healthier canteen assortments by limiting the supply of unhealthy foods. The question arises whether this gives any undesirable side effects with students (e.g. compensation in purchases from school to outside retailers, reactance) and how to handle these so that operating school canteens remains financially viable. The purpose of this paper is to identify perspectives toward healthy school food assortments held by vocational education students and professionals within secondary and vocational schools with responsibility for school food policy (e.g. school canteen workers, teachers, school directors) in the Netherlands.

Design/methodology/approach

Four focus groups were conducted with students at a vocational school (n=25 in total). A semi-structured interview guide was used to conduct discussions. The interview guide also included three school canteen scenario’s (A: 100 percent healthy food, B: 50 percent healthy/50 percent unhealthy foods and C: 100 percent unhealthy food) and a set of nine intervention strategies. A brief survey included questions on the same three scenario’s and nine intervention strategies. A web-based survey was conducted among 68 professionals responsible for school food policy and included their evaluation of the same canteen scenarios and interventions. Survey data were analyzed using descriptive statistics and content analysis. Content analysis was done on the qualitative data.

Findings

School food professionals were highly supportive of Scenario A (100 percent healthy food), as this formed a better fit with their policies and was believed to stronger encourage healthy eating. They did worry about financial feasibility given lower affordability and student reluctance to accept the assortment. Students were less in favor of Scenario A. Students discussed getting value for money and remaining freedom to make unhealthy choices. The authors discuss implications for policy makers who aim to implement measures to improve young people’s eating habits.

Originality/value

This study contributes to the literature on creating healthier school food environments. This study uniquely examines a healthier school canteen from a viability perspective, including the views of students as primary customers. Given the need to progressively increase the number of foods complying to dietary guidelines in canteen assortments, this study provides insights into how and why assortment changes best can be implemented.
The impact of human age on the amount of absorbed energy from mobile phone
Authors: Jovanovic Dejan B. , Stankovic Vladimir , Cvetkovic Nenad N. , Krstic Dejan , Vuckovic Dragan
Published: July 2019

Purpose

The purpose of this paper is to determine the impact of human age on the distribution of electric field and absorbed energy that originates from a mobile phone.

Design/methodology/approach

This research was performed for frequencies of 900, 1800 and 2100 MHz, which are used in a mobile communication system. To obtain the most accurate results, 3 D realistic model of the child’s head has been created whereby the dimensions of this model correspond to the dimensions of a seven-year-old child. Distribution of the electric field and specific absorption rate (SAR) through the child’s head was obtained by numerical analysis based on the finite integration technique.

Findings

The results discover that amount of absorbed energy is greater in the surface layers of the child’s head model when the electromagnetic (EM) characteristics of tissues are adjusted for the child. This deviation corresponds to different EM characteristics of biological tissues and organs of an adult person compared to a child.

Research limitations/implications

The study deals with penetrated electrical field and absorbed EM field energy. There is space for further studies of other EM field effects (e.g. thermal effects).

Practical implications

The analysis of obtained results leads to idea that mobile phones and devices aimed for children using should be modified to provide SAR values inside prescribed standards.

Social implications

The obtained results are foundation for future research on influence of EM fields of mobile devices on human health.

Originality/value

The proposed procedure offers the model for accurate estimation and quality analysis of SAR and EM field distribution inside child head tissue.
Are hospital managers ready for value-based healthcare?
Authors: Walsh Aidan P. , Harrington Denis , Hines Peter
Published: July 2019

Purpose

Hospital organisations are currently experiencing significant challenges that have encouraged a move towards a value-based approach to health care. However, such a transition requires understanding the underlying competencies required to enable such a focus. This paper aims to undertake a systematic review of the available literature on managerial competencies in hospitals and considers these in a value-based health-care context.

Design/methodology/approach

A systematic literature review was conducted to identify research studies that describe the characteristics of management competence in hospital environments.

Findings

Categories and sub-categories of management competence in hospitals were identified and considered in a value-based health-care context.

Research limitations/implications

The systematic literature review identifies a need for further research regarding managerial competencies of managers of hospitals. Competencies for managing in a value-based health-care model also require deeper investigation.

Practical implications

The categories of management competence provide guidance to organisations transitioning towards value-based health care in terms of identifying and developing management competencies. Hospitals should consider the development of a competency model that includes broader categories of competencies than purely clinical or professional competencies.

Originality/value

This study builds upon and advances previous reviews of management competence in hospitals, and the competency categories presented can be used as a basis to identify management competency requirements in hospitals.
Managing performance through employee attributes: implications for employee engagement
Authors: Lappalainen Pia , Saunila Minna , Ukko Juhani , Rantala Tero , Rantanen Hannu
Published: July 2019

Purpose

The purpose of this paper is to examine the connection between performance management and employee engagement. More specifically, the authors address shortcomings in prior literature where employee performance has been controlled narrowly as cognitive task accomplishment. Accumulating evidence shows, however, that such performance-mediating factors as employee engagement constitute critical antecedents of employee and organizational performance. They can most effectively be influenced by attending sensitively to employees’ individual differences, which are ultimately driven by motifs and dispositions.

Design/methodology/approach

The study takes a quantitative approach to exploring predictors of employee engagement. The analysis is based on a sample of 503 online survey respondents from knowledge-intensive organizations.

Findings

The results indicate that employee engagement is driven more by employees’ inherent attributes than environmental factors. The analysis refuted the connection between engagement and social orientation, self-regulation and conscientiousness. Instead, the factors associating with employee engagement were analytical thinking, extroversion, systems thinking, assertiveness and leadership.

Practical implications

In this paper, the authors put forth a novel conceptual model of performance management, introducing new and evidence-based foci for effective people management that expand task performance to contextual performance and supplement quantifying approaches to performance control with the qualifying methodology.

Originality/value

Departing from the previously dominating frameworks of performance management that focused on task performance, this work extends to contextual performance and considers also employees’ psychological traits.