bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian framework for high-throughput T cell receptor pairing
Authors: Holec Patrick V , Berleant Joseph , Bathe Mark , Birnbaum Michael E
Published: September 2018

Motivation

The study of T cell receptor (TCR) repertoires has generated new insights into immune system recognition. However, the ability to robustly characterize these populations has been limited by technical barriers and an inability to reliably infer heterodimeric chain pairings for TCRs.

Results

Here, we describe a novel analytical approach to an emerging immune repertoire sequencing method, improving the resolving power of this low-cost technology. This method relies upon the distribution of a T cell population across a 96-well plate, followed by barcoding and sequencing of the relevant transcripts from each T cell. Multicell Analytical Deconvolution for High Yield Paired-chain Evaluation (MAD-HYPE) uses Bayesian inference to more accurately extract TCR information, improving our ability to study and characterize T cell populations for immunology and immunotherapy applications.

Availability and implementation

The MAD-HYPE algorithm is released as an open-source project under the Apache License and is available from https://github.com/birnbaumlab/MAD-HYPE.

Supplementary information

Supplementary data are available at Bioinformatics online.
The retrospective study of 93 patients with transmigration of mandibular canine and a comparative analysis with a control group
Authors: Plakwicz Paweł , Abramczyk Joanna , Wojtaszek-Lis Julita , Sajkowska Jolanta , Warych Barbara , Gawron Katarzyna , Burzykowski Tomasz , Zadurska Małgorzata , Czochrowska Ewa Monika , Wojtowicz Andrzej , Górska Renata , Kukuła Krzysztof
Published: September 2018

Objectives

The aim of this study was to evaluate characteristics of patients with unilateral transmigration of a mandibular canine in the largest study group presented until now.

Materials and methods

The study group consisted of 93 patients with unilateral transmigration of mandibular canine; the control group included 85 non-affected patients. Type of transmigration, status of deciduous and permanent canines, prevalence of missing teeth, class of occlusion, and space conditions were assessed to draw comparisons between groups.

Results

In this study, 64.5 per cent patients presented type 1 of transmigration; types 2, 3, 4, and 5 were present in, respectively, 23.7, 5.4, 4.3, and 2.1 per cent patients. There was a clear, statistically significant difference (P < 0.0001) between the mean crown and apex migration and angulation for the three groups of canines (transmigrated, contralateral, and control), whereas no differences were observed for the total number of permanent teeth present. In the study group, 73.1 per cent patients retained their primary canine on the affected side and 18.3 per cent on the contralateral side; in the control group, 22.3 per cent subjects had at least one primary canine. There was a statistically significant difference in the distribution of types of malocclusion between the study and the control groups.

Conclusions

Transmigration of mandibular canine was associated with the presence of retained primary canine on the affected side, higher mesial tilting of contralateral mandibular canine when compared to the canines in the control group. Additionally, higher prevalence of Angle’s Class I occlusion in patients with canine transmigration was recorded.
Fish species identification using a convolutional neural network trained on synthetic data
Authors: Allken Vaneeda , Handegard Nils Olav , Rosen Shale , Schreyeck Tiffanie , Mahiout Thomas , Malde Ketil
Published: September 2018

Acoustic-trawl surveys are an important tool for marine stock management and environmental monitoring of marine life. Correctly assigning the acoustic signal to species or species groups is a challenge, and recently trawl camera systems have been developed to support interpretation of acoustic data. Examining images from known positions in the trawl track provides high resolution ground truth for the presence of species. Here, we develop and deploy a deep learning neural network to automate the classification of species present in images from the Deep Vision trawl camera system. To remedy the scarcity of training data, we developed a novel training regime based on realistic simulation of Deep Vision images. We achieved a classification accuracy of 94% for blue whiting, Atlantic herring, and Atlantic mackerel, showing that automatic species classification is a viable and efficient approach, and further that using synthetic data can effectively mitigate the all too common lack of training data.
Instruments and relics
Authors: Higgitt Rebekah
Published: September 2018

Despite the age and prestige of the Royal Society of London, the history of its collections of scientific instruments and apparatus has largely been one of accidental accumulation and neglect. This article tracks their movements and the processes by which objects came to be recognized as possessing value beyond reuse or sale. From at least the mid-nineteenth century, the few surviving objects with links to the society’s early history and its most illustrious Fellows came to be termed ‘relics’, were treated with suitable reverence, put on display and made part of the society’s public self-presentation. If the more quotidian objects survived into the later 1800s, when their potential as objects for collection, research, display, reproduction and loan began to be appreciated, they are likely to have survived to the present day.
Kuznets meets Lucas: structural change and human capital
Authors: Cruz Edgar
Published: September 2018

This paper develops a multi-sector growth model with human capital accumulation. In this model, human capital induces structural change through two channels: changes in relative prices and changes in the investment rate of physical and human capital. We show that the specifications of the model give rise to a generalized balanced growth path (GBGP). Furthermore, We show that the model is consistent with (i) the decline in agriculture, (ii) the hump-shaped of manufacturing, (iii) the rise of the services sector, and (iv) the path of human capital accumulation in the US economy during the 20th century. Given the findings, We outline that imbalances between physical and human capital contribute to explain cross-country differences in the pace of structural change.
Absolute Lymphocyte Count Thresholds: A Simple, Readily Available Tool to Predict the Risk of Cytomegalovirus Infection After Transplantation
Authors: Meesing Atibordee , Razonable Raymund R
Published: September 2018

This study of 64 solid organ and hematopoietic stem cell transplant recipients found that peripheral blood absolute lymphocyte count of <610 and <830/µL, respectively, correlated with cytomegalovirus infection. In an era when sophisticated measures of CMV-specific T cells are emerging, we emphasize the utility of the inexpensive and readily-available absolute lymphocyte count.
ICTV Virus Taxonomy Profile: Fimoviridae
Authors: Elbeaino Toufic , Digiaro Michele , Mielke-Ehret Nicole , Muehlbach Hans-Peter , Martelli Giovanni P. ,   ICTV Report Consortium
Published: September 2018

Members of the family Fimoviridae, order Bunyavirales are plant viruses with segmented, linear, single-stranded, negative-sense RNA genomes. They are distantly related to orthotospoviruses and orthobunyaviruses of the families Tospoviridae and Peribunyaviridae, respectively. The family Fimoviridae includes the genus Emaravirus, which comprises several species with European mountain ash ringspot-associated emaravirus as the type species. Fimoviruses are transmitted to plants by eriophyid mite vectors and induce similar characteristic cytopathologies in their host plants, including the presence of double membrane-bound bodies in the cytoplasm of the virus-infected cells. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Fimoviridae, which is available at www.ictv.global/report/fimoviridae.
Trading off the cost of conflict against expected rewards
Authors: Sidarus Nura , Palminteri Stefano , Chambon Valérian
Published: September 2018

Value-based decision-making involves trading off the cost associated with an action against its expected reward. Research has shown that both physical and mental effort constitute such subjective costs, biasing choices away from effortful actions, and discounting the value of obtained rewards. Facing conflicts between competing action alternatives is considered aversive, as recruiting cognitive control to overcome conflict is effortful. Yet, it remains unclear whether conflict is also perceived as a cost in value-based decisions. The present study investigated this question by embedding irrelevant distractors (flanker arrows) within a reversal-learning task, with intermixed free and instructed trials. Results showed that participants learned to adapt their choices to maximize rewards, but were nevertheless biased to follow the suggestions of irrelevant distractors. Thus, the perceived cost of being in conflict with an external suggestion could sometimes trump internal value representations. By adapting computational models of reinforcement learning, we assessed the influence of conflict at both the decision and learning stages. Modelling the decision showed that conflict was avoided when evidence for either action alternative was weak, demonstrating that the cost of conflict was traded off against expected rewards. During the learning phase, we found that learning rates were reduced in instructed, relative to free, choices. Learning rates were further reduced by conflict between an instruction and subjective action values, whereas learning was not robustly influenced by conflict between one’s actions and external distractors. Our results show that the subjective cost of conflict factors into value-based decision-making, and highlights that different types of conflict may have different effects on learning about action outcomes.
Effects of Orientation Change during Environmental Learning on Age-Related Difference in Spatial Memory
Authors: Yamamoto Naohide , Fox Michael J. , Boys Ellen , Ord Jodi
Published: September 2018

It has been suggested that older adults suffer a greater degree of decline in environmental learning when navigating in an environment than when reading a map of the environment. However, the two types of spatial learning differ not only in perspectives (i.e., navigation is done with a ground-level perspective; a map is read from an aerial perspective) but also in orientations (i.e., orientations vary during navigation; spatial information is drawn from a single orientation in a map), making it unclear which factor critically affects older adults’ spatial learning. The present study addressed this issue by having younger and older participants learn the layout of a large-scale environment through an aerial movie that contained changes in orientations from which the environment was depicted. Results showed that older participants’ memories for the environmental layout were as distorted as those created through a ground-level movie (which involved the same orientation changes), whereas they formed more accurate memories through another aerial movie in which an orientation was fixed. By contrast, younger participants learned the environment equally well from the three movies. Taken together, these findings suggest that there is age-related alteration specifically in the ability to process multiple orientations of an environment while encoding its layout in memory. It is inferred that this alteration stems from functional deterioration of the medial temporal lobe, and possibly that of posterior cingulate areas as well (e.g., the retrosplenial cortex), in late adulthood.
The genomic view of diversification
Authors: Marin Julie , Achaz Guillaume , Crombach Anton , Lambert Amaury
Published: September 2018

Abstract

Evolutionary relationships between species are traditionally represented in the form of a tree, the species tree. Its reconstruction from molecular data is hindered by frequent conflicts between gene genealogies. Usually, these disagreements are explained by incomplete lineage sorting (ILS) due to random coalescences of gene lineages inside the edges of the species tree. This paradigm, the multi-species coalescent (MSC), is constantly violated by the ubiquitous presence of gene flow, leading to incongruences between gene trees that cannot be explained by ILS alone. Here we argue instead in favor of a vision acknowledging the importance of gene flow and where gene histories shape the species tree rather than the opposite. We propose a new framework for modeling the joint evolution of gene and species lineages relaxing the hierarchy between the species tree and gene trees. We implement this framework in two mathematical models called the gene-based diversification models (GBD): 1) GBD-forward following all evolving genomes and 2) GBD-backward based on coalescent theory. They feature four parameters tuning colonization, gene flow, genetic drift and genetic differentiation. We propose a quick inference method based on differences between gene trees. Applied to two empirical data-sets prone to gene flow, we find a better support for the GBD model than for the MSC model. Along with the increasing awareness of the extent of gene flow, this work shows the importance of considering the richer signal contained in genomic histories, rather than in the mere species tree, to better apprehend the complex evolutionary history of species.
Very few sites can reshape a phylogenetic tree
Authors: Francis Warren R. , Canfield Donald E.
Published: September 2018

The history of animal evolution, and the relative placement of extant animal phyla in this history is, in principle, testable from phylogenies derived from molecular sequence data. Though datasets have increased in size and quality in the past years, the contribution of individual genes (and ultimately amino acid sites) to the final phylogeny is unequal across genes. Here we demonstrate that by removing a small fraction of sites that strongly favor one topology, it is possible produce a highly-supported tree of an alternate topology. We explore this approach using a dataset for animal phylogeny, and create a highly-supported tree with a monophyletic group of sponges and ctenophores, a topology not usually recovered. As nearly all gene sets are neither standardized nor representative of the entire genome, we conclude that there are only two possible ways to remedy this problem. One solution would need to use a fixed set of genes, which though not representative, is at least standardized. The other would be to construct phylogenies using all genes, thus limiting analysis to species with sequenced genomes.
Cortical control of locomotor muscle activity through muscle synergies in humans: a neural decoding study
Authors: Yokoyama Hikaru , Kaneko Naotsugu , Ogawa Tetsuya , Kawashima Noritaka , Watanabe Katsumi , Nakazawa Kimitaka
Published: September 2018

Walking movements are orchestrated by the activation of a large number of muscles. The control of numerous muscles during walking is believed to be simplified by flexible activation of groups of muscles called muscle synergies. Although significant corticomuscular connectivity during walking has been reported, the level at which the cortex controls locomotor muscle activity (i.e., muscle synergy or individual muscle level) remains unclear. Here, we examined cortical involvement in muscle control during walking by brain decoding of the activation of muscle synergies and individual muscles from electroencephalographic (EEG) signals using linear decoder models. First, we demonstrated that activation of locomotor muscle synergies was decoded from slow cortical waves with significant accuracy. In addition, we found that decoding accuracy for muscle synergy activation was greater than that for individual muscle activation and that decoding of individual muscle activation was based on muscle synergy-related cortical information. Taken together, these results provide indirect evidence that the cerebral cortex hierarchically controls multiple muscles through a few muscle synergies during walking. Our findings extend the current understanding of the role of the cortex in muscular control during walking and could accelerate the development of effective brain-machine interfaces for people with locomotor disabilities.
The NuA4 acetyltransferase and non-canonical chromatin-associated MRN/ATM activity temporally define senescence-associated secretory programs
Authors: Malaquin Nicolas , Carrier-Leclerc Audrey , Martinez Aurelie , Dessureault Mireille , Ghadaouia Sabrina , Coppe Jean-Philippe , Nadeau Stephanie , Cardin Guillaume , Campisi Judith , Rodier Francis
Published: September 2018

Senescent cells display senescence-associated (SA) phenotypic programs such as proliferation arrest (SAPA) and secretory phenotype (SASP), which mediate their impact on tissue homeostasis. Curiously, senescence-inducing persistent DNA double-strand breaks (pDSBs) cause an immediate DNA damage response (DDR) and SAPA, but SASP requires days to develop, suggesting it requires additional molecular events. Here, we show that pDSBs provoke delayed recruitment of MRN/ATM and KAT5/TRRAP (NuA4/Tip60) complexes to global chromatin. This coincided with activating histone marks on up-regulated SASP genes, whereas depletion of these complexes compromised the SASP. Conversely, histone deacetylase inhibition triggered accelerated MRN/ATM/Tip60-dependent SASP without pDSBs, interlacing acetylation and non-canonical DNA damage-independent, low-level DDR activity in SASP maturation. DDR/acetylation regulation of SA programs is preserved in human cancer cells, suggesting novel targets for modifying treatment-induced SA phenotypes. We propose that delayed chromatin recruitment of acetyltransferases cooperates with non-canonical DDR signaling to ensure SASP activation only in the context of senescence, and not in response to a transient DNA damage-induced proliferation arrest.
Spatial and temporal organization of RecA in theEscherichia coliDNA-damage response
Authors: Ghodke Harshad , Paudel Bishnu P , Lewis Jacob S , Jergic Slobodan , Gopal Kamya , Romero Zachary J , Wood Elizabeth A , Woodgate Roger , Cox Michael M , van Oijen Antoine M
Published: September 2018

The RecA protein orchestrates the cellular response to DNA damage via its multiple roles in the bacterial SOS response. Lack of tools that provide unambiguous access to the various RecA states within the cell have prevented understanding of the spatial and temporal changes in RecA structure/function that underlie control of the damage response. Here, we develop a monomeric C-terminal fragment of the λ repressor as a novel fluorescent probe that specifically interacts with RecA filaments on single-stranded DNA (RecA*). Single-molecule imaging techniques in live cells demonstrate that RecA is largely sequestered in storage structures during normal metabolism. Upon DNA damage, the storage structures dissolve and the cytosolic pool of RecA rapidly nucleates to form early SOS-signaling complexes, maturing into DNA-bound RecA bundles at later time points. Both before and after SOS induction, RecA* largely appears at locations distal from replisomes. Upon completion of repair, RecA storage structures reform.
Autophagy regulates hyaluronan synthase 2 levels in vascular endothelial cells
Authors: Chen Carolyn G. , Gubbiotti Maria A. , Han Xiaorui , Yu Yanglei , Linhardt Robert J. , Iozzo Renato V.
Published: September 2018

Hyaluronan is emerging as a key player regulating wound repair, inflammation, and angiogenesis. Of the three hyaluronan synthases (HAS1-3), HAS2 is the main driver of tumorigenicity by enhancing hyaluronan deposition. We discovered that HAS2 was degraded in vascular endothelial cells via autophagy, a catabolic process evoked by endorepellin and endostatin, two angiostatic and pro-autophagic effectors, and by Torin 1, a specific mTOR inhibitor. Protracted autophagy increased co-localization of HAS2 with three core components of the autophagosome, LC3, p62, and ATG9A, and binding of HAS2 to ATG9A. Importantly, autophagic induction led to an exclusive and marked suppression of secreted hyaluronan with no significant effects on either heparan or chondroitin sulfate levels. Thus, we have unveiled autophagy as a key catabolic mechanism regulating the production of hyaluronan in endothelial cells. Moreover, our study provides a biological link between autophagy and angiogenesis that could lead to potential targets for tumor neovascularization.

Hyaluronan is pro-angiogenic and pro-tumorigenic. We report a novel mechanism through which three autophagic inducers―endorepellin, endostatin, and Torin 1―regulate the levels of hyaluronan synthase-2. Protracted autophagy results in suppression of extracellular hyaluronan, thereby implicating autophagy in the regulation hyaluronan production.
The Perceptual Neural Trace of Memorable Unseen Scenes
Authors: Mohsenzadeh Yalda , Mullin Caitlin , Oliva Aude , Pantazis Dimitrios
Published: September 2018

Some scenes are more memorable than others: they cement in minds with consistencies across observers and time scales. While memory mechanisms are traditionally associated with the end stages of perception, recent behavioral studies suggest that the features driving these memorability effects are extracted early on, and in an automatic fashion. This raises the question: is the neural signal of memorability detectable during early perceptual encoding phases of visual processing? Using the high temporal resolution of magnetoencephalography (MEG), during a rapid serial visual presentation (RSVP) task, we traced the neural temporal signature of memorability across the brain. We found an early and prolonged memorability related signal recruiting a network of regions in both dorsal and ventral streams, detected outside of the constraints of subjective awareness. This enhanced encoding could be the key to successful storage and recognition.
Spatial variation in the biochemical and isotopic composition of corals during bleaching and recovery
Authors: Wall Christopher B , Ritson-Williams Raphael , Popp Brian N , Gates Ruth D
Published: September 2018

Ocean warming and the increased prevalence of coral bleaching events threaten coral reefs. However, the biology of corals during and following bleaching events under field conditions is poorly understood. We examined bleaching and post-bleaching recovery inMontipora capitataandPorites compressacorals that either bleached or did not bleach during a 2014 bleaching event at three reef locations in Kāne‘ohe Bay, O‘ahu. We measured changes in chlorophylls, biomass, and nutritional plasticity using stable isotopes (δ13C, δ15N). Coral traits showed significant variation among bleaching conditions, reef sites, time periods, and their interactions. Bleached colonies of both species had lower chlorophyll and total biomass. WhileM. capitatachlorophyll and biomass recovered three months later,P. compressachlorophyll recovery was location-dependent and total biomass of previously bleached colonies remained low. Biomass energy reserves were not affected by bleaching, insteadM. capitataproteins andP. compressabiomass energy declined over time, andP. compressalipid biomass was site-specific. Stable isotope analyses of host and symbiont tissues did not indicate increased heterotrophic nutrition in bleached colonies of either species, during or after thermal stress. Instead, mass balance calculations revealed variance in δ13C values was best explained by augmented biomass composition, whereas δ15N values reflected spatial and temporal variability in nitrogen sources in addition to bleaching effects on symbiont nitrogen demand. These results emphasize total biomass quantity may change substantially during bleaching and recovery. Consequently, there is a need to consider the influence of biomass composition in the interpretation of isotopic values in corals.
Bacterial clearance enhanced by α2, 3- and α2, 6-sialyllactose via receptor-mediated endocytosis and phagocytosis
Authors: Kim Jimin , Kim Yong Jae , Kim Jae Wha
Published: September 2018

Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its potential application as a therapeutic agent to treat bacterial and viral infections.
Genome-wide admixture is common across the Heliconius radiation
Authors: Kozak Krzysztof M. , McMillan W. Owen , Joron Mathieu , Jiggins Christopher D.
Published: September 2018

How frequent is gene flow between species? The pattern of evolution is typically portrayed as a phylogenetic tree, implying that speciation is a series of splits between lineages. Yet gene flow between good species is increasingly recognized as an important mechanism in the diversification of radiations, often spreading adaptive traits and leading to a complex pattern of phylogenetic incongruence. This process has thus far been studied in cases involving few species, or geographically restricted to spaces like islands, but not on the scale of a continental radiation. Previous studies have documented gene flow, adaptive introgression and hybrid speciation in a small subsection of the charismatic Neotropical butterflies Heliconius. Using genome-wide resequencing of 40 out of 45 species in the genus we demonstrate for the first time that admixture has played a role throughout the evolution of Heliconius and the sister genus Eueides. Modelling of phylogenetic networks based on 6848 orthologous autosomal genes (Maximum Pseudo-Likelihood Networks) or 5,483,419 high quality SNPs (Ancestral Recombination Graph) uncovers nine new cases of interspecific gene flow at up to half of the genome. However, f4 statistics of admixture show that the extent of the process has varied between subgenera. Evidence for introgression is found at all five loci controlling the colour and shape of the mimetic wing patterns, including in the putative hybrid species H. hecalesia, characterised by an unusual hindwing. Due to hybridization and incomplete coalescence during rapid speciation, individual gene trees show rampant discordance. Although reduced gene flow and faster coalescence are expected at the Z chromosome, we discover high levels of conflict between the 416 sex-linked loci. Despite this discordant pattern, both concatenation and multispecies coalescent approaches yield surprisingly consistent and fully supported genome-wide phylogenies. We conclude that the imposition of the bifurcating tree model without testing for interspecific gene flow may distort our perception of adaptive radiations and thus the ability to study trait evolution in a comparative framework.
Pleistocene climate changes explain large-scale genetic variation in a dominant grassland species, Lolium perenne L
Authors: Blanco-Pastor J.L. , Manel S. , Barre P. , Roschanski A.M. , Willner E. , Dehmer K.J. , Hegarty M. , Muylle H. , Ruttink T. , Roldán-Ruiz I. , Ledauphin T. , Escobar-Gutierrez A. , Sampoux J.P.
Published: September 2018

Aim

Grasslands have been pivotal in the development of herbivore breeding since the Neolithic and are still nowadays the most widespread agricultural land-use across Europe. However, it remains unclear whether the current large-scale genetic variation of plant species found in natural grasslands of Europe is the result of human activities or natural processes.

Location

Europe.

Taxon

Lolium perenne L (perennial ryegrass).

Methods

We reconstructed the phylogeographic history of L. perenne, a dominant grassland species, using 481 natural populations including 11 populations from closely related taxa. We combined the Genotyping-by-Sequencing (GBS) and Pool-sequencing (Pool-seq) methods to obtain high-quality allele frequency calls of ~ 500 k SNP loci. We performed genetic structure analyses and demographic reconstructions based on the site frequency spectrum (SFS). We additionally used the same genotyping protocol to assess the genomic diversity of a set of 32 cultivars representative of the L. perenne cultivars widely used for forage purposes.

Results

Expansion across Europe took place during the Würm glaciation (12-110 kya), a cooling period that decreased the dominance of trees in favour of grasses. Splits and admixtures in L. perenne fit historical sea level changes in the Mediterranean basin. The development of agriculture in Europe (7-3.5 kya), that caused an increase in the abundance of grasslands, did not have an effect on the demographic patterns of L. perenne. We found little differentiation between modern cultivars and certain natural variants. However, modern cultivars do not represent the wide genetic variation found in natural populations.

Main conclusions

Demographic events in L. perenne can be explained by the changing climatic conditions during the Pleistocene. Natural populations maintain a wide genomic variability at continental scale that has been underused by recent breeding activities. This variability constitutes valuable standing genetic variation for future adaptation of grasslands to climate change, safeguarding the agricultural services they provide.
Myh10deficiency leads to defective extracellular matrix remodeling and pulmonary disease
Authors: Kim Hyun-Taek , Yin Wenguang , Jin Young-June , Panza Paolo , Gunawan Felix , Grohmann Beate , Buettner Carmen , Sokol Anna M. , Preussner Jens , Guenther Stefan , Kostin Sawa , Ruppert Clemens , Bhagwat Aditya M. , Ma Xuefei , Graumann Johannes , Looso Mario , Guenther Andreas , Adelstein Robert S. , Offermanns Stefan , Stainier Didier Y.R.
Published: September 2018

Impaired alveolar formation and maintenance are features of many pulmonary diseases that are associated with significant morbidity and mortality. In a forward genetic screen for modulators of mouse lung development, we identified the non-muscle myosin II heavy chain gene,Myh10.Myh10mutant pups exhibit cyanosis and respiratory distress, and die shortly after birth from differentiation defects in alveolar epithelium and mesenchyme. From omics analyses and follow up studies, we find decreased Thrombospondin expression accompanied with increased matrix metalloproteinase activity in both mutant lungs and cultured mutant fibroblasts, as well as disrupted extracellular matrix (ECM) remodeling. Loss ofMyh10specifically in mesenchymal cells results in ECM deposition defects and alveolar simplification. Notably, MYH10 expression is down-regulated in the lung of emphysema patients. Altogether, our findings reveal critical roles forMyh10in alveologenesis at least in part via the regulation of ECM remodeling, which may contribute to the pathogenesis of emphysema.
Structural basis of light-induced redox regulation in the Calvin cycle
Authors: McFarlane Ciaran , Shah Nita R. , Kabasakal Burak V. , Cotton Charles A.R. , Bubeck Doryen , Murray James W.
Published: September 2018

In plants, carbon dioxide is fixed via the Calvin cycle in a tightly regulated process. Key to this regulation is the conditionally disordered protein CP12. CP12 forms a complex with two Calvin cycle enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK), inhibiting their activities. The mode of CP12 action was unknown. By solving crystal structures of CP12 bound to GAPDH, and the ternary GAPDH-CP12-PRK complex by electron cryo-microscopy, we reveal that formation of the N-terminal disulfide pre-orders CP12 prior to binding the PRK active site. We find that CP12 binding to GAPDH influences substrate accessibility of all GAPDH active sites in the binary and ternary inhibited complexes. Our model explains how CP12 integrates responses from both redox state and nicotinamide dinucleotide availability to regulate carbon fixation.

One Sentence Summary

How plants turn off carbon fixation in the dark.
Oct1/Pou2f1 is selectively required for gut regeneration and regulates gut malignancy
Authors: Vázquez-Arreguín Karina , Bensard Claire , Schell John C. , Swanson Eric , Chen Xinjian , Rutter Jared , Tantin Dean
Published: September 2018

The transcription factor Oct1/Pou2f1 promotes poised gene expression states, mitotic stability, glycolytic metabolism and other characteristics of stem cell potency. To determine the effect of Oct1 loss on stem cell maintenance and malignancy, we deleted Oct1 in two different mouse gut stem cell compartments. Oct1 deletion preserved homeostasis in vivo and the ability to generate cultured organoids in vitro, but blocked the ability to regenerate after treatment with dextran sodium sulfate, and the ability to maintain organoids after passage. In a chemical model of colon cancer, loss of Oct1 in the colon severely restricted tumorigenicity. In contrast, loss of one or bothOct1alleles progressively increased tumor burden in a colon cancer model driven by loss of heterozygosity of the tumor suppressor geneApc.The different outcomes are consistent with prior findings that Oct1 promotes mitotic stability, and consistent with different gene expression signatures associated with the two models. These results reveal that Oct1 is selectively required for gut regeneration, and has potent effects in colon malignancy, with outcome (pro-oncogenic or tumor suppressive) dictated by tumor etiology.

Author summary

Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 35% of diagnosed patients eventually succumb to disease. The high incidence and mortality due to colon cancer demand a better understanding of factors controlling the physiology and pathophysiology of the gastrointestinal tract. Previously, we and others showed that the widely expressed transcription factor is expressed at higher protein levels in stem cells, including intestinal stem cells. In this study we use a conditional mouseOct1(Pou2f1) allele deleted in two different intestinal stem cell compartments. The results indicate that Oct1 loss is dispensable for maintenance of the mouse gut, but required for regeneration. We also tested Oct1 loss in the context of two different mouse colon cancer models. We find that Oct1 loss has opposing effects in the two models, and further that the two models are associated with different gene expression signatures. The differentially expressed genes are enriched for previously identified Oct1 targets, suggesting that differential gene control by Oct1 is one mechanism underlying different outcomes.
Dynamin binding protein is required forXenopus laeviskidney development
Authors: DeLay Bridget D. , Baldwin Tanya A. , Miller Rachel K.
Published: September 2018

The adult human kidney contains over one million nephrons, with each nephron consisting of a tube containing segments that have specialized functions in nutrient and water absorption and waste excretion. The embryonic kidney ofXenopus laevisconsists of a single functional nephron composed of regions that are analogous to those found in the human nephron, making it a simple model for the study of nephrogenesis. The exocyst complex, which traffics proteins to the cell membrane in vesicles via CDC42, is essential for normal kidney development. Here, we show that the CDC42-GEF, dynamin binding protein (Dnmbp/Tuba), is essential for nephrogenesis inXenopus.dnmbpis expressed inXenopusembryo kidneys during development, and knockdown of Dnmbp using two separate morpholino antisense oligonucleotides results in reduced expression of late pronephric markers, whereas the expression of early markers of nephrogenesis remains unchanged. A greater reduction in expression of markers of differentiated distal and connecting tubules was seen in comparison to proximal tubule markers, indicating that Dnmbp reduction may have a greater impact on distal and connecting tubule differentiation.dnmbpknockout using CRISPR results in a similar reduction of late markers of pronephric tubulogenesis. Overexpression ofdnmbpin the kidney also resulted in disrupted pronephric tubules, suggesting thatdnmbplevels in the developing kidney are tightly regulated, with either increased or decreased levels leading to developmental defects. Together, these data suggest that Dnmbp is required for nephrogenesis.
Integrated Analysis Revealed Hub Genes in Breast Cancer
Authors: Jin Haoxuan , Huang Xiaoyan , Shao Kang , Li Guibo , Wang Jian , Yang Huanming , Hou Yong
Published: September 2018

The aim of this study was to identify the hub genes in breast cancer and provide further insight into the tumorigenesis and development of breast cancer. To explore the hub genes in breast cancer, we performed an integrated bioinformatics analysis. Two gene expression profiles were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by using the “limma” package. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional annotation and potential pathways of the DEGs. Next, protein–protein interaction (PPI) network analysis and weighted gene coexpression network analysis (WGCNA) were conducted to screen for hub genes. To confirm the reliability of the identified hub genes, we obtained TCGA-BRCA data by using WGCNA to screen for genes that were strongly related to breast cancer. By combining the results from the GEO and TCGA datasets, we finally identified 15 real hub genes in breast cancer. Finally, we performed an overall survival analysis to explore the connection between the expression of hub genes and the overall survival time of breast cancer patients. We found that for all hub genes, higher expression was associated with significantly shorter overall survival times among breast cancer patients.
A reverse Turing-test for predicting social deficits in people with Autism
Authors: d’Arc Baudouin Forgeot , Devaine Marie , Daunizeau Jean
Published: September 2018

Social symptoms of autism spectrum disorder (ASD) are typically viewed as consequences of an impaired Theory of Mind, i.e. the ability to understand others’ covert mental states. Here, we test the assumption that such “mind blindness” may be due to the inability to exploit contextual knowledge about, e.g., the stakes of social interactions, to make sense of otherwise ambiguous cues (e.g., idiosyncratic responses to social competition). In this view, social cognition in ASD may simply reduce to non-social cognition, i.e. cognition that is not informed by the social context. We compared 24 adult participants with ASD to 24 neurotypic participants in a repeated dyadic competitive game against artificial agents with calibrated mentalizing sophistication. Critically, participants were framed to believe that they were competing against humans (social framing) or not (non-social framing), hence the “reverse Turing test”. In contrast to control participants, the strategy of people with ASD is insensitive to the game’s framing, i.e. they do not constrain their understanding of others’ behaviour with the contextual knowledge about the game (cf. competitive social framing). They also outperform controls when playing against simple agents, but are outperformed by them against recursive algorithms framed as human opponents. Moreover, computational analyses of trial-by-trial choice sequences in the game show that individuals with ASD rely on a distinctive cognitive strategy with subnormal flexibility and mentalizing sophistication. These computational phenotypes yield 79% diagnosis classification accuracy and explain 62% of the severity of social symptoms in people with ASD.
Fast fluorescence lifetime imaging reveals the aggregation processes of α-synuclein and polyglutamine in aging Caenorhabditis elegans
Authors: Laine Romain F. , Sinnige Tessa , Ma Kai Yu , Haack Amanda J. , Poudel Chetan , Gaida Peter , Curry Nathan , Perni Michele , Nollen Ellen A.A. , Dobson Christopher M. , Vendruscolo Michele , Kaminski Schierle Gabriele S. , Kaminski Clemens F.
Published: September 2018

The nematode worm Caenorhabditis elegans has emerged as an important model organism to study the molecular mechanisms of protein misfolding diseases associated with amyloid formation because of its small size, ease of genetic manipulation and optical transparency. Obtaining a reliable and quantitative read-out of protein aggregation in this system, however, remains a challenge. To address this problem, we here present a fast time-gated fluorescence lifetime imaging (TG-FLIM) method and show that it provides functional insights into the process of protein aggregation in living animals by enabling the rapid characterisation of different types of aggregates. More specifically, in longitudinal studies of C. elegans models of Parkinson’s and Huntington’s diseases, we observed marked differences in the aggregation kinetics and the nature of the protein inclusions formed by α-synuclein and polyglutamine. In particular, we found that α-synuclein inclusions do not display amyloid-like features until late in the life of the worms, whereas polyglutamine forms amyloid characteristics rapidly in early adulthood. Furthermore, we show that the TG-FLIM method is capable of imaging live and non-anaesthetised worms moving in specially designed agarose micro-chambers. Taken together, our results show that the TG-FLIM method enables high-throughput functional imaging of living C. elegans that can be used to study in vivo mechanisms of aggregation and that has the potential to aid the search for therapeutic modifiers of protein aggregation and toxicity.
Complexity Matching and Requisite Variety
Authors: Mahmoodi Korosh , West Bruce J. , Grigolini Paolo
Published: September 2018

Complexity matching emphasizes the condition necessary to efficiently transport information from one complex system to another and the mechanism can be traced back to the 1957Introduction to Cyberneticsby Ross Ashby. Unlike this earlier work we argue that complexity can be expressed in terms of crucial events, which are generated by the processes of spontaneous self-organization. Complex processes, ranging from biological to sociological, must satisfy the homeodynamic condition and host crucial events that have recently been shown to drive the information transport between complex systems. We adopt a phenomenological approach, based on the subordination to periodicity that makes it possible to combine homeodynamics and self-organization induced crucial events. The complexity of crucial events is defined by the waiting-time probability density function (PDF) of the intervals between consecutive crucial events, which have an inverse power law (IPL) PDFψ(τ) ∝1/(τ)μwith 1 <μ< 3. We establish the coupling between two temporally complex systems using a phenomenological approach inspired by models of swarm cognition and prove that complexity matching, namely sharing the same IPL indexμ, facilitates the transport of information, generating perfect synchronization, reminiscent of, but distinct from chaos synchronization. This advanced form of complexity matching is expected to contribute a significant progress in understanding and improving the bio-feedback therapies.

Author Summary

This paper is devoted to the control of complex dynamical systems, inspired to real processes of biological and sociological interest. The concept of complexity we adopt focuses on the assumption that the processes of self-organization generate intermittent fluctuations and that the time distance between two consecutive fluctuations is described by a distribution density with an inverse power law structure making the second moment of these time distances diverge. These fluctuations are called crucial events and are responsible for the ergodicity breaking that is widely revealed by the experimental observation of biological dynamics. We argue that the information transport from one to another complex system is ruled by these crucial events and we propose an efficient theoretical prescription leading to qualitative agreement with experimental results, shedding light into the processes of social learning. The theory of this paper is expected to have important medical applications, such as an improvement of the biofeedback techniques, the heart-brain communication and a significant progress on cognition and the contribution of emotions to cognition.
Template or ligand? Different structural behaviours of aromatic amines in combination with zincophosphite networks
Authors: Holmes William , Cordes David B. , Slawin Alexandra M. Z. , Harrison William T. A.
Published: September 2018

The solution-mediated syntheses and crystal structures of catena-poly[bis(2-amino-3-hydroxypyridinium) [zinc-di-μ-phosphonato] dihydrate], {(C5H7N2O)[Zn(HPO3)2]·2H2O}
n
, (I), and poly[(benzene-1,2-diamine)(μ5-phosphonato)zinc], [Zn(HPO3)(C6H8N2)]
n
, (II) are described. The extended structure of (I) features [010] anionic chains of vertex-sharing ZnO4 tetrahedra and HPO3 pseudopyramids; these chains are characterized by disorder over major [occupancy 0.7962 (13)] and minor [0.2038 (13)] components, which can be superimposed on each other by a nominal translational shift. The 2-amino-3-hydroxypyridinium cations and water molecules of crystallization interact with the ZnPO chains by way of numerous O—H...O and N—H...O hydrogen bonds. The structure of (II) features a direct Zn—N bond to the neutral 1,2-diaminobenzene species as part of ZnO3N tetrahedra as well as HPO3 pseudopyramids. The Zn- and P-centred groupings are linked through their O-atom vertices into infinite (010) sheets and the structure is consolidated by N—H...O hydrogen bonds and N—H...π interactions. The crystal of (I) chosen for data collection was found to be an inversion twin in a 0.56 (2):0.44 (2) domain ratio.
Minority community willingness to pay for earthquake insurance
Authors: Zhang Chun-Min , Qian Zhen-Wei
Published: September 2018

Purpose

The purpose of this paper is to investigate the relationship between potential affecting factors and the local communities’ willingness to pay (WTP) for housing earthquake insurance (HEI) in the context of ethnic minority communities.

Design/methodology/approach

A literature review was done to identify possible factors affecting WTP for HEI. Fieldwork was conducted in 2017 in Dali Minority Autonomous Prefecture, where the first Chinese HEI was launched in 2015. Interviews were done in two earthquake-prone counties, as the main ethnic minority communities in the area. A total of 536 questionnaires were collected and used as empirical data for testing the impacts mechanism.

Findings

Respondents’ risk perception, risk exposure, self-prevention behaviors, government aid, insurance experience and sociodemographic characteristics were hypothesized as theoretical indicators correlated to WTP for HEI. Empirical analysis results predict that WTP for HEI is significantly influenced by risk perception, insurance experience, government aid, and age and out-migrating labors. It is evident that higher risk perception and more insurance experience lead to stronger desire for HEI coverage. However, dependency on government aid negatively affects WTP for HEI. Moreover, WTP for HEI is negative in relation to age and out-migrating labors. Surprisingly, ethnic-culture factors were not statistically significant to WTP for HEI.

Originality/value

This paper is an attempt to identify and verify factors affecting WTP for HEI, bridging the gap of inadequate research on WTP for HEI in ethnic minority communities.