bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of extensive fine-scale diversity by spatio-temporal chaos
Authors: Pearce Michael , Agarwala Atish , Fisher Daniel S. 
Published: August 2019

AbstractIt has become recently apparent that the diversity of microbial life extends far below species level to the finest scales of genetic differences. Remarkably, extensive fine-scale diversity can coexist spatially. How is this diversity stable on long timescales despite selective or ecological differences and other evolutionary processes? Most work has focused on stable coexistence or assumed ecological neutrality. We present an alternative: extensive diversity maintained by ecologically-driven spatio-temporal chaos, with no assumptions about niches or other specialist differences between strains. We study generalized Lotka-Volterra models with anti-symmetric correlations in the interactions inspired by multiple pathogen strains infecting multiple host strains. Generally, these exhibit chaos with increasingly wild population fluctuations driving extinctions. But the simplest spatial structure, many identical islands with migration between them, stabilizes a diverse chaotic state. Some types (sub-species) go globally extinct, but many persist for times exponentially long in the number of islands. All persistent types have episodic local blooms to high abundance, crucial for their persistence as, for many, their average population growth rate is negative. Snapshots of the distribution of abundances show a power-law at intermediate abundances that is essentially indistinguishable from the neutral theory. But the dynamics of the large populations are much faster than birth-death fluctuations. We argue that this spatio-temporally chaotic “phase” should exist in a wide range of models, and that even in rapidly mixed systems, longer lived spores could similarly stabilize a diverse chaotic phase.
Structural mechanism of regioselectivity in an unusual bacterial acyl-CoA dehydrogenase
Authors: Blake-Hedges Jacquelyn M. , Pereira Jose Henrique , Cruz-Morales Pablo , Thompson Mitchell G. , Barajas Jesus F. , Chen Jeffrey , Krishna Rohith N. , Chan Leanne Jade G. , Nimlos Danika , Alonso-Martinez Catalina , Baidoo Edward E.K. , Chen Yan , Gin Jennifer W. , Katz Leonard , Petzold Christopher J. , Adams Paul D. , Keasling Jay D. 
Published: August 2019

AbstractTerminal alkenes are easily derivatized, making them desirable functional group targets for polyketide synthase (PKS) engineering. However, they are rarely encountered in natural PKS systems. One mechanism for terminal alkene formation in PKSs is through the activity of an acyl-CoA dehydrogenase (ACAD). Herein, we use biochemical and structural analysis to understand the mechanism of terminal alkene formation catalyzed by an γ,δ-ACAD from the biosynthesis of the polyketide natural product FK506, TcsD. While TcsD is homologous to canonical α,β-ACADs, it acts regioselectively at the γ,δ-position and only on α,β-unsaturated substrates. Furthermore, this regioselectivity is controlled by a combination of bulky residues in the active site and a lateral shift in the positioning of the FAD cofactor within the enzyme. Substrate modeling suggests that TcsD utilizes a novel set of hydrogen bond donors for substrate activation and positioning, preventing dehydrogenation at the α,β position of substrates. From the structural and biochemical characterization of TcsD, key residues that contribute to regioselectivity and are unique to the protein family were determined and used to identify other putative γ,δ-ACADs that belong to diverse natural product biosynthetic gene clusters. These predictions are supported by the demonstration that a phylogenetically distant homolog of TcsD also regioselectively oxidizes α,β-unsaturated substrates. This work exemplifies a powerful approach to understand unique enzymatic reactions and will facilitate future enzyme discovery, inform enzyme engineering, and aid natural product characterization efforts.
Profilin and formin constitute a pacemaker system for robust actin filament growth
Authors: Funk Johanna , Merino Felipe , Venkova Larisa , Vargas Pablo , Raunser Stefan , Piel Matthieu , Bieling Peter 
Published: August 2019

AbstractThe actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.
MicroRNA Profiles in Calcified and Healthy Aorta Differ: Therapeutic Impact of miR-145 and miR-378
Authors: Tang Ying , Shah Tapan A. , Yurkow Edward J. , Rogers Melissa B. 
Published: August 2019

AbstractOur goal was to elucidate microRNAs (miRNAs) that may repress the excess bone morphogenetic protein (BMP) signaling observed during pathological calcification in theKlothomouse model of kidney disease. We hypothesized that restoring healthy levels of miRNAs that post-transcriptionally repress osteogenic calcific factors may decrease aortic calcification. Our relative abundance profiles of miRNAs in healthy aorta differ greatly from those in calcified mouse aorta. Many of these miRNAs are predicted to regulate proteins involved in BMP signaling and may control osteogenesis. Two differentially regulated miRNAs, miR-145 and miR-378, were selected based on three criteria: reduced levels in calcified aorta, the ability to target more than one protein in the BMP signaling pathway, and conservation of targeted sequences between humans and mice. Forced expression using a lentiviral vector demonstrated that restoring normal levels repressed the synthesis of BMP2 and other pro-osteogenic proteins and inhibited pathological aortic calcification inKlothomice with renal insufficiency. This study identified miRNAs that may impact BMP signaling in both sexes and demonstrated the efficacy of selected miRNAs in reducing aortic calcificationin vivo. Calcification of the aorta and the aortic valve resulting from abnormal osteogenesis is common in those with kidney disease, diabetes, and high cholesterol. Such vascular osteogenesis is a clinically significant feature. The calcification modulating miRNAs described here are candidates for biomarkers and “miRNA replacement therapies” in the context of chronic kidney disease and other pro-calcific conditions.
LUZP1 and the tumour suppressor EPLIN are negative regulators of primary cilia formation
Authors: Gonçalves João , Coyaud Étienne , Laurent Estelle M.N. , Raught Brian , Pelletier Laurence 
Published: August 2019

ABSTRACTCilia/flagella are microtubule-based cellular projections with important sensory and motility functions. Their absence or malfunction is associated with a growing number of human diseases collectively referred to as ciliopathies. However, the fundamental mechanisms underpinning cilia biogenesis and functions remain only partly understood. Here, we show that LUZP1, and its interacting protein EPLIN, are negative regulators of primary cilia formation. LUZP1 is an actin-associated protein that localizes to both actin filaments and the centrosome/basal body. Like EPLIN, LUZP1 is an actin-stabilizing protein and likely regulates actin dynamics at the centrosome. Both proteins interact with ciliogenesis and cilia length regulators, and are potential players in the actin-dependent processes involved in centrosome to basal body conversion. Ciliogenesis deregulation caused by LUZP1 or EPLIN loss may contribute to the pathology of their associated diseases.SUMMARYGonçalves et al. show that LUZP1 and its interactor EPLIN are negative regulators of ciliogenesis. LUZP1 is a novel actin-stabilizing protein localizing at the centrosome and basal body where it may regulate actin-associated processes.
Multi-Dimensional Machine Learning Approaches for Fruit Shape Recognition and Phenotyping in Strawberry
Authors: Feldmann Mitchell J. , Hardigan Michael A. , Famula Randi A. , López Cindy M. , Tabb Amy , Cole Glenn S. , Knapp Steven J. 
Published: August 2019

AbstractBackgroundShape is a critical element of the visual appeal of strawberry fruit and determined by both genetic and non-genetic factors. Current fruit phenotyping approaches for external characteristics in strawberry rely on the human eye to make categorical assessments. However, fruit shape is multi-dimensional, continuously variable, and not adequately described by a single quantitative variable. Morphometric approaches enable the study of complex forms but are often abstract and difficult to interpret. In this study, we developed a mathematical approach for transforming fruit shape classifications from digital images onto an ordinal scale called the principal progression of k clusters (PPKC). We use these human-recognizable shape categories to select features extracted from multiple morphometric analyses that are best fit for genome-wide and forward genetic analyses.ResultsWe transformed images of strawberry fruit into human-recognizable categories using unsupervised machine learning, discovered four principal shape categories, and inferred progression using PPKC. We extracted 67 quantitative features from digital images of strawberries using a suite of morphometric analyses and multi-variate approaches. These analyses defined informative feature sets that effectively captured quantitative differences between shape classes. Classification accuracy ranged from 68.9 – 99.3% for the newly created, genetically correlated phenotypic variables describing a shape.ConclusionsOur results demonstrated that strawberry fruit shapes could be robustly quantified, accurately classified, and empirically ordered using image analyses, machine learning, and PPKC. We generated a dictionary of quantitative traits for studying and predicting shape classes and identifying genetic factors underlying phenotypic variability for fruit shape in strawberry. The methods and approaches we applied in strawberry should apply to other fruits, vegetables, and specialty crops.
A peptide pair coordinates regular ovule initiation patterns with seed number and fruit size
Authors: Kawamoto Nozomi , Pino Del Carpio Dunia , Hofmann Alexander , Mizuta Yoko , Kurihara Daisuke , Higashiyama Tetsuya , Uchida Naoyuki , Torii Keiko U. , Colombo Lucia , Groth Georg , Simon Rüdiger 
Published: August 2019

AbstractOvule development inArabidopsis thalianainvolves pattern formation which ensures that ovules are regularly arranged in the pistils to reduce competition for nutrients and space. Mechanisms underlying pattern formation in plants, such as phyllotaxis, flower morphogenesis or lateral root initiation, have been extensively studied, and genes controlling the initiation of ovules have been identified. However, how a regular spacing of ovules is achieved is not known. Using natural variation analysis combined with quantitative trait locus analysis, we found that the spacing of ovules in the developing fruits is controlled by two secreted peptides, EPFL2 and EPFL9 (also known as Stomagen), and their receptors from the ERECTA (ER) family that act from the carpel wall and the placental tissue. We found that a signalling pathway controlled by EPFL9 acting from the carpel wall through the LRR-receptor kinases ER, ERL1 and ERL2 promotes fruit growth. Regular spacing of ovules depends on EPFL2 expression in the carpel wall and in the inter-ovule spaces, where it acts through ERL1 and ERL2. Loss of EPFL2 signalling results in shorter fruits and irregular spacing of ovules or even ovule twinning. The EPFL2 expression pattern between ovules is under negative-feedback regulation by auxin, which accumulates in the arising ovule primordia. We propose that the auxin-EPFL2 signalling module evolved to control the initiation and regular, equidistant spacing of ovule primordia, which serves to minimise competition between developing seeds. Together, EPFL2 and EPFL9 coordinate ovule patterning and thereby seed number with fruit growth through a set of shared receptors.
Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+-dependent death of cancer cells
Authors: Ciscato Francesco , Filadi Riccardo , Masgras Ionica , Pizzi Marco , Marin Oriano , Damiano Nunzio , Pizzo Paola , Gori Alessandro , Frezzato Federica , Trentin Livio , Bernardi Paolo , Rasola Andrea 
Published: August 2019

AbstractCancer cells undergo changes in metabolic and survival pathways that increase their malignancy. Isoform 2 of the glycolytic enzyme hexokinase (HK2) enhances both glucose metabolism and resistance to death stimuli in many neoplastic cell types. Here we observe that HK2 locates at mitochondria-endoplasmic reticulum (ER) contact sites called MAMs (Mitochondria-Associated Membranes). HK2 displacement from MAMs with a selective peptide triggers mitochondrial Ca2+overload caused by Ca2+release from ER via inositol-3-phosphate receptors (IP3Rs) and by Ca2+entry through plasma membrane. This results in Ca2+-dependent calpain activation, mitochondrial depolarization and cell death. The HK2-targeting peptide causes massive death of chronic lymphocytic leukemia B cells freshly isolated from patients, and an actionable form of the peptide reduces growth of breast and colon cancer cells allografted in mice without noxious effects on healthy tissues. These results identify a signalling pathway primed by HK2 displacement from MAMs that can be activated as anti-neoplastic strategy.
Feedback loops involving ERK, AMPK and TFEB generate non-genetic heterogeneity that allows cells to evade anoikis
Authors: Kumar Saurav , Hari Kishore , Jolly Mohit Kumar , Rangarajan Annapoorni 
Published: August 2019

AbstractSome solid tumor cells escape death triggered by matrix-deprivation and cause cancer spread through metastatic growth. The role of phenotypic plasticity in this adaptation remains unknown. We recently identified a double-negative feedback loop between pAMPK (phospho-AMPK) and pAkt (phospho-Akt) that regulates the switch between attached and detached states of cancer cells. In this study, we show that matrix-detachment itself can give rise to two subpopulations with varying ERK signaling levels and autophagy flux. Cells with elevated ERK activity show autophagy maturation arrest leading to anoikis, whereas those with low ERK activity overcome this block and generate anchorage-independent colonies. Investigating upstream, we show a novel role of AMPK-mediated phosphorylation of PEA15 in inhibiting ERK activity by reducing the formation of MEK-ERK complex. Consequently, cells with higher AMPK activity have lower phospho-ERK, and this heterogeneity is reflected in vivo. Exploring downstream, we demonstrate that ERK inhibition leads to upregulation of TFEB, a major regulator of lysosome biogenesis and autophagy. Overexpression of TFEB not only rescues the defect in autophagy flux, but also re-inforces AMPK signaling, thus revealing a positive feedback loop between AMPK and TFEB. Mathematical modelling of this loop shows that it can give rise to two distinct cellular phenotypes – pAMPKhigh/TFEBhigh/pERKlow and pAMPKlow/TFEBlow/pERKhigh – and phenotype switching, thus offering a mechanistic basis for our observations for non-genetic heterogeneity in anoikis adaptation. Significantly, we observed these heterogeneous cell states in patient-derived circulating tumor cells also. Thus, our work unravels a novel feedback loop that can generate non-genetic heterogeneity within matrix-detached cancer cells; targeting such loops may offer novel therapeutic approaches for restricting metastasis and improving therapeutic efficacy.
Chromosome-length haplotigs for yak and cattle from trio binning assembly of an F1 hybrid
Authors: Rice Edward S. , Koren Sergey , Rhie Arang , Heaton Michael P. , Kalbfleisch Theodore S. , Hardy Timothy , Hackett Peter H. , Bickhart Derek M. , Rosen Benjamin D. , Ley Brian Vander , Maurer Nicholas W. , Green Richard E. , Phillippy Adam M. , Petersen Jessica L. , Smith Timothy P. L. 
Published: August 2019

AbstractBackgroundAssemblies of diploid genomes are generally unphased, pseudo-haploid representations that do not correctly reconstruct the two parental haplotypes present in the individual sequenced. Instead, the assembly alternates between parental haplotypes and may contain duplications in regions where the parental haplotypes are sufficiently different. Trio binning is an approach to genome assembly that uses short reads from both parents to classify long reads from the offspring according to maternal or paternal haplotype origin, and is thus helped rather than impeded by heterozygosity. Using this approach, it is possible to derive two assemblies from an individual, accurately representing both parental contributions in their entirety with higher continuity and accuracy than is possible with other methods.ResultsWe used trio binning to assemble reference genomes for two species from a single individual using an interspecies cross of yak (Bos grunniens) and cattle (Bos taurus). The high heterozygosity inherent to interspecies hybrids allowed us to confidently assign >99% of long reads from the F1 offspring to parental bins using unique k-mers from parental short reads. Both the maternal (yak) and paternal (cattle) assemblies contain over one third of the acrocentric chromosomes, including the two largest chromosomes, in single haplotigs.ConclusionsThese haplotigs are the first vertebrate chromosome arms to be assembled gap-free and fully phased, and the first time assemblies for two species have been created from a single individual. Both assemblies are the most continuous currently available for non-model vertebrates.
5-Chloro-2-ferrocenylbenzo[d]oxazole
Authors: Sánchez-García Jessica J. , Flores-Alamo Marcos , Martínez-Falcón Ezequiel , Klimova Elena I. 
Published: August 2019

The asymmetric unit of the title compound, [Fe(C5H5)(C12H7ClNO)], consists of one ferrocenyl group bonded to chlorobenzo[d]oxazole. The conformation of the ferrocenyl moiety is slightly away from eclipsed. The bond angles between the 5-chloro-benzoxazole and ferrocenyl fragments are N—C—C = 127.4 (7)° and O—C—C = 116.8 (7)°. The benzo[d]oxazole ring is planar (r.m.s. deviation = 0.0042 Å) and makes an angle of 11.3 (4)° with the cyclopentadienyl ring attached to it. The crystal packing is characterized by intermolecular π–π contacts, resulting in chain formation along the b-axis direction. The centroid-to-centroid distance between the six- and five-membered rings is 3.650 (5) Å. Together with a C—H...π interaction, these intermolecular contacts form laminar arrays along the ac plane.
Valuation of an innovation strategy in the diversification of products in the agricultural auto parts sector
Authors: Conceição Elimar Veloso , Sanches Adhemar , Santos David Ferreira Lopes 
Published: August 2019

PurposeThe purpose of this paper is to value an innovation project derived from a product diversification strategy in the agricultural auto parts sector, considering uncertainties and flexibility as sources of value for the project.Design/methodology/approachA case study project is presented and valued using real options, with the possibility of including new information modelled by Bayes’ theorem, which enables the fitting of the probabilities of the project for the purpose of valuation through the decision tree method.FindingsThe results indicate the effect of new information and provide implications for value creation, demonstrating the need for a more profound and systematic approach to the use of investment strategies considering factors endogenous and exogenous to a firm that can and should be considered in the decision-making process.Practical implicationsThis study contributes to an understanding of the relationship of strategy and innovation through product diversification with value creation and serves as a guide for controlling the possibility of investments in diversified companies and agribusiness using the methodology discussed in this paper.Originality/valueValuing the inclusion of new information through Bayesian inference in the analysis of investments is a methodological feature that has received minimal attention in the literature. Therefore, the use of Bayesian theory for the real options model applied to agribusiness is the main innovation of this study to demonstrate new ways of modelling uncertainty in addition to stochastic processes.
The moderating impact of social risk, shame, and guilt on purchase intentions of premium private labels at food discounters
Authors: Loebnitz Natascha , Zielke Stephan , Grunert Klaus G. 
Published: August 2019

Purpose
The purpose of this paper is to investigate situational factors (i.e. social risk) and negative emotions (e.g. shame and guilt) on consumers’ purchase intentions for premium private labels (PPLs) vs national brands (NBs) at discounter (Lidl) in the UK, and the underlying process of this effect.

Design/methodology/approach
The authors conduct a 2 (social risk) × 2 (brand type) between-subjects design experiment employing a Qualtrics online panel in the UK.

Findings
The study shows that NBs still have the edge over PPLs when consumers shop for socially risky situations, which is due to higher product expectations of NBs, and a moderated mediation shows that this effect is more pronounced among consumers that feel negative emotions when shopping at Lidl.

Research limitations/implications
This study included leading NBs, which differ in terms of price compared to selected PPLs. Researchers should include pricing information as an additional factor and investigate Lidl’s options to deal with negative emotions in the online setting.

Practical implications
The results help brand managers to understand consumer reactions toward PPLs vs NBs at the discounter in UK.

Originality/value
NBs have recently joint rather than fight discounters’ product assortment, this study contributes to understand the moderating impact of negative emotions and product expectations as the driving force in consumers’ purchasing decision.