bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of host effects on ectomycorrhizal fungal community compositions in a forest landscape in northern Japan
Authors: Matsuoka Shunsuke , Sugiyama Yoriko , Tateno Ryunosuke , Imamura Shihomi , Kawaguchi Eri , Osono Takashi 
Published: November 2019

AbstractCommunity compositions of ectomycorrhizal (ECM) fungi are similar within the same host taxa. However, careful interpretation is required to determine whether the combination of ECM fungi and plants is explained by the host preference of ECM fungi or by the influence of neighboring conspecific and/or heterospecific hosts. In the present study, we aimed to evaluate the effects of host species on the ECM community compositions in a forest landscape (~ 10 km) where monodominant forest stands of six ECM host species belonging to three families were patchily distributed. The ECM communities were identified with DNA metabarcoding. A total of 180 ECM operational taxonomic units (OTUs) were detected. The ECM community compositions were primarily structured by host species and families, regardless of the soil environments and spatial arrangements of the sampling plots. In addition, 38 ECM OTUs were detected from particular host tree species. Furthermore, the neighboring plots harbored similar fungal compositions, although the host species were different. The relative effect of the spatial factors on the ECM compositions was weaker than that of host species. Our results suggest that the host preference of ECM fungi is a primary determinant of ECM fungal compositions in the forest landscape.
Exposure to hypomethylating agent 5-aza-2’-deoxycytidine (decitabine) causes rapid, severe DNA damage, telomere elongation and mitotic dysfunction in human WIL2-NS cells
Authors: Bull Caroline , Mayrhofer Graham , Fenech Michael 
Published: November 2019

AbstractBackground5-aza-2’-deoxycytidine (5azadC, decitabine) is a DNA hypomethylating agent used in the treatment of myelodysplastic syndromes. Due to cytotoxic side effects dose optimization is essential. This study defines and quantifies the effects of 5azadC on chromosomal stability and telomere length, at clinically relevant dosages.MethodsHuman WIL2-NS cells were maintained in complete medium containing 0, 0.2 or 1.0μM 5azadC for four days, and analysed daily for telomere length (flow cytometry), chromosomal stability (cytokinesis-block micronucleus cytome (CBMN-cyt) assay), and global methylation (%5me-C).ResultsDNA methylation decreased significantly in 1.0 μM 5azadC, relative to control (p<0.0001). Exposure to 1.0μM 5azadC resulted in 170% increase in telomere length (p<0.0001), in parallel with rapid increase in biomarkers of DNA damage; (micronuclei (MN, 6-fold increase), nucleoplasmic bridges (NPB, a 12-fold increase), and nuclear buds (NBud, a 13-fold increase) (all p<0.0001). Fused nuclei (FUS), indicative of mitotic dysfunction, showed a 5- and 13-fold increase in the 0.2μM and 1.0μM conditions, respectively (p = 0.001) after 4 days.ConclusionsThese data show that (i) clinically relevant concentrations of 5azadC are highly genotoxic; (ii) hypomethylation was associated with increased TL and DNA damage; and (iii) longer TL was associated with chromosomal instability. These findings suggest that lower doses of 5azdC may be effective as a hypomethylating agent, while potentially reducing DNA damage and risk for secondary disease.
Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity
Authors: Schipper Lidewij , van Heijningen Steffen , Karapetsas Giorgio , van der Beek Eline M. , van Dijk Gertjan 
Published: November 2019

AbstractIndividual housing from weaning onwards resulted in reduced growth rate during adolescence in male C57Bl/6J mice that were housed individually, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice. Body weight gain of individually housed animals exceeded that of socially housed mice during adulthood, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition. This study shows that post-weaning individual housing of male mice results in impaired adolescent growth and higher susceptibility to obesity in adulthood. Mice are widely used to study obesity and cardiometabolic comorbidities. For (metabolic) research models using mice, (social) housing practices should be carefully considered and regarded as a potential confounder due to their modulating effect on metabolic health outcomes.
Protein Crowding Mediates Membrane Remodeling in Upstream ESCRT-induced Formation of Intraluminal Vesicles
Authors: Liese Susanne , Wenzel Eva Maria , Kjos Ingrid , Rojas Molina Rossana V. , Schultz Sebastian W. , Brech Andreas , Stenmark Harald , Raiborg Camilla , Carlson Andreas 
Published: November 2019

AbstractAs part of the lysosomal degradation pathway, the endosomal sorting complexes required for transport (ESCRT-0-III/VPS4) sequester receptors at the endosome and simultaneously deform the membrane to generate intraluminal vesicles (ILVs). Whereas ESCRT-III/VPS4 have an established function in ILV formation, the role of upstream ESCRTs (0-II) in membrane shape remodeling is not understood. Combining experimental measurements and electron microscopy analysis of ESCRT-III depleted cells with a mathematical model, we show that upstream ESCRT-induced alteration of the Gaussian bending rigidity and their crowding on the membrane induces membrane deformation and facilitates ILV formation: upstream ESCRT-driven budding does not require ATP consumption as only a small energy barrier needs to be overcome. Our model predicts that ESCRTs do not become part of the ILV, but localize with a high density at the membrane neck, where the steep decline in the Gaussian curvature likely triggers ESCRT-III/VPS4 assembly to enable neck constriction and scission.Significance StatementIntraluminal vesicle (ILV) formation plays a crucial role in the attenuation of growth factor receptor signaling, which is mediated by the endosomal sorting complex required for transport (ESCRT-0-III/VPS4). The general dogma has been that the upstream ESCRTs (0-II) sequester the receptors at the surface of endosomes and the downstream ESCRTs (III/VPS4) remodel the endosome membrane leading to the abscission and formation of receptor-containing ILVs. We now show that the upstream ESCRTs not only sequester cargo, but in addition play an essential role for the initiation of membrane shape remodeling in ILV budding. Through a combination of mathematical modeling and experimental measurements we show that upstream ESCRTs facilitate ILV budding by crowding with a high density in the membrane neck region.
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
Authors: Akçimen Fulya , Martins Sandra , Liao Calwing , Bourassa Cynthia V. , Catoire Hélène , Nicholson Garth A. , Riess Olaf , Raposo Mafalda , França Marcondes C. , Vasconcelos João , Lima Manuela , Lopes-Cendes Iscia , Saraiva-Pereira Maria Luiza , Jardim Laura B. , Sequeiros Jorge , Dion Patrick A. , Rouleau Guy A. 
Published: November 2019

AbstractMachado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10−5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.
Evolution toward maximum transport capacity of the Ttg2 ABC system inPseudomonas aeruginosa
Authors: Yero Daniel , Costenaro Lionel , Conchillo-Solé Oscar , Díaz-Lobo Mireia , Mayo Adrià , Ferrer-Navarro Mario , Vilaseca Marta , Gibert Isidre , Daura Xavier 
Published: November 2019

AbstractInPseudomonas aeruginosa, Ttg2D is the soluble periplasmic phospholipid-binding component of an ABC transport system thought to be involved in maintaining the asymmetry of the outer membrane. The crystallographic structure of Ttg2D at 2.5Å resolution reveals that this protein can bind two diacyl phospholipids. Native and denaturing mass spectrometry experiments confirm that Ttg2D binds two phospholipid molecules, which may have different head groups. Analysis of the available structures of Ttg2D orthologs allowed us to classify this protein family as a novel substrate-binding protein fold and to venture the evolutionary events that differentiated the orthologs binding one or two phospholipids. In addition, gene knockout experiments inP. aeruginosaPAO1 and multidrug-resistant strains show that disruption of this system leads to outer membrane permeabilization. This demonstrates the role of this system in low-level intrinsic resistance against certain antibiotics that use a lipid-mediated pathway to permeate through membranes.
The impact of reporter kinetics on the interpretation of data gathered with fluorescent reporters
Authors: Sabatini Bernardo L. 
Published: November 2019

AbstractFluorescent reporters of biological functions are used to monitor biochemical events and signals in cells and tissue. For neurobiology, these have been particularly useful for monitoring signals in the brains of behaving animals. In order to enhance signal-to-noise, fluorescent reporters typically have kinetics that are slower than that of the underlying biological process. This low-pass filtering by the reporter renders the fluorescence transient a leaking integrated version of the biological signal. Here I discuss the effects that low-pass filtering, or more precisely of integrating by convolving with an exponentially decaying kernel, has on the interpretation of the relationship between the reporter fluorescence transient and the events that underlie it. Unfortunately, when the biological events being monitored are impulse-like, such as the firing of an action potential or the release of neurotransmitter, filtering greatly reduces the maximum correlation coefficient that can be found between the events and the fluorescence signal. This can erroneously support the conclusion that the fluorescence transient and the biological signal that it reports are only weakly related. Furthermore, when examining the encoding of behavioral state variables by nervous system, filtering by the reporter kinetics will favor the interpretation that fluorescence transients encode integrals of measured variables as opposed to the variables themselves. For these reasons, it is necessary to take into account the filtering effects of the indicator by deconvolving with the convolution kernel and recovering the underlying biological events before making conclusions about what is encoded in the signals emitted by fluorescent reporters.
Hopper: A Mathematically Optimal Algorithm for Sketching Biological Data
Authors: DeMeo Benjamin , Berger Bonnie 
Published: November 2019

AbstractSingle-cell RNA-sequencing (scRNA-seq) has grown massively in scale since its inception, presenting substantial analytic and computational challenges. Even simple downstream analyses, such as dimensionality reduction and clustering, require days of runtime and hundreds of gigabytes of memory for today’s largest datasets. In addition, current methods often favor common cell types, and miss salient biological features captured by small cell populations. Here we present Hopper, a single-cell toolkit that both speeds up the analysis of single-cell datasets and highlights their transcriptional diversity by intelligent subsampling, or sketching. Hopper realizes the optimal polynomial-time approximation of the Hausdorff distance between the full and downsampled dataset, ensuring that each cell is well-represented by some cell in the sample. Unlike prior sketching methods, Hopper adds points iteratively and allows for additional sampling from regions of interest, enabling fast and targeted multi-resolution analyses. In a dataset of over 1.3 million mouse brain cells, we detect a cluster of just 64 macrophages expressing inflammatory tissues (0.004% of the full dataset) from a Hopper sketch containing just 5,000 cells, and several other small but biologically interesting immune cell populations invisible to analysis of the full data. On an even larger dataset consisting of ~2 million developing mouse organ cells, we show even representation of important cell types in small sketch sizes, in contrast with prior sketching methods. By condensing transcriptional information encoded in large datasets, Hopper grants the individual user with a laptop the same analytic capabilities as large consortium.
Assembly of theDrosophilamushroom body circuit and its regulation by Semaphorin 1a
Authors: Lin Chen-Han , Lin Suewei 
Published: November 2019

SummaryTheDrosophilamushroom body (MB) is a learning and memory center in the fly brain. It is the most extensively studied brain structure in insects, but we know little about the molecular and cellular mechanisms underlying assembly of its neural circuit. The MB is composed of around 2200 intrinsic Kenyon cells (KCs), whose axons are bundled to form multiple MB lobes. The MB lobes are innervated by a large number of extrinsic neurons. Twenty types of dopaminergic neurons (DANs) and 21 types of MB output neurons (MBONs) have been identified. Each type of these extrinsic neurons innervates specific compartments or zones in the MB lobes. Here, we characterize the assembly of the MB circuit and reveal several intriguing features of the process. The DANs and MBONs innervate zones in the MB vertical lobes in specific sequential orders. Innervation of DAN axons in some zones precedes that of MBON dendrites, andvice versain other zones. MBON and DAN innervations are largely independent of each other. Removing one type of extrinsic neuron during early development has a limited effect on the MB lobe innervations of the other type of extrinsic neurons. However, KC axons are essential for zonal elaboration of DAN axons and MBON dendrites. Competition also exists between MB zones for some MBONs, so when the cognate zones for these MBONs are missing, their dendrites are misdirected to other zones. Finally, we identify Semaphorin 1a (Sema1a) as a crucial guidance molecule for MBON dendrites to innervate specific MB lobe zones. Ectopic expression of Sema1a in some DANs is sufficient to re-direct their dendrites to those zones, demonstrating a potential to rewire the MB circuit. Taken together, our work provides an initial characterization of the cellular and molecular mechanisms underlying MB circuit assembly.
DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation
Authors: Pernaute Barbara , Sánchez Nieto Juan Miguel , Pérez-Montero Salvador , di Gregorio Aida , Lima Ana , Lawlor Katerina , Bowling Sarah , Liccardi Gianmaria , Tomás Alejandra , Meier Pascal , Rutter Guy A. , Barbaric Ivana , Rodríguez Tristan A. 
Published: November 2019

AbstractThe changes that drive differentiation create a large potential for the emergence of abnormal cells that need to be removed before they contribute to further development or the germline. This removal is in part achieved by cells becoming hypersensitive to death upon exit of naïve pluripotency. What causes this change in apoptotic response is unknown. Here we identify that it is controlled by the regulator of mitochondrial dynamics DRP1. We show that in mouse, naïve pluripotent cells have fragmented mitochondria due to high DRP1-mediated fission, but upon differentiation, DRP1 activity decreases, inducing mitochondria to fuse and form complex networks. We demonstrate that this decrease in DRP1 activity lowers the apoptotic threshold, as mutation of DRP1 increases the sensitivity to cell death and its over-expression protects against apoptosis. Together, our findings highlight how regulation of mitochondrial dynamics allows cells to adapt their apoptotic response to the changing environment of differentiation.
The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double strand break repair
Authors: Huang Tao , Yuan Shenli , Gao Lei , Li Mengjing , Yu Xiaochen , Zhang Jianhong , Yin Yingying , Liu Chao , Zhang Chuanxin , Lu Gang , Li Wei , Liu Jiang , Chen Zi-Jiang , Liu Hongbin 
Published: November 2019

ABSTRACTThe histone modification writer PRDM9 has been shown to deposit H3K4me3 and H3K36me3 at future double-strand break (DSB) sites during the very early stages of meiosis, but the reader of these marks remains unclear. Here, we demonstrate that ZCWPW1 is an H3K4me3 reader that is required for DSB repair and synapsis in mouse testes. We generated H3K4me3 reader-dead ZCWPW1 mutant mice and found that their spermatocytes were arrested at the pachytene-like stage, which phenocopies theZcwpw1knock–out mice. Based on various ChIP-seq and immunofluorescence analyses using several mutants, we found that ZCWPW1’s occupancy on chromatin is strongly promoted by the histone-modification activity of PRDM9. ZCWPW1 localizes to DMC1-labelled hotspots in a largely PRDM9-dependent manner, where it facilitates completion of synapsis by mediating the DSB repair process. In sum, our study demonstrates the function of ZCWPW1 that acts as part of the selection system for epigenetics-based recombination hotspots in mammals.
From transactions to cooperation
Authors: Casalegno Cecilia , Migheli Matteo , Bonfanti Angelo , Maple Peter 
Published: November 2019

PurposeThe purpose of this paper is to add understanding to whether the supply chain (SC) of ancient grains, einkorn in particular, may activate the virtuous mechanisms that enable pursuing a new equilibrium based on relationships and joint interests.Design/methodology/approachThis study adopts the single case study as a methodological approach. More precisely, it focusses on the SC of ancient grains in Piedmont (Italy) examining in detail Mulino Marino. Interviews with the management of this single player and to some farmers’ local associations were carried out.FindingsThe einkorn SC in Piedmont Region is an interesting case of short, local and direct SC because it aims at delivering a product that is more sustainable in terms of production, nutritional values and properties. In addition, this study confirms previous studies according to which for an effective supply chain management (SCM) it is important to implement the following conditions: the right equilibrium among SC players’ physiologically conflicting interests, players’ integration and transparent information among all the SC stakeholders, including final consumers.Practical implicationsThe study offers implications for food managers involved in the (short) SCM.Originality/valueElements of originality can be identified in this research to the extension of studies on SCM in the ancient grains industry.
Heritage retrofit and cultural empathy; a discussion of challenges regarding the energy performance of historic UK timber-framed dwellings
Authors: Whitman Christopher J. , Prizeman Oriel , Walker Pete , Gwilliam Julie Amanda 
Published: November 2019

Purpose
The energy retrofit of the existing building stock, and specifically the thermal upgrading of the buildings’ envelopes, has been identified as a key action for both the decarbonisation of the built environment and the reduction in fuel poverty. When considering the energy retrofit of heritage buildings it is, however, important to recognise both the technical issues that this entails and the potential impact on their cultural value and the emotional responses to it. The purpose of this paper is to focus on the thermal upgrading of historic timber-framed buildings in the UK.

Design/methodology/approach
The paper begins by exploring the cultural significance of this form of building construction, before examining three case studies using both quantitative and qualitative methodologies.

Findings
The results show that whilst the application of energy retrofit actions to this emblematic typology may have limited success, the emotional connection of the buildings’ occupants often results in the work resulting in higher user satisfaction than would otherwise be expected.

Research limitations/implications
Although limited in number, the three case studies provide an insight into the complex issues surrounding the low energy retrofit of historic timber-framed buildings. Further research into this area is encouraged.

Practical implications
The paper contains the monitoring of specific retrofit details, the results of which should inform future projects.

Social implications
The review of the cultural significance of historic timber-frame buildings in the UK underlines the importance of the conservation and continuing survival of these buildings.

Originality/value
Previous heritage retrofit research in the UK has focussed on solid wall construction with little investigation into the issues surrounding the retrofit of historic timber-frame buildings. This paper explores this previously under-researched area. Additionally, this paper begins to explore the possible links between occupants’ emotional connection to historic buildings and their perceived levels of comfort.
Entrepreneurs’ attitudes toward seasonality in the tourism sector
Authors: Martin Martin Jose Maria , Guaita Martinez Jose Manuel 
Published: November 2019

PurposeThe purpose of this paper is to investigate the factors that condition decision making by entrepreneurs in the tourism sector. Specifically, the authors consider whether the decisions related to seasonal closure are conditioned by non-economic factors related to quality of life.Design/methodology/approachThe study uses data from a survey of entrepreneurs in two highly seasonal tourist locations in Spain: one coastal destination and one mountain destination. The information provided by the survey was used to determine the factors that condition the decision to close for part of the year and to analyze the way in which entrepreneurs evaluate the costs and benefits associated with the period of closure.FindingsThe results show that entrepreneurs acknowledge the cost of shutting down during the off-peak season. However, although they recognize this cost, other elements are important in their decision making such as the quality of life of the entrepreneur, the presence of a more profitable secondary activity in a different destination and the tenure regime of the business. Entrepreneurs attach great importance to factors that justify the closure of establishments for several months a year. This, in turn, means that public policies designed to reduce the intensity of seasonality lose effectiveness.Originality/valueThis paper sheds light on whether there are underlying non-economic motives that lead to a shutdown during the off-peak season. There are no previous studies that analyze the influence of the decision to close and which consider aspects related to the quality of life of entrepreneurs. Therefore, the study presents the first analysis of entrepreneurs’ assessments of the costs and benefits of a seasonal resting period.