bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic Genome Assembly from Low Coverage Illumina and Nanopore Data
Authors: Gatter Thomas , von Löhneysen Sarah , Drozdova Polina , Hartmann Tom , Stadler Peter F. 
Published: February 2020

AbstractWe describe a new approach to assemble genomes from a combination of low-coverage short and long reads.LazyBastardstarts from a bipartite overlap graph between long reads and restrictively filtered short-read unitigs, which are then reduced to a long-read overlap graphG. Edges are removed fromGto obtain first a consistent orientation and then a DAG. Using heuristics based on properties of proper interval graphs, contigs are extracted as maximum weight paths. These are translated into genomic sequence only in the final step. A prototype implementation ofLazyBastard, entirely written in python, not only yields significantly more accurate assemblies of the yeast and fruit fly genomes compared to state-of-the-art pipelines but also requires much less computational effort.FundingRSF / Helmholtz Association 18-44-06201; Deutsche Academische Austauschdienst, DFG STA 850/19-2 within SPP 1738; German Federal Ministery of Education an Research 031A538A, de.NBI-RBC
Optimal microbial pathway variants can be determined by large-scale bioenergetic evaluation in syntrophic propionate oxidation
Authors: Patón Mauricio , Hernández Héctor H. , Rodríguez Jorge 
Published: February 2020

AbstractThe complete understanding of microbial propionate oxidation in syntrophy with hydrogenotrophic methanogenesis remains elusive due to uncertainties in pathways and mechanisms for interspecies electron transfer (IET). Possible pathway variants differ in their intermediate metabolites, on which electron carriers are involved and in which steps are coupled to (and to how many) proton translocations. In this work, a systematic methodology was developed (based on sound biochemical, physiological and bioenergetic principles) to evaluate the feasibility and net ATP yield of large sets of pathway variants under different physiological and environmental conditions. A pathway variant is deemed feasible under given conditions only if all pathway reaction steps have non-positive Gibbs energy change and if all the metabolite concentrations remain within an acceptable physiological range (10−6to 10−2M). Several million combinations of pathway variants and parameters/conditions were evaluated for propionate oxidation, providing an unprecedented mechanistic insight into its biochemical and bioenergetic landscape. Propionate oxidation via lactate appeared as the most ATP yielding pathway under most of the conditions evaluated. Results under typical methanogenic conditions indicate that syntrophic propionate oxidation can sustain life only at hydrogen partial pressures within the range of 1.2 to 4 Pa. These extremely low concentrations constitute a kinetic impossibility and strongly suggest for IET mechanisms other than dissolved hydrogen.ImportanceIn this work an original methodology was developed that quantifies the bioenergetically and physiologically feasible net ATP yields for large numbers of microbial metabolic pathways and their variants under different conditions. This ensures global optimality in finding the pathway variant(s) leading to the highest ATP yield. The methodology is especially relevant to hypothesise which microbial pathway variants are most likely to prevail in microbial ecosystems under high selective pressure for efficient metabolic energy conservation.Syntrophic microbial oxidation of propionate to acetate has extremely low energy available and requires very high metabolic efficiency in order to sustain life. Our results bring mechanistic insights into the optimum pathway variants and the impact of environmental conditions on the ATP yields and other metabolic bottlenecks. Additionally, our results conclude that IET mechanisms other than hydrogen must exist to simultaneously sustain the growth of both propionate oxidisers and hydrogenotrophic methanogens.
Linear Embodied Saliency: a Model of Full-Body Kinematics-based Visual Attention
Authors: Abbott William W. , Harston J. Alex , Faisal A. Aldo 
Published: February 2020

AbstractGaze behaviour and motor actions are fundamentally interlinked in both a spatial and temporal manner. However, the vast majority of gaze behaviour research has focused to date on reductionist head-fixed screen viewing experiments and ignored the motor aspect of visuomotor behaviour, thereby neglecting a critical component of the perception-action loop. We address this with an experimental design to capture, rather than constrain, the full range of simultaneous gaze and motor behaviour in a range of natural daily life tasks. Through building autoregressive models and applying these to our novel datasets we find that beyond simple static regions of interest, we can predict visual attention shifts from freely-moving first person body kinematics, through explaining gaze dynamics in the context of body dynamics, on the timescale of freely moving interactive behaviour in individuals, expanding our understanding of natural visuomotor behaviour.
A non-invasive eDNA tool for detecting sea lamprey larvae in river sediments: analytical validation and field testing in a low abundance ecosystem
Authors: Baltazar-Soares Miguel , Pinder Adrian C. , Harrison Andrew J. , Oliver Will , Picken Jessica , Britton J. Robert , Andreou Demetra 
Published: February 2020

AbstractAnthropogenic activities are increasingly threatening aquatic biodiversity, especially anadromous species. Monitoring and conservation measures are thus required to protect, maintain, and restore imperilled populations. While many species can be surveyed using traditional capture and visual census techniques, species that use riverine habitats in a less conspicuous manner, such as sea lampreyPetromyzon marinus, can be more challenging to monitor. Sea lamprey larvae (ammocoetes) can spend several years in freshwater burrowed within soft sediments, inhibiting their detection and assessment. Here we present an environmental DNA (eDNA) assay to detect ammocoetes burrowed in the sediment. We performed a battery of tests that ensured both species-specificity of the assay as well as the capacity to detect ammocoetes when abundances are low. Experiments on burrowing activity suggested that most of the DNA released into the sediment occurs during burrowing. Overall, we demonstrated this new molecular-based tool is an efficient and effective complement to traditional monitoring activities targeting larval stages of sea lampreys.
Intra-articular AAV-PHP.S mediated chemogenetic targeting of knee-innervating dorsal root ganglion neurons alleviates inflammatory pain in mice
Authors: Chakrabarti Sampurna , Pattison Luke A. , Doleschall Balint , Rickman Rebecca H. , Blake Helen , Callejo Gerard , Heppenstall Paul A. , Smith Ewan St. John 
Published: February 2020

AbstractObjectiveJoint pain is the major clinical symptom of arthritis that affects millions of people. Controlling the excitability of knee-innervating dorsal root ganglion (DRG) neurons (knee neurons) could potentially provide pain relief. Therefore, our objective was to evaluate whether the newly engineered adeno-associated virus (AAV) serotype, AAV-PHP.S, can deliver functional artificial receptors to control knee neuron excitability following intra-articular knee injection.MethodsAAV-PHP.S virus packaged with dTomato fluorescent protein and either excitatory (Gq) or inhibitory (Gi) designer receptors activated by designer drugs (DREADDs) was injected into the knee joint of adult mice. Labelling of DRG neurons by AAV-PHP.S from the knee was evaluated using immunohistochemistry. Functionality of Gq- and Gi-DREADDs was evaluated using whole-cell patch clamp electrophysiology on acutely cultured DRG neurons. Pain behavior in mice was assessed using a digging assay, dynamic weight bearing and rotarod, before and after intra-peritoneal administration of the DREADD activator, Compound 21.ResultsWe show that AAV-PHP.S can deliver functional genes into the DRG neurons when injected into the knee joint in a similar manner to the well-established retrograde tracer, fast blue. Short-term activation of AAV-PHP.S delivered Gq-DREADD increases excitability of knee neurons in vitro, without inducing overt pain in mice when activated in vivo. By contrast, in vivo Gi-DREADD activation alleviated complete Freund’s adjuvant mediated knee inflammation-induced deficits in digging behavior, with a concomitant decrease in knee neuron excitability observed in vitro.ConclusionsWe describe an AAV-mediated chemogenetic approach to specifically control joint pain, which may be utilized in translational arthritic pain research.
Domestication reprogrammed the budding yeast life cycle
Authors: De Chiara Matteo , Barré Benjamin , Persson Karl , Chioma Amadi Onyetuga , Irizar Agurtzane , Schacherer Joseph , Warringer Jonas , Liti Gianni 
Published: February 2020

AbstractDomestication of plants and animals is the foundation for feeding the world population. We report that domestication of the model yeastS. cerevisiaereprogrammed its life cycle entirely. We tracked growth, gamete formation and cell survival across many environments for nearly 1000 genome sequenced isolates and found a remarkable dichotomy between domesticated and wild yeasts. Wild yeasts near uniformly trigger meiosis and sporulate when encountering nutrient depletions, whereas domestication relaxed selection on sexual reproduction and favoured survival as quiescent cells. Domestication also systematically enhanced fermentative over respiratory traits while decreasing stress tolerance. We show that this yeast domestication syndrome was driven by aneuploidies and gene function losses that emerged independently in multiple domesticated lineages during the specie’s recent evolutionary history. We found domestication to be the most dramatic event in budding yeast evolution, raising questions on how much domestication has distorted our understanding of this key model species.
A novel role for cortical acetylcholine in object memory updating
Authors: Jardine Kristen H. , Wideman Cassidy E. , MacGregor Chelsea , Sgarbossa Cassandra , Orr Dean , Mitchnick Krista A. , Winters Boyer D. 
Published: February 2020

AbstractReactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). We have previously implicated cholinergic transmission in object memory destabilization. Here we present a novel rodent paradigm developed to assess the role of this cholinergic mechanism in qualitative memory updating. The post-reactivation object memory modification (PROMM) task exposes rats to contextual information following object memory reactivation. Subsequent object exploratory performance suggests that the contextual information is integrated with the original memory in a reactivation- and time-dependent manner. This effect is blocked by interference with M1muscarinic receptors and several downstream signals in perirhinal cortex. These findings therefore demonstrate a hitherto unacknowledged cognitive function for acetylcholine with important implications for understanding the dynamic nature of long-term memory storage in the normal and aging brain.
Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes
Authors: Wang Jinli , Bonacquisti Emily , Nguyen J. 
Published: February 2020

AbstractA limitation to using exosomes to their fullest potential is their limited secretion from cells, a major bottleneck to efficient exosome production and application. This is especially true for mesenchymal stem cell (MSCs), which can self-renew but have limited expansion capacity, undergoing senescence after only a few passages, with exosomes derived from senescent stem cells showing impaired regenerative capacity compared to young cells. Here we examined the effects of small molecule modulators capable of enhancing exosome secretion from MSCs. Treatment of MSCs with a combination of methyldopamine and norepinephrine robustly increased exosome production by three-fold without altering the ability of the MSC exosomes to induce angiogenesis, polarize macrophages to the anti-inflammatory phenotype, or inhibit fibrosis. These small molecule modulators provide a promising means to increase exosome production by MSCs.
Antisense ncRNAs during early vertebrate development are divided in groups with distinct features
Authors: Pillay Sanjana , Takahashi Hazuki , Carninci Piero , Kanhere Aditi 
Published: February 2020

ABSTRACTLong non-coding RNAs or lncRNAs are a broad class of non-protein coding RNAs that are >200nucleotides in length. A number of lncRNAs are shown to play an important role in gene expression regulation. LncRNAs antisense to a protein-coding gene can act either as positive or negative regulators of overlapping protein-coding mRNAs. Almost 50% of lncRNAs present during development of vertebrates such as zebrafish are of antisense lncRNA class. However, their role in gene expression regulation during development remains enigmatic. To understand the role of antisense lncRNAs in early vertebrate development, we took a computational biology approach to analyze existing as well as novel dataset. Our analysis of RNA sequencing data from zebrafish development indicates that antisense RNAs can be divided into two major classes based on their positive or negative co-expression patterns to the sense protein-coding genes. The ones with negative co-expression patterns or group-1 are maternal antisense lncRNAs that overlap mainly developmental genes. Group-2 with positive expression pattern overlap mainly house-keeping genes. Group-1 antisense lncRNAs are longer and more stable as compared to antisense lncRNAs in group-2. In addition, to answer if antisense RNAs in the two groups are differently localized in cell compartments, we deep-sequenced RNA from cytoplasmic and nuclear compartments during early developmental stages. The analysis of these compartment specific datasets revealed group-1 lncRNAs are cytosolic. Based on the cytosolic nature of group-1 RNAs and their higher complementarity to the overlapping developmental mRNAs, we speculate that the group-1 RNAs might function similar to microRNAs in silencing spurious expression of developmental genes. Group-1 and group-2 RNAs are also distinct in terms of their genomic configuration, conservation, length and transcriptional regulation. These results are not only important in understanding the role of antisense RNAs in development but also for predicting the nature of association between antisense lncRNA and overlapping protein-coding genes.
Domestication of the emblematic white cheese-making fungusPenicillium camembertiand its diversification into two varieties
Authors: Ropars Jeanne , Didiot Estelle , Rodríguez de la Vega Ricardo C. , Bennetot Bastien , Coton Monika , Poirier Elisabeth , Coton Emmanuel , Snirc Alodie , Le Prieur Stéphanie , Giraud Tatiana 
Published: February 2020

SummaryDomestication involves recent adaptation under strong human selection and rapid diversification, and therefore constitutes a good model for studies of these processes. We studied the domestication of the emblematic white moldPenicillium camemberti, used for the maturation of soft cheeses, such as Camembert and Brie, about which surprisingly little was known, despite its economic and cultural importance. Whole genome-based analyses of genetic relationships and diversity revealed that an ancient domestication event led to the emergence of the gray-greenP. biformemold used in cheese-making, by divergence from the blue-green wildP. fuscoglaucumfungus. Another much more recent domestication event led to the generation of theP. camemberticlonal lineage as a sister group toP. biforme. Penicillium biformedisplayed signs of phenotypic adaptation to cheese-making relative toP. fuscoglaucum, in terms of whiter color, faster growth on cheese medium under cave conditions, lower levels of toxin production and greater ability to prevent the growth of other fungi. TheP. camembertilineage displayed even stronger signs of domestication for all these phenotypic features. We also identified two differentiatedP. camembertivarieties, apparently associated with different kinds of cheeses, and with contrasted phenotypic features in terms of color, growth, toxin production and competitive ability. We have, thus, identified footprints of domestication in these fungi, with genetic differentiation between cheese and wild populations, bottlenecks and specific phenotypic traits beneficial for cheese-making. This study has not only fundamental implications for our understanding of domestication but can also have important impacts on cheese-making.
A pyro-phosphodegron controls MYC polyubiquitination to regulate cell survival
Authors: Lolla Padmavathi , Shah Akruti , Unnikannan C.P. , Oddi Vineesha , Bhandari Rashna 
Published: February 2020

ABSTRACTThe transcription factor MYC regulates cell survival and growth, and its level is tightly controlled in normal cells. Here, we report that serine pyrophosphorylation – an enigmatic posttranslational modification triggered by inositol pyrophosphate signaling molecules – controls MYC levels via regulated protein degradation. We find that endogenous MYC is stabilized and less polyubiquitinated in cells with reduced inositol pyrophosphates. We show that the inositol pyrophosphate 5-IP7transfers its high-energy beta phosphate moiety to pre-phosphorylated serine residues in the central PEST domain of MYC. Pyrophosphorylation of MYC promotes its interaction with the E3 ubiquitin ligase FBW7, thereby enhancing MYC polyubiquitination and degradation. FBW7 can bind directly to the PEST domain of MYC in a pyrophosphorylation-dependent manner. A stabilized, pyrophosphorylation-deficient form of MYC increases cell death during growth stress in untransformed cells, and promotes cell proliferation in response to mitogens. Thus, control of MYC stability through a novel pyro-phosphodegron provides unexpected insight into the regulation of cell survival in response to environmental cues.
Cotton leaf curl Multan virus βC1 Protein Induces Autophagy by Disrupting the Interaction of Autophagy-Related Protein 3 with Glyceraldehyde-3-Phosphate Dehydrogenases[OPEN]
Authors: Ismayil Asigul , Yang Meng , Haxim Yakupjan , Wang Yunjing , Li Jinlin , Han Lu , Wang Yan , Zheng Xiyin , Wei Xiang , Nagalakshmi Ugrappa , Hong Yiguo , Hanley-Bowdoin Linda , Liu Yule 
Published: February 2020

Abstract
Autophagy plays an important role in plant–pathogen interactions. Several pathogens including viruses induce autophagy in plants, but the underpinning mechanism remains largely unclear. Furthermore, in virus–plant interactions, viral factor(s) that induce autophagy have yet to be identified. Here, we report that the βC1 protein of Cotton leaf curl Multan betasatellite (CLCuMuB) interacts with cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC), a negative autophagic regulator, to induce autophagy in Nicotiana benthamiana. CLCuMuB βC1 bound to GAPCs and disrupted the interaction between GAPCs and autophagy-related protein 3 (ATG3). A mutant βC1 protein (βC13A) in which I45, Y48, and I53 were all substituted with Ala (A), had a dramatically reduced binding capacity with GAPCs, failed to disrupt the GAPCs-ATG3 interactions and failed to induce autophagy. Furthermore, mutant virus carrying βC13A showed increased symptoms and viral DNA accumulation associated with decreased autophagy in plants. These results suggest that CLCuMuB βC1 activates autophagy by disrupting GAPCs–ATG3 interactions.
Status of lean construction implementation among small and medium building contractors (SMBCs) in Ghana
Authors: Ankomah Emmanuel Nsiah , Ayarkwa Joshua , Agyekum Kofi 
Published: February 2020

PurposeThe purpose of this study is to ascertain the extent to which the practices of small and medium building contractors (SMBCs) conform to lean construction (LC) principles. Ultimately, practical results encourage a discourse on the true potentials and challenges to the holistic uptake of LC principles in the Ghanaian construction industry.Design/methodology/approachThis research is based on a qualitative case study approach. The data was obtained through face-to-face structured interviews.FindingsAcross the cases, it was realized that there is a low-level application of LC principles among SMBCs. There was no indication that lean concepts were used on a company-wide basis in the Ghanaian construction industry. Furthermore, the study revealed that the traditional wasteful approach to managing construction projects was still prevalent among the firms.Practical implicationsThis paper uses the 4P model as a foundation for assessing the extent to which the practices of SMBCs conform to LC principles. Practically, the study also created a certain level of awareness among the SMBCs about LC, LC principles and the benefits of the application of these principles within organizations.Originality/valueThis study contributes to the body of knowledge as it uncovers the status of LC implementation among SMBCs in the Ghanaian construction industry. The findings that are presented in this paper can be used as a starting point to disseminate the research and practice of LC among SMBCs.
Privatization and school mental health
Authors: Weist Mark , Franke Kathleen Blackburn , Lucio Rob , Bass Jefferson , Doan Terry , Blalock Deborah 
Published: February 2020

Purpose
The purpose of this paper is to describe the relationship between privatization and school mental health (SMH) in the USA, as well as to present a case study of the SMH system in South Carolina.

Design/methodology/approach
The authors reviewed data regarding states’ mental health systems (e.g. public, private and hybrid of public and private), mental health budgets and percentages of schools with mental health clinicians.

Findings
The results demonstrate that the majority of states have public mental health systems. There is variability between states regarding general funding, as well as funding for SMH. Further, there was variability in the percentage of schools with SMH clinicians, with South Carolina reporting the greatest percentage. South Carolina’s mental health system, which is a public–private hybrid is reviewed, along with relevant history on the development of SMH programs in the state.

Originality/value
This paper contributes to the general knowledge by describing the provision and funding sources for SMH services within the USA. It yields important implications for integrating public mental health services within schools.