bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Confidence in Root Placement on Phylogenies: An Empirical Study Using Non-Reversible Models for Mammals
Authors: Naser-Khdour Suha , Minh Bui Quang , Lanfear Robert 
Published: August 2020

AbstractUsing time-reversible Markov models is a very common practice in phylogenetic analysis, because although we expect many of their assumptions to be violated by empirical data, they provide high computational efficiency. However, these models lack the ability to infer the root placement of the estimated phylogeny. In order to compensate for the inability of these models to root the tree, many researchers use external information such as using outgroup taxa or additional assumptions such as molecular-clocks. In this study, we investigate the utility of non-reversible models to root empirical phylogenies and introduce a new bootstrap measure, therootstrap, which provides information on the statistical support for any given root position.Availability and implementationrootstrap support is implemented in IQ-TREE 2 and a tutorial is available at the iqtree webpagehttp://www.iqtree.org/doc/Rootstrap. In addition, a python script is available athttps://github.com/suhanaser/Rootstrap. [phylogenetic inference, root estimation, bootstrap, non-reversible models]
CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data
Authors: Kozlov Alexey , Alves Joao M. , Stamatakis Alexandros , Posada David 
Published: August 2020

AbstractWe introduce a maximum likelihood framework called CellPhy for inferring phylogenetic trees from single-cell DNA sequencing (scDNA-seq) data. CellPhy leverages a finite-site Markov genotype substitution model with 16 diploid states, akin to those typically used in statistical phylogenetics. It includes a dedicated error function for single cells that incorporates amplification/sequencing error and allelic dropout (ADO). Moreover, it can explicitly consider the uncertainty of the variant calling process by using genotype likelihoods as input. We implemented CellPhy in a widely used open-source phylogenetic inference package (RAxML-NG) that provides statistical confidence measurements on the estimated tree and scales particularly well on large scDNA-seq datasets with hundreds or thousands of cells. To benchmark CellPhy, we carried out 19,400 coalescent simulations of cell samples from exponentially-growing tumors for which the true phylogeny was known. We evolved single-cell diploid DNA genotypes along the simulated genealogies under different scenarios, including infinite- and finite-sites nucleotide mutation models, trinucleotide mutational signatures, sequencing, and amplification errors, allele dropouts, and cell doublets. Our simulations suggest that CellPhy is robust to amplification/sequencing errors and ADO and outperforms state-of-the-art methods under realistic scDNA-seq scenarios both in terms of accuracy and speed. Also, we sequenced 24 single-cell whole-genomes from a colorectal tumor. Together with three published scDNA-seq data sets, we analyzed these empirical data to illustrate how CellPhy can provide more reliable biological insights than most competing methods. CellPhy is freely available at https://github.com/amkozlov/cellphy.
Multi-organ signaling mobilizes tumor-associated erythroid cells expressing immune checkpoint molecules
Authors: Sano Yasuyo , Yoshida Toshimi , Choo Min-Kyung , Jiménez-Andrade Yanek , Hill Kathryn R. , Georgopoulos Katia , Park Jin Mo 
Published: August 2020

AbstractHematopoietic-derived cells are integral components of the tumor microenvironment and serve as critical mediators of tumor-host interactions. Cells derived from myeloid and lymphoid lineages perform well-established functions linked to cancer development, progression and response to therapy. It is unclear whether erythroid cells exert such host cell functions in cancer, but emerging evidence points to this possibility. Here we show that tumor-promoting environmental stress and tumor-induced physiological disruption trigger renal erythropoietin production and erythropoietin-dependent expansion of splenic erythroid cell populations in mice. These erythroid cells display molecular features indicative of an immature erythroid phenotype and express immune checkpoint molecules. Erythroid cells with similar properties are present in mouse and human tumor tissues. Antibody-mediated erythropoietin blockade or erythroid cell depletion reduces tumor growth. These findings reveal the potential of erythropoietin and erythroid cells as targets for cancer treatment.
Behavioral role of PACAP signaling reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations
Authors: Zhang Limei , Hernández Vito S. , Gerfen Charles R. , Jiang Sunny Z. , Zavala Lilian , Barrio Rafael A. , Eiden Lee E. 
Published: August 2020

AbstractThe neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent chemoanatomical picture of PACAP’s role in brain motor responses to sensory input. A circuit role for PACAP was tested by observing fos activation of brain neurons after olfactory threat cue in wild type and PACAP knockout mice. Neuronal activation, and behavioral response, were blunted in PACAP knock-out mice, accompanied by sharply down-regulated vesicular transporter expression in both GABAergic and glutamatergic neurons expressing PACAP and its receptor. This report signals a new perspective on the role of neuropeptide signaling in supporting excitatory and inhibitory neurotransmission in the nervous system within functionally coherent polysynaptic circuits.
Microbiome-derived metabolites reproduce the mitochondrial dysfunction and decreased insulin sensitivity observed in type 2 diabetes
Authors: Ormsby Michael J. , Hulme Heather , Villar Victor H. , Hamm Gregory , Rodriguez-Blanco Giovanny , Bragg Ryan A. , Strittmatter Nicole , Schofield Christopher J. , Delles Christian , Salt Ian P. , Tardito Saverio , Burchmore Richard , Goodwin Richard J. A. , Wall Daniel M. 
Published: August 2020

AbstractDiabetes is a global health problem that was estimated to be the 7thleading cause of death worldwide in 2016. Type 2 diabetes mellitus (T2DM) is classically associated with genetic and environmental factors, however recent studies have demonstrated that the gut microbiome, which is altered in T2DM patients, is also likely to play a significant role in disease development. Despite this, the identity of microbiome-derived metabolites that influence T2DM onset and/or progression remain elusive. Here we demonstrate that a serum biomarker for T2DM, previously of unknown structure and origin, is actually two microbiome-derived metabolites, 3-methyl-4-(trimethylammonio)butanoate (3M-4-TMAB) and 4-(trimethylammonio)pentanoate (4-TMAP). These metabolites are produced by theLachnospiraceaefamily of bacteria, which are highly prevalent in the gut microbiome of T2DM patients and are associated with high dietary fat intake. Treatment of human liver cells with 3M-4-TMAB and 4-TMAP results in a distinct change in the acylcarnitine profile in these cells and significantly reduced their insulin sensitivity; both indicators of T2DM. These results provide evidence of a mechanistic link between gut microbiome derived metabolites and T2DM.
Inferring Adaptive Introgression Using Hidden Markov Models
Authors: Svedberg Jesper , Shchur Vladimir , Reinman Solomon , Nielsen Rasmus , Corbett-Detig Russell 
Published: August 2020

AbstractAdaptive introgression - the flow of adaptive genetic variation between species or populations - has attracted significant interest in recent years and it has been implicated in a number of cases of adaptation, from pesticide resistance and immunity, to local adaptation. Despite this, methods for identification of adaptive introgression from population genomic data are lacking. Here, we present Ancestry_HMM-S, a Hidden Markov Model based method for identifying genes undergoing adaptive introgression and quantifying the strength of selection acting on them. Through extensive validation, we show that this method performs well on moderately sized datasets for realistic population and selection parameters. We apply Ancestry_HMM-S to a dataset of an admixedDrosophila melanogasterpopulation from South Africa and we identify 17 loci which show signatures of adaptive introgression, four of which have previously been shown to confer resistance to insecticides. Ancestry_HMM-S provides a powerful method for inferring adaptive introgression in datasets that are typically collected when studying admixed populations. This method will enable powerful insights into the genetic consequences of admixture across diverse populations. Ancestry_HMM-S can be downloaded fromhttps://github.com/jesvedberg/Ancestry_HMM-S/.
NPC1-mTORC1 signaling Couples Cholesterol Sensing to Organelle Homeostasis and is a Targetable Pathway in Niemann-Pick type C
Authors: Davis Oliver B. , Shin Hijai R. , Lim Chun-Yan , Wu Emma Y. , Kukurugya Matthew , Maher Claire F. , Perera Rushika M. , Ordonez M. Paulina , Zoncu Roberto 
Published: August 2020

ABSTRACTLysosomes promote cellular homeostasis through macromolecular hydrolysis within their lumen and metabolic signaling by the mTORC1 kinase on their limiting membranes. Both hydrolytic and signaling functions require precise regulation of lysosomal cholesterol content. In Niemann-Pick type C (NPC), loss of the cholesterol exporter, NPC1, causes cholesterol accumulation within lysosomes, leading to mTORC1 hyperactivation, disrupted mitochondrial function and neurodegeneration. The compositional and functional alterations in NPC lysosomes, and how aberrant cholesterol-mTORC1 signaling contributes to organelle pathogenesis are not understood. Through proteomic profiling of NPC lysosomes, we find pronounced proteolytic impairment compounded with hydrolase depletion and enhanced membrane damage. Genetic and pharmacologic mTORC1 inhibition restores lysosomal proteolysis without correcting cholesterol storage, implicating aberrant mTORC1 as a pathogenic driver downstream of cholesterol accumulation. Consistently, mTORC1 inhibition ameliorates mitochondrial dysfunction in a neuronal model of NPC. Thus, cholesterol-mTORC1 signaling controls organelle homeostasis and is a targetable pathway in NPC.
The Multispecies Coalescent in Space and Time
Authors: McKenzie Patrick F. , Eaton Deren A. R. 
Published: August 2020

AbstractA key distinction between species tree inference under the multi-species coalescent model (MSC), and the inference of gene trees in sliding windows along a genome, is in the effect of genetic linkage. Whereas the MSC explicitly assumes genealogies to be unlinked, i.e., statistically independent, genealogies located close together on genomes are spatially auto-correlated. Here we use tree sequence simulations with recombination to explore the effects of species tree parameters on spatial patterns of linkage among genealogies. We decompose coalescent time units to demonstrate differential effects of generation time and effective population size on spatial coalescent patterns, and we define a new metric, “phylogenetic linkage,” for measuring the rate of decay of phylogenetic similarity by comparison to distances among unlinked genealogies. Finally, we provide a simple example where accounting for phylogenetic linkage in sliding window analyses improves local gene tree inference.
The DCC receptor regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation
Authors: Morcom Laura , Gobius Ilan , Marsh Ashley P L , Suárez Rodrigo , Bridges Caitlin , Ye Yunan , Fenlon Laura R , Zagar Yvrick , Douglass Amelia M , Donahoo Amber-Lee S , Fothergill Thomas , Shaikh Samreen , Kozulin Peter , Edwards Timothy J , Cooper Helen M ,   IRC5 Consortium, Sherr Elliott H , Chédotal Alain , Leventer Richard J , Lockhart Paul J , Richards Linda J 
Published: August 2020

AbstractThe forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). DCC and NTN1 are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent inDccandNtn1knockout mice, while other commissures are only partially affected, suggesting an additional aetiology in forebrain commissure formation. Here, we find that these molecules play a critical role in regulating astroglial development and IHF remodelling during CC and HC formation. Human subjects withDCCmutations display disrupted IHF remodelling associated with CC and HC malformations. Thus, axon guidance molecules such as DCC and NTN1 first regulate the formation of a midline substrate for dorsal commissures prior to their role in regulating axonal growth and guidance across it.
Sweet anticipation: Predictability of familiar music in autism
Authors: Da Mota Patricia Alves , Stark Eloise A , Fernandes Henrique M , Ahrends Christine , Cabral Joana , Gebauer Line , Happé Francesca , Vuust Peter , Kringelbach Morten L 
Published: August 2020

AbstractAutism has been characterised by different behavioural and cognitive profiles compared to typically developing (TD) individuals, and increasingly these differences have been associated with differences in structural and functional brain connectivity. It is currently unknown as to whether autistic and TD listeners process music in the same way: emotionally, mnemonically, and perceptually. The present study explores the brain’s dynamical landscape linked to music familiarity in an fMRI dataset from autistic and TD individuals. Group analysis using leading eigenvector dynamics analysis (LEiDA) revealed significantly higher probability of occurrence of a brain network in TD compared to autistic individuals during listening to familiar music. This network includes limbic and paralimbic areas (amygdala, hippocampus, parahippocampal gyrus, and temporal pole). No significant differences were found between autistic and TD individuals while listening to a scrambled, i.e. unfamiliar and more unpredictable, version of the same music track. These findings provide novel neuroimaging insights into how autistic prediction monitoring may shape brain networks during listening to familiar musical excerpts.
COVID-19 pandemic in Southeast Asia: intervention and mitigation efforts
Authors: Fauzi Muhammad Ashraf , Paiman Norazha 
Published: August 2020

PurposeCoronavirus disease 2019 (COVID-19) has sent shockwaves throughout the world in less than two months. Countries in South East Asia are not spared in this plight. As the disease can be transmitted from human to human, extensive control and mitigation efforts have been taken by almost every country where the disease has been reported. Southeast Asian countries or the Association of Southeast Asian Nations (ASEAN), being one of the closest regions with China, have taken various measures to slow down and contain the spread of the pandemic virus.Design/methodology/approachMultiple strategies have been taken by the government to reduce the number of infections in the region. This includes phases of lockdowns in affected areas and federal order to close businesses to reduce the rate of infection among the people. As ASEAN comprises diverse cultures, socioeconomic backgrounds and geographical differences, steps taken are definitely based on what are deemed important and applicable to each country.FindingsThis paper reviews what has been taken by each of the ASEAN members and further recommendations that can be taken to ensure the issue of human security in the region can be preserved.Originality/valueThe originality of this paper is to show mitigation and prevention strategies undertaken by ASEAN nation in combating COVID-19.
Understanding relationship between risks and claims for assessing risks with project data
Authors: Kumar Ratnesh , Iyer K. Chandrashekhar , Singh Surya Prakash 
Published: August 2020

PurposeIn construction management, risks and claims are treated separately, but several studies tacitly acknowledge a strong link between the two. In this context, this research intends to investigate whether risks and claims have a causal relationship? Based on this causal relationship, a claim-based risk assessment model (C-RAM) is developed to quantify occurrences and cost implications of risks using project data.Design/methodology/approachFirst, the causal relationship between risks and claims is established through a conceptual framework for content analysis of the literature on risk management (RM) and claim management (CM). Then, a C-RAM is developed based on the content analysis of 234 claims from 24 settled arbitration awards.FindingsRisks and claims are found to be two stages in the same chain of uncertain events that affect projects, subsequently revealing a causal relationship between risks and claims. Due to this causal relationship, claim documents become a potential source of risk information from past projects. Proposed C-RAM quantifies occurrences of risks with three parameters: number of projects in which a risk occurs, number of ways in which a risk occurs, and number of claims a risk causes if it occurs. Also, cost implications of risks are quantified as percentage of contract sums for interpretation as tangible values.Research limitations/implicationsThough C-RAM is applicable to all types of claims, the results in this paper are based on impacts of risks in past projects that caused claims and reached to arbitration stage.Practical implicationsThe causal relationship between risks and claims will encourage integration of knowledge on RM and CM which is currently treated separately. Practitioners can now visualize claims as cost implications of risks that occurred in projects. Further, C-RAM makes risk assessment (RA) more objective by quantifying the cost implications of risks as percentage of contract sums which can be readily used for contingency estimation.Originality/valueThe relationship between risks and claims, and the potential of claim documents as a source of project risk information, can initiate a new paradigm in RM research based on project data.
Struggling to breathe: COVID-19, protest and the LIS response
Authors: Gibson Amelia N. , Chancellor Renate L. , Cooke Nicole A. , Dahlen Sarah Park , Patin Beth , Shorish Yasmeen L. 
Published: August 2020

PurposeThe purpose of this article is to provide a follow up to “Libraries on the Frontlines: Neutrality and Social Justice,” which was published here in 2017. It addresses institutional responses to protests and uprising in the spring and summer of 2020 after the deaths of Ahmaud Arbery, Breonna Taylor and George Floyd, all of which occurred in the context of the global COVID-19 pandemic. The article expands the previous call for libraries to take a stand for Black lives.Design/methodology/approachThe authors describe the events of 2020 (a global pandemic, multiple murders of unarmed Black people and the consequent global protests) and responses from within library and information science (LIS), from the perspectives as women of color faculty and library professionals.FindingsThe authors comment on how libraries are responding to current events, as well as the possibilities for panethnic solidarity. The authors also consider specifically how libraries and other institutions are responding to the racial uprisings through statements on social media and call for concrete action to ensure that their organizations and information practices are actively antiracist. In so doing, the authors update the claims and expand the appeals they made in 2017,that Black Lives Matter and that librarianship must not remain neutral.Originality/valueThis paper addresses recent institutional and governmental reactions to the COVID-19 pandemic and the racial uprisings of spring and summer 2020. It is original, current and timely as it interrogates ongoing events in a LIS context.
Reflective practice during action learning in management development programmes
Authors: Robertson Jane , Le Sueur Heidi , Terblanche Nicky 
Published: August 2020

Purpose
This study aims to investigate the aspects that influence reflective practice during an action learning approach to management development programmes (MDPs).

Design/methodology/approach
A narrative inquiry approach was used to gather interview and pictorial data from 16 participants who had attended an action learning oriented MDP. Data were translated into interpretive stories using McCormack’s lenses, which were further analysed using thematic analysis.

Findings
Two key themes emerged: dealing with emotions and practising reflection. Participants initially found reflecting uncomfortable, but showed courage by persevering. Participants had to learn how to reflect and set aside time for it, while valuing support and guidance from their action learning facilitator.

Research limitations/implications
The findings and recommendations may not be relevant to all types of action learning as action learning forms and contexts differ.

Practical implications
Reflective practice is the responsibility of both the participant and the action learning facilitator. Participants need to create the time and space to learn, be fully present during reflection, practice mindfulness and have the courage to be uncomfortable while reflecting. Action learning facilitators could encourage reflection by creating a safe learning environment, selecting a diverse action learning team, designing reflection time into the MDP and helping participants apply reflection tools.

Originality/value
Reflective practice enhances learning; yet there is a need to better understand reflective practice in an action learning context. This study provides empirical evidence of the aspects that influence the reflection process and outcomes as well as practical guidelines to participants and facilitators on how to promote reflection.