bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAnorm2 for quantitatively comparing groups of ChIP-seq samples
Authors: Tu Shiqi , Li Mushan , Tan Fengxiang , Chen Haojie , Xu Jian , Waxman David J. , Zhang Yijing , Shao Zhen 
Published: January 2020

AbstractEukaryotic gene transcription is regulated by a large cohort of chromatin associated proteins, and inferring their differential binding sites between cellular contexts requires a rigorous comparison of the corresponding ChIP-seq data. We present MAnorm2, a new computational tool for quantitatively comparing groups of ChIP-seq samples. MAnorm2 uses a hierarchical strategy to normalize ChIP-seq data and then performs differential analysis by assessing within-group variability of ChIP-seq signals under an empirical Bayes framework. In this framework, MAnorm2 considers the abundance of differential ChIP-seq signals between groups of samples and the possibility of different within-group variability between groups. When samples in each group are biological replicates, MAnorm2 can reliably identify differential binding events even between highly similar cellular contexts. Using a number of real ChIP-seq data sets, we observed that MAnorm2 clearly outperformed existing tools for differential ChIP-seq analysis, with the improvement in performance being most dramatic when the groups of samples being compared had distinct global within-group variability.
Targeting a critical step in fungal hexosamine biosynthesis
Authors: Lockhart Deborah E.A. , Stanley Mathew , Raimi Olawale G. , Robinson David A. , Boldovjakova Dominika , Squair Daniel R. , Ferenbach Andrew T. , Fang Wenxia , van Aalten Daan M.F. 
Published: January 2020

SummaryAspergillus fumigatusis a human opportunistic fungal pathogen with a cell wall that protects it from the extracellular environment. Chitin, an essential cell wall component, is synthesised from UDP-GlcNAc that is produced by the hexosamine biosynthetic pathway. Here, we provide genetic and chemical evidence that glucosamine 6-phosphateN-acetyltransferase (Gna1), a key enzyme in this pathway, is an exploitable antifungal drug target. Deletion ofGNA1results in loss of viability and disruption of the cell wall, phenotypes that can be rescued by the product of the enzyme. In a murine model of aspergillosis, theΔgna1mutant strain attenuates virulence. Using a fragment-based approach, we discovered a small heterocyclic scaffold that binds proximal to the active site and can be optimised to a selective sub-micromolar binder. Taken together, we have provided genetic, structural and chemical evidence for Gna1 as an antifungal target inAspergillus fumigatus.
Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early genes
Authors: Lin Yao-Tang , Chiweshe Stephen , McCormick Dominique , Raper Anna , Wickenhagen Arthur , DeFillipis Victor , Gaunt Eleanor , Simmonds Peter , Wilson Sam J , Grey Finn 
Published: January 2020

AbstractThe genomes of RNA and small DNA viruses of vertebrates display significant suppression of CpG dinucleotide frequencies. Artificially increasing dinucleotide frequencies results in substantial attenuation of virus replication, suggesting that these compositional changes may facilitate recognition of non-self RNA sequences. Recently, the interferon inducible protein ZAP, was identified as the host factor responsible for sensing CpG in viral RNA, through direct binding and possibly downstream targeting for degradation. Using an arrayed interferon stimulated gene expression library screen, we identified ZAPS, and its associated factor TRIM25, as direct inhibitors of human cytomegalovirus (HCMV) replication. Exogenous expression of ZAPS and TRIM25 significantly reduced virus replication while knockdown resulted in increased virus replication. HCMV displays a strikingly heterogeneous pattern of CpG representation with a specific suppression of CpGs within the IE1 major immediate early transcript which is absent in subsequently expressed genes. We demonstrated that suppression of CpG dinucleotides in the IE1 gene allows evasion of inhibitory effects of ZAP. During HCMV infection, expression of ZAP and TRIM25 are rapidly reduced, removing pressure to suppress dinucleotide frequencies in viral genes expressed after the immediate early genes, while acute virus replication and high levels of ZAP are mutually exclusive. Finally, we show that TRIM25 regulates alternative splicing between the ZAP short and long isoforms during HCMV infection and interferon induction, with knockdown of TRIM25 resulting in decreased ZAPS and corresponding increased ZAPL expression. These results demonstrate for the first time that ZAP is a potent host restriction factor against large DNA viruses and that HCMV evades ZAP detection through suppression of CpG dinucleotides within the major immediate early transcripts. Furthermore, TRIM25 is required for efficient upregulation of the interferon inducible short isoform of ZAP through regulation of alternative splicing.
MAIT cells are minimally responsive to Mycobacterium tuberculosis within granulomas, but are functionally impaired by SIV in a macaque model of SIV and Mtb co-infection
Authors: Ellis-Connell Amy L. , Balgeman Alexis J. , Larson Erica C. , Rodgers Mark A. , Ameel Cassaundra , Baranowski Tonilynn , Maiello Pauline , Juno Jennifer A. , Scanga Charles A. , O’Connor Shelby L. 
Published: January 2020

ABSTRACTMucosal associated invariant T (MAIT) cells recognize and can directly destroy bacterially infected cells. While a role for MAIT cells has been suggested in severalin vitroand in vivo models ofM.tuberculosis(Mtb) infection, these studies have often focused on MAIT cells within the peripheral blood or are cross-sectional studies rather than longitudinal studies. The role of MAIT cells within granulomas and other sites of Mtb infection is relatively unknown. Furthermore, how HIV/SIV infection might impair MAIT cells at the sites of Mtb infection has not been determined. Using a Mauritian cynomolgus macaque (MCM) model system, we phenotyped MAIT cells in the peripheral blood and BAL prior to and during infection with SIVmac239. To characterize the role of MAIT cells within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb for 6 weeks. MAIT cell frequency and function was examined within the peripheral blood, distal airways, as well as within Mtb-affected lymph nodes (LN) and tissues. Surprisingly, we found no evidence of MAIT cell responsiveness to Mtb within granulomas. Additionally, MAIT cells only minimally responded to mycobacterial stimulus in ex vivo functional assays. In contrast, most MAIT cell activation seemed to occur in samples with highly active SIV replication, including blood and SIV-infected LN. Finally, the ability of MAIT cells to secrete TNFα (TNF) was impaired during SIV and Mtb co-infection, indicating that the two pathogens together could have a synergistically deleterious effect on MAIT cell function. The effect of this functional impairment on overall TB disease burden was unclear, but might be deleterious if MAIT cells are needed to fully activate antimycobacterial immune cells within the granulomas.
Linking coleopteran diversity with agricultural management of maize agroecosystems in Oaxaca, Mexico
Authors: González Cecilia González , García Tania Lara , Jardón-Barbolla Lev , Benítez Mariana 
Published: January 2020

AbstractBiodiversity is known to be influenced by agricultural practices in many ways. However, it is necessary to understand how this relation takes place in particular agroecosystems, sociocultural contexts and for specific biological groups. Also, in order to systematically study and track how biodiversity responds or changes with agricultural practices, it is necessary to find groups that can be used as practical indicators. We conduct a study of beetle (Coleoptera) diversity in maize-based agricultural plots with heterogeneous management practices in the Central Valleys of Oaxaca, Mexico. First, we use a mixture of local knowledge and multivariate statistics to group the plots into two broad and contrasting management categories (traditional vs. industrialized). Then, we present an analysis of Coleopteran diversity for each category, showing higher levels across different diversity indexes for the traditional plots. Also, our results let us postulate the Curculionidae family as an indicator of both management type and overall Coleopteran diversity in the agricultural lands of the study site. We discuss our results in terms of the agricultural matrix quality and its role in joint productive and biodiversity conservation strategies.
Diagnosis of Duchenne Muscular Dystrophy using Raman Hyperspectroscopy
Authors: Ralbovsky Nicole M. , Dey Paromita , Galfano Andrew , Dey Bijan K. , Lednev Igor K. 
Published: January 2020

AbstractDuchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and affects boys in infancy or early childhood. DMD is known to trigger progressive muscle weakness due to skeletal muscle degeneration and ultimately causes death. There are limited treatment regimens available that can either slow or stop the progression of DMD. An accurate and specific method for diagnosing DMD in its earliest stages is needed to prevent progressive muscle degeneration and death. Current methods for diagnosing DMD are often laborious, expensive, invasive, and typically diagnose the disease later on it is progression. In an effort to improve the accuracy and ease of diagnosis, this study focused on developing a novel method for diagnosing DMD which combines Raman hyperspectroscopic analysis of blood serum with advanced statistical analysis. Partial Least Squares Discriminant Analysis (PLS-DA), was applied to the spectral dataset acquired from control andmdxblood serum of 3- and 12-month old mice to build a diagnostic algorithm. Internal cross-validation showed 95.2% sensitivity and 94.6% specificity for identifying diseased spectra. These results were verified using external validation, which achieved 100% successful classification efficiency at the level of individual donor. This proof-of-concept study presents Raman hyperspectroscopic analysis of blood serum as a fast, non-expensive, minimally invasive and early detection method for the diagnosis of Duchenne muscular dystrophy.
The generational questions after land reform in Zimbabwe: a social reproduction perspective
Authors: Chipenda Clement , Tom Tom 
Published: January 2020

Purpose
The purpose of this paper is to provide a contemporary perspective on post land reform Zimbabwe with special focus on the youth. It uses the social reproduction conceptual framework to show that two decades after land reform, there are generational questions which are now arising in the new resettlement areas which need deeper, empirical and more nuanced analysis to comprehend. In a context where some countries in Southern Africa are grappling with the best ways of dealing with their land questions, it shows that from a youth perspective, the Fast Track Land Reform Programme (FTLRP) has important lessons.

Design/methodology/approach
The study was largely qualitative and grounded in an interpretive research paradigm. It employed various data gathering instruments and solicited for responses from 151 young people as well as 11 key informants. The study used the social reproduction perspective as a conceptual and evaluative tool to ascertain the outcomes of the FTLRP from a social reproduction perspective with special focus on young people.

Findings
The study showed that there are some young people in the resettlement areas who blame the land reform programme for the challenging socio-economic situation which they are facing. It also shows that for the youth, the FTLRP has had multi-dimensional impact; while some are complaining, others have managed to use their agency to access natural resources and land, which has seen them “accumulating from below”. For some young people, land reform has positively transformed their lives, while others feel that it has limited their opportunities.

Originality/value
The paper provides new and contemporary insights on post land reform Zimbabwe. This is an area which is increasingly gaining traction in scholarship on the FTLRP. In addition, the paper provides a unique perspective of looking at the issue of the youth from a social reproduction perspective; this is a unique academic contribution. Lastly, the paper is useful insofar as it transcends the debates on the FTLRP to proffer a unique analysis on the social reproduction dimensions of the FTLRP.
Foreign aid and economic growth in sub-Saharan Africa
Authors: Jena Nihar Ranjan , Sethi Narayan 
Published: January 2020

PurposeThe purpose of this paper is to empirically examine the effectiveness of foreign aid in improving economic growth prospects in the sub-Saharan Africa (SSA) region from 1993 to 2017.Design/methodology/approachA sample of 45 SSA countries for the period 1993–2017 is considered for this study. The study uses various econometrics tools such as Pedroni and Kao’s cointegration test, Johansen-Fisher Panel cointegration test, FMOLS and PDOLS in order to ascertain the long-run and short-run dynamics among the variables under consideration.FindingsThe empirical results find that long-run and short-run relationships exist among foreign aid, economic growth, investment, financial deepening, price stability and trade openness of the SSA economies. The authors also find unidirectional causality running from foreign aid to economic growth. The policymakers in these countries are well-advised to implement suitable policy measures to build on the growth momentum created by foreign aid inflows.Originality/valueThe study uses a dynamic macroeconomic modeling framework to assess the impact of aid flows on economic growth in the SSA region. Taking into account the diversity of level of growth experienced by the 45 countries in the region, the study uses an appropriate regression technique, i.e., panel dynamic OLS whose results are robust. The finding is also supported by the Granger-causality test and robust cointegration techniques.
Pricing agricultural inputs from biodiversity-rich ecosystems and habitats without input markets
Authors: Onofri Laura , Volpe Mario 
Published: January 2020

PurposeThe purpose of this paper is to focus on the analysis of an understudied problem in the economic literature. It proposes a valuation methodology for inputs that come from biodiversity-rich ecosystems/habitats and are used in agro-food production at zero input cost because there is not a market for such inputs.Design/methodology/approachFollowing Onofri et al. (2017), the authors computed the value of the marginal productivity of different inputs in three selected case studies (Angola, Mozambique and Brazil). Results are theory based and rigorous but show a strong contingency, case based, relative dimension that is captured, in the framework, by the “relativity ratio.” The ratio expresses the relative weight of the value generated by the input that comes from biodiversity-rich ecosystems/habitats in the per capita monthly available income of the farmer and aims at conveying additional insights to the economic valuation.FindingsIn this paper, the assessment of agricultural inputs value (price) in the absence of inputs markets is done, with an application to three different case studies. The inputs are peculiar since they come from habitats and ecosystems that are very biodiversity-rich.Originality/valueThe paper proposes a practical, though rigorous, methodology for the assessment of the value (price) of agricultural inputs in absence of inputs markets. Markets do not exist since the inputs come from biodiversity-rich habitats and ecosystems.
Factors hindering shared files retrieval
Authors: Bergman Ofer , Israeli Tamar , Whittaker Steve 
Published: January 2020

Purpose
Personal information management (PIM) is an activity in which people store information items in order to retrieve them later. The purpose of this paper is to test and quantify the effect of factors related to collection size, file properties and workload on file retrieval success and efficiency.

Design/methodology/approach
In the study, 289 participants retrieved 1,557 of their shared files in a naturalistic setting. The study used specially developed software designed to collect shared files’ names and present them as targets for the retrieval task. The dependent variables were retrieval success, retrieval time and misstep/s.

Findings
Various factors compromise shared files retrieval including: collection size (large number of files), file properties (multiple versions, size of team sharing the file, time since most recent retrieval and folder depth) and workload (daily e-mails sent and received). The authors discuss theoretical reasons for these negative effects and suggest possible ways to overcome them.

Originality/value
Retrieval is the main reason people manage personal information. It is essential for retrieval to be successful and efficient, as information cannot be used unless it can be re-accessed. Prior PIM research has assumed that factors related to collection size, file properties and workload affect file retrieval. However, this is the first study to systematically quantify the negative effects of these factors. As each of these factors is expected to be exacerbated in the future, this study is a necessary first step toward addressing these problems.
The topic of terrorism on Yahoo! Answers: questions, answers and users’ anonymity
Authors: Chua Alton Y.K. , Banerjee Snehasish 
Published: January 2020

Purpose
The purpose of this paper is to explore the use of community question answering sites (CQAs) on the topic of terrorism. Three research questions are investigated: what are the dominant themes reflected in terrorism-related questions? How do answer characteristics vary with question themes? How does users’ anonymity relate to question themes and answer characteristics?

Design/methodology/approach
Data include 300 questions that attracted 2,194 answers on the community question answering Yahoo! Answers. Content analysis was employed.

Findings
The questions reflected the community’s information needs ranging from the life of extremists to counter-terrorism policies. Answers were laden with negative emotions reflecting hate speech and Islamophobia, making claims that were rarely verifiable. Users who posted sensitive content generally remained anonymous.

Practical implications
This paper raises awareness of how CQAs are used to exchange information about sensitive topics such as terrorism. It calls for governments and law enforcement agencies to collaborate with major social media companies to develop a process for cross-platform blacklisting of users and content, as well as identifying those who are vulnerable.

Originality/value
Theoretically, it contributes to the academic discourse on terrorism in CQAs by exploring the type of questions asked, and the sort of answers they attract. Methodologically, the paper serves to enrich the literature around terrorism and social media that has hitherto mostly drawn data from Facebook and Twitter.
The moderating effects of job design on human capital and NPD performance
Authors: Popaitoon Sujinda 
Published: January 2020

Purpose
In response to calls for the extension of job design research for the strategic team particularly in high-velocity environment, the purpose of this paper is to investigate the moderating roles of job design in the relationships between project team viewed as human capital resources and new product development (NPD) performance in the short and long run. Based on survey data from 117 NPD project teams in high-technology multinational companies (MNCs) in Thailand, this research finds that job design (i.e. autonomous, task identity and feedback) moderates the effects of human capital resources on NPD project success. In addition, job design works in concert with human capital resources to affect managing NPD project-to-project in the long run. Designing jobs by providing autonomy, identity and feedbacks could trigger the stronger contribution not only for fostering knowledge creation in the NPD project team, but also encouraging intrinsic motivation to commit extra effort to achieve NPD goals. This research contributes to the job design literature of how job design works for NPD project team to achieve short-and long-run NPD performance. Implications for these results are discussed.

Design/methodology/approach
Based on survey data from 117 NPD projects in high-technology MNCs in Thailand, this research uses hierarchical regression to do analyses.

Findings
This research finds that job design (i.e. autonomous, task identity and feedback) moderates the effects of human capital resources on the short-run project performance. In addition, job design works in concert with human capital resources to affect managing project-to-project in the long run.

Research limitations/implications
This research contributes to the job design literature of how job design works for NPD project team to achieve short-and long-run NPD performance.

Originality/value
Investigating the moderating roles of job design in the relationship between human capital resources and NPD performance in the short and long run.
Properties of analysts’ consensus cash flow forecasts for Australian firms
Authors: Ahmed Kamran , Houqe Muhammad Nurul , Hillier John , Crockett Steven 
Published: January 2020

Purpose
The purpose of this paper is to determine the properties of analysts’ cash flows from operations (CFO) forecast generated for Australian listed firms as a productive activity, within the wider processes of financial disclosure in Australia.

Design/methodology/approach
Two categories of criteria are adopted: first, basic predictive statistical performance relative to a benchmark model and earnings forecasts; and second, relevance for equity pricing, as indicated by the market reaction to cash flow or forecast error reactions. The final sample comprised 2,138 observations between 2001 and 2016 and several regression models are estimated to determine the relative performance and market reaction.

Findings
Analysts’ consensus cash flow forecasts demonstrate poor predictive performance relative to earnings forecasts. Cash flow forecasts are typically naïve extensions of earnings forecasts. Furthermore, cash flow forecasts appear to be of minimal use for equity market participants in complementing earnings forecasts’ role in informing firms’ equity pricing.

Practical implications
While analysts’ earnings forecasts are useful for making predictions, the role of analysts’ cash flow forecasts in capital market functional efficiency appears quite limited.

Originality/value
This study is one of few that examines comparative usefulness of analysts’ earnings and cash flow forecasts and their predictive power using the Australian setting. Additionally, it enriches the sparse international literature on such forecasts.