bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning to Encode Cellular Responses to Systematic Perturbations with Deep Generative Models
Authors: Xue Yifan , Ding Michael Q. , Lu Xinghua 
Published: January 2020

SummaryComponents of cellular signaling systems are organized as hierarchical networks, and perturbing different components of the system often leads to transcriptomic profiles that exhibit compositional statistical patterns. Mining such patterns to investigate how cellular signals are encoded is an important problem in systems biology. Here, we investigated the capability of deep generative models (DGMs) for modeling signaling systems and learning representations for transcriptomic profiles derived from cells under diverse perturbations. Specifically, we show that the variational autoencoder and the supervised vector-quantized variational autoencoder can accurately regenerate gene expression data. Both models can learn representations that reveal the relationships between different classes of perturbagens and enable mappings between drugs and their target genes. In summary, DGMs can adequately depict how cellular signals are encoded. The resulting representations have broad applications in systems biology, such as studying the mechanism-of-action of drugs.
Molecular Pathways Resultant in Fever due to Inhibitory Effects of Binding PGE2 to Glucocorticoid Receptors
Authors: Schaper Charles D. 
Published: January 2020

AbstractThermoregulation is crucial to homeostasis, but the mechanisms of its dysfunction are still largely mysterious, including fever, which is generally the most disconcerting sign of a serious infection or disease. Theories on body temperature dynamics that aim to explain a fever, such as changes in an internal setpoint, have been proposed, but none can identify the fundamental molecular pathways that produce a fever. Moreover, causative substances, pyrogens such as prostaglandin E2 (PGE2), have not been associated with receptors at the hypothalamus, which is responsible for autonomic control of temperature, and therefore no molecular path has been previously identified that can elucidate the causative reason for fever. Here, molecular pathways resultant in fever are identified for the first time. Based on recent developments made by this lab, which has shown that PGE2 possesses similar binding affinity as the hormone cortisol (CORT) at the critical ligand binding domain (LBD) of glucocorticoid receptors (GR); mathematical modeling and a case study for validation is used to present that competitive inhibition of CORT by PGE2 as the fundamental reason for dysfunctional dynamics of body temperature, including fever. The model characterizing temperature is in the form of a multivariable feedback controller comprised of a superposition of proportional and derivative terms of temperature, CORT, and PGE2 concentration at the hypothalamus thereby linking the cardiovascular, immune, and neural systems. The model constitutes a framework of linear equations that describes a closed-loop system of body temperature effects in response to infectious agents, triggering events, and other causal factors. The model is validated by examination of the transient and spectral characteristics of a three-day case history involving temperature trajectories after physical activity protocols in response to a standard vaccination of pneumococcal and influenza species. The framework for the development of the molecular pathways of fever is further proposed as extensible to other signs and symptoms of disease and emotional dysfunction whose causative source is competitive inhibition of PGE2 and CORT at the LBD of GR.Graphical Abstract
Rerouting of an Esx substrate pair from the ESX-1 type VII secretion system to ESX-5 by modifying a PE/PPE substrate pair
Authors: Damen Merel P.M. , Phan Trang H. , Ummels Roy , Rubio-Canalejas Alba , Bitter Wilbert , Houben Edith N.G. 
Published: January 2020

AbstractType VII secretion systems (T7SSs) secrete a wide range of extracellular proteins that play important roles in bacterial viability and in host-pathogen interactions of pathogenic mycobacteria. There are five subtypes of mycobacterial T7SSs, called ESX-1 to ESX-5, and four classes of T7SS substrates, namely the Esx, PE, PPE and Esp proteins. At least some of these substrates are secreted as heterodimers. The ESX systems mediate the secretion of specific members of the Esx, PE and PPE proteins, raising the question how these substrates are recognized in a system-specific fashion. PE/PPE heterodimers interact with their cognate EspG chaperones, which recently has been shown to determine their designated secretion pathway. Both structural and pulldown analysis suggest that EspG is unable to interact with Esx proteins and therefore the determining factor for system-specificity of these substrates remains unknown. In this study, we have investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 (MMAR_0187/MMAR _0188) inMycobacterium marinum. While this substrate pair was hardly secreted when ectopically expressed, secretion was observed when EsxB_1/EsxA_1 was co-expressed together with PE35/PPE68_1 (MMAR_0185/MMAR_0186), which are encoded by the same operon. Surprisingly, co-expressing EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5chaperone binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in co-secretion of EsxB_1/EsxA_1 via ESX-5. Our data suggest a secretion model in which PE35/PPE68_1 is a determinant factor for the system-specific secretion of EsxB_1/EsxA_1.
Non-invasive monitoring of drug action: a new livein vitroassay design for Chagas’ disease drug discovery
Authors: Fesser Anna F. , Braissant Olivier , Olmo Francisco , Kelly John M. , Mäser Pascal , Kaiser Marcel 
Published: January 2020

AbstractNew assay designs are needed to improve the predictive value of theTrypanosoma cruzi in vitrotests used as part of the Chagas’ disease drug development pipeline. Here, we employed a green fluorescent protein (eGFP)-expressing parasite line and live high-content imaging to monitor the growth ofT. cruziamastigotes in mouse embryonic fibroblasts. A novel assay design allowed us to follow parasite numbers over 6 days, in four-hour intervals, while occupying the microscope for only 24 hours per biological replicate. Dose-response curves were calculated for each time point after addition of test compounds, revealing how EC50 values first decreased over the time of drug exposure, and then leveled off. However, we observed that parasite numbers could vary, even in the untreated controls, and at different sites in the same well, which caused variability in the EC50 values. To overcome this, we established that fold change in parasite number per hour is a more robust and informative measure of drug activity. This was calculated based on an exponential growth model for every biological sample. The net fold change per hour is the result of parasite replication, differentiation, and death. The calculation of this fold change enabled us to determine the tipping point of drug action, i.e. the point immediately before the fold change becomes negative, independent of the drug concentration and exposure time. This time-to-kill over drug concentration revealed specific pharmacodynamic profiles of the benchmark drugs benznidazole and posaconazole.Author SummaryChagas’ disease, caused byTrypanosoma cruzi, is a chronic debilitating infection occurring mostly in Latin America. There is an urgent need for new, well tolerated drugs. However, the latest therapeutic candidates have yielded disappointing outcomes in clinical trials, despite promising preclinical results. This demands new and more predictivein vitroassays. To address this, we have developed an assay design that enables the growth ofT. cruziintracellular forms to be monitored in real time, under drug pressure, for 6 days post-infection. This allowed us to establish the tipping point of drug action, when the parasites stop multiplying and start to die. The resulting pharmacodynamics profiles can provide robust and informative details on anti-chagasic candidates, as demonstrated for the benchmark drugs benznidazole and posaconazole.
A-to-I RNA editing in honeybees shows signals of adaptation and convergent evolution
Authors: Duan Yuange , Dou Shengqian , Porath Hagit T. , Huang Jiaxing , Eisenberg Eli , Lu Jian 
Published: January 2020

SUMMARYSocial insects exhibit extensive phenotypic diversities among the genetically similar individuals, suggesting a role for the epigenetic regulations beyond the genome level. The ADAR-mediated adenosine-to-inosine (A-to-I) RNA editing, an evolutionarily conserved mechanism, facilitates adaptive evolution by expanding proteomic diversities. Here, we characterize the A-to-I RNA editome of honeybees (Apis mellifera), identifying 407 high-confidence A-to-I editing sites. Editing is most abundant in the heads, and shows signatures for positive selection. Editing behavior differs between foragers and nurses, suggesting a role for editing in caste differentiation. Although only five sites are conserved between bees and flies, an unexpectedly large number of genes exhibit editing in both species, albeit at different locations, including the nonsynonymous auto-editing ofAdar. This convergent evolution, where the same target genes independently acquire recoding events in distant diverged clades, together with the signals of adaptation observed in honeybees alone, further supports the notion of recoding being adaptive.
Biodiversity Of Bacteriophages From Lysed Batch Culture Of RecombinantEscherichia ColiBL21(DE3) Examined By Anion Exchange Chromatography And TEM
Authors: Kushkina Alla , Tovkach Fedor 
Published: January 2020

AbstractIt was found that the phage population assaulted a batch culture of an industrial recombinant derivative ofE. coliBL21(DE3) was attenuated that manifested in producing pinprick-type plaques and their inability to propagation in subsequent passages. Because of this, the goals of the present research were to evaluate biodiversity and scrutinize the possible virion structural defects of the attenuated phage population prior to pure phage lines isolation. The anion exchange chromatography (AEC) was chosen as the principal method allowing to get a comparative phage population profile based on the virion net surface charge, as well as to treat the 5-liter virion-contained sample and collect high-quality concentrated and separated phage fractions to further analysis. The isolate consisted of a mix of two phages belonging toMyoviridae(A2-morphotype) andSiphoviridae(B1-morphotype) families. By restriction analysis, the main portion of this phage pool (about 99% of all virions) was identified as the primary population of myophage Lw1, which possessed its own intra-population biodiversity (heterogeneity). It consisted of a major and two minor subpopulations that differed by phage capsid size and shape. The subpopulation III consisted of aberrant tubby-phages with triprolate (expanded at both sides) capsids having low aspect ratio.
The conservation status and population decline of the African penguin deconstructed in space and time
Authors: Sherley Richard B. , Crawford Robert J. M. , de Blocq Andrew D. , Dyer Bruce M. , Geldenhuys Deon , Hagen Christina , Kemper Jessica , Makhado Azwianewi B. , Pichegru Lorien , Tom Desmond , Upfold Leshia , Visagie Johan , Waller Lauren J. , Winker Henning 
Published: January 2020

AbstractUnderstanding changes in abundance is crucial for conservation, but population growth rates often vary over space and time. We use 40 years of count data (1979–2019) and Bayesian state-space models to assess the African penguinSpheniscus demersuspopulation under IUCN Red List Criterion A. We deconstruct the overall decline in time and space to identify where urgent conservation action is needed. The global African penguin population met the threshold forEndangeredwith a high probability (97%), having declined by almost 65% since 1989. An historical low of ~17,900 pairs bred in 2019. Annual declines were faster in the South African population (−4.2%, highest posterior density interval, HPDI: −7.8 to −0.6%) than the Namibian one (−0.3%, HPDI: −3.3 to +2.6%), and since 1999 were almost 10% at South African colonies north of Cape Town. Over the 40-year period, the Eastern Cape colonies went from holding ~25% of the total penguin population to ~40% as numbers decreased more rapidly elsewhere. These changes coincided with an altered abundance and availability of the main prey of African penguins. Our results underline the dynamic nature of population declines in space as well as time and highlight which penguin colonies require urgent conservation attention.
Assessing the adoption of sustainability practices in tourism industry
Authors: Islam Md. Farijul , Zhang Jing , Hasan Najmul 
Published: January 2020

PurposeThe purpose of this study is to assess the key determinants of sustainability practices and policy adoption in small- and medium-sized tourism accommodation firms and its possible impact on the firm’s competitive advantages.Design/methodology/approachA combined model has been developed and tested with a set of relevant hypotheses based on primary data collected from tourism firm’s owners and personnel. Structural equation modeling has been used to test and validate the hypotheses.FindingsThe key results indicate that collaboration and innovation of tourism firms, employee culture, technological infrastructure, tourism intermediary’s sustainability practices and top management support have a significant impact on sustainability practices adoption, whereas government sustainable tourism policy and local’s attitude toward sustainability have an insignificant impact.Practical implicationsThe findings assist managers and owners of tourism accommodation firms to re-address their policy and operational processes toward sustainability. This study is an endeavor to bridge the knowledge gap of current literature on sustainable practice adoption and tourism accommodation firm. This would be ensured through encouraging the economic aspect of sustainability practices and also facilitate social well-being, which is a real contribution that ought to practice to other countries where the tourist area is environmentally adverse tremendous.Social implicationsConsidering sustainability is a social commitment, this study positively changes tourists’ behavioral approach reducing the undesirable use of social resources and maximizing the enduring socio-economic and environmental development for social well-being.Originality/valueThe novelty of this empirical study is that sustainability practices and policies adoption is entirely a new phenomenon. However, the mediating impact of the construct on the competitive advantage of small and medium tourism accommodation firms enhances the effectiveness of emerging tourism economy.
Antecedents of green purchase behavior of cosmetics products
Authors: Jaini Azila , Quoquab Farzana , Mohammad Jihad , Hussin Nazimah 
Published: January 2020

PurposeThere is a growing need to conduct more studies to understand the green purchase behavior of cosmetics products because of its increasing trend in the emerging markets. Considering this, the study aims to shed some light on the factors that affect green purchase behavior of Malaysian consumers in the context of cosmetics product purchase. More specifically, the objective of this study is to examine the effect of altruistic and hedonic values and the mediating effect of personal norm and pro-environmental belief toward green purchase behavior.Design/methodology/approachAn online survey using judgmental sampling technique was used to gather responses from green cosmetics consumers. A questionnaire was designed to measure the study variables, which was then tested for content, and face validity and reliability prior to its administration. The structural equation modeling using the partial least squares approach (SmartPLS, version 3.7) was used to test the study hypotheses.FindingsThe results revealed that hedonic value has a significant and positive effect on pro-environmental belief. However, altruistic value did not exert any significant effect on pro-environmental belief. It is also found that pro-environmental belief positively affects personal norm, and as a consequence, personal norm affects green purchase behavior. The data also support the mediating effect of pro-environmental belief in the relationship between “hedonic value and personal norm.” Nevertheless, pro-environmental belief did not mediate the relationship between altruistic value and personal norm. Lastly, personal norm mediates the relationship between “pro-environmental belief and green purchase behavior”.Practical implicationsThe findings from this study enable managers, marketers and policy makers to execute better green strategies that would boost consumers’ green purchase behavior toward cosmetics products.Originality/valueThis study contributes to the existing literature on green purchase behavior by testing hedonic value as the antecedent and pro-environmental belief as the mediator by using the value-belief-norm theory. Moreover, this is a pioneer study to consider personal norm as the mediator of green purchase behavior.
Flexible leadership in the manufacturing sector
Authors: Alat Priya , Suar Damodar 
Published: January 2020

PurposeThe purpose of this paper is to explore leader flexibility in the manufacturing sector. The objectives are to understand the nature of uncertainties that leaders face and how their personal attributes facilitate them in responding to uncertain situations.Design/methodology/approachA total of 20 middle- and senior-level executives were interviewed, using seven semi-structured questions, from four states in India. Responses were analyzed using thematic analysis.FindingsIn this paper, two themes were identified: the need for flexibility and competencies. The need for flexibility included the factors that warrant adaptability and the performance requirements, such as changes in external environment, reconciling opposing demands, unpredictability of human resources and day-to-day contingencies. Performance requirements included monitoring the environment, anticipating changes, creating shared meanings, developing adaptability in human resources, understanding contradictions and generating alternate solutions. Competencies included balancing different values, roles, and behaviors, coaching and team building skills, planning skills, systems thinking, social skills, conflict management skills and openness to learning.Research limitations/implicationsInterviews were conducted with only executives; interviewing their subordinates may have revealed different perspectives. With the accounts being retrospective, few details may have been missed or exaggerated.Practical implicationsThe findings can be used to apprise leaders of the challenges they may face and develop competencies required for leader flexibility.Originality/valueLeadership research in the manufacturing sector is mostly focused on leaders’ responses to environmental uncertainties. This research identifies the task demands associated with unpredictability of human factors and daily contingencies, and the competencies used to respond.
Relationship between earnings management, CEO compensation, and stock return on Tehran Stock Exchange
Authors: Moardi Mahdi , Salehi Mahdi , Poursasan Simin , Molavi Homa 
Published: January 2020

PurposeThe purpose of this paper is to investigate the relationship between earnings management and chief executive officers’ (CEOs) compensation. Owing to the fact that earnings management does not have only opportunistic effects, but signaling effects, this study focuses on accruals quality to examine earnings management incentives. Thus, accruals quality is described against future cash flow. The empirical evidences suggest that a positive relationship between discretionary accruals and future cash flow provides predictive elements for earnings management, whereas a negative relationship between discretionary accruals and future cash implies to opportunistic elements for earnings management. Should there is no significant relationship between discretionary accruals and future cash flow, there will be no earnings management, and such a result suggests that incentives and managers’ performance in these firms differ.Design/methodology/approachThe statistical population of this research consists of all listed companies on the Tehran Stock Exchange during 2009–2016. Panel data method is applied in order to estimate the research model.FindingsFindings of the study show that there is no significant relationship between discretionary accruals and future cash flow in pharmaceutical and food industries, thus they have neither predictive nor opportunist earnings management, while the results evidence a negative significant relationship between discretionary accruals and future cash flow in machineries, automobile, mineral and chemical industries. Furthermore, it can be alleged that there is no significant difference between CEOs’ compensation in firms with opportunistic earnings management (OEM) and other types of earnings management. It shows that firms do not have appropriate plans for CEOs’ compensation. Moreover, the relationship between earnings management and stock return has been investigated in this study. We document that stock return is influenced by accruals quality and its components. In other words, stock return significantly differs in firms with OEM and firms without any kind of earnings management.Research limitations/implicationsThe authors’ findings provide contributions; for managers, it is noticeable that stock markets have sufficient comprehension about financial statements and the undertaken procedures on them, resulting in a higher return base on fair information. For investors and regulators, using the findings, may have deeper understanding to distinguish between industries that are recognized as opportunistic and non-opportunistic, which, in turn, results in better decision and regulation.Originality/valuePrevious studies have been mostly investigated OEM, while the current study examines both signaling and opportunistic aspects of earnings management.