bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-organized map: the new aproach for study of genetic divergence in kale
Authors: Brito Orlando Gonçalves , de Andrade Júnior Valter Carvalho , Azevedo Alcinei Mistico , Silva Maria Thereza Netta Lopes , de Sá Ludimila Geiciane , Rodrigues Clóvis Henrique Oliveira , Fernandes Ana Clara Gonçalves 
Published: May 2020

AbstractThe objective of this study was to study the genetic divergence between genotypes of kale, to propose a methodology for the use of neural networks of the SOM type and to test its efficiency through Anderson’s discriminant analysis. We evaluated 33 families of half-siblings of kale and three commercial cultivars. The design was a randomized block with four replications with six plants per plot. A total of 14 plant-level quantitative traits were evaluated. Genetic values were predicted at family level via REML / BLUP. For the study of divergence, neural networks of the SOM type (Self-organizing Map) were adopted. We evaluated different network architectures, whose consistencies of the clusters were identified by the Anderson discriminant analysis and by the number of empty clusters. After selecting the best network configuration, a dissimilarity matrix was obtained, from which a dendrogram was constructed using the UPGMA method. The best network architecture was formed with five rows and one column, totaling five neurons and consequently five clusters. The greatest dissimilarity was established between clusters I and V. The crossing between the genotypes of cluster I and those belonging to clusters III and V are the most recommended, since they aim to recombine families with characteristics of interest to the improvement and high dissimilarity. Anderson’s discriminant analysis showed that the genotype classification was 100% correct, indicating the efficiency of the methodology used.
Differential Effects of RASA3 Mutations on Hematopoiesis are Profoundly Influenced by Genetic Background and Molecular Variant
Authors: Robledo Raymond F. , Ciciotte Steven L. , Graber Joel H. , Zhao Yue , Lambert Amy J. , Gwynn Babette , Maki Nathaniel J. , Blanc Lionel , Peters Luanne L. 
Published: May 2020

AbstractStudies of the severely pancytopenicscatmouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survivalin utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage and decreased fetal liver erythropoiesis. Conditional deletion in hematopoietic stem and progenitor cells (HSPCs) usingVav-Crerecapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, leading to pancytopenia and death within two weeks. Notably, RASA3 missense mutations in mouse modelsscat(G125V) andhlb381(H794L) show dramatically different hematopoietic consequences specific to both genetic background and molecular variant. Global transcriptomic studies inscatsuggest potential targets to ameliorate disease progression.Author SummaryHematopoiesis is the process by which blood cells are formed. The individual must have a normal complement of red blood cells to prevent anemia, platelets to control bleeding, and white blood cells to maintain immune functions. All blood cells are derived from hematopoietic stem cells that differentiate into progenitor cells that then develop into mature circulating cells. We studied several mouse strains carrying different mutations in RASA3. We show that RASA3 is required at the earliest stages of blood formation, the stem and progenitor cells, and that the complement of genes other than RASA3, or the genetic background of the mutant strain, profoundly alters the overall effect on blood formation. Further, the molecular nature of the mutation in RASA3 also has a profound and independent effect on overall blood formation. One strain, designatedscat, suffers cyclic anemia characterized by severe anemic crisis episodes interspersed with remissions where the anemia significantly improves. Comparison ofscatcrisis and remission hematopoietic stem and progenitor cells reveals striking differences in gene expression. Analyses of these expression differences provide clues to processes that potentially drive improvement of anemia inscatand provide new avenues to pursue in future studies to identify novel therapeutics for anemia.
IntracellularCryptococcus neoformansdisrupts the transcriptome profile of M1- and M2-polarized host macrophages
Authors: Subramani Aarthi , Griggs Prianca , Frantzen Niah , Mendez James , Tucker Jamila , Murriel Jada , Sircy Linda M. , McClelland Erin E. , Seipelt-Thiemann Rebecca L. , Nelson David E. 
Published: May 2020

AbstractMacrophages serve as a first line of defense against infection with the facultative intracellular pathogen,Cryptococcus neoformans(Cn). However, the ability of these innate phagocytic cells to destroy ingestedCnis strongly influenced by polarization state with classically (M1) activated macrophages better able to control cryptococcal infections than alternatively (M2) activated cells. While earlier studies have demonstrated that intracellularCnminimally affects the expression of M1 and M2 markers, the impact on the broader transcriptome associated with these states remains unclear. To investigate this, we used anin vitrocell culture model of intracellular infection together with RNA sequencing-based transcriptome profiling to measure the impact ofCninfection on gene expression in both polarization states. The gene expression profile of both M1 and M2 cells was extensively altered to become more like naive (M0) macrophages. Gene ontology analysis suggested that this involved changes in the activity of the Janus kinase-signal transducers and activators of transcription (JAK-STAT), p53, and nuclear factor-κB (NF-κB) pathways. Analyses of the principle polarization markers at the protein-level also revealed discrepancies between the RNA- and protein-level responses. In contrast to earlier studies, intracellularCnwas found to increase protein levels of the M1 marker iNos. In addition, we identified common gene expression changes that occurred post-Cninfection, independent of polarization state. This included upregulation of the transcriptional co-regulatorCited1, which was also apparent at the protein level. These changes constitute a transcriptional signature of macrophageCninfection and provide new insights into howCnimpacts gene expression and the phenotype of host phagocytes.
Prevalence, Placenta Development, and Perinatal Outcomes of Women with Hypertensive Disorders of Pregnancy at Komfo Anokye Teaching Hospital
Authors: Awuah S. P. , Okai I. , Ntim E. A. , Bedu-Addo K. 
Published: May 2020

AbstractBackgroundOne of the most common medical problems associated with pregnancy is hypertension. Hypertensive disorders of pregnancy (HDP), which has been attributable to abnormal placentation may have adverse effects on both mother and foetus if left unchecked. The objective of this study was to determine the prevalence of Hypertensive Disorders of Pregnancy (HDP), the morphological variations of human placenta in HDP, and maternal and perinatal outcomes in HDP.Materials and MethodsThis was a prospective case-control study, conducted at Komfo Anokye Teaching Hospital (KATH), Ghana. The progression of pregnancy in normotensive and hypertensive pregnant women, and the eventual perinatal outcomes were closely followed. Statistical analysis was performed using IMB-SPSS version 23. Associations were considered significant at p values of ≤ 0.05.ResultsFrom a total of 214 deliveries recorded during the period of study, 84 (39.25%) were hypertensives. Forty four (52%) of the hypertensives had preeclampsia, 28 (33.3%) had gestational hypertension, 6 (7.1%) had eclampsia, 4 (4.8%) had chronic hypertension, and 2 (2.4%) had preeclampsia superimposed on chronic hypertension. The frequency of placental haematoma, placental infarction, and placental calcification in the normotensives were significantly (p=0.001) lower than that of the hypertensives. The mean placental weight (p = 0.01), placental volume (p = 0.001), placental diameter (p = 0.03), and placental thickness (p = 0.001) of the normotensives were significantly higher than those of the hypertensives. The number of normotensives in whom labour was induced, who had their babies delivered by caesarean section, and who were admitted after they had given birth were significantly (p=0.001) lower than that of hypertensives who underwent similar procedures. No stillbirths were recorded in the normotensives compared with four in the hypertensives. The number of babies delivered to the normotensives who were admitted to the NICU was significantly (p=0.001) lower than those delivered by hypertensives.ConclusionThere was a high prevalence of hypertensive disorders of pregnancy in the study site. The condition adversely affected placental development and perinatal outcomes. These adverse effects can be curtailed by embarking on a vigorous health education drive.
Cerebrospinal fluid endo-lysosomal proteins as potential biomarkers for Huntington’s disease
Authors: Lowe Alexander J. , Sjodin Simon , Rodrigues Filipe B. , Byrne Lauren M. , Blennow Kaj , Tortelli Rosanna , Zetterberg Henrik , Wild Edward J. 
Published: May 2020

AbstractMolecular markers derived from cerebrospinal fluid (CSF) represent an accessible means of exploring the pathobiology of Huntington’s disease (HD) in vivo. The endo-lysosomal/autophagy system is dysfunctional in HD, potentially contributing to disease pathogenesis and representing a potential target for therapeutic intervention. Several endo-lysosomal proteins have shown promise as biomarkers in other neurodegenerative diseases; however, they have yet to be fully explored in HD. We performed parallel reaction monitoring mass spectrometry analysis (PRM-MS) of multiple endo-lysosomal proteins in the CSF of 60 HD mutation carriers and 20 healthy controls. Using generalised linear models controlling for age and CAG, none of the 18 proteins measured displayed significant differences in concentration between HD patients and controls. This was affirmed by principal component analysis, in which no significant difference across disease stage was found in any of the three components representing lysosomal hydrolases, binding/transfer proteins and innate immune system/peripheral proteins. However, several proteins were associated with measures of disease severity and cognition: most notably amyloid precursor protein, which displayed strong correlations with composite Unified Huntington’s Disease Rating Scale, UHDRS Total Functional Capacity, UHDRS Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading. We conclude that although endo-lysosomal proteins are unlikely to have value as disease state CSF biomarkers for Huntington’s disease, several proteins demonstrate associations with clinical severity, thus warranting further, targeted exploration and validation in larger, longitudinal samples.
Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2
Authors: Gao Ang , Chen Zhilin , Segal Florencia Pereyra , Carrington Mary , Streeck Hendrik , Chakraborty Arup K. , Julg Boris 
Published: May 2020

AbstractWe describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.
Crystal structures of SARS-CoV-2 ADP-ribose phosphatase (ADRP): from the apo form to ligand complexes
Authors: Michalska Karolina , Kim Youngchang , Jedrzejczak Robert , Maltseva Natalia I. , Stols Lucy , Endres Michael , Joachimiak Andrzej 
Published: May 2020

ABSTRACTAmong 15 nonstructural proteins (Nsps), the newly emerging SARS-CoV-2 encodes a large, multidomain Nsp3. One of its units is ADP-ribose phosphatase domain (ADRP, also known as macrodomain) which is believed to interfere with the host immune response. Such a function appears to be linked to the protein’s ability to remove ADP-ribose from ADP-ribosylated proteins and RNA, yet the precise role and molecular targets of the enzyme remains unknown. Here, we have determined five, high resolution (1.07 - 2.01 Å) crystal structures corresponding to the apo form of the protein and complexes with 2-(N-morpholino)ethanesulfonic acid (MES), AMP and ADPr. We show that the protein undergoes conformational changes to adapt to the ligand in a manner previously observed before for in close homologs from other viruses. We also identify a conserved water molecule that may participate in hydrolysis. This work builds foundations for future structure-based research of the ADRP, including search for potential antiviral therapeutics.
A Molecular Mechanism for Probabilistic Bet-hedging and its Role in Viral Latency
Authors: Chaturvedi Sonali , Klein Jonathan , Vardi Noam , Bolovan-Fritts Cynthia , Wolf Marie , Du Kelvin , Mlera Luwanika , Calvert Meredith , Moorman Nathaniel J. , Goodrum Felicia , Huang Bo , Weinberger Leor S. 
Published: May 2020

ABSTRACTProbabilistic bet hedging, a strategy to maximize fitness in unpredictable environments by matching phenotypic variability to environmental variability, is theorized to account for the evolution of various fate-specification decisions, including viral latency. However, the molecular mechanisms underlying bet-hedging remain unclear. Here, we report that large variability in protein abundance within individual herpesvirus virion particles enables probabilistic bet hedging between viral replication and latency. Super-resolution imaging of individual virions of the human herpesvirus cytomegalovirus (CMV) showed that virion-to-virion levels of pp71 tegument protein—the major viral transactivator protein—exhibit extreme variability. This super-Poissonian tegument variability promoted alternate replicative strategies: high virion pp71 levels enhance viral replicative fitness but, strikingly, impede silencing, whereas low virion pp71 levels reduce fitness but promote silencing. Overall, the results indicate that stochastic tegument packaging provides a mechanism enabling probabilistic bet hedging between viral replication and latency.SIGNIFICANCEProbabilistic bet hedging is a generalized diversification strategy to maximize fitness in unpredictable environments, and has been proposed as an evolutionary basis for herpesvirus latency. However, the molecular mechanisms enabling probabilistic bet hedging have remained elusive. Here, we find that the human herpesvirus cytomegalovirus—a major cause of birth defects and transplant failures—utilizes stochastic variability in the abundance of a protein packaged into individual viral particles to enable probabilistic bet hedging between alternate viral states.
Discovery of anti-amoebic inhibitors from screening the MMV Pandemic Response Box onBalamuthia mandrillaris, Naegleria fowleriandAcanthamoeba castellanii
Authors: Rice Christopher A. , Troth Emma V. , Russell A. Cassiopeia , Kyle Dennis E. 
Published: May 2020

AbstractPathogenic free-living amoebae,Balamuthia mandrillaris, Naegleria fowleriand severalAcanthamoebaspecies are the etiological agents of severe brain diseases, with case mortality rates >90%. A number of constraints including misdiagnosis and partially effective treatments lead to these high fatality rates. The unmet medical need is for rapidly acting, highly potent new drugs to reduce these alarming mortality rates. Herein, we report the discovery of new drugs as potential anti-amoebic agents. We used the CellTiter-Glo 2.0 high-throughput screening methods to screen the Medicines for Malaria Ventures (MMV) Pandemic Response Box in a search for new active chemical scaffolds. Initially we screened the library as a single-point assay at 10 and 1 µM. From these data, we reconfirmed hits by conducting quantitative dose response assays and identified 12 hits againstB. mandrillaris, 29 againstN. fowleriand 14 againstA. castellaniiranging from nanomolar to low micromolar potency. We further describe 11 novel molecules with activity againstB. mandrillaris, 22 againstN. fowleriand 9 againstA. castellanii.These structures serve as a starting point for medicinal chemistry studies and demonstrate the utility of phenotypic screening for drug discovery to treat diseases caused by free-living amoebae.
Defining the art product: a network perspective
Authors: Wickham Mark , Lehman Kim , Fillis Ian 
Published: May 2020

PurposeThis paper explores the nature of art as a product through a network perspective, accounting for key contributing stakeholders in shaping its essence.Design/methodology/approachThis study adopted a qualitative data collection and analysis design and is centred on a series of face-to-face interviews with established Australian visual artists.FindingsResults support the notion of an art product shaped by interconnections and interdependencies of actors in the art market. In particular, attention is paid to the roles of actors in conceptual, production and distribution networks.Research limitations/implicationsAlthough there are idiosyncrasies that (in part) define the Australian art market context, the issues identified here are nonetheless useful in determining the nature of the interconnectedness of the art market in other similar Western contexts. Many Australian artists have achieved similar recognition and status to other established artists elsewhere. Future cross-cultural comparative research should be carried out in order to assess this relationship in the longer term.Practical implicationsArtists at different stages of their careers can transfer the findings of this research into the development of a series of relevant strategies and tactics for developing their art and culture products more effectively.Originality/valueAlthough philosophical assessments of art as a product have been carried out elsewhere, there is a lack of evaluation from an art versus marketplace lens in considering the perspectives of interested stakeholders
Correlations between facial emotion recognition and cognitive flexibility in autism spectrum disorder
Authors: Fabio Rosa Angela , Esposito Sonia , Carrozza Cristina , Pino Gaetana , Caprì Tindara 
Published: May 2020

Purpose
Various studies have examined the role of executive functions in autism, but there is a lack of research in the current literature on cognitive flexibility in autism spectrum disorders (ASD). The purpose of this study is to investigate whether cognitive flexibility deficits could be related to facial emotion recognition deficits in ASD.

Design/methodology/approach
In total, 20 children with ASD and 20 typically developing children, matched for intelligence quotient and gender, were examined both in facial emotion recognition tasks and in cognitive flexibility tasks through the dimensional change card sorting task.

Findings
Despite cognitive flexibility not being a core deficit in ASD, impaired cognitive flexibility is evident in the present research. Results show that cognitive flexibility is related to facial emotion recognition and support the hypothesis of an executive specific deficit in children with autism.

Research limitations/implications
One of the limit is the use of just one cognitive test to measure cognitive flexibility and facial recognition. This could be important to be taken into account in the new research. By increasing the number of common variables assessing cognitive flexibility, this will allow for a better comparison between studies to characterize impairment in cognitive flexibility in ASD.

Practical implications
Investigating impairment in cognitive flexibility may help to plan training intervention based on the induction of flexibility.

Social implications
If the authors implement cognitive flexibility people with ASD can have also an effect on their social behavior and overcome the typical and repetitive behaviors that are the hallmark of ASD.

Originality/value
The originality is to relate cognitive flexibility deficits to facial emotion.
The complexities of managing historic buildings with BIM
Authors: Charlton James , Kelly Kenneth , Greenwood David , Moreton Leo 
Published: May 2020

PurposeThe adoption of building information modelling (BIM) in managing built heritage is an exciting prospect, but one that presents complexities additional to those of modern buildings. If challenges can be identified and overcome, the adoption of historic BIM (HBIM) could offer efficiencies in how heritage buildings are managed.Design/methodology/approachUsing Durham Cathedral as a case study, we present the workflows applied to create an asset information model to improve the way this unique UNESCO World Heritage Site is managed, and in doing so, set out the challenges and complexities in achieving an HBIM solution.FindingsThis study identifies the need for a better understanding of the distinct needs and context for managing historic assets, and the need for heritage information requirements (HIR) that reflect this.Originality/valueThis study presents first-hand findings based on a unique application of BIM at Durham Cathedral, a UNESCO World Heritage Site. The study provides a better understanding of the challenges and drivers of HBIM adoption across the heritage sector and underlines the need for information requirements that are unique to historical buildings/assets to deliver a coherent and relevant HBIM approach.
Tailoring service recovery messages to consumers’ affective states
Authors: Hill Cummings Krista , Yule Jennifer A. 
Published: May 2020

PurposeThis study aims to propose that providers should tailor recovery responses to consumers’ emotional states to improve evaluations and behavioral intentions.Design/methodology/approachA multi-study approach comprising field and lab data was used. The field study, conducted on the Boston public transport network during a weather crisis, sought to determine how a provider should deliver their recovery response to match the consumer’s affective state. In the lab studies, the importance of tailoring a recovery message to the consumer’s state is experimentally demonstrated while controlling for factors such as consumer brand involvement.FindingsThis study finds that an emotion-focused recovery emphasizing empathy should be given to those in an avoidance affective state (i.e. focused on the avoidance of negative outcomes) such as worry. A problem-focused recovery, in which the focus is on the process that led to the failure and the steps that will be taken to correct it, should be provided to those in an approach state (i.e. concerned with advancement and accomplishment) such as anger. This study also finds this effect is more salient under low involvement conditions.Research limitations/implicationsFuture research should examine how nonverbal behavior during recovery can be tailored to a consumer’s state.Practical implicationsService providers are encouraged to tailor recovery messages to consumers’ affective states.Originality/valueTo the best of the authors’ knowledge, this study is the first to examine matching recovery messages to affective states, an important contribution as service failures can elicit a wide variety of affective states that influence how consumers react to recovery messages.