bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-expression Patterns Explain how a Basic Transcriptional Role for MYC Modulates Wnt and MAPK Pathways in Colon and Lung Adenocarcinomas
Authors: Kucherlapati Melanie Haas 
Published: October 2021

AbstractGenome duplication begins at many epigenetically determined sites by pre-replication, pre-initiation, and replisome complexes; co-expression of their components must be optimally timed for S phase to occur. Oscillations of cyclin dependent kinases (Cdks) and regulator cyclins control cell cycling, many are pharmacological targets in cancer. This study examines gene expression relationships between drivers, cell cycle components, and a subset of proliferation genes in colon (COAD) and lung (LUAD) adenocarcinomas. Several known drivers of COAD and LUAD including APC, CTNNB1, KRAS, MYC, Braf, TP53, Rb1, and EGFR are also observed with focus on Wnt and MAPK signaling activation. Wnt signaling activation has relevance for immune checkpoint inhibitor therapy, as it provides cancer cells with escape mechanisms.MYC and KRAS co-expressed directly with far fewer proliferation genes in LUAD than COAD, suggesting their expression is ectopic to S phase in lung tumors. APC indirectly co-expressed with the same factors in both COAD and LUAD, but was found co-expressed indirectly with MYC and mutated only in COAD. Other Wnt signaling components also co-expressed in low MYC context in COAD, had significantly higher mutation frequencies. These data suggest Wnt signaling activation to be the indirect result of decreased MYC availability in COAD, and ectopic overexpression of MYC in LUAD. Cyclins CCNH, CCNC, and CCNK, co-expressed with far fewer proliferation genes in LUAD. Conversely, Braf had direct co-expression with many proliferation factors in non EGFR activated LUAD. Proliferation in EGFR activated LUAD was completely deregulated with E2F(s) 4/5/6 expression, potentially explaining their low proliferative ability.
Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats
Authors: Ribeiro Ana C. R. , Hawkins Elisa , Jahr Fay M. , McClay Joseph L. , Deshpande Laxmikant S. 
Published: October 2021

AbstractOrganophosphate (OP) chemicals include commonly used pesticides and also chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. While a chronic low-dose OP exposure does not produce acute cholinergic crises, epidemiological studies report long-term neuropsychiatric issues including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of a single, high-dose CPF or studied sub-chronic behavioral effects particularly the motor and cognitive effects of repeated low-dose CPF exposure. However, studies on chronic mood and depression-related morbidities following repeated sub-threshold CPF doses that would mimic occupationally-relevant OP exposures are lacking. Here, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21-days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following an 11-week washout period, CPF-treated rats exhibited a dose-dependent increase in signs of anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) despite a complete recovery of ChE activity at this stage. We speculate that both cholinergic and non-cholinergic mechanisms could play a role in the development of chronic OP-related depressive outcomes. The proposed CPF exposure paradigm could provide an ideal model to further study molecular mechanisms underlying cause and effect relationships between environmental OP exposures and the development of chronic behavioral deficits.
Genetically distant bacteriophages elicit unique genomic changes in Enterococcus faecalis
Authors: Johnson Cydney N. , Araya Dennise Palacios , Schink Viviane , Islam Moutusee , Mangalea Mihnea R. , Decurtis Emily K. , Ngo Tuong-Vi Cindy , Palmer Kelli L. , Duerkop Breck A. 
Published: October 2021

ABSTRACTThe human microbiota harbors diverse bacterial and bacteriophage (phage) communities. Bacteria evolve to overcome phage infection, thereby driving phage evolution to counter bacterial resistance. Understanding how phages promote genetic alterations in medically relevant bacteria is important as phages continue to become established biologics for the treatment of multidrug-resistant (MDR) bacterial infections. Before phages are used as standalone or combination antibacterial therapies, we must obtain a deep understanding of the molecular mechanisms of phage infection and how host bacteria alter their genomes to become resistant. We performed coevolution experiments using a single Enterococcus faecalis strain and two distantly related phages, to determine how phage pressure impacts the evolution of the E. faecalis genome. Whole genome sequencing revealed mutations previously demonstrated to be essential for phage infection. We also identified mutations in several genes previously unreported to be associated with phage infection in E. faecalis. Intriguingly, there was only one shared mutation in the E. faecalis genome in response to each of the two phages tested, demonstrating that infection by genetically distinct phages results in different host responses. This study shows that infection of the same host by disparate phages leads to evolutionary trajectories that result in distinct genetic changes. This implies that bacteria respond to phage pressure through host responses that are tailored to specific phages. This work serves as the basis for the study of E. faecalis genome evolution during phage infection and will inform the design of future therapeutics, such as phage cocktails, intended to target MDR E. faecalis.IMPORTANCEStudies characterizing the genome evolution of bacterial pathogens following phage selective pressure are lacking. Phage therapy is experiencing a rebirth in Western medicine. Such studies are critical for understanding how bacteria subvert phage infection and how phages evolve to counter such mutations. This study utilizes comparative genomic analyses to demonstrate how a pathogenic strain of Enterococcus faecalis responds to infection by two genetically distant phages. We show that genetic alterations in the E. faecalis genome accumulate in a manner that is specific to the infecting phage with little to no overlap in shared fixed mutations. This suggests that bacterial genome evolution in response to phage infection is uniquely tied to phage genotype, and sets a precedence for investigations into how phages drive bacterial genome evolution relevant to phage therapeutic applications.
Differential regulation of cranial and cardiac neural crest by Serum Response Factor
Authors: Dinsmore Colin J. , Soriano Philippe 
Published: October 2021

AbstractSerum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates these competing transcription programs through discrete sets of cofactors, the Ternary Complex Factors (TCFs) and Myocardin Related Transcription Factors (MRTFs). The relative contribution of these two programs toin vivoSRF activity and mutant phenotypes is not fully understood. To study how SRF utilizes its cofactors during development, we generated a knock-inSrfαIallele in mice harboring point mutations that disrupt SRF-MRTF-DNA complex formation but leave SRF-TCF activity unaffected. HomozygousSrfαI/αImutants die at E10.5 with notable cardiovascular phenotypes, and neural crest conditional mutants succumb at birth to defects of the cardiac outflow tract but display none of the craniofacial phenotypes associated with complete loss of SRF in that lineage. Our studies further support an important role for MRTF mediating SRF function in cardiac neural crest and suggest new mechanisms by which SRF regulates transcription during development.
Causal Haplotype Block Identification in Plant Genome-Wide Association Studies
Authors: Wu Xing , Jiang Wei , Fragoso Chris , Huang Jing , Zhou Geyu , Zhao Hongyu , Dellaporta Stephen 
Published: October 2021

AbstractGenome wide association studies (GWAS) can play an essential role in understanding genetic basis of complex traits in plants and animals. Conventional SNP-based linear mixed models (LMM) used in many GWAS that marginally test single nucleotide polymorphisms (SNPs) have successfully identified many loci with major and minor effects. In plants, the relatively small population size in GWAS and the high genetic diversity found many plant species can impede mapping efforts on complex traits. Here we present a novel haplotype-based trait fine-mapping framework, HapFM, to supplement current GWAS methods. HapFM uses genotype data to partition the genome into haplotype blocks, identifies haplotype clusters within each block, and then performs genome-wide haplotype fine-mapping to infer the causal haplotype blocks of trait. We benchmarked HapFM, GEMMA, BSLMM, and GMMAT in both simulation and real plant GWAS datasets. HapFM consistently resulted in higher mapping power than the other GWAS methods in simulations with high polygenicity. Moreover, it resulted in higher mapping resolution, especially in regions of high LD, by identifying small causal blocks in the larger haplotype block. In the Arabidopsis flowering time (FT10) datasets, HapFM identified four novel loci compared to GEMMA’s results, and its average mapping interval of HapFM was 9.6 times smaller than that of GEMMA. In conclusion, HapFM is tailored for plant GWAS to result in high mapping power on complex traits and improved mapping resolution to facilitate crop improvement.
Emergent phases of ecological diversity and dynamics mapped in microcosms
Authors: Hu Jiliang , Amor Daniel R. , Barbier Matthieu , Bunin Guy , Gore Jeff 
Published: October 2021

AbstractNatural ecological communities display striking features, such as high biodiversity and a wide range of dynamics, that have been difficult to explain in a unified framework. Using experimental bacterial microcosms, we perform the first direct test of recent complex systems theory predicting that simple aggregate parameters dictate emergent behaviors of the community. As either the number of species or the strength of species interactions is increased, we show that microbial ecosystems transition between distinct qualitative dynamical phases in the predicted order, from a stable equilibrium where all species coexist, to partial coexistence, to emergence of persistent fluctuations in species abundance. Under the same conditions, high biodiversity and fluctuations allow and require each other. Our results demonstrate predictable emergent diversity and dynamics in ecological communities.One-Sentence SummaryA phase diagram of ecological dynamics and diversity as a function of coarse-grained features of species interaction network.
Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons
Authors: Hwang Fuu-Jiun , Roth Richard H. , Wu Yu-Wei , Sun Yue , Liu Yu , Ding Jun B. 
Published: October 2021

SUMMARYLearning and consolidation of new motor skills require adaptations of neuronal activity and connectivity in the motor cortex and striatum, two key motor regions of the brain. Yet, how neurons undergo synaptic changes and become recruited during motor learning to form a memory engram remains an open question. Here, we train mice on a single-pellet reaching motor learning task and use a genetic approach to identify and manipulate behavior-relevant neurons selectively in the primary motor cortex (M1). We find that the degree of reactivation of M1 engram neurons correlates strongly with motor performance. We further demonstrate that learning-induced dendritic spine reorganization specifically occurs in these M1 engram neurons. In addition, we find that motor learning leads to an increase in the number and strength of outputs from M1 engram neurons onto striatal spiny projection neurons (SPNs) and that these synapses form local clusters along SPN dendrites. These results identify a highly specific synaptic plasticity during the formation of long-lasting motor memory traces in the corticostriatal circuit.HIGHLIGHTS– Motor performance is correlated with the reactivation of motor engram neurons– Motor learning increases spine density and new spine survival selectively on M1 engram neurons– Motor learning strengthens motor engram outputs to the striatum– M1 engram outputs converge onto clusters of dendritic spines on striatal spiny projection neurons
Blood cytokine analysis suggests that SARS-CoV-2 infection results in a sustained tumour promoting environment in cancer patients
Authors: De Winter Fien HR , Hotterbeekx An , Huizing Manon , Konnova Angelina , Fransen Erik , Jongers Bart’s , Jairam Ravi Kumar , Van averbeke Vincent , Moons Pieter , Roelant Ella , Le Blon Debbie , Berghe Wim Vanden , Janssens Annelies , Lybaert Willem , Croes Lieselot , Vulsteke Christof , Malhotra-Kumar Surbhi , Goossens Herman , Berneman Zwi , Peeters Marc , van Dam Peter , Kumar-Singh Samir 
Published: October 2021

AbstractCytokines, chemokines and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n=54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n=42). Of the 35 CCGs, 19 were common to both solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n=52). Of these TNF-α, IFN-β, TSLP and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data urge for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.
Validity of the Web-based, Self-directed, NeuroCognitive Performance Test in MCI
Authors: Doraiswamy P. Murali , Goldberg Terry E. , Qian Min , Linares Alexandra R. , Nwosu Adaora , Nino Izael , D’Antonio Jessica , Philips Julia , Ndouli Charlie , Hellegers Caroline , Michael Andrew M. , Petrella Jeffrey R. , Andrews Howard , Sneed Joel , Devanand Davangere 
Published: October 2021

ABSTRACTDigital cognitive tests offer several potential advantages over established paper-pencil tests but have not yet been fully evaluated for the clinical evaluation of mild cognitive impairment. The NeuroCognitive Performance Test (NCPT) is a web-based, self-directed, modular battery intended for repeated assessments of multiple cognitive domains. Using a sample of 101 MCI subjects, we report in this study that the NCPT composite is significantly correlated with both a composite measure of established tests (r=0.77, p<0.0001) as well as with the ADAS-Cog (r=0.55, p<0.0001). Both test batteries had a similar factor structure that included a large “g” component with a high eigenvalue. Further, both the NCPT and established tests significantly (p< 0.01) predicted the UPSA and FAQ, measures of daily functioning. Despite limitations such as a relatively small sample, absence of control group and cross-sectional nature, these findings are consistent with the growing literature on the promise of self-directed, web-based cognitive assessments for MCI.
SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an overzealous inflammatory cascade
Authors: Samsudin Firdaus , Raghuvamsi Palur , Petruk Ganna , Puthia Manoj , Petrlova Jitka , MacAry Paul , Anand Ganesh S. , Schmidtchen Artur , Bond Peter J. 
Published: October 2021

AbstractAccumulating evidence indicates a potential role for bacterial lipopolysaccharide (LPS) in the overactivation of the immune response during SARS-CoV-2 infection. LPS is recognised by Toll-like receptor 4 (TLR4) in innate immunity. Here, we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the SARS-CoV-2 spike (S) protein. LPS binds to the S2 pocket with a lower affinity compared to S1, suggesting its possible role as an intermediate in the TLR4 cascade. Congruently, nuclear factor-kappa B (NF-κB) activationin vitrois strongly boosted by S2.In vivo, however, a boosting effect is observed for both S1 and S2, with the former potentially facilitated by proteolysis. Collectively, our study suggests the S protein may act as a delivery system for LPS in host innate immune pathways. The LPS binding pockets are highly conserved across different SARS-CoV-2 variants and therefore represent potential therapeutic targets.
“I buy green products for my benefits or yours”: understanding consumers' intention to purchase green products
Authors: Sun Ying , Li Tieshan , Wang Shanyong 
Published: October 2021

PurposeThis research aims to conduct a comprehensive conceptual model and empirical validation of the integration of negative (ego-centric) and positive (altruistic and ego-centric) drivers of green buying based on social dilemma theory and psychological egoism theory.Design/methodology/approachData were collected using a self-administered questionnaire survey and analyzed with hierarchical regression analysis.FindingsThe results indicate that moral obligations, green self-identity, environmental concern and social pressure are positively related to green purchase intention, while perceived cost of green purchasing and price sensitivity are negatively. Meanwhile, social pressure positively moderates the relationship between price sensitivity and consumers' green purchasing intention, but negatively moderates the relationship between perceived cost of green purchasing and consumers' green purchasing intention.Originality/valueFirst, this study is a comprehensive model of the concept and empirical validation of the integration of negative (ego-centric) and positive (altruistic and ego-centric) drivers of green buying. Specially, this study emphasizes the neglected importance of positive ego-centric factors of green consumer behavior. Second, this study explicitly incorporated the moderating effect of social pressure in the context of China. Since green buying is a social dilemma, the changes in this social dilemma after being affected by social pressure under the Chinese collectivist culture are also worth noting. Third, little is known about what motivates green consumption in emerging economies, and this has been hampered by a lack of cultural knowledge, conceptual richness and behavioral research that critically analyses consumer behavior.
Welder learning curves behaviour: “focus on welding productivity with the TIG process of marine platforms stainless steel pipes”
Authors: Macedo Bruno Sobral , Ferreira Miguel Luiz Ribeiro 
Published: October 2021

PurposeThe purpose of the study is to analyse the feasibility of using the potential and exponential curve models to assess the learning of a group of welders, when welding stainless steel piping with the tungsten inert gas process.Design/methodology/approachThe welding productivity data grouped according to the requirements of the ASME SECTION IX code is organised into two groups: average productivity and baseline productivity. When processing the adjustment to the two models, the Excel software Solver tool was used. The criteria for assessing the quality of the fit were: least squared method, Spearman's correlation coefficient and graphical method. The impact of the variation coefficient on the average productivity and the amplitude (difference between the minimum and maximum productivity) was also evaluated on the baseline productivity.FindingsThe curves elaborated based on the average productivity presented better quality of adjustment than those constructed from the baseline productivity. The potential and exponential models presented similar adjustment conditions, with the second having a slightly superior performance. There were no productivity gains due to learning in the studied time interval. The grouping of the average daily productivity data based on the diameter range established in the ASME code section IX presented satisfactory results, enabling its use by the industry.Originality/valueThere is no news of work on piping welding with this focus. The proposal to group the productivity data according to the degree of difficulty of execution established by the ASME code section IX, widely used in the industry, is a significant contribution to monitoring the evolution of learning. In the same way, the results allow to adopt the average productivity determined from the first 20 days of realisation of a project, as a reasonable indicator to estimate the future performance of the work, helping to correct deadlines during the realisation of a project.
Psychosocial factors for safety performance of construction workers: taking stock and looking forward
Authors: Tong Ruipeng , Wang Lulu , Cao Lanxin , Zhang Boling , Yang Xiaoyi 
Published: October 2021

PurposePsychosocial factors have received increasing attention regarding significantly influencing safety in the construction industry. This research attempts to comprehensively summarize psychosocial factors related to safety performance of construction workers. In the context of coronavirus disease 2019, some typical psychosocial factors are selected to further analyze their influence mechanism of safety performance.Design/methodology/approachFirst, a literature review process was conducted to identify and summarize relevant psychosocial factors. Then, considering the impact of the epidemic, hypotheses on the relationship between six selected psychosocial factors (i.e. work stress, role ambiguity, work–family conflict, autonomy, social support and interpersonal conflict) and safety performance were proposed, and a hypothetical model was developed based on job demands-resources theory. Finally, a meta-analysis was used to examine these hypotheses and the model.FindingsThe results showed these psychosocial factors indirectly influenced workers’ safety performance by impacting on their occupational psychology condition (i.e. burnout and engagement). Work stress, role ambiguity, work–family conflict and interpersonal conflict were negatively related to safety performance by promoting burnout and affecting engagement. Autonomy and social support were positively related to safety performance by improving work engagement and reducing burnout.Originality/valueThis research is the pioneer systematically describing the overall picture of psychosocial factors related to the safety performance of construction workers. Through deeply discussed the mechanism of psychosocial factors and safety performance, it could provide a reference for the theory and application of psychosocial factors in the field of construction safety management.