bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into β-manno-oligosaccharide uptake and metabolism inBifidobacterium adolescentisDSMZ 20083 from whole-genome microarray analysis
Authors: Rose Mary Priyanka , Monica P , Kapoor Mukesh 
Published: March 2022

AbstractAimsTo determine the ability of adult-associatedB. adolescentisDSMZ 20083 to utilize dietary β-manno-oligosaccharides and understand the underlying molecular mechanism.Methods and ResultsIn-vitrofermentation and TLC were used to determine the ability ofB. adolescentisDSMZ 20083 to utilize β-manno-oligosaccharides from guar gum, locust bean gum, konjac and copra meal. Further, Whole-genome transcriptome analysis, q-RT-PCR and molecular docking were employed to reconstruct copra meal β-manno-oligosaccharides (CM-β-MOS) utilization pathway inB. adolescentisDSMZ 20083.B. adolescentisDSMZ 20083 grew appreciably (A600nmup to 0.8) on all tested β-manno-oligosaccharides but maximally on CM-β-MOS. Transcriptome analysis revealed differential up-regulation of three distinct gene clusters encoding, ABC transporter cassette (ESBP’s and permeases), MFS transporter, GH1 β-glucosidase and, GH32 β-fructofuranosidases. ABC and MFS possibly transported majorly DP≥2 and DP≥3 CM-β-MOS, respectively. Sugar absorption and utilization pathways; ABC transport system, pyruvate metabolism, glycolysis/gluconeogenesis, pentose, and glucouronate inter-conversions were also up-regulated.ConclusionsB. adolescentisDSMZ 20083 possibly utilizes ABC & MFS transporters to internalise and GH1 β-glucosidase, and GH32 β-fructofuranosidase to deconstruct CM-β-MOS.Significance and Impact of the StudyFirst study reporting possible molecular determinants used byB. adolescentisDSMZ 20083 to utilize β-manno-oligosaccharides and thus, can prove resourceful in precision microbiome modulation.
Origin and persistence of polymorphism in loci targeted by disassortative preference: a general model
Authors: Coron Camille , Costa Manon , Leman Hélène , Llaurens Violaine , Smadi Charline 
Published: March 2022

AbstractThe emergence and persistence of polymorphism within populations generally requires specific selective regimes. Here, we develop an unifying theoretical framework to explore how disassortative mating can generate and maintain polymorphism at the targeted loci. To this aim, we model the dynamics of alleles at a single locus A in a population of haploid individuals, where reproductive success depends on the combination of alleles carried by the parents at locus A. Our theoretical study of the model confirms that the conditions for the persistence of a given level of allelic polymorphism depend on the relative reproductive advantages among pairs of individuals. Interestingly, equilibria with unbalanced allelic frequencies were shown to emerge from successive introduction of mutants.We then investigate the role of the function linking allelic divergence to reproductive advantage on the evolutionary fate of alleles within population. Our results highlight the significance of the shape of this function on both the number of alleles maintained and their level of genetic divergence. Large number of alleles are maintained with substantial turn-over among alleles when disassortative advantage slowly increases when allelic differentiation becomes large. In contrast, few highly differentiated alleles are predicted to be maintained when genetic differentiation has a strong effect on disassortative advantage. These opposite effects predicted by our model shed light on the levels of allelic differentiation and polymorphism empirically observed in loci targeted by disassortative mate choice.
On optimal temozolomide scheduling for slowly growing gliomas
Authors: Segura-Collar Berta , Jiménez-Sánchez Juan , Gargini Ricardo , Dragoj Miodrag , Sepúlveda Juan M. , Pešić Milica , Sánchez-Gómez Pilar , Pérez-García Víctor M. 
Published: March 2022

BackgroundTemozolomide (TMZ) is an oral alkylating agent active against gliomas with a favorable toxicity profile. It is part of the standard of care in the management of glioblastoma, and is commonly used in low-grade gliomas. In-silico mathematical models can potentially be used to personalize treatments and to accelerate the discovery of optimal drug delivery schemes.MethodsAgent-based mathematical models fed with either mouse or patient data were developed for the in-silico studies. The experimental test beds used to confirm the results were: mouse glioma models obtained by retroviral expression of EGFR wt or EGFR vIII in primary progenitors from p16/p19 ko mice and grown in vitro and in vivo in orthotopic allografts, and human glioblastoma U251 cells immobilized in alginate microfibers. The patient data used to parametrize the model were obtained from the TCGA/TCIA databases and the TOG clinical study.ResultsSlow growth ‘virtual’ murine gliomas benefited from increasing TMZ dose separation in silico. In line with the simulation results, improved survival, reduced toxicity, lower expression of resistance factors and reduction of the tumor mesenchymal component were observed in experimental models subject to long-cycle treatment, particularly in slowly-growing tumors. Tissue analysis after long-cycle TMZ treatments revealed epigenetically-driven changes in tumor phenotype, which could explain the reduction in glioma growth speed. In-silico trials provided support for methods of implementation in human patients.ConclusionsIn-silico simulations, and in-vitro and in-vivo studies show that TMZ administration schedules with increased time between doses may reduce toxicity, delay the appearance of resistances and lead to survival benefits mediated by changes in the tumor phenotype in gliomas.IMPORTANCE OF THE STUDYIn-vivo evidence is provided of improvements in survival, resistance, and toxicity from TMZ schemes with long rest periods between doses in slowly-growing GBM mouse models. The results match hypotheses generated in silico using a mathematical model incorporating the main biological features and fed with real patient data. An epigenetically-driven change in tumor phenotype was also revealed experimentally, which could explain the reduction in glioma growth speed under the ‘long cycle’ scheme. To determine the extent to which our results hold for human patients, large sets of simulations were performed on virtual patients. These in-silico trials suggest different ways to bring the benefits observed in experimental models into clinical practice.
A chemical molecule promotes Trop2+ biliary duct organoids differentiation into insulin-secreting cells
Authors: Liu Miao , Yu Wen , Wang Yannan , Yan Bingru , Shang Jie , Zhang Congyi , Wu Huan , Tai Sheng , Jin Liang , Teng Chun-Bo 
Published: March 2022

SummaryCell replacement therapy is a hopeful strategy for diabetes treatment, whereas lack of pancreas donors leads this strategy to a dilemma. Here, we demonstrate that Trop2 is a useful marker to enrich the progenitors with a long-term organoid formation capability from extrahepatic bile ducts in both mouse and human. Based on BMP7 initiation, the Trop2-positive mouse extrahepatic bile duct organoids (mBDOs) could be induced to produce 8.49 ± 0.45% of insulin-secreting cells. We further screened out a chemical small molecule TLY142, which significantly increased the proportion of insulin-secreting cells to 19.9 ± 0.62% and 25.50 ± 4.82% in induced mouse and human extrahepatic bile duct organoids (hBDOs) in vitro, and transplantation of these differentiated organoids into STZ-induced diabetic nude mice remarkably improved their blood glucose and enhanced glucose sensitivity. This study provides a novel strategy that using small molecules promotes biliary duct organoids differentiation into β cells to cure diabetes.Graphic abstract
Cohesin is required for meiotic spindle assembly independent of its role in cohesion in C. elegans
Authors: McNally Karen Perry , Danlasky Brennan , Barroso Consuelo , Gong Ting , Li Wenzhe , Martinez-Perez Enrique , McNally Francis J. 
Published: March 2022

AbstractAccurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by analyzing mutants that lack cohesion between chromosomes. Both a spo-11, rec-8, coh-3, coh-4 quadruple mutant and a spo-11, rec-8 double mutant entered M phase with single chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on single chromatids of the double mutant was sufficient to recruit haspin- dependent Aurora B kinase, which regulated the localization of the spindle-assembly factors CLASP-2 and kinesin-13 to mediate bipolar spindle assembly in the apparent absence of chromosomal bipolarity. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.
An integrated cell atlas of the human lung in health and disease
Authors: Sikkema L , Strobl D , Zappia L , Madissoon E , Markov NS , Zaragosi L , Ansari M , Arguel M , Apperloo L , Bécavin C , Berg M , Chichelnitskiy E , Chung M , Collin A , Gay ACA , Hooshiar Kashani B , Jain M , Kapellos T , Kole TM , Mayr C , von Papen M , Peter L , Ramírez-Suástegui C , Schniering J , Taylor C , Walzthoeni T , Xu C , Bui LT , de Donno C , Dony L , Guo M , Gutierrez AJ , Heumos L , Huang N , Ibarra I , Jackson N , Kadur Lakshminarasimha Murthy P , Lotfollahi M , Tabib T , Talavera-Lopez C , Travaglini K , Wilbrey-Clark A , Worlock KB , Yoshida M ,   Lung Biological Network Consortium, Desai T , Eickelberg O , Falk C , Kaminski N , Krasnow M , Lafyatis R , Nikolíc M , Powell J , Rajagopal J , Rozenblatt-Rosen O , Seibold MA , Sheppard D , Shepherd D , Teichmann SA , Tsankov A , Whitsett J , Xu Y , Banovich NE , Barbry P , Duong TE , Meyer KB , Kropski JA , Pe’er D , Schiller HB , Tata PR , Schultze JL , Misharin AV , Nawijn MC , Luecken MD , Theis F 
Published: March 2022

ABSTRACTOrgan- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.
Actin-dependent recruitment of AGO2 to the zonula adherens
Authors: Bridges Mary Catherine , Nair-Menon Joyce , Risner Alyssa , Jimenez Douglas W. , Daulagala Amanda C. , Kingsley Christina , Davis Madison E. , Kourtidis Antonis 
Published: March 2022

ABSTRACTAdherens junctions are cadherin-based structures critical for cellular architecture. E-cadherin junctions in mature epithelial cell monolayers tether to an apical actomyosin ring to form the zonula adherens (ZA). We have previously shown that the adherens junction protein PLEKHA7 associates with and regulates the function of the core RNA interference (RNAi) component AGO2 specifically at the ZA. However, the mechanism mediating Ago2 recruitment to the ZA remained unexplored. Here, we reveal that this ZA-specific recruitment of AGO2 depends on both the structural and tensile integrity of the actomyosin cytoskeleton. We found that depletion of not only PLEKHA7, but also either of three PLEKHA7-interacting, LIM-domain family proteins, namely LMO7, LIMCH1, and PDLIM1, results in disruption of actomyosin organization and tension, as well as disruption of AGO2 junctional localization and of its miRNA-binding ability. We also show that AGO2 binds Myosin IIB and that PLEKHA7, LMO7, LIMCH1, and PDLIM1 all disrupt interaction of AGO2 with Myosin IIB at the ZA. These results demonstrate that recruitment of Ago2 to the ZA is sensitive to actomyosin perturbations, introducing the concept of a mechanosensitive RNAi machinery, with potential implications in tissue remodeling and in disease.SummaryRecruitment and miRNA-binding activity of the key RNA interference (RNAi) component AGO2 to epithelial zonula adherens depends on apical actomyosin integrity and tension, revealing the existence of a mechanosensitive RNAi machinery at the zonula adherens.Significance StatementPrevious work has shown that PLEKHA7 recruits core RNAi components, including AGO2, to regulate tumor-suppressing miRNAs specifically at the zonula adherens (ZA), through an unknown mechanism.Here, the authors show that three LIM domain-containing proteins, LMO7, LIMCH1, and PDLIM1, are also responsible for AGO2’s recruitment and miRNA activity at the ZA and that all four PLEKHA7, LMO7, LIMCH1, PDLIM1 mediate AGO2 recruitment to the ZA not due to their protein-protein interactions, but through stabilizing actomyosin structure and tension.These findings introduce a mechanosensitive RNAi machinery responsive to actomyosin perturbations, with potentially broad implications in regulation of cellular plasticity.
Predicting the corrosion properties of cast and hot isostatic pressed CoCrMo/W alloys in seawater by machine learning
Authors: Jiang Xue , Yan Yu , Su Yanjing 
Published: March 2022

Purpose
Cobalt-based alloys exhibit a unique combination of wear resistance, strength and corrosion resistance. Localized corrosion of such alloys in seawater system can be several orders of magnitude faster than general corrosion, and direct experimental evidence of the local activation process is still lacking, which makes the accurate prediction for properties difficult, especially for long-term corrosion. The purpose of this study is revealing the relationship between multiple environments and corrosion properties to predict the corrosion of cobalt-based alloys.

Design/methodology/approach
A data-driven method for the prediction of the corrosion behavior of cast and hot isostatic-pressed CoCrMo/W alloys in seawater is proposed. The gradient boosting regression models calculate mean relative errors (MREs) of 0.160 and 0.435 by evaluating a hold-out set for breakdown potential (Eb) and maximum current density (imax), respectively, considering various compositions, synthesis methods and corrosion environments.

Findings
The models can be used to estimate the “unseen” cobalt-based alloy after immersion in 3.5 Wt.% NaCl solution for one, two, four and eight months to obtain high precision with MREs of 7.8% and 9.8% for Eb and imax, respectively.

Originality/value
Machine learning method provides novel and promising insights for the prediction of localized corrosion properties.
Pastoralist conflict: children as catalysts for peace building
Authors: Dzinekou Jonas Yawovi , Kabui Anne Christine 
Published: March 2022

Learning outcomes
The learning outcomes of this paper are as follows: to uncover the social innovation in the peacebuilding model of the Children for Peace Initiative (CPI); to identify the key success factors of the CPI model; to discuss the sustainability of the model of CPI-Kenya; and to apply the contact theory and personal transformation theory to CPI model.

Case overview/synopsis
The case is written to address the issue of intercommunity peacebuilding between the Pokot and Samburu. It focusses on social innovation in peacebuilding implemented in seven villages among the Pokot and Samburu. The activities revolve around the involvement of children as key actors in peacebuilding and the exchange of heifer between the communities to sustain the peace. The heifer is one of the sources of conflict. In this case, this powerful cultural symbol is used to create bonding and friendship between the conflicting communities. While there were many peacebuilding attempts in the pastoralist communities, CPI-Kenya introduced a model that focusses on building a new human relationship between the communities. It includes all the social groups of the communities, making it more successful and sustainable than other previous attempts.The two co-founders, Monica Kinyua and Hilary Bukuno, narrated the story of how the CPI-Kenya started, highlighting the uniqueness of their peace-building approach and the strategy they adopted to build a new relationship between the communities. They shared powerful stories of how CPI managed to bring a peaceful living between the Samburu and Pokot in Baragoi, particularly in Amaya and Longewan villages.In the beginning, the main challenge for the CPI-Kenya team was finding the right approach to implement their peace innovation by making children become the catalyst of peace in their communities. With children at the centre of the CPI model, the best approach was getting entry through schools. The school is an accepted social system that has over time gained trust from all parents who send their children there.The case provides the students with the element that is essential for social innovation in the community. The students can learn from the case the importance of collaboration for social initiative, community engagement and inclusive peacebuilding. It portrays a unique strategy in community leadership and management. Further, the students will learn one concrete application of the human contact theory and personal transformation theory. The case highlight how cultural symbols that are sources of conflict can be turned into the symbol of peace. Starting with one group of people in a community and growing into other groups in the same community through a ripple effect.

Complexity academic level
The case can be used for Master’s and Doctorate.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.
Facilitating EFL teachers’ professional development through CLS of English literature instruction
Authors: Zhang Huaqing , Luo Shaoqian 
Published: March 2022

PurposeAgainst the backdrop of China’s curriculum reform, this paper explores how a Chinese lesson study (CLS) of English literature instruction in a senior high school promotes the teacher participant’s professional development (PD) in teacher beliefs and emotions, teaching contents, teaching approaches and learner outcomes.Design/methodology/approachThis study adopted the CLS approach to explore the teacher participant, Lily’s PD. Three rounds of CLS of short fiction instruction were conducted. Triangulated data including interviews, reflection journals, discussion notes and lesson materials were collected for directed qualitative content analysis.FindingsThe results show that through the CLS, Lily has (1) changed her beliefs about the curriculum and literature instruction, and improved her emotion management and become more resilient and motivated; (2) shifted her teaching focus from forms and facts to meanings; (3) adopted a more learner-centred and inquiry-based teaching approach and (4) received satisfactory learner outcomes including increased learner participation and quality output. The follow-up class observations suggest the sustainability of such development.Originality/valueThis study applies and validates a conceptual framework of teachers’ PD, and establishes the value of promoting curriculum reform and facilitating EFL teachers’ PD through CLS and literature instruction.
Inventory planning under supplier uncertainty in a two-level supply chain
Authors: Yassine Noura 
Published: March 2022

PurposeDue to uncertainty in supply chains caused by the coronavirus disease 2019 (COVID-19), organizations are adjusting their supply chain design to address challenges faced during the pandemic. To safeguard their operations against disruption in order quantities, supply chain members have been looking for alternate suppliers. This paper considers a two-level supply chain consisting of a manufacturer and two suppliers of a certain type of components required for the production of a finished product. The primary supplier (supplier A) is unreliable, in the sense that the quantity delivered is usually less than the ordered quantity. The proportion of the ordered quantity delivered by supplier A is a random variable with a known probability distribution. The secondary supplier (supplier B) always delivers the order in its entirety at a higher cost and can respond instantaneously. In order for supplier B to respond instantaneously, the manufacturer is required to reserve a certain quantity at an additional cost. Once the quantity received from the main supplier is observed, the manufacturer may place an order not exceeding the reserved quantity.Design/methodology/approachA mathematical model describing the production/inventory situation of the supply chain is formulated. The model allows the determination of the manufacturer's optimal ordering policy.FindingsAn expression for the expected total cost per unit time function is derived. The optimal solution is determined by solving a system of nonlinear equations obtained by minimizing the expected total cost function.Practical implicationsThe proposed model can be used by supply chain managers aiming at identifying various ways of handling the uncertainty in the flow of supplies across the chain.Originality/valueThis proposed model addresses a gap in the production/inventory literature.