bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgene directed induction of a stem cell-derived human embryo model
Authors: Weatherbee Bailey AT , Gantner Carlos W , Daza Riza M , Hamazaki Nobuhiko , Iwamoto-Stohl Lisa K. , Shendure Jay , Zernicka-Goetz Magdalena 
Published: June 2023

AbstractThe human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by the inability to observe the embryoin vivo. Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages1. Here, we establish a human post-implantation embryo model comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by hypoblast-and trophoblast-like tissues. We demonstrate that these inducible human embryoids robustly generate several cell types, including amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP signaling. This model also allowed us to identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated3model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.
Calculating and applying pathogen mutational spectra using MutTui
Authors: Ruis Christopher , Tonkin-Hill Gerry , Floto R. Andres , Parkhill Julian 
Published: June 2023

AbstractMutational spectra describe the pattern of mutations acquired during evolution and are driven by factors including mutagens, repair processes and selection. Calculating mutational spectra of pathogen genomic datasets may enable analysis of factors that influence these mutational processes, including replication niches, transmission routes and pathogen biology. Here, we introduce MutTui, which can leverage multiple types of sequence data to calculate and compare mutational spectra of DNA and RNA pathogens. MutTui is available athttps://github.com/chrisruis/MutTui.
AddBiomechanics: Automating model scaling, inverse kinematics, and inverse dynamics from human motion data through sequential optimization
Authors: Werling Keenon , Bianco Nicholas A. , Raitor Michael , Stingel Jon , Hicks Jennifer L. , Collins Steven H. , Delp Scott L. , Liu C. Karen 
Published: June 2023

AbstractCreating large-scale public datasets of human motion biomechanics could unlock data-driven breakthroughs in our understanding of human motion, neuromuscular diseases, and assistive devices. However, the manual effort currently required to process motion capture data and quantify the kinematics and dynamics of movement is costly and limits the collection and sharing of large-scale biomechanical datasets. We present a method, called AddBiomechanics, to automate and standardize the quantification of human movement dynamics from motion capture data. We use linear methods followed by a non-convex bilevel optimization to scale the body segments of a musculoskeletal model, register the locations of optical markers placed on an experimental subject to the markers on a musculoskeletal model, and compute body segment kinematics given trajectories of experimental markers during a motion. We then apply a linear method followed by another non-convex optimization to find body segment masses and fine tune kinematics to minimize residual forces given corresponding trajectories of ground reaction forces. The optimization approach requires approximately 3-5 minutes to determine a subject’s skeleton dimensions and motion kinematics, and less than 30 minutes of computation to also determine dynamically consistent skeleton inertia properties and fine-tuned kinematics and kinetics, compared with about one day of manual work for a human expert. We used AddBiomechanics to automatically reconstruct joint angle and torque trajectories from previously published multi-activity datasets, achieving close correspondence to expert-calculated values, marker root-mean-square errors less than 2 cm, and residual force magnitudes smaller than 2% of peak external force. Finally, we confirmed that AddBiomechanics accurately reproduced joint kinematics and kinetics from synthetic walking data with low marker error and residual loads. We have published the algorithm as an open source cloud service atAddBiomechanics.org, which is available at no cost and asks that users agree to share processed and de-identified data with the community. As of this writing, hundreds of researchers have used the prototype tool to process and share about ten thousand motion files from about one thousand experimental subjects. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to use state-of-the-art biomechanical analysis, do so at lower cost, and share larger and more accurate datasets.
Centrifugal Gel Crushing for Gel-based Proteome Analysis
Authors: Nishida Hiroshi , Kanao Eisuke , Ishihama Yasushi 
Published: June 2023

ABSTRACTWe have developed a centrifugal gel crushing method using a pipette tip. Polyacrylamide gel slices are extruded from the narrowing cavity of a pipette tip by centrifugation in a few minutes to crush them into pieces of appropriate size. The size of the crushed gel could be controlled by several parameters, including centrifugal force and pipette tip cavity. In shotgun proteomics, gel-based LC/MS/MS, so-called GeLC/MS/MS, involves the essential but tedious processes of pre-fractionation by SDS-PAGE, followed by dicing the entire gel lane into several parts, fine dicing, and in-gel digestion after the diced gel is manually transferred to a microtube. In this study, we developed an alternative way to crush the pre-fractionated gel slice into small and irregular-shaped gels by centrifugal extrusion of the sliced gel from the narrow cavity of a pipette tip. As a result, we observed an improved recovery and reproducibility of digested proteins compared to the conventional method of manual dicing. We believe that this simple and rapid method of crushing polyacrylamide gels, which allows for parallel operations and automation, is useful for GeLC/MS/MS analysis and applicable to other approaches including top-down proteomics.Abstract Figure
Mechanism of negativeμ-opioid receptor modulation by sodium ions
Authors: Thomson Neil J. , Zachariae Ulrich 
Published: June 2023

AbstractThe negative allosteric modulation of G-protein coupled receptors (GPCRs) by Na+ions, known as the sodium effect, was first described in the 1970s for opioid receptors (ORs). Since then, it has been detected almost universally amongst class A GPCRs. High-resolution structures of class A GPCRs in the inactive state exhibit a Na+ion bound to a conserved pocket near residue D2.50, whereas the active state structures of GPCRs are incompatible with Na+binding. Correspondingly, Na+ions diminish the affinity of receptor agonists, stabilize the receptors in the inactive state, and reduce basal signalling levels. Despite these observations, a detailed mechanistic explanation of how Na+ions negatively modulate the receptor and inhibit activation has remained elusive. Here, we apply a mutual-information based analysis method to μs-timescale all-atom molecular dynamics simulations of the μ-OR to decipher conformational changes within the protein matrix and protein-internal water molecules that are directly coupled to the binding of Na+. Our results reveal that Na+binding is tightly coupled to a water wire that links the Na+binding site with the agonist binding pocket. Furthermore, Na+binding leads to rearrangements in polar protein networks that propagate conformational changes both to the agonist and the intracellular G-protein binding sites via conserved micro-switch motifs. Our findings provide a mechanistic link between the presence of the ion and altered agonist binding affinity, receptor deactivation and the depression of basal signalling.
M3NetFlow: A novel multi-scale multi-hop graph AI model for integrative multi-omic data analysis
Authors: Zhang Heming , Goedegebuure S. Peter , Ding Li , DeNardo David , Fields Ryan C. , Chen Yixin , Payne Philip , Li Fuhai 
Published: June 2023

SummaryMulti-omic data-driven studies, characterizing complex disease signaling system from multiple levels, are at the forefront of precision medicine and healthcare. The integration and interpretation of multi-omic data are essential for identifying molecular targets and deciphering core signaling pathways of complex diseases. However, it remains an open problem due the large number of biomarkers and complex interactions among them. In this study, we propose a novel Multi-scale Multi-hop Multi-omic graph model,M3NetFlow, to facilitate generic multi-omic data analysis to rank targets and infer core signaling flows/pathways. To evaluate M3NetFlow, we applied it in two independent multi-omic case studies: 1) uncovering mechanisms of synergistic drug combination response (defined as anchor-target guided learning), and 2) identifying biomarkers and pathways of Alzheimer ‘s disease (AD). The evaluation and comparison results showedM3NetFlowachieves the best prediction accuracy (accurate), and identifies a set of essential targets and core signaling pathways (interpretable). The model can be directly applied to other multi-omic data-driven studies. The code is publicly accessible at:https://github.com/FuhaiLiAiLab/M3NetFlow
ASCL1-ERK1/2 Axis: ASCL1 restrains ERK1/2 via the dual specificity phosphatase DUSP6 to promote survival of a subset of neuroendocrine lung cancers
Authors: Martin-Vega Ana , Earnest Svetlana , Augustyn Alexander , Wichaidit Chonlarat , Gazdar Adi , Girard Luc , Peyton Michael , Kollipara Rahul K. , Minna John D. , Johnson Jane E. , Cobb Melanie H. 
Published: June 2023

SummaryThe transcription factor achaete-scute complex homolog 1 (ASCL1) is a lineage oncogene that is central for the growth and survival of small cell lung cancers (SCLC) and neuroendocrine non-small cell lung cancers (NSCLC-NE) that express it. Targeting ASCL1, or its downstream pathways, remains a challenge. However, a potential clue to overcoming this challenage has been information that SCLC and NSCLC-NE that express ASCL1 exhibit extremely low ERK1/2 activity, and efforts to increase ERK1/2 activity lead to inhibition of SCLC growth and surival. Of course, this is in dramatic contrast to the majority of NSCLCs where high activity of the ERK pathway plays a major role in cancer pathogenesis. A major knowledge gap is defining the mechanism(s) underlying the low ERK1/2 activity in SCLC, determining if ERK1/2 activity and ASCL1 function are inter-related, and if manipulating ERK1/2 activity provides a new therapeutic strategy for SCLC. We first found that expression of ERK signaling and ASCL1 have an inverse relationship in NE lung cancers: knocking down ASCL1 in SCLCs and NE-NSCLCs increased active ERK1/2, while inhibition of residual SCLC/NSCLC-NE ERK1/2 activity with a MEK inhibitor increased ASCL1 expression. To determine the effects of ERK activity on expression of other genes, we obtained RNA-seq from ASCL1-expressing lung tumor cells treated with an ERK pathway MEK inhibitor and identified down-regulated genes (such as SPRY4, ETV5, DUSP6, SPRED1) that potentially could influence SCLC/NSCLC-NE tumor cell survival. This led us to discover that genes regulated by MEK inhibition suppress ERK activation and CHIP-seq demonstrated these are bound by ASCL1. In addition, SPRY4, DUSP6, SPRED1 are known suppressors of the ERK1/2 pathway, while ETV5 regulates DUSP6. Survival of NE lung tumors was inhibited by activation of ERK1/2 and a subset of ASCL1-high NE lung tumors expressed DUSP6. Because the dual specificity phosphatase 6 (DUSP6) is an ERK1/2-selective phosphatase that inactivates these kinases and has a pharmacologic inhibitor, we focused mechanistic studies on DUSP6. These studies showed: Inhibition of DUSP6 increased active ERK1/2, which accumulated in the nucleus; pharmacologic and genetic inhibition of DUSP6 affected proliferation and survival of ASCL1-high NE lung cancers; and that knockout of DUSP6 “cured” some SCLCs while in others resistance rapidly developed indicating a bypass mechanism was activated. Thus, our findings fill this knowledge gap and indicate that combined expression of ASCL1, DUSP6 and low phospho-ERK1/2 identify some neuroendocrine lung cancers for which DUSP6 may be a therapeutic target.
FLOWERING LOCUS Cdrives delayed flowering inArabidopsisgrown and selected at elevated CO2
Authors: Henderson-Carter Aleah , Kinmonth-Schultz Hannah , Hileman Lena , Ward Joy K. 
Published: June 2023

SummaryAltered flowering time at elevated [CO2] is well documented, although mechanisms are not well understood. AnArabidopsisgenotype previously selected for high fitness at elevated [CO2] (SG) showed delayed flowering and larger size at flowering when grown at elevated (700 ppm) versus current (380 ppm) [CO2]. This response was correlated with prolonged expression ofFLOWERING LOCUS C(FLC), a vernalization-responsive floral repressor gene.To determine ifFLCdirectly delays flowering at elevated [CO2] in SG, we used vernalization (extended cold) to downregulateFLCexpression. We hypothesized that vernalization would eliminate delayed flowering at elevated [CO2] through the direct reduction ofFLCexpression, eliminating differences in flowering time between current and elevated [CO2].We found that with downregulation ofFLCexpression via vernalization, SG plants grown at elevated [CO2] no longer delayed flowering compared to current [CO2]. Thus, vernalization returned the earlier flowering phenotype, counteracting effects of elevated [CO2] on flowering.This study indicates that elevated [CO2] can delay flowering directly throughFLC, and downregulation ofFLCunder elevated [CO2] reverses this effect. Moreover, this study demonstrates that increasing [CO2] may potentially drive major changes in development throughFLC.
Pneumatically Controlled Non-Equibiaxial Cell Stretching Device with Live-cell Imaging
Authors: Wang Jue , Chatterjee Aritra , Zigan Clarisse , Alborn Maya , Chan Deva D. , Chortos Alex 
Published: June 2023

AbstractObjectiveAdherent cell behavior is influenced by a complex interplay of factors, including chemical and mechanical signals.In vitroexperiments that mimic the mechanical environment experienced by cellsin vivoare crucial for understanding cellular behavior and the progression of disease. In this study, we developed and validated a low-cost pneumatically-controlled cell stretcher with independent control of strain in two directions of a membrane, enabling unequal biaxial stretching and realtime microscopy during actuation.MethodsThe stretching was achieved by two independent pneumatic channels controlled by electrical signals. We used finite element simulations to compute the membrane’s strain field and particle tracking algorithms based on image processing techniques to validate the strain fields and measure the cell orientation and morphology.ResultsThe device can supply uniaxial, equibiaxial, and unequal biaxial stretching up to 15% strain in each direction at a frequency of 1Hz, with a strain measurement error of less than 1%. Through live cell imaging, we determined that distinct stretching patterns elicited differing responses and alterations in cell orientation and morphology, particularly in terms of cell length and area.ConclusionThe device successfully provides a large, uniform, and variable strain field for cell experiments, while also enabling real-time, live cell imaging.SignificanceThis scalable, low-cost platform provides mechanical stimulation to cell cultures by independently controlling strains in two directions. This could contribute to a deeper understanding of cellular response to biorealistic strains and could be useful for futurein vitrodrug testing platforms.
Electrochemical evaluation of the anti-corrosion potential of selected amino acids on magnesium in aqueous sodium chloride solutions
Authors: Ikeuba Alexander I. , Sonde Christopher U. , Chukwudubem Ifeatu E. , Anozie Remigius C. , Ugi Benedict U. , Onyeachu Benedict , Ekerenam Okpo O. , Emori Wilfred 
Published: June 2023

Purpose
In line with current research efforts to develop eco-friendly strategies for corrosion mitigation, the purpose of this study is to appraise the anti-corrosion potential of selected amino acids on magnesium corrosion in sodium chloride solutions.

Design/methodology/approach
The corrosion inhibition of magnesium in aqueous solutions in the presence of benign, eco-friendly and readily available amino acids (alanine, arginine, histidine, lysine, proline) were evaluated using electrochemical methods.

Findings
Amino acids suppressed magnesium corrosion rate in aqueous sodium chloride solutions. The order of inhibition efficiency (%IE) was as follows: alanine < arginine < histidine < lysine < proline. The open circuit potential shift with respect to the blank was less than 0.085 VSCE, indicating that the amino acids are mixed-type corrosion inhibitors. In addition, the %IE of the amino acids was inversely proportional to the molecular weight. The results obtained indicate that the amino acids can serve as sustainable eco-friendly corrosion inhibitors for magnesium with the best inhibition efficiency attributed to proline with an efficiency of 85.1%.

Originality/value
New information on the application of amino acids as green sustainable corrosion inhibitors is provided herein.
Cronyism as a coping strategy: how do female academics deal with the lack of emancipative support?
Authors: Mousa Mohamed , Althalathini Doaa , Abdelgaffar Hala 
Published: June 2023

PurposeThis paper aims to explore how female academics use cronyism to cope with the lack of emancipative support resulting from their intense teaching and research duties, poor representation at senior administrative levels and their exhausting familial commitments.Design/methodology/approachQualitative semi-structured interviews were conducted with 32 female academics working full-time at four public universities in Egypt.FindingsThe findings showed that the low action resources (considering their unreasonable teaching loads, research requirements and supervision engagements), emancipative values (the unfair representation of female academics at senior administrative levels) and civic entitlement (universities not serious about promoting gender equality) are perceived by female academics as a lack of empowerment that necessitates their adoption of cronyism as their main coping strategy. Moreover, in male-dominated societies, female academics who do not have the power to shape their work-related status tend to use undesirable behaviours such as cronyism to mitigate the negative consequences of the shocks they encounter.Originality/valueThis paper contributes by filling a gap in human resources management in which empirical studies on the relationship between cronyism, emancipation and career shocks have been limited so far.
Prevalence and future trend in green supply chain management (GSCM): a systematic literature review
Authors: Balkumar Kartik , Gedam Vidyadhar V. , Himateja Mudunuri , Anbuudayasankar S.P. , Narassima M.S. , Ganesh K. , Dwarakanath M. , Pazhani Subramanian 
Published: June 2023

PurposeOver the last two decades, green supply chain management (GSCM) has enabled businesses to operate in an environmentally friendly manner. The present review examines 234 research articles and proposes a methodical literature review on GSCM, focusing on the aspects of sustainable development.Design/methodology/approachThe work examines conceptual, analytical, empirical and non-empirical research articles, analyzing at all levels of the organization, such as firm, dyad, supply chain and network. The objective of the review is to provide insights into the state and scope of existing research in the domain of GSCM, to identify the prevalence of GSCM and to consolidate the trend of future research. The literature review follows a systematic methodology for analyzing the literature.FindingsThe findings can support researchers in identifying research areas with significant impact and streamline research on GSCM in the future. Practitioners can utilize this structured classification to strategize their green initiatives in their firms.Originality/valueThe work contributes to providing literature that explores a detailed review in GSCM. The proposed literature review captures critical aspects in the domain of GSCM and offers future research directions.
The entrepreneurial accompaniment process and the importance of context
Authors: Abdennadher Sarhan , Boudabbous Sami 
Published: June 2023

PurposeBased on the different stages of the business creation process and using qualitative methods, this study's aim is to understand the functioning of the process of accompaniment entrepreneurs in the Tunisian context.Design/methodology/approachThe authors' exploratory research is qualitative. The data were collected through semi-structured interviews with a manager of an entrepreneurial accompaniment structure and 11 entrepreneurs. The entrepreneurs were subjected to a manual content analysis.FindingsThe results of the authors' research show the importance of the different mechanisms and structures put in place in the Tunisian context to promote private initiative. Tunisia is a diverse and very rich environment for the entrepreneurial process. The results of the authors' research confirm the processual nature of entrepreneurial accompaniment, which is presented as a continuum of five stages: the promoting of the entrepreneurial spirit, the exploration of the entrepreneurial profile, the study of the project and preparation of the business plan, the financing of the creation of a company and the creation of the company.Originality/valueThe authors' study contributes to a better understanding of the close relationship between the entrepreneurial process and accompaniment in order to confirm the procedural nature of the latter. Then, this study highlights the involvement of the context in entrepreneurial accompaniment and the role of this accompaniment in the success of the entrepreneurial project. In addition, the authors' survey confirms the interest of entrepreneurial accompaniment from the stage of promoting the entrepreneurial spirit until the effective creation of the company. Taking into account the specificities of each stage of the creation process, the study shows the interest of a procedural approach to entrepreneurial accompaniment in order to put in place the necessary and above all adequate measures to help the entrepreneur at each stage of the entrepreneurial process and, subsequently, maximize the chances of success of the entrepreneur's business.