bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic CRISPR-Cas nuclease with expanded enzymatic activities
Authors: Jabalera Ylenia , Tascón Igor , Samperio Sara , López-Alonso Jorge P. , Gonzalez-Lopez Monika , Aransay Ana M. , Abascal-Palacios Guillermo , Ubarretxena-Belandia Iban , Perez-Jimenez Raul 
Published: November 2023

SummaryClustered regularly interspaced short palindromic repeats (CRISPR)-associated endonucleases have revolutionized biotechnology for their potential as programmable genome editors. Yet, most natural nucleases and their variants have limitations. Here, we report a fully synthetic CRISPR-associated (Cas) nuclease (α-synCas) designed by Ancestral Sequence Reconstruction (ASR) that displays a set of robust and distinct targeting properties, not found in any other known CRISPR-Cas Class 2 system. We show that α-synCas is a PAMless nuclease able to catalyse RNA-guided, specific cleavage of dsDNA, ssDNA and ssRNA. The synthetic enzyme is also capable of sequence-nonspecific degradation of dsDNA, ssDNA and ssRNA following activation by complementary dsDNA, ssDNA and ssRNA targets. Furthermore, α-synCas exhibits a robust genome editing activity in human cells and bacteria. Cryo-electron microscopy structures of α-synCas ternary and quaternary complexes provide a framework to understand the structural basis for its expanded enzymatic activities. The capability for programmable multimodal targeting of virtually any nucleic acid sequence distinguishes α-synCas as a promising new tool to extend current CRISPR-based technologies.
Delivery mode impacts gut bacteriophage colonization during infancy
Authors: Subramanian Poorani , Romero-Soto Hector N. , Stern David B. , Maxwell George L. , Levy Shira , Hourigan Suchitra K. 
Published: November 2023

ABSTRACTBackgroundCesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory and immune health outcomes. Although gut bacteriophages can alter gut microbiome composition and impact host immune responses, little is known about how delivery mode impacts bacteriophage colonization over time. To begin to address this we examined how delivery mode affected bacteriophage colonization over the first two years of life.ResultsShotgun metagenomic sequencing was conducted on 272 serial stool samples from 55 infants, collected at 1-2 days of life and 2, 6, 12 and 24 months. 33/55 (60%) infants were born by vaginal delivery. DNA viruses were identified, and by host inference, 94% of the viral sequences were found to be bacteriophages. Alpha diversity of the virome was increased in vaginally delivered infants compared to cesarean section delivered infants at 2 months (Shannon index, p=0.022). Beta diversity significantly differed by delivery mode at 2, 6, and 12 months when stratified by peripartum antibiotic use (Bray–Curtis dissimilarity, all p<0.05). Significant differentially abundant predicted bacteriophage hosts by delivery mode were seen at all time points. Moreover, there were differences in predicted bacteriophage functional gene abundances up to 24 months by delivery mode. Many of the functions considered to play a role in host response were increased in vaginal delivery.ConclusionsClear differences in bacteriophage composition and function were seen by delivery mode over the first two years of life. Given that phages are known to affect host immune response, our results suggest that future investigation into how delivery mode may lead to adverse inflammatory outcomes should not only include bacterial microbial colonization but also the potential role of bacteriophages and transkingdom interactions.
Coordination of focal adhesion nanostructure and mechano-signaling drives cardiomyocyte differentiation
Authors: Xiao Jingwei , Zhong Xueying , Ang Jing Wen , Wong Darren Chen Pei , Lee Chang Jie Mick , Foo Roger S-Y , Kanchanawong Pakorn , Low Boon Chuan 
Published: November 2023

AbstractFocal adhesion (FA) organization and signaling are essential for cell growth and differentiation. However, the molecular mechanism that coordinates the FA signaling with cardiomyocyte differentiation has not been fully understood. Here, we provide empirical evidence that BNIP-2, a BCH-domain-containing protein, is the organizer of FA nanostructure that potentiates FA signaling and cell traction force transmission. Mechanistically, BNIP-2 serves as a scaffold for focal adhesion kinase (FAK), paxillin and vinculin to control their molecular organization and assembly/disassembly within FAs. Constitutively active phosphomimetic mutant FAK Y397D shows enhanced binding to BNIP-2, whereas the depletion of BNIP-2 reduces FAK phosphorylation and interaction between FAK and paxillin. Using H9c2 myoblasts and human embryonic stem cells as model systems, we show that BNIP-2 depletion results in aberrant FA dynamics with impairment of traction force, and changes in signature target genes, hereby impeding cardiomyocyte differentiation. BNIP-2 regulation of FA organization and dynamic is therefore pivotal to the mechanotransduction in cardiomyocyte differentiation, shedding new light to how FA-transduced force modulates cell growth and differentiation.
Long noncoding RNA Hottip maintained skeletal homeostasisviasuppressing the enhancer of zeste homolog 2 (Ezh2)/histone methylation regulatory axis
Authors: Li Zhi-Peng , Mai Yong-Xin , Zhou Shu-Ting , Shi Chuan-jian , Shao Jiang , Liang Puping , Liang Wei-cheng , Zhang Jin-fang 
Published: November 2023

AbstractRecent evidence suggests that long noncoding RNAs (lncRNAs) play a crucial role in regulating bone remodeling and skeletal homeostasis by coordinating the development of osteoblasts and osteoclasts. Several lncRNAs have been identified to participate in bone formation and resorption processes. Among them, the well-known oncogenic lncRNA, Hottip, has been reported to be involved in osteogenesis regulation. However, the specific function and underlying mechanisms remain poorly understood.In this study, we investigated the role of lncRNA Hottip in bone remodeling and skeletal homeostasis. Hottip knockout mice exhibited disrupted bone metabolism, abnormal bone tissue, and compromised bone quality, resulting in delayed fracture healing. In vitro experiments demonstrated that Hottip knockdown inhibited osteoblast differentiation while promoting osteoclast differentiation, with the opposite effect observed upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, leading to its degradation and facilitating the transcription of osteogenic genes by suppressing H3K9me3 and H3K27me3. In vivo experiments further validated the potential of Hottip overexpression to promote bone regeneration and accelerate fracture healing.In conclusion, our study reveals Hottip as a critical regulator in the differentiation of osteoblasts and osteoclasts, crucial for maintaining skeletal homeostasis. This lncRNA shows potential as a promising therapeutic target for bone regeneration.
Cell intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow
Authors: Alonso-Matilla Roberto , Lam Alice , Miettinen Teemu P. 
Published: November 2023

ABSTRACTCytokinesis is the process where the mother cell’s cytoplasm separates into daughter cells. This is driven by an actomyosin contractile ring that produces cortical contractility and drives cleavage furrow ingression, resulting in the formation of a thin intercellular bridge. While cytoskeletal reorganization during cytokinesis has been extensively studied, little is known about the spatiotemporal dynamics of the plasma membrane. Here, we image and model plasma membrane lipid and protein dynamics on the cell surface during leukemia cell cytokinesis. We reveal an extensive accumulation and folding of plasma membrane at the cleavage furrow and the intercellular bridge, accompanied by a depletion and unfolding of plasma membrane at the cell poles. These membrane dynamics are caused by two actomyosin-driven biophysical mechanisms: the radial constriction of the cleavage furrow causes local compression of the apparent cell surface area and accumulation of the plasma membrane at the furrow, while actomyosin cortical flows drag the plasma membrane towards the cell division plane as the furrow ingresses. The magnitude of these effects depends on the plasma membrane fluidity, cortex adhesion and cortical contractility. Overall, our work reveals cell intrinsic mechanical regulation of plasma membrane accumulation at the cleavage furrow that is likely to generate localized differences in membrane tension across the cytokinetic cell. This may locally alter endocytosis, exocytosis and mechanotransduction, while also serving as a self-protecting mechanism against cytokinesis failures that arise from high membrane tension at the intercellular bridge.
PEM-based random vibration analysis under service-braking conditions on an irregular track
Authors: Liu Xiaoxue , Liu Yuchen , Zhang Youwei , Guo Hanfei 
Published: November 2023

PurposeAccording to relevant research, non-uniform speed has a significant impact on the vehicle-track systems. Up to now, research work on it is still very limited. In this paper, the PEM is adopted to further transform it into a deterministic process to solve the vehicle’s problem of running at a non-uniform speed.Design/methodology/approachThe multi-body vehicle model has 10 degrees of freedom and the track is regarded as a finite long beam supported by lumped sleepers and ballast blocks. They are connected via linear Hertz springs. The vertical track irregularity is a Gaussian stationary process in the space domain. It is transformed into a uniformly modulated nonstationary random process in the time domain with respect to the non-uniform vehicle speed. By solving the equation of motion of the coupled vehicle-track system with the pseudo-excitation method, the pseudo-response and consequently the power spectral density and the standard deviation of the structural response can be obtained.FindingsTwo kinds of vehicle braking programs are taken in the numerical example and some beneficial conclusions are drawn.Originality/valueThe pseudo-excitation method (PEM) was used to perform the random vibration analysis of a coupled non-uniform speed vehicle-track system. Transforming the track irregularity into a uniformly modulated nonstationary random process in time domain with respect to the non-uniform vehicle speed was undertaken. The pseudo-response of the coupled system is solved by applying the Newmark algorithm with constant space integral steps. The random vibration transfer mechanism of the coupled system is fully discussed.
Exploring the relationship between entrepreneurial ecosystem inputs and outcomes: the role of digital technology adoption
Authors: Marinelli Luca , Bartoloni Sara , Costa Alessandra , Pascucci Federica 
Published: November 2023

PurposeThis work aims to explore the relationship between entrepreneurial ecosystems' (EEs) inputs and outcomes within a digital-technology-driven EE. Specifically, it focuses on how being part of an EE enhances digital technology adoption (DTA) and consequently facilitates EE outcomes.Design/methodology/approachThis paper employs a single-case study approach, focusing on Italian EE. The data analysis is based on the researchers' direct observations and semi-structured interviews with the EE founders' teams and the top management of the small- and medium-sized enterprises (SMEs) operating therein. Given the novelty of the topic and the lack of a clear research framework of analysis, a qualitative method is well suited for studying digital-technology-driven EE, thus gaining rich data about the phenomenon in a real-life context.FindingsThe findings of the study reveal that when specific eco-inputs (financial, knowledge, social and institutional assets) are correctly exploited to enhance DTA, important outcomes, namely, SME competitiveness and new technology-based venture creation and development, are generated.Originality/valueThe paper contributes to a relatively unexplored topic in the existing literature on EEs and digital technology. Specifically, through the proposition of a conceptual model, it sheds light on the relationship among EE inputs, DTA and EE outcomes.
Asset redeployability and corporate cash holdings
Authors: Bradley Wray , Sun Li 
Published: November 2023

PurposeThe purpose of the study is to investigate the impact of asset redeployability on the level of corporate cash holdings.Design/methodology/approachThe authors use regression analysis to examine the relation between asset redeployability and corporate cash holdings.FindingsUsing a large panel sample of US public firms from 1990 to 2020, the authors find a significant positive relation between asset redeployability and cash, which suggests that firms with more redeployable assets hold more cash.Originality/valueThe authors contribute to a growing literature in accounting and finance that investigates the impact of asset redeployability on firm characteristics and also contribute to the literature on the determinants of cash holdings.
Pre-education reflections of online and face-to-face clinical experiences
Authors: Casale Carolyn , Thomas C. Adrainne , Bazzi Ahlam Alma 
Published: November 2023

PurposeThis research study provides insight into students’ perceptions of teaching through virtual and face-to-face clinicals in an introductory education course in a pre-education program at a minority-serving institution.Design/methodology/approachThis study took place at an urban–suburban-centered community college in the Midwestern United States and was reviewed by the higher education institutional review board (IRB). Data were collected from pre-education majors enrolled in a four-hour Introduction to Education with field experiences.FindingsThe findings indicated that both virtual and face-to-face clinicals were beneficial to the development of pre-service teachers, particularly in an early introduction to education course.Research limitations/implicationsThe finding that virtual clinicals are significant to teacher growth is significant to teacher recruitment and preparation.Practical implicationsThe flexibility of a virtual clinical provides greater opportunities for low-income and marginalized populations with limited means and access.Social implicationsThis finding can lead to strategies to diversify teacher candidates.Originality/valueThis study sought to answer the following question: how do pre-education students reflect to understand the roles and responsibilities of teaching through virtual options vs face-to-face clinicals? The interest of this research is to expand pathways into the teaching profession to nontraditional, ethnically and culturally marginalized groups and historically underrepresented groups.
Propofol inhibits the proliferation, invasion, migration, and angiogenesis of oral squamous cell carcinoma through circ_0008898‐mediated pathway
Authors: Dong Hui , Zhou Weifu , Han Long , Zhao Qingjun 
Published: November 2023

AbstractPropofol has been shown to inhibit oral squamous cell carcinoma (OSCC) progression. However, it is not clear whether propofol mediates OSCC progression through regulating circular RNA (circRNA) network. Quantitative real‐time PCR was used to detect circ_0008898, miR‐545‐3p, and CT10 regulator of kinase‐like protein (CRKL) expression. Cell functions were determined using CCK8 assay, Edu staining, MTT assay, transwell assay, wound healing assay, tube formation assay, and flow cytometry. Protein levels were examined by western blot analysis. RNA interaction was confirmed by dual‐luciferase reporter assay and RIP assay. Our data showed that propofol repressed OSCC cell proliferation, invasion, migration, angiogenesis, and promoted apoptosis. circ_0008898 was highly expressed in OSCC, and its expression could be decreased by propofol. circ_0008898 silencing aggravated the suppressive effect of propofol on OSCC progression. In the mechanism, circ_0008898 could target miR‐545‐3p to positively regulate CRKL. MiR‐545‐3p inhibitor abolished the regulation of circ_0008898 silencing on propofol‐mediated OSCC cell progression. MiR‐545‐3p inhibited the progression of propofol‐treated OSCC cells, and this effect was reversed by CRKL overexpression. Also, circ_0008898 knockdown reduced OSCC tumor growth by regulating miR‐545‐3p/CRKL. In conclusion, propofol suppressed OSCC progression, which was achieved through regulating the circ_0008898/miR‐545‐3p/CRKL axis.
Association between participation at home and functional skills in children and adolescents with Down syndrome: A cross‐sectional study
Authors: Brugnaro Beatriz Helena , Kraus de Camargo Olaf , Pfeifer Luzia Iara , Pavão Silvia Letícia , Hlyva Oksana , Rocha Nelci Adriana Cicuto Ferreira 
Published: November 2023

AbstractBackgroundAccording to a biopsychosocial approach to health and disability, participation at home and functional skills are important components of the functioning. Therefore, knowledge about interactions between these components allows for targeting specific interventions.ObjectiveThis study investigated whether participation opportunities (frequency and involvement) for children/adolescents with Down syndrome (DS) in a realistic environment at their own home are associated with the functional skills related to the domains of Daily Activities, Mobility, Social/Cognitive and Responsibility.MethodsThis was an observational study. Forty‐eight children/adolescents with DS participated (mean age: 10.73 ± 3.43; n = 27 females). Participants were evaluated using the Participation and Environment Measure for Children and Youth (PEM‐CY) home environment setting (raw frequency and engagement scores) and Pediatric Evaluation of Disability Inventory speedy version (PEDI‐CAT‐SV) (continuous score).ResultsSignificant and positive correlations were found between the frequency of participation at home with Daily Activities (ro = 0.320), Social/Cognitive (ro = 0.423) and Responsibility (ro = 0.455). For involvement, significant and positive correlations were found with Daily Activities (ro = 0.297), Social/Cognitive (ro = 0.380) and Responsibility (ro = 0.380). For the PEDI‐CAT‐SV Mobility, no significant correlation was found.ConclusionsHigher frequency and involvement of participation at home are associated with greater functional skills assessed, except for Mobility. This study provided pioneering insights about the relationships between the level of home participation and functional skills in DS, generating evidence that could guide approaches to participation‐focused intervention.
The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors
Authors: Zhang Bo , Zhang Hao , Wang Zeyu , Cao Hui , Zhang Nan , Dai Ziyu , Liang Xisong , Peng Yun , Wen Jie , Zhang Xun , Zhang Liyang , Luo Peng , Zhang Jian , Liu Zaoqu , Cheng Quan , Peng Renjun 
Published: November 2023

AbstractBackgroundCentral nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single‐stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes.AimsThis review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors.MethodsWe have summarized studies of circRNA in CNS tumors in Pubmed.ResultsThis review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA‐related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics.ConclusionsCircRNA are increasingly proven to participate in decveloping CNS tumors. An in‐depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.
The gendered violence of injecting‐related stigma among relatively affluent, suburban women who inject drugs
Authors: Dertadian George Christopher , Caruana Theresa , Maher Lisa 
Published: November 2023

AbstractIntroductionIn honouring the legacy of Jude Byrne's life‐long advocacy for women and mothers who use drugs, this paper presents a case study of a group of women about whom we know little about and hear even less from: women who inject drugs in relatively affluent suburbs.MethodsBased on a 2020 qualitative study of people who inject drugs in an affluent area of Sydney known as ‘The Beaches’, we use in‐depth interview data to thematically explore the lived experiences of gendered stigma among women who inject drugs.ResultsEven when women occupy the ‘ideal’ social position in terms of class (middle‐class) and race (White) they remain subject to harmful forms of gendered stigma related to injecting drug use. Participants had internalised negative attitudes around injection drug use as a form of failed femininity and, despite being part of ‘good’ families and neighbourhoods, participants experienced forced child removal.Discussion and ConclusionsTaking the lead from feminist intersectionality scholarship, our data illustrate how stigma and discrimination act as a form of structural violence against women who inject drugs in affluent communities. While the social relations of gender provide some degree of protection by ‘performing proximity to Whiteness’, gendered stigma and violence persist.
Presentations and evaluations: A new look at Husserl's distinction between objectifying and non‐objectifying acts
Authors: Staiti Andrea Sebastiano 
Published: November 2023

AbstractIn this paper, I take a fresh look at Husserl's key distinction between objectifying and non‐objectifying acts, which roughly amounts to a distinction between presentational and evaluative experiences. My goal is to provide a clear and unified reconstruction of Husserl's argument for the thesis that non‐objectifying acts are necessarily founded in objectifying acts, a thesis that is highly controversial in and beyond Husserlian scholarship. In the first section, I reconstruct Husserl's view in the Logical Investigations, according to which only objectifying acts establish an independent intentional relation to their objects, and argue that it is justified by the positing function of objectifying acts. In the second section, I address two problematic interpretations of this view and, after criticizing them, I present what I take to be Husserl's core argument for his position. In the third section, I turn to the revision of the view of the Logical Investigations that Husserl proposes in the wake of his transcendental turn, especially in Ideas I and II. On Husserl's revised view, all acts are objectifying, including emotional acts [Gemütsakte]. This revision has led scholars to consider Husserl's view aporetic. I propose an alternative interpretation that dispels the purported aporia. I conclude with some remarks on the costs and benefits of my reading, as well as the strengths and weaknesses of Husserl's view in general.