bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase separation and molecular ordering of the prion-like domain of the thermosensory protein EARLY FLOWERING 3
Authors: Hutin Stephanie , Kumita Janet R. , Strotmann Vivien I. , Dolata Anika , Ling Wai Li , Louafi Nessim , Popov Anton , Milhiet Pierre-Emmanuel , Blackledge Martin , Nanao Max H. , Wigge Philip A. , Stahl Yvonne , Costa Luca , Tully Mark D. , Zubieta Chloe 
Published: March 2023

AbstractLiquid-liquid phase separation (LLPS) is an important mechanism enabling the dynamic compartmentalisation of macromolecules, including complex polymers such as proteins and nucleic acids, and occurs as a function of the physicochemical environment. In the model plant,Arabidopsis thaliana, LLPS by the protein EARLY FLOWERING3 (ELF3) occurs in a temperature sensitive manner and controls thermoresponsive growth. ELF3 contains a largely unstructured prion-like domain (PrLD) that acts as a driver of LLPS in vivo and in vitro. The PrLD contains a poly-glutamine (polyQ) tract, whose length varies across natural Arabidopsis accessions. Here, we use a combination of biochemical, biophysical and structural techniques to investigate the dilute and condensed phases of the ELF3 PrLD with varying polyQ lengths. We demonstrate that the dilute phase of the ELF3 PrLD forms a monodisperse higher order oligomer that does not depend on the presence of the polyQ sequence. This species undergoes LLPS in a pH and temperature-sensitive manner and the polyQ region of the protein tunes the initial stages of phase separation. The liquid phase rapidly undergoes aging and forms a hydrogel as shown by fluorescence and atomic force microscopies. Furthermore, we demonstrate that the hydrogel assumes a semi-ordered structure as determined by small angle X-ray scattering, electron microscopy and X-ray diffraction. These experiments demonstrate a rich structural landscape for a PrLD protein and provide a framework to describe the structural and biophysical properties of biomolecular condensates.
Dual role of CASP8AP2/FLASH in regulating epithelial-to-mesenchymal (EMT) plasticity
Authors: Catalanotto Madison , Vaz Joel Markus , Abshire Camille , Youngblood Reneau , Chu Min , Levine Herbert , Jolly Mohit Kumar , Dragoi Ana-Maria 
Published: March 2023

ABSTRACTMetastasis consists of sequential steps initiated by cancer cells invading from the primary tumor site into neighboring tissues, followed by entry into the circulatory system and completed by extravasation and growth in distal organs where secondary tumors are formed. Circulating tumor cells, thus, encounter and adapt to multiple environmental changes during their transition from the primary to the secondary tumor sites. Epithelial-to-mesenchymal transition (EMT) is a developmental program that consists of loss of epithelial features concomitant with acquisition of mesenchymal features. Activation of EMT in cancer facilitates acquisition of aggressive traits and cancer invasion. EMT plasticity (EMP), the dynamic transition between multiple hybrid states in which cancer cells display both epithelial and mesenchymal phenotypes, confers survival advantages for cancer cells in the constantly changing environment. Therefore, understanding the molecular mechanisms regulating intermediate phenotypic states along the E–M spectrum is critical. Core EMT transcription factors (EMT-TFs), ZEB, SNAI and TWIST families, play an important role in EMT and its plasticity. In the present study we characterize FLASH as a regulator of EMP and multiple EMT-TFs. We demonstrate that loss of FLASH gives rise to a hybrid E/M phenotype with high epithelial scores even in the presence of TGFβ, as determined by computational methods using expression of predetermined sets of epithelial and mesenchymal genes. We demonstrate that FLASH is regulating expression of multiple cell junction proteins with an established role in cancer progression and that its role in EMT is independent of its histone biogenesis role. Further, we show that FLASH expression in cancer lines is inversely correlated with the epithelial score, consistent with its function as a repressor of the epithelial phenotype. Nonetheless, activation of a distinct set of mesenchymal markers concomitant with epithelial markers reveals the complex role of FLASH in EMT and indicates that intermediate E/M states could arise from opposing control by FLASH on different families of EMT-TFs.
Pump-free and high-throughput generation of monodisperse hydrogel beads by microfluidic step emulsification for dLAMP-on-a-chip
Authors: George Jijo Easo , Manna Riddha , Roy Shomdutta , Kumari Savita , Paul Debjani 
Published: March 2023

AbstractStep emulsification (SE), which generates droplets by a sharp change in confinement, has emerged as a potential alternative to flow-focusing technology. Water/dispersed phase is continuously pumped through a shallow inlet channel into a deep chamber pre-filled with the oil/continuous phase. The need for one or more pumps to maintain a continuous flow for droplet generation, and the consequent use of high sample volumes, limit this technique to research labs. Here, we report a pumpfree SE technique for rapid and high-throughput generation of monodisperse hydrogel (agarose) beads using <40µl sample volume. Instead of using syringe pumps, we sequentially pipetted oil and liquid agarose into a microfluidic SE device to generate between 20000 and 80000 agarose beads in ∼ 2 min. We also demonstrated the encapsulation of loop-mediated isothermal amplification mixture inside these beads at the time of their formation. Finally, using these beads as reaction chambers, we amplified nucleic acids fromP. falciparumand SARS-CoV-2 inside them. The pump-free operation, tiny sample volume, and high-throughput generation of droplets by SE make our technique suitable for point-of-care diagnostics.
An open-source photogrammetry workflow for reconstructing 3D models
Authors: Zhang Chi , Maga A. Murat 
Published: March 2023

AbstractAcquiring accurate 3D biological models efficiently and economically is important for morphological data collection and analysis in organismal biology. In recent years, structure-from-motion (SFM) photogrammetry has become increasingly popular in biological research due to its flexibility and being relatively low cost. SFM photogrammetry registers 2D images for reconstructing camera positions as the basis for 3D modeling and texturing. However, most studies of organismal biology still rely on commercial software to reconstruct the 3D model from photographs, which impedes the adoption of this workflow in our field due the blocking issues such as cost and affordability. Also, prior investigations in photogrammetry did not sufficiently assess the geometric accuracy of the models reconstructed. Consequently, this study has two goals. First, we present an affordable and highly flexible structure-from-motion photogrammetry pipeline based on the open-source package OpenDroneMap (ODM) and its user interface WebODM. Second, we assess the geometric accuracy of the photogrammetric models acquired from the ODM pipeline by comparing them to the models acquired via microCT scanning, the de facto method to image skeleton. Our sample comprises fifteenAplodontia rufa(mountain beaver) skulls. Using models derived from microCT scans of the samples as reference, our results show that the geometry of the models derived from ODM is sufficiently accurate for gross metric and morphometric analysis as the measurement errors are usually around or below 2%, and morphometric analysis captures consistent patterns of shape variations in both modalities. However, subtle but distinct differences between the photogrammetric and microCT-derived 3D models can affect the landmark placement, which in return affect the downstream shape analysis, especially when the variance within a sample is relatively small. At the minimum, we strongly advise not combining 3D models derived from these two modalities for geometric morphometric analysis. Our findings can be indictive of similar issues in other SFM photogrammetry tools since the underlying pipelines are similar. We recommend that users run a pilot test of geometric accuracy before using photogrammetric models for morphometric analysis. For the research community, we provide detailed guidance on using our pipeline for building 3D models from photographs.
Transcription repression of Cry2 via Per2 interaction promotes adipogenesis
Authors: Li Weini , Xiong Xuekai , Kiperman Tali , Ma Ke 
Published: March 2023

AbstractThe circadian clock is driven by a transcriptional-translational feedback loop, and Cryptochrome 2 (Cry2) represses CLOCK/Bmal1-induced transcription activation. Despite the established role of clock in adipogenic regulation, whether the Cry2 repressor activity functions in adipocyte biology remains unclear. Here we identify a critical cysteine residue of Cry2 that mediates interaction with Per2, and demonstrate that this mechanism is required for clock transcriptional repression that inhibits Wnt signaling to promote adipogenesis. Cry2 protein is enriched in white adipose depots and was robustly induced by adipocyte differentiation. Via site-directed mutagenesis, we identified that a conserved Cry2 Cysteine at 432 within the loop interfacing with Per2 mediates heterodimer complex formation that confers transcription repression. C432 mutation disrupted Per2 association without affecting Bmal1 binding, leading to loss of repression of clock transcription activation. In preadipocytes, whereas Cry2 enhanced adipogenic differentiation, the repression-defective C432 mutant suppressed this process. Furthermore, silencing of Cry2 attenuated, while stabilization of Cry2 by KL001 markedly augmented adipocyte maturation. Mechanistically, we show that transcriptional repression of Wnt pathway components underlies Cry2 modulation of adipogenesis. Collectively, our findings elucidate a Cry2-mediated repression mechanism that promotes adipocyte development, and implicate its potential as a clock intervention target for obesity.
Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A
Authors: Cacioppo Roberta , Akman H. Begum , Tuncer Taner , Erson-Bensan A. Elif , Lindon Catherine 
Published: March 2023

ABSTRACTAurora Kinase A (AURKA) is an oncogenic kinase with major roles in mitosis, but also exerts cell cycle- and kinase-independent functions linked to cancer. Therefore control of its expression, as well as its activity, is crucial. A short and a long 3’UTR isoform exist for AURKA mRNA, resulting from alternative polyadenylation (APA). We initially observed that in Triple Negative Breast Cancer, where AURKA is typically overexpressed, the short isoform is predominant and this correlates with faster relapse times of patients. The short isoform is characterized by higher translational efficiency since translation and decay rate of the long isoform are targeted byhsa-let-7atumor-suppressor miRNA. Additionally,hsa-let-7aregulates the cell cycle periodicity of translation of the long isoform, whereas the short isoform is translated highly and constantly throughout interphase. Finally, disrupted production of the long isoform led to an increase in proliferation and migration rates of cells. In sum, we uncovered a new mechanism dependent on the cooperation between APA and miRNA targeting likely to be a route of oncogenic activation of human AURKA.
Methods that bridge business models and business processes: a synthesis of the literature
Authors: Lara Machado Paola , van de Ven Montijn , Aysolmaz Banu , Athanasopoulou Alexia , Ozkan Baris , Turetken Oktay 
Published: March 2023

PurposeBusiness models are increasingly recognized as a concept to support innovation in organizations. The implementation and operation of a new or altered business model involves the (re-)design of an organization's business processes and their successful execution. This study reviews and synthesizes the existing body of literature to guide organizations in systematically moving from a business model design to the implementation and operation of the business model through their underlying business processes.Design/methodology/approachA systematic literature review of the methods that bridge business models and business processes is performed. The selected 34 studies are classified according to the method's characteristics and the support in the design, implementation and operation of business models.FindingsThe results of the systematic review provide an overview of existing methods that organizations can adopt when moving from business model design into the implementation and operation of their business model using processes.Originality/valueThis work provides a comprehensive overview and detailed insight into the existing methods that align business models and business processes. It increases the understanding on how these two concepts can be synthesized to support more effective digital innovation in organizations. Based on the review results, knowledge gaps are identified and an agenda for future research bridging the fields of business models and business processes is proposed.
Connecting and reconnecting: a phenomenological study of the meanings extra care tenants attribute to using the internet for social contact
Authors: Wales Jill , Cook Glenda , Bailey Cathy 
Published: March 2023

Purpose
This paper aims to explore the perceptions and experiences of a group of extra care tenants, who, as novice internet users, began to maintain their social relationships online. Housing transitions in later life may jeopardise existing social relationships, leading to loneliness and social isolation. More recently, Covid-19 restrictions have limited familial face-to-face contact and wider social interactions. Thus, extra care tenants, who are not already online, may benefit from acquiring internet skills. This paper aims to enhance understanding of the participants’ transition from novices to experienced internet users and the impact on their social relationships and sense of self.

Design/methodology/approach
A longitudinal, hermeneutic phenomenological study was conducted over eight months in two extra care housing schemes in north east England. Ten participants (56–98 years) with age-related physical, sensory and cognitive losses were recruited to the study. A series of semi-structured interviews and participant diaries captured the participants’ experience as they developed internet skills and communicated online.

Findings
All participants, including a blind individual, learnt to communicate online. Personalised adaptive strategies, peer support, training and management involvement facilitated internet uptake. Participants felt their social relationships were supported, and they regained biographical continuity, through being and feeling they belonged in the modern digital world.

Originality/value
The online experiences of extra care tenants are rarely voiced. Their perceptions may assist others to engage online, maintaining social connections, which could otherwise be lost.
The Secure Quality Involvement (SeQuIn) tool: benchmarking co-production in secure services
Authors: McKeown Mick , Byrne Charlotte , Cade Holly , Harris Jo , Wright Karen 
Published: March 2023

Purpose
Secure mental health services in one UK region have acted within a network to develop a range of involvement practices. A new quality benchmarking tool has been created to appraise the implementation of these involvement practices. The purpose of this paper is to report upon a qualitative evaluation of this development.

Design/methodology/approach
Staff and service users involved in the co-production of the benchmarking tool were engaged in a series of focus groups and participatory inquiry approaches enacted in the course of scheduled network meetings. Data thus collected was subject to thematic analysis.

Findings
Four distinct themes were identified which were titled: Taking time, taking care; The value not the label; An instrument of the network; and All people working together. These are discussed in relation to recent theorising of co-production.

Research limitations/implications
Effectively, this study represents a case study of developments within one region. As such, the findings may have limited transferability to other contexts.

Practical implications
Staff and service users can work together effectively to the benefit of each other and overall forensic services. The benchmarking tool provides a readymade mechanism to appraise quality improvements.

Social implications
Despite a prevailing culture of competition in wider health-care policy, cooperation leads to enhanced quality.

Originality/value
The benchmarking tool is a unique development of a longstanding involvement network, demonstrating the positive implications for enacting co-production within secure services.
Efficacy and safety of anaplastic lymphoma kinase inhibitors for non–small cell lung cancer: A systematic review and network meta‐analysis
Authors: Peng Tzu‐Rong , Liao Pei‐Fei , Wu Ta‐Wei 
Published: March 2023

AbstractBackgroundTo assess the efficacy and safety of anaplastic lymphoma kinase inhibitors (ALKIs) for the treatment of advanced‐stage ALK rearrangement‐positive non–small cell lung cancer (NSCLC).MethodsWe searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) that included patients with ALK‐positive NSCLC receiving ALKIs. The outcomes of the study included overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and treatment‐related adverse events (TRAEs) of grade ≥3.ResultsA total of 12 RCTs consisting of 3169 patients with eight treatment options were included in this study. Our results showed that ALKIs have superior efficacy in OS, PFS, and ORR than chemotherapy or crizotinib (first‐generation ALKI). Our study showed that only alectinib has a significant improvement in OS compared to chemotherapy (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.40–0.94). Alectinib appeared to have better OS than crizotinib (HR, 0.66; 95% CI, 0.45–0.95). Ensartinib has a significant PFS advantage over alectinib (HR, 0.62; 95% CI, 0.40–0.96). The surface under the ranking curve indicated that ensartinib (99.0%) was the highest rank regarding PFS. Moreover, both ensartinib and ceritinib showed significantly higher TRAEs of grade ≥3 compared with chemotherapy (risk ratios [RR], 2.74; 95% CI, 1.45–5.18; RR, 1.80; 95% CI, 1.26–2.57, respectively).ConclusionsThese results indicated that alectinib could be associated with the best therapeutic efficacy and well‐tolerance AEs in the treatment of ALK‐positive NSCLC.
A systematic review of the trends in ecological science in the megabiodiverse Peru: Research gaps and future directions
Authors: Sotomayor Diego A. , Caro Claudia , Morales Richar 
Published: March 2023

AbstractPeru is a megabiodiverse country that is experiencing a considerable amount of anthropogenic change which is risking its ecosystems. Ecological science may provide the answers on how to cope with change by exploring new ways of sustainably using ecosystems. Here we review the current state and trends of ecological studies using a database search aiming to answer these questions: (i) who has been studying Peruvian ecosystems and how impactful was that research? (ii) what are the most studied political and ecological regions in the country? (iii) what are the most studied taxa? (iv) what are the most studied variables? and (v) what are the most studied topics and their relation with the Sustainable Development Goals (SDGs)? To answer these questions, we conducted a systematic review using the Scopus database (1974–2022) and found 465 articles that conducted ecological research in Peru. We found a vast and increasing diversity of journals and authors publishing research on Peru's ecosystems, with an important participation of Peruvian scientists, especially in the last 15 years. The Amazonian regions of the country were most studied, with some political and ecological regions almost assessed, such as Huancavelica, Ayacucho, Apurimac and Tacna and the pacific tropical forest, paramo and palm tree savanna, respectively. Most studies dealt with single species, primarily animals, and secondly plants. Species composition and/or distribution was the main variable of study and conservation was the main topic. Life on Land (SDG 15) was more represented than other SDGs (58.4% of articles), leaving several others almost unstudied. Overall, we found that ecological research on Peruvian ecosystems is biased to certain regions, taxa and topics. This represents important opportunities for new projects, research collaborations and alignment to global sustainability agendas for more meaningful knowledge production, especially considering the significant increase in research output seen in the last 15 years.
An eye to the future: Acute and long‐term neuro‐ophthalmological and neurological complications of COVID‐19
Authors: Wesselingh Robb , Wesselingh Steve L. 
Published: March 2023

AbstractCOVID‐19 has had a significant impact on the global population and has produced compelling evidence of non‐pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID‐19 and gain a deeper understanding of how COVID‐19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID‐19 infection may result in neurological or neuro‐ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID‐19 disease on the neural axis including hypoxia and the systemic hyper‐inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro‐invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro‐ophthalmological disorders. Finally, we explore the evidence for long‐term neurological and neuro‐ophthalmological complications of COVID‐19, with a focus on neurodegeneration.