bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting LINC00152 activates cAMP/Ca2+/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer
Authors: Saatci Ozge , Alam Rashed , Huynh-Dam Kim-Tuyen , Isik Aynur , Uner Meral , Belder Nevin , Ersan Pelin Gulizar , Cetin Metin , Tokat Unal Metin , Gedik Mustafa Emre , Bal Hilal , Sahin Ozlem Sener , Riazalhosseini Yasser , Thieffry Denis , Gautheret Daniel , Ogretmen Besim , Aksoy Sercan , Uner Aysegul , Akyol Aytekin , Sahin Ozgur 
Published: November 2023

AbstractTamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER+) breast cancer, constituting around 75% of all cases. However, emergence of resistance is common, necessitating the identification of novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen resistance via blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting LINC00152 reduces the mRNA stability of phosphodiesterase 4D (PDE4D), leading to activation of cAMP/PKA/CREB axis and increased expression of TRPC1 Ca2+channel. This causes cytosolic Ca2+overload and generation of reactive oxygen species (ROS) that is, on one hand, accompanied by downregulation of FTH1, a member of the iron sequestration unit, thus increasing intracellular Fe2+levels; and on the other hand, inhibition of the peroxidase activity upon reduced GPX4 and xCT levels. These ultimately induce lipid peroxidation and ferroptotic cell death in combination with tamoxifen. Overexpressing PDE4D rescues LINC00152 inhibition-mediated tamoxifen sensitization by de-activating the cAMP/Ca2+/ferroptosis axis. Importantly, high LINC00152 expression is significantly correlated with high PDE4D/low ferroptosis and worse survival in multiple cohorts of tamoxifen- or tamoxifen-containing endocrine therapy-treated ER+ breast cancer patients. Overall, we identified LINC00152 inhibition as a novel mechanism of ferroptosis induction and tamoxifen sensitization, thereby revealing LINC00152 and its effectors as actionable therapeutic targets to improve clinical outcome in refractory ER+ breast cancer.
Atlas of Fshr Expression from Novel Reporter Mice
Authors: Chen Hong-Qian , Fang Hui-Qing , Liu Jin-Tao , Chang Shi-Yu , Chai Wen-huan , Cheng Li-Ben , Sun Ming-Xin , Yang Zhi-wei , Feng Jian-Rui , Liu Ze-Min , Li Xiao-Li , Zhang Yong-Hong , Rosen Clifford , Liu Peng 
Published: November 2023

AbstractThe FSH-FSHR signaling pathway has traditionally been considered an essential regulator in reproductive development and fertility. But there has been emerging evidence of FSHR expression in extragonadal tissues/organs. This poses new questions and long-term debates regarding the physiological role of the FSH-FSHR pathway, and underscores the need for reliable, in vivo analysis of FSHR expression in animal models. However, conventional methods have proven insufficient for examining FSHR expression due to limitations, such as the scarcity of ‘reliable’ antibodies, rapid turnover/degradation of transcripts, and a lack of robust in vivo tools. To address this challenge, we developed Fshr-ZsGreen ‘knockin’ reporter mice under the control of Fshr endogenous promoter using CRISPR/Cas9 genome-editing technology to append a P2A-ZsGreen targeting vector into a locus between the last exon and the stop codon of Fshr. With this novel genetic tool, we provide a reliable readout of Fshr expression at single-cell resolution level in vivo and in real time. Reporter animals were also subjected to additional analyses, including immunohistochemical staining, ddRT-PCR, andin situhybridization, to define the accurate expression profile of FSHR in gonadal and extragonadal organs/tissues. Our compelling results not only demonstrated Fshr expression in intragonadal tissues but also, strikingly, unveiled notably increased expression in Leydig cells, osteoblast lineage cells, endothelial cells in vascular structures, and epithelial cells in bronchi of the lung and renal tubes. The genetic decoding of the widespread pattern of Fshr expression highlights its physiological relevance beyond reproduction and fertility, and opens new avenues for therapeutic options for age-related disorders of the bones, lungs, kidneys, and hearts, among other tissues/organs. Exploiting the power of the Fshr knockin reporter animals, this report provides the first comprehensive genetic record of the spatial distribution of FSHR expression, correcting a long-term misconception about Fshr expression and offering prospects for extensive exploration of FSH-FSHR biology.
Mitotic Block and Epigenetic Repression Underlie Neurodevelopmental Defects and Neurobehavioral Deficits in Congenital Heart Disease
Authors: Gabriel George C. , Yagi Hisato , Tan Tuantuan , Bais Abha S. , Glennon Benjamin J. , Stapleton Margaret C. , Huang Lihua , Reynolds William T. , Shaffer Marla G. , Ganapathiraju Madhavi , Simon Dennis , Panigrahy Ashok , Wu Yijen L. , Lo Cecilia W. 
Published: November 2023

AbstractPoor neurodevelopment is often observed with congenital heart disease (CHD), especially with mutations in chromatin modifiers. Here analysis of mice with hypoplastic left heart syndrome (HLHS) arising from mutations in Sin3A associated chromatin modifierSap130, and adhesion proteinPcdha9,revealed neurodevelopmental and neurobehavioral deficits reminiscent of those in HLHS patients. Microcephaly was associated with impaired cortical neurogenesis, mitotic block, and increased apoptosis. Transcriptional profiling indicated dysregulated neurogenesis by REST, altered CREB signaling regulating memory and synaptic plasticity, and impaired neurovascular coupling modulating cerebral blood flow. Many neurodevelopmental/neurobehavioral disease pathways were recovered, including autism and cognitive impairment. These same pathways emerged from genome-wide DNA methylation and Sap130 chromatin immunoprecipitation sequencing analyses, suggesting epigenetic perturbation. Mice withPcdha9mutation or forebrain-specificSap130deletion without CHD showed learning/memory deficits and autism-like behavior. These novel findings provide mechanistic insights indicating the adverse neurodevelopment in HLHS may involve cell autonomous/nonautonomous defects and epigenetic dysregulation and suggest new avenues for therapy.
Non-antibiotic drugs break colonization resistance against pathogenicGammaproteobacteria
Authors: Grießhammer Anne , de la Cuesta-Zuluaga Jacobo , Zahir Taiyeb , Müller Patrick , Gekeler Cordula , Chang Hsuan , Schmitt Katharina , Planker Chiara , Bohn Erwin , Nguyen Taylor H. , Huang Kerwyn Casey , Maier Lisa 
Published: November 2023

SummaryNon-antibiotic drugs can alter the composition of the gut microbiome, with largely undefined implications for human health. Here we compared the susceptibility of commensal and pathogenic bacteria to non-antibiotic drugs and found that pathogens show higher drug resistance, which could favor their expansion after treatment. We then developed a model system to screen for drug-microbiome interactions that increase the risk of enteropathogenic infections. Approximately 35% of the >50 drugs we tested increased the abundance ofSalmonellaTyphimurium in synthetic and human stool-derived microbial communities. This was due to direct effects of non-antibiotics on individual commensals, altered microbial interactions within communities and the potential ofSalmonellato exploit different metabolic niches. Non-antibiotic drugs that favoredSalmonellaexpansionin vitroalso promoted other enteric pathogens and increasedSalmonellaloads in gnotobiotic and conventional mice. These findings may inform future strategies to control pathogen proliferation and to assess individual microbiota-drug-pathogen risks for infection.
The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA
Authors: Xie Yixuan , Hemberger Helena , Till Nicholas A. , Chai Peiyuan , Watkins Christopher P. , Lebedenko Charlotta G. , Caldwell Reese M. , George Benson M. , Bertozzi Carolyn R. , Garcia Benjamin A. , Flynn Ryan A. 
Published: November 2023

AbstractWe recently identified glycoRNA—a previously undescribed glycoconjugate—which consists of RNAs modified with secretory N-glycans and presented on the cell surface. While previous work supported a covalent linkage between RNA and glycans, the direct chemical nature of the RNA-glycan connection was not described. Here we develop a sensitive and scalable protocol to detect and characterize native glycoRNAs. Leveraging periodate oxidation and aldehyde ligation (rPAL) and Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), we identified the modified RNA base 3-(3-amino-3-carboxypropyl)uridine (acp3U) as a site of attachment of N-glycans in glycoRNA. The sensitivity and robustness of rPAL provided the first evidence of a direct glycan-RNA linkage, and its flexibility will enable further characterization of glycoRNA biology.
Characterisation and reprogramming of bacteriophage mv4 integrase recombination specificity
Authors: Debatisse Kevin , Lopez Pierre , Poli Maryse , Rousseau Philippe , Campos Manuel , Coddeville Michèle , Cocaign-Bousquet Muriel , Le Bourgeois Pascal 
Published: November 2023

ABSTRACTBacteriophage mv4 is a temperate bacterial virus able to integrate its genome at the 3’ end of the tRNASERofLactobacillus delbrueckiisubsp.bulgaricuschromosome through site-specific recombination. Previous investigations revealed that themv4Int/attP/attBrecombination module was atypical compared to conventional heterobivalent tyrosine recombinases, such as the paradigmaticLambdavirus lambdaintegrase, suggesting alternative recombination mechanism.In vitrorecombination assays with random DNA libraries were used to comprehensively delineate the mv4 recombination system. We showed thatmv4Int is a 369-aa protein that exhibits all structural hallmarks of integrases from the Tn916family and interacts cooperatively with its recombination sites. We established thatmv4Int distinguishes itself from classical heterobivalent integrases by a greater tolerance to nucleotide variations inattBand core-attPsites. We demonstrated that, upon considering nucleotide degeneracy, the 21-bp core-attPandattBrecombination sites share structural similarities with classical heterobivalent integrase systems, with two 7-bp inverted-repeat regions corresponding tomv4Int core-binding sites surrounding a 7-bp strand-exchange region. Furthermore, our study highlighted compositional biases and nucleotide interdependencies within the core-binding regions that exerted a significant influence on the outcomes of recombination events.
Perceived relationship between green logistics practices and sustainability performance: a multi-methodology approach
Authors: Jayarathna Chamari Pamoshika , Agdas Duzgun , Dawes Les 
Published: November 2023

PurposeDespite the wide use of quantitative assessment to identify the relationship between green logistics (GL) practices and the sustainability performance (SP) of firms, results of these studies are inconsistent. A lack of theoretical foundation has been cited as a potential reason for these contradictory findings. This study aims to explore the relationship between GL practices and SP qualitatively and to provide a theoretical foundation for this link.Design/methodology/approachFollowing a multi-methodology approach, the authors used the grounded theory method (GTM) to investigate perceived relationships through qualitative analysis and adopted the system thinking (ST) approach to identify causal relationships using causal loop diagrams (CLDs).FindingsThe authors identified different sustainability practices under three major categories: logistics capabilities, resource-related practices and people-related practices. This analysis showed the relationships among these practices are non-linear. Based on the results, the authors developed three propositions and introduced a theoretical foundation for the relationship between GL practices and SP.Practical implicationsManagerial personnel can use the theoretical foundation provided by this study when making decisions on GL practices adoption. This theoretical foundation suggests applying a holistic approach that can help optimize SP by selecting suitable practices. On the other hand, researchers can use a multi-methodology approach suggested by this study to explore complex social issues.Originality/valueThis study contributes to the knowledge from a methodology perspective as no previous studies have been conducted to identifying the relationship between GL practices and SP by combining GTM and ST approaches. This combination can be extended to build system dynamics models for sustainable logistics impacts bringing novelty to the research field of sustainable logistics.
When, how and why should we involve trusted contacts when serious concerns are raised about a student's well-being?
Authors: Forbes-McKay Katrina E. , Henderson Sarah 
Published: November 2023

PurposeThis study investigates the relationship between mental well-being (MWB) and social support (SS) whilst addressing the paucity of research on students' support for emergency contact schemes (ECSs) and their views on how and when such schemes should be implemented.Design/methodology/approachIn total, 113 students recruited via opportunistic sampling completed an online survey including the Interpersonal Support Evaluation List - shortened version (Cohen et al. 1985), Warwick–Edinburgh Mental Wellbeing Scale (Tennant et al. 2007) and questions about ECS. A correlational design used the Pearson product-moment correlation to explore the relationship between MWB and SS. A between-subjects design using independent measures t-test investigated differences in SS and MWB between those with and without a “trusted person” (TP).FindingsThe preferred name was “Named Trusted Person Scheme” (NTPS), the preferred TP was parent/guardian or partner, and the preferred means of contact was Personal Tutor to mobile phone. Most students (96%) supported the use of an NTPS when serious concerns were raised about mental or physical health, personal safety or student engagement. Those opposed were concerned about a loss of agency, identifying a TP or the TP worsening the situation. MWB was positively correlated with SS, and those with a TP had higher levels of MWB and SS than those without.Originality/valueThis study addresses the under-explored area of students' support for ECS, whilst enhancing our understanding of the relationship between MWB and SS especially amongst those without a person they can trust. This research provides valuable insights for universities looking to implement or refine such schemes, with the potential to improve students' MWB, academic achievement and retention by enhancing support.
Films as emergent educational resources in Indian upper primary social studies classrooms: a multimodal inquiry
Authors: Thoppil Sanjna Sebastian , Pandy Sanjay 
Published: November 2023

PurposeThis study explores the relevance of film texts in Indian social studies classrooms for students at the upper primary level. It examines how different types of visual texts can facilitate awareness, critical thinking, discussion and action.Design/methodology/approachUsing multimodal discourse analysis (MDA), this paper critically evaluates five selective films from regional cinemas in India and explores their teaching implications for social studies. The study argues that films are vital multimodal resources that can challenge the prevailing narratives in social studies pedagogy. It conveys how the suggestive revised taxonomy could benefit the students. It proposes a classification system for film analysis with discussion and states how films can bring out interrelated themes and encourage deeper, critical inquiry within the curriculum. The study finds discourse around the films and qualitatively stresses dialogue exchange with sentiment analysis using MAXQDA software. Developed by VERBI software, MAXQDA is a product whose name is inspired by the German Sociologist Max Weber, while the ‘QDA' stands for Qualitative Data Analysis.FindingsThe films act as multimodal texts, navigators, metaphors, communicative circuits and catalysts. The paper concludes that films can improve and expand multimodal learning of social studies in three ways: films help learners connect emotionally with the concepts, films make the learning process more appealing and extend it beyond classroom boundaries and films offer a unique insight into the socio-cultural subtleties that are often limited in textbooks.Originality/valueThis research pioneers an intersectionality-driven framework for film analysis in the curriculum for Indian upper primary social studies, offering innovative pedagogical tools to enrich Indian curriculum insights and bridge existing knowledge gaps.
Comparison of full‐thickness skin graft and punch grafting in the reconstruction of plantar defects
Authors: Lee Sang Gyun , Nam Kyoung Ae , Oh Byung Ho , Chung Kee Yang , Roh Mi Ryung 
Published: November 2023

AbstractAcral melanoma commonly occurs on weight‐bearing areas of the sole. Reconstruction of such areas presents a surgical challenge due to limited availability and mobility of local skin. Thus, we aimed to compare the scar outcome of full‐thickness skin graft (FTSG) and punch grafting in the reconstruction of plantar defects after melanoma surgery. We retrospectively reviewed six patients who underwent both FTSG for nonweight‐bearing areas and punch grafting for weight‐bearing areas. We compared results of FTSG and punch grafting within the same patient. Photos of completely healed scars were graded using the Stony Brook Scar Evaluation Scale (SBSES). The averages of the FTSG scores and the punch graft scores, as measured by the SBSES, were statistically compared. Punch grafting yielded a better outcome than FTSG, according to the SBSES. The average of the punch grafting scars was 4.67, which was significantly greater (p = 0.004) than that of FTSG scar scores at 1.83. For weight‐bearing areas, punch grafting should be considered as the first option of reconstruction, with FTSG as a second option for nonweight‐bearing areas. Overall, this combined approach provides an effective and safe method for reconstruction of extensive plantar wounds.
Anifrolumab for systemic lupus erythematosus: A clinical study of Japanese patients in Kanazawa University Hospital
Authors: Fushida Natsumi , Horii Motoki , Oishi Kyosuke , Matsushita Takashi 
Published: November 2023

AbstractWe investigated the effectiveness of anifrolumab in treating systemic lupus erythematosus (SLE). We treated seven patients with SLE (age range, 31–68 years; median age, 48 years); one male and six females) with anifrolumab between January 2022 and February 2023 at Kanazawa University Hospital. The period between the onset and initiation of anifrolumab treatment was 60–276 months (median, 234 months), and the SLE disease activity index‐2000 (SLEDAI‐2 K) before treatment was 2–6 months (median, 3 months). Five patients experienced skin rashes or alopecia, and their cutaneous lupus erythematosus disease area and severity index (CLASI) activity scores were 2–9 (median, 4). Six patients continued treatment with anifrolumab, but one did not because of uncontrolled pleurisy and pericarditis. Our results demonstrated that anifrolumab was effective in treating SLE and reducing both SLEDAI‐2 K and CLASI activity scores (median decrease, 100%). Furthermore, the oral corticosteroid dosage could be reduced in all patients who were able to continue treatment. Our findings indicate that anifrolumab is effective not only for reducing disease and eruption activities, but also facilitates tapering of corticosteroid dosage.
Sensing the environment by bacterial plant pathogens: What do their numerous chemoreceptors recognize?
Authors: Matilla Miguel A. , Krell Tino 
Published: November 2023

AbstractBacteria have evolved multiple sensing strategies to efficiently adapt to their natural hosts and environments. In the context of plant pathology, chemotaxis allows phytopathogenic bacteria to direct their movement towards hosts through the detection of a landscape of plant‐derived molecules, facilitating the initiation of the infective process. The importance of chemotaxis for the lifestyle of phytopathogens is also reflected in the fact that they have, on average, twice as many chemoreceptors as bacteria that do not interact with plants. Paradoxically, the knowledge about the function of plant pathogen chemoreceptors is scarce. Notably, many of these receptors seem to be specific to plant‐interacting bacteria, suggesting that they may recognize plant‐specific compounds. Here, we highlight the need to advance our knowledge of phytopathogen chemoreceptor function, which may serve as a base for the development of anti‐infective therapies for the control of phytopathogens.
Morpho‐ecospaces, or how to measure biodiversity in a different way
Authors: Haug Joachim T. , Baranov Viktor , Braig Florian , Haug Carolin 
Published: November 2023

AbstractThe current biodiversity crisis warrants accurate measuring of biodiversity, often achieved by counting species or higher taxonomic units, with morphological or molecular methods. Alternatively, trait‐centred approaches categorise organisms into distinct ecological roles and then count the number of occupied roles to measure biodiversity. Even combinations of trait‐based and taxonomic approaches are utilised. However, when investigating the theoretical aspects, all these approaches have significant shortcomings, which complicate a reliable biodiversity measurement, that is, the ignorance of polymorphic species, the sensitivity to the initial classification or the knowledge gap concerning the ecology of the organisms. We outline a non‐discrete ecospace approach for which neither pronounced taxonomic expertise nor in‐depth knowledge about the ecology of the organisms is required. A morphospace based on quantitative morphological properties is used as a proxy for an ecospace, thus resulting in a continuous morpho‐ecospace. With this, decision‐making concerning taxonomy or ecology is reduced, as morphology is directly used instead of being first interpreted. Differences usually not considered due to polymorphism or ontogeny can be included in this approach, as well as fossils without species determination. This morpho‐ecospace approach is easily applicable and can be combined with already existing approaches, making it broadly applicable.
Influence of diameter and length on primary stability in various implant site densities—An in vitro study in polyurethane blocks
Authors: Gottlow Johan , Sennerby Lars 
Published: November 2023

AbstractBackgroundThe influence of dental implant length and diameter on primary stability in various bone densities is not well understood.AimTo in vitro study the effect of length and diameter on resonance frequency analysis (RFA), insertion torque (IT) and displacement (DP) measurements of dental implants in different implant site densities.Materials and methodsDental implants of four different diameters (Ø 3.5, 4.0, 4.5 and 5.0 mm) and three different lengths (7, 11 and 15 mm) (Neoss Ltd, Harrogate, UK) were placed in polyurethane blocks of three different densities (Sawbones Europe AB, Malmö, Sweden). The primary stability was assessed by RFA (ISQ) (Osstell, Osstell AB, Gothenburg, Sweden) and insertion torque measurements (ITmax in N cm) (iChiropo™, Bien‐Air Dental SA, Bienne, Switzerland). In addition, the blocks were mounted in a rig and a lateral force of 25 N cm was applied to the implants and the DP was measured in μm with a micrometer gauge placed on the opposite side of the load transducer. Statistical analyses using linear and quadratic models were applied.ResultsImplant length, diameter and block density were found to be significant independent predictors of RFA, ITmax, and DP measurements. Implant length had a strong effect, while the effect of diameter in general was subtle, particularly in the softest block.ConclusionsImplant length affects primary stability more than implant diameter in polyurethane blocks of uniform density along the whole length of the tested implants.