bluuebunny/crossref_metadata_2025_split huggingface dataset:
A metabolically controlled contact site between lipid droplets and vacuoles
Authors: Diep Duy Trong Vien , Collado Javier Fernández , Hugenroth Marie , Wälte Mike , Schmidt Oliver , Fernández-Busnadiego Ruben , Bohnert Maria 
Published: April 2023

SUMMARYThe lipiddroplet (LD)organization proteins Ldo16 and Ldo45 affect multiple aspects of LD biology in yeast. They are linked to the LD biogenesis machinery seipin, and their loss causes defects in LD positioning, protein targeting, and breakdown. However, their molecular roles remained enigmatic. Here we report that Ldo16/45 form a tether-complex with Vac8 for creation ofvacuolelipid droplet (vCLIP) contact sites, which can form in the absence of seipin. The phosphatidylinositol transfer protein Pdr16 is a further vCLIP-resident recruited by Ldo45. While only an LD-subpopulation is engaged in vCLIPs at glucose-replete conditions, nutrient stress results in vCLIP expansion, and vCLIP defects impair lipophagy upon prolonged starvation. In summary, Ldo16/45 are multifunctional proteins that orchestrate formation of a metabolically-regulated contact site. Our studies suggest an unexpected link between LD biogenesis and breakdown, and open the door to a deeper understanding of how lipid homeostasis is maintained during metabolic challenges.
Active Transcription and Epigenetic Reactions Synergistically Regulate Meso-Scale Genomic Organization
Authors: Kant Aayush , Guo Zixian , Vinayak  , Neguembor Maria Victoria , Li Wing Shun , Agrawal Vasundhara , Pujadas Emily , Almassalha Luay , Backman Vadim , Lakadamyali Melike , Cosma Maria Pia , Shenoy Vivek B. 
Published: April 2023

AbstractIn interphase nuclei, chromatin is organized into interspersed dense domains with characteristic sizes, both in the nuclear interior and periphery. However, the quantitative impact of transcription and histone modifications on the size and distribution of these domains remains unclear. Here, we introduce a mesoscale theoretical model that investigates the relationship between heterochromatic domain sizes and loop extrusion rates from these domains. The model considers chromatin-chromatin and chromatin-lamina interactions, methylation and acetylation kinetics, and diffusion of epigenetic marks and nucleoplasm. Our model generates testable predictions that help reveal the biophysics underlying chromatin organization in the presence of transcription-driven loop extrusion. This process is kinetically captured through the conversion of heterochromatin to euchromatin in response to RNAPII activity. We discovered that a balance between diffusive and reactive fluxes governs the steady-state sizes of heterochromatin domains. Using theory and simulations, we predicted that a loss of transcription results in increased chromatin compaction and larger heterochromatin domain sizes. To validate our predictions, we employed complementary super-resolution and nano-imaging techniques on five different cell lines with impaired transcription. We quantitatively assessed how domain sizes scale with loop extrusion rates at the hetero-euchromatin interfaces. Our analysis of previously obtained super-resolution images of nuclei revealed that excessive loop extrusion leads to smaller heterochromatin domains. The model successfully recapitulated these observations, explaining how transcription loss can counteract the effects of cohesin overloading. As the general biophysical mechanisms regulating heterochromatin domain sizes are independent of cell type, our findings have significant implications for understanding the role of transcription in global genome organization.
Myocardial IGF2R is a critical mediator of inflammation and fibrosis after ischemia-reperfusion injury
Authors: Wu Zhichao , Huang Wei , He Xingyu , Dutta Suchandrima , Paul Christian , Fan Guo-Chang , Kanisicak Onur , Xu Meifeng , Liang Jialiang , Wang Yigang 
Published: April 2023

ABSTRACTIschemia-reperfusion (I/R) injury is a common occurrence in various surgical procedures used to treat heart diseases. However, the role of insulin-like growth factor 2 receptor (IGF2R) during the process of myocardial I/R remains unclear. Therefore, this study aims to investigate the expression, distribution, and functionality of IGF2R in various I/R-associated models (such as reoxygenation, revascularization, and heart transplant). Loss-of-function studies (including myocardial conditional knockout and CRISPR interference) were performed to clarify the role of IGF2R in I/R injuries. Following hypoxia, IGF2R expression increased, but this effect was reversed upon restoration of oxygen levels. Loss of myocardial IGF2R was found to enhance the cardiac contractile functions, and reduced cell infiltration or cardiac fibrosis of I/R mouse models compared to the genotype control. CRISPR-inhibition of IGF2R decreased cell apoptotic death under hypoxia. RNA sequencing analysis indicated that myocardial IGF2R played a critical role in regulating the inflammatory response, innate immune response, and apoptotic process following I/R. Integrated analysis of the mRNA profiling, pulldown assays, and mass spectrometry identified granulocyte-specific factors as potential targets of myocardial IGF2R in the injured heart. In conclusion, myocardial IGF2R emerges as a promising therapeutic target to ameliorate inflammation or fibrosis following I/R injuries.
A mosquito parasite is locally adapted to its host but not temperature
Authors: Lyberger Kelsey , Farner Johannah , Couper Lisa , Mordecai Erin A. 
Published: April 2023

AbstractClimate change will alter interactions between parasites and their hosts. Warming may affect patterns of local adaptation, shifting the environment to favor the parasite or host and thus changing the prevalence of disease. We assessed local adaptation in the facultative ciliate parasiteLambornella clarki, which infects the western tree hole mosquitoAedes sierrensis. We conducted laboratory infection experiments with mosquito larvae and parasites collected from across a climate gradient, pairing sympatric or allopatric populations across three temperatures that were either matched or mismatched to the source environment.L. clarkiparasites were locally adapted to their hosts, with 2.6x higher infection rates on sympatric compared to allopatric populations, but were not locally adapted to temperature. Infection peaked at the intermediate temperature of 13°C. Our results highlight the importance of host selective pressure on parasites, despite the impact of temperature on infection success.
Long-term Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System by Transplantation of Bone Marrow Mononuclear Cells
Authors: Wang Jing-Ping , Hung Chun-Hao , Liou Yao-Huei , Liu Ching-Chen , Yeh Kun-Hai , Wang Keh-Yang , Lai Zheng-Sheng , Chatterjee Biswanath , Hsu Tzu-Chi , Lee Tung-Liang , Shyu Yu-Chiau , Hsiao Pei-Wen , Chen Liuh-Yow , Chuang Trees-Juen , Albert Yu Chen-Hsin , Liao Nah-Shih , Shen Che-Kun James 
Published: April 2023

AbstractA causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termedKlf1K74R/K74RorKlf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of theKlf1(K74R) mice, as exemplified by their higher anti- cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property ofKlf1(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higherin vitrocancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of theKlf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.
Pharyngeal Mechanosensory Neurons Control Food Swallow inDrosophila melanogaster
Authors: Qin Jierui , Yang Tingting , Li Kexin , Liu Ting , Zhang Wei 
Published: April 2023

AbstractAs the first step of food ingestion, the swallow is under rigorous sensorimotor control. Nevertheless, the mechanisms underlying swallow control at a molecular and circuitry level remain largely unknown. Here, we find that mutation of the mechanotransduction channel genesnompC, Tmc, orpiezoimpairs the regular pumping rhythm of the cibarium during feeding of the fruit flyDrosophila melanogaster. A group of multi-dendritic mechanosensory neurons, which co-express the three channels, wrap the cibarium and are crucial for coordinating the filling and emptying of the cibarium. Inhibition of them causes difficulty in food emptying in the cibarium, while their activation leads to difficulty in cibarium filling. Synaptic and functional connections are detected between the pharyngeal mechanosensory neurons and the motor circuit that controls swallow. This study elucidates the role of mechanosensation in swallow, and provides insights for a better understanding of the neural basis of food swallow.HighlightsnompC+,piezo+andTmc+neurons in the pharynx sense mechanical force during swallowingPharyngeal mechanoreceptor neurons regulate swallow rhythmDysfunction of pharyngeal mechanosensory neurons causes dysphagiaPharyngeal mechanosensory neurons connect with brain motor neurons to coordinate swallow pattern
MaizeCOI1quadruple-knockout mutants exhibit elevated DELLA protein accumulation, stunted growth, and reduced photosynthetic efficiency
Authors: Feiz Leila , Shyu Christine , Wu Shan , Ahern Kevin R. , Gull Iram , Rong Ying , Artymowicz Caroline J. , Piñeros Miguel A. , Fei Zhangjun , Brutnell Thomas P. , Jander Georg 
Published: April 2023

AbstractThe F-box protein Coronatine Insensitive (COI) is a receptor for the jasmonic acid signaling pathway in plants. To investigate the functions of the six maize COI proteins (COI1a, COI1b, COI1c, COI1d, COI2a, and COI2b), we made single, double, and quadruple loss-of-function mutants. Double-mutantcoi2a coi2bpollen was inviable, and no homozygous mutant plants were obtained. Thecoi1quadruple mutant (coi1-4x) exhibited shortened internode lengths, decreased photosynthesis, leaf discoloration, microelement deficiencies, and accumulation of DWARF9, a DELLA-family protein that represses the gibberellic acid signaling pathway. Co-expression of maizeCOIandDWARF9genes inNicotiana benthamianashowed that the COI proteins lead to proteasome-dependent DELLA degradation. Many genes expressed at lower levels in thecoi1-4xmutant are normally induced by gibberellic acid. The majority of these genes are predicted to be bundle sheath or mesophyll-enriched including those encoding C4-specific photosynthetic enzymes. Ectopic expression of maizeCOIgenes inN. benthamianashowed that COI2a is fully localized in the nucleus and interacts with maize JAZ proteins, the canonical COI repressor partners. However, maize COI1a and COI1c proteins showed only partial nuclear localization and failed to bind to most of the JAZ proteins tested. These results show divergent functions of the six COI proteins in the regulation of maize growth and defense pathways.
Competing endogenous RNA networks reveal long non-coding RNAs as potential prognostic biomarkers in gastric cancer: A systematic review and meta-analysis
Authors: Salehi-Mazandarani Sadra , Donyavi Mohammad Hossein , Vedaei Amirhossein , Najimi Alireza , Farajzadegan Ziba , Nikpour Parvaneh 
Published: April 2023

AbstractAimsGastric cancer (GC) represents a global health-care challenge. In recent years, a large number of competing endogenous RNA (ceRNA) network studies have elucidated critical long non-coding RNAs (lncRNAs) as potential prognostic biomarkers in GC. Nevertheless, there is no systematic review and meta-analysis regarding them. Here, we propose a systematic review and meta-analysis for lncRNAs as prognostic biomarkers based on the ceRNA network studies in GC.Main methodsThe Web of Science, Embase, PubMed, Scopus, ProQuest and Google Scholar databases were searched to collect eligible ceRNA network studies in which lncRNAs were reported as prognostic biomarkers until 27thJune 2022. The pooled hazard ratios (HRs) were assessed to evaluate the prognostic effect of the lncRNAs. Prognostic values of highly reported lncRNAs were also examined. Furthermore, sensitivity analysis, and publication bias were evaluated.Key findingsTotally, 35 studies were included in the systematic review among which 13 studies were eligible for meta-analysis. Pooled examination of HRs based on the univariate and multivariate reports revealed that the expression changes of the lncRNAs correlate with overall survival (OS) of GC patients. Two lncRNAs includingCCDC144NL-AS1andLINC01094were highly reported as potential prognostic biomarkers based on the ceRNA network studies. Prognostic value of these two lncRNAs was furthermore confirmed by meta-analysis.SignificanceOur meta-analysis demonstrated potential application of lncRNAs introduced based on the ceRNA network studies as promising prognostic biomarkers in GC. Further functional studies are needed to elucidate the molecular mechanisms underlying these lncRNAs’ functions in GC.
Gene expression and alternative splicing contribute to adaptive divergence of ecotypes
Authors: Innes Peter A. , Goebl April M. , Smith Chris C.R. , Rosenberger Kaylee , Kane Nolan C. 
Published: April 2023

ABSTRACTRegulation of gene expression is a critical link between genotype and phenotype explaining substantial heritable variation within species. However, we are only beginning to understand the ways that specific gene regulatory mechanisms contribute to adaptive divergence of populations. In plants, the post-transcriptional regulatory mechanism of alternative splicing (AS) plays an important role in both development and abiotic stress response, making it a compelling potential target of natural selection. AS allows organisms to generate multiple different transcripts/proteins from a single gene and thus may provide a source of evolutionary novelty. Here we examine whether variation in alternative splicing and gene expression levels might contribute to adaptation and incipient speciation of dune-adapted prairie sunflowers in Great Sand Dunes National Park, Colorado, USA. We conducted a common garden experiment to assess transcriptomic variation among ecotypes and analyzed differential expression, differential splicing, and gene coexpression. We show that individual genes are strongly differentiated for both transcript level and alternative isoform proportions, even when grown in a common environment, and that gene coexpression networks are disrupted between ecotypes. Furthermore, we examined how genome-wide patterns of sequence divergence correspond to divergence in transcript levels and isoform proportions and find evidence for bothcisandtrans-regulation. Together our results emphasize that alternative splicing has been an underappreciated mechanism providing source material for natural selection at micro-evolutionary time scales.
Mouse Homolog of Human IRF8G388SMutation Provides Novel Insight into Osteoclastogenesis and Tooth Root Resorption
Authors: Das Amitabh , Yesupatham Sathish Kumar , Allison Devon , Tanwar Himanshi , Gnanasekaran JebaMercy , Kear Bernice , Wang Xiaobei , Wang Sheng , Zachariadou Christina , Abbasi Yasaman , Chung Man-Kyo , Ozato Keiko , Liu Chengyu , Foster Brian L. , Thumbigere-Math Vivek 
Published: April 2023

ABSTRACTPreviously, we reported a novel mutation in the Interferon Regulatory Factor 8 (IRF8) gene associated with multiple idiopathic cervical root resorption (MICRR), an aggressive form of tooth root resorption mediated by increased osteoclast activity. The IRF8 G388S variant in the highly conserved C-terminal motif is predicted to alter the protein structure, likely impairing IRF8 function. To investigate the molecular basis of MICRR and IRF8 function, we generatedIrf8knock-in (KI) mice using CRISPR/Cas9 modeling the humanIRF8G388Smutation. The heterozygous (Het) and homozygous (Homo)Irf8 KImice showed no gross morphological defects, and the development of hematopoietic cells was unaffected and similar to that in wild-type (WT) mice. TheIrf8 KIHet and Homo mice showed no difference in macrophage gene signatures important for antimicrobial defenses and inflammatory cytokine production. Consistent with the phenotype observed in MICRR patients,Irf8 KIHet and Homo mice demonstrated significantly increased osteoclast formation and resorption activityin vivoandin vitrowhen compared to WT mice. The oral ligature insertedIrf8 KIHet and Homo mice displayed increased osteoclast-mediated alveolar bone loss and tooth root resorption compared to WT mice. The increased osteoclastogenesis noted in KI mice is due to the inability of mutantIrf8G388S isoform to negatively inhibit NFATc1-dependent transcriptional activation and downstream osteoclast specific transcripts. This translational study delineates the IRF8 domain important for osteoclast function and provides novel insights into theIRF8mutation associated with MICRR.Irf8G388Smutation mainly affects osteoclastogenesis while sparing immune cell development and function. TheIrf8 KImice serve as a novel translational model for studying the etiopathology of MICRR and developing targeted therapies for MICRR and other skeletal disorders mediated by increased osteoclast activity.
A deep convolutional neural network for predicting electricity consumption at Grey Nuns building in Canada
Authors: Elshaboury Nehal , Mohammed Abdelkader Eslam , Al-Sakkaf Abobakr , Bagchi Ashutosh 
Published: April 2023

Purpose
The energy efficiency of buildings has been emphasized along with the continual development in the building and construction sector that consumes a significant amount of energy. To this end, the purpose of this research paper is to forecast energy consumption to improve energy resource planning and management.

Design/methodology/approach
This study proposes the application of the convolutional neural network (CNN) for estimating the electricity consumption in the Grey Nuns building in Canada. The performance of the proposed model is compared against that of long short-term memory (LSTM) and multilayer perceptron (MLP) neural networks. The models are trained and tested using monthly electricity consumption records (i.e. from May 2009 to December 2021) available from Concordia’s facility department. Statistical measures (e.g. determination coefficient [R2], root mean squared error [RMSE], mean absolute error [MAE] and mean absolute percentage error [MAPE]) are used to evaluate the outcomes of models.

Findings
The results reveal that the CNN model outperforms the other model predictions for 6 and 12 months ahead. It enhances the performance metrics reported by the LSTM and MLP models concerning the R2, RMSE, MAE and MAPE by more than 4%, 6%, 42% and 46%, respectively. Therefore, the proposed model uses the available data to predict the electricity consumption for 6 and 12 months ahead. In June and December 2022, the overall electricity consumption is estimated to be 195,312 kWh and 254,737 kWh, respectively.

Originality/value
This study discusses the development of an effective time-series model that can forecast future electricity consumption in a Canadian heritage building. Deep learning techniques are being used for the first time to anticipate the electricity consumption of the Grey Nuns building in Canada. Additionally, it evaluates the effectiveness of deep learning and machine learning methods for predicting electricity consumption using established performance indicators. Recognizing electricity consumption in buildings is beneficial for utility providers, facility managers and end users by improving energy and environmental efficiency.
Evaluating industrial competitiveness strategy in achieving environmental sustainability
Authors: Iqbal Mubasher , Kalim Rukhsana , Arshed Noman 
Published: April 2023

Purpose
This study has incorporated competitiveness by considering it a significant factor behind determining as well as moderating industrial value added in the environmental Kuznets curve (EKC) framework. This study aims to explore the moderating role of competitiveness policy in EKC with an aim to promote business led sustainability at national level.

Design/methodology/approach
Considering the environmental deterioration aspect of industrialization, this study tests the existence of EKC for SAARC countries using the data from 1996 to 2021 using second-generation static panel data model.

Findings
Estimated results have validated that moderating effect is responsible for improving environmental sustainability in SAARC countries. Furthermore, population density is responsible for increasing while trade openness is responsible for decreasing carbon emissions.

Originality/value
Higher industrial activities are a symbol of upward-moving economic growth. But its other impact is in the form of environmental deterioration. However, the relationship between industrialization and environmental quality can be identified through EKC.
How blockchain technology generates a trust-based competitive advantage in the wine industry: a resource based view perspective
Authors: Silvestri Raffaele , Adamashvili Nino , Fiore Mariantonietta , Galati Antonino 
Published: April 2023

Purpose
This study aims to explore whether the blockchain technology (BCT), as a unique and distinctive resource, affects the development of unique capabilities and the integration and reconfiguration of internal physical and human resources necessary to gain a trusted competitive advantage.

Design/methodology/approach
A case study approach has been used to identify the internal resources and capabilities that affect the decision to implement BCT and to determine whether this new technology can become a strategic internal resource in the wine industry.

Findings
Results show the role of two strategic resources: human resources, such as IT specialists and software developers for BCT applications, and skills of companies’ management to grant sensitive and confidential data to IT specialists and the ability to read the analytics from the BCT application, becoming a distinctive enabling assets.

Research limitations/implications
The main limitation of this study is related to the analysis of a single case, which, on the one hand, does not allow generalisation of the empirical findings but, on the other hand, is themost appropriatemethod for the explorative nature of this research.

Practical implications
Our findings have useful practical implications for wineries and agri-food companies in overall because they can support managers and entrepreneurs in effectively implementing these innovative digital technologies in their valuecreation process.

Originality/value
The study of this underexplored topic gives interesting insights into the resources needed for the successful adoption of this emerging technology, which can support wineries in improving the value-creating process. In particular, compared to the previous studies, this research analyses the adoption process under the resource-based theory lens.