bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Noncoding RNA MALAT1 is Dynamically Regulated in Leader Cells during Collective Cancer Invasion
Authors: Zhu Ninghao , Ahmed Mona , Liao Joseph C. , Wong Pak Kin 
Published: July 2022

AbstractCancer cells invade collectively with leader-follower organization. However, how leader cells are regulated during the dynamic invasion process remains poorly understood. Using a FRET nanobiosensor that tracks lncRNA dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that lncRNA MALAT1 is dynamically regulated in the invading fronts of cancer cells and patient-derived organoids. The abundance, diffusivity, and distribution of MALAT1 transcripts are distinct between leader and follower cells. MALAT1 expression increases when a cell acquires the leader cell role and decreases when the migration process stops. Transient knockdown of MALAT1 prevents the formation of leader cells and abolishes the migration of cancer cells. Taken together, our single cell analysis suggests MALAT1 dynamically regulates leader cells during collective cancer invasion.
ADOLESCENT EXPOSURE TO LOW-DOSE THC DISRUPTS ENERGY BALANCE AND ADIPOSE ORGAN HOMEOSTASIS IN ADULTHOOD
Authors: Lin Lin , Jung Kwang-Mook , Le Johnny , Colleluori Georgia , Wood Courtney , Lee Hye-Lim , Palese Francesca , Squire Erica , Su Shiqi , Torrens Alexa , Fotio Yannick , Tang Lingyi , Yu Clinton , Yang Qin , Huang Lan , DiPatrizio Nicholas , Jang Cholsoon , Cinti Saverio , Piomelli Daniele 
Published: July 2022

SUMMARYOne of cannabis’ most iconic effects is the stimulation of hedonic high-calorie eating – the ‘munchies’ – yet habitual cannabis users are on average leaner than non-users. We asked whether this unexpected phenotype might result from lasting changes in energy balance established during adolescence, when habitual use of the drug often begins. We found that daily low-dose administration of cannabis’ intoxicating constituent, Δ9-tetrahydrocannabinol (THC), to adolescent mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, and enhanced thermogenesis. Multi-omics analyses revealed that this phenotype is associated with multiple molecular anomalies in the adipose organ, which include ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring ‘pseudo-lean’ state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.
Individual differences in oxycodone addiction-like behaviors in a large cohort of heterogeneous stock (HS) rats
Authors: Kallupi Marsida , de Guglielmo Giordano , Carrette Lieselot LG , Simpson Sierra , Kononoff Jenni , Kimbrough Adam , Smith Lauren C , Shankar Kokila , Avelar Alicia , Conlisk Dana , Brennan Molly , Tieu Lani , Sedighim Sharona , Boomhower Brent , Maturin Lisa , Fannon McKenzie J , Martinez Angelica , Crook Caitlin , Dirik Selen , Velarde Nathan , Schweitzer Paul , Bonnet-Zahedi Selene , Othman Dyar N. , Sichel Benjamin , Guess Kwynn , Peng Beverly , Hu Andrew S. , Chun Lucas E. , Milan Kristel , Lau Justin , Zheng Yicen , Vang Ashley , Solberg Woods Leah C. , Palmer Abraham A. , George Olivier 
Published: July 2022

AbstractFamily and twin studies demonstrate that genetic factors determine 20-60% of the vulnerability to opioid use disorder. However, the genes/alleles that mediate the risk of developing addiction-related behaviors, including the sensitivity to the analgesic efficacy of opioids, the development of tolerance, dependence, and escalation of oxycodone taking and seeking, have been ill-defined, thus hindering efforts to design pharmacological interventions to enable precision medicine strategies. Here we characterized oxycodone addiction-like behaviors in heterogeneous stock (HS) rats, that show high genetic diversity that mimics the high genetic variability in humans. HS rats were allowed to self-administer oxycodone for two h/daily for four days (ShA) and then moved to 12h/daily (LgA) for 14 days. Animals were screened for motivation to self-administer oxycodone using a progressive-ratio (PR) schedule of reinforcement and for the development of withdrawal-induced hyperalgesia and tolerance to the analgesic effects of oxycodone using the von-Frey and tail immersion tests, respectively. To reduce cohort-specific effects, we used cohorts of 46-60 rats and normalized the response level within cohorts using a Z-score. To take advantage of the four opioid-related behaviors and further identify subjects that are consistently vulnerable vs. resilient to compulsive oxycodone use, we computed an Addiction Index by averaging normalized responding (Z-scores) for the four behavioral tests. Results showed high individual variability between vulnerable and resilient rats, likely to facilitate the detection of gene variants associated with vulnerable vs. resilient individuals. Such data will have considerable translational value for designing follow-up studies in humans.
Enhanced Single RNA Imaging Reveals Dynamic Gene Expression in Live Animals
Authors: Hu Yucen , Xu Jingxiu , Gao Erqing , Fan Xueyuan , Wei Jieli , Xu Suhong , Ma Weirui 
Published: July 2022

AbstractImaging endogenous mRNAs in live animals is technically challenging. Here we describe an MS2 based signal Amplification with Suntag System that enables live-cell RNA imaging of high temporal resolution and with 8xMS2 stem-loops, which overcomes the obstacle of inserting a 1,300 nt 24xMS2 into the genome for the imaging of endogenous mRNAs. Using this tool we were able to image the activation of gene expression and the dynamics of endogenous mRNAs in the epidermis of live C. elegans.
Tumor landscape of epithelial ovarian cancer highlights that EGR1 drives tumor invasion at single-cell resolution
Authors: Zhang Yuanfu , Sun Shu , Qi Yue , Dai Yifan , Hao Yangyang , Xin Mengyu , Xu Rongji , Chen Hongyan , Wu Xiaoting , Liu Qian , Kong Congcong , Zhang Guangmei , Wang Peng , Guo Qiuyan 
Published: July 2022

AbstractIdentifying underlying molecular mechanisms and biomarkers of epithelial ovarian carcinoma (EOC) proliferation and metastasis remains challenging. Patients of EOC are usually diagnosed at an advanced stage and the availability of invasion-related targets is limited. Herein, we explored the single-cell RNA sequencing (scRNA-seq) dataset of EOC and defined tumor physiological reprograming compared to bulk RNA-seq. The energy metabolism and anti-apoptotic pathway was found as critical contributors to intratumor heterogeneity. Moreover, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis were positively correlated, which have biologically activity trajectories during epithelial mesenchymal transition (EMT). The HMGH1, EGR1 and RUNX1 were found to be critical inducers of the EMT process in EOC. Experimental validation revealed that suppressed EGR1 decreased the expression of FAS and HSPG2 and associating with EMT progression in EOC. In tumor microenvironment (TME), CAFs were found have significant contribution to tumor immune infiltration and metastasis and accumulation of CAFs was associated with poorer patient survival. In conclusion, physiological features and molecular mechanisms in the TME of EOC were revealed and provided effective targets for the suppression of tumor metastasis.
Neural contributions to reduced fluid intelligence across the adult lifespan
Authors: Mitchell Daniel J. , Mousley Alexa L. S. , Shafto Meredith A. , Cam-CAN  , Duncan John 
Published: July 2022

AbstractFluid intelligence – the ability to solve novel, complex problems – declines steeply during healthy human aging. Using functional magnetic resonance imaging (fMRI), fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data, a large, population-based, healthy, adult lifespan cohort. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localise the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodelled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of non-physical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline.Significance StatementGlobal populations are living longer, driving urgency to understand age-related cognitive declines. Fluid intelligence is of prime importance, because it reflects performance across many domains, and declines especially steeply during healthy aging. Despite consensus that fluid intelligence is associated with particular frontoparietal brain regions, little research has investigated suggestions that under-responsiveness of these regions mediates age-related decline. We replicate a recent demonstration of such mediation, showing specific association with brain regions most activated by cognitive demand, and robustness to moderate confounding by unmodelled variables. By showing that this mediation model is moderated by the variety of regular physical activities, more reliably than by their frequency or duration, we identify a potential modifiable lifestyle factor that may help promote successful aging.
Galectin-8 is a major ligand of LILRB4 prompting MDSC functions in the tumor microenvironment
Authors: Wang Yiting , Sun Yufan , Deng Shouyan , Song Teng , Wang Yungang , Xu Jie 
Published: July 2022

AbstractThe LILRB4 myeloid receptor has been implicated in an immunosuppressive microenvironment, with specific antibodies under preclinical or clinical development for tumor immunotherapy. However, it remains largely unknown which natural ligand may trigger LILRB4 to expand myeloid derived suppressive cells (MDSC), and the relevant downstream signaling pathways are also under debate. Here we show that Galectin-8 is a high-affinity functional ligand of LILRB4, and its ligation induces MDSC by activating STAT3 as well as inhibiting NF-κB. Importantly, Galectin-8 but not APOE could induce MDSC, and both ligands bind LILRB4 in a non-competitive manner. Antibodies recognizing a defined epitope on LILRB4 could efficiently block Galectin-8 binding and neutralize its effects on MDSC induction and relevant signaling pathways. Galectin-8 expression promoted B16 tumor growth in mice, and knockout of LILRB4 attenuated tumor growth in this context. The LILRB4-specific Galectin-8 blocking antibody efficiently suppressed MDSC expansion and tumor growthin vivo. These results identify Galectin-8 as a functionally important ligand of LILRB4, highlighting the blockade of LILRB4-Galectin-8 interaction as a promising strategy for cancer immunotherapy.
Conserved and transcript-specific functions of the RESC factors, RESC13 and RESC14, in kinetoplastid RNA editing
Authors: Sortino Katherine , Tylec Brianna L. , Chen Runpu , Sun Yijun , Read Laurie K. 
Published: July 2022

ABSTRACTUridine insertion/deletion RNA editing is an extensive post-transcriptional modification of mitochondrial mRNAs in kinetoplastid organisms, includingTrypanosoma brucei. This process is carried out usingtrans-acting gRNAs and complex protein machinery. The essential RNA Editing Substrate Binding Complex (RESC) serves as the scaffold that modulates protein and RNA interactions during editing, and contains the Guide RNA Binding Complex (GRBC), the RNA Editing Mediator Complexes (REMCs), and organizer proteins. Despite the importance of RESC in editing, the functions of each protein comprising this complex are not completely understood. Here, we further define the roles of a REMC protein, RESC13, and a RESC organizer, RESC14, using high-throughput sequencing on two large pan-edited mRNAs, A6 and COIII. When comparing our analyses to that of a previously published small pan-edited mRNA, RPS12, we find that RESC13 has conserved functions across the three transcripts with regards to editing initiation, gRNA utilization, gRNA exchange, and restricting the formation of long mis-edited junctions that likely arise from its ability to modulate RNA structure. However, RESC13 does have transcript-specific effects on the types of long junctions whose formation it restricts. RESC14 has a conserved effect on gRNA utilization across the three transcripts analyzed, but has transcript-specific effects on editing initiation, gRNA exchange, and junction formation. Our data suggest that transcript-specific effects of both proteins are due to differences in transcript length and sequences as well as transcript-specific protein interactions. These findings highlight the importance of studying multiple transcripts to determine the function of editing factors.
Advancing right to health considerations in national responses against health sector corruption: the case for action
Authors: Alexiadou Elisavet Athanasia 
Published: July 2022

Purpose
Health sector corruption constitutes a pervasive challenge and a major obstacle to the equitable enjoyment of the right to health by exacerbating health inequalities within societies, while often eroding public trust primarily amid public health crises that threaten human security. The purpose of this paper is to examine the value of advancing right to health considerations in national legislative and regulatory responses against health sector corruption.

Design/methodology/approach
This paper builds on existing evidence, with focusing attention on international standards that are relevant to the topic under discussion. The literature research included publicly available reports, peer-reviewed studies and other documents primarily of human rights bodies at the United Nations level.

Findings
Advancing right to health considerations in national responses against health sector corruption offers comprehensive guidance for the deployment of a strong regulatory anti-corruption framework for action by the governments as part of their health rights obligations. Essentially, the implementation of such a national framework for action, encompassing accountability, participatory decision-making and transparency, constitutes a necessary and an important step towards maintaining well-functioning health systems and a robust social pressure for continued political commitment with the ultimate goal the provision of equitable access to quality health services at all times.

Originality/value
By using a rights-based approach, the paper identifies a national framework for state action consisting of legal obligations and tools towards guiding governments, while at the same time empowering civil society groups to demand the implementation of core human rights principles of transparency, participation and accountability within health system governance. It provides insights for the future development, reinforcement and/or reform of national law, policies and practices towards minimizing and eradicating vulnerabilities to health sector corruption.
Modelling of factors influencing organizational readiness for change in start-ups during the COVID-19 emergency
Authors: Sreenivasan Aswathy , Suresh M. 
Published: July 2022

Purpose
The purpose of this paper is to “identify”, “analyze” and “construct” a framework to quantify the relationships between several determinants of organizational preparedness for change in the start-ups during the COVID-19 emergencies.

Design/methodology/approach
Total interpretive structural modelling (TISM) is used to find characteristics that assist in analyzing the readiness or preparedness level before initiating a change deployment process in start-ups. A cross-impact matrix multiplication applied to classification (MICMAC) analysis is performed to determine the driving and dependent elements of change in start-ups.

Findings
From literature research and an expert interview, this study selected ten variables of change preparedness to explore inner interconnections and comprehend the inner connections factors. The findings depict that clarity of mission and goals, reward system, technological advancement and motivational readiness have been considered the most important readiness factor for deploying organizational change in start-ups during the COVID-19 emergencies.

Practical implications
This research will aid the management and researchers gain a better understanding of the factors that influence change preparedness. Constant observation of current changes in the start-ups and the external environment will aid in improving the quality of products or services provided by the start-ups during the COVID-19. The start-ups can use these criteria linked to change readiness. The priority of each element is determined using MICMAC analysis and ranking using the TISM technique, which assists start-ups in ordering the enablers from highest to lowest priority.

Originality/value
There is no research regarding factors influencing organizational readiness for change in start-ups during the COVID-19 emergencies. This research gap is filled by analyzing aspects linked to organizational readiness for change in start-ups. This gap inspired the present study, which uses the “Total Interpretive Structural Modelling (TISM)” technique to uncover change determinants and investigate hierarchical interconnections among factors influencing organizational readiness to change in start-ups during the COVID-19 emergencies.
Impact energy absorption and fracture mechanism of FFF made fiberglass reinforced polymer composites
Authors: Prajapati Ashish R. , Dave Harshit K. , Raval Harit K. 
Published: July 2022

Purpose
The fiber reinforced polymer composites are becoming more critical because of their exceptional mechanical properties and lightweight structures. Fused filament fabrication (FFF) is a three-dimensional (3D) printing technique that can manufacture composite structures. However, the effect of impact performance on the structural integrity of FFF made composites compared to the pre-preg composites is a primary concern for the practical usage of 3D printed parts. Therefore, this paper aims to investigate the effect of different processing parameters on the impact performance of 3D printed composites.

Design/methodology/approach
This paper investigates the impact of build orientation, fiber stacking sequence and fiber angle on the impact properties. Two build orientations, three fiber stacking sequences and two different fiber angles have been selected for this study. Charpy impact testing is carried out to investigate the impact energy absorption of the parts. Onyx as a matrix material and two different types of fibers, that is, fiberglass and high strength high temperature (HSHT) fiberglass as reinforcements, are used for the fabrication.

Findings
Results indicate that build orientation and fiber angle largely affect the impact performance of composite parts. The composite part built with XYZ orientation, 0º/90º fiber angle and B type fiber stacking sequence resulted into maximum impact energy. However, comparing both types of fiber reinforcement, HSHT fiberglass resulted in higher impact energy than regular fiberglass.

Originality/value
This study evaluates the damage modes during the impact testing of the 3D printed composite parts. The impact energy absorbed by the composite samples during the impact testing is measured to compare the effect of different processing conditions. The investigation of different types of fiberglass reinforced with Onyx material is very limited for the FFF-based process. The results also provide a database to select the different parameters to obtain the required impact properties.
Knowledge diffusion–application association during the COVID-19 pandemic: investigating the role of technology intervention
Authors: Lathabhavan Remya , V. Moovendhan 
Published: July 2022

Purpose
Knowledge management during the pandemic has been a challenging task due to the sudden intervention of technology in the organisational environment and the unexpected shift to the work-from-home culture. This study aims to investigate the role of technology intervention in the relationship between knowledge diffusion and knowledge application.

Design/methodology/approach
A cross-sectional study was conducted and data were collected from 541 employees who were working from home during the pandemic in India.

Findings
This study found significant relationships between knowledge diffusion and technology intervention. This study also observed the mediating role of technology intervention in the relationship between knowledge diffusion and knowledge application.

Originality/value
Tis study stands with other pioneering studies that have explored the role of technology intervention in the knowledge diffusion–application relationship using the job demand-resource model.
Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus
Authors: Doyle Alfred D. , Masuda Mia Y. , Pyon Grace C. , Luo Huijun , Putikova Arina , LeSuer William E. , Flashner Samuel , Rank Matthew A. , Nakagawa Hiroshi , Kita Hirohito , Wright Benjamin L. 
Published: July 2022

AbstractBackgroundEosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation.MethodsImmortalized esophageal epithelial cells (EPC2) were cultured in air‐liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC‐dextran flux, and RT‐PCR. Additionally, SDS‐treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing.ResultsWhen EPC2 cells were exposed to SDS (5 μg/ml) for 96 h, TEER decreased (p = 0.03), and FITC‐dextran flux increased (p = 0.0002). mRNA expression of IL‐33 increased 4.5‐fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS‐treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL‐33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes.ConclusionExposure to SDS decreases esophageal barrier integrity, stimulates IL‐33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis.