bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated spatial transcriptomics and lipidomics of precursor lesions of pancreatic cancer identifies enrichment of long chain sulfatide biosynthesis as an early metabolic alteration
Authors: Sans Marta , Chen Yihui , Thege Fredrik I. , Dou Rongzhang , Min Jimin , Yip-Schneider Michele , Zhang Jianjun , Wu Ranran , Irajizad Ehsan , Makino Yuki , Rajapakshe Kimal I. , Hurd Mark W. , León-Letelier Ricardo A. , Vykoukal Jody , Dennison Jennifer B. , Do Kim-Anh , Wolff Robert A. , Guerrero Paola A. , Kim Michael P. , Schmidt C Max , Maitra Anirban , Hanash Samir , Fahrmann Johannes F. 
Published: August 2023

AbstractBackgroundThe development of diverse spatial profiling technologies has provided an unprecedented insight into molecular mechanisms driving cancer pathogenesis. Here, we conducted the first integrated cross-species assessment of spatial transcriptomics and spatial metabolomics alterations associated with progression of intraductal papillary mucinous neoplasms (IPMN),bona fidecystic precursors of pancreatic ductal adenocarcinoma (PDAC).MethodsMatrix Assisted Laster Desorption/Ionization (MALDI) mass spectrometry (MS)-based spatial imaging and Visium spatial transcriptomics (ST) (10X Genomics) was performed on human resected IPMN tissues (N= 23) as well as pancreata from a mutantKras;Gnasmouse model of IPMN. Findings were further compared with lipidomic analyses of cystic fluid from 89 patients with histologically confirmed IPMNs, as well as single-cell and bulk transcriptomic data of PDAC and normal tissues.ResultsMALDI-MS analyses of IPMN tissues revealed long-chain hydroxylated sulfatides, particularly the C24:0(OH) and C24:1(OH) species, to be selectively enriched in the IPMN and PDAC neoplastic epithelium. Integrated ST analyses confirmed that the cognate transcripts engaged in sulfatide biosynthesis, includingUGT8, Gal3St1, andFA2H, were co-localized with areas of sulfatide enrichment. Lipidomic analyses of cystic fluid identified several sulfatide species, including the C24:0(OH) and C24:1(OH) species, to be significantly elevated in patients with IPMN/PDAC compared to those with low-grade IPMN. Targeting of sulfatide metabolism via the selective galactosylceramide synthase inhibitor, UGT8-IN-1, resulted in ceramide-induced lethal mitophagy and subsequent cancer cell deathin vitro, and attenuated tumor growth of mutantKras;Gnasallografts. Transcript levels ofUGT8andFA2Hwere also selectively enriched in PDAC transcriptomic datasets compared to non-cancerous areas, and elevated tumoralUGT8was prognostic for poor overall survival.ConclusionEnhanced sulfatide metabolism is an early metabolic alteration in cystic pre-cancerous lesions of the pancreas that persists through invasive neoplasia. Targeting sulfatide biosynthesis might represent an actionable vulnerability for cancer interception.
SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels
Authors: Eberhardt Natalia , Noval Maria Gabriela , Kaur Ravneet , Sajja Swathy , Amadori Letizia , Das Dayasagar , Cilhoroz Burak , Stewart O’Jay , Fernandez Dawn M. , Shamailova Roza , Guillen Andrea Vasquez , Jangra Sonia , Schotsaert Michael , Gildea Michael , Newman Jonathan D. , Faries Peter , Maldonado Thomas , Rockman Caron , Rapkiewicz Amy , Stapleford Kenneth A. , Narula Navneet , Moore Kathryn J. , Giannarelli Chiara 
Published: August 2023

AbstractCOVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection. While the systemic inflammatory response to SARS-CoV-2 infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques to locally promote inflammation remains unknown. Here, we report that SARS-CoV-2 viral RNA (vRNA) is detectable and replicates in coronary atherosclerotic lesions taken at autopsy from patients with severe COVID-19. SARS-CoV-2 localizes to plaque macrophages and shows a stronger tropism for arterial lesions compared to corresponding perivascular fat, correlating with the degree of macrophage infiltration.In vitroinfection of human primary macrophages highlights that SARS-CoV-2 entry is increased in cholesterol-loaded macrophages (foam cells) and is dependent, in part, on neuropilin-1 (NRP-1). Furthermore, although viral replication is abortive, SARS-CoV-2 induces a robust inflammatory response that includes interleukins IL-6 and IL-1β, key cytokines known to trigger ischemic cardiovascular events. SARS-CoV-2 infection of human atherosclerotic vascular explants recapitulates the immune response seen in cultured macrophages, including pro-atherogenic cytokine secretion. Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events.
FCS-Like Zinc finger 14 (FLZ14) mediates the crosstalk between TORC and SnRK1 in response to sugar availability
Authors: Artins Anthony , Urrea-Castellanos Reynel , Martin-Sánchez Marcos , Alexandre Moraes Thiago , Fernie Alisdair R. , Satake Akiko , Caldana Camila 
Published: August 2023

AbstractMatching resource availability to growth is crucial for plant fitness. We identified that FCS- Like Zinc finger 14 (FLZ14) gauges carbon (C) status to adjust growth by inhibiting the TARGET OF RAPAMYCIN (TOR) activity in short days via REGULATORY- ASSOCIATED PROTEIN OF TARGET OF RAPAMYCIN 1B (RAPTOR1B). Besides being transcriptionally induced by sugars, the amplitude ofFLZ14induction correlates to the diel sugar status, indicating thatFLZ14responses to sugar oscillationsin planta.Genetic evidence elucidated that FLZ14 is involved in the crosstalk between TORC and SUCROSE NON-FERMENTING RELATED KINASE 1 (SnRK1). In short photoperiods,FLZ14andKIN10genetically interact to set the pace of TORC activity. By contrast, under long day photoperiods,FLZ14andRAPTOR1Bgenetically interact, most likely to downregulate SnRK1 signalling. This report highlights the function of a sugar-responsive gene in mediating the crosstalk between TORC and SnRK1 to fine-tune growth.
The longitudinal single-cell panorama of cynomolgus monkey ovary throughout lifespan revealed a conserved ovarian clock between primates
Authors: Yan Long , Long Xin , Zhao Yan , Zhao FeiYan , Tu Wan , Yang Qiuyun , Qian Jingjing , Zhai Jinglei , Wang Meijiao , Hu Yuqiong , He Beijia , Su Youqiang , Jiang Xiangxiang , Gao Fei , Wang Hongmei , Guo Fan 
Published: August 2023

AbstractOvarian function is critical for female fertility and impacts reproductive longevity. It is of great importance to accurately predict the aging process within the ovary for fertility assessment and disease diagnosis. However, cell metrics for evaluating the ovarian aging rate are still in urgent need, and molecular insights into ovarian development and dysfunction during the primate life course are also limited. Here, we reported large-scale ovarian cell atlas of consecutive development of cynomolgus monkeys across 22 years with 20 time points, covering the foetal, newborn, prepubertal, pubertal, adult, perimenopausal and menopausal stages. We characterized and validated distinct molecular signatures of each cluster of cells within primate ovaries, and uncovered a previously undocumented RHOXF1-positive oocyte type during primordial follicle assembly in primates. Furthermore, the constitution and developmental trajectories of primate germ cells, granulosa cells and stromal / theca cells were also elucidated, and their precursors were identified. More importantly, dynamics of cellular compositions were unravelled through the ovarian development, featured by granulosa, epithelial, stromal, and immune cells that showed strong temporal heterogeneity spanning lifetime, whilst referred to the key function during the corresponding stages. Based on the correlations of each cell type with age and stage-specific molecular dynamics, we further constructed a transcriptomic ovarian clock which could perceive an effective biological age prediction of the ovary and further applied to humans. The findings reveal granulosa, epithelial, and stromal cells as the highest performance predictors of ovarian biological age, while highlighting the crucial role of AGE-RAGE and Relaxin signaling pathways in regulating ovarian aging. Our work not only provide valuable resource for obtaining insights into the development, aging and dysfunction of key organs, but also establish a transcriptomic clock to predict biological ovarian aging thus to be potential clinical implementation in future.
Enhancing CRISPR prime editing by reducing misfolded pegRNA interactions
Authors: Zhang Weiting , Petri Karl , Ma Junyan , Lee Hyunho , Tsai Chia-Lun , Joung J. Keith , Yeh Jing-Ruey Joanna 
Published: August 2023

AbstractCRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here we show that sequence complementarity between the 5’ and the 3’ regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as 6-fold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.
Integrative phenotypic-transcriptomic analysis of soybean plants subjected to multifactorial stress combination
Authors: Peláez-Vico María Ángeles , Sinha Ranjita , Induri Sai Preethi , Lyu Zhen , Venigalla Sai Darahas , Vasireddy Dinesh , Singh Pallav , Immadi Manish Sridhar , Pascual Lidia S. , Shostak Benjamin , Mendoza-Cózatl David , Joshi Trupti , Fritschi Felix B. , Zandalinas Sara I. , Mittler Ron 
Published: August 2023

ABSTRACTGlobal warming, climate change, and industrial pollution are altering our environment subjecting crops to an increasing number and complexity of abiotic stress conditions, concurrently or sequentially. Recent studies revealed that a combination of 3 or more stresses simultaneously impacting a plant (termed ‘multifactorial stress combination’; MFSC) can cause a drastic decline in plant growth and survival, even if the level of each stress involved in the MFSC has a negligible effect on plants. However, the impacts of MFSC on crops are largely unknown. We subjected soybean plants to a MFSC of up to five different stresses (water deficit, salinity, low phosphate, acidity, and cadmium), in an increasing level of complexity, and conducted integrative transcriptomic-phenotypic analysis of reproductive and vegetative tissues. We reveal that MFSC has a negative cumulative effect on soybean yield, that each set of MFSC condition elicits a unique transcriptomic response (that is different between flowers and leaves), and that selected genes expressed in leaves or flowers are linked to the effects of MFSC on different vegetative, physiological, and/or reproductive parameters. We further reveal that the transcriptomic response of soybean andArabidopsisto MFSC shares common features associated with reactive oxygen and iron/copper signaling/metabolism. Our study provides unique phenotypic and transcriptomic datasets for dissecting the mechanistic effects of MFSC on the vegetative, physiological, and reproductive processes of a crop plant.
Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament
Authors: Liu Tianyang , Cao Luyan , Mladenov Miroslav , Jegou Antoine , Way Michael , Moores Carolyn A. 
Published: August 2023

SUMMARYRegulation of the assembly and turnover of branched actin filament networks nucleated by the Arp2/3 complex is essential during many cellular processes including cell migration and membrane trafficking. Cortactin plays a key role in stabilizing actin filament branches by interacting with the Arp2/3 complex and actin filaments via its N-terminal Acidic domain (NtA) and 6.5 central unstructured 37 amino acid repeats, respectively1, but the mechanism of this is unclear. We determined the structure of cortactin-stabilized Arp2/3 actin branches using cryo-electron microscopy. We find that cortactin interacts with the new daughter filament nucleated by the Arp2/3 complex at the branch site rather than the initial mother actin filament. Cortactin preferentially binds activated Arp3 in contrast to other nucleation promoting factors (NPFs)2,3. Cortactin also stabilizes the F-actin-like interface of activated Arp3 with the first actin subunit of the new filament, and its central repeats extend along successive daughter filament subunits. Cortactin binding to Arp3 is incompatible with NPF interaction and its preference for activated Arp3 explains why it is retained at the actin branch. Our data have uncovered why cortactin displaces NPFs, while at the same time promoting synergy to regulate branched actin network dynamics.
Alcohol Responsive Genes in the Neutrophils of Acute-On-Chronic Liver Failure Reveal Modulation of Intracellular Calcium, ROS, and Phagocytosis
Authors: Saha Rohini , Chakraborty Ditam , Roshan Aditya , Sharma Shalini , Loganathan Tamizhini , Shalimar  , Acharya Pragyan 
Published: August 2023

AbstractAcute-on-chronic liver failure (ACLF) is characterized by rapid depletion of hepatic reserves, innate immunity-driven pathogenesis and high short-term mortality. Elevation of neutrophil counts is associated with mortality in alcoholic-ACLF. In India, one of the most common etiologies in ACLF for both chronic and acute injury is alcohol. We used a combination of clinical transcriptomics and a novelin vitrolaboratory model to look at gene signatures unique in alcoholic ACLF patients and study phenotypic changes upon alcohol treatment. CCL20 and IL1β were two of the top overexpressed genes in alcoholic-ACLF which were validated in the alcohol-neutrophil model, using neutrophils isolated from CLD patients (acute-on-chronic model), and healthy individual (acute model). In the alcoholic-neutrophil models, 300 mg/dL dose of ethanol for 24 hours, caused reduced ROS generation, reduced phagocytic ability and dampening of intracellular calcium reserves. We conclude that the effects of alcohol at least partially explain immune dysfunction in ACLF such as dampening of ROS and phagocytosis in neutrophils while retaining inflammatory roles such as expression of CCL20 and IL1β. Systematic curation of previously published alcohol related liver tissue transcriptomic data also confirmed overlapping genes with alcoholic-ACLF circulating neutrophils. Docking of ethanol with CCL20 and IL1β showed spontaneous binding.
Construction SMEs labour productivity: causal layered analysis
Authors: Adebowale Oluseyi Julius , Agumba Justus Ngala 
Published: August 2023

Purpose
Small and medium-sized contractors are critical to micro and macroeconomic performance. These contractors in South Africa have long been confronted with the problem of business failure because of a plethora of factors, including poor productivity. The purpose of this study is to investigate salient issues undermining the productivity of small and medium-sized contractors in South Africa. This study proposes alternative possibilities to engender productivity improvement.

Design/methodology/approach
Qualitative data were collected using semi-structured interviews with 15 contractors in Gauteng Province, South Africa. The research data were analysed using content and causal layered analyses.

Findings
Challenges to contractors’ productivity were associated with inadequately skilled workers, management competence and political factors. Skills development, construction business and political factors were dominant stakeholders’ perceptions. Metaphors for construction labour productivity are presented and reconstructed as alternative directions for productivity improvement.

Practical implications
Contractors lose a substantial amount of South African Rand to poor productivity. Alternative directions provided in this study can be leveraged to increase profitability in construction organizations, enhance the social well-being of South Africans and ultimately improve the contribution of contractors to the South African economy.

Originality/value
The causal layered analysis (CLA) applied in this study is novel to construction labour productivity research. The four connected layers of CLA, which make a greater depth of inquiry possible, were explored to investigate labour productivity in construction organizations.
Corruption fight in the Czech Republic: sustainability reports evidence
Authors: Kristek Tomas 
Published: August 2023

Purpose
The lack of transparency contributes to the growing corruption problem in various spheres of society. This paper aims to analyse the sustainability report disclosures published by Czech companies in 2021 and registered by the Association of Social Sustainability of the Czech Republic.

Design/methodology/approach
Based on three hypotheses, the relationships between the level of disclosed anti-corruption information and selected variables related to the corporate environment are tested using content analysis and the Mann–Whitney test.

Findings
This paper reveals that Czech firms provide more information if they operate in a higher-risk environment (energy, materials and financial services) or are state-owned (or with a state ownership stake). It also reveals that companies participating in corporate social responsibility (CSR) initiatives (UN Global Compact and Global Reporting Initiative) increase their credibility and social responsibility with more disclosed information.

Research limitations/implications
A limitation of this paper is the smaller number of selected companies matching the chosen criteria. In addition, a certain degree of subjectivity is likely to have manifested in the process of coding the reports and in the use of the content analysis method.

Originality/value
The paper contributes to research that addresses the fight against corruption and CSR issues with a specific study in a small, Central European country and provides new empirical data on the anti-corruption fight problem.
Relative informative power and stock return predictability: a new perspective from Egypt
Authors: Hendawy Enas , McMillan David G. , Sakr Zaki M. , Shahwan Tamer Mohamed 
Published: August 2023

PurposeThis paper aims to introduce a new perspective on long-term stock return predictability by focusing on the relative (individual and hybrid) informative power of a wide range of accounting (firm-related), technical and macroeconomic factors while considering the past performance of the stocks using machine learning algorithms.Design/methodology/approachThe sample includes a panel data set of 94 non-financial firms listed in Egyptian Exchange 100 index from 2014: Q1 to 2019: Q4. Relativity has been investigated by comparing relevant factors’ individual and combined informative power and differentiating between losers and winners based on historical stock returns. To predict the quarterly stock returns, Gaussian process regression (GPR) has been used. The robustness of the results is examined through the out-of-sample test. This study also uses linear regression (LR) as a benchmark model.FindingsThe past performance and the presence of other predictors influence the informative power of relevant factors and hence their predictive ability. The out-of-sample results show a trade-off between GPR and LR with proven superiority to GPR in limited experiments. The individual informative power outperforms the hybrid power, in which macroeconomic indicators outperform the remaining sets of indicators for losers, while winners show mixed results in terms of various performance evaluation metrics. Prediction accuracy is generally higher for losers than for winners.Practical implicationsThis study provides interesting insight into the dynamic nature of the predictor variables in terms of stock return predictability. Hence, this study also deepens the understanding of asset pricing in a way that directly contributes to practitioners’ portfolio diversification strategies.Originality/valueIn concern of the chaos of factors in the literature and its accompanying misleading conclusions, this study takes another look at the approach that studies stock return predictability. To the best of the authors’ knowledge, this is the first study in the Egyptian context that re-examines the predictive power of the previously discovered factors from a different perspective that highlights their relative nature.
New social media nones: how and why Americans have changed their use of social media to consume political news
Authors: Morris David S. , Morris Jonathan S. 
Published: August 2023

Purpose
Social media (SM) platforms have become major sources for generating, sharing and gathering political and election news. Although there appears to be an assumption that reliance on SM for political news consumption will continue to gain in popularity, there are reasons to believe that many Americans are retreating from using SM for political news. The purpose of this study is to examine if Americans are reducing reliance on SM for political news and to analyze why retreat may be happening.

Design/methodology/approach
Using longitudinal panel data from Pew’s American Trends Panel study, the authors tracked 993 respondents from February of 2016 to November of 2019 to monitor their reliance on SM for political news leading up to the 2020 US presidential election.

Findings
The results of this study indicate that a sizeable percentage of people (about a third) are retreating from SM platforms for political news consumption and some are abandoning it altogether – people we refer to as new SM “nones.” The authors find that retreat from SM is associated with increased distrust of the information found on the platforms. Concerns about fake news, incivility on SM and information overload were unrelated to retreat from use of SM for political news consumption.

Originality/value
The findings of this study are novel and suggest that reliance on SM for political news by the public may have waxed, seen its zenith and may now be waning largely because of distrust in the information found on SM platforms.