bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-organ cell specific mitochondrial quantitative interactomics
Authors: Bakhtina AA , Campbell MD , Sibley BD , Sanchez-Contreras M , Sweetwyne MT , Bruce JE 
Published: June 2024

ABSTRACTAlmost every organ consists of many cell types, each with its unique functions. Proteomes of these cell types are thus unique too. But it is reasonable to assume that interactome (inter and intra molecular interactions of proteins) are also distinct since protein interactions are what ultimately carry out the function. Podocytes and tubules are two cell types within kidney with vastly different functions: podocytes envelop the blood vessels in the glomerulus and act as filters while tubules are located downstream of the glomerulus and are responsible for reabsorption of important nutrients. It has been long known that for tubules mitochondria plays an important role as they require a lot of energy to carry out their functions. In podocytes, however, it has been assumed that mitochondria might not matter as much in both normal physiology and pathology1. Here we have applied quantitative cross-linking mass spectrometry to compare mitochondrial interactomes of tubules and podocytes using a transgenic mitochondrial tagging strategy to immunoprecipitate cell-specific mitochondria directly from whole kidney. We have uncovered that mitochondrial proteomes of these cell types are quite similar, although still showing unique features that correspond to known functions, such as high energy production through TCA cycle in tubules and requirements for detoxification in podocytes which are on the frontline of filtration where they encounter toxic compounds and therefore, as a non-renewing cell type they must have ways to protect themselves from cellular toxicity. But we gained much deeper insight with the interactomics data. We were able to find pathways differentially regulated in podocytes and tubules based on changing cross-link levels and not just protein levels. Among these pathways are betaine metabolism, lysine degradation, and many others. We have also demonstrated how quantitative interactomics could be used to detect different activity levels of an enzyme even when protein abundances of it are the same between cell types. We have validated this finding with an orthogonal activity assay. Overall, this work presents a new view of mitochondrial biology for two important, but functionally distinct, cell types within the mouse kidney showing both similarities and unique features. This data can continue to be explored to find new aspects of mitochondrial biology, especially in podocytes, where mitochondria has been understudied. In the future this methodology can also be applied to other organs to uncover differences in the function of cell types.
Predicting the Tumor Microenvironment Composition and Immunotherapy Response in Non-Small Cell Lung Cancer from Digital Histopathology Images
Authors: Patkar Sushant , Chen Alex , Basnet Alina , Bixby Amber , Rajendran Rahul , Chernet Rachel , Faso Susan , Kumar Prashant A. , Desai Devashish , El-Zammar Ola , Curtiss Christopher , Carello Saverio J. , Nasr Michel , Choyke Peter , Harmon Stephanie , Turkbey Baris , Jamaspishvili Tamara 
Published: June 2024

AbstractImmune checkpoint inhibitors (ICI) have become integral to treatment of non-small cell lung cancer (NSCLC). However, reliable biomarkers predictive of immunotherapy efficacy are limited. Here, we introduce HistoTME, a novel weakly supervised deep learning approach to infer the tumor microenvironment (TME) composition directly from histopathology images of NSCLC patients. We show that HistoTME accurately predicts the expression of 30 distinct cell type-specific molecular signatures directly from whole slide images, achieving an average Pearson correlation of 0.5 with the ground truth on independent tumor cohorts. Furthermore, we find that HistoTME-predicted microenvironment signatures and their underlying interactions improve prognostication of lung cancer patients receiving immunotherapy, achieving an AUROC of 0.75[95% CI: 0.61-0.88] for predicting treatment responses following first-line ICI treatment, utilizing an external clinical cohort of 652 patients. Collectively, HistoTME presents an effective approach for interrogating the TME and predicting ICI response, complementing PD-L1 expression, and bringing us closer to personalized immuno-oncology.
Species Distribution ofCannabis sativa: Past, Present and future
Authors: Halpin-McCormick Anna , Maaz Tai McClellan , Kantar Michael B. , Barton Kasey E. , Masalia Rishi R. , Batora Nick , Law Kerin , Kuntz Eleanor J. 
Published: June 2024

AbstractCannabis sativaL. is an annual flowering herb of Eurasian origin that has long been associated with humans. Domesticated independently at multiple locations at different times for different purposes (food, fiber, and medicine), these long-standing human associations have influenced its distribution. However, changing environmental conditions and climatic fluctuations have also contributed to the distribution of the species and define where it is optimally cultivated. Here we explore the shifts in distribution thatC. sativamay have experienced in the past and explore the likely shifts in the future. Modeling under paleoclimatic scenarios shows niche expansion and contraction in Eurasia through the timepoints examined. Temperature and precipitation variables and soil variable data were combined for species distribution modeling in the present day and showed high and improved predictive ability together as opposed to when examined in isolation. The five most important variables explaining ∼65% of the total variation were soil organic carbon content (ORCDRC), pH index measured in water solution (PHIHOX), annual mean temperature (BIO-1), mean temperature of the coldest quarter (BIO-11) and soil organic carbon density (OCDENS) (AUC = 0.934). Climate model projections where efforts are made to curb emissions (RCP45/SSP245) and the business as usual (RCP85/SSP585) models were evaluated. Under projected future climate scenarios, shifts worldwide are predicted with a loss of ∼43% in suitability areas with scores above 0.4 observed by 2050 and continued but reduced rates of loss by 2070. Changes in habitat range have large implications for the conservation of wild relatives as well as for the cultivation ofCannabisas the industry moves toward outdoor cultivation practices.
Targeted isolation of bacteria with potential to competitively excludeStaphylococcus aureusin the upper respiratory tract of pigs
Authors: Vlasblom Abel A. , Patel Shriram , Lawlor Peadar G. , Claesson Marcus J. , Crespo-Piazuelo Daniel , Eckenberger Julia , Huseyin Chloe E. , Elend Christian , Wagenaar Jaap A. , Zomer Aldert L. , Duim Birgitta 
Published: June 2024

AbstractConsidering global antimicrobial resistance (AMR) prevalence, alternative or complementary strategies to antimicrobial use, are of interest. Livestock-associated methicillin-resistantStaphylococcus aureus(LA-MRSA) is of particular interest as despite significant AMU reduction, LA-MRSA prevalence in pig husbandry has not decreased. We performed targeted isolation of bacterial species with potential antagonism against LA-MRSA in pig farms. Duplicate piglet nasal swabs from three European countries (Germany, Ireland and The Netherlands) were taken longitudinally from birth up to 10 weeks, one for amplicon sequencing and qPCR, and the other was cryopreserved for culturing. We identified potential probiotic species by anticorrelation analysis of bacterial abundance from amplicon sequencing data with quantitativeS. aureusestimates from qPCR data from the samples. A literature-screen was performed on the species identified, to determine their probiotic potential. Following this, 1302 isolates were grown from selected cryopreserved swabs and identified using MALDI-TOF and additional 16S rRNA gene sequencing to isolate the anticorrelating species. Ninety-five isolates of interest were screened for absence of tetracycline resistance and hemolytic activity and whole genome sequencing was conducted to verify their taxonomy and to assess their AMR and virulence gene profile. Additional phenotypic antimicrobial resistance testing selected three differentLactococcus lactisstrains. During anin vitrochallenge using spent medium, all three strains demonstrated inhibition against twoS. aureusstrains. TheseL. lactisstrains may have the ability to be used safely to reduce LA-MRSA carriage in the nasal passages of pigs but furtherin vivotesting is necessary to confirm this potential.ImportanceAn approach to tackle antimicrobial resistance in livestock is to use competitive exclusion agents. We employed a sequencing guided isolation approach to identify bacterial species within silicoantagonism to livestock-associatedStaphylococcus aureus(LA-MRSA) in the nasal microbiome of piglets. Based on this, threeLactococcus lactisisolates were found to be suitable for further probiotic testing. This strategy can be used to effectively identify, isolate, and screen bacteria that live in antagonism with opportunistic pathogens such as LA-MRSA in a complex microbiome.
Enabling non-viral DNA delivery using lipid nanoparticles co-loaded with endogenous anti-inflammatory lipids
Authors: Patel Manthan N. , Tiwari Sachchidanand , Wang Yufei , O’Neill Sarah , Wu Jichuan , Omo-Lamai Serena , Espy Carolann , Chase Liam S. , Majumdar Aparajeeta , Hoffman Evan , Shah Anit , Sárközy András , Katzen Jeremy , Pardi Norbert , Brenner Jacob S. 
Published: June 2024

AbstractLipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responsesin vivoenabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs’ expression by performing a small LNP formulation screen, driving up expression 50-foldin vitro. Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA’s long-term and promoter-controlled expression.
Direct modulation of CRH nerve terminal function by noradrenaline and corticosterone
Authors: Power Emmet M. , Ganeshan Dharshini , Paul Jamieson , Igarashi Hiroyuki , Inoue Wataru , Iremonger Karl J. 
Published: June 2024

AbstractNerve terminals are the final point of regulation before neurosecretion. As such, neuromodulators acting on nerve terminals can exert significant influence on neural signalling. Hypothalamic corticotropin-releasing hormone (CRH) neurons send axonal projections to the median eminence where CRH is secreted to stimulate the hypothalamic-pituitary-adrenal (HPA) axis. Noradrenaline and corticosterone are two of the most important neuromodulators of HPA axis function; noradrenaline excites CRH neurons and corticosterone inhibits CRH neurons by negative feedback. Here, we used GCaMP6f Ca2+imaging and measurement of nerve terminal CRH secretion using sniffer cells to determine whether these neuromodulators act directly on CRH nerve terminals. Contrary to expectations, noradrenaline inhibited action potential-dependent Ca2+elevations in CRH nerve terminals and suppressed evoked CRH secretion. This inhibitory effect was blocked by α2-adrenoreceptor antagonism. Corticosterone also suppressed evoked CRH peptide secretion from nerve terminals, independent of action potential-dependent Ca2+levels. This inhibition was prevented by the glucocorticoid receptor antagonist, RU486, and indicates that CRH nerve terminals may be a site of fast glucocorticoid negative feedback. Together these findings establish median eminence nerve terminals as a key site for regulation of the HPA axis.SignificanceCorticotropin-releasing hormone (CRH) neurons control the stress axis. Noradrenaline and corticosterone are two signalling molecules that control CRH neuron cell body excitability. However, their effect on CRH nerve terminal function is unknown. To examine this, we performed live Ca2+imaging and measured CRH secretion. We found that noradrenaline suppressed nerve terminal Ca2+levels and inhibited nerve terminal CRH secretion. Corticosterone had no effect on nerve terminal Ca2+, but inhibited nerve terminal CRH secretion. This suggests that CRH nerve terminals may be a site of fast corticosteroid negative feedback. Together, these data demonstrate that CRH nerve terminals are a critical point of regulation in the control of the stress axis.
Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity
Authors: Katsanos Christos S. , Tran Lee , Hoffman Nyssa , Roust Lori R. , De Filippis Eleanna , Mandarino Lawrence J. , Johnsson Kailin , Belohlavek Marek , Buras Matthew R. 
Published: June 2024

AbstractContextHumans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown.ObjectiveWe investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR).MethodsThe studies were performed in a postprandial state associated with steady-state plasma TG concentrations. The arterio-venous blood sampling technique was employed to determine the extraction of circulating lipids across the forearm muscle before and after insulin infusion. We distinguished kinetics of TGs and NEFAs from ingested origin from those from endogenous origin across muscle by incorporating stable isotope-labeled triolein in the ingested fat.ResultsInsulin infusion rapidly suppressed the extraction of plasma TGs from endogenous, but not ingested, origin in the muscle of the Lean-IS, but this response was absent in the muscle of the Obese-IR. Furthermore, in the muscle of the Lean-IS, insulin infusion decreased the extraction of circulating NEFAs from both ingested and endogenous origin; however, this response was absent for NEFAs from ingested origin in the muscle of the Obese-IR subjects.ConclusionsPartitioning of circulating lipids away from the skeletal muscle when plasma insulin increases during the postprandial period is impaired in humans with obesity and insulin resistance.
A General Framework for Characterizing Optimal Communication in Brain Networks
Authors: Fakhar Kayson , Hadaeghi Fatemeh , Seguin Caio , Dixit Shrey , Messé Arnaud , Zamora-López Gorka , Misic Bratislav , Hilgetag Claus C. 
Published: June 2024

AbstractCommunication in brain networks is the foundation of cognitive function and behavior. A multitude of evolutionary pressures, including the minimization of metabolic costs while maximizing communication efficiency, contribute to shaping the structure and dynamics of these networks. However, how communication efficiency is characterized depends on the assumed model of communication dynamics. Traditional models include shortest path signaling, random walker navigation, broadcasting, and diffusive processes. Yet, a general and model-agnostic framework for characterizing optimal neural communication remains to be established.Our study addresses this challenge by assigning communication efficiency through game theory, based on a combination of structural data from human cortical networks with computational models of brain dynamics. We quantified the exact influence exerted by each brain node over every other node using an exhaustive multi-site virtual lesioning scheme, creating optimal influence maps for various models of brain dynamics. These descriptions show how communication patterns unfold in the given brain network if regions maximize their influence over one another. By comparing these influence maps with a large variety of brain communication models, we found that optimal communication most closely resembles a broadcasting model in which regions leverage multiple parallel channels for information dissemination. Moreover, we show that the most influential regions within the cortex are formed by its rich-club. These regions exploit their topological vantage point by broadcasting across numerous pathways, thereby significantly enhancing their effective reach even when the anatomical connections are weak.Our work provides a rigorous and versatile framework for characterizing optimal communication across brain networks and reveals the most influential brain regions and the topological features underlying their optimal communication.
Examining emotional intelligence evolution with age: insights from Bulgarian digital entrepreneurs of different generations
Authors: Todorova Ana 
Published: June 2024

PurposeThis article aims to explore the relationship between age and emotional intelligence, as the latter emerges as essential to professional performance and an individual’s ability to adapt to an ever-changing world. The study examines the emotional intelligence of Bulgarian digital entrepreneurs from different generations.Design/methodology/approachThe developed methodology for studying the emotional intelligence of digital business owners is based on Daniel Goleman’s model of emotional intelligence. The sample consists of 1,175 participants; the statistical error for the studied population is 2.8%. The demographic groups covered by the study are as follows: 1965 (Baby Boomers); 1965–1979 (Generation X); 1980–1995 (Generation Y); and 1995 (Generation Z). Data were collected using an anonymous form and subsequently analysed.FindingsThe comparison between the different generations of Bulgarian digital entrepreneurs reflects an increasing trend with age in the ability to exercise and apply emotional intelligence. The findings also show that although emotional intelligence is seen as the result of five components – self-awareness, self-regulation, motivation, empathy and social skills, the predominance of only one of these competencies does not guarantee high emotional intelligence. At the same time, self-awareness stands out as an ever-evolving component of emotional intelligence.Originality/valueThis paper integrates the concept of the development of emotional intelligence with age and confirms that general emotional intelligence may increase with age. Therefore, the study adds value to the literature on entrepreneurship, organisational behaviour and human resource management.
The hustle is real: an examination of the self-related consequences of consuming idealized self-promotional content on LinkedIn
Authors: Oliver Sebastian , Marder Ben , Lavertu Laura , Cowan Kirsten , Javornik Ana , Osadchaya Elena 
Published: June 2024

PurposeEveryday users of professional networks such as LinkedIn are flooded by posts presenting the achievements of their connections (e.g. I got a new job/award). The present research takes a self-discrepancy perspective to examine the mixed-emotional and behavioral consequences of viewing such idealized self-promotional content on professional networks.Design/methodology/approachThe emotional and behavioral consequences following viewership of idealized self-promotional content on LinkedIn are explored through one pilot study (N = 109) and one online experiment (N = 714), which is evaluated using structural equation modeling.FindingsViewership of idealized self-promotional content on professional social networking sites acts as an emotional double-edged sword for LinkedIn users. Users feel both dejection and symhedonia (i.e. happiness for others), dependent on their reported career-based self-discrepancy. We find the experience of symhedonia to be bound by the relational closeness of the poster (acquaintance vs close friend). Furthermore, we show how resultant emotions drive self-regulatory compensatory IT-use behaviors (i.e. direct resolution, fluid compensation, dissociation, and escapism).Originality/valueWe offer four distinct contributions. Firstly, we disentangle inconsistent findings of mixed emotions by introducing symhedonia to IT literature. Secondly, we investigate the boundary condition of relational closeness. Thirdly, we extend our findings by investigating compensatory-consumption behaviors that stem from mixed-affective outcomes. Finally, we do so in the context of professional networks, which are greatly understudied and are distinctive from personal networks. Practical implications are discussed.
Chatbot symbolic recovery and customer forgiveness: a moderated mediation model
Authors: Zaki Heba Salah , Al-Romeedy Bassam Samir 
Published: June 2024

Purpose
Artificial intelligence-based chatbots are frequently used to handle customer complaints in the hospitality and tourism sectors; however, little is known about their recovery strategies. Further, the widespread usage of chatbots is anticipated to affect customers' favorable responses. Therefore, this study aims to examine how chatbots’ symbolic recovery influences customer forgiveness through customer empathy and explore the moderating effect of time pressure on it. Moreover, it investigates the effect of customer forgiveness on customer reconciliation and customer continuous trust.

Design/methodology/approach
Structural equation modeling was used to analyze data collected from 994 customers who have experienced chatbot recovery in tourism and hospitality during the past four months.

Findings
The results show that chatbots’ symbolic recovery stimulates customer forgiveness, which subsequently positively affects customer reconciliation and customer continuous trust. Moreover, customer empathy partially mediates the effect of chatbots’ symbolic recovery on customer forgiveness, and time pressure plays a moderating role in the relationship between chatbots’ symbolic recovery and customer forgiveness.

Practical implications
The results offer highly persuasive insights that may be used to promote chatbots’ symbolic recovery in tourism organizations. The effectiveness of chatbots’ symbolic recovery in achieving customer forgiveness will motivate tourism organizations to use chatbots efficiently in service recovery.

Originality/value
This study extends the theoretical scope of chatbot research by investigating the symbolic recovery capabilities of chatbots. Moreover, it expands the application of SOR theory in the context of chatbot service recovery and reveals the underlying mechanism behind the impact of chatbots’ symbolic recovery on customer forgiveness, thus building and testing an integrative model of chatbot service recovery.