bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of intestine in metabolic dysregulation in murine Wilson disease
Authors: Sarode Gaurav V. , Mazi Tagreed A. , Neier Kari , Shibata Noreene M. , Jospin Guillaume , Harder Nathaniel H.O. , Heffern Marie C. , Sharma Ashok K. , More Shyam K. , Dave Maneesh , Schroeder Shannon M. , Wang Li , LaSalle Janine M. , Lutsenko Svetlana , Medici Valentina 
Published: January 2023

ABSTRACTBackground and aimsMajor clinical manifestations of Wilson disease (WD) are related to copper accumulation in the liver and the brain, and little is known about other tissues involvement in metabolic changes in WD.In vitrostudies suggested that the loss of intestinal ATP7B could contribute to metabolic dysregulation in WD. We tested this hypothesis by evaluating gut microbiota and lipidome in two mouse models of WD and by characterizing a new mouse model with a targeted deletion ofAtp7bin intestine.MethodsCecal content 16S sequencing and untargeted hepatic and plasma lipidome analyses in the Jackson Laboratory toxic-milk and theAtp7bnull global knockout mouse models of WD were profiled and integrated. Intestine-specificAtp7bknockout mice (Atp7bΔIEC) was generated using B6.Cg-Tg(Vil1-cre)997Gum/J mice andAtp7bLox/Loxmice, and characterized using targeted lipidome analysis following a high-fat diet challenge.ResultsGut microbiota diversity was reduced in animal models of WD. Comparative prediction analysis revealed amino acid, carbohydrate, and lipid metabolism functions to be dysregulated in the WD gut microbial metagenome. Liver and plasma lipidomic profiles showed dysregulated tri- and diglyceride, phospholipid, and sphingolipid metabolism in WD models. When challenged with a high-fat diet,Atp7bΔIECmice exhibited profound alterations to fatty acid desaturation and sphingolipid metabolism pathways as well as altered APOB48 distribution in intestinal epithelial cells.ConclusionCoordinated changes of gut microbiome and lipidome analyses underlie systemic metabolic manifestations in murine WD. Intestine-specific ATP7B deficiency affected both intestinal and systemic response to a high-fat challenge. WD is a systemic disease in which intestinal-specific ATP7B loss and diet influence phenotypic presentations.
Engineered symbiotic bacteria interferingNosemaredox system inhibit microsporidia parasitism in honeybees
Authors: Lang Haoyu , Wang Hao , Wang Haoqing , Xie Xianbing , Hu Xiaosong , Zhang Xue , Zheng Hao 
Published: January 2023

AbstractNosema ceranaeis an emergent microsporidia parasite of the European honey bee (Apis mellifera), which causes serious nosemosis implicated in honeybee colony losses worldwide.N. ceranaeis an obligate intracellular eukaryotic parasite that mainly invades the midgut of honeybees. Recent studies find that bee gut microbiota is potentially involved in protecting against parasitism. Here, using laboratory-generated bees mono-associated with gut members, we find thatSnodgrassella alviinhibited microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly,N. ceranaeemploys the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knocked down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of theN. ceranaeparasite. Finally, we genetically modified the symbioticS. alvito deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineeredS. alviinduces RNA interference and represses parasite gene expression, thereby inhibits the parasitism by up to 99.8%. Specifically,N. ceranaewas most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts againstN. ceranaeand provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.
Region-Based Epigenetic Clock Design Improves RRBS-Based Age Prediction
Authors: Simpson Daniel J. , Zhao Qian , Olova Nelly N. , Dabrowski Jan , Xie Xiaoxiao , Crespo Eric Latorre , Chandra Tamir 
Published: January 2023

AbstractRecent studies suggest that epigenetic rejuvenation can be achieved using drugs that mimic calorie restriction and techniques such as reprogramming induced rejuvenation. To effectively test rejuvenationin vivo, mouse models are the safest alternative. However, we have found that the recent epigenetic clocks developed for mouse reduced-representation bisulphite sequencing (RRBS) data have significantly poor performance when applied to external datasets. We show that the sites captured and the coverage of key CpGs required for age prediction vary greatly between datasets, which likely contributes to the lack of transferability in RRBS clocks. To mitigate these coverage issues in RRBS-based age prediction, we present two novel design strategies that use average methylation over large regions rather than individual CpGs, whereby regions are defined by sliding windows (e.g. 5 kb), or density-based clustering of CpGs. We observe improved correlation and error in our regional blood clocks (RegBCs) compared to published individual-CpG-based techniques when applied to external datasets. The RegBCs are also more robust when applied to low coverage data and detect a negative age acceleration in mice undergoing calorie restriction. Our RegBCs offer a proof of principle that age prediction of RRBS datasets can be improved by accounting for multiple CpGs over a region, which negates the lack of read depth currently hindering individual-CpG-based approaches.
Listeria monocytogenesrequires DHNA-dependent intracellular redox homeostasis facilitated by Ndh2 for survival and virulence
Authors: Smith Hans B. , Lee Kijeong , Stevenson David M. , Amador-Noguez Daniel , Sauer John-Demian 
Published: January 2023

ABSTRACTListeria monocytogenesis a remarkably well-adapted facultative intracellular pathogen that can thrive in a wide range of ecological niches.L. monocytogenesmaximizes its ability to generate energy from diverse carbon sources using a respiro-fermentative metabolism that can function under both aerobic and anaerobic conditions. Cellular respiration maintains redox homeostasis by regenerating NAD+while also generating a proton motive force (PMF). The end products of the menaquinone (MK) biosynthesis pathway are essential to drive both aerobic and anaerobic cellular respiration. We previously demonstrated that intermediates in the MK biosynthesis pathway, notably 1,4-dihydroxy-2-naphthoate (DHNA), are required for the survival and virulence ofL. monocytogenesindependent of their role in respiration. Furthermore, we found that restoration of NAD+/NADH ratio through expression of water-forming NADH oxidase (NOX) could rescue phenotypes associated with DHNA deficiency. Here we extend these findings to demonstrate that endogenous production or direct supplementation of DHNA restored both the cellular redox homeostasis and metabolic output of fermentation inL. monocytogenes. Further, exogenous supplementation of DHNA rescues thein vitrogrowth andex vivovirulence ofL. monocytogenesDHNA-deficient mutants. Finally, we demonstrate that exogenous DHNA restores redox balance inL. monocytogenesspecifically through the recently annotated NADH dehydrogenase Ndh2, independent of the extracellular electron transport (EET) pathway. These data suggest that the production of DHNA may represent an additional layer of metabolic adaptability byL. monocytogenesto drive energy metabolism in the absence of respiration-favorable conditions.
Relationship between the ACTN3, ACE, AGT, BDKRB2 and IL6 genes and the intake of creatine HCl, whey protein and glutamine, with changes in strength and fat percentage, before an undulating strength program in lower limbs in athletes from Valle del Cauca. Colombia
Authors: Estrada Gerardo David González , Paz Efraín , Sanclemente Felipe 
Published: January 2023

ABSTRACTChanges in power, strength and muscle mass gain were measured with a group of university athletes (n=11), separating them into two groups, one with supplementation and the other without. supplementation, to determine if the intake of sports supplements had an influence or not on individuals with similar genotypic profiles, or the results of the tests only depended on the predisposition to strength and muscle gain of the ACE, ACTN3, AGT, IL6 and BDKRB2 genes. Genotyping was performed based on PCR, RFLP and polyacrylamide electrophoresis tests. The supplemented group ingested whey protein, creatine HCl, and glutamine. All individuals underwent undulating strength training for four months and jump power tests (SJ, CMJ, and ABA), 1RM, and bioimpedance were performed at three different times.Changes were obtained in all the athletes, but the group that obtained the greatest gains in all the tests, except the CMJ jump, was the supplemented group and also had a genotypic profile that registered the lowest TGS. In conclusion, we observed significant improvements in individuals with lower TGS and taking sports supplements, surpassing the group that did not take supplements, but had a greater genetic predisposition in strength activities.
Decreasing ELK3 expression improves Bone Morphogenetic Protein Receptor 2 signaling and pulmonary vascular cell function in PAH
Authors: Ali Md Khadem , Zhao Lan , Perez Vinicio de Jesus , Nicolls Mark R. , Spiekerkoetter Edda F. 
Published: January 2023

AbstractELK3 is upregulated in blood and pulmonary vascular cells of PAH patients and may play a significant role in PAH potentially through modulating BMPR2 signaling.
Age-dependent structural and morphological changes of the stem cell niche disrupt spatiotemporal regulation of stem cells and drive tissue disintegration
Authors: Urman Michelle A. , John Nimmy S. , Lee ChangHwan 
Published: January 2023

AbstractAging induces a progressive decline in tissue function, which has been attributed to a decrease in stem cell function. A major factor driving this decline is the aging of the stem cell niche but elucidating molecular mechanisms of the niche aging and its effects on stem cell regulation remain a challenge. Here, we use theCaenorhabditis elegansdistal tip cell (DTC), the mesenchymal niche that employs Notch signaling to regulate germline stem cells (GSCs), as anin vivoniche aging model and delineate the molecular details of the DTC/niche aging process and its consequences on GSC function and tissue integrity. Using Notch-dependent transcriptional activation as a direct readout of GSC-DTC/niche interaction and its transcriptional activity as a readout for GSC function, we find that an age-dependent reduction in Notch transcription occurs both at the tissue and the cellular levels, but with its activity at the chromosomal loci remains unaffected. This overall reduction is due to an age-dependent progressive shift in the spatial pattern of Notch-dependent transcription in the germline, resulting in a shift of the GSC pool location and disruption of the tissue integrity. We show that the position of the DTC/niche nucleus determines the location of the Notch-responsive GSC pool, with its correlation to the structure and morphology of the DTC/niche, which also changes during aging. Our findings demonstrate that the stem cell niche undergoes structural and morphological changes during aging and reveal a critical link between these changes and the spatiotemporal regulation of stem cell function.
Mechanical forces in extendable tissue matrix orient cell divisions via microtubule stabilization inArabidopsis
Authors: Hoermayer Lukas , Montesinos Juan Carlos , Spona Leonhard , Yoshida Saiko , Marhava Petra , Caballero-Mancebo Silvia , Benková Eva , Heisenberg Carl-Philip , Friml Jiří 
Published: January 2023

AbstractPlant morphogenesis relies exclusively on oriented cell expansion and division. Nonetheless, the mechanism(s) determining division plane orientation remain elusive. Here we studied tissue healing after laser-assisted wounding in roots and uncovered how mechanical forces of cell expansion stabilize and reorient microtubule cytoskeleton for orientation of cell division. We revealed that root tissue functions as interconnected cell matrix with a radial gradient of tissue extendibility causing a predictable tissue deformation after wounding. This causes instant redirection of expansion in the surrounding cells and reorientation of microtubule arrays ultimately predicting cell division orientation. Microtubules are destabilized under low tension, whereas stretching of cells, either through wounding or external aspiration immediately induce their polymerisation. The higher microtubule abundance in the stretched cell parts leads to reorientation microtubule arrays and ultimately cell division planes. This provides a long-sought mechanism for flexible re-arrangement of cell divisions by mechanical forces for tissue reconstruction and plant architecture.
Biallelic Variants inMAD2L1BP(p31comet) Cause Female Infertility Characterized by Oocyte Maturation Arrest
Authors: Huang Lingli , Li Wenqing , Dai Xingxing , Zhao Shuai , Xu Bo , Wang Fengsong , Jin Ren-Tao , Luo Lihua , Wu Liming , Jiang Xue , Cheng Yu , Zou Jiaqi , Xu Caoling , Tong Xianhong , Fan Heng-yu , Zhao Han , Bao Jianqiang 
Published: January 2023

AbstractHuman oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. However, the genetic factors underlying this human disease remain largely unknown. The spindle assembly checkpoint (SAC) is an intricate surveillance mechanism that ensures accurate segregation of chromosomes throughout cell cycles. Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known asp31comet, binds MAD2 and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell cycle progression. In this study, by whole-exome sequencing (WES), we identified homozygous and compound heterozygousMAD2L1BPvariants in three families with female patients diagnosed with primary infertility owing to oocyte metaphase I (MI) arrest. Functional studies revealed that the protein variants resulting from the C-terminal truncation of MAD2L1BP lost their binding ability to MAD2. cRNA microinjection of full-length or truncated MAD2L1BP uncovered their discordant roles in driving the extrusion of polar body 1 (PB1) in mouse oocytes. Furthermore, the patient’s oocytes carrying the mutatedMAD2L1BPvariants resumed polar body extrusion (PBE) when rescued by microinjection of full-lengthMAD2L1BPcRNAs. Together, our studies identified and characterized novel biallelic variants inMAD2L1BPresponsible for human oocyte maturation arrest at MI, and thus prompted new therapeutic avenues for curing female primary infertility.
Neural substrates of cognitive impairment in a NMDAR hypofunction mouse model of schizophrenia and rescue by risperidone
Authors: Delgado-Sallent Cristina , Gener Thomas , Nebot Pau , López-Cabezón Cristina , Puig M. Victoria 
Published: January 2023

ABSTRACTNMDAR hypofunction is a pathophysiological mechanism relevant for schizophrenia. Acute administration of the NMDAR antagonist phencyclidine (PCP) induces psychosis in patients and animals while subchronic PCP (sPCP) produces cognitive dysfunction for weeks. We investigated the neural correlates of memory and perceptual impairments in mice treated with sPCP and the rescuing abilities of the atypical antipsychotic drug risperidone administered daily for two weeks. We recorded neural activities in the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC) during memory acquisition, short-term, and long-term memory in the novel object recognition test and during auditory perception and mismatch negativity (MMN) and examined the effects of sPCP and sPCP followed by risperidone. We found that the information about the new object and its short-term storage were associated with mPFC→dHPC high gamma connectivity whereas long-term memory retrieval depended on dHPC→mPFC theta connectivity. sPCP impaired short-term and long-term memory, which was associated with increased mPFC and decreased dHPC neural network activities, and disrupted mPFC-dHPC connectivity. Risperidone rescued the memory deficits and attenuated hippocampal desynchronization. sPCP also impaired auditory perception and its neural correlates (evoked potentials and MMN) in the mPFC, which were also ameliorated by risperidone. Our study suggests that during NMDAR hypofunction the mPFC and the dHPC disconnect possibly underlying cognitive impairment in schizophrenia, and that risperidone targets this circuit to ameliorate cognitive abilities in patients.
Internet of Things (IoT) acceptance model – assessing consumers' behavior toward the adoption intention of IoT
Authors: Negm Eiman 
Published: January 2023

PurposeThis study identifies key facets leading to consumers' Internet of Things (IoT) adoption intention.Design/methodology/approachApplying four technology acceptance theories (theory of planned behavior, technology acceptance model, pleasure-arousal-dominance theory and technology readiness index), the author uses deductive quantitative research to develop a model, explaining IoT adoption intentions. Administrated questionnaires are distributed in Egypt among generation-Z and millennials in malls. A total of 400 questionnaires are used for hypotheses testing, applying structural equation modeling (SEM) path coefficient analysis.FindingsResults of this study show that attitude, dominance, perceived usefulness, innovativeness and insecurity impact consumers' IoT adoption intentions; subjective norms, perceived behavior control, pleasure, arousal, perceived ease, optimism and discomfort hold insignificant impact on consumers' IoT adoption intentions.Research limitations/implicationsExploring IoT facets and how these facets impact consumers' adoption intentions, this study helps grasp technology acceptance in theory and practice, guiding scholar and practitioners (e.g. IoT developers, retailers, marketers and other field experts) to consider consumers' mindset when developing, improving and marketing IoT.Originality/valueThe contribution stems from the incorporation of various frameworks used to explain technology acceptance. By studying several theories jointly, the research extracts and identifies a significant set of facets (technical and psychological) to build a comprehensive theory of IoT acceptance, showing consumers' IoT adoption is not entirely similar to adoption of other past innovations. This understanding allows marketers to focus on content that needs to be promoted to boost consumers' IoT purchase plans. Future researchers could replicate the results to IoT categories (e.g. home appliances, cars, healthcare, education, sportswear, etc.) to improve external validity of the findings, among other future research opportunities.
A study on the mediating effect of brand trust between perceived legitimacy of influencers and attitude toward brand: evidence from Turkey
Authors: Bora Semiz Buket , Paylan Mehmet ali 
Published: January 2023

PurposeThis study aims to test the effect that the perceived legitimacy of influencers has on the attitude toward the brand from the consumer point of view, as well as the mediating effect brand trust has on the relationship between the perceived legitimacy of influencers and attitude toward the brand.Design/methodology/approachBy using Google Forms to distribute links on various social media platforms, data were collected between January 15, 2021, and February 20, 2021. The population participants were all over 18 and had social media accounts. In the questionnaire, participants were asked to write down three influencers that they followed. They were then asked to answer the other statements in the survey with these three influencers in mind. Participants were included through convenience sampling from the population. A total of 514 people answered the questionnaire. These questions were then subjected to a statistical analysis using PLS-SEM.FindingsThe results showed that cognitive, moral and pragmatic legitimacies significantly affect brand trust. Moreover, the moral and pragmatic legitimacies significantly affect the attitude towards the brand. Regarding the mediation effect, results showed that brand trust has a mediating effect between the perceived legitimacy of influencers and attitude towards the brand.Research limitations/implicationsOne of the main limitations of this study is that the data were collected by convenience sampling. Therefore, the research results cannot be generalised. Another limitation is that the study measures general perceptions of influencers' legitimacy, so it has not been addressed in terms of a specific product group, follower or influencer self-branding issues.Practical implicationsThe managerial contribution of this research centers on the ability to evaluate the influencers and their legitimacy in society; not only by their follower count but also by the legitimacy factors that can be named under the name of primary legitimacy norms. Managers will then be able to use this framework to determine which influencers they want to work with.Originality/valueWhen the literature was reviewed, no study was found that examined and measured the perceived legitimacy of influencers in terms of social norms, values and morals. This research aims to add the concept of the perceived legitimacy of influencers to the discussion in the literature, embody the legitimate framework of influencers' activities and provide a more general conceptual basis for persuasiveness in influencer marketing.
Chatbots, virtual-try-on (VTO), e-WOM: modeling the determinants of attitude’ and continued intention with PEEIM as moderator in online shopping
Authors: Tandon Urvashi 
Published: January 2023

Purpose
The purpose of this study is to develop an empirical model by understanding the relative significance of interactive technological forces, such as chatbots, virtual try-on technology (VTO) and e-word-of-mouth (e-WOM), to improve interactive marketing experiences among consumers. This study also validates the moderating role of the perceived effectiveness of e-commerce institutional mechanism (PEEIM) as a moderator between attitude and continued intention.

Design/methodology/approach
Data were collected through personal visits and an online survey. The link to the survey questionnaire was shared on different social media platforms and social networking sites. A total of 362 responses obtained in the online and offline modes were considered for this study.

Findings
e-WOM emerged as the strongest predictor of attitude, followed by chatbots and VTO. The results of this study revealed that PEEIM did not moderate the relationship between attitude and continued intention.

Originality/value
Using the self-determination theory and behavioral reasoning theory as theoretical frameworks, this study is an initial endeavor in the online shopping context to empirically validate interactive forces like chatbots, VTO, e-WOM and PEEIM as moderators together to arrive at a holistic framework. These forces, in turn, act as significant contributors to online shopping satisfaction.