bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food
Authors: Dearden Laura , Furigo Isadora C. , Pantaleão Lucas C. , Wong L W. P. , Fernandez-Twinn Denise S. , de Almeida-Faria Juliana , Kentistou Katherine A. , Carreira Maria V. , Bidault Guillaume , Vidal-Puig Antonio , Ong Ken K. , Perry John R. B. , Donato Jose , Ozanne Susan E. 
Published: June 2022

AbstractIn uteroexposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells culturedin vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neuronsin vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and over-expression of miR-505-5p decreased neuronal fatty acid metabolismin vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased high-fat diet intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced high-fat diet intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods.
Evaluation of training data, ground truth and shape variability in the semantic segmentation of HeLa cells observed with electron microscopy
Authors: Karabağ C. , Reyes-Aldasoro C.C. 
Published: June 2022

AbstractThis paper describes the quantitative and qualitative evaluation of training data, ground truth and the variability of the shape of HeLa cells as observed with electron microscopy in the process of semantic segmentation. HeLa cells are a widely used immortal cell line, but the principles described here could apply to other cells. From a data set of 8, 000×8, 000×517 voxels, a region of interest (ROI) of 2, 000×2, 000×300 was cropped for quantitative evaluation with the qualitative evaluation performed on a larger section of interest. Patches of data and labels were used to train a U-Net architecture from scratch, which was compared also with a traditional image processing algorithm. The correctness of ground truth, that is, the inclusion of one or more nuclei within a region of interest was evaluated with a hand-drawn ground truth of the ROI. The impact of the extent of training data was evaluated by comparing results from 36,000 data and label patches extracted from the odd slices in the central region, to 135,000 patches obtained from every other slice in the set. Accuracy and Jaccard similarity index were higher for the larger training set with multiple nuclei in the ground truth. However, when the U-Nets were used to segment the section of interest beyond the ROI, results were not as good as expected, suggesting that the very complicated nature of the shapes of HeLa cells cannot be learned from a single cell. Data, code and ground truth have been made publicly released through Empair, GitHub and Zenodo.
Sexual selection leads to positive allometry but not sexual dimorphism in the expression of horn shape in the blue wildebeest, Connochaetes taurinus
Authors: Gerstenhaber Chlöe , Knapp Andrew 
Published: June 2022

AbstractSexual selection is thought to be an important driver of adaptation, speciation and extinction. Empirically testing these predictions across macroevolutionary timescales first requires an understanding of the morphology of secondary sexual traits in extant taxa. We used three-dimensional geometric morphometrics to analyse a large sample of the skull of the blue wildebeest, Connochaetes taurinus, in which horns are found in both sexes but only used in intrasexual competition in males. We show that the horns fit several predictions of secondary sexual traits; overall skull shape is significantly correlated with size (R2 = 0.38, p = 0.001), and the sexually selected horns show drastically higher growth rates and variation than any other skull element, supporting previous findings. We also find that despite showing significant sexual dimorphism in shape and size (R2 = 0.21, p = 0.001), allometric growth trajectories of sexes are identical (R2 = 0.01, p = 0.635) and dimorphism is not readily detectable without prior knowledge of sex, and is not possible when shape is corrected for size. Our results show that even with strong sexual selection operating in only one sex, the expression of secondary sexual traits may show characteristic and indistinguishable patterns of growth and variance in both sexes.
3D melanoma spheroid model for the development of positronium biomarker
Authors: Karimi Hanieh , Moskal Paweł , Stępień Ewa Ł. 
Published: June 2022

AbstractIt was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium imaging utilizes properties of a positronium atoms, which are built from the electron and positron produced in the body during PET examinations.We hypothesized whether positronium imaging would be sensitive to in vitro discrimination of tumour-like three-dimensional structures (spheroids) build of melanoma cell lines with different cancer activity and biological properties.The lifetime of ortho-Positronium (o-Ps) was evaluated in melanoma spheroids from two cell lines (WM266-4 and WM115) differing in the stage of malignancy. Additionally, we considered such parameters: as cell size, proliferation rate and malignancy to evaluate their relationship with o-Ps lifetime. We demonstrate the pilot results for the o-Ps lifetime measurement in extracellular matrix free spheroids. With the statistical significance of two standard deviations, we demonstrated that the higher the degree of malignancy and the rate of proliferation of neoplastic cells the shorter the lifetime of ortho-positronium. In particular we observed following indications encouraging further research: (i) WM266-4 spheroids characterized with higher proliferation rate and malignancy showed shorter o-Ps lifetime compared to WM115 spheroids characterized by lower growth rate, (ii) Both cell lines showed a decrease in the lifetime of o-Ps after spheroid generation in 8th day comparing to 4th day in culture and the mean o-Ps lifetime is longer for spheroids formed from WM115 cells than these from WM266-4 cells, regardless spheroid age. The results of these study revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.
Comparison of Cosine, Modified Cosine, and Neutral Loss Based Spectrum Alignment For Discovery of Structurally Related Molecules
Authors: Bittremieux Wout , Schmid Robin , Huber Florian , van der Hooft Justin JJ , Wang Mingxun , Dorrestein Pieter C 
Published: June 2022

AbstractSpectrum alignment of tandem mass spectrometry (MS/MS) data using the modified cosine similarity and subsequent visualization as molecular networks have been demonstrated to be a useful strategy to discover analogs of molecules from untargeted MS/MS-based metabolomics experiments. Recently, a neutral loss matching approach has been introduced as an alternative to MS/MS-based molecular networking, with an implied performance advantage in finding analogs that cannot be discovered using existing MS/MS spectrum alignment strategies. To comprehensively evaluate the scoring properties of neutral loss matching, the cosine similarity, and the modified cosine similarity, similarity measures of 955,228 peptide MS/MS spectrum pairs and 10 million small molecule MS/MS spectrum pairs were compared. This comparative analysis revealed that the modified cosine similarity outperformed neutral loss matching and the cosine similarity in all cases. The data further indicated that the performance of MS/MS spectrum alignment depends on the location and type of the modification, as well as the chemical compound class of fragmented molecules.
Methylation in NDUFA13 gene promoter disrupts communication between collaborative transcription factors – potential mechanism for onset of breast cancer
Authors: Johanna Hörberg , Björn Hallbäck , Kevin Moreau , Reymer Anna 
Published: June 2022

AbstractSelective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element may change the binding preferences of the protein thus causing the dysregulation of transcription programs. Here we investigate a molecular mechanism driving the downregulation of NDUFA13 gene, due to hypermethylation, which is associated with multiple cancers. Using bioinformatic analyses of breast cancer cell line MCF7, we identify a hypermethylated region containing the binding sites of two TFs dimers, CEBPB and E2F1-DP1, located 130 b.p. from the gene transcription start site. All-atom extended MD simulations of wild-type and methylated DNA alone and in complex with either one or both TFs dimers provide mechanistic insights into the cooperative asymmetric binding order of the two dimers; the CEBPB binding should occur first to facilitate the E2F1-DP1-DNA association. The CpG methylation within the E2F1-DP1 response element and the linker decreases the cooperativity effects and renders the E2F1-DP1 binding site less recognizable by the TF dimer. Taken together, the identified CpG methylation site may contribute to the downregulation of NDUFA13 gene and has a potential as a biomarker for breast cancer.
Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97
Authors: Bothe Sebastian , Hänzelmann Petra , Böhler Stephan , Kehrein Josef , Wiedemann Christoph , Hellmich Ute A. , Brenk Ruth , Schindelin Hermann , Sotriffer Christoph 
Published: June 2022

AbstractBiosensor techniques have become increasingly important for fragment-based drug discovery during the last years. Here, we describe a biolayer interferometry-based fragment screen targeting the AAA+ ATPase p97, an essential protein with key roles in protein homeostasis and a possible target for cancer chemotherapy. Currently available p97 inhibitors target its ATPase activity and globally impair p97-mediated processes. In contrast, inhibition of cofactor binding to the N-domain by a protein-protein-interaction inhibitor would enable the selective targeting of specific p97 functions. We demonstrate that a region known as SHP-motif binding site can be targeted with small molecules. Guided by molecular dynamics simulations, the binding sites of selected screening hits were postulated and experimentally validated using protein- and ligand-based NMR techniques, as well as X-ray crystallography, ultimately resulting in the first structure of a small molecule in complex with the N-domain of p97. The identified fragments provide insights into how this region could be targeted and present first chemical starting points for the development of a protein-protein interaction inhibitor preventing the binding of selected cofactors to p97.
Herpes simplex virus 1 protein pUL21 stimulates cellular ceramide transport by activating CERT
Authors: Benedyk Tomasz H. , Connor Viv , Caroe Eve R. , Shamin Maria , Svergun Dmitri I. , Deane Janet E. , Jeffries Cy M. , Crump Colin M. , Graham Stephen C. 
Published: June 2022

AbstractHerpes simplex virus (HSV)-1 dramatically alters the architecture and protein composition of cellular membranes during infection, but its effects upon membrane lipid composition remain unclear. HSV-1 pUL21 is a virus-encoded protein phosphatase adaptor that promotes dephosphorylation of multiple cellular and virus proteins, including the cellular ceramide transport protein CERT. CERT mediates non- vesicular transport of ceramide from the ER to the trans-Golgi network, whereupon ceramide is converted to sphingomyelin and other sphingolipids that play important roles in cell proliferation, cell signalling and membrane trafficking. Using click chemistry to profile the kinetics of sphingolipid metabolism in cultured cells, we show that pUL21-mediated dephosphorylation activates CERT and increases the rate of ceramide to sphingomyelin conversion. Purified pUL21 and full-length CERT interact with sub-micromolar affinity and we map the domains responsible for the interaction. Solving the solution structure of the pUL21 C-terminal domain in complex with the CERT PH and START domains using small-angle X-ray scattering allows us to identify a single amino acid mutation on the surface of pUL21 that disrupts CERT binding in vitro and in cultured cells. Sphingolipid profiling demonstrates that ceramide to sphingomyelin conversion is severely diminished in the context of HSV- 1 infection, a defect that is compounded when infecting with a virus encoding the mutated form of pUL21 that lacks the ability to activate CERT. However, virus replication and spread are not significantly altered when pUL21-mediated CERT dephosphorylation is abolished, highlighting that dephosphorylation of other cellular and/or viral targets underpins the important role of pUL21 in HSV-1 biology.SignificanceHerpes simplex virus (HSV)-1 causes a life-long dormant infection of neurons, sporadically reactivating to manifest as cold-sores or genital herpes. While the impact of HSV-1 upon the protein content of infected cells has been well studied, we know relatively little about its impact upon cellular lipids. Using bioorthogonal labelling in cultured cells we show that HSV-1 protein pUL21 activates the key cellular lipid transport protein CERT to accelerate the conversion of ceramide to sphingomyelin. HSV-1 infection dramatically alters the kinetics of ceramide metabolism, leading to ceramide accumulation. Mutation of HSV-1 pUL21 to prevent CERT activation further enhances ceramide accumulation but this does not alter the replication or spread of HSV-1, highlighting that other cellular and/or viral proteins represent the critical targets of pUL21-mediated dephosphorylation in cultured cells.
SLAMseq resolves the kinetics of maternal and zygotic gene expression in early zebrafish embryogenesis
Authors: Bhat Pooja , Cabrera-Quio Luis E. , Herzog Veronika A. , Fasching Nina , Pauli Andrea , Ameres Stefan L. 
Published: June 2022

AbstractThe maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation of maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute the compound embryonic transcriptome in zebrafish. While mitochondrial zygotic transcripts prevailed prior to MZT, we uncover the spurious transcription of hundreds of short and intron-poor nuclear genes as early as the 2-cell stage. Upon ZGA, most zygotic transcripts originate from thousands of maternal-zygotic (MZ) genes that are transcribed at rates comparable to those of hundreds of purely zygotic genes and replenish maternal mRNAs at distinct timescales. Rapid replacement of MZ transcripts involves transcript decay features unrelated to major maternal degradation pathways and promotesde novosynthesis of the core gene expression machinery by increasing poly(A)-tail length and translation efficiency. SLAMseq hence provides unprecedented insights into the timescales, molecular features and regulation of MZT during zebrafish embryogenesis.
Reputation and its consequences in Fintech services: the case of mobile banking
Authors: Nguyen Yen Thi Hoang , Tapanainen Tommi , Nguyen Hai Thi Thanh 
Published: June 2022

PurposeRecently, traditional financial institutions are facing strong competition from disruptive innovators (Fintech firms) forcing them to increasingly invest in new IT solutions to maintain their competitive edge. However, there are still advantages that traditional financial institutions enjoy, of which the primary one may be reputation. Surprisingly, the firm reputation link to use intention has not received much attention in the literature, prompting this research. The purpose of this study is to examine the firm reputation link to use intention in the context of mobile banking.Design/methodology/approach The results are based on a survey of 783 participants in Vietnam.FindingsThe study confirmed that reputation plays an important role in promoting use intention for mobile banking. Additionally, perceived risk and trust are also linked to perceived usefulness (PU) and perceived ease-of-use (PEOU).Originality/valueThis study is among the first to link perceived risk and trust to PU and PEOU in a mobile banking context. Based on the Theory of Reasoned Action, the study adds to the literature by connecting two separated research themes: technology adoption and reputation. It also suggests avenues for both traditional banks and Fintech firms to set their business strategies to enhance their reputation or collaborate for mutual benefits.
Customers’ perceptions of hotel AI-enabled voice assistants: does brand matter?
Authors: Cai Ruiying , Cain Lisa Nicole , Jeon Hyeongjin 
Published: June 2022

Purpose
Extending the technology acceptance model (TAM) to a new context, the purpose of this paper is to propose an integrative model of the brand of artificial intelligence-enabled voice assistants (AI-EVA) and customers’ perceptions and behavioral intentions of using AI-EVA in hotels. Moderating effects of construal levels and hotel scales were examined.

Design/methodology/approach
This paper adopted a mixed method approach. A qualitative and phenomenological methodology was adopted in Study 1 to explore hotel customers’ experience with AI-EVA. Study 2 applied experimental design to investigate the effects of the brand of AI-EVA and construal level on customers’ perceptions and behavioral intentions of using AI-EVA. Based on Studies 1 and 2 results, Study 3 examined how the brand of AI-EVA and hotel scale affect customers’ perceptions and behavioral intentions of using AI-EVA during hotel stays.

Findings
This research found that customers perceive a higher level of perceived usefulness, perceived ease of use and anthropomorphism when AI-EVA is branded (vs off-brand). Perceived usefulness positively affects customers’ intention to use and to spread positive word-of-mouth. Anxiety of using AI-enabled devices and privacy concerns inhibit customers’ intention to use AI-EVA. Anthropomorphism increases customers’ willingness to spread positive word-of-mouth. Construal level moderates the effect of the brand of AI-EVAs on perceived ease of use and anthropomorphism. Hotel scale moderates the effect of brand on perceived usefulness.

Originality/value
This paper is one of the first attempts to uncover and integrate different factors underlying customers’ perceptions of using AI-EVA in an extended TAM in hotel settings. This paper provides an integrative model extending the TAM to a new context by deploying a mixed-method approach across three studies.
Reimagining financial inclusion in the post COVID-19 world: the case of Grameen America
Authors: Mousa Rania , Ozili Peterson K. 
Published: June 2022

Purpose
The purpose of this paper is to analyze Grameen America's response to COVID-19 pandemic. This is accomplished by identifying and analyzing the key initiatives implemented by Grameen America within the framework of selected United Nations' Sustainability Development Goals (UN’s SD Goals).

Design/methodology/approach
This study has used qualitative content analysis to analyze financial and nonfinancial information of Grameen Bank.

Findings
This study follows a qualitative content analysis method to precisely gauge the shift in Grameen’s strategy and focus, as well as to assess the impact of its initiatives on the small business community before and after the pandemic. The findings showcase that Grameen’s longstanding mission to alleviate poverty is in line with the UN’s SD Goal 1. Also, Grameen’s commitment to create partnerships with external organizations to offer credit and noncredit services and support is consistent with UN’s SD Goal 17.

Research limitations/implications
Notwithstanding the significant contributions of this case study, the findings are limited in some respects. First, this case study focuses on the Grameen America’s unique experience regarding its response to COVID-19 pandemic. This may affect the interpretation and generalization of the findings of this study. Performing comparative views across wide range of relevant microlending institutions could help improve the generalization of the findings. Also, this case study examines the impact on women and minority groups who were particularly affected by the pandemic. The results should, therefore, be interpreted with care as circumstances may change over time.

Practical implications
The implication for practice is that policymakers should encourage the creation of more member-based financial and non-financial institutions that can help members integrate financially and socially into society. Also, practitioners should increase their ethical duties and responsibilities to their members in society in good and bad times as members tend to value the ethical aspect of financial businesses.

Social implications
The social implication of the findings is that helping members of society to cope with the difficulties brought about by COVID increased the sense of belonging among members and made them feel cared for, thereby increasing financial and social inclusion among underserved people.

Originality/value
Prior literature addressed the initiatives of microlending institutions such as Grameen Bank to achieve financial inclusion among financially vulnerable women. This case study contributes to the literature on financial inclusion and poverty alleviation by examining Grameen America’s response to the pandemic by identifying and assessing Grameen America (GA’s) key initiatives and their impact within the framework of the UN’s SD Goals in the post COVID-19 world.
Alibi corroboration: an examination of laypersons’ expectations
Authors: Warren Kelly , Snow Mark , Abbott Heidi 
Published: June 2022

Purpose
The study aims to examine what laypersons expect those corroborating an alibi to remember about an interaction with an alibi provider.

Design/methodology/approach
Participants (N = 314) were presented with a mock crime scenario and answered questions about an alibi provider (i.e. the criminal suspect) and alibi corroborators. Participants also completed a lineup task based on the scenario and rated the likelihood of their own ability to corroborate the suspect’s alibi.

Findings
Overall, participants believed that it was moderately likely that an alibi corroborator with no prior relationship with the suspect would be able to vouch for the suspect, provide a description and to remember his general physical characteristics. Those who were inaccurate in their lineup decision demonstrated lower expectations of their own ability to corroborate the suspect’s alibi relative to those who were accurate in their decision.

Originality/value
To the best of the authors’ knowledge, this is the first known study to assess what those judging an alibi expect when making a decision about the outcome of a case. Results demonstrate that laypeople have arguably unrealistic expectations of alibi corroborators, potentially jeopardizing innocent people’s ability to prove their innocence.